Analysis of laterality and percentage of tumor involvement in 1386 prostatectomized specimens for selection of unilateral focal cryotherapy.

PubMed

Mouraviev, Vladimir; Mayes, Janice M; Madden, John F; Sun, Leon; Polascik, Thomas J

2007-04-01

In total, 1386 paraffin embedded radical prostatectomy specimens from patients with clinically localized prostate cancer (PCa) excised between 2002-06 were analyzed. Pathologic assessment paid particular attention to laterality and percentage of tumor involvement (PTI) along with pathologic Gleason Score (pGS). Completely unilateral cancers were identified in 254 (18.3%) patients, and in 39% cases of them the signs of clinically significant PCa were revealed. The majority of unilateral tumors (72%) were low volume with a PTI of < or =5. This study suggests that only a select group of men diagnosed with PCa have completely unilateral cancers that would be amenable to focal ablation therapy targeting 1 lobe. Further study is needed to develop predictive models for those patients likely to have small, unilateral cancers that may be amenable to focal therapy.

Identification of the epigenetic reader CBX2 as a potential drug target in advanced prostate cancer.

PubMed

Clermont, Pier-Luc; Crea, Francesco; Chiang, Yan Ting; Lin, Dong; Zhang, Amy; Wang, James Z L; Parolia, Abhijit; Wu, Rebecca; Xue, Hui; Wang, Yuwei; Ding, Jiarui; Thu, Kelsie L; Lam, Wan L; Shah, Sohrab P; Collins, Colin C; Wang, Yuzhuo; Helgason, Cheryl D

2016-01-01

While localized prostate cancer (PCa) can be effectively cured, metastatic disease inevitably progresses to a lethal state called castration-resistant prostate cancer (CRPC). Emerging evidence suggests that aberrant epigenetic repression by the polycomb group (PcG) complexes fuels PCa progression, providing novel therapeutic opportunities. In the search for potential epigenetic drivers of CRPC, we analyzed the molecular profile of PcG members in patient-derived xenografts and clinical samples. Overall, our results identify the PcG protein and methyl-lysine reader CBX2 as a potential therapeutic target in advanced PCa. We report that CBX2 was recurrently up-regulated in metastatic CRPC and that elevated CBX2 expression was correlated with poor clinical outcome in PCa cohorts. Furthermore, CBX2 depletion abrogated cell viability and induced caspase 3-mediated apoptosis in metastatic PCa cell lines. Mechanistically explaining this phenotype, microarray analysis in CBX2-depleted cells revealed that CBX2 controls the expression of many key regulators of cell proliferation and metastasis. Taken together, this study provides the first evidence that CBX2 inhibition induces cancer cell death, positioning CBX2 as an attractive drug target in lethal CRPC.

Performance comparisons between PCA-EA-LBG and PCA-LBG-EA approaches in VQ codebook generation for image compression

NASA Astrophysics Data System (ADS)

Tsai, Jinn-Tsong; Chou, Ping-Yi; Chou, Jyh-Horng

2015-11-01

The aim of this study is to generate vector quantisation (VQ) codebooks by integrating principle component analysis (PCA) algorithm, Linde-Buzo-Gray (LBG) algorithm, and evolutionary algorithms (EAs). The EAs include genetic algorithm (GA), particle swarm optimisation (PSO), honey bee mating optimisation (HBMO), and firefly algorithm (FF). The study is to provide performance comparisons between PCA-EA-LBG and PCA-LBG-EA approaches. The PCA-EA-LBG approaches contain PCA-GA-LBG, PCA-PSO-LBG, PCA-HBMO-LBG, and PCA-FF-LBG, while the PCA-LBG-EA approaches contain PCA-LBG, PCA-LBG-GA, PCA-LBG-PSO, PCA-LBG-HBMO, and PCA-LBG-FF. All training vectors of test images are grouped according to PCA. The PCA-EA-LBG used the vectors grouped by PCA as initial individuals, and the best solution gained by the EAs was given for LBG to discover a codebook. The PCA-LBG approach is to use the PCA to select vectors as initial individuals for LBG to find a codebook. The PCA-LBG-EA used the final result of PCA-LBG as an initial individual for EAs to find a codebook. The search schemes in PCA-EA-LBG first used global search and then applied local search skill, while in PCA-LBG-EA first used local search and then employed global search skill. The results verify that the PCA-EA-LBG indeed gain superior results compared to the PCA-LBG-EA, because the PCA-EA-LBG explores a global area to find a solution, and then exploits a better one from the local area of the solution. Furthermore the proposed PCA-EA-LBG approaches in designing VQ codebooks outperform existing approaches shown in the literature.

Silibinin inhibits prostate cancer cells- and RANKL-induced osteoclastogenesis by targeting NFATc1, NF-κB, and AP-1 activation in RAW264.7 cells.

PubMed

Kavitha, Chandagirikoppal V; Deep, Gagan; Gangar, Subhash C; Jain, Anil K; Agarwal, Chapla; Agarwal, Rajesh

2014-03-01

Currently, there are limited therapeutic options against bone metastatic prostate cancer (PCA), which is primarily responsible for high mortality and morbidity in PCA patients. Enhanced osteoclastogenesis is an essential feature associated with metastatic PCA in the bone microenvironment. Silibinin, an effective chemopreventive agent, is in phase II clinical trials in PCA patients but its efficacy against PCA cells-induced osteoclastogenesis is largely unknown. Accordingly, here we examined silibinin effect on PCA cells-induced osteoclastogenesis employing human PCA (PC3MM2, PC3, and C4-2B) and murine macrophage RAW264.7 cells. We also assessed silibinin effect on receptor activator of nuclear factor κB ligand (RANKL)-induced signaling associated with osteoclast differentiation in RAW264.7 cells. Further, we analyzed silibinin effect on osteomimicry biomarkers in PCA cells. Results revealed that silibinin (30-90 μM) inhibits PCA cells-induced osteoclast activity and differentiation in RAW264.7 cells via modulating expression of several cytokines (IGF-1, TGF-β, TNF-α, I-TAC, M-CSF, G-CSF, GM-CSF, etc.) that are important in osteoclastogenesis. Additionally, in RAW264.7 cells, silibinin decreased the RANKL-induced expression and nuclear localization of NFATc1, which is considered the master regulator of osteoclastogenesis. Furthermore, silibinin decreased the RANKL-induced DNA binding activity of NFATc1 and its regulators NF-κB and AP1, and the protein expression of osteoclast specific markers (TRAP, OSCAR, and cathepsin K). Importantly, silibinin also decreased the expression of osteomimicry biomarkers (RANKL, Runx2, osteocalcin, and PTHrP) in cell culture (PC3 and C4-2B cells) and/or in PC3 tumors. Together, our findings showing that silibinin inhibits PCA cells-induced osteoclastogenesis, suggest that silibinin could be useful clinically against bone metastatic PCA. © 2013 Wiley Periodicals, Inc.

Localized prostate cancer in elderly men aged 80-89, findings from a population-based registry.

PubMed

Vatandoust, S; Kichenadasse, G; O'Callaghan, M; Vincent, A D; Kopsaftis, T; Walsh, S; Borg, M; Karapetis, C S; Moretti, K

2018-03-30

To investigate the rate of death due to Prostate Cancer (PCa) and disease characteristics in patients diagnosed with Localized Prostate Cancer (LPCa) at age 80-89 years in comparison with men diagnosed at age 70-79. This is a retrospective study of data from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC). Included were men diagnosed between 2005 and 2014, aged ≥70 with no evidence of metastatic disease at presentation. Propensity score matching and competing risk Fine and Grey regression were used to assess the chance of treatment (curative v non-curative) and treatment effect on PCa specific-mortality. Of the 1951 eligible patients, 1428 (76%) aged 70-79, and 460 (24%) aged 80-89 yr at diagnosis (median age of 74 (IQR=72-76) and 83 (IQR=81-85) respectively). The 80-89 group had higher Gleason scores and PSA values (all p<0.001) in comparison with the younger group. The 80-89 group were less likely to be treated with curative treatment (OR=0.12, 95CI=[0.09, 0.16], p < 0.001). Proportion of deaths attributable to PCa was similar in both groups: 73 of 263 deaths (28%) in the 80-89 group vs 97 of 310 deaths (31%) in the 70-79 group. The risk of PCa mortality in individuals treated with curative intent was reduced in both groups. The proportion of PCa deaths was similar in both groups. These findings support carefully selected individualized management of elderly patients diagnosed with localized PCa. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer.

PubMed

Castro, Elena; Goh, Chee; Olmos, David; Saunders, Ed; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Dadaev, Tokhir; Govindasami, Koveela; Guy, Michelle; Sawyer, Emma; Wilkinson, Rosemary; Ardern-Jones, Audrey; Ellis, Steve; Frost, Debra; Peock, Susan; Evans, D Gareth; Tischkowitz, Marc; Cole, Trevor; Davidson, Rosemarie; Eccles, Diana; Brewer, Carole; Douglas, Fiona; Porteous, Mary E; Donaldson, Alan; Dorkins, Huw; Izatt, Louise; Cook, Jackie; Hodgson, Shirley; Kennedy, M John; Side, Lucy E; Eason, Jacqueline; Murray, Alex; Antoniou, Antonis C; Easton, Douglas F; Kote-Jarai, Zsofia; Eeles, Rosalind

2013-05-10

To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1). PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.

Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer

PubMed Central

Castro, Elena; Goh, Chee; Olmos, David; Saunders, Ed; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Dadaev, Tokhir; Govindasami, Koveela; Guy, Michelle; Sawyer, Emma; Wilkinson, Rosemary; Ardern-Jones, Audrey; Ellis, Steve; Frost, Debra; Peock, Susan; Evans, D. Gareth; Tischkowitz, Marc; Cole, Trevor; Davidson, Rosemarie; Eccles, Diana; Brewer, Carole; Douglas, Fiona; Porteous, Mary E.; Donaldson, Alan; Dorkins, Huw; Izatt, Louise; Cook, Jackie; Hodgson, Shirley; Kennedy, M. John; Side, Lucy E.; Eason, Jacqueline; Murray, Alex; Antoniou, Antonis C.; Easton, Douglas F.; Kote-Jarai, Zsofia; Eeles, Rosalind

2013-01-01

Purpose To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. Patients and Methods This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1). Results PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Conclusion Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients. PMID:23569316

Outcome predictors of radical cystectomy in patients with cT4 prostate cancer: a multi-institutional study of 62 patients.

PubMed

Spahn, Martin; Morlacco, Alessandro; Boxler, Silvan; Joniau, Steven; Briganti, Alberto; Montorsi, Francesco; Gontero, Paolo; Bader, Pia; Frohneberg, Detlef; van Poppel, Hein; Karnes, Robert Jeffrey

2017-11-01

To identify which patients with macroscopic bladder-infiltrating T4 prostate cancer (PCa) might have favourable outcomes when treated with radical cystectomy (RC). We evaluated 62 patients with cT4cN0-1 cM0 PCa treated with RC and pelvic lymph node dissection between 1972 and 2011. In addition to descriptive statistics, the Kaplan-Meier method and log-rank tests were used to depict survival rates. Univariate and multivariate Cox regression analysis tested the association between predictors and progression-free, PCa-specific and overall survival. Of the 62 patients, 19 (30.6%) did not have clinical progression during follow-up, two (3.2%) had local recurrence, and 32 (51.6%) had haematogenous and nine (14.5%) combined pelvic and distant metastasis. Forty patients (64.5%) died, 34 (54.8%) from PCa and six (9.7%) from other causes. The median (range) survival time of the 19 patients who were metastasis-free at last follow-up was 86 (1-314) months, 8/19 patients had a follow-up of >5 years, and five patients survived metastasis-free for >15 years. Patients without seminal vesicle invasion (SVI) had the best outcomes, with an estimated 10-year PCa-specific survival of 75% compared with 24% for patients with SVI. For cT4 PCa RC can be an appropriate treatment for local control and part of a multimodality-treatment approach. Although recurrences are probable, these do not necessarily translate into cancer-specific death. Men without SVI had a 75% 10-year PCa-specific survival. Although outcomes for patients with SVI are not as favourable, there can be good local control; however, these patients are at higher risk of progression and may need more aggressive systemic treatment. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Temporal Processing of Dynamic Positron Emission Tomography via Principal Component Analysis in the Sinogram Domain

NASA Astrophysics Data System (ADS)

Chen, Zhe; Parker, B. J.; Feng, D. D.; Fulton, R.

2004-10-01

In this paper, we compare various temporal analysis schemes applied to dynamic PET for improved quantification, image quality and temporal compression purposes. We compare an optimal sampling schedule (OSS) design, principal component analysis (PCA) applied in the image domain, and principal component analysis applied in the sinogram domain; for region-of-interest quantification, sinogram-domain PCA is combined with the Huesman algorithm to quantify from the sinograms directly without requiring reconstruction of all PCA channels. Using a simulated phantom FDG brain study and three clinical studies, we evaluate the fidelity of the compressed data for estimation of local cerebral metabolic rate of glucose by a four-compartment model. Our results show that using a noise-normalized PCA in the sinogram domain gives similar compression ratio and quantitative accuracy to OSS, but with substantially better precision. These results indicate that sinogram-domain PCA for dynamic PET can be a useful preprocessing stage for PET compression and quantification applications.

Metformin effects on biochemical recurrence and metabolic signaling in the prostate.

PubMed

Winters, Brian; Plymate, Stephen; Zeliadt, Steven B; Holt, Sarah; Zhang, Xiaotun; Hu, Elaine; Lin, Daniel W; Morrissey, Colm; Wooldridge, Bryan; Gore, John L; Porter, Michael P; Wright, Jonathan L

2015-11-01

Metformin has received considerable attention as a potential anti-cancer agent. Animal and in-vitro prostate cancer (PCa) models have demonstrated decreased tumor growth with metformin, however the precise mechanisms are unknown. We examine the effects of metformin on PCa biochemical recurrence (BCR) in a large clinical database followed by evaluating metabolic signaling changes in a cohort of men undergoing prostate needle biopsy (PNB). Men treated for localized PCa were identified in a comprehensive clinical database between 2001 and 2010. Cox regression was performed to determine association with BCR relative to metformin use. We next identified a separate case-control cohort of men undergoing prostate needle biopsy (PNB) stratified by metformin use. Differences in mean IHC scores were compared with linear regression for phosphorylated IR, IGF-IR, AKT, and AMPK. One thousand seven hundred and thirty four men were evaluated for BCR with mean follow up of 41 months (range 1-121 months). "Ever" metformin use was not associated with BCR (HR 1.12, 0.77-1.65), however men reporting both pre/post-treatment metformin use had a 45% reduction in BCR (HR = 0.55 (0.31-0.96)). For the tissue-based study, 48 metformin users and 42 controls underwent PNB. Significantly greater staining in phosphorylated nuclear (p-IR, p-AKT) and cytoplasmic (p-IR, p-IGF-1R) insulin signaling proteins were seen in patients with PCa detected compared to those with negative PNB (P-values all <0.006). When stratified by metformin use, IGF-1R remained significantly elevated (P = 0.01) in men with PCa detected whereas p-AMPK (P = 0.05) was elevated only in those without PCa. Metformin use is associated with reduced BCR after treatment of localized PCa when considering pre-diagnostic and cumulative dosing. In men with cancer detected on PNB, insulin signaling markers were significantly elevated compared to negative PNB patients. The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in negative PNBs suggests altered metabolic pathway activation precipitated by metformin use. © 2015 Wiley Periodicals, Inc.

Metformin Effects on Biochemical Recurrence and Metabolic Signaling in the Prostate

PubMed Central

Winters, Brian; Plymate, Stephen; Zeliadt, Steven B; Holt, Sarah; Zhang, Xiaotun; Hu, Elaine; Lin, Daniel W.; Morrissey, Colm; Wooldridge, Bryan; Gore, John L; Porter, Michael P; Wright, Jonathan L

2015-01-01

Background Metformin has received considerable attention as a potential anti-cancer agent. Animal and in-vitro prostate cancer (PCa) models have demonstrated decreased tumor growth with metformin, however the precise mechanisms are unknown. We examine the effects of metformin on PCa biochemical recurrence (BCR) in a large clinical database followed by evaluating metabolic signaling changes in a cohort of men undergoing prostate needle biopsy (PNB). Methods Men treated for localized PCa were identified in a comprehensive clinical database between 2001 and 2010. Cox regression was performed to determine association with BCR relative to metformin use. We next identified a separate case-control cohort of men undergoing prostate needle biopsy (PNB) stratified by metformin use. Differences in mean IHC scores were compared with linear regression for phosphorylated IR, IGF-IR, AKT, and AMPK. Results 1,734 men were evaluated for BCR with mean follow up of 41 months (range 1-121 months). ‘Ever’ metformin use was not associated with BCR (HR 1.12, 0.77-1.65), however men reporting both pre/post-treatment metformin use had a 45% reduction in BCR (HR=0.55 (0.31-0.96)). For the tissue-based study, 48 metformin users and 42 controls underwent PNB. Significantly greater staining in phosphorylated nuclear (p-IR, p-AKT) and cytoplasmic (p-IR, p-IGF-1R) insulin signaling proteins were seen in patients with PCa detected compared to those with negative PNB (p-values all < 0.006). When stratified by metformin use, IGF-1R remained significantly elevated (p=0.01) in men with PCa detected whereas p-AMPK (p=0.05) was elevated only in those without PCa. Conclusion Metformin use is associated with reduced BCR after treatment of localized PCa when considering pre-diagnostic and cumulative dosing. In men with cancer detected on PNB, insulin signaling markers were significantly elevated compared to negative PNB patients. The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in negative PNBs suggests altered metabolic pathway activation precipitated by metformin use. PMID:26201966

The impact of socioeconomic status on stage specific prostate cancer survival and mortality before and after introduction of PSA test in Finland.

PubMed

Seikkula, Heikki A; Kaipia, Antti J; Ryynänen, Heidi; Seppä, Karri; Pitkäniemi, Janne M; Malila, Nea K; Boström, Peter J

2018-03-01

Socioeconomic status (SES) has an impact on prostate cancer (PCa) outcomes. Men with high SES have higher incidence and lower mortality of PCa versus lower SES males. PCa cases diagnosed in Finland in 1985-2014 (N = 95,076) were identified from the Finnish Cancer Registry. Information on education level (EL) was obtained from Statistics Finland. EL was assessed with three-tiered scale: basic, upper secondary and higher education. PCa stage at diagnosis was defined as localized, metastatic or unknown. Years of diagnosis 1985-1994 were defined as pre-PSA period and thereafter as post-PSA period. We report PCa-specific survival (PCSS) and relative risks (RR) for PCa specific mortality (PCSM) among cancer cases in Finland, where healthcare is 100% publicly reimbursed and inequality in healthcare services low. Men with higher EL had markedly better 10-year PCSS: 68 versus 63% in 1985-1994 and 90 versus 85% in 1995-2004 compared to basic EL in localized PCa. The RR for PCSM among men with localized PCa and higher EL compared to basic EL was 0.76(95%confidence interval (CI) 0.66-0.88) in 1985-1994 and 0.61(95%CI 0.53-0.70) in 1995-2004. Variation in PCSS and PCSM between EL categories was evident in metastatic PCa, too. The difference in PCSM between EL categories was larger in the first 10-year post-PSA period than before that but decreased thereafter in localized PCa, suggesting PSA testing became earlier popular among men with high EL. In summary, higher SES/EL benefit PCa survival both in local and disseminated disease and the effect of EL was more pronounced in early post-PSA period. © 2017 UICC.

A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling.

PubMed

Klein, Eric A; Cooperberg, Matthew R; Magi-Galluzzi, Cristina; Simko, Jeffry P; Falzarano, Sara M; Maddala, Tara; Chan, June M; Li, Jianbo; Cowan, Janet E; Tsiatis, Athanasios C; Cherbavaz, Diana B; Pelham, Robert J; Tenggara-Hunter, Imelda; Baehner, Frederick L; Knezevic, Dejan; Febbo, Phillip G; Shak, Steven; Kattan, Michael W; Lee, Mark; Carroll, Peter R

2014-09-01

Prostate tumor heterogeneity and biopsy undersampling pose challenges to accurate, individualized risk assessment for men with localized disease. To identify and validate a biopsy-based gene expression signature that predicts clinical recurrence, prostate cancer (PCa) death, and adverse pathology. Gene expression was quantified by reverse transcription-polymerase chain reaction for three studies-a discovery prostatectomy study (n=441), a biopsy study (n=167), and a prospectively designed, independent clinical validation study (n=395)-testing retrospectively collected needle biopsies from contemporary (1997-2011) patients with low to intermediate clinical risk who were candidates for active surveillance (AS). The main outcome measures defining aggressive PCa were clinical recurrence, PCa death, and adverse pathology at prostatectomy. Cox proportional hazards regression models were used to evaluate the association between gene expression and time to event end points. Results from the prostatectomy and biopsy studies were used to develop and lock a multigene-expression-based signature, called the Genomic Prostate Score (GPS); in the validation study, logistic regression was used to test the association between the GPS and pathologic stage and grade at prostatectomy. Decision-curve analysis and risk profiles were used together with clinical and pathologic characteristics to evaluate clinical utility. Of the 732 candidate genes analyzed, 288 (39%) were found to predict clinical recurrence despite heterogeneity and multifocality, and 198 (27%) were predictive of aggressive disease after adjustment for prostate-specific antigen, Gleason score, and clinical stage. Further analysis identified 17 genes representing multiple biological pathways that were combined into the GPS algorithm. In the validation study, GPS predicted high-grade (odds ratio [OR] per 20 GPS units: 2.3; 95% confidence interval [CI], 1.5-3.7; p<0.001) and high-stage (OR per 20 GPS units: 1.9; 95% CI, 1.3-3.0; p=0.003) at surgical pathology. GPS predicted high-grade and/or high-stage disease after controlling for established clinical factors (p<0.005) such as an OR of 2.1 (95% CI, 1.4-3.2) when adjusting for Cancer of the Prostate Risk Assessment score. A limitation of the validation study was the inclusion of men with low-volume intermediate-risk PCa (Gleason score 3+4), for whom some providers would not consider AS. Genes representing multiple biological pathways discriminate PCa aggressiveness in biopsy tissue despite tumor heterogeneity, multifocality, and limited sampling at time of biopsy. The biopsy-based 17-gene GPS improves prediction of the presence or absence of adverse pathology and may help men with PCa make more informed decisions between AS and immediate treatment. Prostate cancer (PCa) is often present in multiple locations within the prostate and has variable characteristics. We identified genes with expression associated with aggressive PCa to develop a biopsy-based, multigene signature, the Genomic Prostate Score (GPS). GPS was validated for its ability to predict men who have high-grade or high-stage PCa at diagnosis and may help men diagnosed with PCa decide between active surveillance and immediate definitive treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Disruption of MEK/ERK/c-Myc signaling radiosensitizes prostate cancer cells in vitro and in vivo.

PubMed

Ciccarelli, Carmela; Di Rocco, Agnese; Gravina, Giovanni Luca; Mauro, Annunziata; Festuccia, Claudio; Del Fattore, Andrea; Berardinelli, Paolo; De Felice, Francesca; Musio, Daniela; Bouché, Marina; Tombolini, Vincenzo; Zani, Bianca Maria; Marampon, Francesco

2018-06-29

Prostate cancer (PCa) cell radioresistance causes the failure of radiation therapy (RT) in localized or locally advanced disease. The aberrant accumulation of c-Myc oncoprotein, known to promote PCa onset and progression, may be due to the control of gene transcription and/or MEK/ERK-regulated protein stabilization. Here, we investigated the role of MEK/ERK signaling in PCa. LnCAP, 22Rv1, DU145, and PC3 PCa cell lines were used in in vitro and in vivo experiments. U0126, trametinib MEK/ERK inhibitors, and c-Myc shRNAs were used. Radiation was delivered using an x-6 MV photon linear accelerator. U0126 in vivo activity alone or in combination with irradiation was determined in murine xenografts. Inhibition of MEK/ERK signaling down-regulated c-Myc protein in PCa cell lines to varying extents by affecting expression of RNA and protein, which in turn determined radiosensitization in in vitro and in vivo xenograft models of PCa cells. The crucial role played by c-Myc in the MEK/ERK pathways was demonstrated in 22Rv1 cells by the silencing of c-Myc by means of short hairpin mRNA, which yielded effects resembling the targeting of MEK/ERK signaling. The clinically approved compound trametinib used in vitro yielded the same effects as U0126 on growth and C-Myc expression. Notably, U0126 and trametinib induced a drastic down-regulation of BMX, which is known to prevent apoptosis in cancer cells. The results of our study suggest that signal transduction-based therapy can, by disrupting the MEK/ERK/c-Myc axis, reduce human PCa radioresistance caused by increased c-Myc expression in vivo and in vitro and restores apoptosis signals.

Tumor and Plasma Met Levels in Non-Metastatic Prostate Cancer.

PubMed

Kaye, Deborah R; Pinto, Peter A; Cecchi, Fabiola; Reilly, Joseph; Semerjian, Alice; Rabe, Daniel C; Gupta, Gopal; Choyke, Peter L; Bottaro, Donald P

2016-01-01

To measure Met protein content in prostate biopsies guided by fused magnetic resonance and ultrasound imaging, and to measure soluble Met (sMet) protein concentration in plasma samples from patients presenting evidence of prostate cancer. 345 patients had plasma samples drawn prior to image-guided biopsy of the prostate. Of these, 32% had benign biopsies. Of the 236 that were positive for prostate adenocarcinoma (PCa), 132 treated by total prostatectomy had Gleason scores of 6 (17%), 7, (55%), 8 (16%), or 9-10 (12%). 23% had evidence of local invasion. Plasma samples were also obtained from 80 healthy volunteers. Tissue Met and plasma sMet were measured by two-site immunoassay; values were compared among clinically defined groups using non-parametric statistical tests to determine significant differences or correlations. PCa tumor Met correlated significantly with plasma sMet, but median values were similar among benign and malignant groups. Median plasma sMet values were also similar among those groups, although both medians were significantly above normal. Median Met content in primary PCa tumors and sMet concentrations were independent of Gleason score, final pathologic stage and age. Plasma sMet is not predictive of PCa or its severity in patients with organ-confined or locally invasive disease. Quantitative analysis of Met protein content and activation state in PCa tumor biopsy samples was highly feasible and may have value in follow-up to genomic and/or transcriptomic-based screens that show evidence of oncogenically relevant MET gene features that occur at relatively low frequency in non-metastatic PCa.

Imaging of prostate cancer with PET/CT using 18F-Fluorocholine

PubMed Central

Vali, Reza; Loidl, Wolfgang; Pirich, Christian; Langesteger, Werner; Beheshti, Mohsen

2015-01-01

While 18F-Fluorodeoxyglucose (18F-FDG) Positron-Emission Tomography (PET) has limited value in prostate cancer (PCa), it may be useful for specific subgroups of PCa patients with hormone-resistant poorly differentiated cell types. 18F-Fluorocholine (18F-FCH) PET/CT has been increasingly used in primary and recurrent PCa and has been shown to add valuable information. Although there is a correlation between the foci of activity and the areas of malignancy in the prostate gland, the clinical value of 18F-FCH is still controversial for detection of the malignant focus in the prostate. For the T-staging of PCa at diagnosis the value of 18F-FCH is limited. This is probably due to limited resolution of PET system and positive findings in benign prostate diseases. Conversely, 18F-FCH PET/CT is a promising imaging modality for the delineation of local and distant nodal recurrence and bone metastases and is poised to have an impact on therapy management. In this review, recent studies of 18F-FCH PET/CT in PCa are summarized. PMID:25973332

Improving couples' quality of life through a Web-based prostate cancer education intervention.

PubMed

Song, Lixin; Rini, Christine; Deal, Allison M; Nielsen, Matthew E; Chang, Hao; Kinneer, Patty; Teal, Randall; Johnson, David C; Dunn, Mary W; Mark, Barbara; Palmer, Mary H

2015-03-01

To evaluate the feasibility and acceptability of a newly developed web-based, couple-oriented intervention called Prostate Cancer Education and Resources for Couples (PERC). Quantitative, qualitative, mixed-methods approach. Oncology outpatient clinics at the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center at UNC–Chapel Hill. 26 patients with localized prostate cancer (PCa) and their partners. Pre- and postpilot quantitative assessments and a postpilot qualitative interview were conducted. General and PCa-specific symptoms, quality of life, psychosocial factors, PERC’s ease of use, and web activities. Improvement was shown in some PCa-specific and general symptoms (small effect sizes for patients and small-to-medium effect sizes for partners), overall quality of life, and physical and social domains of quality of life for patients (small effect sizes). Web activity data indicated high PERC use. Qualitative and quantitative analyses indicated that participants found PERC easy to use and understand,as well as engaging, of high quality, and relevant. Overall, participants were satisfied with PERC and reported that PERC improved their knowledge about symptom management and communication as a couple. PERC was a feasible, acceptable method of reducing the side effects of PCa treatment–related symptoms and improving quality of life. PERC has the potential to reduce the negative impacts of symptoms and enhance quality of life for patients with localized PCa and their partners, particularly for those who live in rural areas and have limited access to post-treatment supportive care.

DNA-PKcs Expression Is a Predictor of Biochemical Recurrence After Permanent Iodine 125 Interstitial Brachytherapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Molina, Sarah; Department of Radiation Oncology, CHU/Université de Poitiers, Poitiers; Guerif, Stéphane

Purpose: Predictive factors for biochemical recurrence (BCR) in localized prostate cancer (PCa) after brachytherapy are insufficient to date. Cellular radiosensitivity depends on DNA double-strand breaks, mainly repaired by the nonhomologous end-joining (NHEJ) system. We analyzed whether the expression of NHEJ proteins can predict BCR in patients treated by brachytherapy for localized PCa. Methods and Materials: From 983 PCa cases treated by brachytherapy between March 2000 and March 2012, 167 patients with available biopsy material suitable for in situ analysis were included in the study. The median follow-up time was 47 months. Twenty-nine patients experienced BCR. All slides were reviewed to reassessmore » the Gleason score. Expression of the key NHEJ proteins DNA-PKcs, Ku70, and Ku80, and the proliferation marker Ki67, was studied by immunohistochemistry performed on tissue microarrays. Results: The Gleason scores after review (P=.06) tended to be associated with BCR when compared with the score initially reported (P=.74). Both the clinical stage (P=.02) and the pretreatment prostate-specific antigen level (P=.01) were associated with biochemical failure. Whereas the expression of Ku80 and Ki67 were not predictive of relapse, positive DNA-PKcs nuclear staining (P=.003) and higher Ku70 expression (P=.05) were associated with BCR. On multivariate analysis, among pretreatment variables, only DNA-PKcs (P=.03) and clinical stage (P=.02) remained predictive of recurrence. None of the patients without palpable PCa and negative DNA-PKcs expression experienced biochemical failure, compared with 32% of men with palpable and positive DNA-PKcs staining that recurred. Conclusions: Our results suggest that DNA-PKcs could be a predictive marker of BCR after brachytherapy, and this might be a useful tool for optimizing the choice of treatment in low-risk PCa patients.« less

Exercise and prostate cancer: From basic science to clinical applications.

PubMed

Campos, Christian; Sotomayor, Paula; Jerez, Daniel; González, Javier; Schmidt, Camila B; Schmidt, Katharina; Banzer, Winfried; Godoy, Alejandro S

2018-06-01

Prostate cancer (PCa) is a disease of increasing medical significance worldwide. In developed countries, PCa is the most common non-skin cancer in men, and one of the leading causes of cancer-related deaths. Exercise is one of the environmental factors that have been shown to influence cancer risk. Moreover, systemic reviews and meta-analysis have suggested that total physical activity is related to a decrease in the risk of developing PCa. In addition, epidemiological studies have shown that exercise, after diagnosis, has benefits regarding PCa development, and positive outcome in patients under treatment. The standard treatment for locally advanced or metastatic PCa is Androgen deprivation therapy (ADT). ADT produces diverse side effects, including loss of libido, changes in body composition (increase abdominal fat), and reduced muscle mass, and muscle tone. Analysis of numerous research publications showed that aerobic and/or resistance training improve patient's physical condition, such us, cardiorespiratory fitness, muscle strength, physical function, body composition, and fatigue. Therefore, exercise might counteract several ADT treatment-induced side effects. In addition of the aforementioned benefits, epidemiological, and in vitro studies have shown that exercise might decrease PCa development. Thus, physical activity might attenuate the risk of PCa and supervised exercise intervention might improve deleterious effects of cancer treatment, such as ADT side effects. This review article provides evidence indicating that exercise could complement, and potentiate, the current standard treatments for advanced PCa, probably by creating an unfavorable microenvironment that can negatively affect tumor development, and progression. © 2018 Wiley Periodicals, Inc.

Expression of spermidine/spermine N(1) -acetyl transferase (SSAT) in human prostate tissues is related to prostate cancer progression and metastasis.

PubMed

Huang, Wei; Eickhoff, Jens C; Mehraein-Ghomi, Farideh; Church, Dawn R; Wilding, George; Basu, Hirak S

2015-08-01

Prostate cancer (PCa) in many patients remains indolent for the rest of their lives, but in some patients, it progresses to lethal metastatic disease. Gleason score is the current clinical method for PCa prognosis. It cannot reliably identify aggressive PCa, when GS is ≤ 7. It is shown that oxidative stress plays a key role in PCa progression. We have shown that in cultured human PCa cells, an activation of spermidine/spermine N(1) -acetyl transferase (SSAT; EC 2.3.1.57) enzyme initiates a polyamine oxidation pathway and generates copious amounts of reactive oxygen species in polyamine-rich PCa cells. We used RNA in situ hybridization and immunohistochemistry methods to detect SSAT mRNA and protein expression in two tissue microarrays (TMA) created from patient's prostate tissues. We analyzed 423 patient's prostate tissues in the two TMAs. Our data show that there is a significant increase in both SSAT mRNA and the enzyme protein in the PCa cells as compared to their benign counterpart. This increase is even more pronounced in metastatic PCa tissues as compared to the PCa localized in the prostate. In the prostatectomy tissues from early-stage patients, the SSAT protein level is also high in the tissues obtained from the patients who ultimately progress to advanced metastatic disease. Based on these results combined with published data from our and other laboratories, we propose an activation of an autocrine feed-forward loop of PCa cell proliferation in the absence of androgen as a possible mechanism of castrate-resistant prostate cancer growth. © 2015 Wiley Periodicals, Inc.

Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer.

PubMed

Xu, S; Adisetiyo, H; Tamura, S; Grande, F; Garofalo, A; Roy-Burman, P; Neamati, N

2015-07-14

Survivin and monoamine oxidase A (MAOA) levels are elevated in prostate cancer (PCa) compared to normal prostate glands. However, the relationship between survivin and MAOA in PCa is unclear. We examined MAOA expression in the prostate lobes of a conditional PTEN-deficient mouse model mirroring human PCa, with or without survivin knockout. We also silenced one gene at a time and examined the expression of the other. We further evaluated the combination of MAOA inhibitors and survivin suppressants on the growth, viability, migration and invasion of PCa cells. Survivin and MAOA levels are both increased in clinical PCa tissues and significantly associated with patients' survival. Survivin depletion delayed MAOA increase during PCa progression, and silencing MAOA decreased survivin expression. The combination of MAOA inhibitors and the survivin suppressants (YM155 and SC144) showed significant synergy on the inhibition of PCa cell growth, migration and invasion with concomitant decrease in survivin and MMP-9 levels. There is a positive feedback loop between survivin and MAOA expression in PCa. Considering that survivin suppressants and MAOA inhibitors are currently available in clinical trials and clinical use, their synergistic effects in PCa support a rapid translation of this combination to clinical practice.

Genetic variations in genes involved in testosterone metabolism are associated with prostate cancer progression: A Spanish multicenter study.

PubMed

Henríquez-Hernández, Luis Alberto; Valenciano, Almudena; Foro-Arnalot, Palmira; Álvarez-Cubero, María Jesús; Cozar, José Manuel; Suárez-Novo, José Francisco; Castells-Esteve, Manel; Fernández-Gonzalo, Pablo; De-Paula-Carranza, Belén; Ferrer, Montse; Guedea, Ferrán; Sancho-Pardo, Gemma; Craven-Bartle, Jordi; Ortiz-Gordillo, María José; Cabrera-Roldán, Patricia; Rodríguez-Melcón, Juan Ignacio; Herrera-Ramos, Estefanía; Rodríguez-Gallego, Carlos; Lara, Pedro C

2015-07-01

Prostate cancer (PCa) is an androgen-dependent disease. Nonetheless, the role of single nucleotide polymorphisms (SNPs) in genes encoding androgen metabolism remains an unexplored area. To investigate the role of germline variations in cytochrome P450 17A1 (CYP17A1) and steroid-5α-reductase, α-polypeptides 1 and 2 (SRD5A1 and SRD5A2) genes in PCa. In total, 494 consecutive Spanish patients diagnosed with nonmetastatic localized PCa were included in this multicenter study and were genotyped for 32 SNPs in SRD5A1, SRD5A2, and CYP17A1 genes using a Biotrove OpenArray NT Cycler. Clinical data were available. Genotypic and allelic frequencies, as well as haplotype analyses, were determined using the web-based environment SNPator. All additional statistical analyses comparing clinical data and SNPs were performed using PASW Statistics 15. The call rate obtained (determined as the percentage of successful determinations) was 97.3% of detection. A total of 2 SNPs in SRD5A1-rs3822430 and rs1691053-were associated with prostate-specific antigen level at diagnosis. Moreover, G carriers for both SNPs were at higher risk of presenting initial prostate-specific antigen levels>20ng/ml (Exp(B) = 2.812, 95% CI: 1.397-5.657, P = 0.004) than those who are AA-AA carriers. Haplotype analyses showed that patients with PCa nonhomozygous for the haplotype GCTTGTAGTA were at an elevated risk of presenting bigger clinical tumor size (Exp(B) = 3.823, 95% CI: 1.280-11.416, P = 0.016), and higher Gleason score (Exp(B) = 2.808, 95% CI: 1.134-6.953, P = 0.026). SNPs in SRD5A1 seem to affect the clinical characteristics of Spanish patients with PCa. Copyright © 2015 Elsevier Inc. All rights reserved.

Incidental prostate cancer in patients with muscle-invasive bladder cancer who underwent radical cystoprostatectomy.

PubMed

Tanaka, Toshikazu; Koie, Takuya; Ohyama, Chikara; Hashimoto, Yasuhiro; Imai, Atsushi; Tobisawa, Yuki; Hatakeyama, Shingo; Yamamoto, Hayato; Yoneyama, Tohru; Horiguchi, Hirotaka; Kodama, Hirotake; Yoneyama, Takahiro

2017-11-01

The aim of this study was to analyze the features of incidentally detected prostate cancer (PCa) in radical cystoprostatectomy (RCP) specimens to determine their pathological characteristics and clinical significance. In this retrospective study, we reviewed the clinical and pathological records of 431 consecutive patients with muscle-invasive bladder cancer who underwent RCP at Hirosaki University. Of these, we focused on 237 male patients with prostate-specific antigen (PSA) measurements and digital rectal examinations (DRE) that were recorded prior to the RCP. Significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, pathological T3 or higher stage, lymph node involvement or three or more multifocal lesions within the prostate specimen. We compared clinically significant and insignificant PCa. In this study, a total of 43 patients (18.1%) were diagnosed with incidental PCa via RCP specimens. Age, preoperative PSA levels and pathological T stage in patients with clinically significant PCa were considerably higher than in those with insignificant cancer. Apical involvement was found in 16 patients, including 11 of those with clinically significant PCa. By the end of the follow-up period, none of the enrolled patients had a biochemical recurrence after surgery or died from PCa. According to our findings, preoperative risk factors were not reliable enough to accurately predict clinically significant PCa. Although there was no biochemical relapse or clinical recurrence of PCa in this study, the potential oncologic risk of prostate-sparing RCP must be considered. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Diagnosis and treatment for clinically localized prostate cancer. Adherence to the European Association of Urology clinical guidelines in a nationwide population-based study - GESCAP group.

PubMed

Gómez-Veiga, F; Rodríguez-Antolín, A; Miñana, B; Hernández, C; Suárez, J F; Fernández-Gómez, J M; Unda, M; Burgos, J; Alcaraz, A; Rodríguez, P; Medina, R; Castiñeiras, J; Moreno, C; Pedrosa, E; Cózar, J M

To assess the adherence to European Association of Urology (EAU) guidelines in the management of prostate cancer (PCa) in Spain. Epidemiological, population-based, study including a national representative sample of 3,918 incident patients with histopathological confirmation during 2010; 95% of the patient's sample was followed up for at least one year. Diagnosis along with treatment related variables (for localized PCa -low, intermediate, high and locally-advanced by D'Amico risk stratification) was recorded. Differences between groups were tested with Chi-squared and Kruskal-Wallis tests. Mean (SD) age of PCa patients was 68.48 (8.18). Regarding diagnostic by biopsy procedures, 64.56% of all patients had 8-12 cores in first biopsy and 46.5% of the patients over 75 years, with PSA<10ng/mL were biopsied. Staging by Computer Tomography (CT) or Bone Scan (BS) was used for determining tumor extension in 60.09% of high-risk cases and was applied differentially depending on patients' age; 3,293 (84.05%) patients received a treatment for localized PCa. Radical prostatectomy was done in 1,277 patients and 206 out of these patients also had a lymphadenectomy, being 4.64% low-risk, 22.81% intermediate-risk and 36.00% high-risk patients; 86.08% of 1,082 patients who had radiotherapy were treated with 3D or IMRT and 35.77% received a dose ≥75Gy; 419 patients were treated with brachytherapy (BT): 54.81% were low-risk patients, 22.84% intermediate-risk and 12.98% high-risk. Hormonotherapy (HT, n=521) was applied as single therapy in 9.46% of low-risk and 17.92% of intermediate-risk patients. Additionally, HT was combined with RT in 14.34% of lower-risk patients and 58.26% of high-risk patients, and 67.19% low-intermediate risk with RT and/or BT received neoadjuvant/concomitant/adjuvant HT. Finally, 83.75% of high-risk patients undergoing RT and/or BT also received HT. Although EAU guidelines for PCa management are easily available in Europe, the adherence to their recommendations is low, finding the highest discrepancies in the need for a prostate biopsy and the diagnostic methods. Improve information and educational programs could allow a higher adherence to the guidelines and reduce the variability in daily practice. (Controlled-trials.com: ISRCTN19893319). Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

PubMed Central

Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

2011-01-01

Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

Clinicopathological characteristics of incidental prostate cancer discovered from radical cystoprostatectomy specimen: a multicenter French study.

PubMed

Pignot, Géraldine; Salomon, Laurent; Neuzillet, Yann; Masson-Lecomte, Alexandra; Lebacle, Cédric; Patard, Jean-Jacques; Lunardi, Pierre; Rischmann, Pascal; Pasticier, Gilles; Bernhard, Jean-Christophe; Cohen, Jérémy; Timsit, Marc-Olivier; Verkarre, Virginie; Peyronnet, Benoit; Verhoest, Gregory; Le Goux, Constance; Zerbib, Marc; Brecheteau, François; Bigot, Pierre; Larre, Stéphane; Murez, Thibault; Thuret, Rodolphe; Lacarriere, Emeric; Champy, Cécile; Roupret, Morgan; Comperat, Eva; Berger, Julien; Descazeaud, Aurélien; Toledano, Harry; Bastide, Cyrille; Lavilledieu, Sébastien; Avances, Christophe; Delage, Francky; Valeri, Antoine; Molimard, Benoit; Houlgatte, Alain; Gres, Pascal; Donnaint, Alain; Kleinclauss, François; Legal, Sophie; Doerfler, Arnaud; Koutlidis, Nicolas; Cormier, Luc; Hetet, Jean-François; Colls, Philippe; Arvin-Berod, Alexis; Rambeaud, Jean-Jacques; Quintens, Hervé; Soulie, Michel; Pfister, Christian

2014-02-01

The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated. We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa. Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7%). Most tumors (90.1%) were organ-confined (pT2), whereas 9.9% of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9%), 6 in 575 cases (61.7%), 7 (3 + 4) in 149 cases (16.0%), 7 (4 + 3) in 38 cases (4.1%), and >7 in 40 cases (4.3%). After a median follow-up of 25.5 months (interquartile range 14.2-47.4), 35.4% of patients had bladder cancer recurrence and 23.8% died of bladder cancer. Only 16 patients (1.9%) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa. The rate of incidentally diagnosed PCa in RCP specimens was 21.7%. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9% of cases during follow-up.

A urinary biomarker-based risk score correlates with multiparametric MRI for prostate cancer detection.

PubMed

Hendriks, Rianne J; van der Leest, Marloes M G; Dijkstra, Siebren; Barentsz, Jelle O; Van Criekinge, Wim; Hulsbergen-van de Kaa, Christina A; Schalken, Jack A; Mulders, Peter F A; van Oort, Inge M

2017-10-01

Prostate cancer (PCa) diagnostics would greatly benefit from more accurate, non-invasive techniques for the detection of clinically significant disease, leading to a reduction of over-diagnosis and over-treatment. The aim of this study was to determine the association between a novel urinary biomarker-based risk score (SelectMDx), multiparametric MRI (mpMRI) outcomes, and biopsy results for PCa detection. This retrospective observational study used data from the validation study of the SelectMDx score, in which urine was collected after digital rectal examination from men undergoing prostate biopsies. A subset of these patients also underwent a mpMRI scan of the prostate. The indications for performing mpMRI were based on persistent clinical suspicion of PCa or local staging after PCa was found upon biopsy. All mpMRI images were centrally reviewed in 2016 by an experienced radiologist blinded for the urine test results and biopsy outcome. The PI-RADS version 2 was used. In total, 172 patients were included for analysis. Hundred (58%) patients had PCa detected upon prostate biopsy, of which 52 (52%) had high-grade disease correlated with a significantly higher SelectMDx score (P < 0.01). The median SelectMDx score was significantly higher in patients with a suspicious significant lesion on mpMRI compared to no suspicion of significant PCa (P < 0.01). For the prediction of mpMRI outcome, the area-under-the-curve of SelectMDx was 0.83 compared to 0.66 for PSA and 0.65 for PCA3. There was a positive association between SelectMDx score and the final PI-RADS grade. There was a statistically significant difference in SelectMDx score between PI-RADS 3 and 4 (P < 0.01) and between PI-RADS 4 and 5 (P < 0.01). The novel urinary biomarker-based SelectMDx score is a promising tool in PCa detection. This study showed promising results regarding the correlation between the SelectMDx score and mpMRI outcomes, outperforming PCA3. Our results suggest that this risk score could guide clinicians in identifying patients at risk for significant PCa and selecting patients for further radiological diagnostics to reduce unnecessary procedures. © 2017 Wiley Periodicals, Inc.

Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy.

PubMed

Rubio-Briones, Jose; Borque, Angel; Esteban, Luis M; Casanova, Juan; Fernandez-Serra, Antonio; Rubio, Luis; Casanova-Salas, Irene; Sanz, Gerardo; Domínguez-Escrig, Jose; Collado, Argimiro; Gómez-Ferrer, Alvaro; Iborra, Inmaculada; Ramírez-Backhaus, Miguel; Martínez, Francisco; Calatrava, Ana; Lopez-Guerrero, Jose A

2015-09-11

PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference's nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. We detect 28% of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20% at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95%:0.68-0.79) and 0.786 for HGPCa (C.I.95%:0.71-0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40% could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31% for the threshold probability of 40%. PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40% should be counseled to undergo an IBx if opportunistic screening is required.

Activation of Beta-Catenin Signaling in Androgen Receptor–Negative Prostate Cancer Cells

PubMed Central

Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W.; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba S.; Troncoso, Patricia; Maity, Sankar N.; Navone, Nora M.

2012-01-01

Purpose To study Wnt/beta-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the beta-catenin–androgen receptor (AR) interaction. Experimental Design We performed beta-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of beta-catenin–mediated transcription), and sequenced the beta-catenin gene in MDA PCa 118a, MDA PCa 118b, MDA PCa 2b, and PC-3 prostate cancer (PCa) cells. We knocked down beta-catenin in AR-negative MDA PCa 118b cells and performed comparative gene-array analysis. We also immunohistochemically analyzed beta-catenin and AR in 27 bone metastases of human CRPCs. Results Beta-catenin nuclear accumulation and TOP-flash reporter activity were high in MDA PCa 118b but not in MDA PCa 2b or PC-3 cells. MDA PCa 118a and 118b cells carry a mutated beta-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA PCa 118b cells with downregulated beta-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant beta-catenin. Finally, we found nuclear localization of beta-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher’s exact test), suggesting that reduced AR expression enables Wnt/beta-catenin signaling. Conclusion We identified a previously unknown downstream target of beta-catenin, HAS2, in PCa, and found that high beta-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone-metastatic PCa. These findings may guide physicians in managing these patients. PMID:22298898

Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer

PubMed Central

Xu, S; Adisetiyo, H; Tamura, S; Grande, F; Garofalo, A; Roy-Burman, P; Neamati, N

2015-01-01

Background: Survivin and monoamine oxidase A (MAOA) levels are elevated in prostate cancer (PCa) compared to normal prostate glands. However, the relationship between survivin and MAOA in PCa is unclear. Methods: We examined MAOA expression in the prostate lobes of a conditional PTEN-deficient mouse model mirroring human PCa, with or without survivin knockout. We also silenced one gene at a time and examined the expression of the other. We further evaluated the combination of MAOA inhibitors and survivin suppressants on the growth, viability, migration and invasion of PCa cells. Results: Survivin and MAOA levels are both increased in clinical PCa tissues and significantly associated with patients' survival. Survivin depletion delayed MAOA increase during PCa progression, and silencing MAOA decreased survivin expression. The combination of MAOA inhibitors and the survivin suppressants (YM155 and SC144) showed significant synergy on the inhibition of PCa cell growth, migration and invasion with concomitant decrease in survivin and MMP-9 levels. Conclusions: There is a positive feedback loop between survivin and MAOA expression in PCa. Considering that survivin suppressants and MAOA inhibitors are currently available in clinical trials and clinical use, their synergistic effects in PCa support a rapid translation of this combination to clinical practice. PMID:26103574

Clinical map document based on XML (cMDX): document architecture with mapping feature for reporting and analysing prostate cancer in radical prostatectomy specimens.

PubMed

Eminaga, Okyaz; Hinkelammert, Reemt; Semjonow, Axel; Neumann, Joerg; Abbas, Mahmoud; Koepke, Thomas; Bettendorf, Olaf; Eltze, Elke; Dugas, Martin

2010-11-15

The pathology report of radical prostatectomy specimens plays an important role in clinical decisions and the prognostic evaluation in Prostate Cancer (PCa). The anatomical schema is a helpful tool to document PCa extension for clinical and research purposes. To achieve electronic documentation and analysis, an appropriate documentation model for anatomical schemas is needed. For this purpose we developed cMDX. The document architecture of cMDX was designed according to Open Packaging Conventions by separating the whole data into template data and patient data. Analogue custom XML elements were considered to harmonize the graphical representation (e.g. tumour extension) with the textual data (e.g. histological patterns). The graphical documentation was based on the four-layer visualization model that forms the interaction between different custom XML elements. Sensible personal data were encrypted with a 256-bit cryptographic algorithm to avoid misuse. In order to assess the clinical value, we retrospectively analysed the tumour extension in 255 patients after radical prostatectomy. The pathology report with cMDX can represent pathological findings of the prostate in schematic styles. Such reports can be integrated into the hospital information system. "cMDX" documents can be converted into different data formats like text, graphics and PDF. Supplementary tools like cMDX Editor and an analyser tool were implemented. The graphical analysis of 255 prostatectomy specimens showed that PCa were mostly localized in the peripheral zone (Mean: 73% ± 25). 54% of PCa showed a multifocal growth pattern. cMDX can be used for routine histopathological reporting of radical prostatectomy specimens and provide data for scientific analysis.

Clinical map document based on XML (cMDX): document architecture with mapping feature for reporting and analysing prostate cancer in radical prostatectomy specimens

PubMed Central

2010-01-01

Background The pathology report of radical prostatectomy specimens plays an important role in clinical decisions and the prognostic evaluation in Prostate Cancer (PCa). The anatomical schema is a helpful tool to document PCa extension for clinical and research purposes. To achieve electronic documentation and analysis, an appropriate documentation model for anatomical schemas is needed. For this purpose we developed cMDX. Methods The document architecture of cMDX was designed according to Open Packaging Conventions by separating the whole data into template data and patient data. Analogue custom XML elements were considered to harmonize the graphical representation (e.g. tumour extension) with the textual data (e.g. histological patterns). The graphical documentation was based on the four-layer visualization model that forms the interaction between different custom XML elements. Sensible personal data were encrypted with a 256-bit cryptographic algorithm to avoid misuse. In order to assess the clinical value, we retrospectively analysed the tumour extension in 255 patients after radical prostatectomy. Results The pathology report with cMDX can represent pathological findings of the prostate in schematic styles. Such reports can be integrated into the hospital information system. "cMDX" documents can be converted into different data formats like text, graphics and PDF. Supplementary tools like cMDX Editor and an analyser tool were implemented. The graphical analysis of 255 prostatectomy specimens showed that PCa were mostly localized in the peripheral zone (Mean: 73% ± 25). 54% of PCa showed a multifocal growth pattern. Conclusions cMDX can be used for routine histopathological reporting of radical prostatectomy specimens and provide data for scientific analysis. PMID:21078179

Contemporary management of men with high-risk localized prostate cancer in the United States.

PubMed

Weiner, A B; Matulewicz, R S; Schaeffer, E M; Liauw, S L; Feinglass, J M; Eggener, S E

2017-09-01

Surgery and radiation-based therapies are standard management options for men with clinically localized high-risk prostate cancer (PCa). Contemporary patterns of care are unknown. We hypothesize the use of surgery has steadily increased in more recent years. Using the National Cancer Data Base for 2004-2013, all men diagnosed with high-risk localized PCa were identified using National Comprehensive Cancer Network criteria. Temporal trends in initial management were assessed. Multivariable logistic regression was used to evaluate demographic and clinical factors associated with undergoing radical prostatectomy (RP). In total, 127 391 men were identified. Use of RP increased from 26% in 2004 to 42% in 2013 (adjusted risk ratio (RR) 1.51, 95% CI 1.42-1.60, P<0.001), while external beam radiation therapy (EBRT) decreased from 49% to 42% (P<0.001). African American men had lower odds of undergoing RP (unadjusted rate of 28%, adjusted RR 0.69, 95% CI 0.66-0.72, <0.001) compared to White men (37%). Age was inversely associated with likelihood of receiving RP. Having private insurance was significantly associated with the increased use of RP (vs Medicare, adjusted odds ratio 1.04, 95% CI 1.01-1.08, P=0.015). Biopsy Gleason scores 8-10 with and without any primary Gleason 5 pattern were associated with decreased odds of RP (vs Gleason score ⩽6, both P<0.001). Academic and comprehensive cancer centers were more likely to perform RP compared to community hospitals (both P<0.001). The likelihood of receiving RP for high-risk PCa dramatically increased from 2004 to 2013. By 2013, the use of RP and EBRT were similar. African American men, elderly men and those without private insurance were less likely to receive RP.

Prostate-Specific Antigen (PSA) Screening and New Biomarkers for Prostate Cancer (PCa)

PubMed Central

Rittenhouse, Harry; Hu, Xinhai; Cammann, Henning; Jung, Klaus

2014-01-01

Abstract PSA screening reduces PCa-mortality but the disadvantages overdiagnosis and overtreatment require multivariable risk-prediction tools to select appropriate treatment or active surveillance. This review explains the differences between the two largest screening trials and discusses the drawbacks of screening and its meta-analysisxs. The current American and European screening strategies are described. Nonetheless, PSA is one of the most widely used tumor markers and strongly correlates with the risk of harboring PCa. However, while PSA has limitations for PCa detection with its low specificity there are several potential biomarkers presented in this review with utility for PCa currently being studied. There is an urgent need for new biomarkers especially to detect clinically significant and aggressive PCa. From all PSA-based markers, the FDA-approved prostate health index (phi) shows improved specificity over percent free and total PSA. Another kallikrein panel, 4K, which includes KLK2 has recently shown promise in clinical research studies but has not yet undergone formal validation studies. In urine, prostate cancer gene 3 (PCA3) has also been validated and approved by the FDA for its utility to detect PCa. The potential correlation of PCA3 with cancer aggressiveness requires more clinical studies. The detection of the fusion of androgen-regulated genes with genes of the regulatory transcription factors in tissue of ~50% of all PCa-patients is a milestone in PCa research. A combination of the urinary assays for TMPRSS2:ERG gene fusion and PCA3 shows an improved accuracy for PCa detection. Overall, the field of PCa biomarker discovery is very exciting and prospective. PMID:27683457

Targeted Androgen Pathway Suppression in Localized Prostate Cancer: A Pilot Study

PubMed Central

Mostaghel, Elahe A.; Nelson, Peter S.; Lange, Paul; Lin, Daniel W.; Taplin, Mary Ellen; Balk, Steven; Ellis, William; Kantoff, Philip; Marck, Brett; Tamae, Daniel; Matsumoto, Alvin M.; True, Lawrence D.; Vessella, Robert; Penning, Trevor; Hunter Merrill, Rachel; Gulati, Roman; Montgomery, Bruce

2014-01-01

Purpose Ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer (PCa) survival and proliferation. The failure to completely ablate tissue androgens may limit suppression of PCa growth. We evaluated combinations of CYP17A and 5-α-reductase inhibitors for reducing prostate androgen levels, AR signaling, and PCa volumes. Patients and Methods Thirty-five men with intermediate/high-risk clinically localized PCa were randomly assigned to goserelin combined with dutasteride (ZD), bicalutamide and dutasteride (ZBD), or bicalutamide, dutasteride, and ketoconazole (ZBDK) for 3 months before prostatectomy. Controls included patients receiving combined androgen blockade with luteinizing hormone-releasing hormone agonist and bicalutamide. The primary outcome measure was tissue dihydrotestosterone (DHT) concentration. Results Prostate DHT levels were substantially lower in all experimental arms (0.02 to 0.04 ng/g v 0.92 ng/g in controls; P < .001). The ZBDK group demonstrated the greatest percentage decline in serum testosterone, androsterone, and dehydroepiandrosterone sulfate (P < .05 for all). Staining for AR and the androgen-regulated genes prostate-specific antigen and TMPRSS2 was strongly suppressed in benign glands and moderately in malignant glands (P < .05 for all). Two patients had pathologic complete response, and nine had ≤ 0.2 cm3 of residual tumor (defined as a near-complete response), with the largest numbers of complete and near-complete responses in the ZBDK group. Conclusion Addition of androgen synthesis inhibitors lowers prostate androgens below that achieved with standard therapy, but significant AR signaling remains. Tissue-based analysis of steroids and AR signaling is critical to informing the search for optimal local and systemic control of high-risk prostate cancer. PMID:24323034

Tumor Volume and Metabolism of Prostate Cancer Determined by Proton Magnetic Resonance Spectroscopic Imaging at 3T Without Endorectal Coil Reveal Potential Clinical Implications in the Context of Radiation Oncology;Prostate cancer; Magnetic resonance spectroscopic imaging; Radiation oncology; Tumor volume; Biomarkers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crehange, Gilles, E-mail: gcrehange@cgfl.fr; Parfait, Sebastien; Liegard, Melanie

2011-07-15

Purpose: To determine whether a relationship exists between the tumor volume (TV) or relative choline content determined using magnetic resonance spectroscopy imaging (MRSI) at 3T and the clinical prognostic parameters for patients with localized prostate cancer (PCa). Methods and Materials: A total of 72 men (mean age, 67.8 {+-} 6.2 years) were stratified as having low-risk (n = 26), intermediate-risk (n = 24), or high-risk (n = 22) PCa. MRSI was performed at 3T using a phased-array coil. Spectra are expressed as the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamines plus creatine/citrate ratios. The mean ratiomore » of the most pathologic voxels and the MRSI-based TV were also determined. Results: The mean values of the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamine plus creatine/citrate ratios were greater for Stage T2b or greater tumors vs. Stage T2a or less tumors: 7.53 {+-} 13.60 vs. 2.31 {+-} 5.65 (p = .018), 8.98 {+-} 14.58 vs. 2.56 {+-} 5.70 (p = .016), and 10.32 {+-} 15.47 vs. 3.55 {+-} 6.16 (p = .014), respectively. The mean MRSI-based TV for Stage T2b or greater and Stage T2a or less tumors was significantly different (2.23 {+-} 2.62 cm{sup 3} vs. 1.26 {+-} 2.06 cm{sup 3}, respectively; p = .030). This TV correlated with increased prostate-specific antigen levels (odds ratio, 1.293; p = .012). Patients with high-risk PCa had a larger TV than did the patients with intermediate-risk PCa. A similar result was found for the intermediate-risk group compared with the low-risk group (odds ratio, 1.225; p = .041). Conclusion: Biomarkers expressing the relative choline content and TV were significant parameters for the localization of PCa and could be helpful for determining the prognosis more accurately.« less

Prostate atypia: does repeat biopsy detect clinically significant prostate cancer?

PubMed

Dorin, Ryan P; Wiener, Scott; Harris, Cory D; Wagner, Joseph R

2015-05-01

While the treatment pathway in response to benign or malignant prostate biopsies is well established, there is uncertainty regarding the risk of subsequently diagnosing prostate cancer when an initial diagnosis of prostate atypia is made. As such, we investigated the likelihood of a repeat biopsy diagnosing prostate cancer (PCa) in patients in which an initial biopsy diagnosed prostate atypia. We reviewed our prospectively maintained prostate biopsy database to identify patients who underwent a repeat prostate biopsy within one year of atypia (atypical small acinar proliferation; ASAP) diagnosis between November 1987 and March 2011. Patients with a history of PCa were excluded. Chart review identified patients who underwent radical prostatectomy (RP), radiotherapy (RT), or active surveillance (AS). For some analyses, patients were divided into two subgroups based on their date of service. Ten thousand seven hundred and twenty patients underwent 13,595 biopsies during November 1987-March 2011. Five hundred and sixty seven patients (5.3%) had ASAP on initial biopsy, and 287 (50.1%) of these patients underwent a repeat biopsy within one year. Of these, 122 (42.5%) were negative, 44 (15.3%) had atypia, 19 (6.6%) had prostatic intraepithelial neoplasia, and 102 (35.6%) contained PCa. Using modified Epstein's criteria, 27/53 (51%) patients with PCa on repeat biopsy were determined to have clinically significant tumors. 37 (36.3%) proceeded to RP, 25 (24.5%) underwent RT, and 40 (39.2%) received no immediate treatment. In patients who underwent surgery, Gleason grade on final pathology was upgraded in 11 (35.5%), and downgraded 1 (3.2%) patient. ASAP on initial biopsy was associated with a significant risk of PCa on repeat biopsy in patients who subsequently underwent definitive local therapy. Patients with ASAP should be counseled on the probability of harboring both clinically significant and insignificant prostate cancer. © 2015 Wiley Periodicals, Inc.

Primary cutaneous amyloidosis associated with autoimmune hepatitis-primary biliary cirrhosis overlap syndrome and Sjögren syndrome

PubMed Central

Yan, Xin; Jin, Jinglan

2018-01-01

Abstract Rationale: Primary cutaneous amyloidosis (PCA) is a localized skin disorder characterized by the abnormal deposition of amyloid in the extracellular matrix of the dermis. The association between PCA and other diseases, although rare, has been documented for various autoimmune diseases. PCA associated with autoimmune hepatitis-primary biliary cirrhosis (AIH-PBC) overlap syndrome and Sjögren syndrome (SS) has not been previously reported in the literature. Patient concerns: A 50-year-old woman presented with progressive abnormal liver enzyme levels and was referred to our department. Diagnoses: Due to the patient's symptoms, laboratory test results, radiographic findings, and pathologic results, she was diagnosed with PCA associated with AIH-PBC overlap syndrome and SS. Interventions: She was subsequently treated with a combination of ursodeoxycholic acid (UDCA), prednisone, and azathioprine. Outcomes: While this treatment can achieve therapeutic success, it cannot prevent complications from cirrhosis. This patient remains alive but experienced an emergent gastrointestinal hemorrhage. Lessons: While we acknowledge that this is a single case, these findings extend our knowledge of immunological diseases associated with PCA and suggest a common, immune-mediated pathogenic pathway between PCA, AIH-PBC overlap syndrome, and SS. After 12 years of follow up, clinical manifestations have developed, and these autoimmune diseases have progressed. The combination of UDCA, prednisone, and azathioprine can achieve therapeutic success but cannot prevent disease progression. Routine follow up for this patient is necessary to document disease progression. PMID:29465536

Evaluation of Vitronectin Expression in Prostate Cancer and the Clinical Significance of the Association of Vitronectin Expression with Prostate Specific Antigen in Detecting Prostate Cancer.

PubMed

Niu, Yue; Zhang, Ling; Bi, Xing; Yuan, Shuai; Chen, Peng

2016-03-05

To detect the expression of vitronectin (VTN) in the tissues and blood serum of prostate cancer (PCa) patients, and evaluate its clinical significance and to evaluate the significance of the combined assay of VTN and prostate specific antigens (PSA) in PCa diagnosis. To detect the expression of VTN as a potential marker for PCa diagnosis and prognosis, immunohistochemistry was performed on the tissues of 32 patients with metastatic PCa (PCaM), 34 patients with PCa without metastasis (PCa), and 41 patients with benign prostatic hyperplasia (BPH). The sera were then subjected to Western blot analysis. All cases were subsequently examined to determine the concentrations of PSA and VTN in the sera. The collected data were collated and analyzed. The positive expression rates of VTN in the tissues of the BPH and PCa groups (including PCa and PCaM groups) were 75.61% and 45.45%, respectively (P = .005). VTN was more highly expressed in the sera of the BPH patients (0.83 ± 0.07) than in the sera of the PCa patients (0.65 ± 0.06) (P < .05). It was also more highly expressed in the sera of the PCa patients than in the sera of the PCaM patients (0.35 ± 0.08) (P < .05). In the diagnosis of BPH and PCa, the Youden indexes of PSA detection, VTN detection, and combined detection were 0.2620, 0.3468, and 0.5635; the kappa values were 0.338, 0.304, and 0.448, respectively, and the areas under the receiver operating characteristic curve were 0.625, 0.673, and 0.703 (P < .05), respectively. VTN levels in sera may be used as a potential marker of PCa for the diagnosis and assessment of disease progression and metastasis. The combined detection of VTN and PSA in sera can be clinically applied in PCa diagnosis. .

Nanomedicine for prostate cancer using nanoemulsion: A review.

PubMed

Sasikumar, Aravindsiva; Kamalasanan, Kaladhar

2017-08-28

Prostate cancer (PCa) is a worldwide issue, with burgeoning rise in prevalence, morbidity and mortality. Targeted drug delivery, a long sort solution in this regard using controlled release (CR) - nanocarriers, is still a challenge. There is an emerging criticism that, the challenges are due to less appreciation for the biological barriers and lack of corresponding newer technologies. Over the years, more understanding about the biological barriers has come with the progress in characterization techniques. Correspondingly, there is a change in opinion about approaches in clinical trial that; focus of the end point need to be shifted towards disease stabilization for these explorative technologies. Currently, there is a requirement to overcome these newly identified challenges to develop newer affordable therapeutics. The ongoing clinical protocol for therapy using CR-nanocarriers is intravenous injection followed by local targeting to cancer site. This is the most accepted protocol and new CR-nanocarriers are being developed to suit this protocol. In this review, recent progress in treatment of PCa using CR-nanocarriers is analyzed with respect to newly identified biological barriers and design challenges. Possibilities of exploring nanoemulsion (NE) platform for targeted drug delivery to PCa are examined. Repurposing of drugs and combination therapy using NE platform targeted to PCa can be explored for design and development of affordable nanomedicine. In 20yrs. from now there expected to be numerous affordable nanomedicine technologies available in market exploring these lines. Copyright © 2017 Elsevier B.V. All rights reserved.

A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthal, Seth A., E-mail: rosents@sutterhealth.org; Hunt, Daniel; Sartor, A. Oliver

Purpose: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS). Methods and Materials: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥7 or clinical stage ≥T2 and GS ≥8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT.more » AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. Results: A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61). Conclusions: NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for the feasibility of clinical trial accrual and tolerability using CT for PCa.« less

Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis.

PubMed

Dell'Atti, Lucio

2015-03-31

We retrospectively reviewed data of patients with incidental prostate cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. 11 out of 64 patients (17.2%) who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as significant PCa, while 8 cases (72.7%) were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79). During the follow-up, biochemical recurrence occurred in 1 patient (9%). Concerning the cancer specific survival there was no statistical significance (P = 0.326) between the clinically significant and clinical insignificant cancer group. In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

Active surveillance for localized prostate cancer: an analysis of patient contacts and utilization of healthcare resources.

PubMed

Thomsen, Frederik B; Berg, Kasper D; Røder, M Andreas; Iversen, Peter; Brasso, Klaus

2015-02-01

Evidence supports active surveillance (AS) as a means to reduce overtreatment of low-risk prostate cancer (PCa). The consequences of close and long-standing follow-up with regard to outpatient visits, tests and repeated biopsies are widely unknown. This study investigated the trajectory and costs of AS in patients with localized PCa. In total, 317 PCa patients were followed in a prospective, single-arm AS cohort. The primary outcomes were number of patient contacts, prostate-specific antigen (PSA) tests, biopsies, hospital admissions due to biopsy complications and patients eventually undergoing curative treatment. The secondary outcome was cost. The 5 year cumulative incidence of discontinued AS in a competing-risk model was 40%. During the first 5 years of AS patients underwent a median of two biopsy sets, and patients were seen in an outpatient clinic including PSA testing three to four times annually. In total, 38 of the 406 biopsy sessions led to hospital admission and 87 of the 317 patients required treatment for bladder outlet obstruction (BOO). With a median of 3.7 years' follow-up, the total cost of AS was euro (€) 1,240,286. Assuming all patients had otherwise undergone primary radical prostatectomy, the cost difference favoured AS with a net benefit of €662,661 (35% reduction). AS entails a close clinical follow-up with a considerable risk of rebiopsy complication, treatment of BOO and subsequent delayed definitive therapy. This risk should be weighed against a potential economic benefit and reduction in the risk of overtreatment compared to immediate radical treatment.

Differential blood-based diagnosis between benign prostatic hyperplasia and prostate cancer: miRNA as source for biomarkers independent of PSA level, Gleason score, or TNM status.

PubMed

Leidinger, Petra; Hart, Martin; Backes, Christina; Rheinheimer, Stefanie; Keck, Bastian; Wullich, Bernd; Keller, Andreas; Meese, Eckart

2016-08-01

Since the benefit of prostate-specific antigen (PSA) screening remains controversial, new non-invasive biomarkers for prostate carcinoma (PCa) are still required. There is evidence that microRNAs (miRNAs) in whole peripheral blood can separate patients with localized prostate cancer from healthy individuals. However, the potential of blood-based miRNAs for the differential diagnosis of PCa and benign prostatic hyperplasia (BPH) has not been tested. We compared the miRNome from blood of PCa and BPH patients and further investigated the influence of the tumor volume, tumor-node-metastasis (TNM) classification, Gleason score, pretreatment risk status, and the pretreatment PSA value on the miRNA pattern. By microarray approach, we identified seven miRNAs that were significantly deregulated in PCa patients compared to BPH patients. Using quantitative real time PCR (qRT-PCR), we confirmed downregulation of hsa-miR-221* (now hsa-miR-221-5p) and hsa-miR-708* (now hsa-miR-708-3p) in PCa compared to BPH. Clinical parameters like PSA level, Gleason score, or TNM status seem to have only limited impact on the overall abundance of miRNAs in patients' blood, suggesting a no influence of these factors on the expression of deregulated miRNAs.

Prognostic significance of epithelial/stromal caveolin-1 expression in prostatic hyperplasia, high grade prostatic intraepithelial hyperplasia and prostatic carcinoma and its correlation with microvessel density.

PubMed

Mohammed, Dareen A; Helal, Duaa S

2017-03-01

Caveolin-1 may play a role in cancer development and progression. The aim was to record the expression and localization of caveolin-1 in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostatic carcinoma (PCa). Microvessel density was evaluated with CD34 immunostain. Correlations with known prognostic factors of PCa were recorded. Immunohistochemical expression of caveolin-1 and the MVD was evaluated in 65 cases; BPH (25), HGPIN (20) and PCa (20). Stromal caveolin-1expression was significantly higher in BPH than HGPIN and PCca. There was significant inverse relation between stromal caveolin-1 expression and extension to lymph node and seminal vesicle in carcinoma cases. Epithelial caveolin-1 was significantly higher in carcinomas than in BPH and HGPIN. Epithelial expression in carcinoma was significantly associated with preoperative PSA, Gleason score and lymph node extension. MVD was significantly higher in PCa than in BPH and HGPIN. There were significant relations between MVD and preoperative PSA, Gleason score, lymph node and seminal vesicle extension. Stromal caveolin-1 was associated with low MVD while epithelial caveolin-1 with high MVD. Caveolin-1 plays an important role in prostatic carcinogenesis and metastasis. Stromal expression of caveolin-1 in PCa is lowered in relation to BPH and HGPIN. In PCa; stromal caveolin-1 was associated with good prognostic parameters. Epithelial caveolin-1 is significantly increased in PCa than BPH and HGPIN. It is associated with clinically aggressive disease. Caveolin-1 may play a role in angiogenesis. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

DNA vaccination for prostate cancer, from preclinical to clinical trials - where we stand?

PubMed Central

2012-01-01

Development of various vaccines for prostate cancer (PCa) is becoming an active research area. PCa vaccines are perceived to have less toxicity compared with the available cytotoxic agents. While various immune-based strategies can elicit anti-tumour responses, DNA vaccines present increased efficacy, inducing both humoural and cellular immunity. This immune activation has been proven effective in animal models and initial clinical trials are encouraging. However, to validate the role of DNA vaccination in currently available PCa management paradigms, strong clinical evidence is still lacking. This article provides an overview of the basic principles of DNA vaccines and aims to provide a summary of preclinical and clinical trials outlining the benefits of this immunotherapy in the management of PCa. PMID:23046944

Is robotic surgery cost-effective: yes.

PubMed

Liberman, Daniel; Trinh, Quoc-Dien; Jeldres, Claudio; Zorn, Kevin C

2012-01-01

With the expanding use of new technology in the treatment of clinically localized prostate cancer (PCa), the financial burden on the healthcare system and the individual has been important. Robotics offer many potential advantages to the surgeon and the patient. We assessed the potential cost-effectiveness of robotics in urological surgery and performed a comparative cost analysis with respect to other potential treatment modalities. The direct and indirect costs of purchasing, maintaining, and operating the robot must be compared to alternatives in treatment of localized PCa. Some expanding technologies including intensity-modulated radiation therapy are significantly more expensive than robotic surgery. Furthermore, the benefits of robotics including decreased length of stay and return to work are considerable and must be measured when evaluating its cost-effectiveness. Robot-assisted laparoscopic surgery comes at a high cost but can become cost-effective in mostly high-volume centers with high-volume surgeons. The device when utilized to its maximum potential and with eventual market-driven competition can become affordable.

Risk Stratification Among Men With Prostate Imaging Reporting and Data System Version 2 Category 3 Transition Zone Lesions: Is Biopsy Always Necessary?

PubMed Central

Felker, Ely R.; Raman, Steven S.; Margolis, Daniel J.; Lu, David S. K.; Shaheen, Nicholas; Natarajan, Shyam; Sharma, Devi; Huang, Jiaoti; Dorey, Fred; Marks, Leonard S.

2017-01-01

OBJECTIVE The objective of our study was to determine the clinical and MRI characteristics of clinically significant prostate cancer (PCA) (Gleason score ≥ 3 + 4) in men with Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) category 3 transition zone (TZ) lesions. MATERIALS AND METHODS From 2014 to 2016, 865 men underwent prostate MRI and MRI/ultrasound (US) fusion biopsy (FB). A subset of 90 FB-naïve men with 96 PI-RADSv2 category 3 TZ lesions was identified. Patients were imaged at 3 T using a body coil. Images were assigned a PI-RADSv2 category by an experienced radiologist. Using clinical data and imaging features, we performed univariate and multivariate analyses to identify predictors of clinically significant PCA. RESULTS The mean patient age was 66 years, and the mean prostate-specific antigen density (PSAD) was 0.13 ng/mL2. PCA was detected in 34 of 96 (35%) lesions, 14 of which (15%) harbored clinically significant PCA. In univariate analysis, DWI score, prostate volume, and PSAD were significant predictors (p < 0.05) of clinically significant PCA with a suggested significance for apparent diffusion coefficient (ADC) and prostate-specific antigen value (p < 0.10). On multivariate analysis, PSAD and lesion ADC were the most important covariates. The combination of both PSAD of 0.15 ng/mL2 or greater and an ADC value of less than 1000 mm2/s yielded an AUC of 0.91 for clinically significant PCA (p < 0.001). If FB had been restricted to these criteria, only 10 of 90 men would have undergone biopsy, resulting in diagnosis of clinically significant PCA in 60% with eight men (9%) misdiagnosed (false-negative). CONCLUSION The yield of FB in men with PI-RADSv2 category 3 TZ lesions for clinically significant PCA is 15% but significantly improves to 60% (AUC > 0.9) among men with PSAD of 0.15 ng/mL2 or greater and lesion ADC value of less than 1000 mm2/s. PMID:28858541

Diagnostic and predictive value of urine PCA3 gene expression for the clinical management of patients with altered prostatic specific antigen.

PubMed

Rodón, N; Trías, I; Verdú, M; Román, R; Domínguez, A; Calvo, M; Banus, J M; Ballesta, A M; Maestro, M L; Puig, X

2014-04-01

Analyze the impact of the introduction of the study of PCA3 gene in post-prostatic massage urine in the clinical management of patients with PSA altered, evaluating its diagnostic ability and predictive value of tumor aggressiveness. Observational, prospective, multicenter study of patients with suspected prostate cancer (PC) candidates for biopsy. We present a series of 670 consecutive samples of urine collected post-prostatic massage for three years in which we determined the "PCA3 score" (s-PCA3). Biopsy was only indicated in cases with s-positive PCA3. The s-PCA3 was positive in 43.7% of samples. In the 124 biopsies performed, the incidence of PC or atypical small acinar proliferation was 54%, reaching 68,6% in s-PCA3≥100. Statistically significant relationship between the s-PCA3 and tumor grade was demonstrated. In cases with s-PCA3 between 35 and 50 only 23% of PC were high grade (Gleason≥7), compared to 76.7% in cases with s-PCA3 over 50. There was a statistically significant correlation between s-PCA3 and cylinders affected. Both relationships were confirmed by applying a log-linear model. The incorporation of PCA3 can avoid the need for biopsies in 54% of patients. s-PCA3 positivity increases the likelihood of a positive biopsy, especially in higher s-PCA3 100 (68.6%). s-PCA3 is also an indicator of tumor aggressiveness and provides essential information in making treatment decisions. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Contrast-Enhanced Ultrasound Angiogenesis Imaging by Mutual Information Analysis for Prostate Cancer Localization.

PubMed

Schalk, Stefan G; Demi, Libertario; Bouhouch, Nabil; Kuenen, Maarten P J; Postema, Arnoud W; de la Rosette, Jean J M C H; Wijkstra, Hessel; Tjalkens, Tjalling J; Mischi, Massimo

2017-03-01

The role of angiogenesis in cancer growth has stimulated research aimed at noninvasive cancer detection by blood perfusion imaging. Recently, contrast ultrasound dispersion imaging was proposed as an alternative method for angiogenesis imaging. After the intravenous injection of an ultrasound-contrast-agent bolus, dispersion can be indirectly estimated from the local similarity between neighboring time-intensity curves (TICs) measured by ultrasound imaging. Up until now, only linear similarity measures have been investigated. Motivated by the promising results of this approach in prostate cancer (PCa), we developed a novel dispersion estimation method based on mutual information, thus including nonlinear similarity, to further improve its ability to localize PCa. First, a simulation study was performed to establish the theoretical link between dispersion and mutual information. Next, the method's ability to localize PCa was validated in vivo in 23 patients (58 datasets) referred for radical prostatectomy by comparison with histology. A monotonic relationship between dispersion and mutual information was demonstrated. The in vivo study resulted in a receiver operating characteristic (ROC) curve area equal to 0.77, which was superior (p = 0.21-0.24) to that obtained by linear similarity measures (0.74-0.75) and (p <; 0.05) to that by conventional perfusion parameters (≤0.70). Mutual information between neighboring time-intensity curves can be used to indirectly estimate contrast dispersion and can lead to more accurate PCa localization. An improved PCa localization method can possibly lead to better grading and staging of tumors, and support focal-treatment guidance. Moreover, future employment of the method in other types of angiogenic cancer can be considered.

Initial results of 3-dimensional 1H-magnetic resonance spectroscopic imaging in the localization of prostate cancer at 3 Tesla: should we use an endorectal coil?

PubMed

Yakar, Derya; Heijmink, Stijn W T P J; Hulsbergen-van de Kaa, Christina A; Huisman, Henkjan; Barentsz, Jelle O; Fütterer, Jurgen J; Scheenen, Tom W J

2011-05-01

The purpose of this study was to compare the diagnostic performance of 3 Tesla, 3-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) in the localization of prostate cancer (PCa) with and without the use of an endorectal coil (ERC). Our prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. Between October 2004 and January 2006, 18 patients with histologically proven PCa on biopsy and scheduled for radical prostatectomy were included and underwent 3D-MRSI with and without an ERC. The prostate was divided into 14 regions of interest (ROIs). Four readers independently rated (on a 5-point scale) their confidence that cancer was present in each of these ROIs. These findings were correlated with whole-mount prostatectomy specimens. Areas under the receiver-operating characteristic curve were determined. A difference with a P < 0.05 was considered significant. A total of 504 ROIs were rated for the presence and absence of PCa. Localization of PCa with MRSI with the use of an ERC had a significantly higher areas under the receiver-operating characteristic curve (0.68) than MRSI without the use of an ERC (0.63) (P = 0.015). The use of an ERC in 3D MRSI in localizing PCa at 3 Tesla slightly but significantly increased the localization performance compared with not using an ERC.

Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017.

PubMed

Giri, Veda N; Knudsen, Karen E; Kelly, William K; Abida, Wassim; Andriole, Gerald L; Bangma, Chris H; Bekelman, Justin E; Benson, Mitchell C; Blanco, Amie; Burnett, Arthur; Catalona, William J; Cooney, Kathleen A; Cooperberg, Matthew; Crawford, David E; Den, Robert B; Dicker, Adam P; Eggener, Scott; Fleshner, Neil; Freedman, Matthew L; Hamdy, Freddie C; Hoffman-Censits, Jean; Hurwitz, Mark D; Hyatt, Colette; Isaacs, William B; Kane, Christopher J; Kantoff, Philip; Karnes, R Jeffrey; Karsh, Lawrence I; Klein, Eric A; Lin, Daniel W; Loughlin, Kevin R; Lu-Yao, Grace; Malkowicz, S Bruce; Mann, Mark J; Mark, James R; McCue, Peter A; Miner, Martin M; Morgan, Todd; Moul, Judd W; Myers, Ronald E; Nielsen, Sarah M; Obeid, Elias; Pavlovich, Christian P; Peiper, Stephen C; Penson, David F; Petrylak, Daniel; Pettaway, Curtis A; Pilarski, Robert; Pinto, Peter A; Poage, Wendy; Raj, Ganesh V; Rebbeck, Timothy R; Robson, Mark E; Rosenberg, Matt T; Sandler, Howard; Sartor, Oliver; Schaeffer, Edward; Schwartz, Gordon F; Shahin, Mark S; Shore, Neal D; Shuch, Brian; Soule, Howard R; Tomlins, Scott A; Trabulsi, Edouard J; Uzzo, Robert; Vander Griend, Donald J; Walsh, Patrick C; Weil, Carol J; Wender, Richard; Gomella, Leonard G

2018-02-01

Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.

Percutaneous Cryoablation of Solitary, Sporadic Renal Cell Carcinoma: Outcome Analysis Based on Clear-Cell versus Papillary Subtypes.

PubMed

Haddad, Mustafa M; Schmit, Grant D; Kurup, A Nicholas; Schmitz, John J; Boorjian, Stephen A; Geske, Jennifer; Thompson, R Houston; Callstrom, Matthew R; Atwell, Thomas D

2018-06-07

To evaluate treatment outcomes with percutaneous cryoablation (PCA) based on renal cell carcinoma (RCC) histology. Patients treated with PCA for a solitary, sporadic stage T1a RCC from 2003 to 2016 were identified from a single institution's renal ablation registry. Patients with multiple tumors, history of RCC, or genetic syndromes associated with RCC (n = 60); no specific RCC subtype determined from core biopsy (n = 66); RCC subtype other than clear-cell or papillary (n = 7); or less than 3 mo of follow-up imaging (n = 5) were excluded. In total, 173 patients met study inclusion criteria. Oncologic outcomes, clinical outcomes, and complications were evaluated based on tumor subtype. Of the 173 patients who underwent PCA for a stage T1a RCC, 130 (75%) had clear-cell RCC (ccRCC) and 43 (25%) had papillary RCC (pRCC). Median tumor size was 2.9 cm (range, 1.3-4.0 cm). Technically successful cryoablation was achieved in all 173 patients. Local tumor recurrence developed in 6 patients with ccRCC (4.6%), new renal tumors developed in 1 patient (0.8%), and metastatic RCC developed in 1 patient (0.8%) who also had local tumor recurrence. No patients with pRCC showed local tumor recurrence, new renal tumors, or metastatic disease. The 5-year disease-free survival rate in patients with ccRCC was 88%, compared with 100% in patients with pRCC (P = .48). Nine patients (5.2%), all with ccRCC, experienced major complications (P = .11). Percutaneous ablation is a viable treatment option for patients with clinical stage T1a pRCC and ccRCC. Percutaneous ablation may be a very favorable treatment strategy particularly for pRCC. Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.

Impact of a robotic surgical system on treatment choice for men with clinically organ-confined prostate cancer.

PubMed

Kobayashi, Takashi; Kanao, Kent; Araki, Motoo; Terada, Naoki; Kobayashi, Yasuyuki; Sawada, Atsuro; Inoue, Takahiro; Ebara, Shin; Watanabe, Toyohiko; Kamba, Tomomi; Sumitomo, Makoto; Nasu, Yasutomo; Ogawa, Osamu

2018-04-01

Introducing a new surgical technology may affect behaviors and attitudes of patients and surgeons about clinical practice. Robot-assisted laparoscopic radical prostatectomy (RALP) was approved in 2012 in Japan. We investigated whether the introduction of this system affected the treatment of organ-confined prostate cancer (PCa) and the use of radical prostatectomy (RP). We conducted a retrospective multicenter study on 718 patients with clinically determined organ-confined PCa treated at one of three Japanese academic institutions in 2011 (n = 338) or 2013 (n = 380). Two patient groups formed according to the treatment year were compared regarding the clinical characteristics of PCa, whether referred or screened at our hospital, comorbidities and surgical risk, and choice of primary treatment. Distribution of PCa risk was not changed by the introduction of RALP. Use of RP increased by 70% (from 127 to 221 cases, p < 0.0001), whereas the number of those undergoing radiotherapy or androgen deprivation therapy decreased irrespective of the disease risk of PCa. Increased use of RP (from 34 to 100 cases) for intermediate- or high-risk PCa patients with mild perioperative risk (American Society of Anesthesiologists score 2) accounted for 70% of the total RP increase, whereas the number of low- or very low-risk PCa patients with high comorbidity scores (Charlson Index ≥ 4) increased from 8 to 25 cases, accounting for 18%. Use of expectant management (active surveillance, watchful waiting) in very low-risk PCa patients was 15% in 2011 and 12% in 2013 (p = 0.791). Introduction of a robotic surgical system had little effect on the risk distribution of PCa. Use of RP increased, apparently due to increased indications in patients who are candidates for RP but have mild perioperative risk. Although small, there was an increase in the number of RPs performed on patients with severe comorbidities but with low-risk or very low-risk PCa.

Prostate cancer risk prediction in a urology clinic in Mexico

PubMed Central

Liang, Yuanyuan; Messer, Jamie C; Louden, Christopher; Jimenez-Rios, Miguel A; Thompson, Ian M; Camarena-Reynoso, Hector R

2012-01-01

Objectives To evaluate factors affecting the risk of prostate cancer (PCa) and high-grade disease (HGPCa, Gleason score ≥7) in a Mexican referral population, with comparison to the Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (PCPTRC). Methods and Materials From a retrospective study of 826 patients who underwent prostate biopsy between January 2005 and December 2009 at the Instituto Nacional de Cancerología, Mexico, logistic regression was used to assess the effects of age, prostate-specific antigen (PSA), digital rectal exam (DRE), first-degree family history of PCa, and history of a prior prostate biopsy on PCa and HGPCa separately. Internal discrimination, goodness-of-fit and clinical utility of the resulting models were assessed with comparison to the PCPTRC. Results Rates of both PCa (73.2%) and HGPCa (33.3%) were high among referral patients in this Mexican urology clinic. The PCPTRC generally underestimated the risk of PCa but overestimated the risk of HGPCa. Four factors influencing PCa on biopsy were logPSA, DRE, family history and a prior biopsy history (all p<0.001). The internal AUC of the logistic model was 0.823 compared to 0.785 of the PCPTRC for PCa (p<0.001). The same four factors were significantly associated with HGPCa as well and the AUC was 0.779 compared to 0.766 of the PCPTRC for HGPCa (p=0.13). Conclusions Lack of screening programs or regular urological checkups in Mexico imply that men typically first reach specialized clinics with a high cancer risk. This renders diagnostic tools developed on comparatively healthy populations, such as the PCPTRC, of lesser utility. Continued efforts are needed to develop and externally validate new clinical diagnostic tools specific to high-risk referral populations incorporating new biomarkers and more clinical characteristics. PMID:22306115

Cytoreductive prostate radiotherapy in oligometastatic prostate cancer: a single centre analysis of toxicity and clinical outcome.

PubMed

Riva, Giulia; Marvaso, Giulia; Augugliaro, Matteo; Zerini, Dario; Fodor, Cristiana; Musi, Gennaro; De Cobelli, Ottavio; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja

2017-01-01

The current standard of care for patients with metastatic prostate cancer (mPCa) at diagnosis is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to define the role of a local radiotherapy (RT) treatment in the mPCa setting. We retrospectively reviewed data of patients with PCa and bone oligometastases at diagnosis treated in our institution with ADT followed by cytoreductive prostate-RT with or without RT on metastases. Biochemical and clinical failure (BF, CF), overall survival (OS) and RT-toxicity were assessed. We identified 22 patients treated with ADT and external-beam RT on primary between June 2008 and March 2016. All of them but four were also treated for bone metastases. RT on primary with moderately and extremely hypofractionated regimes started after 10.3 months (3.9-51.7) from ADT. After a median follow-up of 26.4 months (10.3-55.5), 20 patients are alive. Twelve patients showed BF after a median time of 23 months (14.5-104) and CF after a median of 23.6 months (15.3-106.1) from the start of ADT. Three patients became castration resistant, starting a new therapy; median time to castration resistance was 31.03 months (range: 29.9-31.5 months). According to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC), only one patient developed acute grade 3 genitourinary toxicity. No late grade >2 adverse events were observed. Prostate RT in oligometastatic patients is safe and offers long-lasting local control. When compared to ADT alone, RT on primary seems to improve biochemical control and long-term survival; however, this hypothesis should be investigated in prospective studies. Further research is warranted.

Relevance of Occlusion Test in Endovascular Coiling of Posterior Cerebral Artery (P2 Segment) Aneurysms

PubMed Central

Jayakumar, P. N.; Desai, S.; Srikanth, S. G.; Ravishankar, S.; Kovoor, J. M. E.

2004-01-01

Summary P2 segment aneurysms are located on the posterior cerebral artery (PCA) between the junction of the posterior communicating artery with the PCA and the quadrigeminal cisternal part of the PCA. We reviewed our experience with endovascular coiling in such aneurysms. Clinical and pre-procedural data from four patients, referred for endovascular treatment of P2 segment aneurysms, were retrospectively studied for factors influencing post-interventional neurological deficits caused by ischemia of the PCA distal territory. Balloon occlusion was done in three patients and patient tolerance was assessed using clinical and anatomic criteria. Embryologic and anatomic features of the PCA were reviewed. Balloon occlusion test and endovascular coiling of aneurysms was possible in three patients. Control angiogram after embolization showed elimination of aneurysms from the circulation and the distal PCA filled through leptomeningeal anastomoses. One patient deteriorated due to aneurysmal rupture soon after the balloon occlusion test and coiling could not be done. In the other three patients post-intervention CT and MRI images showed PCA territory infarcts in spite of demonstration of good collateral circulation distal to the occluded PCA. In conclusion, P2 aneurysms can be effectively treated by endovascular coiling without a balloon occlusion test. While the balloon occlusion test does not contribute to clinical decision-making it may be associated with potential morbidity and mortality. PMID:20587236

Cathepsin B expression in prostate cancer of native Japanese and Japanese-American patients: an immunohistochemical study.

PubMed

Sinha, Akhouri A; Morgan, Jenifer L; Betre, Konjit; Wilson, Michael J; Le, Chap; Marks, Leonard S

2008-01-01

Japanese-American (J-A) men who have immigrated to the U.S.A. and acquired the Western lifestyle usually have more invasive prostate cancer (PCa) than native Japanese (NJ) living in Japan. The specific reasons for these differences remain unknown. The objective of this study was to examine immunostainings of cathepsin B (CB) and its endogenous inhibitor stefin A (SA) in tissue microarray (TMA) and radical prostatectomy (RP) tissue sections in the hope of obtaining insights into the invasiveness of PCa in Japanese patients. TMA and RP sections were evaluated in 50 men (25 NJ and 25 J-A) for CB and SA reaction products. The CB and SA immunostainings were imaged directly from microscope slides to a computer using a high performance charge coupled device (CCD) digital camera, quantified using Metamorph software, analyzed using the two-sample t-test, and confirmed by multiple regression analysis. The CB and SA proteins were localized in the carcinomatous glands and isolated cancer cells in the TMA and RP sections. The Gleason scores and pre-surgery serum total prostate-specific antigen (PSA) levels did not differ significantly in the NJ and J-A patients (p = 0.14, p = 0.16, respectively). The Chi-square analysis of clinical stage versus place of birth showed that the NJ patients had significantly more T2a and T2b clinical stages than the J-A patients who had more advanced T2c and T3a stages (p = 0.003). The CB and SA immunostainings and their ratios in Gleason score 6 tumors did not show any difference, but the CB:SA ratios in score > or = 7 tumors approached significance levels. The overall matching of specimens according to the Gleason grade/score, pre-RP serum total PSA levels, clinical stage and age prior to evaluation of immunostainings greatly minimizes subjectivity associated with the evaluation of markers in this ethnic sub-population of PCa patients. CB and SA immunostaining is similar in Japanese patients who have organ-confined and moderately-differentiated PCa. Analysis of the reaction product data provides indirect evidence that invasiveness of PCa is similar in the two Japanese patient populations.

Commentary on "randomized clinical trial of vitamin D3 doses on prostatic vitamin D metabolite levels and Ki67 labeling in prostate cancer patients." Wagner D, Trudel D, Van der Kwast T, Nonn L, Giangreco AA, Li D, Dias A, Cardoza M, Laszlo S, Hersey K, Klotz L, Finelli A, Fleshner N, Vieth R, Department of Nutritional Sciences, University of Toronto, Ontario, Canada.: J Clin Endocrinol Metab 2013;98(4):1498-507 [Epub 2013 Mar 5].

PubMed

Olumi, Aria F

2014-02-01

Vitamin D3 might benefit prostate cancer (PCa) patients because prostate cells can locally synthesize the active hormone calcitriol. Our objective was to determine the effects of oral vitamin D3 on vitamin D metabolites and PCa proliferative activity in prostate tissue. We conducted a double-blind randomized clinical trial at surgical oncology clinics in Toronto, Canada. PCa patients (Gleason 6 or 7) participated in the study. Of 66 subjects who were enrolled, 63 completed the dosing protocol. Vitamin D3 (400, 10000, or 40000 IU/d) was orally administered before radical prostatectomy. We evaluated vitamin D metabolite levels and Ki67 labeling in surgical prostate tissue. Safety measures, PTH, and prostate-specific antigen (PSA) were also assessed. Prostate tissue and serum levels of vitamin D metabolites, including calcitriol, increased dose dependently (P<.03) and were significantly higher in the 40000-IU/d group than in every other dose group (P<.03). Prostate vitamin D metabolites correlated positively with serum levels (P<.0001). Ki67 measures did not differ significantly among vitamin D dose groups. However, cross-sectional analysis indicated that the calcitriol level attained in prostate was inversely associated with Ki67 intensity and Ki67 (3+) percent positive nuclei in PCa and benign tissue (P<.05). Safety measures did not change adversely with dosing. Compared with the 400-IU/d group, serum PTH and PSA were lower in the combined higher-dose groups at the end of the study (P< .02). Oral vitamin D3 raised prostate calcitriol levels (level 1 evidence) and modestly lowered both PSA and PTH. Although Ki67 expression did not differ among dose groups, its levels correlated inversely with prostate calcitriol. These suggestions of clinical benefit justify continued clinical research. Copyright © 2014 Elsevier Inc. All rights reserved.

Local Treatment of Metastatic Prostate Cancer: What is the Evidence So Far?

PubMed

Leonel Almeida, Pedro; Jorge Pereira, Bruno

2018-01-01

Advances in technological, laboratorial, and imaging studies and new treatments available in the last decades significantly improved prostate cancer survival rates. However, this did not occur in metastatic prostate cancer (mPCa) at diagnosis which, in young and fit patients, will become invariably resistant to the established treatments. Progression will lead to an impairment in patients' quality of life and disease-related death. The authors intend to perform a literature review of the advantages of primary treatment of mPCa. Articles were retrieved and filtered for relevance from PubMed, SciELO, and ScienceDirect until March 2017. Primary treatment is currently indicated only in cases of nonmetastatic PCa. Nonetheless, there might be some benefits in doing local treatment in mPCa in order to control local disease, prevent new metastasis, and improve the efficacy of chemotherapy and hormonotherapy with similar complications rate when compared to locally confined cancer. Independent factors that have a negative influence are age above 70 years, cT4 stage or high-grade disease, PSA ≥ 20 ng/ml, and pelvic lymphadenopathies. The presence of 3 or more of these factors conditions CSS and OS is the same between patients who performed local treatment and those who did not. Metastasis degree and location number can also influence outcome. Meanwhile, patients with visceral metastases have worse results. There is growing evidence supporting local treatment in cases of metastatic prostate cancer at diagnosis in the context of a multimodal approach. However, it should be kept in mind that most of the existing studies are retrospective and it would be important to make consistent prospective studies with well-defined patient selection criteria in order to sustain the existing data and understand the main indications to select patients and perform primary treatment in mPCa.

Ex vivo MRI evaluation of prostate cancer: Localization and margin status prediction of prostate cancer in fresh radical prostatectomy specimens.

PubMed

Heidkamp, Jan; Hoogenboom, Martijn; Kovacs, Iringo E; Veltien, Andor; Maat, Arie; Sedelaar, J P Michiel; Hulsbergen-van de Kaa, Christina A; Fütterer, Jurgen J

2018-02-01

To investigate the ability of high field ex vivo magnetic resonance imaging (MRI) to localize prostate cancer (PCa) and to predict the margin status in fresh radical prostatectomy (RP) specimens using histology as the reference standard. This Institutional Review Board (IRB)-approved study had written informed consent. Patients with biopsy-proved PCa and a diagnostic multiparametric 3T MRI examination of the prostate prior to undergoing RP were prospectively included. A custom-made container provided reference between the 7T ex vivo MRI obtained from fresh RP specimens and histological slicing. On ex vivo MRI, PCa was localized and the presence of positive surgical margins was determined in a double-reading session. These findings were compared with histological findings obtained from completely cut, whole-mount embedded, prostate specimens. In 12 RP specimens, histopathology revealed 36 PCa lesions, of which 17 (47%) and 20 (56%) were correlated with the ex vivo MRI in the first and second reading session, respectively. Nine of 12 (75%) index lesions were localized in the first session, in the second 10 of 12 (83%). Seven and 8 lesions of 11 lesions with Gleason score >6 and >0.5 cc were localized in the first and second session, respectively. In the first session none of the four histologically positive surgical margins (sensitivity 0%) and 9 of 13 negative margins (specificity 69%) were detected. In second session the sensitivity and specificity were 25% and 88%, respectively. Ex vivo MRI enabled accurate localization of PCa in fresh RP specimens, and the technique provided information on the margin status with high specificity. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:439-448. © 2017 International Society for Magnetic Resonance in Medicine.

A novel-type phosphatidylinositol phosphate-interactive, Ca-binding protein PCaP1 in Arabidopsis thaliana: stable association with plasma membrane and partial involvement in stomata closure.

PubMed

Nagata, Chisako; Miwa, Chika; Tanaka, Natsuki; Kato, Mariko; Suito, Momoe; Tsuchihira, Ayako; Sato, Yori; Segami, Shoji; Maeshima, Masayoshi

2016-05-01

The Ca(2+)-binding protein-1 (PCaP1) of Arabidopsis thaliana is a new type protein that binds to phosphatidylinositol phosphates and Ca(2+)-calmodulin complex as well as free Ca(2+). Although biochemical properties, such as binding to ligands and N-myristoylation, have been revealed, the intracellular localization, tissue and cell specificity, integrity of membrane association and physiological roles of PCaP1 are unknown. We investigated the tissue and intracellular distribution of PCaP1 by using transgenic lines expressing PCaP1 linked with a green fluorescence protein (GFP) at the carboxyl terminus of PCaP1. GFP fluorescence was obviously detected in most tissues including root, stem, leaf and flower. In these tissues, PCaP1-GFP signal was observed predominantly in the plasma membrane even under physiological stress conditions but not in other organelles. The fluorescence was detected in the cytosol when the 25-residue N-terminal sequence was deleted from PCaP1 indicating essential contribution of N-myristoylation to the plasma membrane anchoring. Fluorescence intensity of PCaP1-GFP in roots was slightly decreased in seedlings grown in medium supplemented with high concentrations of iron for 1 week and increased in those grown with copper. In stomatal guard cells, PCaP1-GFP was strictly, specifically localized to the plasma membrane at the epidermal-cell side but not at the pore side. A T-DNA insertion mutant line of PCaP1 did not show marked phenotype in a life cycle except for well growth under high CO2 conditions. However, stomata of the mutant line did not close entirely even in high osmolarity, which usually induces stomata closure. These results suggest that PCaP1 is involved in the stomatal movement, especially closure process, in leaves and response to excessive copper in root and leaf as a mineral nutrient as a physiological role.

Metabolic syndrome is not associated with greater evidences of proliferative inflammatory atrophy and inflammation in patients with suspected prostate cancer.

PubMed

Russo, Giorgio I; Cimino, Sebastiano; Giranio, Giorgia; Regis, Federica; Favilla, Vincenzo; Privitera, Salvatore; Motta, Fabio; Caltabiano, Rosario; Stenzl, Arnulf; Todenhöfer, Tilman; Morgia, Giuseppe

2018-05-01

To evaluate the association between metabolic syndrome (MetS) and proliferative inflammatory atrophy (PIA) in patients with suspected prostate cancer (PCa). From June 2015 to July 2016, we conducted the FIERY (Flogosis Increased Events of pRostatic biopsY) study at the Urology section, Department of Surgery of the University of Catania (Local registration number: #131/2015). A total of 205 patients with elevated prostate-specific antigen (≥ 4 ng/ml) or clinical suspicion of PCa who underwent primary transperineal prostate biopsy were included in this cross-sectional study. The assessment of PIA, HGPIN, and PCa were performed by 2 experienced pathologists and samples were investigated for the presence of an inflammatory infiltrate, according to the Irani score. Primary and secondary Gleason grade of tumor in positive biopsies were evaluated according to the 2016 ISUP Modified Gleason System. In the entire cohort, median age was 68.0 (interquartile range: 62.0-74.5), median prostate-specific antigen was 6.5 (interquartile range: 5.51-9.57). The prevalence of MetS was 34.1%, the detection rate of PCa was 32.7%, the rate of PIA was 28.3%, the rate of HGPIN was 32.2%, whereas the rate of severe intraprostatic inflammation (Irani-score ≥4) was 28.8%. When comparing clinical and histological variables in patients without and with PIA, metabolic aberrations where not significantly different in both groups. We did not find statistical association in detection rate of PCa (29.3% vs. 34.0%; P = 0.07) and HGPIN (27.6% vs. 34.0%; P = 0.37) in patients with and without PIA, respectively. When considering metabolic aberrations, MetS was not associated with Irani-score ≥4 (28.6% vs. 28.4%; P = 0.96) and none of each component was statistically predictive of severe inflammation. At the multivariable logistic regression analysis, PIA, HGPIN, and MetS were not associated with greater risk of PCa. In this study, we did not show an association between MetS and PIA and PCa. Although the small sample size and the cross-sectional nature of the study, we do not suppose that MetS could be associated with greater evidence of PIA. Further studies should be conducted to evaluate the exact nature of this pathological lesion. Copyright © 2018 Elsevier Inc. All rights reserved.

Epigenetics in prostate cancer: biologic and clinical relevance.

PubMed

Jerónimo, Carmen; Bastian, Patrick J; Bjartell, Anders; Carbone, Giuseppina M; Catto, James W F; Clark, Susan J; Henrique, Rui; Nelson, William G; Shariat, Shahrokh F

2011-10-01

Prostate cancer (PCa) is one of the most common human malignancies and arises through genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications, and microRNAs (miRNA) and produce heritable changes in gene expression without altering the DNA coding sequence. To review progress in the understanding of PCa epigenetics and to focus upon translational applications of this knowledge. PubMed was searched for publications regarding PCa and DNA methylation, histone modifications, and miRNAs. Reports were selected based on the detail of analysis, mechanistic support of data, novelty, and potential clinical applications. Aberrant DNA methylation (hypo- and hypermethylation) is the best-characterized alteration in PCa and leads to genomic instability and inappropriate gene expression. Global and locus-specific changes in chromatin remodeling are implicated in PCa, with evidence suggesting a causative dysfunction of histone-modifying enzymes. MicroRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen receptor signaling and apoptosis. There are important connections between common genetic alterations (eg, E twenty-six fusion genes) and the altered epigenetic landscape. Owing to the ubiquitous nature of epigenetic alterations, they provide potential biomarkers for PCa detection, diagnosis, assessment of prognosis, and post-treatment surveillance. Altered epigenetic gene regulation is involved in the genesis and progression of PCa. Epigenetic alterations may provide valuable tools for the management of PCa patients and be targeted by pharmacologic compounds that reverse their nature. The potential for epigenetic changes in PCa requires further exploration and validation to enable translation to the clinic. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Validation study of genes with hypermethylated promoter regions associated with prostate cancer recurrence

PubMed Central

Stott-Miller, Marni; Zhao, Shanshan; Wright, Jonathan L.; Kolb, Suzanne; Bibikova, Marina; Klotzle, Brandy; Ostrander, Elaine A.; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L.

2014-01-01

Background One challenge in prostate cancer (PCa) is distinguishing indolent from aggressive disease at diagnosis. DNA promoter hypermethylation is a frequent epigenetic event in PCa, but few studies of DNA methylation in relation to features of more aggressive tumors or PCa recurrence have been completed. Methods We used the Infinium® HumanMethylation450 BeadChip to assess DNA methylation in tumor tissue from 407 patients with clinically localized PCa who underwent radical prostatectomy. Recurrence status was determined by follow-up patient surveys, medical record review, and linkage with the SEER registry. The methylation status of 14 genes for which promoter hypermethylation was previously correlated with advanced disease or biochemical recurrence was evaluated. Average methylation level for promoter region CpGs in patients who recurred compared to those with no evidence of recurrence was analyzed. For two genes with differential methylation, time to recurrence was examined. Results During an average follow-up of 11.7 years, 104 (26%) patients recurred. Significant promoter hypermethylation in at least 50% of CpG sites in two genes, ABHD9 and HOXD3, was found in tumors from patients who recurred compared to those without recurrence. Evidence was strongest for HOXD3 (lowest P = 9.46x10−6), with higher average methylation across promoter region CpGs associated with reduced recurrence-free survival (P = 2×10−4). DNA methylation profiles did not differ by recurrence status for the other genes. Conclusions These results validate the association between promoter hypermethylation of ADHB9 and HOXD3 and PCa recurrence. Impact Tumor DNA methylation profiling may help distinguish PCa patients at higher risk for disease recurrence. PMID:24718283

On a PCA-based lung motion model

NASA Astrophysics Data System (ADS)

Li, Ruijiang; Lewis, John H.; Jia, Xun; Zhao, Tianyu; Liu, Weifeng; Wuenschel, Sara; Lamb, James; Yang, Deshan; Low, Daniel A.; Jiang, Steve B.

2011-09-01

Respiration-induced organ motion is one of the major uncertainties in lung cancer radiotherapy and is crucial to be able to accurately model the lung motion. Most work so far has focused on the study of the motion of a single point (usually the tumor center of mass), and much less work has been done to model the motion of the entire lung. Inspired by the work of Zhang et al (2007 Med. Phys. 34 4772-81), we believe that the spatiotemporal relationship of the entire lung motion can be accurately modeled based on principle component analysis (PCA) and then a sparse subset of the entire lung, such as an implanted marker, can be used to drive the motion of the entire lung (including the tumor). The goal of this work is twofold. First, we aim to understand the underlying reason why PCA is effective for modeling lung motion and find the optimal number of PCA coefficients for accurate lung motion modeling. We attempt to address the above important problems both in a theoretical framework and in the context of real clinical data. Second, we propose a new method to derive the entire lung motion using a single internal marker based on the PCA model. The main results of this work are as follows. We derived an important property which reveals the implicit regularization imposed by the PCA model. We then studied the model using two mathematical respiratory phantoms and 11 clinical 4DCT scans for eight lung cancer patients. For the mathematical phantoms with cosine and an even power (2n) of cosine motion, we proved that 2 and 2n PCA coefficients and eigenvectors will completely represent the lung motion, respectively. Moreover, for the cosine phantom, we derived the equivalence conditions for the PCA motion model and the physiological 5D lung motion model (Low et al 2005 Int. J. Radiat. Oncol. Biol. Phys. 63 921-9). For the clinical 4DCT data, we demonstrated the modeling power and generalization performance of the PCA model. The average 3D modeling error using PCA was within 1 mm (0.7 ± 0.1 mm). When a single artificial internal marker was used to derive the lung motion, the average 3D error was found to be within 2 mm (1.8 ± 0.3 mm) through comprehensive statistical analysis. The optimal number of PCA coefficients needs to be determined on a patient-by-patient basis and two PCA coefficients seem to be sufficient for accurate modeling of the lung motion for most patients. In conclusion, we have presented thorough theoretical analysis and clinical validation of the PCA lung motion model. The feasibility of deriving the entire lung motion using a single marker has also been demonstrated on clinical data using a simulation approach.

Health-related quality of life after salvage high-intensity focused ultrasound (HIFU) treatment for locally radiorecurrent prostate cancer.

PubMed

Berge, Viktor; Baco, Eduard; Dahl, Alv A; Karlsen, Steinar Johan

2011-09-01

To evaluate health-related quality of life (HRQOL) after salvage high-intensity focused ultrasound (HIFU) for locally radiorecurrent prostate cancer (PCa). Since June 2006 we have treated 61 patients consecutively by salvage HIFU. All patients were offered the University of California, Los Angeles Prostate Cancer Index (UCLA-PCI) questionnaire at baseline and at follow-up. Scores ranged from 0 (worst) to 100 (best). Clinically significant changes were defined as a minimum difference of 10 points between the baseline score and the score at follow-up.   Fifty-seven patients (93%) had evaluable data at baseline, compared with 46 (75%) after treatment. The mean time lapse between HIFU treatment and questionnaire response was 17.5 months (range 6-29 months). The mean score for urinary function decreased from 79.7 ± 12.1 prior to HIFU to 67.4 ± 17.8 after HIFU (P < 0.001). The mean score for sexual function decreased from 32.1 ± 24.1 prior to HIFU to 17.2 ± 17.0 after HIFU (P < 0.001). There were no significant effects on bowel function. There was a significant reduction in the mean score for Physical HRQOL, but the mean score for Mental HRQOL was did not change significantly. Treatment of localized radiorecurrent PCa by salvage HIFU is associated with clinically significant reductions in urinary and sexual function domains after a mean follow-up of 17.5 months. © 2011 The Japanese Urological Association.

Defining a standard set of patient-centered outcomes for men with localized prostate cancer.

PubMed

Martin, Neil E; Massey, Laura; Stowell, Caleb; Bangma, Chris; Briganti, Alberto; Bill-Axelson, Anna; Blute, Michael; Catto, James; Chen, Ronald C; D'Amico, Anthony V; Feick, Günter; Fitzpatrick, John M; Frank, Steven J; Froehner, Michael; Frydenberg, Mark; Glaser, Adam; Graefen, Markus; Hamstra, Daniel; Kibel, Adam; Mendenhall, Nancy; Moretti, Kim; Ramon, Jacob; Roos, Ian; Sandler, Howard; Sullivan, Francis J; Swanson, David; Tewari, Ashutosh; Vickers, Andrew; Wiegel, Thomas; Huland, Hartwig

2015-03-01

Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment. To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value. We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices. The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set. We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons. We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care. Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Differentiation of neuropsychological features between posterior cortical atrophy and early onset Alzheimer's disease.

PubMed

Li, Jieying; Wu, Liyong; Tang, Yi; Zhou, Aihong; Wang, Fen; Xing, Yi; Jia, Jianping

2018-05-10

Posterior cortical atrophy (PCA) is a group of clinical syndromes characterized by visuospatial and visuoperceptual impairment, with memory relatively preserved. Although PCA is pathologically almost identical to Alzheimer's disease (AD), they have different cognitive features. Those differences have only rarely been reported in any Chinese population. The purpose of the study is to establish neuropsychological tests that distinguish the clinical features of PCA from early onset AD (EOAD). Twenty-one PCA patients, 20 EOAD patients, and 20 healthy controls participated in this study. Patients had disease duration of ≤4 years. All participants completed a series of neuropsychological tests to evaluate their visuospatial, visuoperceptual, visuo-constructive, language, executive function, memory, calculation, writing, and reading abilities. The cognitive features of PCA and EOAD were compared. All the neuropsychological test scores showed that both the PCA and EOAD patients were significantly more impaired than people in the control group. However, PCA patients were significantly more impaired than EOAD patients in visuospatial, visuoperceptual, and visuo-constructive function, as well as in handwriting, and reading Chinese characters. The profile of neuropsychological test results highlights cognitive features that differ between PCA and EOAD. One surprising result is that the two syndromes could be distinguished by patients' ability to read and write Chinese characters. Tests based on these characteristics could therefore form a brief PCA neuropsychological examination that would improve the diagnosis of PCA.

A prospective cohort study of treatment decision-making for prostate cancer following participation in a multidisciplinary clinic.

PubMed

Hurwitz, Lauren M; Cullen, Jennifer; Elsamanoudi, Sally; Kim, Daniel J; Hudak, Jane; Colston, Maryellen; Travis, Judith; Kuo, Huai-Ching; Porter, Christopher R; Rosner, Inger L

2016-05-01

Patients diagnosed with prostate cancer (PCa) are presented with several treatment options of similar efficacy but varying side effects. Understanding how and why patients make their treatment decisions, as well as the effect of treatment choice on long-term outcomes, is critical to ensuring effective, patient-centered care. This study examined treatment decision-making in a racially diverse, equal-access, contemporary cohort of patients with PCa counseled on treatment options at a multidisciplinary clinic. A prospective cohort study was initiated at the Walter Reed National Military Medical Center (formerly Walter Reed Army Medical Center) in 2006. Newly diagnosed patients with PCa were enrolled before attending a multidisciplinary clinic. Patients completed surveys preclinic and postclinic to assess treatment preferences, reasons for treatment choice, and decisional regret. As of January 2014, 925 patients with PCa enrolled in this study. Surgery (54%), external radiation (20%), and active surveillance (12%) were the most common primary treatments for patients with low- and intermediate-risk PCa, whereas patients with high-risk PCa chose surgery (34%) or external radiation with neoadjuvant hormones (57%). Treatment choice differed by age at diagnosis, race, comorbidity status, and calendar year in both univariable and multivariable analyses. Patients preferred to play an active role in the decision-making process and cited doctors at the clinic as the most helpful source of treatment-related information. Almost all patients reported satisfaction with their decision. This is one of the first prospective cohort studies to examine treatment decision-making in an equal-access, multidisciplinary clinic setting. Studies of this cohort would aid in understanding and improving the PCa decision-making process. Published by Elsevier Inc.

Competing-risks mortality after radiotherapy vs. observation for localized prostate cancer: a population-based study.

PubMed

Abdollah, Firas; Sun, Maxine; Schmitges, Jan; Thuret, Rodolphe; Tian, Zhe; Shariat, Shahrokh F; Briganti, Alberto; Jeldres, Claudio; Perrotte, Paul; Montorsi, Francesco; Karakiewicz, Pierre I

2012-09-01

Contemporary patients with localized prostate cancer (PCa) are more frequently treated with radiotherapy. However, there are limited data on the effect of this treatment on cancer-specific mortality (CSM). Our objective was to test the relationship between radiotherapy and survival in men with localized PCa and compare it with those treated with observation. A population-based cohort identified 68,797 men with cT1-T2 PCa treated with radiotherapy or observation between the years 1992 and 2005. Propensity-score matching was used to minimize potential bias related to treatment assignment. Competing-risks analyses tested the effect of treatment type (radiotherapy vs. observation) on CSM, after accounting to other-cause mortality. All analyses were carried out within PCa risk, baseline comorbidity status, and age groups. Radiotherapy was associated with more favorable 10-year CSM rates than observation in patients with high-risk PCa (8.8 vs. 14.4%, hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.50-0.68). Conversely, the beneficial effect of radiotherapy on CSM was not evident in patients with low-intermediate risk PCa (3.7 vs. 4.1%, HR: 0.91, 95% CI: 0.80-1.04). Radiotherapy was beneficial in elderly patients (5.6 vs. 7.3%, HR: 0.70, 95% CI: 0.59-0.80). Moreover, it was associated with improved CSM rates among patients with no comorbidities (5.7 vs. 6.5%, HR: 0.81, 95% CI: 0.67-0.98), one comorbidity (4.6 vs. 6.0%, HR: 0.87, 95% CI: 0.75-0.99), and more than two comorbidities (4.2 vs. 5.0%, HR: 0.79, 95% CI: 0.65-0.96). Radiotherapy substantially improves CSM in patients with high-risk PCa, with little or no benefit in patients with low-/intermediate-risk PCa relative to observation. These findings must be interpreted within the context of the limitations of observational data. Copyright © 2012 Elsevier Inc. All rights reserved.

Use of routinely available clinical, nutritional, and functional criteria to classify cachexia in advanced cancer patients.

PubMed

Vigano, Antonio A L; Morais, José A; Ciutto, Lorella; Rosenthall, Leonard; di Tomasso, Jonathan; Khan, Sarah; Olders, Henry; Borod, Manuel; Kilgour, Robert D

2017-10-01

Cachexia is a highly prevalent syndrome in cancer and chronic diseases. However, due to the heterogeneous features of cancer cachexia, its identification and classification challenge clinical practitioners. To determine the clinical relevance of a cancer cachexia classification system in advanced cancer patients. Beginning with the four-stage classification system proposed for cachexia [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca) and refractory cachexia (RCa)], we assigned patients to these cachexia stages according to five classification criteria available in clinical practice: 1) biochemistry (high C-reactive protein or leukocytes, or hypoalbuminemia, or anemia), 2) food intake (normal/decreased), weight loss: 3) moderate (≤5%) or 4) significant (>5%/past six months) and 5) performance status (Eastern Cooperative Oncology Group Performance Status ≥ 3). We then determined if symptom severity, body composition changes, functional levels, hospitalizations and survival rates varied significantly across cachexia stages. Two-hundred and ninety-seven advanced cancer patients with primary gastrointestinal and lung tumors were included. Patients were classified into Ca (36%), PCa and RCa (21%, respectively) and NCa (15%). Significant (p < 0.05) differences were observed among cachexia stages for most of the outcome measures (symptoms, body composition, handgrip strength, emergency room visits and length of hospital stays) according to cachexia severity. Survival also differed between cachexia stages (except between PCa and Ca). Five clinical criteria can be used to stage cancer cachexia patients and predict important clinical, nutritional and functional outcomes. The lack of statistical difference between PCa and Ca in almost all clinical outcomes examined suggests either that the PCa group includes patients already affected by early cachexia or that more precise criteria are needed to differentiate PCa from Ca patients. More studies are required to validate these findings. Copyright © 2016. Published by Elsevier Ltd.

Increased PSA expression on prostate cancer exosomes in in vitro condition and in cancer patients.

PubMed

Logozzi, Mariantonia; Angelini, Daniela F; Iessi, Elisabetta; Mizzoni, Davide; Di Raimo, Rossella; Federici, Cristina; Lugini, Luana; Borsellino, Giovanna; Gentilucci, Alessandro; Pierella, Federico; Marzio, Vittorio; Sciarra, Alessandro; Battistini, Luca; Fais, Stefano

2017-09-10

Prostate specific antigen (PSA) test is the most common, clinically validated test for the diagnosis of prostate cancer (PCa). While neoplastic lesions of the prostate may cause aberrant levels of PSA in the blood, the quantitation of free or complexed PSA poorly discriminates cancer patients from those developing benign lesions, often leading to invasive and unnecessary surgical procedures. Microenvironmental acidity increases exosome release by cancer cells. In this study we evaluated whether acidity, a critical phenotype of malignancy, could influence exosome release and increase the PSA expression in nanovesicles released by PCa cells. To this aim, we exploited Nanoparticle Tracking Analysis (NTA), an immunocapture-based ELISA, and nanoscale flow-cytometry. The results show that microenvironmental acidity induces an increased release of nanovesicles expressing both PSA and the exosome marker CD81. In order to verify whether the changes induced by the local selective pressure of extracellular acidity may correspond to a clinical pathway we used the same approach to evaluate the levels of PSA-expressing exosomes in the plasma of PCa patients and controls, including subjects with benign prostatic hypertrophy (BPH). The results show that only PCa patients have high levels of nanovesicles expressing both CD81 and PSA. This study shows that tumor acidity exerts a selective pressure leading to the release of extracellular vesicles that express both PSA and exosome markers. A comparable scenario was shown in the plasma of prostate cancer patients as compared to both BPH and healthy controls. These results suggest that microenvironmental acidity may represent a key factor which determines qualitatively and quantitatively the release of extracellular vesicles by malignant tumors, including prostate cancer. This condition leads to the spill-over of nanovesicles into the peripheral blood of prostate cancer patients, where the levels of tumor biomarkers expressed by exosomes, such as PSA-exosomes, may represent a novel, non-invasive clinical tool for the screening and early diagnosis of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Prostate cancer gene 3 and multiparametric magnetic resonance can reduce unnecessary biopsies: decision curve analysis to evaluate predictive models.

PubMed

Busetto, Gian Maria; De Berardinis, Ettore; Sciarra, Alessandro; Panebianco, Valeria; Giovannone, Riccardo; Rosato, Stefano; D'Errigo, Paola; Di Silverio, Franco; Gentile, Vincenzo; Salciccia, Stefano

2013-12-01

To overcome the well-known prostate-specific antigen limits, several new biomarkers have been proposed. Since its introduction in clinical practice, the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance imaging (mMRI) has the ability to better describe several aspects of PC. A prospective study of 171 patients with negative prostate biopsy findings and a persistent high prostate-specific antigen level was conducted to assess the role of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI before a second transrectal ultrasound-guided prostate biopsy. The accuracy and reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four multivariate logistic regression models were analyzed, in terms of discrimination and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting the biopsy outcome. A decision curve analysis was also plotted. Repeated transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and 90%, respectively. Evaluating the regression models, the best discrimination (area under the curve 0.808) was obtained using the full model (base clinical model plus mMRI and PCA3). The decision curve analysis, to evaluate the cost/benefit ratio, showed good performance in predicting PC with the model that included mMRI and PCA3. mMRI increased the accuracy and sensitivity of the PCA3 test, and the use of the full model significantly improved the cost/benefit ratio, avoiding unnecessary biopsies. Copyright © 2013 Elsevier Inc. All rights reserved.

Decision Support and Shared Decision Making About Active Surveillance Versus Active Treatment Among Men Diagnosed with Low-Risk Prostate Cancer: a Pilot Study.

PubMed

Myers, Ronald E; Leader, Amy E; Censits, Jean Hoffman; Trabulsi, Edouard J; Keith, Scott W; Petrich, Anett M; Quinn, Anna M; Den, Robert B; Hurwitz, Mark D; Lallas, Costas D; Hegarty, Sarah E; Dicker, Adam P; Zeigler-Johnson, Charnita M; Giri, Veda N; Ayaz, Hasan; Gomella, Leonard G

2018-02-01

This study aimed to explore the effects of a decision support intervention (DSI) and shared decision making (SDM) on knowledge, perceptions about treatment, and treatment choice among men diagnosed with localized low-risk prostate cancer (PCa). At a multidisciplinary clinic visit, 30 consenting men with localized low-risk PCa completed a baseline survey, had a nurse-mediated online DS session to clarify preference for active surveillance (AS) or active treatment (AT), and met with clinicians for SDM. Participants also completed a follow-up survey at 30 days. We assessed change in treatment knowledge, decisional conflict, and perceptions and identified predictors of AS. At follow-up, participants exhibited increased knowledge (p < 0.001), decreased decisional conflict (p < 0.001), and more favorable perceptions of AS (p = 0.001). Furthermore, 25 of the 30 participants (83 %) initiated AS. Increased family and clinician support predicted this choice (p < 0.001). DSI/SDM prepared patients to make an informed decision. Perceived support of the decision facilitated patient choice of AS.

A Biopsy-based 17-gene Genomic Prostate Score as a Predictor of Metastases and Prostate Cancer Death in Surgically Treated Men with Clinically Localized Disease.

PubMed

Van Den Eeden, Stephen K; Lu, Ruixiao; Zhang, Nan; Quesenberry, Charles P; Shan, Jun; Han, Jeong S; Tsiatis, Athanasios C; Leimpeter, Amethyst D; Lawrence, H Jeffrey; Febbo, Phillip G; Presti, Joseph C

2018-01-01

A 17-gene biopsy-based reverse transcription polymerase chain reaction assay, which provides a Genomic Prostate Score (GPS-scale 0-100), has been validated as an independent predictor of adverse pathology and biochemical recurrence after radical prostatectomy (RP) in men with low- and intermediate-risk prostate cancer (PCa). To evaluate GPS as a predictor of PCa metastasis and PCa-specific death (PCD) in a large cohort of men with localized PCa and long-term follow-up. A retrospective study using a stratified cohort sampling design was performed in a cohort of men treated with RP within Kaiser Permanente Northern California. RNA from archival diagnostic biopsies was assayed to generate GPS results. We assessed the association between GPS and time to metastasis and PCD in prespecified uni- and multivariable statistical analyses, based on Cox proportional hazard models accounting for sampling weights. The final study population consisted of 279 men with low-, intermediate-, and high-risk PCa between 1995 and 2010 (median follow-up 9.8 yr), and included 64 PCD and 79 metastases. Valid GPS results were obtained for 259 (93%). In univariable analysis, GPS was strongly associated with time to PCD, hazard ratio (HR)/20 GPS units=3.23 (95% confidence interval [CI] 1.84-5.65; p<0.001), and time to metastasis, HR/20 units=2.75 (95% CI 1.63-4.63; p<0.001). The association between GPS and both end points remained significant after adjusting for National Comprehensive Cancer Network, American Urological Association, and Cancer of the Prostate Risk Assessment (CAPRA) risks (p<0.001). No patient with low- or intermediate-risk disease and a GPS of<20 developed metastases or PCD (n=31). In receiver operating characteristic analysis of PCD at 10 yr, GPS improved the c-statistic from 0.78 (CAPRA alone) to 0.84 (GPS+CAPRA; p<0.001). A limitation of the study was that patients were treated during an era when definitive treatment was standard of care with little adoption of active surveillance. GPS is a strong independent predictor of long-term outcomes in clinically localized PCa in men treated with RP and may improve risk stratification for men with newly diagnosed disease. Many prostate cancers are slow growing and unlikely to spread or threaten a man's life, while others are more aggressive and require treatment. Increasingly, doctors are using new molecular tests, such as the17-gene Genomic Prostate Score (GPS), which can be performed at the time of initial diagnosis to help determine how aggressive a given patient's cancer may be. In this study, performed in a large community-based healthcare network, GPS was shown to be a strong predictor as to whether a man's prostate cancer will spread and threaten his life after surgery, providing information that may help patients and their doctors decide on the best course of management of their disease. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment

PubMed Central

Hosseini-Beheshti, Elham; Choi, Wendy; Weiswald, Louis-Bastien; Kharmate, Geetanjali; Ghaffari, Mazyar; Roshan-Moniri, Mani; Hassona, Mohamed D.; Chan, Leslie; Chin, Mei Yieng; Tai, Isabella T.; Rennie, Paul S.; Fazli, Ladan; Guns, Emma S. Tomlinson

2016-01-01

Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Current research on tumour-related extracellular vesicles (EVs) suggests that exosomes play a significant role in paracrine signaling pathways, thus potentially influencing cancer progression via multiple mechanisms. In fact, during the last decade numerous studies have revealed the role of EVs in the progression of various pathological conditions including cancer. Moreover, differences in the proteomic, lipidomic, and cholesterol content of exosomes derived from PCa cell lines versus benign prostate cell lines confirm that exosomes could be excellent biomarker candidates. As such, as part of an extensive proteomic analysis using LCMS we previously described a potential role of exosomes as biomarkers for PCa. Current evidence suggests that uptake of EV's into the local tumour microenvironment encouraging us to further examine the role of these vesicles in distinct mechanisms involved in the progression of PCa and castration resistant PCa. For the purpose of this study, we hypothesized that exosomes play a pivotal role in cell-cell communication in the local tumour microenvironment, conferring activation of numerous survival mechanisms during PCa progression and development of therapeutic resistance. Our in vitro results demonstrate that PCa derived exosomes significantly reduce apoptosis, increase cancer cell proliferation and induce cell migration in LNCaP and RWPE-1 cells. In conjunction with our in vitro findings, we have also demonstrated that exosomes increased tumor volume and serum PSA levels in vivo when xenograft bearing mice were administered DU145 cell derived exosomes intravenously. This research suggests that, regardless of androgen receptor phenotype, exosomes derived from PCa cells significantly enhance multiple mechanisms that contribute to PCa progression. PMID:26840259

Beyond textbook neuroanatomy: The syndrome of malignant PCA infarction.

PubMed

Gogela, Steven L; Gozal, Yair M; Rahme, Ralph; Zuccarello, Mario; Ringer, Andrew J

2015-01-01

Given its limited vascular territory, occlusion of the posterior cerebral artery (PCA) usually does not result in malignant infarction. Challenging this concept, we present 3 cases of unilateral PCA infarction with secondary malignant progression, resulting from extension into what would classically be considered the posterior middle cerebral artery (MCA) territory. Interestingly, these were true PCA infarctions, not "MCA plus" strokes, since the underlying occlusive lesion was in the PCA. We hypothesize that congenital and/or acquired variability in the distribution and extent of territory supplied by the PCA may underlie this rare clinical entity. Patients with a PCA infarction should thus be followed closely and offered early surgical decompression in the event of malignant progression.

Racial Differences in the Surgical Care of Medicare Beneficiaries With Localized Prostate Cancer.

PubMed

Schmid, Marianne; Meyer, Christian P; Reznor, Gally; Choueiri, Toni K; Hanske, Julian; Sammon, Jesse D; Abdollah, Firas; Chun, Felix K H; Kibel, Adam S; Tucker-Seeley, Reginald D; Kantoff, Philip W; Lipsitz, Stuart R; Menon, Mani; Nguyen, Paul L; Trinh, Quoc-Dien

2016-01-01

There is extensive evidence suggesting that black men with localized prostate cancer (PCa) have worse cancer-specific mortality compared with their non-Hispanic white counterparts. To evaluate racial disparities in the use, quality of care, and outcomes of radical prostatectomy (RP) in elderly men (≥ 65 years) with nonmetastatic PCa. This retrospective analysis of outcomes stratified according to race (black vs non-Hispanic white) included 2020 elderly black patients (7.6%) and 24,462 elderly non-Hispanic white patients (92.4%) with localized PCa who underwent RP within the first year of PCa diagnosis in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 1992 and 2009. The study was performed in 2014. Process of care (ie, time to treatment, lymph node dissection), as well as outcome measures (ie, complications, emergency department visits, readmissions, PCa-specific and all-cause mortality, costs) were evaluated using Cox proportional hazards regression. Multivariable conditional logistic regression and quantile regression were used to study the association of racial disparities with process of care and outcome measures. The proportion of black patients with localized prostate cancer who underwent RP within 90 days was 59.4% vs 69.5% of non-Hispanic white patients (P <  001). In quantile regression of the top 50% of patients, blacks had a 7-day treatment delay compared with non-Hispanic whites. (P <  001). Black patients were less likely to undergo lymph node dissection (odds ratio [OR], 0.76 [95% CI, 0.66-0.80]; P < .001) but had higher odds of postoperative visits to the emergency department (within 30 days: OR, 1.48 [95% CI, 1.18-1.86]); after 30 days or more (OR, 1.45 [95% CI, 1.19-1.76]) and readmissions (within 30 days: OR, 1.28 [95% CI, 1.02-1.61]); ≥ 30 days (OR, 1.27 [95% CI, 1.07-1.51]) compared with non-Hispanic whites. The surgical treatment of black patients was associated with a higher incremental annual cost (the top 50% of blacks spent $1185.50 (95% CI , $804.85-1 $1566.10; P < .001) more than the top 50% of non-Hispanic whites). There was no difference in PCa-specific mortality (P = .16) or all-cause mortality (P = .64) between black and non-Hispanic white men. Blacks treated with RP for localized PCa are more likely to experience adverse events and incur higher costs compared with non-Hispanic white men; however, this does not translate into a difference in PCa-specific or all-cause mortality.

Castration-resistant prostate cancer: targeted therapies.

PubMed

Leo, S; Accettura, C; Lorusso, V

2011-01-01

Castration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited. To review the concepts and rationale behind targeted agents currently in late-stage clinical testing for patients with CRPC. Novel targeted therapies in clinical trials were identified from registries. The Medline database was searched for all relevant reports published from 1996 to October 2009. Bibliographies of the retrieved articles and major international meeting abstracts were hand-searched to identify additional studies. Advances in our understanding of the molecular mechanisms underlying prostate cancer (PCa) progression have translated into a variety of treatment approaches. Agents targeting androgen receptor activation and local steroidogenesis, angiogenesis, immunotherapy, apoptosis, chaperone proteins, the insulin-like growth factor (IGF) pathway, RANK ligand, endothelin receptors, and the Src family kinases are entering or have recently completed accrual to phase III trials for patients with CRPC. There has been an increase in the understanding of the mechanisms of progression of CRPC. A number of new agents targeting mechanisms of PCa progression with early promising results are in clinical trials and have the potential to provide novel treatment options for CRPC in the near future. Copyright © 2011 S. Karger AG, Basel.

On a PCA-based lung motion model

PubMed Central

Li, Ruijiang; Lewis, John H; Jia, Xun; Zhao, Tianyu; Liu, Weifeng; Wuenschel, Sara; Lamb, James; Yang, Deshan; Low, Daniel A; Jiang, Steve B

2014-01-01

Respiration-induced organ motion is one of the major uncertainties in lung cancer radiotherapy and is crucial to be able to accurately model the lung motion. Most work so far has focused on the study of the motion of a single point (usually the tumor center of mass), and much less work has been done to model the motion of the entire lung. Inspired by the work of Zhang et al (2007 Med. Phys. 34 4772–81), we believe that the spatiotemporal relationship of the entire lung motion can be accurately modeled based on principle component analysis (PCA) and then a sparse subset of the entire lung, such as an implanted marker, can be used to drive the motion of the entire lung (including the tumor). The goal of this work is twofold. First, we aim to understand the underlying reason why PCA is effective for modeling lung motion and find the optimal number of PCA coefficients for accurate lung motion modeling. We attempt to address the above important problems both in a theoretical framework and in the context of real clinical data. Second, we propose a new method to derive the entire lung motion using a single internal marker based on the PCA model. The main results of this work are as follows. We derived an important property which reveals the implicit regularization imposed by the PCA model. We then studied the model using two mathematical respiratory phantoms and 11 clinical 4DCT scans for eight lung cancer patients. For the mathematical phantoms with cosine and an even power (2n) of cosine motion, we proved that 2 and 2n PCA coefficients and eigenvectors will completely represent the lung motion, respectively. Moreover, for the cosine phantom, we derived the equivalence conditions for the PCA motion model and the physiological 5D lung motion model (Low et al 2005 Int. J. Radiat. Oncol. Biol. Phys. 63 921–9). For the clinical 4DCT data, we demonstrated the modeling power and generalization performance of the PCA model. The average 3D modeling error using PCA was within 1 mm (0.7 ± 0.1 mm). When a single artificial internal marker was used to derive the lung motion, the average 3D error was found to be within 2 mm (1.8 ± 0.3 mm) through comprehensive statistical analysis. The optimal number of PCA coefficients needs to be determined on a patient-by-patient basis and two PCA coefficients seem to be sufficient for accurate modeling of the lung motion for most patients. In conclusion, we have presented thorough theoretical analysis and clinical validation of the PCA lung motion model. The feasibility of deriving the entire lung motion using a single marker has also been demonstrated on clinical data using a simulation approach. PMID:21865624

Potential impact of 68Ga-PSMA-11 PET/CT on prostate cancer definitive radiation therapy planning.

PubMed

Calais, Jérémie; Kishan, Amar U; Cao, Minsong; Fendler, Wolfgang P; Eiber, Matthias; Herrmann, Ken; Ceci, Francesco; Reiter, Robert E; Rettig, Matthew B; Hegde, John V; Shaverdian, Narek; King, Christopher R; Steinberg, Michael L; Czernin, Johannes; Nickols, Nicholas G

2018-04-13

Background: Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) detects PCa metastasis with superior accuracy with potential impact definitive radiation therapy (RT) planning for non-metastatic PCa. Objectives: i) To determine how often definitive PCa RT planning based on standard target volumes cover 68 Ga-PSMA-11 PET/CT defined disease, and ii) To assess the potential impact of 68 Ga-PSMA-11 PET/CT on definitive PCa RT planning. Patients and Methods: This is a post-hoc analysis of an intention to treat population of 73 patients with localized PCa without prior local therapy who underwent 68 Ga-PSMA PET/CT for initial staging as part of an Investigational New Drug trial. 11/73 were intermediate-risk (15%), 33/73 were high-risk (45%), 22/73 were very high risk (30%), and 7/73 were N1 (9.5%). Clinical target volumes (CTVs) that included the prostate, seminal vesicles, and pelvic lymph nodes (LNs) using Radiation Therapy Oncology Group (RTOG) consensus guidelines were contoured on the CT portion of the PET/CT by a radiation oncologist blinded to the PET findings. 68 Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. PSMA-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. Results: All patients had PSMA-positive primary prostate lesion(s). 25/73 (34%) and 7/73 (9.5%) had PSMA-positive pelvic nodal and distant metastases, respectively. The sites of nodal metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper-diaphragm (4%), and presacral (1.5%). The median size of the nodal lesions was 6 mm (range 4-24 mm). RT planning based on the CTVs covered 69/73 (94.5%) of primary disease and 20/25 (80%) of pelvic nodal disease, on a per-patient analysis. Conclusion: 68 Ga-PSMA-11 PET/CT had a major impact on intended definitive PCa RT planning in 12/73 of patients (16.5%) when RT fields covered the prostate, seminal vesicles and the pelvic LNs, and in 25/66 of patients (37%) when RT fields covered only the prostate and seminal vesicles (without pelvic LNs). Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

European Randomized Study of Screening for Prostate Cancer Risk Calculator: External Validation, Variability, and Clinical Significance.

PubMed

Gómez-Gómez, Enrique; Carrasco-Valiente, Julia; Blanca-Pedregosa, Ana; Barco-Sánchez, Beatriz; Fernandez-Rueda, Jose Luis; Molina-Abril, Helena; Valero-Rosa, Jose; Font-Ugalde, Pilar; Requena-Tapia, Maria José

2017-04-01

To externally validate the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC) and to evaluate its variability between 2 consecutive prostate-specific antigen (PSA) values. We prospectively catalogued 1021 consecutive patients before prostate biopsy for suspicion of prostate cancer (PCa). The risk of PCa and significant PCa (Gleason score ≥7) from 749 patients was calculated according to ERSPC-RC (digital rectal examination-based version 3 of 4) for 2 consecutive PSA tests per patient. The calculators' predictions were analyzed using calibration plots and the area under the receiver operating characteristic curve (area under the curve). Cohen kappa coefficient was used to compare the ability and variability. Of 749 patients, PCa was detected in 251 (33.5%) and significant PCa was detected in 133 (17.8%). Calibration plots showed an acceptable parallelism and similar discrimination ability for both PSA levels with an area under the curve of 0.69 for PCa and 0.74 for significant PCa. The ERSPC showed 226 (30.2%) unnecessary biopsies with the loss of 10 significant PCa. The variability of the RC was 16% for PCa and 20% for significant PCa, and a higher variability was associated with a reduced risk of significant PCa. We can conclude that the performance of the ERSPC-RC in the present cohort shows a high similitude between the 2 PSA levels; however, the RC variability value is associated with a decreased risk of significant PCa. The use of the ERSPC in our cohort detects a high number of unnecessary biopsies. Thus, the incorporation of ERSPC-RC could help the clinical decision to carry out a prostate biopsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Opioid Patient Controlled Analgesia (PCA) use during the Initial Experience with the IMPROVE PCA Trial: A Phase III Analgesic Trial for Hospitalized Sickle Cell Patients with Painful Episodes

PubMed Central

Dampier, Carlton D.; Smith, Wally R.; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C.; Minniti, Caterina P.; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A. Kyle; McClish, Donna; McKinlay, Sonja M.; Miller, Scott T.; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J.; Weiner, Debra L.

2015-01-01

Opioid analgesics administered by patient-controlled analgesia (PCA) are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations, a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents, mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI and in the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI 0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage. PMID:21953763

Polycaprolactone/maltodextrin nanocarrier for intracellular drug delivery: formulation, uptake mechanism, internalization kinetics, and subcellular localization.

PubMed

Korang-Yeboah, Maxwell; Gorantla, Yamini; Paulos, Simon A; Sharma, Pankaj; Chaudhary, Jaideep; Palaniappan, Ravi

2015-01-01

Prostate cancer (PCa) disease progression is associated with significant changes in intracellular and extracellular proteins, intracellular signaling mechanism, and cancer cell phenotype. These changes may have direct impact on the cellular interactions with nanocarriers; hence, there is the need for a much-detailed understanding, as nanocarrier cellular internalization and intracellular sorting mechanism correlate directly with bioavailability and clinical efficacy. In this study, we report the differences in the rate and mechanism of cellular internalization of a biocompatible polycaprolactone (PCL)/maltodextrin (MD) nanocarrier system for intracellular drug delivery in LNCaP, PC3, and DU145 PCa cell lines. PCL/MD nanocarriers were designed and characterized. PCL/MD nanocarriers significantly increased the intracellular concentration of coumarin-6 and fluorescein isothiocyanate-labeled bovine serum albumin, a model hydrophobic and large molecule, respectively. Fluorescence microscopy and flow cytometry analysis revealed rapid internalization of the nanocarrier. The extent of nanocarrier cellular internalization correlated directly with cell line aggressiveness. PCL/MD internalization was highest in PC3 followed by DU145 and LNCaP, respectively. Uptake in all PCa cell lines was metabolically dependent. Extraction of endogenous cholesterol by methyl-β-cyclodextrin reduced uptake by 75%±4.53% in PC3, 64%±6.01% in LNCaP, and 50%±4.50% in DU145, indicating the involvement of endogenous cholesterol in cellular internalization. Internalization of the nanocarrier in LNCaP was mediated mainly by macropinocytosis and clathrin-independent pathways, while internalization in PC3 and DU145 involved clathrin-mediated endocytosis, clathrin-independent pathways, and macropinocytosis. Fluorescence microscopy showed a very diffused and non-compartmentalized subcellular localization of the PCL/MD nanocarriers with possible intranuclear localization and minor colocalization in the lysosomes with time.

Prostate-cancer diagnosis by non-invasive prostatic Zinc mapping using X-Ray Fluorescence (XRF)

NASA Astrophysics Data System (ADS)

Cortesi, Marco

At present, the major screening tools (PSA, DRE, TRUS) for prostate cancer lack sensitivity and specificity, and none can distinguish between low-grade indolent cancer and high-grade lethal one. The situation calls for the promotion of alternative approaches, with better detection sensitivity and specificity, to provide more efficient selection of patients to biopsy and with possible guidance of the biopsy needles. The prime objective of the present work was the development of a novel non-invasive method and tool for promoting detection, localization, diagnosis and follow-up of PCa. The method is based on in-vivo imaging of Zn distribution in the peripheral zone of the prostate, by a trans-rectal X-ray fluorescence (XRF) probe. Local Zn levels, measured in 1--4 mm3 fresh tissue biopsy segments from an extensive clinical study involving several hundred patients, showed an unambiguous correlation with the histological classification of the tissue (Non-Cancer or PCa), and a systematic positive correlation of its depletion level with the cancer-aggressiveness grade (Gleason classification). A detailed analysis of computer-simulated Zn-concentration images (with input parameters from clinical data) disclosed the potential of the method to provide sensitive and specific detection and localization of the lesion, its grade and extension. Furthermore, it also yielded invaluable data on some requirements, such as the image resolution and counting-statistics, requested from a trans-rectal XRF probe for in-vivo recording of prostatic-Zn maps in patients. By means of systematic table-top experiments on prostate-phantoms comprising tumor-like inclusions, followed by dedicated Monte Carlo simulations, the XRF-probe and its components have been designed and optimized. Multi-parameter analysis of the experimental data confirmed the simulation estimations of the XRF detection system in terms of: delivered dose, counting statistics, scanning resolution, target-volume size and the accuracy of locating at various depths of small-volume tumor-like inclusions in tissue-phantoms. The clinical study, the Monte Carlo simulations and the analysis of Zn-map images provided essential information and promising vision on the potential performance of the Zn-based PCa detection concept. Simulations focusing on medical-probe design and its performance at permissible radiation doses yielded positive results - confirmed by a series of systematic laboratory experiments with a table-top XRF system.

Non-invasive urinary metabolomic profiling discriminates prostate cancer from benign prostatic hyperplasia.

PubMed

Pérez-Rambla, Clara; Puchades-Carrasco, Leonor; García-Flores, María; Rubio-Briones, José; López-Guerrero, José Antonio; Pineda-Lucena, Antonio

2017-01-01

Prostate cancer (PCa) is one of the most common malignancies in men worldwide. Serum prostate specific antigen (PSA) level has been extensively used as a biomarker to detect PCa. However, PSA is not cancer-specific and various non-malignant conditions, including benign prostatic hyperplasia (BPH), can cause a rise in PSA blood levels, thus leading to many false positive results. In this study, we evaluated the potential of urinary metabolomic profiling for discriminating PCa from BPH. Urine samples from 64 PCa patients and 51 individuals diagnosed with BPH were analysed using 1 H nuclear magnetic resonance ( 1 H-NMR). Comparative analysis of urinary metabolomic profiles was carried out using multivariate and univariate statistical approaches. The urine metabolomic profile of PCa patients is characterised by increased concentrations of branched-chain amino acids (BCAA), glutamate and pseudouridine, and decreased concentrations of glycine, dimethylglycine, fumarate and 4-imidazole-acetate compared with individuals diagnosed with BPH. PCa patients have a specific urinary metabolomic profile. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be useful to discriminate PCa from BPH in a clinical context.

Low-Molecular-Weight Protein Tyrosine Phosphatase Predicts Prostate Cancer Outcome by Increasing the Metastatic Potential.

PubMed

Ruela-de-Sousa, Roberta R; Hoekstra, Elmer; Hoogland, A Marije; Queiroz, Karla C Souza; Peppelenbosch, Maikel P; Stubbs, Andrew P; Pelizzaro-Rocha, Karin; van Leenders, Geert J L H; Jenster, Guido; Aoyama, Hiroshi; Ferreira, Carmen V; Fuhler, Gwenny M

2016-04-01

Low-risk patients suffering from prostate cancer (PCa) are currently placed under active surveillance rather than undergoing radical prostatectomy. However, clear parameters for selecting the right patient for each strategy are not available, and new biomarkers and treatment modalities are needed. Low-molecular-weight protein tyrosine phosphatase (LMWPTP) could present such a target. To correlate expression levels of LMWPTP in primary PCa to clinical outcome, and determine the role of LMWPTP in prostate tumor cell biology. Acid phosphatase 1, soluble (ACP1) expression was analyzed on microarray data sets, which were subsequently used in Ingenuity Pathway Analysis. Immunohistochemistry was performed on a tissue microarray containing material of 481 PCa patients whose clinicopathologic data were recorded. PCa cell line models were used to investigate the role of LMWPTP in cell proliferation, migration, adhesion, and anoikis resistance. The association between LMWPTP expression and clinical and pathologic outcomes was calculated using chi-square correlations and multivariable Cox regression analysis. Functional consequences of LMWPTP overexpression or downregulation were determined using migration and adhesion assays, confocal microscopy, Western blotting, and proliferation assays. LMWPTP expression was significantly increased in human PCa and correlated with earlier recurrence of disease (hazard ratio [HR]:1.99; p<0.001) and reduced patient survival (HR: 1.53; p=0.04). Unbiased Ingenuity analysis comparing cancer and normal prostate suggests migratory propensities in PCa. Indeed, overexpression of LMWPTP increases PCa cell migration, anoikis resistance, and reduces activation of focal adhesion kinase/paxillin, corresponding to decreased adherence. Overexpression of LMWPTP in PCa confers a malignant phenotype with worse clinical outcome. Prospective follow-up should determine the clinical potential of LMWPTP overexpression. These findings implicate low-molecular-weight protein tyrosine phosphatase as a novel oncogene in prostate cancer and could offer the possibility of using this protein as biomarker or target for treatment of this disease. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chylous ascites after resection of giant adrenocortical carcinoma.

PubMed

Habibi, Mani; Karakoyun, Rojbin; Demirci, Erkan; Alikanoglu, Arsenal Sezgin

2016-12-01

Postoperative chylous ascites (PCA) is a rare clinical state that occurs during abdominal surgery. Despite its rarity, the need to diagnose and treat PCA is increasing in importance with the increased number of wide resections and lymph node dissections being performed and the serious consequences of treatment. Here we describe the PCA complications we observed after resection for treating a case of giant adrenocortical carcinoma and we have the brief review of the PCA complication.

Prostate Specific Antigen (PSA) as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT) in Combination with Additional External Beam Radiation Therapy (EBRT) for High Risk Prostate Cancer.

PubMed

Ecke, Thorsten H; Huang-Tiel, Hui-Juan; Golka, Klaus; Selinski, Silvia; Geis, Berit Christine; Koswig, Stephan; Bathe, Katrin; Hallmann, Steffen; Gerullis, Holger

2016-11-10

High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer (PCa). Seventy-nine male patients (median age 71 years, range 50 to 79) with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval) with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA) value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index), Gleason score, D'Amico risk classification for PCa, digital rectal examination (DRE), PSA value after one/three/five year(s) follow-up (FU), time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis ( p = 0.009), PSA on date of first HDR-BT ( p = 0.033), and PSA on date of first follow-up after one year ( p = 0.025) have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities.

Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Diagnosis in Biopsy-naive Men with Suspected Prostate Cancer Based on Elevated Prostate-specific Antigen Values: Results from a Randomized Prospective Blinded Controlled Trial.

PubMed

Tonttila, Panu P; Lantto, Juha; Pääkkö, Eija; Piippo, Ulla; Kauppila, Saila; Lammentausta, Eveliina; Ohtonen, Pasi; Vaarala, Markku H

2016-03-01

Multiparametric magnetic resonance imaging (MP-MRI) may improve the detection of clinically significant prostate cancer (PCa). To compare MP-MRI transrectal ultrasound (TRUS)-fusion targeted biopsy with routine TRUS-guided random biopsy for overall and clinically significant PCa detection among patients with suspected PCa based on prostate-specific antigen (PSA) values. This institutional review board-approved, single-center, prospective, randomized controlled trial (April 2011 to December 2014) included 130 biopsy-naive patients referred for prostate biopsy based on PSA values (PSA <20 ng/ml or free-to-total PSA ratio ≤0.15 and PSA <10 ng/ml). Patients were randomized 1:1 to the MP-MRI or control group. Patients in the MP-MRI group underwent prebiopsy MP-MRI followed by 10- to 12-core TRUS-guided random biopsy and cognitive MRI/TRUS fusion targeted biopsy. The control group underwent TRUS-guided random biopsy alone. MP-MRI 3-T phased-array surface coil. The primary outcome was the number of patients with biopsy-proven PCa in the MP-MRI and control groups. Secondary outcome measures included the number of positive prostate biopsies and the proportion of clinically significant PCa in the MP-MRI and control groups. Between-group analyses were performed. Overall, 53 and 60 patients were evaluable in the MP-MRI and control groups, respectively. The overall PCa detection rate and the clinically significant cancer detection rate were similar between the MP-MRI and control groups, respectively (64% [34 of 53] vs 57% [34 of 60]; 7.5% difference [95% confidence interval (CI), -10 to 25], p=0.5, and 55% [29 of 53] vs 45% [27 of 60]; 9.7% difference [95% CI, -8.5 to 27], p=0.8). The PCa detection rate was higher than assumed during the planning of this single-center trial. MP-MRI/TRUS-fusion targeted biopsy did not improve PCa detection rate compared with TRUS-guided biopsy alone in patients with suspected PCa based on PSA values. In this randomized clinical trial, additional prostate magnetic resonance imaging (MRI) before prostate biopsy appeared to offer similar diagnostic accuracy compared with routine transrectal ultrasound-guided random biopsy in the diagnosis of prostate cancer. Similar numbers of cancers were detected with and without MRI. ClinicalTrials.gov identifier: NCT01357512. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Immunoseroproteomic Profiling in African American Men with Prostate Cancer: Evidence for an Autoantibody Response to Glycolysis and Plasminogen-Associated Proteins*

PubMed Central

Sanchez, Tino W.; Zhang, Guangyu; Li, Jitian; Dai, Liping; Mirshahidi, Saied; Wall, Nathan R.; Yates, Clayton; Wilson, Colwick; Montgomery, Susanne; Zhang, Jian-Ying; Casiano, Carlos A.

2016-01-01

African American (AA) men suffer from a disproportionately high incidence and mortality of prostate cancer (PCa) compared with other racial/ethnic groups. Despite these disparities, African American men are underrepresented in clinical trials and in studies on PCa biology and biomarker discovery. We used immunoseroproteomics to profile antitumor autoantibody responses in AA and European American (EA) men with PCa, and explored differences in these responses. This minimally invasive approach detects autoantibodies to tumor-associated antigens that could serve as clinical biomarkers and immunotherapeutic agents. Sera from AA and EA men with PCa were probed by immunoblotting against PC3 cell proteins, with AA sera showing stronger immunoreactivity. Mass spectrometry analysis of immunoreactive protein spots revealed that several AA sera contained autoantibodies to a number of proteins associated with both the glycolysis and plasminogen pathways, particularly to alpha-enolase (ENO1). The proteomic data is deposited in ProteomeXchange with identifier PXD003968. Analysis of sera from 340 racially diverse men by enzyme-linked immunosorbent assays (ELISA) showed higher frequency of anti-ENO1 autoantibodies in PCa sera compared with control sera. We observed differences between AA-PCa and EA-PCa patients in their immunoreactivity against ENO1. Although EA-PCa sera reacted with higher frequency against purified ENO1 in ELISA and recognized by immunoblotting the endogenous cellular ENO1 across a panel of prostate cell lines, AA-PCa sera reacted weakly against this protein by ELISA but recognized it by immunoblotting preferentially in metastatic cell lines. These race-related differences in immunoreactivity to ENO1 could not be accounted by differential autoantibody recognition of phosphoepitopes within this antigen. Proteomic analysis revealed differences in the posttranslational modification profiles of ENO1 variants differentially recognized by AA-PCa and EA-PCa sera. These intriguing results suggest the possibility of race-related differences in the antitumor autoantibody response in PCa, and have implications for defining novel biological determinants of PCa health disparities. PMID:27742740

Clinical performance of serum [-2]proPSA derivatives, %p2PSA and PHI, in the detection and management of prostate cancer.

PubMed

Huang, Ya-Qiang; Sun, Tong; Zhong, Wei-De; Wu, Chin-Lee

2014-01-01

Prostate-specific antigen (PSA) has been widely used as a serum marker for prostate cancer (PCa) screening or progression monitoring, which dramatically increased rate of early detection while significantly reduced PCa-specific mortality. However, a number of limitations of PSA have been noticed. Low specificity of PSA may lead to overtreatment in men who presenting with a total PSA (tPSA) level of < 10 ng/mL. As a type of free PSA (fPSA), [-2]proPSA is differentially expressed in peripheral zone of prostate gland and found to be elevated in serum of men with PCa. Two p2PSA-based derivatives, prostate health index (PHI) and %p2PSA, which were defined as [(p2PSA/fPSA) × √ tPSA] and [(p2PSA/fPSA) × 100] respectively, have been suggested to be increased in PCa and can better distinguish PCa from benign prostatic diseases than tPSA or fPSA. We performed a systematic review of the available scientific evidences to evaluate the potentials of %p2PSA and PHI in clinical application. Mounting evidences suggested that both %p2PSA and PHI possess higher area under the ROC curve (AUC) and better specificity at a high sensitivity for PCa detection when compare with tPSA and %fPSA. It indicated that measurements of %p2PSA and PHI significantly improved the accuracy of PCa detection and diminished unnecessary biopsies. Furthermore, elevations of %p2PSA and PHI are related to more aggressive diseases. %p2PSA and PHI might be helpful in reducing overtreatment on indolent cases or assessing the progression of PCa in men who undergo active surveillance. Further studies are needed before being applied in routine clinical practice.

High SRPX2 protein expression predicts unfavorable clinical outcome in patients with prostate cancer

PubMed Central

Zhang, Meng; Li, Xiaoli; Fan, Zhirui; Zhao, Jing; Liu, Shuzheng; Zhang, Mingzhi; Li, Huixiang; Goscinski, Mariusz Adam; Fan, Huijie; Suo, Zhenhe

2018-01-01

Background Sushi repeat-containing protein X-linked 2 (SRPX2) is overexpressed in a variety of different tumor tissues and correlated with poor prognosis in patients. Little research focuses on the role of SRPX2 expression in prostate cancer (PCa), and the clinicopathological significance of the protein expression in this tumor is relatively unknown. However, our previous transcriptome data from those cancer stem-like cells indicated the role of SRPX2 in PCa. Materials and methods In this study, RT-PCR and Western blotting were firstly used to examine the SRPX2 expression in three PCa cell lines including LNCaP, DU145, and PC3, and then SRPX2 protein expression was immunohistochemically investigated and statistically analyzed in a series of 106 paraffin-embedded PCa tissue specimens. Results Significantly lower levels of SRPX2 expression were verified in the LNCaP cells, compared with the expression in the aggressive DU145 and PC3 cells, in both mRNA and protein levels. Immunohistochemically, there were variable SRPX2 protein expressions in the clinical samples. Moreover, high levels of SRPX2 expression in the PCa tissues were significantly associated with Gleason score (P=0.008), lymph node metastasis (P=0.009), and distant metastasis (P=0.021). Furthermore, higher levels of SRPX2 expression in the PCa tissues were significantly associated with shorter overall survival (OS) (P<0.001). Conclusion Our results demonstrate that SRPX2 is highly expressed in aggressive PCa cells in vitro, and its protein expression in PCa is significantly associated with malignant clinical features and shorter OS, strongly indicating its prognostic value in prostate cancers. PMID:29881288

Machine learning-based analysis of MR radiomics can help to improve the diagnostic performance of PI-RADS v2 in clinically relevant prostate cancer.

PubMed

Wang, Jing; Wu, Chen-Jiang; Bao, Mei-Ling; Zhang, Jing; Wang, Xiao-Ning; Zhang, Yu-Dong

2017-10-01

To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 [95% CI 0.923-0.976]) than PI-RADS (Az: 0.878 [0.834-0.914], p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 [0.945-0.988] vs. 0.940 [0.905-0.965], p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 [0.960-0.995]) and PCa versus TZ (Az: 0.968 [0.940-0.985]). Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa. • Machine-based analysis of MR radiomics outperformed in TZ cancer against PI-RADS. • Adding MR radiomics significantly improved the performance of PI-RADS. • DKI-derived Dapp and Kapp were two strong markers for the diagnosis of PCa.

Patient-controlled hospital admission for patients with severe mental disorders: a nationwide prospective multicentre study.

PubMed

Thomsen, C T; Benros, M E; Maltesen, T; Hastrup, L H; Andersen, P K; Giacco, D; Nordentoft, M

2018-04-01

To assess whether implementing patient-controlled admission (PCA) can reduce coercion and improve other clinical outcomes for psychiatric in-patients. During 2013-2016, 422 patients in the PCA group were propensity score matched 1:5 with a control group (n = 2110) that received treatment as usual (TAU). Patients were followed up for at least one year using the intention to treat principle utilising nationwide registers. In a paired design, the outcomes of PCA patients during the year after signing a contract were compared with the year before. No reduction in coercion (risk difference = 0.001; 95% CI: -0.038; 0.040) or self-harming behaviour (risk difference = 0.005; 95% CI: -0.008; 0.018) was observed in the PCA group compared with the TAU group. The PCA group had more in-patient bed days (mean difference = 28.4; 95% CI: 21.3; 35.5) and more medication use (P < 0.0001) than the TAU group. Before and after analyses showed reduction in coercion (P = 0.0001) and in-patient bed days (P = 0.0003). Implementing PCA did not reduce coercion, service use or self-harm behaviour when compared with TAU. Beneficial effects of PCA were observed only in the before and after PCA comparisons. Further research should investigate whether PCA affects other outcomes to better establish its clinical value. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Low-rank plus sparse decomposition for exoplanet detection in direct-imaging ADI sequences. The LLSG algorithm

NASA Astrophysics Data System (ADS)

Gomez Gonzalez, C. A.; Absil, O.; Absil, P.-A.; Van Droogenbroeck, M.; Mawet, D.; Surdej, J.

2016-05-01

Context. Data processing constitutes a critical component of high-contrast exoplanet imaging. Its role is almost as important as the choice of a coronagraph or a wavefront control system, and it is intertwined with the chosen observing strategy. Among the data processing techniques for angular differential imaging (ADI), the most recent is the family of principal component analysis (PCA) based algorithms. It is a widely used statistical tool developed during the first half of the past century. PCA serves, in this case, as a subspace projection technique for constructing a reference point spread function (PSF) that can be subtracted from the science data for boosting the detectability of potential companions present in the data. Unfortunately, when building this reference PSF from the science data itself, PCA comes with certain limitations such as the sensitivity of the lower dimensional orthogonal subspace to non-Gaussian noise. Aims: Inspired by recent advances in machine learning algorithms such as robust PCA, we aim to propose a localized subspace projection technique that surpasses current PCA-based post-processing algorithms in terms of the detectability of companions at near real-time speed, a quality that will be useful for future direct imaging surveys. Methods: We used randomized low-rank approximation methods recently proposed in the machine learning literature, coupled with entry-wise thresholding to decompose an ADI image sequence locally into low-rank, sparse, and Gaussian noise components (LLSG). This local three-term decomposition separates the starlight and the associated speckle noise from the planetary signal, which mostly remains in the sparse term. We tested the performance of our new algorithm on a long ADI sequence obtained on β Pictoris with VLT/NACO. Results: Compared to a standard PCA approach, LLSG decomposition reaches a higher signal-to-noise ratio and has an overall better performance in the receiver operating characteristic space. This three-term decomposition brings a detectability boost compared to the full-frame standard PCA approach, especially in the small inner working angle region where complex speckle noise prevents PCA from discerning true companions from noise.

Health status monitoring for ICU patients based on locally weighted principal component analysis.

PubMed

Ding, Yangyang; Ma, Xin; Wang, Youqing

2018-03-01

Intelligent status monitoring for critically ill patients can help medical stuff quickly discover and assess the changes of disease and then make appropriate treatment strategy. However, general-type monitoring model now widely used is difficult to adapt the changes of intensive care unit (ICU) patients' status due to its fixed pattern, and a more robust, efficient and fast monitoring model should be developed to the individual. A data-driven learning approach combining locally weighted projection regression (LWPR) and principal component analysis (PCA) is firstly proposed and applied to monitor the nonlinear process of patients' health status in ICU. LWPR is used to approximate the complex nonlinear process with local linear models, in which PCA could be further applied to status monitoring, and finally a global weighted statistic will be acquired for detecting the possible abnormalities. Moreover, some improved versions are developed, such as LWPR-MPCA and LWPR-JPCA, which also have superior performance. Eighteen subjects were selected from the Physiobank's Multi-parameter Intelligent Monitoring for Intensive Care II (MIMIC II) database, and two vital signs of each subject were chosen for online monitoring. The proposed method was compared with several existing methods including traditional PCA, Partial least squares (PLS), just in time learning combined with modified PCA (L-PCA), and Kernel PCA (KPCA). The experimental results demonstrated that the mean fault detection rate (FDR) of PCA can be improved by 41.7% after adding LWPR. The mean FDR of LWPR-MPCA was increased by 8.3%, compared with the latest reported method L-PCA. Meanwhile, LWPR spent less training time than others, especially KPCA. LWPR is first introduced into ICU patients monitoring and achieves the best monitoring performance including adaptability to changes in patient status, sensitivity for abnormality detection as well as its fast learning speed and low computational complexity. The algorithm is an excellent approach to establishing a personalized model for patients, which is the mainstream direction of modern medicine in the following development, as well as improving the global monitoring performance. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Chylous ascites after resection of giant adrenocortical carcinoma

PubMed Central

Karakoyun, Rojbin; Demirci, Erkan; Alikanoglu, Arsenal Sezgin

2016-01-01

Postoperative chylous ascites (PCA) is a rare clinical state that occurs during abdominal surgery. Despite its rarity, the need to diagnose and treat PCA is increasing in importance with the increased number of wide resections and lymph node dissections being performed and the serious consequences of treatment. Here we describe the PCA complications we observed after resection for treating a case of giant adrenocortical carcinoma and we have the brief review of the PCA complication. PMID:28149812

Tau PET binding distinguishes patients with early-stage posterior cortical atrophy from amnestic Alzheimer disease dementia

PubMed Central

Day, Gregory S.; Gordon, Brian A.; Jackson, Kelley; Christensen, Jon J.; Ponisio, Maria Rosana; Su, Yi; Ances, Beau M; Benzinger, Tammie L.S.; Morris, John C.

2017-01-01

Background Flortaucipir (tau) PET binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Methods Flortaucipir and florbetapir (β-amyloid) PET-imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxel-wise level, controlling for age. Results PCA patients (median age-at-onset, 59 [51–61] years) were younger at symptom-onset than similarly-staged individuals with amnestic AD (75 [60–85] years) or CN controls (73 [61–90] years; p=0.002). Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Conclusions and Relevance Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype. PMID:28394771

[The value of PHI/PCA3 in the early diagnosis of prostate cancer].

PubMed

Tan, S J; Xu, L W; Xu, Z; Wu, J P; Liang, K; Jia, R P

2016-01-12

To investigate the value of prostate health index (PHI) and prostate cancer gene 3 (PCA3) in the early diagnosis of prostate cancer (PCa). A total of 190 patients with abnormal serum prostate specific antigen (PSA) or abnormal digital rectal examination were enrolled. They were all underwent initial biopsy and 11 of them were also underwent repeated biopsy. In addition, 25 healthy cases (with normal digital rectal examination and PSA<4 ng/ml) were the control group.The PHI and PCA3 were detected by using immunofluorescence and Loop-Mediated Isothermal Amplification (LAMP). The sensitivity and specificity of diagnosis were determined by ROC curve.In addition, the relationship between PHI/PSA and the Gleason score and clinical stage were analyzed. A total of 89 patients were confirmed PCa by Pathological diagnosis. The other 101 patients were diagnosed as benign prostatic hyperplasia (BPH). The sensitivity and specificity of PCA3 test were 85.4% was 92.1%. Area under curve (AUC) of PHI is higher than AUC of PSA (0.727>0.699). The PHI in peripheral blood was positively correlated with Gleason score and clinical stage. The detection of PCA3 and PHI shows excellent detecting effectiveness. Compared with single PSA, the combined detection of PHI and PCA3 improved the diagnostic specificity. It can provide a new method for the early diagnosis in prostate cancer and avoid unnecessary biopsies.

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia.

PubMed

Day, Gregory S; Gordon, Brian A; Jackson, Kelley; Christensen, Jon J; Rosana Ponisio, Maria; Su, Yi; Ances, Beau M; Benzinger, Tammie L S; Morris, John C

2017-01-01

Flortaucipir (tau) positron emission tomography (PET) binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau-PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Flortaucipir and florbetapir (β-amyloid) PET imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxelwise level, controlling for age. PCA patients [median age-at-onset, 59 (51 to 61) years] were younger at symptom onset than similarly staged individuals with amnestic AD [75 (60 to 85) years] or CN controls [73 (61 to 90) years; P=0.002]. Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype.

Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell patients with painful episodes.

PubMed

Dampier, Carlton D; Smith, Wally R; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C; Minniti, Caterina P; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A Kyle; McClish, Donna; McKinlay, Sonja M; Miller, Scott T; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J; Weiner, Debra L

2011-12-01

Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations,a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI—higher demand dose with low constant infusion or LDHI—lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents,mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI andin the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage.

Transcatheter Arterial Embolization with a Mixture of Absolute Ethanol and Iodized Oil for Poorly Visualized Endophytic Renal Masses Prior to CT-Guided Percutaneous Cryoablation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michimoto, Kenkichi, E-mail: michikoo@jikei.ac.jp; Shimizu, Kanichiro; Kameoka, Yoshihiko

PurposeTo retrospectively evaluate the feasibility of transcatheter arterial embolization (TAE) using a mixture of absolute ethanol and iodized oil to improve localization of endophytic renal masses on unenhanced computed tomography (CT) prior to CT-guided percutaneous cryoablation (PCA).Materials and MethodsOur institutional review board approved this retrospective study. From September 2011 to June 2015, 17 patients (mean age, 66.8 years) with stage T1a endophytic renal masses (mean diameter, 26.5 mm) underwent TAE using a mixture of absolute ethanol and iodized oil to improve visualization of small and endophytic renal masses on unenhanced CT prior to CT-guided PCA. TAE was considered successful that accumulated iodizedmore » oil depicted whole of the tumor edge on CT. PCA was considered successful when the iceball covered the entire tumor with over a 5 mm margin. Oncological and renal functional outcomes and complications were also evaluated.ResultsTAE was successfully performed in 16 of 17 endophytic tumors. The 16 tumors were performed under CT-guided PCA with their distinct visualization of localization and safe ablated margin. During the mean follow-up period of 15.4 ± 5.1 months, one patient developed local recurrence. Estimated glomerular filtration rate declined by 8 % with statistical significance (P = 0.01). There was no procedure-related significant complication.ConclusionTAE using a mixture of absolute ethanol and iodized oil to improve visualization of endophytic renal masses facilitated tumor localization on unenhanced CT, permitting depiction of the tumor edge as well as a safe margin for ablation during CT-guided PCA, with an acceptable decline in renal function.« less

Innovations in imaging modalities for recurrent and metastatic prostate cancer: a systematic review.

PubMed

Albisinni, Simone; Aoun, Fouad; Marcelis, Quentin; Jungels, Claude; Al Hajj Obeid, Walid; Zanaty, Marc; Tubaro, Andrea; Roumeguere, Thierry; DE Nunzio, Cosimo

2018-01-31

The last decade has witnessed tremendous changes in the management of advanced and metastatic castration resistant prostate cancer (mCRPC). In the current systematic review, we analyze novel imaging techniques in the setting of recurrent and metastatic PCa, exploring available data and highlighting future exams which could enter clinical practice in the upcoming years. The National Library of Medicine Database was searched for relevant articles published between January 2012 and August 2017. A wide search was performed including the combination of following words: "Prostate" AND "Cancer" AND ("Metastatic" OR "Recurrent") AND "imaging" AND ("MRI" OR "PET"). The selection procedure followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) principles and is presented using a PRISMA flow chart. Novel imaging techniques, as multiparametric MRI, whole-body MRI and Choline and PSMA PET imaging techniques are currently revolutioning the treatment planning in patients with advanced and metastatic PCa, allowing a better characterization of the disease. Multiparametric MRI performs well in the detection of local recurrences, with sensitivity rates of 67-98% and overall diagnostic accuracy of 83-93%, depending on the type of magnetic field strength (1.5 vs 3T). Whole body MRI instead shows a high specificity (>95%) for bone metastases. PET imaging, and in particular PSMA PET/CT, showed promising results in the detection of both local and distant recurrences, even for low PSA values (<0.5ng/ml). Sensitivity varies from 77-98% depending on PSA value and PSA velocity. Whole body-MRI, NaF PET, Choline-PET/CT and PSMA PET/CT are flourishing techniques which find great application in the field of recurrent and metastatic PCa, in the effort to reduce treatment of "PSA only" and rather focus our therapies on clinical tumor entities. Standardization is urgently needed to allow adequate comparison of results and diffusion on a large scale.

Co-Expression of Putative Cancer Stem Cell Markers CD44 and CD133 in Prostate Carcinomas.

PubMed

Kalantari, Elham; Asgari, Mojgan; Nikpanah, Seyedehmoozhan; Salarieh, Naghme; Asadi Lari, Mohammad Hossein; Madjd, Zahra

2017-10-01

Cancer stem cells (CSCs) are the main players of prostate tumorigenesis thus; characterization of CSCs can pave the way for understanding the early detection, drug resistance, metastasis and relapse. The current study was conducted to evaluate the expression level and clinical significance of the potential CSC markers CD44 and CD133 in a series of prostate tissues. One hundred and forty eight prostate tissues composed of prostate cancer (PCa), high-grade prostatic intraepithelial neoplasia (HGPIN), and benign prostate hyperplasia (BPH) were immunostained for the putative CSC markers CD44 and CD133. Subsequently, the correlation between the expression of these markers and the clinicopathological variables was examined. A higher level of CD44 expression was observed in 42% of PCa, 57% of HGPIN, and 42% BPH tissues. In the case of CD133 expression PCa, HGPIN, and BPH samples demonstrated high immunoreactivity in 46%, 43%, and 42% of cells, respectively. Statistical analysis showed an inverse significant correlation between CD44 expression with Gleason score of PCa (P = 0.02), while no significant correlation was observed between CD133 expression and clinicopathological parameters. A significant reciprocal correlation was observed between the expression of two putative CSC markers CD44 and CD133 in PCa specimens while not indicating clinical significance. Further clinical investigation is required to consider these markers as targets of new therapeutic strategies for PCa.

Incidental Prostate Adenocarcinoma in Cystoprostatectomy Specimens: Partial Versus Complete Prostate Sampling.

PubMed

Filter, Emily R; Gabril, Manal Y; Gomez, Jose A; Wang, Peter Z T; Chin, Joseph L; Izawa, Jonathan; Moussa, Madeleine

2017-08-01

The rate of incidental prostate adenocarcinoma (PCa) detection in radical cystoprostatectomy (RCP) varies widely, ranging from 15% to 54%. Such variability may be explained by institutional differences in prostate grossing protocols. Either partial or complete submission of the prostate gland in RCP may result in detection of clinically insignificant or significant incidental PCa. The aim of the study was to compare the clinical significance of PCa in RCP specimens in partial versus complete sampling. Seventy-two out of 158 RCP cases showed incidental PCa. The pathologic features, including Gleason score, margin status, extraprostatic extension (EPE), seminal vesicle invasion (SVI), PCa stage, and tumor volume, were assessed. The 72 cases were divided into partial (n = 21, 29.1%) and complete sampling (n = 51, 70.8%) groups. EPE was detected in 13/72 (18.1%) with 11/13 (84.6%) cases in the complete group. Positive margins were present in 11/72 (15.3%) with 9/11 (81.8%) in the complete group. SVI was detected in 4/72 (5.6%) with 3/4 (75.0%) in the complete group. Overall, 4/72 (5.6%) had a Gleason score >7, all of which were in the complete group. Our data suggest that complete sampling of the prostate may be the ideal approach to grossing RCP specimens, allowing for greater detection of clinically significant incidental PCa.

Applying robust variant of Principal Component Analysis as a damage detector in the presence of outliers

NASA Astrophysics Data System (ADS)

Gharibnezhad, Fahit; Mujica, Luis E.; Rodellar, José

2015-01-01

Using Principal Component Analysis (PCA) for Structural Health Monitoring (SHM) has received considerable attention over the past few years. PCA has been used not only as a direct method to identify, classify and localize damages but also as a significant primary step for other methods. Despite several positive specifications that PCA conveys, it is very sensitive to outliers. Outliers are anomalous observations that can affect the variance and the covariance as vital parts of PCA method. Therefore, the results based on PCA in the presence of outliers are not fully satisfactory. As a main contribution, this work suggests the use of robust variant of PCA not sensitive to outliers, as an effective way to deal with this problem in SHM field. In addition, the robust PCA is compared with the classical PCA in the sense of detecting probable damages. The comparison between the results shows that robust PCA can distinguish the damages much better than using classical one, and even in many cases allows the detection where classic PCA is not able to discern between damaged and non-damaged structures. Moreover, different types of robust PCA are compared with each other as well as with classical counterpart in the term of damage detection. All the results are obtained through experiments with an aircraft turbine blade using piezoelectric transducers as sensors and actuators and adding simulated damages.

Methylation of subtelomeric repeat D4Z4 in peripheral blood leukocytes is associated with biochemical recurrence in localized prostate cancer patients.

PubMed

Han, Yuyan; Xu, Junfeng; Kim, Jeri; Wu, Xifeng; Gu, Jian

2017-08-01

Global DNA methylation may affect chromosome structure and genomic stability and is involved in carcinogenesis. In this study, we aimed to investigate whether methylation of pericentromeric repeat NBL2 and subtelomeric repeat D4Z4 in peripheral blood was associated with the aggressiveness of prostate cancer (PCa). We measured the methylation status of different CpG sites of NBL2 and D4Z4 in 795 PCa patients and compared their methylation levels among patients with different Gleason Score at diagnosis. We then analyzed the association of the NBL2 and D4Z4 methylation with the risk of biochemical recurrence (BCR) in patients receiving radical prostatectomy or radiotherapy using a multivariate Cox proportional hazards model. In addition, we used the Kaplan-Meier survival function and log-rank tests to assess BCR-free survival associated with D4Z4 methylation. There was no significant difference in methylation level of NBL2 and D4Z4 between clinically defined aggressive and non-aggressive PCa at diagnosis. However, the methylation of D4Z4 was associated with BCR, while the methylation of NBL2 was not. In tertile analysis, patients in the highest tertile of D4Z4 methylation had an increased risk of BCR (HR = 2.17, 95% CI 1.36-3.48) compared to patients in the lower tertiles after adjustment of age, body mass index, smoking status, pack year, D'Amico risk groups and treatments. Among the four CpG sites in this region, the association was mostly attributable to the methylation of the second CpG site of D4Z4. These data suggest that higher methylation in D4Z4 was associated with worse prognosis of localized PCa patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Role of Proteomics in Biomarker Development for Improved Patient Diagnosis and Clinical Decision Making in Prostate Cancer

PubMed Central

Tonry, Claire L.; Leacy, Emma; Raso, Cinzia; Finn, Stephen P.; Armstrong, John; Pennington, Stephen R.

2016-01-01

Prostate Cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Although increased expression of prostate-specific antigen (PSA) is an effective indicator for the recurrence of PCa, its intended use as a screening marker for PCa is of considerable controversy. Recent research efforts in the field of PCa biomarkers have focused on the identification of tissue and fluid-based biomarkers that would be better able to stratify those individuals diagnosed with PCa who (i) might best receive no treatment (active surveillance of the disease); (ii) would benefit from existing treatments; or (iii) those who are likely to succumb to disease recurrence and/or have aggressive disease. The growing demand for better prostate cancer biomarkers has coincided with the development of improved discovery and evaluation technologies for multiplexed measurement of proteins in bio-fluids and tissues. This review aims to (i) provide an overview of these technologies as well as describe some of the candidate PCa protein biomarkers that have been discovered using them; (ii) address some of the general limitations in the clinical evaluation and validation of protein biomarkers; and (iii) make recommendations for strategies that could be adopted to improve the successful development of protein biomarkers to deliver improvements in personalized PCa patient decision making. PMID:27438858

The epigenetics of prostate cancer diagnosis and prognosis: update on clinical applications.

PubMed

Blute, Michael L; Damaschke, Nathan A; Jarrard, David F

2015-01-01

There is a major deficit in our ability to detect and predict the clinical behavior of prostate cancer (PCa). Epigenetic changes are associated with PCa development and progression. This review will focus on recent results in the clinical application of diagnostic and prognostic epigenetic markers. The development of high throughput technology has seen an enormous increase in the discovery of new markers that encompass epigenetic changes including those in DNA methylation and histone modifications. Application of these findings to urine and other biofluids, but also cancer and noncancerous prostate tissue, has resulted in new biomarkers. There has been a recent commercial development of a DNA methylation-based assay for identifying PCa risk from normal biopsy tissue. Other biomarkers are currently in the validation phase and encompass combinations of multiple genes. Epigenetic changes improve the specificity and sensitivity of PCa diagnosis and have the potential to help determine clinical prognosis. Additional studies will not only provide new and better biomarker candidates, but also have the potential to inform new therapeutic strategies given the reversibility of these processes.

Metabolic syndrome and low high-density lipoprotein cholesterol are associated with adverse pathological features in patients with prostate cancer treated by radical prostatectomy.

PubMed

Lebdai, Souhil; Mathieu, Romain; Leger, Julie; Haillot, Olivier; Vincendeau, Sébastien; Rioux-Leclercq, Nathalie; Fournier, Georges; Perrouin-Verbe, Marie-Aimée; Doucet, Laurent; Azzouzi, Abdel Rahmene; Rigaud, Jérome; Renaudin, Karine; Charles, Thomas; Bruyere, Franck; Fromont, Gaelle

2018-02-01

Previous studies have suggested a link between metabolic syndrome (MetS) and prostate cancer (PCa). In the present study, we aimed to assess the association between MetS and markers of PCa aggressiveness on radical prostatectomy (RP). All patients consecutively treated for PCa by RP in 6 academic institutions between August 2013 and July 2016 were included. MetS was defined as at least 3 of 5 components (obesity, elevated blood pressure, diabetes, low high-density lipoprotein (HDL)-cholesterol, and hypertriglyceridemia). Demographic, biological, and clinical parameters were prospectively collected, including: age, biopsy results, preoperative serum prostate-specific antigen, surgical procedure, and pathological data of RP specimen. Locally advanced disease was defined as a pT-stage ≥3. International Society of Urological Pathology (ISUP) groups were used for pathological grading. Qualitative and quantitative variables were compared using chi-square and Wilcoxon tests; logistic regression analyses assessed the association of MetS and its components with pathological data. Statistical significance was defined as a P<0.05. Among 567 men, 249 (44%) had MetS. In a multivariate model including preoperative prostate-specific antigen, biopsy ISUP-score, clinical T-stage, age, and ethnicity: we found that MetS was an independent risk factor for positive margins, and ISUP group ≥4 on the RP specimen (odds ratio [OR] = 1.5; 95% CI: 1.1-2.3; P = 0.035; OR = 2.0; 95% CI: 1.1-4.0; P = 0.044, respectively). In addition, low HDL-cholesterol level was associated with locally advanced PCa (OR = 1.6; 95% CI: 1.1-2.4; P = 0.024). Risks of adverse pathological features increased with the number of MetS components: having ≥ 4 MetS components was significantly associated with higher risk of ISUP group ≥ 4 and higher risk of positive margins (OR = 1.9; 95% CI: 1.1-3.3; P = 0.017; OR = 1.8; 95% CI: 1.1-2.8; P = 0.007, respectively). MetS was an independent predictive factor for higher ISUP group and positive margins at RP. Low HDL-cholesterol alone, and having 4 and more MetS components were also associated with higher risk of adverse pathological features. Copyright © 2018. Published by Elsevier Inc.

The language profile of Posterior Cortical Atrophy

PubMed Central

Crutch, Sebastian J.; Lehmann, Manja; Warren, Jason D.; Rohrer, Jonathan D.

2015-01-01

Background Posterior Cortical Atrophy (PCA) is typically considered to be a visual syndrome, primarily characterised by progressive impairment of visuoperceptual and visuospatial skills. However patients commonly describe early difficulties with word retrieval. This paper details the first systematic analysis of linguistic function in PCA. Characterising and quantifying the aphasia associated with PCA is important for clarifying diagnostic and selection criteria for clinical and research studies. Methods Fifteen patients with PCA, 7 patients with logopenic/phonological aphasia (LPA) and 18 age-matched healthy participants completed a detailed battery of linguistic tests evaluating auditory input processing, repetition and working memory, lexical and grammatical comprehension, single word retrieval and fluency, and spontaneous speech. Results Relative to healthy controls, PCA patients exhibited language impairments across all the domains examined, but with anomia, reduced phonemic fluency and slowed speech rate the most prominent deficits. PCA performance most closely resembled that of LPA patients on tests of auditory input processing, repetition and digit span, but was relatively stronger on tasks of comprehension and spontaneous speech. Conclusions The study demonstrates that in addition to the well-reported degradation of vision, literacy and numeracy, PCA is characterised by a progressive oral language dysfunction with prominent word retrieval difficulties. Overlap in the linguistic profiles of PCA and LPA, which are both most commonly caused by Alzheimer’s disease, further emphasises the notion of a phenotypic continuum between typical and atypical manifestations of the disease. Clarifying the boundaries between AD phenotypes has important implications for diagnosis, clinical trial recruitment and investigations into biological factors driving phenotypic heterogeneity in AD. Rehabilitation strategies to ameliorate the phonological deficit in PCA are required. PMID:23138762

Prostate Cancer Cell–Stromal Cell Cross-Talk via FGFR1 Mediates Antitumor Activity of Dovitinib in Bone Metastases

PubMed Central

Wan, Xinhai; Corn, Paul G.; Yang, Jun; Palanisamy, Nallasivam; Starbuck, Michael W.; Efstathiou, Eleni; Li-Ning Tapia, Elsa M.; Zurita, Amado J.; Aparicio, Ana; Ravoori, Murali K.; Vazquez, Elba S.; Robinson, Dan R.; Wu, Yi-Mi; Cao, Xuhong; Iyer, Matthew K.; McKeehan, Wallace; Kundra, Vikas; Wang, Fen; Troncoso, Patricia; Chinnaiyan, Arul M.; Logothetis, Christopher J.; Navone, Nora M.

2015-01-01

Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell–bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors. PMID:25186177

Prostate cancer cell-stromal cell crosstalk via FGFR1 mediates antitumor activity of dovitinib in bone metastases.

PubMed

Wan, Xinhai; Corn, Paul G; Yang, Jun; Palanisamy, Nallasivam; Starbuck, Michael W; Efstathiou, Eleni; Li Ning Tapia, Elsa M; Tapia, Elsa M Li-Ning; Zurita, Amado J; Aparicio, Ana; Ravoori, Murali K; Vazquez, Elba S; Robinson, Dan R; Wu, Yi-Mi; Cao, Xuhong; Iyer, Matthew K; McKeehan, Wallace; Kundra, Vikas; Wang, Fen; Troncoso, Patricia; Chinnaiyan, Arul M; Logothetis, Christopher J; Navone, Nora M

2014-09-03

Bone is the most common site of prostate cancer (PCa) progression to a therapy-resistant, lethal phenotype. We found that blockade of fibroblast growth factor receptors (FGFRs) with the receptor tyrosine kinase inhibitor dovitinib has clinical activity in a subset of men with castration-resistant PCa and bone metastases. Our integrated analyses suggest that FGF signaling mediates a positive feedback loop between PCa cells and bone cells and that blockade of FGFR1 in osteoblasts partially mediates the antitumor activity of dovitinib by improving bone quality and by blocking PCa cell-bone cell interaction. These findings account for clinical observations such as reductions in lesion size and intensity on bone scans, lymph node size, and tumor-specific symptoms without proportional declines in serum prostate-specific antigen concentration. Our findings suggest that targeting FGFR has therapeutic activity in advanced PCa and provide direction for the development of therapies with FGFR inhibitors. Copyright © 2014, American Association for the Advancement of Science.

The Role of Central Metabolism in Prostate Cancer Progression

DTIC Science & Technology

2009-10-01

metabolites of dietary ω-3 and - 6 PUFAs directly affect PCa and the ability to do so depends on intake and metabolic enzyme expression. Omega -3 and - 6 ...The Role of Central Metabolism in Prostate Cancer Progression 5b. GRANT NUMBER W81XWH-08-1-0694 5c. PROGRAM ELEMENT NUMBER 6 . AUTHOR(S) Thomas...ABSTRACT We hypothesize that by enriching the diet with -3 PUFAs PCa tumor progression will be significantly reduced. Patients with localized PCa

Clinical Significance of Retinoic Acid Receptor Beta Promoter Methylation in Prostate Cancer: A Meta-Analysis.

PubMed

Dou, MengMeng; Zhou, XueLiang; Fan, ZhiRui; Ding, XianFei; Li, LiFeng; Wang, ShuLing; Xue, Wenhua; Wang, Hui; Suo, Zhenhe; Deng, XiaoMing

2018-01-01

Retinoic acid receptor beta (RAR beta) is a retinoic acid receptor gene that has been shown to play key roles during multiple cancer processes, including cell proliferation, apoptosis, migration and invasion. Numerous studies have found that methylation of the RAR beta promoter contributed to the occurrence and development of malignant tumors. However, the connection between RAR beta promoter methylation and prostate cancer (PCa) remains unknown. This meta-analysis evaluated the clinical significance of RAR beta promoter methylation in PCa. We searched all published records relevant to RAR beta and PCa in a series of databases, including PubMed, Embase, Cochrane Library, ISI Web of Science and CNKI. The rates of RAR beta promoter methylation in the PCa and control groups (including benign prostatic hyperplasia and normal prostate tissues) were summarized. In addition, we evaluated the source region of available samples and the methods used to detect methylation. To compare the incidence and variation in RAR beta promoter methylation in PCa and non-PCa tissues, the odds ratio (OR) and 95% confidence interval (CI) were calculated accordingly. All the data were analyzed with the statistical software STATA 12.0. Based on the inclusion and exclusion criteria, 15 articles assessing 1,339 samples were further analyzed. These data showed that the RAR beta promoter methylation rates in PCa tissues were significantly higher than the rates in the non-PCa group (OR=21.65, 95% CI: 9.27-50.57). Subgroup analysis according to the source region of samples showed that heterogeneity in Asia was small (I2=0.0%, P=0.430). Additional subgroup analysis based on the method used to detect RAR beta promoter methylation showed that the heterogeneity detected by MSP (methylation-specific PCR) was relatively small (I2=11.3%, P=0.343). Although studies reported different rates for RAR beta promoter methylation in PCa tissues, the total analysis demonstrated that RAR beta promoter methylation may be correlated with PCa carcinogenesis and that the RAR beta gene is particularly susceptible. Additional studies with sufficient data are essential to further evaluate the clinical features and prognostic utility of RAR beta promoter methylation in PCa. © 2018 The Author(s). Published by S. Karger AG, Basel.

PCA3 Reference Set Application: T2-Erg-Martin Sanda-Emory (2014) — EDRN Public Portal

Cancer.gov

We hypothesize that combining T2:erg (T2:erg) fusion and PCA3 detection in urine collected after digital rectal exam can improve the specificity of identifying clinically significant prostate cancer presence over the standard PSA and DRE. To address this hypothesis we propose to validate the performance of the urinary T2:erg in a multiplex model predicting the diagnosis of clinically significant prostate cancer on subsequent prostate biopsy using post-DRE pre biopsy urine specimens from a cohort of 900 men on the EDRN’s PCA3 trial.

Enhanced expression of SRPK2 contributes to aggressive progression and metastasis in prostate cancer.

PubMed

Zhuo, Yang Jia; Liu, Ze Zhen; Wan, Song; Cai, Zhi Duan; Xie, Jian Jiang; Cai, Zhou da; Song, Sheng da; Wan, Yue Ping; Hua, Wei; Zhong, Wei de; Wu, Chin Lee

2018-06-01

Serine/Arginine-Rich Protein-Specific Kinase-2 (SRSF protein kinase-2, SRPK2) is up-regulated in multiple human tumors. However, the expression, function and clinical significance of SRPK2 in prostate cancer (PCa) has not yet been understood. We therefore aimed to determine the association of SRPK2 with tumor progression and metastasis in PCa patients in our present study. The expression of SRPK2 was detected by some public datasets and validated using a clinical tissue microarray (TMA) by immunohistochemistry. The association of SRPK2 expression with various clinicopathological characteristics of PCa patients was subsequently statistically analyzed based on the The Cancer Genome Atlas (TCGA) dataset and clinical TMA. The effects of SRPK2 on cancer cell proliferation, migration, invasion, cell cycle progression, apoptosis and tumor growth were then respectively investigated using in vitro and in vivo experiments. First, public datasets showed that SRPK2 expression was greater in PCa tissues when compared with non-cancerous tissues. Statistical analysis demonstrated that high expression of SRPK2 was significantly correlated with a higher Gleason Score, advanced pathological stage and the presence of tumor metastasis in the TCGA Dataset (all P < 0.01). Similar correlations between SRPK2 and a higher Gleason Score or advanced pathological stage were also identified in the TMA (P < 0.05). Kaplan-Meier curve analyses showed that the biochemical recurrence (BCR)-free time of PCa patients with SRPK2 high expression was shorter than for those with SRPK2 low expression (P < 0.05). Second, cell function experiments in PCa cell lines revealed that enhanced SRPK2 expression could promote cell proliferation, migration, invasion and cell cycle progression but suppress tumor cell apoptosis in vitro. Xenograft experiments showed that SRPK2 promoted tumor growth in vivo. In conclusion, our data demonstrated that SRPK2 may play an important role in the progression and metastasis of PCa, which suggests that it might be a potential therapeutic target for PCa clinical therapy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A comprehensive evaluation of CHEK2 germline mutations in men with prostate cancer.

PubMed

Wu, Yishuo; Yu, Hongjie; Zheng, S Lilly; Na, Rong; Mamawala, Mufaddal; Landis, Tricia; Wiley, Kathleen; Petkewicz, Jacqueline; Shah, Sameep; Shi, Zhuqing; Novakovic, Kristian; McGuire, Michael; Brendler, Charles B; Ding, Qiang; Helfand, Brian T; Carter, H Ballentine; Cooney, Kathleen A; Isaacs, William B; Xu, Jianfeng

2018-06-01

Germline mutations in CHEK2 have been associated with prostate cancer (PCa) risk. Our objective is to examine whether germline pathogenic CHEK2 mutations can differentiate risk of lethal from indolent PCa. A case-case study of 703 lethal PCa patients and 1455 patients with low-risk localized PCa of European, African, and Chinese origin was performed. Germline DNA samples from these patients were sequenced for CHEK2. Mutation carrier rates and their association with lethal PCa were analyzed using the Fisher exact test and Kaplan-Meier survival analysis. In the entire study population, 40 (1.85%) patients were identified as carrying one of 15 different germline CHEK2 pathogenic or likely pathogenic mutations. CHEK2 mutations were detected in 16 (2.28%) of 703 lethal PCa patients compared with 24 (1.65%) of 1455 low-risk PCa patients (P = 0.31). No association was found between CHEK2 mutation status and early-diagnosis or PCa-specific survival time. However, the most common mutation in CHEK2, c.1100delC (p.T367 fs), had a significantly higher carrier rate (1.28%) in lethal PCa patients than low-risk PCa patients of European American origin (0.16%), P = 0.0038. The estimated Odds Ratio of this mutation for lethal PCa was 7.86. The carrier rate in lethal PCa was also significantly higher than that (0.46%) in 32 461 non-Finnish European subjects from the Exome Aggregation Consortium (ExAC) (P = 0.01). While overall CHEK2 mutations were not significantly more common in men with lethal compared to low-risk PCa, the specific CHEK2 mutation, c.1100delC, appears to contribute to an increased risk of lethal PCa in European American men. © 2018 Wiley Periodicals, Inc.

The Potential of MicroRNAs as Prostate Cancer Biomarkers.

PubMed

Fabris, Linda; Ceder, Yvonne; Chinnaiyan, Arul M; Jenster, Guido W; Sorensen, Karina D; Tomlins, Scott; Visakorpi, Tapio; Calin, George A

2016-08-01

Short noncoding RNAs known as microRNAs (miRNAs) control protein expression through the degradation of RNA or the inhibition of protein translation. The miRNAs influence a wide range of biologic processes and are often deregulated in cancer. This family of small RNAs constitutes potentially valuable markers for the diagnosis, prognosis, and therapeutic choices in prostate cancer (PCa) patients, as well as potential drugs (miRNA mimics) or drug targets (anti-miRNAs) in PCa management. To review the currently available data on miRNAs as biomarkers in PCa and as possible tools for early detection and prognosis. A systematic review was performed searching the PubMed database for articles in English using a combination of the following terms: microRNA, miRNA, cancer, prostate cancer, miRNA profiling, diagnosis, prognosis, therapy response, and predictive marker. We summarize the existing literature regarding the profiling of miRNA in PCa detection, prognosis, and response to therapy. The articles were reviewed with the main goal of finding a common recommendation that could be translated from bench to bedside in future clinical practice. The miRNAs are important regulators of biologic processes in PCa progression. A common expression profile characterizing each tumor subtype and stage has still not been identified for PCa, probably due to molecular heterogeneity as well as differences in study design and patient selection. Large-scale studies that should provide additional important information are still missing. Further studies, based on common clinical parameters and guidelines, are necessary to validate the translational potential of miRNAs in PCa clinical management. Such common signatures are promising in the field and emerge as potential biomarkers. The literature shows that microRNAs hold potential as novel biomarkers that could aid prostate cancer management, but additional studies with larger patient cohorts and common guidelines are necessary before clinical implementation. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis

PubMed Central

Wu, Jason Boyang; Shao, Chen; Li, Xiangyan; Li, Qinlong; Hu, Peizhen; Shi, Changhong; Li, Yang; Chen, Yi-Ting; Yin, Fei; Liao, Chun-Peng; Stiles, Bangyan L.; Zhau, Haiyen E.; Shih, Jean C.; Chung, Leland W.K.

2014-01-01

Tumors from patients with high-grade aggressive prostate cancer (PCa) exhibit increased expression of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines. Despite the association between MAOA and aggressive PCa, it is unclear how MAOA promotes PCa progression. Here, we found that MAOA functions to induce epithelial-to-mesenchymal transition (EMT) and stabilize the transcription factor HIF1α, which mediates hypoxia through an elevation of ROS, thus enhancing growth, invasiveness, and metastasis of PCa cells. Knockdown and overexpression of MAOA in human PCa cell lines indicated that MAOA induces EMT through activation of VEGF and its coreceptor neuropilin-1. MAOA-dependent activation of neuropilin-1 promoted AKT/FOXO1/TWIST1 signaling, allowing FOXO1 binding at the TWIST1 promoter. Importantly, the MAOA-dependent HIF1α/VEGF-A/FOXO1/TWIST1 pathway was activated in high-grade PCa specimens, and knockdown of MAOA reduced or even eliminated prostate tumor growth and metastasis in PCa xenograft mouse models. Pharmacological inhibition of MAOA activity also reduced PCa xenograft growth in mice. Moreover, high MAOA expression in PCa tissues correlated with worse clinical outcomes in PCa patients. These findings collectively characterize the contribution of MAOA in PCa pathogenesis and suggest that MAOA has potential as a therapeutic target in PCa. PMID:24865426

Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis.

PubMed

Wu, Jason Boyang; Shao, Chen; Li, Xiangyan; Li, Qinlong; Hu, Peizhen; Shi, Changhong; Li, Yang; Chen, Yi-Ting; Yin, Fei; Liao, Chun-Peng; Stiles, Bangyan L; Zhau, Haiyen E; Shih, Jean C; Chung, Leland W K

2014-07-01

Tumors from patients with high-grade aggressive prostate cancer (PCa) exhibit increased expression of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades monoamine neurotransmitters and dietary amines. Despite the association between MAOA and aggressive PCa, it is unclear how MAOA promotes PCa progression. Here, we found that MAOA functions to induce epithelial-to-mesenchymal transition (EMT) and stabilize the transcription factor HIF1α, which mediates hypoxia through an elevation of ROS, thus enhancing growth, invasiveness, and metastasis of PCa cells. Knockdown and overexpression of MAOA in human PCa cell lines indicated that MAOA induces EMT through activation of VEGF and its coreceptor neuropilin-1. MAOA-dependent activation of neuropilin-1 promoted AKT/FOXO1/TWIST1 signaling, allowing FOXO1 binding at the TWIST1 promoter. Importantly, the MAOA-dependent HIF1α/VEGF-A/FOXO1/TWIST1 pathway was activated in high-grade PCa specimens, and knockdown of MAOA reduced or even eliminated prostate tumor growth and metastasis in PCa xenograft mouse models. Pharmacological inhibition of MAOA activity also reduced PCa xenograft growth in mice. Moreover, high MAOA expression in PCa tissues correlated with worse clinical outcomes in PCa patients. These findings collectively characterize the contribution of MAOA in PCa pathogenesis and suggest that MAOA has potential as a therapeutic target in PCa.

Isolation of candidate genes for apomictic development in buffelgrass (Pennisetum ciliare).

PubMed

Singh, Manjit; Burson, Byron L; Finlayson, Scott A

2007-08-01

Asexual reproduction through seeds, or apomixis, is a process that holds much promise for agricultural advances. However, the molecular mechanisms underlying apomixis are currently poorly understood. To identify genes related to female gametophyte development in apomictic ovaries of buffelgrass (Pennisetum ciliare (L.) Link), Suppression Subtractive Hybridization of ovary cDNA with leaf cDNA was performed. Through macroarray screening of subtracted cDNAs two genes were identified, Pca21 and Pca24, that showed differential expression between apomictic and sexual ovaries. Sequence analysis showed that both Pca21 and Pca24 are novel genes not previously characterized in plants. Pca21 shows homology to two wheat genes that are also expressed during reproductive development. Pca24 has similarity to coiled-coil-helix-coiled-coil-helix (CHCH) domain containing proteins from maize and sugarcane. Northern blot analysis revealed that both of these genes are expressed throughout female gametophyte development in apomictic ovaries. In situ hybridizations localized the transcript of these two genes to the developing embryo sacs in the apomictic ovaries. Based on the expression patterns it was concluded that Pca21 and Pca24 likely play a role during apomictic development in buffelgrass.

[Studies on localized low-risk prostate cancer : Do we know enough?

PubMed

Weißbach, L; Roloff, C

2018-06-05

Treatment of localized low-risk prostate cancer (PCa) is undergoing a paradigm shift: Invasive treatments such as surgery and radiation therapy are being replaced by defensive strategies such as active surveillance (AS) and watchful waiting (WW). The aim of this work is to evaluate the significance of current studies regarding defensive strategies (AS and WW). The best-known AS studies are critically evaluated for their significance in terms of input criteria, follow-up criteria, and statistical significance. The difficulties faced by randomized studies in answering the question of the best treatment for low-risk cancer in two or even more study groups with known low tumor-specific mortality are clearly shown. Some studies fail because of the objective, others-like PIVOT-are underpowered. ProtecT, a renowned randomized, controlled trial (RCT), lists systematic and statistical shortcomings in detail. The time and effort required for RCTs to answer the question of which therapy is best for locally limited low-risk cancer is very large because the low specific mortality rate requires a large number of participants and a long study duration. In any case, RCTs create hand-picked cohorts for statistical evaluation that have little to do with care in daily clinical practice. The necessary randomization is also offset by the decision-making of the informed patient. If further studies of low-risk PCa are needed, they will need real-world conditions that an RCT can not provide. To obtain clinically relevant results, we need to rethink things: When planning the study, biometricians and clinicians must understand that the statistical methods used in RCTs are of limited use and they must select a method (e.g. propensity scores) appropriate for health care research.

Automated Detection of Clinically Significant Prostate Cancer in mp-MRI Images Based on an End-to-End Deep Neural Network.

PubMed

Wang, Zhiwei; Liu, Chaoyue; Cheng, Danpeng; Wang, Liang; Yang, Xin; Cheng, Kwang-Ting

2018-05-01

Automated methods for detecting clinically significant (CS) prostate cancer (PCa) in multi-parameter magnetic resonance images (mp-MRI) are of high demand. Existing methods typically employ several separate steps, each of which is optimized individually without considering the error tolerance of other steps. As a result, they could either involve unnecessary computational cost or suffer from errors accumulated over steps. In this paper, we present an automated CS PCa detection system, where all steps are optimized jointly in an end-to-end trainable deep neural network. The proposed neural network consists of concatenated subnets: 1) a novel tissue deformation network (TDN) for automated prostate detection and multimodal registration and 2) a dual-path convolutional neural network (CNN) for CS PCa detection. Three types of loss functions, i.e., classification loss, inconsistency loss, and overlap loss, are employed for optimizing all parameters of the proposed TDN and CNN. In the training phase, the two nets mutually affect each other and effectively guide registration and extraction of representative CS PCa-relevant features to achieve results with sufficient accuracy. The entire network is trained in a weakly supervised manner by providing only image-level annotations (i.e., presence/absence of PCa) without exact priors of lesions' locations. Compared with most existing systems which require supervised labels, e.g., manual delineation of PCa lesions, it is much more convenient for clinical usage. Comprehensive evaluation based on fivefold cross validation using 360 patient data demonstrates that our system achieves a high accuracy for CS PCa detection, i.e., a sensitivity of 0.6374 and 0.8978 at 0.1 and 1 false positives per normal/benign patient.

Epithelial-to-mesenchymal transition leads to disease-stage differences in circulating tumor cell detection and metastasis in pre-clinical models of prostate cancer.

PubMed

Lowes, Lori E; Goodale, David; Xia, Ying; Postenka, Carl; Piaseczny, Matthew M; Paczkowski, Freeman; Allan, Alison L

2016-11-15

Metastasis is the cause of most prostate cancer (PCa) deaths and has been associated with circulating tumor cells (CTCs). The presence of ≥5 CTCs/7.5mL of blood is a poor prognosis indicator in metastatic PCa when assessed by the CellSearch® system, the "gold standard" clinical platform. However, ~35% of metastatic PCa patients assessed by CellSearch® have undetectable CTCs. We hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and subsequent loss of necessary CTC detection markers, with important implications for PCa metastasis. Two pre-clinical assays were developed to assess human CTCs in xenograft models; one comparable to CellSearch® (EpCAM-based) and one detecting CTCs semi-independent of EMT status via combined staining with EpCAM/HLA (human leukocyte antigen). In vivo differences in CTC generation, kinetics, metastasis and EMT status were determined using 4 PCa models with progressive epithelial (LNCaP, LNCaP-C42B) to mesenchymal (PC-3, PC-3M) phenotypes. Assay validation demonstrated that the CellSearch®-based assay failed to detect a significant number (~40-50%) of mesenchymal CTCs. In vivo, PCa with an increasingly mesenchymal phenotype shed greater numbers of CTCs more quickly and with greater metastatic capacity than PCa with an epithelial phenotype. Notably, the CellSearch®-based assay captured the majority of CTCs shed during early-stage disease in vivo, and only after establishment of metastases were a significant number of undetectable CTCs present. This study provides important insight into the influence of EMT on CTC generation and subsequent metastasis, and highlights that novel technologies aimed at capturing mesenchymal CTCs may only be useful in the setting of advanced metastatic disease.

Are concurrent systematic cores needed at the time of targeted biopsy in patients with prior negative prostate biopsies?

PubMed

Albisinni, S; Aoun, F; Noel, A; El Rassy, E; Lemort, M; Paesmans, M; van Velthoven, R; Roumeguère, T; Peltier, A

2018-01-01

MRI-guided targeted biopsies are advised in patients who have undergone an initial series of negative systematic biopsies, in whom prostate cancer (PCa) suspicion remains elevated. The aim of the study was to evaluate whether, in men with prior negative prostate biopsies, systematic cores are also warranted at the time of an MRI-targeted repeat biopsy. We enrolled patients with prior negative biopsy undergoing real time MRI/TRUS fusion guided prostate biopsy at our institute between 2014 and 2016. Patients with at least one index lesion on multiparametric MRI were included. All eligible patients underwent both systematic random biopsies (12-14 cores) and targeted biopsies (2-4 cores). The study included 74 men with a median age of 65 years, PSA level of 9.27ng/mL, and prostatic volume of 45ml. The overall PCa detection rate and the clinically significant cancer detection rate were 56.7% and 39.2%, respectively. Targeted cores demonstrated similar clinically significant PCa detection rate compared to systematic cores (33.8% vs. 28.4%, P=0.38) with significantly less tissue sampling. Indeed, a combination approach was significantly superior to a targeted-only in overall PCa detection (+16.7% overall detection rate, P=0.007). Although differences in clinically significant PCa detection were statistically non-significant (P=0.13), a combination approach did allow detecting 7 extra clinically significant PCas (+13.8%). In patients with elevated PSA and prior negative biopsies, concurrent systematic sampling may be needed at the time of targeted biopsy in order to maximize PCa detection rate. Larger studies are needed to validate our findings. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Diffusion Weighted Image Denoising Using Overcomplete Local PCA

PubMed Central

Manjón, José V.; Coupé, Pierrick; Concha, Luis; Buades, Antonio; Collins, D. Louis; Robles, Montserrat

2013-01-01

Diffusion Weighted Images (DWI) normally shows a low Signal to Noise Ratio (SNR) due to the presence of noise from the measurement process that complicates and biases the estimation of quantitative diffusion parameters. In this paper, a new denoising methodology is proposed that takes into consideration the multicomponent nature of multi-directional DWI datasets such as those employed in diffusion imaging. This new filter reduces random noise in multicomponent DWI by locally shrinking less significant Principal Components using an overcomplete approach. The proposed method is compared with state-of-the-art methods using synthetic and real clinical MR images, showing improved performance in terms of denoising quality and estimation of diffusion parameters. PMID:24019889

Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death

PubMed Central

Na, Rong; Zheng, S. Lilly; Han, Misop; Yu, Hongjie; Jiang, Deke; Shah, Sameep; Ewing, Charles M.; Zhang, Liti; Novakovic, Kristian; Petkewicz, Jacqueline; Gulukota, Kamalakar; Helseth, Donald L.; Quinn, Margo; Humphries, Elizabeth; Wiley, Kathleen E.; Isaacs, Sarah D.; Wu, Yishuo; Liu, Xu; Zhang, Ning; Wang, Chi-Hsiung; Khandekar, Janardan; Hulick, Peter J.; Shevrin, Daniel H.; Cooney, Kathleen A.; Shen, Zhoujun; Partin, Alan W.; Carter, H. Ballentine; Carducci, Michael A.; Eisenberger, Mario A.; Denmeade, Sam R.; McGuire, Michael; Walsh, Patrick C.; Helfand, Brian T.; Brendler, Charles B.; Ding, Qiang; Xu, Jianfeng; Isaacs, William B.

2017-01-01

Background Germline mutations in BRCA1/2 and ATM have been associated with prostate cancer (PCa) risk. Objective To directly assess whether germline mutations in these three genes distinguish lethal from indolent PCa and whether they confer any effect on age at death. Design, setting, and participants A retrospective case-case study of 313 patients who died of PCa and 486 patients with low-risk localized PCa of European, African, and Chinese descent. Germline DNA of each of the 799 patients was sequenced for these three genes. Outcome measurements and statistical analysis Mutation carrier rates and their effect on lethal PCa were analyzed using the Fisher’s exact test and Cox regression analysis, respectively. Results and limitations The combined BRCA1/2 and ATM mutation carrier rate was significantly higher in lethal PCa patients (6.07%) than localized PCa patients (1.44%), p = 0.0007. The rate also differed significantly among lethal PCa patients as a function of age at death (10.00%, 9.08%, 8.33%, 4.94%, and 2.97% in patients who died ≤60 yr, 61–65 yr, 66–70 yr, 71–75 yr, and over 75 yr, respectively, p = 0.046) and time to death after diagnosis (12.26%, 4.76%, and 0.98% in patients who died ≤5 yr, 6–10 yr, and > 10 yr after a PCa diagnosis, respectively, p = 0.0006). Survival analysis in the entire cohort revealed mutation carriers remained an independent predictor of lethal PCa after adjusting for race and age, prostate-specific antigen, and Gleason score at the time of diagnosis (hazard ratio = 2.13, 95% confidence interval: 1.24–3.66, p = 0.004). A limitation of this study is that other DNA repair genes were not analyzed. Conclusions Mutation status of BRCA1/2 and ATM distinguishes risk for lethal and indolent PCa and is associated with earlier age at death and shorter survival time. Patient summary Prostate cancer patients with inherited mutations in BRCA1/2 and ATM are more likely to die of prostate cancer and do so at an earlier age. PMID:27989354

Prolactin- and testosterone-induced carboxypeptidase-D correlates with increased nitrotyrosines and Ki67 in prostate cancer.

PubMed

Thomas, Lynn N; Merrimen, Jennifer; Bell, David G; Rendon, Ricardo; Too, Catherine K L

2015-11-01

Carboxypeptidase-D (CPD) cleaves C-terminal arginine for conversion to nitric oxide (NO) by nitric oxide synthase (NOS). Prolactin (PRL) and androgens stimulate CPD gene transcription and expression, which increases intracellular production of NO to promote viability of prostate cancer (PCa) cells in vitro. The current study evaluated whether hormonal upregulation of CPD and NO promote PCa cell viabilty in vivo, by correlating changes in expression of CPD and nitrotyrosine residues (products of NO action) with proliferation marker Ki67 and associated proteins during PCa development and progression. Fresh prostate tissues, obtained from 40 men with benign prostatic hyperplasia (BPH) or PCa, were flash-frozen at the time of surgery and used for RT-qPCR analysis of CPD, androgen receptor (AR), PRL receptor (PRLR), eNOS, and Ki67 levels. Archival paraffin-embedded tissues from 113 men with BPH or PCa were used for immunohistochemical (IHC) analysis of CPD, nitrotyrosines, phospho-Stat5 (for activated PRLR), AR, eNOS/iNOS, and Ki67. RT-qPCR and IHC analyses showed strong AR and PRLR expression in benign and malignant prostates. CPD mRNA levels increased ∼threefold in PCa compared to BPH, which corresponded to a twofold increase in Ki67 mRNA levels. IHC analysis showed a progressive increase in CPD from 11.4 ± 2.1% in benign to 21.8 ± 3.2% in low-grade (P = 0.007), 40.7 ± 4.0% in high-grade (P < 0.0001) and 50.0 ± 9.5% in castration-recurrent PCa (P < 0.0001). Immunostaining for nitrotyrosines and Ki67 mirrored these increases during PCa progression. CPD, nitrotyrosines, and Ki67 tended to co-localize, as did phospho-Stat5. CPD, nitrotyrosine, and Ki67 levels were higher in PCa than in benign and tended to co-localize, along with phospho-Stat5. The strong correlation in expression of these proteins in benign and malignant prostate tissues, combined with abundant AR and PRLR, supports in vitro evidence that the CPD-Arg-NO pathway is involved in the regulation of PCa cell proliferation. It further highlights a role for PRL in the development and progression of PCa. © 2015 Wiley Periodicals, Inc.

Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer?

PubMed

Doluoglu, Omer Gokhan; Ceylan, Cavit; Kilinc, Fatih; Gazel, Eymen; Resorlu, Berkan; Odabas, Oner

2016-01-01

We investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer. The data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure), history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded. In total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2%) patients and PCa+NIH IV prostatitis in 23 (22.7%) patients. The median total PSA level was 7.4 (3.5-20.0) ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6-20.0) ng/mL in the PCa group (p=0.67). The PSA level was≤10ng/mL in 60 (76.9%) patients in the PCa group and in 16 (69.6%) patients in the PCa+NIH IV prostatitis group (p=0.32). Our study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa.

Red meat and poultry, cooking practices, genetic susceptibility and risk of prostate cancer: results from a multiethnic case–control study

PubMed Central

Stern, Mariana C.

2012-01-01

Red meat, processed and unprocessed, has been considered a potential prostate cancer (PCA) risk factor; epidemiological evidence, however, is inconclusive. An association between meat intake and PCA may be due to potent chemical carcinogens that are generated when meats are cooked at high temperatures. We investigated the association between red meat and poultry intake and localized and advanced PCA taking into account cooking practices and polymorphisms in enzymes that metabolize carcinogens that accumulate in cooked meats. We analyzed data for 1096 controls, 717 localized and 1140 advanced cases from the California Collaborative Prostate Cancer Study, a multiethnic, population-based case–control study. We examined nutrient density-adjusted intake of red meat and poultry and tested for effect modification by 12 SNPs and 2 copy number variants in 10 carcinogen metabolism genes: GSTP1, PTGS2, CYP1A2, CYP2E1, EPHX1, CYP1B1, UGT1A6, NAT2, GSTM1 and GSTT1. We observed a positive association between risk of advanced PCA and high intake of red meat cooked at high temperatures (trend P = 0.026), cooked by pan-frying (trend P = 0.035), and cooked until well-done (trend P = 0.013). An inverse association was observed for baked poultry and advanced PCA risk (trend P = 0.023). A gene-by-diet interaction was observed between an SNP in the PTGS2 gene and the estimated levels of meat mutagens (interaction P = 0.008). Our results support a role for carcinogens that accumulate in meats cooked at high temperatures as potential PCA risk factors, and may support a role for heterocyclic amines (HCAs) in PCA etiology. PMID:22822096

Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

NASA Astrophysics Data System (ADS)

Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

2016-05-01

Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63-0.66), 0.73 (95% CI: 0.72-0.74), 2.23 (95% CI: 1.91-2.62), 0.48 (95% CI: 0.44-0.52), 5.31 (95% CI: 4.19-6.73) and 0.75 (95% CI: 0.74-0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.

68Ga-HBED-CC-PSMA PET/CT Versus Histopathology in Primary Localized Prostate Cancer: A Voxel-Wise Comparison

PubMed Central

Zamboglou, Constantinos; Schiller, Florian; Fechter, Tobias; Wieser, Gesche; Jilg, Cordula Annette; Chirindel, Alin; Salman, Nasr; Drendel, Vanessa; Werner, Martin; Mix, Michael; Meyer, Philipp Tobias; Grosu, Anca Ligia

2016-01-01

Purpose: We performed a voxel-wise comparison of 68Ga-HBED-CC-PSMA PET/CT with prostate histopathology to evaluate the performance of 68Ga-HBED-CC-PSMA for the detection and delineation of primary prostate cancer (PCa). Methodology: Nine patients with histopathological proven primary PCa underwent 68Ga-HBED-CC-PSMA PET/CT followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and histopathologically prepared. Histopathological information was matched to ex-vivo CT. PCa volume (PCa-histo) and non-PCa tissue in the prostate (NPCa-histo) were processed to obtain a PCa-model, which was adjusted to PET-resolution (histo-PET). Each histo-PET was coregistered to in-vivo PSMA-PET/CT data. Results: Analysis of spatial overlap between histo-PET and PSMA PET revealed highly significant correlations (p < 10-5) in nine patients and moderate to high coefficients of determination (R²) from 42 to 82 % with an average of 60 ± 14 % in eight patients (in one patient R2 = 7 %). Mean SUVmean in PCa-histo and NPCa-histo was 5.6 ± 6.1 and 3.3 ± 2.5 (p = 0.012). Voxel-wise receiver-operating characteristic (ROC) analyses comparing the prediction by PSMA-PET with the non-smoothed tumor distribution from histopathology yielded an average area under the curve of 0.83 ± 0.12. Absolute and relative SUV (normalized to SUVmax) thresholds for achieving at least 90 % sensitivity were 3.19 ± 3.35 and 0.28 ± 0.09, respectively. Conclusions: Voxel-wise analyses revealed good correlations of 68Ga-HBED-CC-PSMA PET/CT and histopathology in eight out of nine patients. Thus, PSMA-PET allows a reliable detection and delineation of PCa as basis for PET-guided focal therapies. PMID:27446496

Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report

PubMed Central

Francio, Vinicius T.; Boesch, Ron; Tunning, Michael

2015-01-01

Objective: Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. Clinical features: A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Intervention and Outcome: Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient’s perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. Conclusion: PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option. PMID:25729084

Consensus classification of posterior cortical atrophy

PubMed Central

Crutch, Sebastian J.; Schott, Jonathan M.; Rabinovici, Gil D.; Murray, Melissa; Snowden, Julie S.; van der Flier, Wiesje M.; Dickerson, Bradford C.; Vandenberghe, Rik; Ahmed, Samrah; Bak, Thomas H.; Boeve, Bradley F.; Butler, Christopher; Cappa, Stefano F.; Ceccaldi, Mathieu; de Souza, Leonardo Cruz; Dubois, Bruno; Felician, Olivier; Galasko, Douglas; Graff-Radford, Jonathan; Graff-Radford, Neill R.; Hof, Patrick R.; Krolak-Salmon, Pierre; Lehmann, Manja; Magnin, Eloi; Mendez, Mario F.; Nestor, Peter J.; Onyike, Chiadi U.; Pelak, Victoria S.; Pijnenburg, Yolande; Primativo, Silvia; Rossor, Martin N.; Ryan, Natalie S.; Scheltens, Philip; Shakespeare, Timothy J.; González, Aida Suárez; Tang-Wai, David F.; Yong, Keir X. X.; Carrillo, Maria; Fox, Nick C.

2017-01-01

Introduction A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Methods Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. Results A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. Discussion There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work. PMID:28259709

Consensus classification of posterior cortical atrophy.

PubMed

Crutch, Sebastian J; Schott, Jonathan M; Rabinovici, Gil D; Murray, Melissa; Snowden, Julie S; van der Flier, Wiesje M; Dickerson, Bradford C; Vandenberghe, Rik; Ahmed, Samrah; Bak, Thomas H; Boeve, Bradley F; Butler, Christopher; Cappa, Stefano F; Ceccaldi, Mathieu; de Souza, Leonardo Cruz; Dubois, Bruno; Felician, Olivier; Galasko, Douglas; Graff-Radford, Jonathan; Graff-Radford, Neill R; Hof, Patrick R; Krolak-Salmon, Pierre; Lehmann, Manja; Magnin, Eloi; Mendez, Mario F; Nestor, Peter J; Onyike, Chiadi U; Pelak, Victoria S; Pijnenburg, Yolande; Primativo, Silvia; Rossor, Martin N; Ryan, Natalie S; Scheltens, Philip; Shakespeare, Timothy J; Suárez González, Aida; Tang-Wai, David F; Yong, Keir X X; Carrillo, Maria; Fox, Nick C

2017-08-01

A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Classification of clinical significance of MRI prostate findings using 3D convolutional neural networks

NASA Astrophysics Data System (ADS)

Mehrtash, Alireza; Sedghi, Alireza; Ghafoorian, Mohsen; Taghipour, Mehdi; Tempany, Clare M.; Wells, William M.; Kapur, Tina; Mousavi, Parvin; Abolmaesumi, Purang; Fedorov, Andriy

2017-03-01

Prostate cancer (PCa) remains a leading cause of cancer mortality among American men. Multi-parametric magnetic resonance imaging (mpMRI) is widely used to assist with detection of PCa and characterization of its aggressiveness. Computer-aided diagnosis (CADx) of PCa in MRI can be used as clinical decision support system to aid radiologists in interpretation and reporting of mpMRI. We report on the development of a convolution neural network (CNN) model to support CADx in PCa based on the appearance of prostate tissue in mpMRI, conducted as part of the SPIE-AAPM-NCI PROSTATEx challenge. The performance of different combinations of mpMRI inputs to CNN was assessed and the best result was achieved using DWI and DCE-MRI modalities together with the zonal information of the finding. On the test set, the model achieved an area under the receiver operating characteristic curve of 0.80.

Treatment trends and Medicare reimbursements for localized prostate cancer in elderly patients.

PubMed

Dell'oglio, Paolo; Valiquette, Anne Sophie; Leyh-Bannurah, Sami-Ramzi; Tian, Zhe; Trudeau, Vincent; Larcher, Alessandro; Shariat, Shahrokh F; Capitanio, Umberto; Briganti, Alberto; Graefen, Markus; Montorsi, Francesco; Karakiewicz, Pierre I

2018-03-19

The absolute and proportional numbers of elderly patients diagnosed with localized prostate cancer (PCa) are on the rise. We examined treatment trends and reimbursement figures in localized PCa patients aged ≥80 years. Between 2000 and 2008, we identified 30 217 localized PCa patients aged ≥80 years in Surveillance, Epidemiology and End Results (SEER)-Medicare-linked database. Alternative treatment modalities consisted of conservative management (CM), radiation therapy (RT), radical prostatectomy (RP), and primary androgen-deprivation therapy (PADT). For all four modalities, utilization and reimbursements were examined. PADT was the most frequently used treatment modality between 2000 and 2005. CM became the dominant treatment modality from 2006-2008. RP rates were marginal and RT ranked third and its annual rate increased from 20.77% in 2000 to 29.13% in 2008. Median individual reimbursement of RT was highest and ranged from $29 343 in 2000 to $31 090 in 2008, followed by RP (from $20 560 in 2000 to $19 580 in 2008), PADT (from $18 901 in 2000 to $8000 in 2008) and CM (from $1824 in 2000 to $1938 in 2008). RT contributed to most of the cumulative annual reimbursements from 2003 (49.24%) to 2008 (72.97%). PADT ranked first from 2000 (54.56%) to 2002 (50.49%), but decreased by 19.40% in 2008. CM's contribution increased from 4.42% in 2000 to 6.96% in 2008. RP share of reimbursements was stable during the study period. Our results, focusing on localized PCa treatment in patients aged ≥80 years, showed an important increase in rates, median cost, and proportion of cumulative cost related to RT.

Incidental prostate cancer in radical cystoprostatectomy specimens.

PubMed

Jin, Xiao-Dong; Chen, Zhao-Dian; Wang, Bo; Cai, Song-Liang; Yao, Xiao-Lin; Jin, Bai-Ye

2008-09-01

To investigate the rates of prostate cancer (PCa) in radical cystoprostatectomy (RCP) specimens for bladder cancer in mainland China. To determine the follow-up outcome of patients with two concurrent cancers and identify whether prostate-specific antigen (PSA) is a useful tool for the detection of PCa prior to surgery. From January 2002 to January 2007, 264 male patients with bladder cancer underwent RCP at our center. All patients underwent digital rectal examination (DRE) and B ultrasound. Serum PSA levels were tested in 168 patients. None of the patients had any evidence of PCa before RCP. Entire prostates were embedded and sectioned at 5 mm intervals. Incidental PCa was observed in 37 of 264 (14.0%) RCP specimens. Of these, 12 (32.4%) were clinically significant according to an accepted definition. The PSA levels were not significantly different between patients with PCa and those without PCa, nor between patients with significant PCa and those with insignificant PCa. Thirty-four patients with incidental PCa were followed up. During a mean follow-up period of 26 months, two patients with PSA > 4 ng/mL underwent castration. None of the patients died of PCa. The incidence of PCa in RCP specimens in mainland China is lower than that in most developed countries. PSA cannot identify asymptomatic PCa prior to RCP. In line with published reports, incidental PCa does not impact the prognosis of bladder cancer patients undergoing RCP. (c) 2008, Asian Journal of Andrology, SIMM and SJTU. All rights reserved.

Folded concave penalized learning in identifying multimodal MRI marker for Parkinson’s disease

PubMed Central

Liu, Hongcheng; Du, Guangwei; Zhang, Lijun; Lewis, Mechelle M.; Wang, Xue; Yao, Tao; Li, Runze; Huang, Xuemei

2016-01-01

Background Brain MRI holds promise to gauge different aspects of Parkinson’s disease (PD)-related pathological changes. Its analysis, however, is hindered by the high-dimensional nature of the data. New method This study introduces folded concave penalized (FCP) sparse logistic regression to identify biomarkers for PD from a large number of potential factors. The proposed statistical procedures target the challenges of high-dimensionality with limited data samples acquired. The maximization problem associated with the sparse logistic regression model is solved by local linear approximation. The proposed procedures then are applied to the empirical analysis of multimodal MRI data. Results From 45 features, the proposed approach identified 15 MRI markers and the UPSIT, which are known to be clinically relevant to PD. By combining the MRI and clinical markers, we can enhance substantially the specificity and sensitivity of the model, as indicated by the ROC curves. Comparison to existing methods We compare the folded concave penalized learning scheme with both the Lasso penalized scheme and the principle component analysis-based feature selection (PCA) in the Parkinson’s biomarker identification problem that takes into account both the clinical features and MRI markers. The folded concave penalty method demonstrates a substantially better clinical potential than both the Lasso and PCA in terms of specificity and sensitivity. Conclusions For the first time, we applied the FCP learning method to MRI biomarker discovery in PD. The proposed approach successfully identified MRI markers that are clinically relevant. Combining these biomarkers with clinical features can substantially enhance performance. PMID:27102045

Prostate Cancer Patients-Negative Biopsy Controls Discrimination by Untargeted Metabolomics Analysis of Urine by LC-QTOF: Upstream Information on Other Omics

NASA Astrophysics Data System (ADS)

Fernández-Peralbo, M. A.; Gómez-Gómez, E.; Calderón-Santiago, M.; Carrasco-Valiente, J.; Ruiz-García, J.; Requena-Tapia, M. J.; Luque de Castro, M. D.; Priego-Capote, F.

2016-12-01

The existing clinical biomarkers for prostate cancer (PCa) diagnosis are far from ideal (e.g., the prostate specific antigen (PSA) serum level suffers from lack of specificity, providing frequent false positives leading to over-diagnosis). A key step in the search for minimum invasive tests to complement or replace PSA should be supported on the changes experienced by the biochemical pathways in PCa patients as compared to negative biopsy control individuals. In this research a comprehensive global analysis by LC-QTOF was applied to urine from 62 patients with a clinically significant PCa and 42 healthy individuals, both groups confirmed by biopsy. An unpaired t-test (p-value < 0.05) provided 28 significant metabolites tentatively identified in urine, used to develop a partial least squares discriminant analysis (PLS-DA) model characterized by 88.4 and 92.9% of sensitivity and specificity, respectively. Among the 28 significant metabolites 27 were present at lower concentrations in PCa patients than in control individuals, while only one reported higher concentrations in PCa patients. The connection among the biochemical pathways in which they are involved (DNA methylation, epigenetic marks on histones and RNA cap methylation) could explain the concentration changes with PCa and supports, once again, the role of metabolomics in upstream processes.

PSMA PET in prostate cancer – a step towards personalized medicine

PubMed Central

Bouchelouche, Kirsten; Choyke, Peter L.

2017-01-01

Purpose of review Increasing attention is being given to personalized medicine in oncology, where therapies are tailored to the particular characteristics of the individual cancer patient. In recent years, there has been greater focus on PSMA in prostate cancer (PCa) as a target for imaging and therapy with radionuclides. This review highlights the recent advancements in PSMA PET in PCa during the past year. Recent findings Several reports on PSMA PET/CT in PCa patients are demonstrating promising results, especially for detection of biochemical recurrence. 18F-PSMA PET/CT may be superior to 68Ga-PSMA PET/CT. The detection rate of PSMA PET is influenced by PSA level. PSMA PET/CT may have a higher detection rate than choline PET/CT. Only a few reports have been published on PSMA PET/MRI, and this modality remains to be elucidated further. Conclusion Molecular imaging with PSMA PET is paving the way for personalized medicine in PCa. However, large prospective clinical studies are needed to further evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa. PSMA is an excellent target for imaging and therapy with radionuclides, and the “image and treat” strategy has the potential to become a milestone in the management of PCa patients. PMID:26967720

The clinical effectiveness and cost-effectiveness of the PROGENSA® prostate cancer antigen 3 assay and the Prostate Health Index in the diagnosis of prostate cancer: a systematic review and economic evaluation.

PubMed

Nicholson, Amanda; Mahon, James; Boland, Angela; Beale, Sophie; Dwan, Kerry; Fleeman, Nigel; Hockenhull, Juliet; Dundar, Yenal

2015-10-01

There is no single definitive test to identify prostate cancer in men. Biopsies are commonly used to obtain samples of prostate tissue for histopathological examination. However, this approach frequently misses cases of cancer, meaning that repeat biopsies may be necessary to obtain a diagnosis. The PROGENSA(®) prostate cancer antigen 3 (PCA3) assay (Hologic Gen-Probe, Marlborough, MA, USA) and the Prostate Health Index (phi; Beckman Coulter Inc., Brea, CA, USA) are two new tests (a urine test and a blood test, respectively) that are designed to be used to help clinicians decide whether or not to recommend a repeat biopsy. To evaluate the clinical effectiveness and cost-effectiveness of the PCA3 assay and the phi in the diagnosis of prostate cancer. Multiple publication databases and trial registers were searched in May 2014 (from 2000 to May 2014), including MEDLINE, EMBASE, The Cochrane Library, ISI Web of Science, Medion, Aggressive Research Intelligence Facility database, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number Register and World Health Organization International Clinical Trials Registry Platform. The assessment of clinical effectiveness involved three separate systematic reviews, namely reviews of the analytical validity, the clinical validity of these tests and the clinical utility of these tests. The assessment of cost-effectiveness comprised a systematic review of full economic evaluations and the development of a de novo economic model. The perspective of the evaluation was the NHS in England and Wales. Men suspected of having prostate cancer for whom the results of an initial prostate biopsy were negative or equivocal. The use of the PCA3 score or phi in combination with existing tests (including histopathology results, prostate-specific antigen level and digital rectal examination), multiparametric magnetic resonance imaging and clinical judgement. In addition to documents published by the manufacturers, six studies were identified for inclusion in the analytical validity review. The review identified issues concerning the precision of the PCA3 assay measurements. It also highlighted issues relating to the storage requirements and stability of samples intended for analysis using the phi assay. Fifteen studies met the inclusion criteria for the clinical validity review. These studies reported results for 10 different clinical comparisons. There was insufficient evidence to enable the identification of appropriate test threshold values for use in a clinical setting. In addition, the implications of adding either the PCA3 assay or the phi to clinical assessment were not clear. Furthermore, the addition of the PCA3 assay or the phi to clinical assessment plus magnetic resonance imaging was not found to improve discrimination. No published papers met the inclusion criteria for either the clinical utility review or the cost-effectiveness review. The results from the cost-effectiveness analyses indicated that using either the PCA3 assay or the phi in the NHS was not cost-effective. The main limitations of the systematic review of clinical validity are that the review conclusions are over-reliant on findings from one study, the descriptions of clinical assessment vary widely within reviewed studies and many of the reported results for the clinical validity outcomes do not include either standard errors or confidence intervals. The clinical benefit of using the PCA3 assay or the phi in combination with existing tests, scans and clinical judgement has not yet been confirmed. The results from the cost-effectiveness analyses indicate that the use of these tests in the NHS would not be cost-effective. This study is registered as PROSPERO CRD42014009595. The National Institute for Health Research Health Technology Assessment programme.

Aberrant expression of miR-141 and nuclear receptor small heterodimer partner in clinical samples of prostate cancer.

PubMed

Khorasani, Maryam; Teimoori-Toolabi, Ladan; Farivar, Taghi Naserpour; Asgari, Mojgan; Abolhasani, Maryam; Shahrokh, Hossein; Afgar, Ali; Kalantari, Elham; Peymani, Amir; Mahdian, Reza

2018-01-01

Prostate cancer (PCa) is the second most common cancer in men worldwide. Currently, prostate-specific antigen (PSA) test and digital rectal exam are the main screening tests used for PCa diagnosis. However, due to the low specificity of these tests, new alternative biomarkers such as deregulated RNAs and microRNAs have been implemented. Aberrant expressions of small heterodimer partner gene (SHP, NR0B2) and mir-141 are reported in various cancers. The aim of this study was to investigate the SHP and miR-141 expression level in tissue samples of prostate cancer. The expression level of SHP gene and miR-141 was assessed by real time PCR and their relative amounts were calculated by the Δ⁢ΔCT method. Also, IHC technique was used to determine the expression level of SHP protein. The miR-141 was significantly up-regulated in the samples of metastatic tumors compared to localized tumor samples (P< 0.001, 31.17-fold change). Tumor samples showed lower SHP mRNA expression levels than BPH samples (p= 0.014, 4.7-fold change). The results of paired t-test analysis showed there was no significant difference between the SHP gene expression in PCa samples and their matched tumor-adjacent normal tissue (p= 0.5). The data obtained in our study confirm the involvement of miR-141 in PCa progression and metastasis. These effects could be mediated by AR via down-regulation of its co-repressor protein, i.e., SHP.

Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories.

PubMed

Arthur, Rhonda; Møller, Henrik; Garmo, Hans; Holmberg, Lars; Stattin, Pår; Malmstrom, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Robinson, David; Jungner, Ingmar; Hemelrijck, Mieke Van

2016-06-01

Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 μg/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 μg/L compared to PSA 4.0-9.9 μg/L. Hypertriglyceridemia was also positively associated with PSA>20 μg/L. Hyperglycemic men had a greater odds of intermediate- and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Diagnostic Pathway with Multiparametric Magnetic Resonance Imaging Versus Standard Pathway: Results from a Randomized Prospective Study in Biopsy-naïve Patients with Suspected Prostate Cancer.

PubMed

Porpiglia, Francesco; Manfredi, Matteo; Mele, Fabrizio; Cossu, Marco; Bollito, Enrico; Veltri, Andrea; Cirillo, Stefano; Regge, Daniele; Faletti, Riccardo; Passera, Roberto; Fiori, Cristian; De Luca, Stefano

2017-08-01

An approach based on multiparametric magnetic resonance imaging (mpMRI) might increase the detection rate (DR) of clinically significant prostate cancer (csPCa). To compare an mpMRI-based pathway with the standard approach for the detection of prostate cancer (PCa) and csPCa. Between November 2014 and April 2016, 212 biopsy-naïve patients with suspected PCa (prostate specific antigen level ≤15 ng/ml and negative digital rectal examination results) were included in this randomized clinical trial. Patients were randomized into a prebiopsy mpMRI group (arm A, n=107) or a standard biopsy (SB) group (arm B, n=105). In arm A, patients with mpMRI evidence of lesions suspected for PCa underwent mpMRI/transrectal ultrasound fusion software-guided targeted biopsy (TB) (n=81). The remaining patients in arm A (n=26) with negative mpMRI results and patients in arm B underwent 12-core SB. The primary end point was comparison of the DR of PCa and csPCa between the two arms of the study; the secondary end point was comparison of the DR between TB and SB. The overall DRs were higher in arm A versus arm B for PCa (50.5% vs 29.5%, respectively; p=0.002) and csPCa (43.9% vs 18.1%, respectively; p<0.001). Concerning the biopsy approach, that is, TB in arm A, SB in arm A, and SB in arm B, the overall DRs were significantly different for PCa (60.5% vs 19.2% vs 29.5%, respectively; p<0.001) and for csPCa (56.8% vs 3.8% vs 18.1%, respectively; p<0.001). The reproducibility of the study could have been affected by the single-center nature. A diagnostic pathway based on mpMRI had a higher DR than the standard pathway in both PCa and csPCa. In this randomized trial, a pathway for the diagnosis of prostate cancer based on multiparametric magnetic resonance imaging (mpMRI) was compared with the standard pathway based on random biopsy. The mpMRI-based pathway had better performance than the standard pathway. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, Eunpi; Fred Hutchinson Cancer Research Center, Seattle, Washington; Mostaghel, Elahe A.

Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at themore » discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression. Preliminary analysis of the clinical data is also promising, with excellent PSA nadir and no relapse to date in this high-risk population.« less

Motor features in posterior cortical atrophy and their imaging correlates☆

PubMed Central

Ryan, Natalie S.; Shakespeare, Timothy J.; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M.; Leung, Kelvin K.; Fox, Nick C.; Crutch, Sebastian J.

2014-01-01

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. PMID:25086839

Fatty acid binding protein 4 enhances prostate cancer progression by upregulating matrix metalloproteinases and stromal cell cytokine production

PubMed Central

Huang, Mingguo; Narita, Shintaro; Inoue, Takamitsu; Koizumi, Atsushi; Saito, Mitsuru; Tsuruta, Hiroshi; Numakura, Kazuyuki; Satoh, Shigeru; Nanjo, Hiroshi; Sasaki, Takehiko; Habuchi, Tomonori

2017-01-01

Fatty acid binding protein 4 (FABP4) is an abundant protein in adipocytes, and its production is influenced by high-fat diet (HFD) or obesity. The prostate stromal microenvironment induces proinflammatory cytokine production, which is key for the development and progression of prostate cancer (PCa). Here, we show that high FABP4 expression and its secretion by PCa cells directly stimulated PCa cell invasiveness by upregulating matrix metalloproteinases through phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways. In addition, prostate stromal cells augmented PCa cell invasiveness by secreting interleukin-8 and -6 in response to FABP4. This was abrogated by the FABP4 specific inhibitor, BMS309403. Furthermore, a mouse xenograft experiment showed HFD enhanced PCa metastasis and invasiveness by the upregulation of FABP4 and interleukin-8. Clinically, the serum level of FABP4 was significantly associated with an aggressive type of PCa rather than obesity. Taken together, FABP4 may enhance PCa progression and invasiveness by upregulating matrix metalloproteinases and cytokine production in the PCa stromal microenvironment, especially under HFD or obesity. PMID:29340091

Testing the impact of a multimedia video CD of patient-controlled analgesia on pain knowledge and pain relief in patients receiving surgery.

PubMed

Chen, Hsing-Hsia; Yeh, Mei-Ling; Yang, Hui-Ju

2005-07-01

This study aimed to develop a multimedia video CD (VCD) of patient-controlled analgesia (PCA) and test its effects on pain knowledge and pain relief in patients receiving surgery. This multimedia VCD of PCA was created to convey fundamental knowledge to both patients and their family members and help patients properly utilize PCA devices to relieve pain and improve recovery. The content of multimedia VCD of PCA included pre-admission pain education, introduction of PCA, nursing care procedures, and questions and answers. This study used a quasi-experimental research design to test effects of the multimedia education program in the experimental group of 30 subjects compared to the control subjects of equal number (without the multimedia VCD of PCA). (1) The intervention of multimedia VCD of PCA resulted in a statistically significant difference in pain knowledge between the experimental and control groups. (2) Subjects in the experimental group obtained a better outcome of pain relief compared to control subjects. (3) Subjects in the experimental group indicated that the multimedia VCD of PCA indeed helped them effectively operate their PCA devices to relieve surgery pain. The clinical application of the multimedia VCD of PCA could help patients improve knowledge on pain, learn how to use PCA devices, achieve proper pain relief, and increase effectiveness of recovery activities.

A novel fusion method of improved adaptive LTP and two-directional two-dimensional PCA for face feature extraction

NASA Astrophysics Data System (ADS)

Luo, Yuan; Wang, Bo-yu; Zhang, Yi; Zhao, Li-ming

2018-03-01

In this paper, under different illuminations and random noises, focusing on the local texture feature's defects of a face image that cannot be completely described because the threshold of local ternary pattern (LTP) cannot be calculated adaptively, a local three-value model of improved adaptive local ternary pattern (IALTP) is proposed. Firstly, the difference function between the center pixel and the neighborhood pixel weight is established to obtain the statistical characteristics of the central pixel and the neighborhood pixel. Secondly, the adaptively gradient descent iterative function is established to calculate the difference coefficient which is defined to be the threshold of the IALTP operator. Finally, the mean and standard deviation of the pixel weight of the local region are used as the coding mode of IALTP. In order to reflect the overall properties of the face and reduce the dimension of features, the two-directional two-dimensional PCA ((2D)2PCA) is adopted. The IALTP is used to extract local texture features of eyes and mouth area. After combining the global features and local features, the fusion features (IALTP+) are obtained. The experimental results on the Extended Yale B and AR standard face databases indicate that under different illuminations and random noises, the algorithm proposed in this paper is more robust than others, and the feature's dimension is smaller. The shortest running time reaches 0.329 6 s, and the highest recognition rate reaches 97.39%.

Posterior cortical atrophy variant of Alzheimer's dementia-A case report.

PubMed

Mukku, Shiva Shanker Reddy; Chintala, Haripriya; Nagaraj, Chandana; Mangalore, Sandhya; Sivakumar, Palanimuthu T; Varghese, Mathew

2018-05-17

Alzheimer's dementia (AD) is the commonest type of dementia presenting with initial episodic memory decline followed by involvement of other cognitive domains. Posterior cortical atrophy (PCA) is one of the variants of Alzheimer's dementia (AD) characterized by the atypical presentation of relatively persevered memory in the initial stage. PCA is an uncommon early onset dementia affecting adults between 50 and 65 years. It presents predominantly with visuo-spatial and visuo-perceptual deficits. PCA is a phenotype with varied etiology most common being Alzheimer's disease. The complex and atypical presentation with preserved memory and insight in patients with PCA poses challenge to clinicians in diagnosing at initial stages. There is also paucity of research on prevalence, course, prognosis and management of PCA. In this article we describe a middle aged gentlemen presenting with clinical features suggestive of PCA. We also discussed relevant literature. Copyright © 2018 Elsevier B.V. All rights reserved.

The Present and Future of Prostate Cancer Urine Biomarkers

PubMed Central

Rigau, Marina; Olivan, Mireia; Garcia, Marta; Sequeiros, Tamara; Montes, Melania; Colás, Eva; Llauradó, Marta; Planas, Jacques; de Torres, Inés; Morote, Juan; Cooper, Colin; Reventós, Jaume; Clark, Jeremy; Doll, Andreas

2013-01-01

In order to successfully cure patients with prostate cancer (PCa), it is important to detect the disease at an early stage. The existing clinical biomarkers for PCa are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid over-treatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two thirds of the biopsies performed are still unnecessary. Thus the discovery of non-invasive PCa biomarkers remains urgent. In recent years, the utilization of urine has emerged as an attractive option for the non-invasive detection of PCa. Moreover, a great improvement in high-throughput “omic” techniques has presented considerable opportunities for the identification of new biomarkers. Herein, we will review the most significant urine biomarkers described in recent years, as well as some future prospects in that field. PMID:23774836

PSMA Ligands for Radionuclide Imaging and Therapy of Prostate Cancer: Clinical Status

PubMed Central

Lütje, Susanne; Heskamp, Sandra; Cornelissen, Alexander S.; Poeppel, Thorsten D.; van den Broek, Sebastiaan A. M. W.; Rosenbaum-Krumme, Sandra; Bockisch, Andreas; Gotthardt, Martin; Rijpkema, Mark; Boerman, Otto C.

2015-01-01

Prostate cancer (PCa) is the most common malignancy in men worldwide, leading to substantial morbidity and mortality. At present, imaging of PCa has become increasingly important for staging, restaging, and treatment selection. Until recently, choline-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for these purposes. However, its application is limited to patients with high PSA levels and Gleason scores. Prostate-specific membrane antigen (PSMA) is a promising new target for specific imaging of PCa, because it is upregulated in the majority of PCa. Moreover, PSMA can serve as a target for therapeutic applications. Currently, several small-molecule PSMA ligands with excellent in vivo tumor targeting characteristics are being investigated for their potential in theranostic applications in PCa. Here, a review of the recent developments in PSMA-based diagnostic imaging and therapy in patients with PCa with radiolabeled PSMA ligands is provided. PMID:26681984

SU-E-T-426: Feasibility of Stereotactic Body Radiation Therapy (SBRT) Treatment of Pancreatic Cancer Using Volumetric Modulated Arc Therapy (VMAT) with Active Breathing Control (ABC)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Y; Jackson, J; Davies, G

2015-06-15

Purpose: SBRT shows excellent tumor control and toxicity rates for patients with locally advanced pancreatic cancer (PCA). Herein, we evaluate the feasibility of using VMAT with ABC for PCA SBRT. Methods: Nine PCA patients previously treated via SBRT utilizing 11-beam step-and-shoot IMRT technique in our center were retrospectively identified, among whom eight patients received 3300cGy in 5 fractions while one received 3000cGy in 5 fractions. A VMAT plan was generated on each patient’s planning CT in Pinnacle v9.8 on Elekta Synergy following the same PCA SBRT clinical protocol. Three partial arcs (182°–300°, 300°-60°, and 60°-180°) with 2°/4° control-point spacing weremore » used. The dosimetric difference between the VMAT and the original IMRT plans was analyzed. IMRT QA was performed for the VMAT plans using MapCheck2 in MapPHAN and the total delivery time was recorded. To mimic the treatment situation with ABC, where patients hold their breath for 20–30 seconds, the delivery was intentionally interrupted every 20–30 seconds. For each plan, the QA was performed with and without beam interruption. Gamma analysis (2%/2mm) was used to compare the planned and measured doses. Results: All VMAT plans with 2mm dose grid passed the clinic protocol with similar PTV coverage and OARs sparing, where PTV V-RxDose was 92.7±2.1% (VMAT) vs. 92.1±2.6% (IMRT), and proximal stomach V15Gy was 3.60±2.69 cc (VMAT) vs. 4.80±3.13 cc (IMRT). The mean total MU and delivery time of the VMAT plans were 2453.8±531.1 MU and 282.1±56.0 seconds. The gamma passing rates of absolute dose were 94.9±3.4% and 94.5±4.0% for delivery without and with interruption respectively, suggesting the dosimetry of VMAT delivery with ABC for SBRT won’t be compromised. Conclusion: This study suggests that PCA SBRT using VMAT with ABC is a feasible technique without compromising plan dosimetry. The combination of VMAT with ABC will potentially reduce the SBRT treatment time.« less

Proteomic Profiling of Exosomes Leads to the Identification of Novel Biomarkers for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duijvesz, Diederick; Burnum-Johnson, Kristin E.; Gritsenko, Marina A.

Introduction: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, biomarker discovery from body fluids is often hampered by the high abundance of many proteins unrelated to disease. An attractive alternative biomarker discovery approach is the isolation of small vesicles (exosomes, ~100 nm). They contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific marker discovery. Profiling prostate cancer-derived exosomes could reveal new markers for this malignancy. Materials and Methods: Exosomes were isolated from 2 immortalized primary prostate epithelial cellsmore » (PNT2C2 and RWPE-1) and 2 PCa cell lines (PC346C and VCaP) by ultracentrifugation. Proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS) mode, followed by the Accurate Mass and Time (AMT) tag approach. Exosomal proteins were validated by Western blotting. A Tissue Micro Array, containing 481 different PCa samples (radical prostatectomy), was used to correlate candidate markers with several clinical-pathological parameters such as PSA, Gleason score, biochemical recurrence, and (PCa-related) death. Results: Proteomic characterization resulted in the identification of 263 proteins by at least 2 peptides. Specifically analysis of exosomes from PNT2C2, RWPE-1, PC346C, and VCaP identified 248, 233, 169, and 216 proteins, respectively. Statistical analyses revealed 52 proteins differently expressed between PCa and control cells, 9 of which were more abundant in PCa. Validation by Western blotting confirmed a higher abundance of FASN, XPO1 and PDCD6IP (ALIX) in PCa exosomes. The Tissue Micro 4 Array showed strong correlation of higher Gleason scores and local recurrence with increased cytoplasmic XPO1 (P<0.001). Conclusions: Differentially abundant proteins of cell line-derived exosomes make a clear subdivision between benign and malignant origin. Validation showed a preferential abundance of PDCD6IP, FASN and XPO1. Cytoplasmic XPO1 is the most promising candidate biomarker.« less

Computer-aided diagnosis of prostate cancer using a deep convolutional neural network from multiparametric MRI.

PubMed

Song, Yang; Zhang, Yu-Dong; Yan, Xu; Liu, Hui; Zhou, Minxiong; Hu, Bingwen; Yang, Guang

2018-04-16

Deep learning is the most promising methodology for automatic computer-aided diagnosis of prostate cancer (PCa) with multiparametric MRI (mp-MRI). To develop an automatic approach based on deep convolutional neural network (DCNN) to classify PCa and noncancerous tissues (NC) with mp-MRI. Retrospective. In all, 195 patients with localized PCa were collected from a PROSTATEx database. In total, 159/17/19 patients with 444/48/55 observations (215/23/23 PCas and 229/25/32 NCs) were randomly selected for training/validation/testing, respectively. T 2 -weighted, diffusion-weighted, and apparent diffusion coefficient images. A radiologist manually labeled the regions of interest of PCas and NCs and estimated the Prostate Imaging Reporting and Data System (PI-RADS) scores for each region. Inspired by VGG-Net, we designed a patch-based DCNN model to distinguish between PCa and NCs based on a combination of mp-MRI data. Additionally, an enhanced prediction method was used to improve the prediction accuracy. The performance of DCNN prediction was tested using a receiver operating characteristic (ROC) curve, and the area under the ROC curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Moreover, the predicted result was compared with the PI-RADS score to evaluate its clinical value using decision curve analysis. Two-sided Wilcoxon signed-rank test with statistical significance set at 0.05. The DCNN produced excellent diagnostic performance in distinguishing between PCa and NC for testing datasets with an AUC of 0.944 (95% confidence interval: 0.876-0.994), sensitivity of 87.0%, specificity of 90.6%, PPV of 87.0%, and NPV of 90.6%. The decision curve analysis revealed that the joint model of PI-RADS and DCNN provided additional net benefits compared with the DCNN model and the PI-RADS scheme. The proposed DCNN-based model with enhanced prediction yielded high performance in statistical analysis, suggesting that DCNN could be used in computer-aided diagnosis (CAD) for PCa classification. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Genetic variants in RNA-induced silencing complex genes and prostate cancer.

PubMed

Nikolić, Z; Savić Pavićević, D; Vučić, N; Cerović, S; Vukotić, V; Brajušković, G

2017-04-01

The purpose of this study is to evaluate the potential association between genetic variants in genes encoding the components of RNA-induced silencing complex and prostate cancer (PCa) risk. Genetic variants chosen for this study are rs3742330 in DICER1, rs4961280 in AGO2, rs784567 in TARBP2, rs7813 in GEMIN4 and rs197414 in GEMIN3. The study involved 355 PCa patients, 360 patients with benign prostatic hyperplasia and 318 healthy controls. For individuals diagnosed with PCa, clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS) and clinical stage were determined. Genotyping was performed using high-resolution melting analysis, PCR-RFLP, TaqMan SNP Genotyping Assay and real-time PCR-based genotyping assay using specific probes. Allelic and genotypic associations were evaluated by unconditional linear and logistic regression methods. The study provided no evidence of association between the analyzed genetic variants and PCa risk. Nevertheless, allele A of rs784567 was found to confer the reduced risk of higher serum PSA level at diagnosis (P = 0.046; Difference = -66.64, 95 % CI -131.93 to 1.35, for log-additive model). Furthermore, rs4961280, as well as rs3742330, were shown to be associated with GS. These variants, together with rs7813, were found to be associated with the lower clinical stage of PCa. Also, rs3742330 minor allele G was found to be associated with lower PCa aggressiveness (P = 0.036; OR 0.14, 95 % CI 0.023-1.22, for recessive model). According to our data, rs3742330, rs4961280 and rs7813 qualify for potentially protective genetic variants against PCa progression. These variants were not shown to be associated with PCa risk.

Cryosurgery would be An Effective Option for Clinically Localized Prostate Cancer: A Meta-analysis and Systematic Review

PubMed Central

Gao, Liang; Yang, Lu; Qian, Shengqiang; Tang, Zhuang; Qin, Feng; Wei, Qiang; Han, Ping; Yuan, Jiuhong

2016-01-01

Cryosurgery (CS) has been used on patients with clinically localized PCa for more than 10 years. However, clinical studies evaluating its effectiveness and safety have reported conflicting results. This systematic assessment was performed to obtain comprehensive evidence regarding the potential benefits and safety of CS compared with those of radiotherapy (RT) and radical prostatectomy (RP), respectively. All controlled trials comparing CS with RT or RP and single-arm studies reporting results of CS therapy were identified through comprehensive searches of PubMed, the Cochrane Library and Embase. Ten publications from seven trials, with totally 1252 patients, were included in the meta-analysis, which revealed no significant differences in comparisons of CS vs RT and CS vs RP for overall survival and disease specific survival. However, a significantly lower disease-free survival could be observed for CS than RP. Moreover, a systematic review of literature focusing on comparative data of databases and materials of single-arm trials revealed satisfactory survival results in both primary and salvage CS. Our results showed that cryosurgery would be a relatively effective method for clinically localized prostate cancer with survival results comparable to radiotherapy and radical prostatectomy. However, the large percentage of complications caused by cryosurgery should be carefully monitored. PMID:27271239

Robust prediction of protein subcellular localization combining PCA and WSVMs.

PubMed

Tian, Jiang; Gu, Hong; Liu, Wenqi; Gao, Chiyang

2011-08-01

Automated prediction of protein subcellular localization is an important tool for genome annotation and drug discovery, and Support Vector Machines (SVMs) can effectively solve this problem in a supervised manner. However, the datasets obtained from real experiments are likely to contain outliers or noises, which can lead to poor generalization ability and classification accuracy. To explore this problem, we adopt strategies to lower the effect of outliers. First we design a method based on Weighted SVMs, different weights are assigned to different data points, so the training algorithm will learn the decision boundary according to the relative importance of the data points. Second we analyse the influence of Principal Component Analysis (PCA) on WSVM classification, propose a hybrid classifier combining merits of both PCA and WSVM. After performing dimension reduction operations on the datasets, kernel-based possibilistic c-means algorithm can generate more suitable weights for the training, as PCA transforms the data into a new coordinate system with largest variances affected greatly by the outliers. Experiments on benchmark datasets show promising results, which confirms the effectiveness of the proposed method in terms of prediction accuracy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Facilitating Neuronal Connectivity Analysis of Evoked Responses by Exposing Local Activity with Principal Component Analysis Preprocessing: Simulation of Evoked MEG

PubMed Central

Gao, Lin; Zhang, Tongsheng; Wang, Jue; Stephen, Julia

2014-01-01

When connectivity analysis is carried out for event related EEG and MEG, the presence of strong spatial correlations from spontaneous activity in background may mask the local neuronal evoked activity and lead to spurious connections. In this paper, we hypothesized PCA decomposition could be used to diminish the background activity and further improve the performance of connectivity analysis in event related experiments. The idea was tested using simulation, where we found that for the 306-channel Elekta Neuromag system, the first 4 PCs represent the dominant background activity, and the source connectivity pattern after preprocessing is consistent with the true connectivity pattern designed in the simulation. Improving signal to noise of the evoked responses by discarding the first few PCs demonstrates increased coherences at major physiological frequency bands when removing the first few PCs. Furthermore, the evoked information was maintained after PCA preprocessing. In conclusion, it is demonstrated that the first few PCs represent background activity, and PCA decomposition can be employed to remove it to expose the evoked activity for the channels under investigation. Therefore, PCA can be applied as a preprocessing approach to improve neuronal connectivity analysis for event related data. PMID:22918837

Facilitating neuronal connectivity analysis of evoked responses by exposing local activity with principal component analysis preprocessing: simulation of evoked MEG.

PubMed

Gao, Lin; Zhang, Tongsheng; Wang, Jue; Stephen, Julia

2013-04-01

When connectivity analysis is carried out for event related EEG and MEG, the presence of strong spatial correlations from spontaneous activity in background may mask the local neuronal evoked activity and lead to spurious connections. In this paper, we hypothesized PCA decomposition could be used to diminish the background activity and further improve the performance of connectivity analysis in event related experiments. The idea was tested using simulation, where we found that for the 306-channel Elekta Neuromag system, the first 4 PCs represent the dominant background activity, and the source connectivity pattern after preprocessing is consistent with the true connectivity pattern designed in the simulation. Improving signal to noise of the evoked responses by discarding the first few PCs demonstrates increased coherences at major physiological frequency bands when removing the first few PCs. Furthermore, the evoked information was maintained after PCA preprocessing. In conclusion, it is demonstrated that the first few PCs represent background activity, and PCA decomposition can be employed to remove it to expose the evoked activity for the channels under investigation. Therefore, PCA can be applied as a preprocessing approach to improve neuronal connectivity analysis for event related data.

Dramatically Polarized Opinion on the Role of Brachytherapy Boost in Management of High-risk Prostate Cancer: A Survey of North American Genitourinary Expert Radiation Oncologists.

PubMed

McClelland, Shearwood; Sandler, Kiri A; Degnin, Catherine; Chen, Yiyi; Mitin, Timur

2018-06-01

Three randomized clinical trials have established brachytherapy (BT) boost in combination with external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT) as superior to definitive EBRT and ADT alone in terms of biochemical control (but not overall survival) at the expense of increased toxicity in men with high-risk (HR) prostate cancer (PCa). The current view regarding these 2 treatment algorithms among North American genitourinary (GU) experts is not known. A survey was distributed to 88 practicing North American GU physicians serving on decision-making committees of cooperative group research organizations. Questions pertained to opinions regarding BT as monotherapy for low-risk PCa and BT boost for HR PCa. Responders were asked to self-identify as BT experts versus non-experts. Treatment recommendations were correlated with practice patterns using the Fisher exact test. Forty-two radiation oncologists completed the survey, of whom 23 (55%) recommend EBRT and ADT alone and 19 (45%) recommend addition of BT boost. Twenty-five participants (60%) identified themselves as BT experts. Nearly 90% of those recommending BT boost were BT experts versus approximately 10% of non-BT experts (P < .001). Responders who recommended BT monotherapy as first-choice treatment for low-risk PCa were more likely to recommend BT boost for HR PCa (P < .0001). There is a dramatic polarization in opinions regarding incorporation of BT boost into EBRT + ADT therapy for patients with HR PCa among North American GU radiation oncology experts, who serve on decision-making committees and influence the national treatment guidelines and future clinical trials. Those who identify themselves as BT experts are significantly more likely to recommend BT boost. These findings are likely to influence the national guidelines and implementation of BT boost in current and future North American PCa clinical studies. Copyright © 2018 Elsevier Inc. All rights reserved.

EVALUATION OF THE I-STAT PORTABLE CLINICAL ANALYZER FOR MEASUREMENT OF IONIZED CALCIUM AND SELECTED BLOOD CHEMISTRY VALUES IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

PubMed

Tarbert, Danielle K; Behling-Kelly, Erica; Priest, Heather; Childs-Sanford, Sara

2017-06-01

Thei-STAT® portable clinical analyzer (PCA) provides patient-side results for hematologic, biochemical, and blood gas values when immediate results are desired. This analyzer is commonly used in nondomestic animals; however, validation of this method in comparison with traditional benchtop methods should be performed for each species. In this study, the i-STAT PCA was compared with the Radiometer ABL 800 Flex benchtop analyzer using 24 heparinized whole blood samples obtained from healthy E. maximus . In addition, the effect of sample storage was evaluated on the i-STAT PCA. Analytes evaluated were hydrogen ion concentration (pH), glucose, potassium (K + ), sodium (Na + ), bicarbonate (HCO 3 - ), total carbon dioxide (TCO 2 ), partial pressure of carbon dioxide (PCO 2 ), and ionized calcium (iCa 2+ ). Statistical analysis using correlation coefficients, Passing-Bablok regression analysis, and Bland-Altman plots found good agreement between results from samples run immediately after phlebotomy and 4 hr postsampling on the i-STAT PCA with the exception of K + , which is known to change with sample storage. Comparison of the results from the two analyzers at 4 hr postsampling found very strong or strong correlation in all values except K + , with statistically significant bias in all values except glucose and PCO 2 . Despite bias, mean differences assessed via Bland-Altman plots were clinically acceptable for all analytes excluding K + . Within the reference range for iCa 2+ , the iCa 2+ values obtained by the i-STAT PCA and Radiometer ABL 800 Flex were close in value, however in light of the constant and proportionate biases detected, overestimation at higher values and underestimation at lower values of iCa 2+ by the i-STAT PCA would be of potential concern. This study supports the use of the i-STAT PCA for the evaluation of these analytes, with the exception of K + , in the Asian elephant.

Gabor-based kernel PCA with fractional power polynomial models for face recognition.

PubMed

Liu, Chengjun

2004-05-01

This paper presents a novel Gabor-based kernel Principal Component Analysis (PCA) method by integrating the Gabor wavelet representation of face images and the kernel PCA method for face recognition. Gabor wavelets first derive desirable facial features characterized by spatial frequency, spatial locality, and orientation selectivity to cope with the variations due to illumination and facial expression changes. The kernel PCA method is then extended to include fractional power polynomial models for enhanced face recognition performance. A fractional power polynomial, however, does not necessarily define a kernel function, as it might not define a positive semidefinite Gram matrix. Note that the sigmoid kernels, one of the three classes of widely used kernel functions (polynomial kernels, Gaussian kernels, and sigmoid kernels), do not actually define a positive semidefinite Gram matrix either. Nevertheless, the sigmoid kernels have been successfully used in practice, such as in building support vector machines. In order to derive real kernel PCA features, we apply only those kernel PCA eigenvectors that are associated with positive eigenvalues. The feasibility of the Gabor-based kernel PCA method with fractional power polynomial models has been successfully tested on both frontal and pose-angled face recognition, using two data sets from the FERET database and the CMU PIE database, respectively. The FERET data set contains 600 frontal face images of 200 subjects, while the PIE data set consists of 680 images across five poses (left and right profiles, left and right half profiles, and frontal view) with two different facial expressions (neutral and smiling) of 68 subjects. The effectiveness of the Gabor-based kernel PCA method with fractional power polynomial models is shown in terms of both absolute performance indices and comparative performance against the PCA method, the kernel PCA method with polynomial kernels, the kernel PCA method with fractional power polynomial models, the Gabor wavelet-based PCA method, and the Gabor wavelet-based kernel PCA method with polynomial kernels.

Morbidity of focal therapy in the treatment of localized prostate cancer.

PubMed

Barret, Eric; Ahallal, Youness; Sanchez-Salas, Rafael; Galiano, Marc; Cosset, Jean-Marc; Validire, Pierre; Macek, Petr; Durand, Matthieu; Prapotnich, Dominique; Rozet, François; Cathelineau, Xavier

2013-04-01

Focal therapy (FT) for prostate cancer (PCa) seems to be part of a natural evolution in the quest to improve the management of early organ-confined disease. To assess the morbidity of the initial experience of FT in a tertiary referral center for PCa management. From 2009 to 2011, a total of 1213 patients with clinically localized PCa were treated at our institution. Of these patients, 547 were considered to have indolent disease according to the D'Amico criteria for low-risk disease plus unilateral disease with a maximum of three positive biopsies. A total of 106 patients underwent FT using high-intensity focused ultrasonography (HIFU), brachytherapy, cryotherapy, or vascular-targeted photodynamic therapy (VTP). Complications were prospectively recorded and graded according to the Clavien-Dindo scale. Data were prospectively collected and retrospectively analyzed. This study included 106 patients, median age 66.5 yr (interquartile range [IQR]): 61-73), who had a prostate hemiablation; 50 patients (47%) had cryotherapy, 23 patients (22%) had VTP, 21 patients (20%) received HIFU, and 12 patients (11%) had brachytherapy. The median prostate-specific antigen (PSA) level was 6.1 ng/ml (IQR: 5-8.1), all the patients had a biopsy Gleason score of 6, and the median prostate weight was 43 g (IQR: 33-55). The median International Prostate Symptom Score was 6 (IQR: 3-10), and the median International Index of Erectile Function score was 20 (IQR: 15-23). After treatment, the median PSA at 3, 6, and 12 mo was 3.1 2.9, and 2.7 ng/ml (IQR: 2-5.1, 1.1-4.7, and 1-4.4), respectively. Thirteen percent of the patients experienced treatment-related complications. There were 11 minor medical complications (10 grade 1 complications and 1 grade 2 complication), 2 grade 3 complications, and no grade 4 or higher complications. FT for a highly selected population with PCa is feasible and had an acceptable morbidity with <2% major complications. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Detection of candidate biomarkers of prostate cancer progression in serum: a depletion-free 3D LC/MS quantitative proteomics pilot study.

PubMed

Larkin, S E T; Johnston, H E; Jackson, T R; Jamieson, D G; Roumeliotis, T I; Mockridge, C I; Michael, A; Manousopoulou, A; Papachristou, E K; Brown, M D; Clarke, N W; Pandha, H; Aukim-Hastie, C L; Cragg, M S; Garbis, S D; Townsend, P A

2016-10-25

Prostate cancer (PCa) is the most common male cancer in the United Kingdom and we aimed to identify clinically relevant biomarkers corresponding to stage progression of the disease. We used enhanced proteomic profiling of PCa progression using iTRAQ 3D LC mass spectrometry on high-quality serum samples to identify biomarkers of PCa. We identified >1000 proteins. Following specific inclusion/exclusion criteria we targeted seven proteins of which two were validated by ELISA and six potentially interacted forming an 'interactome' with only a single protein linking each marker. This network also includes accepted cancer markers, such as TNF, STAT3, NF-κB and IL6. Our linked and interrelated biomarker network highlights the potential utility of six of our seven markers as a panel for diagnosing PCa and, critically, in determining the stage of the disease. Our validation analysis of the MS-identified proteins found that SAA alongside KLK3 may improve categorisation of PCa than by KLK3 alone, and that TSR1, although not significant in this model, might also be a clinically relevant biomarker.

The performance of the new prognostic grade and stage groups in conservatively treated prostate cancer.

PubMed

Chen, Cheng; Chen, Ye; Hu, Lin-Kun; Jiang, Chang-Chuan; Xu, Ren-Fang; He, Xiao-Zhou

2018-02-27

We evaluated the prognosis of the new grade groups and American Joint Committee on Cancer (AJCC) stage groups in men with prostate cancer (PCa) who were treated conservatively. A total of 13 798 eligible men were chosen from the Surveillance Epidemiology and End Results database. The new grade and AJCC stage groups were investigated on prostate biopsy specimens. Kaplan-Meier survival analysis and multivariable hazards models were applied to estimate the association of new grade and stage groups with overall survival (OS) and PCa-specific survival (CSS). Mean follow-up was 42.65 months (95% confidence interval: 42.47-42.84) in the entire cohort. The 3-year OS and CSS rates stepped down for grade groups 1-5 and AJCC stage groups I-IVB, respectively. After adjusting for clinical and pathological characteristics, all grade groups and AJCC stage groups were associated with higher all-cause and PCa-specific mortality compared to the reference group (all P ≤ 0.003). In conclusion, we evaluated the oncological outcome of the new grade and AJCC stage groups on biopsy specimens of conservatively treated PCa. These two novel clinically relevant classifications can assist physicians to determine different therapeutic strategies for PCa patients.

The 20th Annual Prostate Cancer Foundation Scientific Retreat report.

PubMed

Miyahira, Andrea K; Simons, Jonathan W; Soule, Howard R

2014-06-01

The 20th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 24 to 26, 2013, in National Harbor, Maryland. This event is held annually for the purpose of convening a diverse group of leading experimental and clinical researchers from academia, industry, and government to present and discuss critical and emerging topics relevant to prostate cancer (PCa) biology, and the diagnosis, prognosis, and treatment of PCa patients, with a focus on results that will lend to treatments for the most life-threatening stages of this disease. The themes that were highlighted at this year's event included: (i) mechanisms of PCa initiation and progression: cellular origins, neurons and neuroendocrine PCa, long non-coding RNAs, epigenetics, tumor cell metabolism, tumor-immune interactions, and novel molecular mechanisms; (ii) advancements in precision medicine strategies and predictive biomarkers of progression, survival, and drug sensitivities, including the analysis of circulating tumor cells and cell-free tumor DNA-new methods for liquid biopsies; (iii) new treatments including epigenomic therapy and immunotherapy, discovery of new treatment targets, and defining and targeting mechanisms of resistance to androgen-axis therapeutics; and (iv) new experimental and clinical epidemiology methods and techniques, including PCa population studies using patho-epidemiology. © 2014 Wiley Periodicals, Inc.

Impact of Frequent Interruption on Nurses' Patient-Controlled Analgesia Programming Performance.

PubMed

Campoe, Kristi R; Giuliano, Karen K

2017-12-01

The purpose was to add to the body of knowledge regarding the impact of interruption on acute care nurses' cognitive workload, total task completion times, nurse frustration, and medication administration error while programming a patient-controlled analgesia (PCA) pump. Data support that the severity of medication administration error increases with the number of interruptions, which is especially critical during the administration of high-risk medications. Bar code technology, interruption-free zones, and medication safety vests have been shown to decrease administration-related errors. However, there are few published data regarding the impact of number of interruptions on nurses' clinical performance during PCA programming. Nine acute care nurses completed three PCA pump programming tasks in a simulation laboratory. Programming tasks were completed under three conditions where the number of interruptions varied between two, four, and six. Outcome measures included cognitive workload (six NASA Task Load Index [NASA-TLX] subscales), total task completion time (seconds), nurse frustration (NASA-TLX Subscale 6), and PCA medication administration error (incorrect final programming). Increases in the number of interruptions were associated with significant increases in total task completion time ( p = .003). We also found increases in nurses' cognitive workload, nurse frustration, and PCA pump programming errors, but these increases were not statistically significant. Complex technology use permeates the acute care nursing practice environment. These results add new knowledge on nurses' clinical performance during PCA pump programming and high-risk medication administration.

Prostate-specific membrane antigen for prostate cancer theranostics: from imaging to targeted therapy.

PubMed

Arsenault, Frédéric; Beauregard, Jean-Mathieu; Pouliot, Frédéric

2018-06-22

In recent years, major advances in molecular imaging of prostate cancers (PCa) were made with the development and clinical validation of highly accurate PET tracers to stage and restage the disease. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in PCa, and its expression has led to the development of PSMA-binding radiopharmaceuticals for molecular imaging or radioligand therapy (RLT). We herein review the recent literature published on diagnostic and therapeutic (i.e. theranostic) PSMA tracers. Development in small PSMA-targeted molecules labeled with gallium-68 and fluorine-18 show promising results for primary staging and detection of disease at biochemical recurrence using PET/computed tomography (PET/CT). Studies show a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and bone scan) or choline PET tracers, especially for restaging after prostate-specific antigen failure following loco-regional therapy. In addition, some PSMA tracers can be labeled with beta-minus and alpha particle emitters, yielding encouraging response rates and low toxicity, and potentially offering a new line of targeted therapy for metastatic castration-resistant PCa. PSMA-targeted tracers have shown unprecedented accuracy to stage and restage PCa using PET/CT. Given their specific biodistribution toward PCa tissue, PSMA RLT now offers new therapeutic possibilities to target metastatic PCa. Prospective multicenter randomized studies investigating the clinical impact management impacts of PSMA-targeted molecules are urgently needed.

Leupaxin acts as a mediator in prostate carcinoma progression through deregulation of p120catenin expression.

PubMed

Kaulfuss, S; von Hardenberg, S; Schweyer, S; Herr, A M; Laccone, F; Wolf, S; Burfeind, P

2009-11-12

Recently, we could show that the focal adhesion protein leupaxin (LPXN) is expressed in human prostate carcinomas (PCa) and induces invasiveness of androgen-independent PCa cells. In this study we show that LPXN enhanced the progression of existing PCa in vivo by breeding transgenic mice with prostate-specific LPXN expression and TRAMP mice (transgenic adenocarcinoma of mouse prostate). Double transgenic LPXN/TRAMP mice showed a significant increase in poorly differentiated PCa and distant metastases as compared with control TRAMP mice. Additional studies on primary PCa cells generated from both transgenic backgrounds confirmed the connection regarding LPXN overexpression and increased motility and invasiveness of PCa cells. One mediator of LPXN-induced invasion was found to be the cell-cell adhesion protein p120catenin (p120CTN). Both in vitro and in vivo experiments revealed that p120CTN expression negatively correlates with LPXN expression, followed by a redistribution of beta-catenin. Downregulation of LPXN using small interfering RNAs (siRNAs) resulted in a membranous localization of beta-catenin, whereas strong nuclear accumulation of beta-catenin was observed in p120CTN knockdown cells leading to enhanced transcription of the beta-catenin target gene matrix metalloprotease-7. In conclusion, the present results indicate that LPXN enhances the progression of PCa through downregulation of p120CTN expression and that LPXN could function as a marker for aggressive PCa in the future.

Comparison of 68Ga-PSMA-11 and 18F-Fluciclovine PET/CT in a Case Series of 10 Patients with Prostate Cancer Recurrence.

PubMed

Calais, Jeremie; Fendler, Wolfgang P; Herrmann, Ken; Eiber, Matthias; Ceci, Francesco

2018-05-01

This was a head-to-head comparison between 68 Ga-labeled prostate-specific membrane antigen (PSMA)-11 and 18 F-fluciclovine PET/CT in a series of 10 patients with prostate cancer (PCa) recurrence. Methods: In total, 288 patients with PCa recurrence were enrolled in a prospective study of 68 Ga-PSMA-11 PET/CT imaging for recurrent disease localization (ClinicalTrials.gov identifier NCT02940262). We retrospectively identified 10 patients who underwent clinically indicated 18 F-fluciclovine PET/CT prior to enrollment. Results: The median time between the 2 scans was 2.2 mo (range, 0.2-4.2 mo). The median prostate-specific antigen (PSA) value was 1.0 ng/mL (mean, 4.7 ng/mL; range, 0.13-18.1 ng/mL) and 1.1 ng/mL (mean, 6.2 ng/mL; range, 0.24-31.3 ng/mL) at the time of 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT, respectively. Five of 10 patients (50%) were negative with 18 F-fluciclovine but positive with 68 Ga-PSMA-11 PET/CT. Two of 10 patients (20%) were positive with both 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT, but 68 Ga-PSMA-11 PET/CT showed additional lymph nodes metastasis. Three of 10 patients (30%) were negative with both 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT. Conclusion: This case series suggests improved detection rates for 68 Ga-PSMA-11 PET/CT when compared with 18 F-fluciclovine PET/CT in patients with recurrent PCa. Prospective trials designed to directly compare the two should be initiated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Value of Endorectal MRI in Romanian Men for High Risk of Prostate Cancer: MRI Findings Compared with Saturation Biopsy.

PubMed

Lebovici, A; Sfrangeu, S A; Caraiani, C; Lucan, C; Suciu, M; Elec, F; Iacob, Gh; Buruian, M

2015-01-01

To evaluate the potentials of T2 weighted (T2W)MRI and diffusion weighted (DW) MRI for prostate cancer(PCa) detection, local staging and treatment planning in high-risk group. Endorectal MRI was performed in 17 Romanian men (median age: 66 years; range: 58 75 years), prostate specific antigen (PSA) serum levels (median: 20 ng mL; range: 8.6 100 ng mL) with positive findings for PCa(median Gleason score: 8; range: 7 - 9). Imaging findings were compared to standarised 20-core transperineal saturation biopsy. The prostate was divided into 16 standart sectors(10 posterior and 6 anterior). Overall, prostate cancer was detected in 16 patients(94%) on DW-MRI alone and in all 17 patients (100%) on T2W-MRI alone, and on combined imaging. On T2W-MRI165 sectors out of 272 were suspicious for PCa and 124 (75%)were cancer positive. On DW-MRI 126 sectors out of 272 were suspicious for PCa and 118 (95%) were cancer positive. On the combined imaging approach 134 sectors out of 272 were suspicious for PCa and 126 (94%) were cancer positive. This resulted in diagnostic accuracies per sector of 76% for T2WMRI, 86% for DW-MRI and 89% for combined imaging. Multifocal PCa was confirmed both on MR imaging and by biopsy in 8 of the 17 men (47%) Extra capsular extension(ECE) or seminal vesicles invasion (SVI) was highly suspected in 8 (47%) respectively 7 (41%) of the 17 patients. 6 patients(35%) presented both ECE and SVI. MRI findings were taken into account for treatment planning and none of these patients underwent radical prostatectomy and instead was treated with palliative cryotherapy, radiotherapy and hormone therapy. Endorectal MRI is highly accurate in PCa detection in the high-risk group and seems to have an important role in local staging and treatment planning for Romanian population. Celsius.

Prognostic value of transformer 2β expression in prostate cancer.

PubMed

Diao, Yan; Wu, Dong; Dai, Zhijun; Kang, Huafeng; Wang, Ziming; Wang, Xijing

2015-01-01

Deregulation of transformer 2β (Tra2β) has been implicated in several cancers. However, the role of Tra2β expression in prostate cancer (PCa) is unclear. Therefore, this study was to investigate the expression of Tra2β in PCa and evaluated its association with clinicopathological variables and prognosis. Thirty paired fresh PCa samples were analyzed for Tra2β expression by Western blot analysis. Immunohistochemistry (IHC) assay was performed in 160 PCa samples after radical prostatectomy and adjacent non-cancerous tissues. Tra2β protein expression was divided into high expression group and low expression group by IHC. We also investigated the association of Tra2β expression with clinical and pathologic parameters. Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the association between Tra2β protein expression and prognosis of PCa patients. Our results showed that Tra2β was significantly upregulated in PCa tissues by western blot and IHC. Our data indicated that high expression of Tra2β was significantly associated with lymph node metastasis (P=0.002), clinical stage (P=0.015), preoperative prostate-specific antigen (P=0.003), Gleason score (P=0.001), and biochemical recurrence (P=0.021). High Tra2β expression was a significant predictor of poor biochemical recurrence free survival and overall survival both in univariate and multivariate analysis. We show that Tra2β was significantly upregulated in PCa patients after radical prostatectomy, and multivariate analysis confirmed Tra2β as an independent prognostic factor.

Locally linear embedding: dimension reduction of massive protostellar spectra

NASA Astrophysics Data System (ADS)

Ward, J. L.; Lumsden, S. L.

2016-09-01

We present the results of the application of locally linear embedding (LLE) to reduce the dimensionality of dereddened and continuum subtracted near-infrared spectra using a combination of models and real spectra of massive protostars selected from the Red MSX Source survey data base. A brief comparison is also made with two other dimension reduction techniques; principal component analysis (PCA) and Isomap using the same set of spectra as well as a more advanced form of LLE, Hessian locally linear embedding. We find that whilst LLE certainly has its limitations, it significantly outperforms both PCA and Isomap in classification of spectra based on the presence/absence of emission lines and provides a valuable tool for classification and analysis of large spectral data sets.

Motor features in posterior cortical atrophy and their imaging correlates.

PubMed

Ryan, Natalie S; Shakespeare, Timothy J; Lehmann, Manja; Keihaninejad, Shiva; Nicholas, Jennifer M; Leung, Kelvin K; Fox, Nick C; Crutch, Sebastian J

2014-12-01

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia

PubMed Central

Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-01-01

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa. PMID:29100363

Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia.

PubMed

Jia, Gaozhen; Dong, Zhenyang; Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

2017-09-29

The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa.

Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas

2012-07-15

Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostatemore » cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.« less

Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche.

PubMed

Sánchez, Catherine A; Andahur, Eliana I; Valenzuela, Rodrigo; Castellón, Enrique A; Fullá, Juan A; Ramos, Christian G; Triviño, Juan C

2016-01-26

The different prostate cancer (PCa) cell populations (bulk and cancer stem cells, CSCs) release exosomes that contain miRNAs that could modify the local or premetastatic niche. The analysis of the differential expression of miRNAs in exosomes allows evaluating the differential biological effect of both populations on the niche, and the identification of potential biomarkers and therapeutic targets. Five PCa primary cell cultures were established to originate bulk and CSCs cultures. From them, exosomes were purified by precipitation for miRNAs extraction to perform a comparative profile of miRNAs by next generation sequencing in an Illumina platform. 1839 miRNAs were identified in the exosomes. Of these 990 were known miRNAs, from which only 19 were significantly differentially expressed: 6 were overexpressed in CSCs and 13 in bulk cells exosomes. miR-100-5p and miR-21-5p were the most abundant miRNAs. Bioinformatics analysis indicated that differentially expressed miRNAs are highly related with PCa carcinogenesis, fibroblast proliferation, differentiation and migration, and angiogenesis. Besides, miRNAs from bulk cells affects osteoblast differentiation. Later, their effect was evaluated in normal prostate fibroblasts (WPMY-1) where transfection with miR-100-5p, miR-21-5p and miR-139-5p increased the expression of metalloproteinases (MMPs) -2, -9 and -13 and RANKL and fibroblast migration. The higher effect was achieved with miR21 transfection. As conclusion, miRNAs have a differential pattern between PCa bulk and CSCs exosomes that act collaboratively in PCa progression and metastasis. The most abundant miRNAs in PCa exosomes are interesting potential biomarkers and therapeutic targets.

Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes.

PubMed

Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M; Aleixandre, Rosa N; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2016-01-01

New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic.

Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes

PubMed Central

Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M.; Aleixandre, Rosa N.; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

2016-01-01

New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic. PMID:27279911

Innovations in diagnostic imaging of localized prostate cancer.

PubMed

Pummer, Karl; Rieken, Malte; Augustin, Herbert; Gutschi, Thomas; Shariat, Shahrokh F

2014-08-01

In recent years, various imaging modalities have been developed to improve diagnosis, staging, and localization of early-stage prostate cancer (PCa). A MEDLINE literature search of the time frame between 01/2007 and 06/2013 was performed on imaging of localized PCa. Conventional transrectal ultrasound (TRUS) is mainly used to guide prostate biopsy. Contrast-enhanced ultrasound is based on the assumption that PCa tissue is hypervascularized and might be better identified after intravenous injection of a microbubble contrast agent. However, results on its additional value for cancer detection are controversial. Computer-based analysis of the transrectal ultrasound signal (C-TRUS) appears to detect cancer in a high rate of patients with previous biopsies. Real-time elastography seems to have higher sensitivity, specificity, and positive predictive value than conventional TRUS. However, the method still awaits prospective validation. The same is true for prostate histoscanning, an ultrasound-based method for tissue characterization. Currently, multiparametric MRI provides improved tissue visualization of the prostate, which may be helpful in the diagnosis and targeting of prostate lesions. However, most published series are small and suffer from variations in indication, methodology, quality, interpretation, and reporting. Among ultrasound-based techniques, real-time elastography and C-TRUS seem the most promising techniques. Multiparametric MRI appears to have advantages over conventional T2-weighted MRI in the detection of PCa. Despite these promising results, currently, no recommendation for the routine use of these novel imaging techniques can be made. Prospective studies defining the value of various imaging modalities are urgently needed.

The monoamine oxidase A gene promoter repeat and prostate cancer risk.

PubMed

White, Thomas A; Kwon, Erika M; Fu, Rong; Lucas, Jared M; Ostrander, Elaine A; Stanford, Janet L; Nelson, Peter S

2012-11-01

Amine catabolism by monoamine oxidase A (MAOA) contributes to oxidative stress, which plays a role in prostate cancer (PCa) development and progression. An upstream variable-number tandem repeat (uVNTR) in the MAOA promoter influences gene expression and activity, and may thereby affect PCa susceptibility. Caucasian (n = 2,572) men from two population-based case-control studies of PCa were genotyped for the MAOA-VNTR. Logistic regression was used to assess PCa risk in relation to genotype. Common alleles of the MAOA-VNTR were not associated with the relative risk of PCa, nor did the relationship differ by clinical features of the disease. The rare 5-copy variant (frequency: 0.5% in cases; 1.8% in controls), however, was associated with a reduced PCa risk (odds ratio, OR = 0.30, 95% CI 0.13-0.71). A rare polymorphism of the MAOA promoter previously shown to confer low expression was associated with a reduced risk of developing PCa. This novel finding awaits confirmation in other study populations. Copyright © 2012 Wiley Periodicals, Inc.

Time-dependent analysis of dosage delivery information for patient-controlled analgesia services.

PubMed

Kuo, I-Ting; Chang, Kuang-Yi; Juan, De-Fong; Hsu, Steen J; Chan, Chia-Tai; Tsou, Mei-Yung

2018-01-01

Pain relief always plays the essential part of perioperative care and an important role of medical quality improvement. Patient-controlled analgesia (PCA) is a method that allows a patient to self-administer small boluses of analgesic to relieve the subjective pain. PCA logs from the infusion pump consisted of a lot of text messages which record all events during the therapies. The dosage information can be extracted from PCA logs to provide easily understanding features. The analysis of dosage information with time has great help to figure out the variance of a patient's pain relief condition. To explore the trend of pain relief requirement, we developed a PCA dosage information generator (PCA DIG) to extract meaningful messages from PCA logs during the first 48 hours of therapies. PCA dosage information including consumption, delivery, infusion rate, and the ratio between demand and delivery is presented with corresponding values in 4 successive time frames. Time-dependent statistical analysis demonstrated the trends of analgesia requirements decreased gradually along with time. These findings are compatible with clinical observations and further provide valuable information about the strategy to customize postoperative pain management.

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial.

PubMed

Chin, Joseph L; Billia, Michele; Relle, James; Roethke, Matthias C; Popeneciu, Ionel V; Kuru, Timur H; Hatiboglu, Gencay; Mueller-Wolf, Maya B; Motsch, Johann; Romagnoli, Cesare; Kassam, Zahra; Harle, Christopher C; Hafron, Jason; Nandalur, Kiran R; Chronik, Blaine A; Burtnyk, Mathieu; Schlemmer, Heinz-Peter; Pahernik, Sascha

2016-09-01

Magnetic resonance imaging-guided transurethral ultrasound ablation (MRI-TULSA) is a novel minimally invasive technology for ablating prostate tissue, potentially offering good disease control of localized cancer and low morbidity. To determine the clinical safety and feasibility of MRI-TULSA for whole-gland prostate ablation in a primary treatment setting of localized prostate cancer (PCa). A single-arm prospective phase 1 study was performed at three tertiary referral centers in Canada, Germany, and the United States. Thirty patients (median age: 69 yr; interquartile range [IQR]: 67-71 yr) with biopsy-proven low-risk (80%) and intermediate-risk (20%) PCa were treated and followed for 12 mo. MRI-TULSA treatment was delivered with the therapeutic intent of conservative whole-gland ablation including 3-mm safety margins and 10% residual viable prostate expected around the capsule. Primary end points were safety (adverse events) and feasibility (technical accuracy and precision of conformal thermal ablation). Exploratory outcomes included quality of life, prostate-specific antigen (PSA), and biopsy at 12 mo. Median treatment time was 36min (IQR: 26-44) and prostate volume was 44ml (IQR: 38-48). Spatial control of thermal ablation was ±1.3mm on MRI thermometry. Common Terminology Criteria for Adverse Events included hematuria (43% grade [G] 1; 6.7% G2), urinary tract infections (33% G2), acute urinary retention (10% G1; 17% G2), and epididymitis (3.3% G3). There were no rectal injuries. Median pretreatment International Prostate Symptom Score 8 (IQR: 5-13) returned to 6 (IQR: 4-10) at 3 mo (mean change: -2; 95% confidence interval [CI], -4 to 1). Median pretreatment International Index of Erectile Function 13 (IQR: 6-28) recovered to 13 (IQR: 5-25) at 12 mo (mean change: -1; 95% CI, -5 to 3). Median PSA decreased 87% at 1 mo and was stable at 0.8 ng/ml (IQR: 0.6-1.1) to 12 mo. Positive biopsies showed 61% reduction in total cancer length, clinically significant disease in 9 of 29 patients (31%; 95% CI, 15-51), and any disease in 16 of 29 patients (55%; 95% CI, 36-74). MRI-TULSA was feasible, safe, and technically precise for whole-gland prostate ablation in patients with localized PCa. Phase 1 data are sufficiently compelling to study MRI-TULSA further in a larger prospective trial with reduced safety margins. We used magnetic resonance imaging-guided transurethral ultrasound to heat and ablate the prostate in men with prostate cancer. We showed that the treatment can be targeted within a narrow range (1mm) and has a well-tolerated side effect profile. A larger study is under way. NCT01686958, DRKS00005311. Copyright © 2016. Published by Elsevier B.V.

Comparison of prostate cancer gene 3 score, prostate health index and percentage free prostate-specific antigen for differentiating histological inflammation from prostate cancer and other non-neoplastic alterations of the prostate at initial biopsy.

PubMed

De Luca, Stefano; Passera, Roberto; Bollito, Enrico; Manfredi, Matteo; Scarpa, Roberto Mario; Sottile, Antonino; Randone, Donato Franco; Porpiglia, Francesco

2014-12-01

To determine if prostate cancer gene 3 (PCA3) score, Prostate Health Index (PHI), and percent free prostate-specific antigen (%fPSA) may be used to differentiate prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH) and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA and negative digital rectal examination (DRE). in the present prospective study, 274 patients, undergoing PCA3 score, PHI and %fPSA assessments before initial biopsy, were enrolled. Three multivariate logistic regression models were used to test PCA3 score, PHI and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the 'gray zone' of PSA (4-10 ng/ml) cohort (188 individuals). The determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (Odds Ratio [OR]=0.97, 0.96 and 0.94, respectively). Unit increase of PHI was the only risk factor for prostatitis vs. BPH (OR=1.06), and unit increase of PCA3 score for HG-PIN vs. prostatitis (OR=0.98). In the 'gray zone' PSA cohort, the determinants for prostatitis vs. PCa were PCA3 score, PHI and %fPSA (OR=0.96, 0.94 and 0.92, respectively), PCA3 score and PHI for prostatitis vs. BPH (OR=0.96 and 1.08, respectively), and PCA3 score for prostatitis vs. HG-PIN (OR=0.97). The clinical benefit of using PCA3 score and PHI to estimate prostatitis vs. PCa was comparable; even %fPSA had good diagnostic performance, being a faster and cheaper marker. PHI was the only determinant for prostatitis vs. BPH, while PCA3 score for prostatitis vs. HG-PIN. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Expression of the TPα and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer: clinical significance and diagnostic potential.

PubMed

Mulvaney, Eamon P; Shilling, Christine; Eivers, Sarah B; Perry, Antoinette S; Bjartell, Anders; Kay, Elaine W; Watson, R William; Kinsella, B Therese

2016-11-08

The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.

Multiscale 3D Shape Analysis using Spherical Wavelets

PubMed Central

Nain, Delphine; Haker, Steven; Bobick, Aaron; Tannenbaum, Allen

2013-01-01

Shape priors attempt to represent biological variations within a population. When variations are global, Principal Component Analysis (PCA) can be used to learn major modes of variation, even from a limited training set. However, when significant local variations exist, PCA typically cannot represent such variations from a small training set. To address this issue, we present a novel algorithm that learns shape variations from data at multiple scales and locations using spherical wavelets and spectral graph partitioning. Our results show that when the training set is small, our algorithm significantly improves the approximation of shapes in a testing set over PCA, which tends to oversmooth data. PMID:16685992

Multiscale 3D shape analysis using spherical wavelets.

PubMed

Nain, Delphine; Haker, Steven; Bobick, Aaron; Tannenbaum, Allen R

2005-01-01

Shape priors attempt to represent biological variations within a population. When variations are global, Principal Component Analysis (PCA) can be used to learn major modes of variation, even from a limited training set. However, when significant local variations exist, PCA typically cannot represent such variations from a small training set. To address this issue, we present a novel algorithm that learns shape variations from data at multiple scales and locations using spherical wavelets and spectral graph partitioning. Our results show that when the training set is small, our algorithm significantly improves the approximation of shapes in a testing set over PCA, which tends to oversmooth data.

A prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol.

PubMed

Hofman, Michael S; Murphy, Declan G; Williams, Scott G; Nzenza, Tatenda; Herschtal, Alan; Lourenco, Richard De Abreu; Bailey, Dale L; Budd, Ray; Hicks, Rodney J; Francis, Roslyn J; Lawrentschuk, Nathan

2018-05-03

Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision-making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is a new whole-body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA-PET/CT has improved diagnostic performance compared with conventional imaging; (ii) PSMA-PET/CT should be used as a first-line diagnostic test for staging; (iii) the improved diagnostic performance of PSMA-PET/CT will result in significant management impact; and (iv) there are economic benefits if PSMA-PET/CT is incorporated into the management algorithm. The proPSMA trial is a prospective, multicentre study in which patients with untreated high-risk PCa will be randomized to gallium-68-PSMA-11 PET/CT or conventional imaging, consisting of CT of the abdomen/pelvis and bone scintigraphy with single-photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high-risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate-specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line-imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow-up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer-term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. This trial will provide data to establish whether PSMA-PET/CT should replace conventional imaging in the primary staging of select high-risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

The Association Between Calcium Channel Blocker Use and Prostate Cancer Outcome

PubMed Central

Poch, Michael A.; Mehedint, Diana; Green, Dawn J.; Payne-Ondracek, Rochelle; Fontham, Elizabeth T.H.; Bensen, Jeannette T.; Attwood, Kristopher; Wilding, Gregory E.; Guru, Khurshid A.; Underwood, Willie; Mohler, James L.; Heemers, Hannelore V.

2018-01-01

BACKGROUND Epidemiological studies indicate that calcium channel blocker (CCB) use is inversely related to prostate cancer (PCa) incidence. The association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) and outcome after RP was examined. METHODS Medication use, PCa aggressiveness and post-RP outcome were retrieved from a prospectively populated database that contains clinical and outcome for RP patients at Roswell Park Cancer Institute (RPCI) from 1993 to 2010. The database was queried for anti-hypertensive medication use at diagnosis for patients with ≥1 year follow-up. Recurrence was defined using NCCN guidelines. Chi-Square tests assessed the relationship between CCB use and PCa aggressiveness. Cox regression models compared the distribution of progression-free survival (PFS) and overall survival (OS) with adjustment for covariates. Results for association between CCB usage and PCa aggressiveness were validated using data from the population-based North Carolina-Louisiana Prostate Cancer Project (PCaP). RESULTS 48%, 37%, and 15% of RPCI’s RP patients (n = 875) had low, intermediate, and high aggressive PCa, respectively. 104 (11%) had a history of CCB use. Patients taking CCBs were more likely to be older, have a higher BMI and use additional anti-hypertensive medications. Diagnostic PSA levels, PCa aggressiveness, and margin status were similar for CCB users and non-users. PFS and OS did not differ between the two groups. Tumor aggressiveness was associated with PFS. CCB use in the PCaP study population was not associated with PCa aggressiveness. CONCLUSIONS CCB use is not associated with PCa aggressiveness at diagnosis, PFS or OS. PMID:23280547

Prostate cancer characterization by optical contrast enhanced photoacoustics

NASA Astrophysics Data System (ADS)

Xu, Guan; Qin, Ming; Mukundan, Ananya; Siddiqui, Javed; Takada, Marilia; Vilar-Saavedra, Paulo; Tomlins, Scott A.; Kopelman, Raoul; Wang, Xueding

2016-03-01

During the past decades, prostate cancer (PCa), with an annual incident rate much higher than any other cancer, is the most commonly diagnosed cancer in American men. PCa has a relatively low progression rate yet the survival percentage decreases dramatically once the cancer has metastasized. Identifying aggressive from indolent PCa to prevent metastasis and death is critical to improving outcomes for patients with PCa. Standard procedure for assessing the aggressiveness of PCa involves the removal of tumor tissues by transrectal (TR) ultrasound (US) guided needle biopsy. The microscopic architecture of the biopsied tissue is visualized by histological or immunohistochemical staining procedures. The heterogeneity of the microscopic architecture is characterized by a Gleason score, a quantitative description of the aggressiveness of PCa. Due to the inability to identify the cancer cells, most noninvasive imaging modalities can only provide diagnosis of PCa at limited accuracy. This study investigates the feasibility of identifying PCa tumors and characterizing the aggressiveness of PCa by photoacoustic imaging assisted by cancer targeting polyacrylamide (PAA) nanoparticles (NPs). PAA is a biocompatible material used in clinics for the past 20 years. PAA NPs can protect capsulated optical contrast agents from interference by enzymes and enable prolonged systematic circulation in the living biological environment. The cancer targeting mechanism is achieved by conjugating the NPs to F3 peptides, which trace nucleolin overexpressed on the surface of cancer cells. Preliminary studies have shown that the NPs are capable of staining the PCa cells in vivo.

Serum markers for prostate cancer: a rational approach to the literature.

PubMed

Steuber, Thomas; O'Brien, Matthew Frank; Lilja, Hans

2008-07-01

Due to its universal applicability for early detection and prediction of cancer stage and disease recurrence, widespread implementation of serum-based prostate-specific antigen (PSA) measurements has a significant influence on current treatment strategies for men with prostate cancer (PCa). However, over-detection and the resultant over-treatment of indolent cancers have been strongly implicated to occur. Using current recommended guidelines, the PSA test suffers from both limited sensitivity and specificity to enable efficacious population-based cancer detection. Therefore, novel biomarkers are much needed to complement PSA by enhancing its diagnostic and prognostic performance. The present literature on serum markers for PCa was reviewed. PSA derivatives, molecular PSA isoforms, and novel molecular targets in blood were summarized and weighted against their potential to improve decision-making of men with PCa. Current evidence suggests that no single analyte is likely to achieve the desired level of diagnostic and prognostic accuracy for PCa. However, the combination of biomarkers with clinical and demographic data, for example, using established standard nomograms, has produced progress toward the goal of both optimal screening and risk assessment. Furthermore, potential candidate molecular markers for PCa can be derived from high-throughput technologies. Current studies demonstrate that understanding dynamic PSA changes over time may offer diagnostic and prognostic information. Bridging the gap between basic science and clinical practice represents the main goal in the near future to enable physicians to tailor risk-adjusted screening and treatment strategies for current patients with PCa.

Transrectal real-time tissue elastography targeted biopsy coupled with peak strain index improves the detection of clinically important prostate cancer.

PubMed

Ma, Qi; Yang, Dong-Rong; Xue, Bo-Xin; Wang, Cheng; Chen, Han-Bin; Dong, Yun; Wang, Cai-Shan; Shan, Yu-Xi

2017-07-01

The focus of the present study was to evaluate transrectal real-time tissue elastography (RTE)-targeted two-core biopsy coupled with peak strain index for the detection of prostate cancer (PCa) and to compare this method with 10-core systematic biopsy. A total of 141 patients were enrolled for evaluation. The diagnostic value of peak strain index was assessed using a receiver operating characteristic curve. The cancer detection rates of the two approaches and corresponding positive cores and Gleason score were compared. The cancer detection rate per core in the RTE-targeted biopsy (44%) was higher compared with that in systematic biopsy (30%). The peak strain index value of PCa was higher compared with that of the benign lesion. PCa was detected with the highest sensitivity (87.5%) and specificity (85.5%) using the threshold value of a peak strain index of ≥5.97 with an area under the curve value of 0.95. When the Gleason score was ≥7, RTE-targeted biopsy coupled with peak strain index detected 95.6% of PCa cases, but 84.4% were detected using systematic biopsy. Peak strain index as a quantitative parameter may improve the differentiation of PCa from benign lesions in the prostate peripheral zone. Transrectal RTE-targeted biopsy coupled with peak strain index may enhance the detection of clinically significant PCa, particularly when combined with systematic biopsy.

Decreased expression of serine protease inhibitor family G1 (SERPING1) in prostate cancer can help distinguish high-risk prostate cancer and predicts malignant progression.

PubMed

Peng, Shengmeng; Du, Tao; Wu, Wanhua; Chen, Xianju; Lai, Yiming; Zhu, Dingjun; Wang, Qiong; Ma, Xiaoming; Lin, Chunhao; Li, Zean; Guo, Zhenghui; Huang, Hai

2018-06-11

The aim of this study was to investigate the associations of serine proteinase inhibitor family G1 (SERPING1) down-regulation with poor prognosis in patients with prostate cancer (PCa). Furthermore, we aim to find more novel and effective PCa molecular markers to provide an early screening of PCa, distinguish patients with aggressive PCa, predict the prognosis, or reduce the economic burden of PCa. SERPING1 protein expression in both human PCa and normal prostate tissues was detected by immunohistochemical staining, which intensity was analyzed in association with clinical pathological parameters such Gleason score, pathological grade, clinical stage, tumor stage, lymph node metastasis, and distant metastasis. Moreover, we used The Cancer Genome Atlas (TCGA) Database, Taylor Database, and Oncomine dataset to validate our immunohistochemical results and investigated the value of SERPING1 in PCa at mRNA level. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the relationship between SERPING1 and prognosis of patients with PCa. The outcome showed that SERPING1 was expressed mainly in cytoplasm of grand cells of prostate tissue and was significantly expressed less in PCa (P<0.001). Furthermore, in the tissue microarray of our samples, decreasing expression of SERPING1 was correlated with the higher Gleason score (P = 0.004), the higher pathological grade (P = 0.01) and the advanced tumor stage (P = 0.005) at protein level. In TCGA dataset and Taylor Dataset, low-expressed SERPING1 was correlated with the younger patient (P = 0.02 in TCGA, P = 0.044 in Taylor) and the higher Gleason score (P = 0.019 in TCGA, P<0.001 in Taylor) at mRNA level. Kaplan-Meier analysis revealed that the lower mRNA of SERPING1 predicted lower overall survivals (P = 0.027 in TCGA), lower disease-free survival (P = 0.029) and lower biochemical recurrence-free survival (P = 0.011 in Taylor). Data from Oncomine database shown that SERPING1 low expression implying higher malignancy of prostate lesions. Using multivariate analysis, we also found that SERPING1 expression was independent prognostic marker of poor disease-free survival and biochemical recurrence-free survival. SERPING1 may play an important role in PCa and can be serve as a novel marker in diagnosis and prognostic prediction in PCa. In addition, levels of SERPING1 can help identify low-risk prostate to provide reference for patients with PCa to accept active surveillance and reduce overtreatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Meta-analysis of CDKN2A methylation to find its role in prostate cancer development and progression, and also to find the effect of CDKN2A expression on disease-free survival (PRISMA).

PubMed

Cao, Zipei; Wei, Lijuan; Zhu, Weizhi; Yao, Xuping

2018-03-01

Reduction of cyclin-dependent kinase inhibitor 2A (CDKN2A) (p16 and p14) expression through DNA methylation has been reported in prostate cancer (PCa). This meta-analysis was conducted to assess the difference of p16 and p14 methylation between PCa and different histological types of nonmalignant controls and the correlation of p16 or p14 methylation with clinicopathological features of PCa. According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, articles were searched in PubMed, Embase, EBSCO, Wanfang, and CNKI databases. The strength of correlation was calculated by the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Trial sequential analysis (TSA) was used to estimate the required population information for significant results. A total of 20 studies published from 1997 to 2017 were identified in this meta-analysis, including 1140 PCa patients and 530 cases without cancer. Only p16 methylation in PCa was significantly higher than in benign prostatic lesions (OR = 4.72, P = .011), but had a similar level in PCa and adjacent tissues or high-grade prostatic intraepithelial neoplasias (HGPIN). TSA revealed that this analysis on p16 methylation is a false positive result in cancer versus benign prostatic lesions (the estimated required information size of 5116 participants). p16 methylation was not correlated with PCa in the urine and blood. Besides, p16 methylation was not linked to clinical stage, prostate-specific antigen (PSA) level, and Gleason score (GS) of patients with PCa. p14 methylation was not correlated with PCa in tissue and urine samples. No correlation was observed between p14 methylation and clinical stage or GS. CDKN2A mutation and copy number alteration were not associated with prognosis of PCa in overall survival and disease-free survival. CDKN2A expression was not correlated with the prognosis of PCa in overall survival (492 cases) (P > .1), while CDKN2A expression was significantly associated with a poor disease-free survival (P < .01). CDKN2A methylation may not be significantly associated with the development, progression of PCa. Although CDKN2A expression had an unfavorable prognosis in disease-free survival. More studies are needed to confirm our results.

The use of the finasteride-adjusted Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator in a Mexican referral population: a validation study.

PubMed

Liang, Yuanyuan; Ketchum, Norma S; Louden, Christopher; Jimenez-Rios, Miguel A; Thompson, Ian M; Camarena-Reynoso, Hector R

2012-01-01

To perform the first validation study of the finasteride-adjusted Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (finPCPTRC) in a contemporary referral population in Mexico. 837 patients referred to the Instituto Nacional de Cancerología, Mexico City, Mexico, between 2005 and 2009 were used to validate the finPCPTRC by examining various measures of discrimination and calibration. Net benefit curve analysis was used to gain insight into the use of the finPCPTRC for clinical decisions. Prostate cancer (PCa) incidence (72.8%) was high in this Mexican referral cohort and 45.7% of men who were diagnosed with PCa had high-grade lesions (HGPCa, Gleason score >6). 1.3% of the patients were taking finasteride. The finPCPTRC was a superior diagnostic tool compared to prostate-specific antigen alone when discriminating patients with PCa from those without PCa (AUC = 0.784 vs. AUC = 0.687, p < 0.001) and when discriminating patients with HGPCa from those without HGPCa (AUC = 0.768 vs. AUC = 0.739, p < 0.001). The finPCPTRC underestimated the risk of PCa but overestimated the risk of HGPCa (both p < 0.001). Compared with other strategies to opt for biopsy, the net benefit would be larger with utilization of the finPCPTRC for patients accepting higher risks of HGPCa. Rates of biopsy-detectable PCa and HGPCa were high and 1.3% of this referral cohort in Mexico was taking finasteride. The risks of PCa or HGPCa calculated by the finPCPTRC were not well calibrated for this referral Mexican population and new clinical diagnostic tools are needed. Copyright © 2012 S. Karger AG, Basel.

Validation of PI-RADS version 2 for the detection of prostate cancer.

PubMed

Hofbauer, Sebastian L; Kittner, Beatrice; Maxeiner, Andreas; Heckmann, Robin; Reimann, Maximillian; Wiemer, Laura; Asbach, Patrick; Haas, Matthias; Penzkofer, Tobias; Stephan, Carsten; Friedersdorff, Frank; Fuller, Florian; Miller, Kurt; Cash, Hannes

2018-05-04

The second version of the Prostate Imaging Reporting and Data System (PI-RADSv2) was introduced in 2015 to standardize the interpretation and reporting of multiparametric prostate magnetic resonance imaging (mpMRI). Recently, low cancer detection rates (CDR) for PI-RADSv2 category 4 lesions were reported. Therefore the aim of the study was to evaluate the CDR of PI-RADSv2 in a large prospective cohort. The study included 704 consecutive men with primary or prior negative biopsies who underwent MRI/ultrasound fusion-guided targeted biopsy (TB) and 10-core systematic prostate biopsy (SB) between September 2015 and May 2017. All lesions were rated according to PI-RADSv2 and lesions with PI-RADSv2 category ≥ 3 were biopsied. An ISUP (International Society of Urological Pathology) score of 2 or greater (i.e. Gleason 3+4 or greater) was defined as clinically significant prostate cancer (csPCa). The overall CDR for PI-RADSv2 categories 3, 4, and 5 was 39%, 72%, and 91% for all PCa, and 23%, 49%, and 77% for all csPCa, respectively. Fifty-nine (16%) clinically significant tumors would have been missed if only TB was performed. The PI-RADSv2 score was significantly associated with the presence of PCa (p<0.001), the presence of csPCa (p<0.001), and the ISUP grading (p<0.001). PI-RADSv2 is significantly associated with the presence of csPCa. The CDR for PI-RADSv2 category 4 lesions was considerably higher than previously reported. When performing TB, the combination with a SB still warrants the highest detection of csPCa. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Multiparametric prostate MRI: technical conduct, standardized report and clinical use.

PubMed

Manfredi, Matteo; Mele, Fabrizio; Garrou, Diletta; Walz, Jochen; Fütterer, Jurgen J; Russo, Filippo; Vassallo, Lorenzo; Villers, Arnauld; Emberton, Mark; Valerio, Massimo

2018-02-01

Multiparametric prostate MRI (mp-MRI) is an emerging imaging modality for diagnosis, characterization, staging, and treatment planning of prostate cancer (PCa). The technique, results reporting, and its role in clinical practice have been the subject of significant development over the last decade. Although mp-MRI is not yet routinely used in the diagnostic pathway, almost all urological guidelines have emphasized the potential role of mp-MRI in several aspects of PCa management. Moreover, new MRI sequences and scanning techniques are currently under evaluation to improve the diagnostic accuracy of mp-MRI. This review presents an overview of mp-MRI, summarizing the technical applications, the standardized reporting systems used, and their current roles in various stages of PCa management. Finally, this critical review also reports the main limitations and future perspectives of the technique.

Semaphorin 3 C drives epithelial-to-mesenchymal transition, invasiveness, and stem-like characteristics in prostate cells.

PubMed

Tam, Kevin J; Hui, Daniel H F; Lee, Wilson W; Dong, Mingshu; Tombe, Tabitha; Jiao, Ivy Z F; Khosravi, Shahram; Takeuchi, Ario; Peacock, James W; Ivanova, Larissa; Moskalev, Igor; Gleave, Martin E; Buttyan, Ralph; Cox, Michael E; Ong, Christopher J

2017-09-13

Prostate cancer (PCa) is among the most commonly-occurring cancers worldwide and a leader in cancer-related deaths. Local non-invasive PCa is highly treatable but limited treatment options exist for those with locally-advanced and metastatic forms of the disease underscoring the need to identify mechanisms mediating PCa progression. The semaphorins are a large grouping of membrane-associated or secreted signalling proteins whose normal roles reside in embryogenesis and neuronal development. In this context, semaphorins help establish chemotactic gradients and direct cell movement. Various semaphorin family members have been found to be up- and down-regulated in a number of cancers. One family member, Semaphorin 3 C (SEMA3C), has been implicated in prostate, breast, ovarian, gastric, lung, and pancreatic cancer as well as glioblastoma. Given SEMA3C's roles in development and its augmented expression in PCa, we hypothesized that SEMA3C promotes epithelial-to-mesenchymal transition (EMT) and stem-like phenotypes in prostate cells. In the present study we show that ectopic expression of SEMA3C in RWPE-1 promotes the upregulation of EMT and stem markers, heightened sphere-formation, and cell plasticity. In addition, we show that SEMA3C promotes migration and invasion in vitro and cell dissemination in vivo.

Minireview: The Molecular and Genomic Basis for Prostate Cancer Health Disparities

PubMed Central

Bollig-Fischer, Aliccia

2013-01-01

Despite more aggressive screening across all demographics and gradual declines in mortality related to prostate cancer (PCa) in the United States, race disparities persist. For African American men (AAM), PCa is more often an aggressive disease showing increased metastases and greater PCa-related mortality compared with European American men. The earliest research points to how distinctions are likely the result of a combination of factors, including ancestry genetics and lifestyle variables. More recent research considers that cancer, although influenced by external forces, is ultimately a disease primarily driven by aberrations observed in the molecular genetics of the tumor. Research studying PCa predominantly from European American men shows that indolent and advanced or metastatic prostate tumors have distinguishing molecular genomic make-ups. Early yet increasing evidence suggests that clinically distinct PCa from AAM also display molecular distinctions. It is reasonable to predict that further study will reveal molecular subtypes and various frequencies for PCa subtypes among diverse patient groups, thereby providing insight as to the genomic lesions and gene signatures that are functionally implicated in carcinogenesis or aggressive PCa in AAM. That knowledge will prove useful in developing strategies to predict who will develop advanced PCa among AAM and will provide the rationale to develop effective individualized treatment strategies to overcome disparities. PMID:23608645

Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy.

PubMed

Peters, Max; van der Voort van Zyp, Jochem R N; Moerland, Marinus A; Hoekstra, Carel J; van de Pol, Sandrine; Westendorp, Hendrik; Maenhout, Metha; Kattevilder, Rob; Verkooijen, Helena M; van Rossum, Peter S N; Ahmed, Hashim U; Shah, Taimur T; Emberton, Mark; van Vulpen, Marco

2016-04-01

Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to develop a multivariable, internally validated prognostic model for survival after whole-gland salvage I-125-brachytherapy. Whole-gland salvage I-125-brachytherapy patients treated in the Netherlands from 1993-2010 were included. Eligible patients had a transrectal ultrasound-guided biopsy-confirmed localised recurrence after biochemical failure (clinical judgement, ASTRO or Phoenix-definition). Recurrences were assessed clinically and with CT and/or MRI. Metastases were excluded using CT/MRI and technetium-99m scintigraphy. Multivariable Cox-regression was used to assess the predictive value of clinical characteristics in relation to PCa-specific and overall mortality. PCa-specific mortality was defined as patients dying with distant metastases present. Missing data were handled using multiple imputation (20 imputed sets). Internal validation was performed and the C-statistic calculated. Calibration plots were created to visually assess the goodness-of-fit of the final model. Optimism-corrected survival proportions were calculated. All analyses were performed according to the TRIPOD statement. Median total follow-up was 78months (range 5-139). A total of 62 patients were treated, of which 28 (45%) died from PCa after mean (±SD) 82 (±36) months. Overall, 36 patients (58%) patients died after mean 84 (±40) months. PSA doubling time (PSADT) remained a predictive factor for both types of mortality (PCa-specific and overall): corrected hazard ratio's (HR's) 0.92 (95% CI: 0.86-0.98, p=0.02) and 0.94 (95% CI: 0.90-0.99, p=0.01), respectively (C-statistics 0.71 and 0.69, respectively). Calibration was accurate up to 96month follow-up. Over 80% of patients can survive 8years if PSADT>24months (PCaSS) and >33months (OS). Only approximately 50% survival is achieved with a PSADT of 12months. A PSADT of respectively >24months and >33months can result in >80% probability of PCa- specific and overall survival 8years after whole-gland salvage I-125-brachytherapy. Survival should be weighed against toxicity from a salvage procedure. Larger series and external validation are necessary. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

How does health literacy affect quality of life among men with newly diagnosed clinically localized prostate cancer? Findings from the North Carolina-Louisiana Prostate Cancer Project (PCaP).

PubMed

Song, Lixin; Mishel, Merle; Bensen, Jeannette T; Chen, Ronald C; Knafl, George J; Blackard, Bonny; Farnan, Laura; Fontham, Elizabeth; Su, L Joseph; Brennan, Christine S; Mohler, James L; Godley, Paul A

2012-08-01

Health literacy deficits affect half of the US overall patient population, especially the elderly, and are linked to poor health outcomes among noncancer patients. Yet little is known about how health literacy affects cancer populations. The authors examined the relation between health-related quality of life (HRQOL) and health literacy among men with prostate cancer. Data analysis included 1581 men with newly diagnosed clinically localized prostate cancer from a population-based study, the North Carolina-Louisiana Prostate Cancer Project (PCaP). Participants completed assessment of health literacy using Rapid Estimate of Adult Literacy in Medicine (REALM) and HRQOL using the Short Form-12 General Health Survey (SF12). Bivariate and multivariate regression was used to determine the potential association between REALM and HRQOL, while controlling for sociodemographic and illness-related variables. Higher health literacy level was significantly associated with better mental well-being (SF12-Mental Component Summary [MCS]; P < .001) and physical well-being (SF12-Physical Component Summary [PCS]; P < .001) in bivariate analyses. After controlling for sociodemographic (age, marital status, race, income, and education) and illness-related factors (types of cancer treatment, tumor aggressiveness, and comorbidities), health literacy remained significantly associated with SF12-MCS scores (P < .05) but not with SF12-PCS scores. Among patients with newly diagnosed localized prostate cancer, those with low health literacy levels were more vulnerable to mental distress than those with higher health literacy levels, but physical well-being was no different. These findings suggest that health literacy may be important in patients managing prostate cancer and the effects of treatment, and provide the hypothesis that supportive interventions targeting patients with lower health literacy may improve their HRQOL. Copyright © 2011 American Cancer Society.

PTEN genomic deletion predicts prostate cancer recurrence and is associated with low AR expression and transcriptional activity

PubMed Central

2012-01-01

Background Prostate cancer (PCa), a leading cause of cancer death in North American men, displays a broad range of clinical outcome from relatively indolent to lethal metastatic disease. Several genomic alterations have been identified in PCa which may serve as predictors of progression. PTEN, (10q23.3), is a negative regulator of the phosphatidylinositol 3-kinase (PIK3)/AKT survival pathway and a tumor suppressor frequently deleted in PCa. The androgen receptor (AR) signalling pathway is known to play an important role in PCa and its blockade constitutes a commonly used treatment modality. In this study, we assessed the deletion status of PTEN along with AR expression levels in 43 primary PCa specimens with clinical follow-up. Methods Fluorescence In Situ Hybridization (FISH) was done on formalin fixed paraffin embedded (FFPE) PCa samples to examine the deletion status of PTEN. AR expression levels were determined using immunohistochemistry (IHC). Results Using FISH, we found 18 cases of PTEN deletion. Kaplan-Meier analysis showed an association with disease recurrence (P=0.03). Concurrently, IHC staining for AR found significantly lower levels of AR expression within those tumors deleted for PTEN (P<0.05). To validate these observations we interrogated a copy number alteration and gene expression profiling dataset of 64 PCa samples, 17 of which were PTEN deleted. We confirmed the predictive value of PTEN deletion in disease recurrence (P=0.03). PTEN deletion was also linked to diminished expression of PTEN (P<0.01) and AR (P=0.02). Furthermore, gene set enrichment analysis revealed a diminished expression of genes downstream of AR signalling in PTEN deleted tumors. Conclusions Altogether, our data suggest that PTEN deleted tumors expressing low levels of AR may represent a worse prognostic subset of PCa establishing a challenge for therapeutic management. PMID:23171135

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) Significantly Improve Prostate Cancer Detection at Initial Biopsy in a Total PSA Range of 2–10 ng/ml

PubMed Central

Perdonà, Sisto; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; D’Esposito, Vittoria; Cosimato, Vincenzo; Buonerba, Carlo; Di Lorenzo, Giuseppe; Musi, Gennaro; De Cobelli, Ottavio; Chun, Felix K.; Terracciano, Daniela

2013-01-01

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2–10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2–10 ng/ml at initial biopsy, outperforming currently used %fPSA. PMID:23861782

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) significantly improve prostate cancer detection at initial biopsy in a total PSA range of 2-10 ng/ml.

PubMed

Ferro, Matteo; Bruzzese, Dario; Perdonà, Sisto; Marino, Ada; Mazzarella, Claudia; Perruolo, Giuseppe; D'Esposito, Vittoria; Cosimato, Vincenzo; Buonerba, Carlo; Di Lorenzo, Giuseppe; Musi, Gennaro; De Cobelli, Ottavio; Chun, Felix K; Terracciano, Daniela

2013-01-01

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming currently used %fPSA.

Segregating the Effects of Seed Traits and Common Ancestry of Hardwood Trees on Eastern Gray Squirrel Foraging Decisions.

PubMed

Sundaram, Mekala; Willoughby, Janna R; Lichti, Nathanael I; Steele, Michael A; Swihart, Robert K

2015-01-01

The evolution of specific seed traits in scatter-hoarded tree species often has been attributed to granivore foraging behavior. However, the degree to which foraging investments and seed traits correlate with phylogenetic relationships among trees remains unexplored. We presented seeds of 23 different hardwood tree species (families Betulaceae, Fagaceae, Juglandaceae) to eastern gray squirrels (Sciurus carolinensis), and measured the time and distance travelled by squirrels that consumed or cached each seed. We estimated 11 physical and chemical seed traits for each species, and the phylogenetic relationships between the 23 hardwood trees. Variance partitioning revealed that considerable variation in foraging investment was attributable to seed traits alone (27-73%), and combined effects of seed traits and phylogeny of hardwood trees (5-55%). A phylogenetic PCA (pPCA) on seed traits and tree phylogeny resulted in 2 "global" axes of traits that were phylogenetically autocorrelated at the family and genus level and a third "local" axis in which traits were not phylogenetically autocorrelated. Collectively, these axes explained 30-76% of the variation in squirrel foraging investments. The first global pPCA axis, which produced large scores for seed species with thin shells, low lipid and high carbohydrate content, was negatively related to time to consume and cache seeds and travel distance to cache. The second global pPCA axis, which produced large scores for seeds with high protein, low tannin and low dormancy levels, was an important predictor of consumption time only. The local pPCA axis primarily reflected kernel mass. Although it explained only 12% of the variation in trait space and was not autocorrelated among phylogenetic clades, the local axis was related to all four squirrel foraging investments. Squirrel foraging behaviors are influenced by a combination of phylogenetically conserved and more evolutionarily labile seed traits that is consistent with a weak or more diffuse coevolutionary relationship between rodents and hardwood trees rather than a direct coevolutionary relationship.

A cadmium-transporting P1B-type ATPase in yeast Saccharomyces cerevisiae.

PubMed

Adle, David J; Sinani, Devis; Kim, Heejeong; Lee, Jaekwon

2007-01-12

Detoxification and homeostatic acquisition of metal ions are vital for all living organisms. We have identified PCA1 in yeast Saccharomyces cerevisiae as an overexpression suppressor of copper toxicity. PCA1 possesses signatures of a P1B-type heavy metal-transporting ATPase that is widely distributed from bacteria to humans. Copper resistance conferred by PCA1 is not dependent on catalytic activity, but it appears that a cysteine-rich region located in the N terminus sequesters copper. Unexpectedly, when compared with two independent natural isolates and an industrial S. cerevisiae strain, the PCA1 allele of the common laboratory strains we have examined possesses a missense mutation in a predicted ATP-binding residue conserved in P1B-type ATPases. Consistent with a previous report that identifies an equivalent mutation in a copper-transporting P1B-type ATPase of a Wilson disease patient, the PCA1 allele found in laboratory yeast strains is nonfunctional. Overexpression or deletion of the functional allele in yeast demonstrates that PCA1 is a cadmium efflux pump. Cadmium as well as copper and silver, but not other metals examined, dramatically increase PCA1 protein expression through post-transcriptional regulation and promote subcellular localization to the plasma membrane. Our study has revealed a novel metal detoxification mechanism in yeast mediated by a P1B-type ATPase that is unique in structure, substrate specificity, and mode of regulation.

The Use of Dietary Supplements to Alleviate Androgen Deprivation Therapy Side Effects during Prostate Cancer Treatment

PubMed Central

Dueregger, Andrea; Heidegger, Isabel; Ofer, Philipp; Perktold, Bernhard; Ramoner, Reinhold; Klocker, Helmut; Eder, Iris E.

2014-01-01

Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT. PMID:25338271

Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways.

PubMed

Ward, Ashley B; Mir, Hina; Kapur, Neeraj; Gales, Dominique N; Carriere, Patrick P; Singh, Shailesh

2018-06-14

Despite recent advances in diagnosis and treatment, prostate cancer (PCa) remains the leading cause of cancer-related deaths in men. Current treatments offered in the clinics are often toxic and have severe side effects. Hence, to treat and manage PCa, new agents with fewer side effects or having potential to reduce side effects of conventional therapy are needed. In this study, we show anti-cancer effects of quercetin, an abundant bioflavonoid commonly used to treat prostatitis, and defined quercetin-induced cellular and molecular changes leading to PCa cell death. Cell viability was assessed using MTT. Cell death mode, mitochondrial outer membrane potential, and oxidative stress levels were determined by flow cytometry using Annexin V-7 AAD dual staining kit, JC-1 dye, and ROS detection kit, respectively. Antibody microarray and western blot were used to delineate the molecular changes induced by quercetin. PCa cells treated with various concentrations of quercetin showed time- and dose-dependent decrease in cell viability compared to controls, without affecting normal prostate epithelial cells. Quercetin led to apoptotic and necrotic cell death in PCa cells by affecting the mitochondrial integrity and disturbing the ROS homeostasis depending upon the genetic makeup and oxidative status of the cells. LNCaP and PC-3 cells that have an oxidative cellular environment showed ROS quenching after quercetin treatment while DU-145 showed rise in ROS levels despite having a highly reductive environment. Opposing effects of quercetin were also observed on the pro-survival pathways of PCa cells. PCa cells with mutated p53 (DU-145) and increased ROS showed significant reduction in the activation of pro-survival Akt pathway while Raf/MEK were activated in response to quercetin. PC-3 cells lacking p53 and PTEN with reduced ROS levels showed significant activation of Akt and NF-κB pathway. Although some of these changes are commonly associated with oncogenic response, the cumulative effect of these alterations is PCa cell death. Our results demonstrated quercetin exerts its anti-cancer effects by modulating ROS, Akt, and NF-κB pathways. Quercetin could be used as a chemopreventive option as well as in combination with chemotherapeutic drugs to improve clinical outcomes of PCa patients.

Comprehensive assessment of renal tumour complexity in a large percutaneous cryoablation cohort.

PubMed

Bhindi, Bimal; Thompson, Robert Houston; Mason, Ross J; Haddad, Mustafa M; Geske, Jennifer R; Kurup, Anil Nicholas; Hannon, James D; Boorjian, Stephen A; Leibovich, Bradley C; Atwell, Thomas D; Schmit, Grant D

2017-06-01

To evaluate the association between renal tumour complexity and outcomes in a large cohort of patients undergoing percutaneous cryoablation (PCA). Patients with renal tumours treated with PCA were identified using our prospectively maintained ablation registry (2003-2015). Salvage procedures and inherited tumour syndromes were excluded. The associations between R.E.N.A.L. nephrometry score (NS) and risk of complications, renal function impairment, local failure and cancer-specific mortality (CSM) were evaluated using univariate and multivariable logistic, linear and Cox regression models. The cohort included 618 tumours treated during 580 procedures in 565 patients. The median (interquartile range [IQR]) follow-up was 34 (14.66) months. Complications (any grade) during a procedure (n[total] = 87, 15%) were more frequent with higher NS (NS 4-6: 10%; NS 7-9: 14%; NS 10-12: 36%; P < 0.001). Higher NS was independently associated with risk of complications (odds ratio [OR; per 1 point] = 1.3; 95% confidence interval [CI] 1.2-1.5; P < 0.001). Of all the NS components, tumour size was the most strongly associated with complication risk (OR 3.4; 95% CI 2.2-5.2; P < 0.001). The median (IQR) decline in glomerular filtration rate (GFR) from baseline was 9% (0, 22) at last follow-up. Each additional point in NS was associated with a 1.3% (95% CI 0.4-2.1; P = 0.005) greater GFR decline from baseline. NS was not significantly associated with local failure (n [total] = 14, 2%; NS 4-6: 2%; NS 7-9: 3%; NS 10-12: 5%; P = 0.32) or CSM (n [total] = 8, 2%; NS 4-6: 2%; NS 7-9: 3%; NS 10-12: 2%; P = 0.88). In high-complexity tumours PCA was associated with a tumour size-driven increased risk of post-procedural complications. Higher NS was associated with a small, clinically minor additional decline in renal function. Risks for local failure and CSM were low, regardless of tumour complexity. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson's disease.

PubMed

Xu, San-Qing; Li, Xu-Fang; Zhu, Hui-Yun; Liu, Yan; Fang, Feng; Chen, Ling

2013-10-01

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.

Hypoxia on the Expression of Hepatoma Upregulated Protein in Prostate Cancer Cells

PubMed Central

Espinoza, Ingrid; Sakiyama, Marcelo J.; Ma, Tangeng; Fair, Logan; Zhou, Xinchun; Hassan, Mohamed; Zabaleta, Jovanny; Gomez, Christian R.

2016-01-01

Hepatoma upregulated protein (HURP) is a multifunctional protein with clinical promise. This protein has been demonstrated to be a predictive marker for the outcome in high-risk prostate cancer (PCa) patients, besides being a resistance factor in PCa. Although changes in oxygen tension (pO2) are associated with PCa aggressiveness, the role of hypoxia in the regulation of tumor progression genes such as HURP has not yet been described. We hypothesized that pO2 alteration is involved in the regulation of HURP expression in PCa cells. In the present study, PCa cells were incubated at 2% O2 (hypoxia) and 20% O2 (normoxia) conditions. Hypoxia reduced cell growth rate of PCa cells, when compared to the growth rate of cells cultured under normoxia (p < 0.05). The decrease in cell viability was accompanied by fivefold (p < 0.05) elevated rate of vascular endothelial growth factor (VEGF) release. The expression of VEGF and the hypoxia-inducible metabolic enzyme carbonic anhydrase 9 were elevated maximally nearly 61-fold and 200-fold, respectively (p < 0.05). Noted in two cell lines (LNCaP and C4-2B) and independent of the oxygen levels, HURP expression assessed at both mRNA and protein levels was reduced. However, the decrease was more pronounced in cells cultured under hypoxia (p < 0.05). Interestingly, the analysis of patients’ specimens by Western blot revealed a marked increase of HURP protein (fivefold), when compared to control (cystoprostatectomy) tissue (p < 0.05). Immunohistochemistry analysis showed an increase in the immunostaining intensity of HURP and the hypoxia-sensitive molecules, hypoxia-inducible factor 1-alpha (HIF-1α), VEGF, and heat-shock protein 60 (HSP60) in association with tumor grade. The data also suggested a redistribution of subcellular localization for HURP and HIF-1α from the nucleus to the cytoplasmic compartment in relation to increasing tumor grade. Analysis of HURP Promoter for HIF-1-binding sites revealed presence of four putative HIF binding sites on the promoter of DLGAP5/HURP gene in the non-translated region upstream from the start codon, suggesting association between HIF-1α and the regulation of HURP protein. Taken together, our findings suggest a modulatory role of hypoxia on the expression of HURP. Additionally our results provide basis for utilization of tumor-associated molecules as predictors of aggressive PCa. PMID:27379206

King's Health Partners' Prostate Cancer Biobank (KHP PCaBB).

PubMed

Saifuddin, S R; Devlies, W; Santaolalla, A; Cahill, F; George, G; Enting, D; Rudman, S; Cathcart, P; Challacombe, B; Dasgupta, P; Galustian, C; Chandra, A; Chowdhury, S; Gillett, C; Van Hemelrijck, M

2017-11-22

The KHP PCaBB was established in 2013 and recruits donors from the Urology or Oncology Departments at Guy's Hospital in London (UK). Prostate cancer patients may be approached to give their consent for biobanking at any point in their treatment pathway, which allows residual material from their earlier diagnosis to be transferred and used by the Biobank. Currently, patients are specifically asked to donate samples of blood and surplus prostate tissue as well as permitting access to their clinical and pathological data that continues to be added throughout the course of their disease. Between 2013 and 2015, 549 prostate cancer patients gave their consent to the biobank and, the tissue repository collected 489 blood samples, 120 frozen prostate tissue samples and 1064 formalin fixed paraffin embedded diagnostic blocks.Prostate cancer has become a chronic disease in a large proportion of men, with many men receiving multiple subsequent treatments, and their treatment trajectory often spanning over decades. Therefore, this resource aims to provide an ideal research platform to explore potential variations in treatment response as well as disease markers in the different risk categories for prostate cancer.A recent audit of the KHP PCaBB revealed that between 2013 and 2015, 1796 patients were diagnosed with prostate cancer at King's Health Partners (KHP), out of which 549 (30.6%) gave their consent to KHP PCaBB. Comparisons between demographic and clinical characteristics of patients who had consented compared to the total patient population revealed that the KHP PCaBB is demographically representative of the total prostate cancer patient population seen in Guy's and St Thomas' NHS Foundation Trust (GSTT). We observed no differences in distribution of ethnicity (p = 0.507) and socioeconomic status (p = 0.097). Some differences were observed in clinical characteristics, specifically with treatment type - which differed significantly between the patients who had given consent and total patient population.The KHP PCaBB has thereby amassed a rich data and tissue repository that is largely reflective of both the demographic and clinical diversity within the total prostate cancer patient population seen at KHP, making it an ideal platform for prostate cancer research.

Fish intake, cooking practices, and risk of prostate cancer: results from a multi-ethnic case-control study.

PubMed

Joshi, Amit D; John, Esther M; Koo, Jocelyn; Ingles, Sue A; Stern, Mariana C

2012-03-01

Studies conducted to assess the association between fish consumption and prostate cancer (PCA) risk are inconclusive. However, few studies have distinguished between fatty and lean fish, and no studies have considered the role of different cooking practices, which may lead to differential accumulation of chemical carcinogens. In this study, we investigated the association between fish intake and localized and advanced PCA taking into account fish types (lean vs. fatty) and cooking practices. We analyzed data for 1,096 controls, 717 localized and 1,140 advanced cases from the California Collaborative Prostate Cancer Study, a multiethnic, population-based case-control study. We used multivariate conditional logistic regression to estimate odds ratios using nutrient density converted variables of fried fish, tuna, dark fish and white fish consumption. We tested for effect modification by cooking methods (high- vs. low-temperature methods) and levels of doneness. We observed that high white fish intake was associated with increased risk of advanced PCA among men who cooked with high-temperature methods (pan-frying, oven-broiling and grilling) until fish was well done (p (trend) = 0.001). No associations were found among men who cooked fish at low temperature and/or just until done (white fish x cooking method p (interaction) = 0.040). Our results indicate that consideration of fish type (oily vs. lean), specific fish cooking practices and levels of doneness of cooked fish helps elucidate the association between fish intake and PCA risk and suggest that avoiding high-temperature cooking methods for white fish may lower PCA risk.

The Health Effects of Masculine Self-Esteem Following Treatment for Localized Prostate Cancer Among Gay Men.

PubMed

Allensworth-Davies, Donald; Talcott, James A; Heeren, Timothy; de Vries, Brian; Blank, Thomas O; Clark, Jack A

2015-12-24

To identify factors associated with masculine self-esteem in gay men following treatment for localized prostate cancer (PCa) and to determine the association between masculine self-esteem, PCa-specific factors, and mental health factors in these patients. A national cross-sectional survey of gay PCa survivors was conducted in 2010-2011. To be eligible for the study, men needed to be age 50 or older, reside in the United States, self-identify as gay, able to read, write, and speak English, and to have been treated for PCa at least 1 year ago. One hundred eleven men returned surveys. After simultaneously adjusting for the factors in our model, men aged 50-64 years and men aged 65-74 years reported lower masculine self-esteem scores than men aged 75 years or older. Lower scores were also reported by men who reported recent severe stigma. Men who reported feeling comfortable revealing their sexual orientation to their doctor reported higher masculine self-esteem scores than men who were not. The mental component score from the SF-12 was also positively correlated with masculine self-esteem. PCa providers are in a position to reduce feelings of stigma and promote resiliency by being aware that they might have gay patients, creating a supportive environment where gay patients can discuss specific sexual concerns, and engaging patients in treatment decisions. These efforts could help not only in reducing stigma but also in increasing masculine self-esteem, thus greatly influencing gay patients' recovery, quality of life, and compliance with follow-up care.

Evaluation of skin melanoma in spectral range 450-950 nm using principal component analysis

NASA Astrophysics Data System (ADS)

Jakovels, D.; Lihacova, I.; Kuzmina, I.; Spigulis, J.

2013-06-01

Diagnostic potential of principal component analysis (PCA) of multi-spectral imaging data in the wavelength range 450- 950 nm for distant skin melanoma recognition is discussed. Processing of the measured clinical data by means of PCA resulted in clear separation between malignant melanomas and pigmented nevi.

Change detection of medical images using dictionary learning techniques and PCA

NASA Astrophysics Data System (ADS)

Nika, Varvara; Babyn, Paul; Zhu, Hongmei

2014-03-01

Automatic change detection methods for identifying the changes of serial MR images taken at different times are of great interest to radiologists. The majority of existing change detection methods in medical imaging, and those of brain images in particular, include many preprocessing steps and rely mostly on statistical analysis of MRI scans. Although most methods utilize registration software, tissue classification remains a difficult and overwhelming task. Recently, dictionary learning techniques are used in many areas of image processing, such as image surveillance, face recognition, remote sensing, and medical imaging. In this paper we present the Eigen-Block Change Detection algorithm (EigenBlockCD). It performs local registration and identifies the changes between consecutive MR images of the brain. Blocks of pixels from baseline scan are used to train local dictionaries that are then used to detect changes in the follow-up scan. We use PCA to reduce the dimensionality of the local dictionaries and the redundancy of data. Choosing the appropriate distance measure significantly affects the performance of our algorithm. We examine the differences between L1 and L2 norms as two possible similarity measures in the EigenBlockCD. We show the advantages of L2 norm over L1 norm theoretically and numerically. We also demonstrate the performance of the EigenBlockCD algorithm for detecting changes of MR images and compare our results with those provided in recent literature. Experimental results with both simulated and real MRI scans show that the EigenBlockCD outperforms the previous methods. It detects clinical changes while ignoring the changes due to patient's position and other acquisition artifacts.

Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells

PubMed Central

Chao, Hsueh-Ping; Deng, Qu; Jeter, Collene; Liu, Can; Honorio, Sofia; Li, Hangwen; Davis, Tammy; Suraneni, Mahipal; Laffin, Brian; Qin, Jichao; Li, Qiuhui; Yang, Tao; Whitney, Pamela; Shen, Jianjun; Huang, Jiaoti; Tang, Dean G.

2015-01-01

Human cancers are heterogeneous containing stem-like cancer cells operationally defined as cancer stem cells (CSCs) that possess great tumor-initiating and long-term tumor-propagating properties. In this study, we systematically dissect the phenotypic, functional and tumorigenic heterogeneity in human prostate cancer (PCa) using xenograft models and >70 patient tumor samples. In the first part, we further investigate the PSA−/lo PCa cell population, which we have recently shown to harbor self-renewing long-term tumor-propagating cells and present several novel findings. We show that discordant AR and PSA expression in both untreated and castration-resistant PCa (CRPC) results in AR+PSA+, AR+PSA−, AR−PSA−, and AR−PSA+ subtypes of PCa cells that manifest differential sensitivities to therapeutics. We further demonstrate that castration leads to a great enrichment of PSA−/lo PCa cells in both xenograft tumors and CRPC samples and systemic androgen levels dynamically regulate the relative abundance of PSA+ versus PSA−/lo PCa cells that impacts the kinetics of tumor growth. We also present evidence that the PSA−/lo PCa cells possess distinct epigenetic profiles. As the PSA−/lo PCa cell population is heterogeneous, in the second part, we employ two PSA− (Du145 and PC3) and two PSA+ (LAPC9 and LAPC4) PCa models as well as patient tumor cells to further dissect the clonogenic and tumorigenic subsets. We report that different PCa models possess distinct tumorigenic subpopulations that both commonly and uniquely express important signaling pathways that could represent therapeutic targets. Our results have important implications in understanding PCa cell heterogeneity, response to clinical therapeutics, and cellular mechanisms underlying CRPC. PMID:26246472

Assessment of long-term outcomes associated with urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion at repeat biopsy.

PubMed

Merdan, Selin; Tomlins, Scott A; Barnett, Christine L; Morgan, Todd M; Montie, James E; Wei, John T; Denton, Brian T

2015-11-15

In men with clinically localized prostate cancer who have undergone at least 1 previous negative biopsy and have elevated serum prostate-specific antigen (PSA) levels, long-term health outcomes associated with the assessment of urinary prostate cancer antigen 3 (PCA3) and the transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG) have not been investigated previously in relation to the decision to recommend a repeat biopsy. The authors performed a decision analysis using a decision tree for men with elevated PSA levels. The probability of cancer was estimated using the Prostate Cancer Prevention Trial Risk Calculator (version 2.0). The use of PSA alone was compared with the use of PCA3 and T2:ERG scores, with each evaluated independently, in combination with PSA to trigger a repeat biopsy. When PCA3 and T2:ERG score evaluations were used, predefined thresholds were established to determine whether the patient should undergo a repeat biopsy. Biopsy outcomes were defined as either positive (with a Gleason score of <7, 7, or >7) or negative. Probabilities and estimates of 10-year overall survival and 15-year cancer-specific survival were derived from previous studies and a literature review. Outcomes were defined as age-dependent and Gleason score-dependent 10-year overall and 15-year cancer-specific survival rates and the percentage of biopsies avoided. Incorporating the PCA3 score (biopsy threshold, 25; generated based on the urine PCA3 level normalized to the amount of PSA messenger RNA) or the T2:ERG score (biopsy threshold, 10; based on the urine T2:ERG level normalized to the amount of PSA messenger RNA) into the decision to recommend repeat biopsy would have avoided 55.4% or 64.7% of repeat biopsies for the base-case patient, respectively, and changes in the 10-year survival rate were only 0.93% or 1.41%, respectively. Multi-way sensitivity analyses suggested that these results were robust with respect to the model parameters. The use of PCA3 or T2:ERG testing for repeat biopsy decisions can substantially reduce the number of biopsies without significantly affecting 10-year survival. © 2015 American Cancer Society.

Co-trained convolutional neural networks for automated detection of prostate cancer in multi-parametric MRI.

PubMed

Yang, Xin; Liu, Chaoyue; Wang, Zhiwei; Yang, Jun; Min, Hung Le; Wang, Liang; Cheng, Kwang-Ting Tim

2017-12-01

Multi-parameter magnetic resonance imaging (mp-MRI) is increasingly popular for prostate cancer (PCa) detection and diagnosis. However, interpreting mp-MRI data which typically contains multiple unregistered 3D sequences, e.g. apparent diffusion coefficient (ADC) and T2-weighted (T2w) images, is time-consuming and demands special expertise, limiting its usage for large-scale PCa screening. Therefore, solutions to computer-aided detection of PCa in mp-MRI images are highly desirable. Most recent advances in automated methods for PCa detection employ a handcrafted feature based two-stage classification flow, i.e. voxel-level classification followed by a region-level classification. This work presents an automated PCa detection system which can concurrently identify the presence of PCa in an image and localize lesions based on deep convolutional neural network (CNN) features and a single-stage SVM classifier. Specifically, the developed co-trained CNNs consist of two parallel convolutional networks for ADC and T2w images respectively. Each network is trained using images of a single modality in a weakly-supervised manner by providing a set of prostate images with image-level labels indicating only the presence of PCa without priors of lesions' locations. Discriminative visual patterns of lesions can be learned effectively from clutters of prostate and surrounding tissues. A cancer response map with each pixel indicating the likelihood to be cancerous is explicitly generated at the last convolutional layer of the network for each modality. A new back-propagated error E is defined to enforce both optimized classification results and consistent cancer response maps for different modalities, which help capture highly representative PCa-relevant features during the CNN feature learning process. The CNN features of each modality are concatenated and fed into a SVM classifier. For images which are classified to contain cancers, non-maximum suppression and adaptive thresholding are applied to the corresponding cancer response maps for PCa foci localization. Evaluation based on 160 patient data with 12-core systematic TRUS-guided prostate biopsy as the reference standard demonstrates that our system achieves a sensitivity of 0.46, 0.92 and 0.97 at 0.1, 1 and 10 false positives per normal/benign patient which is significantly superior to two state-of-the-art CNN-based methods (Oquab et al., 2015; Zhou et al., 2015) and 6-core systematic prostate biopsies. Copyright © 2017 Elsevier B.V. All rights reserved.

The Pattern of Brain Amyloid Load in Posterior Cortical Atrophy Using 18F-AV45: Is Amyloid the Principal Actor in the Disease?

PubMed Central

Beaufils, Emilie; Ribeiro, Maria Joao; Vierron, Emilie; Vercouillie, Johnny; Dufour-Rainfray, Diane; Cottier, Jean-Philippe; Camus, Vincent; Mondon, Karl; Guilloteau, Denis; Hommet, Caroline

2014-01-01

Background Posterior cortical atrophy (PCA) is characterized by progressive higher-order visuoperceptual dysfunction and praxis declines. This syndrome is related to a number of underlying diseases, including, in most cases, Alzheimer's disease (AD). The aim of this study was to compare the amyloid load with 18F-AV45 positron emission tomography (PET) between PCA and AD subjects. Methods We performed 18F-AV45 PET, cerebrospinal fluid (CSF) biomarker analysis and a neuropsychological assessment in 11 PCA patients and 12 AD patients. Results The global and regional 18F-AV45 uptake was similar in the PCA and AD groups. No significant correlation was observed between global 18F-AV45 uptake and CSF biomarkers or between regional 18F-AV45 uptake and cognitive and affective symptoms. Conclusion This 18F-AV45 PET amyloid imaging study showed no specific regional pattern of cortical 18F-AV45 binding in PCA patients. These results confirm that a distinct clinical phenotype in amnestic AD and PCA is not related to amyloid distribution. PMID:25538727

Combined serum and EPS-urine proteomic analysis using iTRAQ technology for discovery of potential prostate cancer biomarkers.

PubMed

Zhang, Mo; Chen, Lizhu; Yuan, Zhengwei; Yang, Zeyu; Li, Yue; Shan, Liping; Yin, Bo; Fei, Xiang; Miao, Jianing; Song, Yongsheng

2016-11-01

Prostate cancer (PCa) is one of the most common malignant tumors and a major cause of cancer-related death for men worldwide. The aim of our study was to identify potential non-invasive serum and expressed prostatic secretion (EPS)-urine biomarkers for accurate diagnosis of PCa. Here, we performed a combined isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to compare protein profiles using pooled serum and EPS-urine samples from 4 groups of patients: benign prostate hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), localized PCa and metastatic PCa. The differentially expressed proteins were rigorously selected and further validated in a large and independent cohort using classical ELISA and Western blot assays. Finally, we established a multiplex biomarker panel consisting of 3 proteins (serum PF4V1, PSA, and urinary CRISP3) with an excellent diagnostic capacity to differentiate PCa from BPH [area under the receiver operating characteristic curve (AUC) of 0.941], which showed an evidently greater discriminatory ability than PSA alone (AUC, 0.757) (P<0.001). Importantly, even when PSA level was in the gray zone (4-10 ng/mL), a combination of PF4V1 and CRISP3 could achieve a relatively high diagnostic efficacy (AUC, 0.895). Furthermore, their combination also had the potential to distinguish PCa from HGPIN (AUC, 0.934). Our results demonstrated that the combined application of serum and EPS-urine biomarkers can improve the diagnosis of PCa and provide a new prospect for non-invasive PCa detection.

Posterior cortical atrophy: an investigation of scan paths generated during face matching tasks

PubMed Central

Meek, Benjamin P.; Locheed, Keri; Lawrence-Dewar, Jane M.; Shelton, Paul; Marotta, Jonathan J.

2013-01-01

When viewing a face, healthy individuals focus more on the area containing the eyes and upper nose in order to retrieve important featural and configural information. In contrast, individuals with face blindness (prosopagnosia) tend to direct fixations toward individual facial features—particularly the mouth. Presented here is an examination of face perception deficits in individuals with Posterior Cortical Atrophy (PCA). PCA is a rare progressive neurodegenerative disorder that is characterized by atrophy in occipito-parietal and occipito-temporal cortices. PCA primarily affects higher visual processing, while memory, reasoning, and insight remain relatively intact. A common symptom of PCA is a decreased effective field of vision caused by the inability to “see the whole picture.” Individuals with PCA and healthy control participants completed a same/different discrimination task in which images of faces were presented as cue-target pairs. Eye-tracking equipment and a novel computer-based perceptual task—the Viewing Window paradigm—were used to investigate scan patterns when faces were presented in open view or through a restricted-view, respectively. In contrast to previous prosopagnosia research, individuals with PCA each produced unique scan paths that focused on non-diagnostically useful locations. This focus on non-diagnostically useful locations was also present when using a restricted viewing aperture, suggesting that individuals with PCA have difficulty processing the face at either the featural or configural level. In fact, it appears that the decreased effective field of view in PCA patients is so severe that it results in an extreme dependence on local processing, such that a feature-based approach is not even possible. PMID:23825453

Association of microRNA-21 expression with clinicopathological characteristics and the risk of progression in advanced prostate cancer patients receiving androgen deprivation therapy.

PubMed

Guan, Yangbo; Wu, You; Liu, Yifei; Ni, Jian; Nong, Shaojun

2016-08-01

Despite androgen deprivation therapy (ADT) remains the mainstay therapy for advanced prostate cancer (PCa), the patients have widely variable durations of response to ADT. Unfortunately, there is limited knowledge of pre-treatment prognostic factors for response to ADT. Recently, microRNA-21 (miR-21) has been reported to play an important role in development of castration resistance of CaP. However, little is known about the expression of miR-21 in advanced PCa biopsy tissues, and data on its potential predictive value in advanced PCa are completely lacking. In this study, paraffin-embedded prostate carcinoma tissues obtained by needle biopsy from 85 advanced PCa patients were evaluated for the expression levels of miR-21 by quantitative real-time PCR (qRT-PCR). In situ hybridization (ISH) analysis was performed to further confirm the qRT-PCR results. Kaplan-Meier analysis and Cox proportional hazards regression models were performed to investigate the correlation between miR-21 expression and time to progression of advanced PCa patients. Compared with adjacent non-cancerous prostate tissues, the expression level of miR-21 was significantly increased in PCa tissues (PCa vs. non-cancerous prostate: 1.3273 ± 0.3207 vs. 0.9970 ± 0.2054, P < 0.001). By and large, in ISH analysis miR-21 was expressed at a higher level in tumor areas than in adjacent non-cancerous areas. Additionally, PCa patients with higher expression of miR-21 were significantly more likely to be of high Gleason score and high clinical stage (P < 0.05). There was no significant association between miR-21 expression and the initial prostate-specific antigen (PSA) level or age at diagnosis. Moreover, Kaplan-Meier survival analysis found that PCa patients with high miR-21 expression have shorter progression-free survival than those with low miR-21 expression. Furthermore, Multivariate Cox analysis revealed both miR-21 expression status (P = 0.040) and clinical stage (P = 0.042) were all independent predictive factor for progression-free survival for advanced PCa. These findings suggest for the first time that the up-regulation of miR-21 may serve as an independent predictor of progress-free survival in patients with advanced PCa. Prostate 76:986-993, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Measuring the Indonesian provinces competitiveness by using PCA technique

NASA Astrophysics Data System (ADS)

Runita, Ditha; Fajriyah, Rohmatul

2017-12-01

Indonesia is a country which has vast teritoty. It has 34 provinces. Building local competitiveness is critical to enhance the long-term national competitiveness especially for a country as diverse as Indonesia. A competitive local government can attract and maintain successful firms and increase living standards for its inhabitants, because investment and skilled workers gravitate from uncompetitive regions to more competitive ones. Altough there are other methods to measuring competitiveness, but here we have demonstrated a simple method using principal component analysis (PCA). It can directly be applied to correlated, multivariate data. The analysis on Indonesian provinces provides 3 clusters based on the competitiveness measurement and the clusters are Bad, Good and Best perform provinces.

Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer?

PubMed

Gold, Samuel A; Hale, Graham R; Bloom, Jonathan B; Smith, Clayton P; Rayn, Kareem N; Valera, Vladimir; Wood, Bradford J; Choyke, Peter L; Turkbey, Baris; Pinto, Peter A

2018-05-21

Multiparametric magnetic resonance imaging (mpMRI) has improved clinicians' ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx. A literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed "PCa mimics," that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement. Despite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from "PCa mimics" or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy. A better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options.

Hypoxia-Induced Signaling Promotes Prostate Cancer Progression: Exosomes Role as Messenger of Hypoxic Response in Tumor Microenvironment

PubMed Central

Deep, Gagan; Panigrahi, Gati K.

2017-01-01

Prostate cancer (PCA) is the leading malignancy in men and the second leading cause of cancer-related deaths. Hypoxia (low O2 condition) is considered an early event in prostate carcinogenesis associated with an aggressive phenotype. In fact, clinically, hypoxia and hypoxia-related biomarkers are associated with treatment failure and disease progression. Hypoxia-inducible factor 1 (HIF-1) is the key factor that is activated under hypoxia, and mediates adaptation of cells to hypoxic conditions through regulating the expression of genes associated with angiogenesis, epithelial-to-mesenchymal transition (EMT), metastasis, survival, proliferation, metabolism, stemness, hormone-refractory progression, and therapeutic resistance. Besides HIF-1, several other signaling pathways including PI3K/Akt/mTOR, NADPH oxidase (NOX), Wnt/β-catenin, and Hedgehog are activated in cancer cells under hypoxic conditions, and also contribute in hypoxia-induced biological effects in HIF-1-dependent and -independent manners. Hypoxic cancer cells cause extensive changes in the tumor microenvironment both local and distant, and recent studies have provided ample evidence supporting the crucial role of nanosized vesicles “exosomes” in mediating hypoxia-induced tumor microenvironment remodeling. Exosomes’ role has been reported in hypoxia-induced angiogenesis, stemness, activation of cancer-associated fibroblasts (CAFs), and EMT. Together, existing literature suggests that hypoxia plays a predominant role in PCA growth and progression, and PCA could be effectively prevented and treated via targeting hypoxia/hypoxia-related signaling pathways. PMID:27279239

Brachyury as a potential modulator of androgen receptor activity and a key player in therapy resistance in prostate cancer

PubMed Central

Pinto, Filipe; Pértega-Gomes, Nelma; Vizcaíno, José R.; Andrade, Raquel P.; Cárcano, Flavio M.; Reis, Rui Manuel

2016-01-01

Prostate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of cancer-related deaths in men. Acquisition of resistance to conventional therapy is a major problem for PCa patient management. Several mechanisms have been described to promote therapy resistance in PCa, such as androgen receptor (AR) activation, epithelial-to-mesenchymal transition (EMT), acquisition of stem cell properties and neuroendocrine transdifferentiation (NEtD). Recently, we identified Brachyury as a new biomarker of PCa aggressiveness and poor prognosis. In the present study we aimed to assess the role of Brachyury in PCa therapy resistance. We showed that Brachyury overexpression in prostate cancer cells lines increased resistance to docetaxel and cabazitaxel drugs, whereas Brachyury abrogation induced decrease in therapy resistance. Through ChiP-qPCR assays we further demonstrated that Brachyury is a direct regulator of AR expression as well as of the biomarker AMACR and the mesenchymal markers Snail and Fibronectin. Furthermore, in vitro Brachyury was also able to increase EMT and stem properties. By in silico analysis, clinically human Brachyury-positive PCa samples were associated with biomarkers of PCa aggressiveness and therapy resistance, including PTEN loss, and expression of NEtD markers, ERG and Bcl-2. Taken together, our results indicate that Brachyury contributes to tumor chemotherapy resistance, constituting an attractive target for advanced PCa patients. PMID:27049720

Consensus statement on definition, diagnosis, and management of high-risk prostate cancer patients on behalf of the Spanish Groups of Uro-Oncology Societies URONCOR, GUO, and SOGUG.

PubMed

Henríquez, I; Rodríguez-Antolín, A; Cassinello, J; Gonzalez San Segundo, C; Unda, M; Gallardo, E; López-Torrecilla, J; Juarez, A; Arranz, J

2018-03-01

Prostate cancer (PCa) is the most prevalent malignancy in men and the second cause of mortality in industrialized countries. Based on Spanish Register of PCa, the incidence of high-risk PCa is 29%, approximately. In spite of the evidence-based beneficial effect of radiotherapy and androgen deprivation therapy in high-risk PCa, these patients (pts) are still a therapeutic challenge for all specialists involved, in part due to the absence of comparative studies to establish which of the present disposable treatments offer better results. Nowadays, high-risk PCa definition is not well consensual through the published oncology guides. Clinical stage, tumour grade, and number of risk factors are relevant to be considered on PCa prognosis. However, these factors are susceptible to change depending on when surgical or radiation therapy is considered to be the treatment of choice. Other factors, such as reference pathologist, different diagnosis biopsy schedules, surgical or radiotherapy techniques, adjuvant treatments, biochemical failures, and follow-up, make it difficult to compare the results between different therapeutic options. This article reviews important issues concerning high-risk PCa. URONCOR, GUO, and SOGUG on behalf of the Spanish Groups of Uro-Oncology Societies have reached a consensus addressing a practical recommendation on definition, diagnosis, and management of high-risk PCa.

Waist-hip Ratio (WHR), a Better Predictor for Prostate Cancer than Body Mass Index (BMI): Results from a Chinese Hospital-based Biopsy Cohort.

PubMed

Tang, Bo; Han, Cheng-Tao; Zhang, Gui-Ming; Zhang, Cui-Zhu; Yang, Wei-Yi; Shen, Ying; Vidal, Adriana C; Freedland, Stephen J; Zhu, Yao; Ye, Ding-Wei

2017-03-08

To investigate whether waist-hip ratio (WHR) is a better predictor of prostate cancer (PCa) incidence than body mass index (BMI) in Chinese men. Of consecutive patients who underwent prostate biopsies in one tertiary center between 2013 and 2015, we examined data on 1018 with PSA ≤20 ng/ml. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the associations between BMI, WHR and PCa incidence. Area under the ROC (AUC) was used to evaluate the accuracy of different prognostic models. A total of 255 men and 103 men were diagnosed with PCa and high grade PCa (HGPCa, Gleason score ≥8). WHR was an independent risk factor for both PCa (OR = 1.07 95%Cl 1.03-1.11) and HGPCa (OR = 1.14 95%Cl 1.09-1.19) detection, while BMI had no relationship with either PCa or HGPCa detection. Adding WHR to a multivariable model increased the AUC for detecting HGPCa from 0.66 (95%Cl 0.60-0.72) to 0.71 (95%Cl 0.65-0.76). In this Chinese cohort, WHR was significantly predictive of PCa and HGPCa. Adding WHR to a multivariable model increased the diagnostic accuracy for detecting HGPCa. If confirmed, including WHR measurement may improve PCa and HGPCa detection.

Waist-hip Ratio (WHR), a Better Predictor for Prostate Cancer than Body Mass Index (BMI): Results from a Chinese Hospital-based Biopsy Cohort

PubMed Central

Tang, Bo; Han, Cheng-Tao; Zhang, Gui-Ming; Zhang, Cui-Zhu; Yang, Wei-Yi; Shen, Ying; Vidal, Adriana C.; Freedland, Stephen J.; Zhu, Yao; Ye, Ding-Wei

2017-01-01

To investigate whether waist-hip ratio (WHR) is a better predictor of prostate cancer (PCa) incidence than body mass index (BMI) in Chinese men. Of consecutive patients who underwent prostate biopsies in one tertiary center between 2013 and 2015, we examined data on 1018 with PSA ≤20 ng/ml. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the associations between BMI, WHR and PCa incidence. Area under the ROC (AUC) was used to evaluate the accuracy of different prognostic models. A total of 255 men and 103 men were diagnosed with PCa and high grade PCa (HGPCa, Gleason score ≥8). WHR was an independent risk factor for both PCa (OR = 1.07 95%Cl 1.03–1.11) and HGPCa (OR = 1.14 95%Cl 1.09–1.19) detection, while BMI had no relationship with either PCa or HGPCa detection. Adding WHR to a multivariable model increased the AUC for detecting HGPCa from 0.66 (95%Cl 0.60–0.72) to 0.71 (95%Cl 0.65–0.76). In this Chinese cohort, WHR was significantly predictive of PCa and HGPCa. Adding WHR to a multivariable model increased the diagnostic accuracy for detecting HGPCa. If confirmed, including WHR measurement may improve PCa and HGPCa detection. PMID:28272469

Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chopra, Supriya; Princess Margaret Hospital, University Health Network, Toronto; Toi, Ants

2012-03-01

Purpose: Rational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive for site of local recurrence (LR) after external beam RT. Methods and Materials: Prospective databases were reviewed to identify men with LR after RT from 1997 through 2009. Patients with biochemical failure and biopsy-confirmed Pca more than 2 years after RT were evaluated. Prediction for site of recurrence based on the following pretreatment factors was determined on independent and cluster-sextant basis: presence of malignancy, dominant vs. nondominant percentage core length (PCL) involvement,more » PCL {>=} or <40%, and Gleason score. Sites of dominant PCL were defined as sextants with peak PCL involvement minus 10%, and >5% for each patient. Results: Forty-one patients with low-intermediate risk Pca constituted the study cohort. Median time to biopsy after RT was 51 months (range, 24-145). Of 246 sextants, 74 were involved with tumor at baseline. When sextants are treated as independent observations the presence of malignancy (77% vs. 22%, p = 0.0001), dominant PCL (90% vs. 46%, p = 0.0001), and PCL {>=}40% (89% vs. 68 %, p = 0.04) were found to be significant predictors for LR, although PCL {>=}40% did not retain statistical significance if sextants were considered correlated. The vast majority of patients (95%) recurred at the original site of dominant PCL or PCL {>=}40%, and 44% also recurred in regions of nondominant PCL <40% (n = 8) and/or benign sampling (n = 14) at baseline. Conclusions: LR after RT predominantly occurs in regions bearing higher histological tumor burden but are not isolated to these sites. Our data highlights the value of spatially resolved baseline pathological sampling and may assist in the design of clinical trials tailoring RT dose prescriptions to subregions of the prostate gland.« less

PAin SoluTions In the Emergency Setting (PASTIES); a protocol for two open-label randomised trials of patient-controlled analgesia (PCA) versus routine care in the emergency department

PubMed Central

Smith, Jason E; Rockett, Mark; Squire, Rosalyn; Hayward, Christopher J; Creanor, Siobhan; Ewings, Paul; Barton, Andy; Pritchard, Colin; Benger, Jonathan Richard

2013-01-01

Introduction Pain is the commonest reason that patients present to an emergency department (ED), but it is often not treated effectively. Patient controlled analgesia (PCA) is used in other hospital settings but there is little evidence to support its use in emergency patients. We describe two randomised trials aiming to compare PCA to nurse titrated analgesia (routine care) in adult patients who present to the ED requiring intravenous opioid analgesia for the treatment of moderate to severe pain and are subsequently admitted to hospital. Methods and analysis Two prospective multi-centre open-label randomised trials of PCA versus routine care in emergency department patients who require intravenous opioid analgesia followed by admission to hospital; one trial involving patients with traumatic musculoskeletal injuries and the second involving patients with non-traumatic abdominal pain. In each trial, 200 participants will be randomised to receive either routine care or PCA, and followed for the first 12 h of their hospital stay. The primary outcome measure is hourly pain score recorded by the participant using a visual analogue scale (VAS) over the 12 h study period, with the primary statistical analyses based on the area under the curve of these pain scores. Secondary outcomes include total opioid use, side effects, time spent asleep, patient satisfaction, length of hospital stay and incremental cost effectiveness ratio. Ethics and dissemination The study is approved by the South Central—Southampton A Research Ethics Committee (REC reference 11/SC/0151). Data collection will be completed by August 2013, with statistical analyses starting after all final data queries are resolved. Dissemination plans include presentations at local, national and international scientific meetings held by relevant Colleges and societies. Publications should be ready for submission during 2014. A lay summary of the results will be available to study participants on request, and disseminated via a publically accessible website. Registration details The study is registered with the European Clinical Trials Database (EudraCT Number: 2011-000194-31) and is on the ISCRTN register (ISRCTN25343280). PMID:23418302

PD-1/PD-L1 pathway inhibitors in advanced prostate cancer.

PubMed

Isaacsson Velho, Pedro; Antonarakis, Emmanuel S

2018-05-01

Pharmacological inhibition of immune checkpoint receptors or their ligands represents a transformative breakthrough in the management of multiple cancers. However, immune checkpoint inhibitors have yet to be FDA-approved for the management of metastatic prostate cancer (PCa), the commonest non-cutaneous malignancy in men. Areas covered: We review our current understanding of the PD-1/PD-L1 pathway in cancer, the use of anti-PD-1/PD-L1 therapeutics in PCa, and potential subgroups of PCa patients who may derive the greatest benefit from these agents (such as men with tumors that have expression of PD-L1 and/or high mutational load). We also review the prior and current clinical trials evaluating the blockade of PD-1/PD-L1 in PCa, highlighting some of the key ongoing studies of greatest relevance to the field. Expert commentary: Clinical trials investigating PD-1/PD-L1 inhibitors should be encouraged in patients with PCa. While it is unlikely that immune checkpoint monotherapies will produce long-lasting responses in a substantial proportion of patients, there is early evidence of activity in some patient subsets. These subgroups may include those with high PD-L1 expression, those with hypermutated or microsatellite-unstable tumors, and those enriched for germline and/or somatic DNA-repair gene mutations (e.g. intraductal/ductal histology, primary Gleason pattern 5, and perhaps AR-V7-positive tumors).

Does adding ketamine to morphine patient-controlled analgesia safely improve post-thoracotomy pain?

PubMed

Mathews, Timothy J; Churchhouse, Antonia M D; Housden, Tessa; Dunning, Joel

2012-02-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'is the addition of ketamine to morphine patient-controlled analgesia (PCA) following thoracic surgery superior to morphine alone'. Altogether 201 papers were found using the reported search, of which nine represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This consisted of one systematic review of PCA morphine with ketamine (PCA-MK) trials, one meta-analysis of PCA-MK trials, four randomized controlled trials of PCA-MK, one meta-analysis of trials using a variety of peri-operative ketamine regimes and two cohort studies of PCA-MK. Main outcomes measured included pain score rated on visual analogue scale, morphine consumption and incidence of psychotomimetic side effects/hallucination. Two papers reported the measurements of respiratory function. This evidence shows that adding ketamine to morphine PCA is safe, with a reported incidence of hallucination requiring intervention of 2.9%, and a meta-analysis finding an incidence of all central nervous system side effects of 18% compared with 15% with morphine alone, P = 0.31, RR 1.27 with 95% CI (0.8-2.01). All randomized controlled trials of its use following thoracic surgery found no hallucination or psychological side effect. All five studies in thoracic surgery (n = 243) found reduced morphine requirements with PCA-MK. Pain scores were significantly lower in PCA-MK patients in thoracic surgery papers, with one paper additionally reporting increased patient satisfaction. However, no significant improvement was found in a meta-analysis of five papers studying PCA-MK in a variety of surgical settings. Both papers reporting respiratory outcomes found improved oxygen saturations and PaCO(2) levels in PCA-MK patients following thoracic surgery. We conclude that adding low-dose ketamine to morphine PCA is safe and post-thoracotomy may provide better pain control than PCA with morphine alone (PCA-MO), with reduced morphine consumption and possible improvement in respiratory function. These studies thus support the routine use of PCA-MK instead of PCA-MO to improve post-thoracotomy pain control.

Watchful waiting and active surveillance approach in patients with low risk localized prostatic cancer: an experience of out-patients clinic with 12-year follow-up.

PubMed

Kravchick, Sergey; Peled, Ronit; Cytron, Shmuel

2011-12-01

In this study we evaluated the safety of expectant approach in the patients with low risk prostate cancer in the reality of community based out-patients clinics. 48 men were enrolled into the study. The inclusion criteria were age ranged from 60 to 75 years and the Epstein criteria for low risk prostate cancer. Patients were managed expectantly while curative treatment was offered when indicated. Initial and final Charlson comorbidity index (CCI) and BMI were assessed for all men. Patients' median follow-up was 81.1 ± 29.1 years. During this study 41.7% of the patients chose active forms of treatment. Cancer was found in 20.8% (n-10) of our patients. Two first sessions of re-biopsy diagnosed 92% of T1c upgrading. Six men with CCI ≥2 died from concomitant disease and no one died from PCa. Significant correlation was found between BMI and final CCI ≥2 (p-0.001). Expectant approach can be considered as self alternative to active treatment model in selected group of patients with well differentiated PCa, however 20.8% of these patients are still at risk of having aggressive form of cancer. Expectant approach is particular beneficial for the patients with CCI 1-2 and high BMI.

A prospective cohort and extended comprehensive-cohort design provided insights about the generalizability of a pragmatic trial: the ProtecT prostate cancer trial.

PubMed

Donovan, Jenny L; Young, Grace J; Walsh, Eleanor I; Metcalfe, Chris; Lane, J Athene; Martin, Richard M; Tazewell, Marta K; Davis, Michael; Peters, Tim J; Turner, Emma L; Mills, Nicola; Khazragui, Hanan; Khera, Tarnjit K; Neal, David E; Hamdy, Freddie C

2018-04-01

Randomized controlled trials (RCTs) deliver robust internally valid evidence but generalizability is often neglected. Design features built into the Prostate testing for cancer and Treatment (ProtecT) RCT of treatments for localized prostate cancer (PCa) provided insights into its generalizability. Population-based cluster randomization created a prospective study of prostate-specific antigen (PSA) testing and a comprehensive-cohort study including groups choosing treatment or excluded from the RCT, as well as those randomized. Baseline information assessed selection and response during RCT conduct. The prospective study (82,430 PSA-tested men) represented healthy men likely to respond to a screening invitation. The extended comprehensive cohort comprised 1,643 randomized, 997 choosing treatment, and 557 excluded with advanced cancer/comorbidities. Men choosing treatment were very similar to randomized men except for having more professional/managerial occupations. Excluded men were similar to the randomized socio-demographically but different clinically, representing less healthy men with more advanced PCa. The design features of the ProtecT RCT provided data to assess the representativeness of the prospective cohort and generalizability of the findings of the RCT. Greater attention to collecting data at the design stage of pragmatic trials would better support later judgments by clinicians/policy-makers about the generalizability of RCT findings in clinical practice. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

A Seven-Gene Locus for Synthesis of Phenazine-1-Carboxylic Acid by Pseudomonas fluorescens 2-79

PubMed Central

Mavrodi, Dmitri V.; Ksenzenko, Vladimir N.; Bonsall, Robert F.; Cook, R. James; Boronin, Alexander M.; Thomashow, Linda S.

1998-01-01

Pseudomonas fluorescens 2-79 produces the broad-spectrum antibiotic phenazine-1-carboxylic acid (PCA), which is active against a variety of fungal root pathogens. In this study, seven genes designated phzABCDEFG that are sufficient for synthesis of PCA were localized within a 6.8-kb BglII-XbaI fragment from the phenazine biosynthesis locus of strain 2-79. Polypeptides corresponding to all phz genes were identified by analysis of recombinant plasmids in a T7 promoter/polymerase expression system. Products of the phzC, phzD, and phzE genes have similarities to enzymes of shikimic acid and chorismic acid metabolism and, together with PhzF, are absolutely necessary for PCA production. PhzG is similar to pyridoxamine-5′-phosphate oxidases and probably is a source of cofactor for the PCA-synthesizing enzyme(s). Products of the phzA and phzB genes are highly homologous to each other and may be involved in stabilization of a putative PCA-synthesizing multienzyme complex. Two new genes, phzX and phzY, that are homologous to phzA and phzB, respectively, were cloned and sequenced from P. aureofaciens 30-84, which produces PCA, 2-hydroxyphenazine-1-carboxylic acid, and 2-hydroxyphenazine. Based on functional analysis of the phz genes from strains 2-79 and 30-84, we postulate that different species of fluorescent pseudomonads have similar genetic systems that confer the ability to synthesize PCA. PMID:9573209

Impact of trait anxiety on psychological well-being in men with prostate cancer.

PubMed

Taoka, Rikiya; Matsunaga, Hisato; Kubo, Tatsuhiko; Suzuki, Toru; Yamamoto, Shingo

2014-01-01

The aim of the present study was to determine state anxiety following radical treatment for localized prostate cancer (PCa), and the impact of trait anxiety on psychological well-being in affected patients. The present study was a cross-sectional survey of 70 men with localized PCa performed between February 2012 and July 2012. Of those, 21, 24, and 25 patients were treated by radical retropubic prostatectomy (RRP), permanent prostate brachytherapy (PPB), and external beam radiotherapy (EBRT), respectively. State anxiety, trait anxiety, and general health were assessed using the State-Trait Anxiety Inventory and 8 Items Short Form Health Survey (SF-8). The rate of very high and high state anxiety in patients who received RRP was 47.6%, while that in patients who received PPB and EBRT was 40.0% and 37.5%, respectively. In contrast, the rate of very high and high trait anxiety in the RRP group was much lower (23.7%). Trait anxiety showed a high correlation with state anxiety and the mental health component summary of SF-8 (correlation coefficient=0.715, -0.504). Trait anxiety was associated with the degree of state anxiety regarding treatments for PCa, followed by change in state anxiety, which might have effects on psychological well-being. Information regarding state anxiety as a consequence of treatments and trait anxiety measurement tool are important considerations for treatment decision-making in newly diagnosed PCa patients.

A Rice Phenolic Efflux Transporter Is Essential for Solubilizing Precipitated Apoplasmic Iron in the Plant Stele*

PubMed Central

Ishimaru, Yasuhiro; Kakei, Yusuke; Shimo, Hugo; Bashir, Khurram; Sato, Yutaka; Sato, Yuki; Uozumi, Nobuyuki; Nakanishi, Hiromi; Nishizawa, Naoko K.

2011-01-01

Iron deficiency is one of the major agricultural problems, as 30% of the arable land of the world is too alkaline for optimal crop production, rendering plants short of available iron despite its abundance. To take up apoplasmic precipitated iron, plants secrete phenolics such as protocatechuic acid (PCA) and caffeic acid. The molecular pathways and genes of iron uptake strategies are already characterized, whereas the molecular mechanisms of phenolics synthesis and secretion have not been clarified, and no phenolics efflux transporters have been identified in plants yet. Here we describe the identification of a phenolics efflux transporter in rice. We identified a cadmium-accumulating rice mutant in which the amount of PCA and caffeic acid in the xylem sap was dramatically reduced and hence named it phenolics efflux zero 1 (pez1). PEZ1 localized to the plasma membrane and transported PCA when expressed in Xenopus laevis oocytes. PEZ1 localized mainly in the stele of roots. In the roots of pez1, precipitated apoplasmic iron increased. The growth of PEZ1 overexpression lines was severely restricted, and these lines accumulated more iron as a result of the high solubilization of precipitated apoplasmic iron in the stele. We show that PEZ1 is responsible for an increase of PCA concentration in the xylem sap and is essential for the utilization of apoplasmic precipitated iron in the stele. PMID:21602276

To Share or Not to Share: Malaysian Healthcare Professionals' Views on Localized Prostate Cancer Treatment Decision Making Roles.

PubMed

Lee, Yew Kong; Lee, Ping Yein; Cheong, Ai Theng; Ng, Chirk Jenn; Abdullah, Khatijah Lim; Ong, Teng Aik; Razack, Azad Hassan Abdul

2015-01-01

To explore the views of Malaysian healthcare professionals (HCPs) on stakeholders' decision making roles in localized prostate cancer (PCa) treatment. Qualitative interviews and focus groups were conducted with HCPs treating PCa. Data was analysed using a thematic approach. Four in-depth interviews and three focus group discussions were conducted between December 2012 and March 2013 using a topic guide. Interviews were audio-recorded, transcribed verbatim, and analysed thematically. The participants comprised private urologists (n = 4), government urologists (n = 6), urology trainees (n = 6), government policy maker (n = 1) and oncologists (n = 3). HCP perceptions of the roles of the three parties involved (HCPs, patients, family) included: HCP as the main decision maker, HCP as a guide to patients' decision making, HCP as a facilitator to family involvement, patients as main decision maker and patient prefers HCP to decide. HCPs preferred to share the decision with patients due to equipoise between prostate treatment options. Family culture was important as family members often decided on the patient's treatment due to Malaysia's close-knit family culture. A range of decision making roles were reported by HCPs. It is thus important that stakeholder roles are clarified during PCa treatment decisions. HCPs need to cultivate an awareness of sociocultural norms and family dynamics when supporting non-Western patients in making decisions about PCa.

To Share or Not to Share: Malaysian Healthcare Professionals' Views on Localized Prostate Cancer Treatment Decision Making Roles

PubMed Central

Lee, Yew Kong; Lee, Ping Yein; Cheong, Ai Theng; Ng, Chirk Jenn; Abdullah, Khatijah Lim; Ong, Teng Aik; Razack, Azad Hassan Abdul

2015-01-01

Aim To explore the views of Malaysian healthcare professionals (HCPs) on stakeholders’ decision making roles in localized prostate cancer (PCa) treatment. Methods Qualitative interviews and focus groups were conducted with HCPs treating PCa. Data was analysed using a thematic approach. Four in-depth interviews and three focus group discussions were conducted between December 2012 and March 2013 using a topic guide. Interviews were audio-recorded, transcribed verbatim, and analysed thematically. Findings The participants comprised private urologists (n = 4), government urologists (n = 6), urology trainees (n = 6), government policy maker (n = 1) and oncologists (n = 3). HCP perceptions of the roles of the three parties involved (HCPs, patients, family) included: HCP as the main decision maker, HCP as a guide to patients’ decision making, HCP as a facilitator to family involvement, patients as main decision maker and patient prefers HCP to decide. HCPs preferred to share the decision with patients due to equipoise between prostate treatment options. Family culture was important as family members often decided on the patient’s treatment due to Malaysia’s close-knit family culture. Conclusions A range of decision making roles were reported by HCPs. It is thus important that stakeholder roles are clarified during PCa treatment decisions. HCPs need to cultivate an awareness of sociocultural norms and family dynamics when supporting non-Western patients in making decisions about PCa. PMID:26559947

Toward a strategy of patient-centered access to primary care.

PubMed

Berry, Leonard L; Beckham, Dan; Dettman, Amy; Mead, Robert

2014-10-01

Patient-centered access (PCA) to primary care services is rapidly becoming an imperative for efficiently delivering high-quality health care to patients. To enhance their PCA-related efforts, some medical practices and health systems have begun to use various tactics, including team-based care, satellite clinics, same-day and group appointments, greater use of physician assistants and nurse practitioners, and remote access to health services. However, few organizations are addressing the PCA imperative comprehensively by integrating these various tactics to develop an overall PCA management strategy. Successful integration means taking into account the changing competitive and reimbursement landscape in primary care, conducting an evidence-based assessment of the barriers and benefits of PCA implementation, and attending to the particular needs of the institution engaged in this important effort. This article provides a blueprint for creating a multifaceted but coordinated PCA strategy-one aimed squarely at making patient access a centerpiece of how health care is delivered. The case of a Wisconsin-based health system is used as an illustrative example of how other institutions might begin to conceive their fledgling PCA strategies without proposing it as a one-size-fits-all model. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Automated diagnosis of prostate cancer in multi-parametric MRI based on multimodal convolutional neural networks

NASA Astrophysics Data System (ADS)

Le, Minh Hung; Chen, Jingyu; Wang, Liang; Wang, Zhiwei; Liu, Wenyu; (Tim Cheng, Kwang-Ting; Yang, Xin

2017-08-01

Automated methods for prostate cancer (PCa) diagnosis in multi-parametric magnetic resonance imaging (MP-MRIs) are critical for alleviating requirements for interpretation of radiographs while helping to improve diagnostic accuracy (Artan et al 2010 IEEE Trans. Image Process. 19 2444-55, Litjens et al 2014 IEEE Trans. Med. Imaging 33 1083-92, Liu et al 2013 SPIE Medical Imaging (International Society for Optics and Photonics) p 86701G, Moradi et al 2012 J. Magn. Reson. Imaging 35 1403-13, Niaf et al 2014 IEEE Trans. Image Process. 23 979-91, Niaf et al 2012 Phys. Med. Biol. 57 3833, Peng et al 2013a SPIE Medical Imaging (International Society for Optics and Photonics) p 86701H, Peng et al 2013b Radiology 267 787-96, Wang et al 2014 BioMed. Res. Int. 2014). This paper presents an automated method based on multimodal convolutional neural networks (CNNs) for two PCa diagnostic tasks: (1) distinguishing between cancerous and noncancerous tissues and (2) distinguishing between clinically significant (CS) and indolent PCa. Specifically, our multimodal CNNs effectively fuse apparent diffusion coefficients (ADCs) and T2-weighted MP-MRI images (T2WIs). To effectively fuse ADCs and T2WIs we design a new similarity loss function to enforce consistent features being extracted from both ADCs and T2WIs. The similarity loss is combined with the conventional classification loss functions and integrated into the back-propagation procedure of CNN training. The similarity loss enables better fusion results than existing methods as the feature learning processes of both modalities are mutually guided, jointly facilitating CNN to ‘see’ the true visual patterns of PCa. The classification results of multimodal CNNs are further combined with the results based on handcrafted features using a support vector machine classifier. To achieve a satisfactory accuracy for clinical use, we comprehensively investigate three critical factors which could greatly affect the performance of our multimodal CNNs but have not been carefully studied previously. (1) Given limited training data, how can these be augmented in sufficient numbers and variety for fine-tuning deep CNN networks for PCa diagnosis? (2) How can multimodal MP-MRI information be effectively combined in CNNs? (3) What is the impact of different CNN architectures on the accuracy of PCa diagnosis? Experimental results on extensive clinical data from 364 patients with a total of 463 PCa lesions and 450 identified noncancerous image patches demonstrate that our system can achieve a sensitivity of 89.85% and a specificity of 95.83% for distinguishing cancer from noncancerous tissues and a sensitivity of 100% and a specificity of 76.92% for distinguishing indolent PCa from CS PCa. This result is significantly superior to the state-of-the-art method relying on handcrafted features.

Brain networks in posterior cortical atrophy: a single case tractography study and literature review.

PubMed

Migliaccio, Raffaella; Agosta, Federica; Toba, Monica N; Samri, Dalila; Corlier, Fabian; de Souza, Leonardo C; Chupin, Marie; Sharman, Michael; Gorno-Tempini, Maria L; Dubois, Bruno; Filippi, Massimo; Bartolomeo, Paolo

2012-01-01

Posterior cortical atrophy (PCA) is rare neurodegenerative dementia, clinically characterized by a progressive decline in higher-visual object and space processing. After a brief review of the literature on the neuroimaging in PCA, here we present a study of the brain structural connectivity in a patient with PCA and progressive isolated visual and visuo-motor signs. Clinical and cognitive data were acquired in a 58-years-old patient (woman, right-handed, disease duration 18 months). Brain structural and diffusion tensor (DT) magnetic resonance imaging (MRI) were obtained. A voxel-based morphometry (VBM) study was performed to explore the pattern of gray matter (GM) atrophy, and a fully automatic segmentation was assessed to obtain the hippocampal volumes. DT MRI-based tractography was used to assess the integrity of long-range white matter (WM) pathways in the patient and in six sex- and age-matched healthy subjects. This PCA patient had a clinical syndrome characterized by left visual neglect, optic ataxia, and left limb apraxia, as well as mild visuo-spatial episodic memory impairment. VBM study showed bilateral posterior GM atrophy with right predominance; DT MRI tractography demonstrated WM damage to the right hemisphere only, including the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus, as compared to age-matched controls. The homologous left-hemisphere tracts were spared. No difference was found between left and right hippocampal volumes. These data suggest that selective visuo-spatial deficits typical of PCA might not result from cortical damage alone, but by a right-lateralized network-level dysfunction including WM damage along the major visual pathways. Copyright © 2011 Elsevier Srl. All rights reserved.

MRI in early prostate cancer detection: how to manage indeterminate or equivocal PI-RADS 3 lesions?

PubMed

Schoots, Ivo G

2018-02-01

This review focuses on indeterminate lesions on prostate magnetic resonance imaging (MRI), assigned as PI-RADS category 3. The prevalence of PI-RADS 3 index lesion in the diagnostic work-up is significant, varying between one in three (32%) to one in five (22%) men, depending on patient cohort of first biopsies, previously negative biopsies, and active surveillance biopsies. A management strategy must be developed for this group of men with an indeterminate suspicion of having clinically significant prostate cancer (csPCa). Currently available data show that the actual prevalence of csPCa after targeted biopsy in PI-RADS 3 lesions vary between patients groups from one in five (21%) to one in six (16%), depending on previous biopsy status. Although this prevalence is lower in comparison to PI-RADS 4 and PI-RADS 5 lesions, still a considerable proportion of men harbor significant disease. Men with such a PI-RADS 3 lesion should therefore be adequately managed. In general, the clinical approach of using a threshold of PI-RADS ≥4 instead of PI-RADS ≥3 to select MRI for targeted biopsies is not supported by data from our explorative literature search using current definitions of csPCa. A possible adaptation to the threshold of PI-RADS ≥4 in combination with other clinical markers could be considered within an active surveillance protocol, where the balance between the individual risk of missing csPCa and the constant process of repeating prostate biopsies is crucial. In the future, improvements in MR imaging and interpretation, combined with molecular biomarkers and multivariate risk models will all be employed in prostate cancer detection and monitoring. These combinations will aid decision-making in challenging circumstances, such as unclear and diagnostic equivocal results for csPCa at early detection.

Dosimetry and first clinical evaluation of the new 18F-radiolabeled bombesin analogue BAY 864367 in patients with prostate cancer.

PubMed

Sah, Bert-Ram; Burger, Irene A; Schibli, Roger; Friebe, Matthias; Dinkelborg, Ludger; Graham, Keith; Borkowski, Sandra; Bacher-Stier, Claudia; Valencia, Ray; Srinivasan, Ananth; Hany, Thomas F; Mu, Linjing; Wild, Peter J; Schaefer, Niklaus G

2015-03-01

The aim of this first-in-man study was to demonstrate the feasibility, safety, and tolerability, as well as provide dosimetric data and evaluate the imaging properties, of the bombesin analogue BAY 864367 for PET/CT in a small group of patients with primary and recurrent prostate cancer (PCa). Ten patients with biopsy-proven PCa (5 with primary PCa and 5 with prostate-specific antigen recurrence after radical prostatectomy) were prospectively selected for this exploratory clinical trial with BAY 864367, a new (18)F-labeled bombesin analogue. PET scans were assessed at 6 time points, up to 110 min after intravenous administration of 302 ± 11 MBq of BAY 864367. Imaging results were compared with (18)F-fluorocholine PET/CT scans. Dosimetry was calculated using the OLINDA/EXM software. Three of 5 patients with primary disease showed positive tumor delineation in the prostate, and 2 of 5 patients with biochemical relapse showed a lesion suggestive of recurrence on the BAY 864367 scan. Tumor-to-background ratio averaged 12.9 ± 7.0. The ratio of malignant prostate tissue to normal prostate tissue was 4.4 ± 0.6 in 3 patients with tracer uptake in the primary PCa. Mean effective dose was 4.3 ± 0.3 mSv/patient (range, 3.7-4.9 mSv). BAY 864367, a novel (18)F-labeled bombesin tracer, was successfully investigated in a first-in-man clinical trial of PCa and showed favorable dosimetric values. Additionally, the application was safe and well tolerated. The tracer delineated tumors in a subset of patients, demonstrating the potential of gastrin-releasing-peptide receptor imaging. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Ultrasound-contrast-agent dispersion and velocity imaging for prostate cancer localization.

PubMed

van Sloun, Ruud Jg; Demi, Libertario; Postema, Arnoud W; de la Rosette, Jean Jmch; Wijkstra, Hessel; Mischi, Massimo

2017-01-01

Prostate cancer (PCa) is the second-leading cause of cancer death in men; however, reliable tools for detection and localization are still lacking. Dynamic Contrast Enhanced UltraSound (DCE-US) is a diagnostic tool that is suitable for analysis of vascularization, by imaging an intravenously injected microbubble bolus. The localization of angiogenic vascularization associated with the development of tumors is of particular interest. Recently, methods for the analysis of the bolus convective dispersion process have shown promise to localize angiogenesis. However, independent estimation of dispersion was not possible due to the ambiguity between convection and dispersion. Therefore, in this study we propose a new method that considers the vascular network as a dynamic linear system, whose impulse response can be locally identified. To this end, model-based parameter estimation is employed, that permits extraction of the apparent dispersion coefficient (D), velocity (v), and Péclet number (Pe) of the system. Clinical evaluation using data recorded from 25 patients shows that the proposed method can be applied effectively to DCE-US, and is able to locally characterize the hemodynamics, yielding promising results (receiver-operating-characteristic curve area of 0.84) for prostate cancer localization. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative effectiveness of prostate cancer treatments for patient-centered outcomes: A systematic review and meta-analysis (PRISMA Compliant).

PubMed

Jayadevappa, Ravishankar; Chhatre, Sumedha; Wong, Yu-Ning; Wittink, Marsha N; Cook, Ratna; Morales, Knashawn H; Vapiwala, Neha; Newman, Diane K; Guzzo, Thomas; Wein, Alan J; Malkowicz, Stanley B; Lee, David I; Schwartz, Jerome S; Gallo, Joseph J

2017-05-01

In the context of prostate cancer (PCa) characterized by the multiple alternative treatment strategies, comparative effectiveness analysis is essential for informed decision-making. We analyzed the comparative effectiveness of PCa treatments through systematic review and meta-analysis with a focus on outcomes that matter most to newly diagnosed localized PCa patients. We performed a systematic review of literature published in English from 1995 to October 2016. A search strategy was employed using terms "prostate cancer," "localized," "outcomes," "mortality," "health related quality of life," and "complications" to identify relevant randomized controlled trials (RCTs), prospective, and retrospective studies. For observational studies, only those adjusting for selection bias using propensity-score or instrumental-variables approaches were included. Multivariable adjusted hazard ratio was used to assess all-cause and disease-specific mortality. Funnel plots were used to assess the level of bias. Our search strategy yielded 58 articles, of which 29 were RCTs, 6 were prospective studies, and 23 were retrospective studies. The studies provided moderate data for the patient-centered outcome of mortality. Radical prostatectomy demonstrated mortality benefit compared to watchful waiting (all-cause HR = 0.63 CI = 0.45, 0.87; disease-specific HR = 0.48 CI = 0.40, 0.58), and radiation therapy (all-cause HR = 0.65 CI = 0.57, 0.74; disease-specific HR = 0.51 CI = 0.40, 0.65). However, we had minimal comparative information about tradeoffs between and within treatment for other patient-centered outcomes in the short and long-term. Lack of patient-centered outcomes in comparative effectiveness research in localized PCa is a major hurdle to informed and shared decision-making. More rigorous studies that can integrate patient-centered and intermediate outcomes in addition to mortality are needed.

The Health Effects of Masculine Self-Esteem Following Treatment for Localized Prostate Cancer Among Gay Men

PubMed Central

Talcott, James A.; Heeren, Timothy; de Vries, Brian; Blank, Thomas O.; Clark, Jack A.

2016-01-01

Abstract Purpose: To identify factors associated with masculine self-esteem in gay men following treatment for localized prostate cancer (PCa) and to determine the association between masculine self-esteem, PCa-specific factors, and mental health factors in these patients. Methods: A national cross-sectional survey of gay PCa survivors was conducted in 2010–2011. To be eligible for the study, men needed to be age 50 or older, reside in the United States, self-identify as gay, able to read, write, and speak English, and to have been treated for PCa at least 1 year ago. One hundred eleven men returned surveys. Results: After simultaneously adjusting for the factors in our model, men aged 50–64 years and men aged 65–74 years reported lower masculine self-esteem scores than men aged 75 years or older. Lower scores were also reported by men who reported recent severe stigma. Men who reported feeling comfortable revealing their sexual orientation to their doctor reported higher masculine self-esteem scores than men who were not. The mental component score from the SF-12 was also positively correlated with masculine self-esteem. Conclusion: PCa providers are in a position to reduce feelings of stigma and promote resiliency by being aware that they might have gay patients, creating a supportive environment where gay patients can discuss specific sexual concerns, and engaging patients in treatment decisions. These efforts could help not only in reducing stigma but also in increasing masculine self-esteem, thus greatly influencing gay patients' recovery, quality of life, and compliance with follow-up care. PMID:26698658

A reversible Renilla luciferase protein complementation assay for rapid identification of protein–protein interactions reveals the existence of an interaction network involved in xyloglucan biosynthesis in the plant Golgi apparatus

PubMed Central

Lund, Christian H.; Bromley, Jennifer R.; Stenbæk, Anne; Rasmussen, Randi E.; Scheller, Henrik V.; Sakuragi, Yumiko

2015-01-01

A growing body of evidence suggests that protein–protein interactions (PPIs) occur amongst glycosyltransferases (GTs) required for plant glycan biosynthesis (e.g. cell wall polysaccharides and N-glycans) in the Golgi apparatus, and may control the functions of these enzymes. However, identification of PPIs in the endomembrane system in a relatively fast and simple fashion is technically challenging, hampering the progress in understanding the functional coordination of the enzymes in Golgi glycan biosynthesis. To solve the challenges, we adapted and streamlined a reversible Renilla luciferase protein complementation assay (Rluc-PCA), originally reported for use in human cells, for transient expression in Nicotiana benthamiana. We tested Rluc-PCA and successfully identified luminescence complementation amongst Golgi-localizing GTs known to form a heterodimer (GAUT1 and GAUT7) and those which homooligomerize (ARAD1). In contrast, no interaction was shown between negative controls (e.g. GAUT7, ARAD1, IRX9). Rluc-PCA was used to investigate PPIs amongst Golgi-localizing GTs involved in biosynthesis of hemicelluloses. Although no PPI was identified among six GTs involved in xylan biosynthesis, Rluc-PCA confirmed three previously proposed interactions and identified seven novel PPIs amongst GTs involved in xyloglucan biosynthesis. Notably, three of the novel PPIs were confirmed by a yeast-based split-ubiquitin assay. Finally, Gateway-enabled expression vectors were generated, allowing rapid construction of fusion proteins to the Rluc reporters and epitope tags. Our results show that Rluc-PCA coupled with transient expression in N. benthamiana is a fast and versatile method suitable for analysis of PPIs between Golgi resident proteins in an easy and mid-throughput fashion in planta. PMID:25326916

A reversible Renilla luciferase protein complementation assay for rapid identification of protein-protein interactions reveals the existence of an interaction network involved in xyloglucan biosynthesis in the plant Golgi apparatus

DOE PAGES

Lund, C. H.; Bromley, J. R.; Stenbaek, A.; ...

2014-10-18

A growing body of evidence suggests that protein–protein interactions (PPIs) occur amongst glycosyltransferases (GTs) required for plant glycan biosynthesis (e.g. cell wall polysaccharides and N-glycans) in the Golgi apparatus, and may control the functions of these enzymes. However, identification of PPIs in the endomembrane system in a relatively fast and simple fashion is technically challenging, hampering the progress in understanding the functional coordination of the enzymes in Golgi glycan biosynthesis. To solve the challenges, we adapted and streamlined a reversible Renilla luciferase protein complementation assay (Rluc-PCA), originally reported for use in human cells, for transient expression in Nicotiana benthamiana. Wemore » tested Rluc-PCA and successfully identified luminescence complementation amongst Golgi-localizing GTs known to form a heterodimer (GAUT1 and GAUT7) and those which homooligomerize (ARAD1). In contrast, no interaction was shown between negative controls (e.g. GAUT7, ARAD1, IRX9). Rluc-PCA was used to investigate PPIs amongst Golgi-localizing GTs involved in biosynthesis of hemicelluloses. Although no PPI was identified among six GTs involved in xylan biosynthesis, Rluc-PCA confirmed three previously proposed interactions and identified seven novel PPIs amongst GTs involved in xyloglucan biosynthesis. Notably, three of the novel PPIs were confirmed by a yeast-based split-ubiquitin assay. Finally, Gateway-enabled expression vectors were generated, allowing rapid construction of fusion proteins to the Rluc reporters and epitope tags. In conclusion, our results show that Rluc-PCA coupled with transient expression in N. benthamiana is a fast and versatile method suitable for analysis of PPIs between Golgi resident proteins in an easy and mid-throughput fashion in planta.« less

AXIN2 expression predicts prostate cancer recurrence and regulates invasion and tumor growth.

PubMed

Hu, Brian R; Fairey, Adrian S; Madhav, Anisha; Yang, Dongyun; Li, Meng; Groshen, Susan; Stephens, Craig; Kim, Philip H; Virk, Navneet; Wang, Lina; Martin, Sue Ellen; Erho, Nicholas; Davicioni, Elai; Jenkins, Robert B; Den, Robert B; Xu, Tong; Xu, Yucheng; Gill, Inderbir S; Quinn, David I; Goldkorn, Amir

2016-05-01

Treatment of prostate cancer (PCa) may be improved by identifying biological mechanisms of tumor growth that directly impact clinical disease progression. We investigated whether genes associated with a highly tumorigenic, drug resistant, progenitor phenotype impact PCa biology and recurrence. Radical prostatectomy (RP) specimens (±disease recurrence, N = 276) were analyzed by qRT-PCR to quantify expression of genes associated with self-renewal, drug resistance, and tumorigenicity in prior studies. Associations between gene expression and PCa recurrence were confirmed by bootstrap internal validation and by external validation in independent cohorts (total N = 675) and in silico. siRNA knockdown and lentiviral overexpression were used to determine the effect of gene expression on PCa invasion, proliferation, and tumor growth. Four candidate genes were differentially expressed in PCa recurrence. Of these, low AXIN2 expression was internally validated in the discovery cohort. Validation in external cohorts and in silico demonstrated that low AXIN2 was independently associated with more aggressive PCa, biochemical recurrence, and metastasis-free survival after RP. Functionally, siRNA-mediated depletion of AXIN2 significantly increased invasiveness, proliferation, and tumor growth. Conversely, ectopic overexpression of AXIN2 significantly reduced invasiveness, proliferation, and tumor growth. Low AXIN2 expression was associated with PCa recurrence after RP in our test population as well as in external validation cohorts, and its expression levels in PCa cells significantly impacted invasiveness, proliferation, and tumor growth. Given these novel roles, further study of AXIN2 in PCa may yield promising new predictive and therapeutic strategies. © 2016 Wiley Periodicals, Inc.

Targeting monoamine oxidase A in advanced prostate cancer.

PubMed

Flamand, Vincent; Zhao, Hongjuan; Peehl, Donna M

2010-11-01

Inhibitors of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine, are commonly used to treat neurological conditions including depression. Recently, we and others identified high expression of MAOA in normal basal prostatic epithelium and high-grade primary prostate cancer (PCa). In contrast, MAOA is low in normal secretory prostatic epithelium and low-grade PCa. An irreversible inhibitor of MAOA, clorgyline, induced secretory differentiation in primary cultures of normal basal epithelial cells and high-grade PCa. Furthermore, clorgyline inhibited several oncogenic pathways in PCa cells, suggesting clinical value of MAOA inhibitors as a pro-differentiation and anti-oncogenic therapy for high-risk PCa. Here, we extended our studies to a model of advanced PCa, VCaP cells, which were derived from castration-resistant metastatic PCa and express a high level of MAOA. Growth of VCaP cells in the presence or absence of clorgyline was evaluated in vitro and in vivo. Gene expression changes in response to clorgyline were determined by microarray and validated by quantitative real-time polymerase chain reaction. Treatment with clorgyline in vitro inhibited growth and altered the transcriptional pattern of VCaP cells in a manner consistent with the pro-differentiation and anti-oncogenic effects seen in treated primary PCa cells. Src, beta-catenin, and MAPK oncogenic pathways, implicated in androgen-independent growth and metastasis, were significantly downregulated. Clorgyline treatment of mice bearing VCaP xenografts slowed tumor growth and induced transcriptome changes similar to those noted in vitro. Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa.

From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study

PubMed Central

Aghakhanyan, Gayane; Bonanni, Paolo; Randazzo, Giovanna; Nappi, Sara; Tessarotto, Federica; De Martin, Lara; Frijia, Francesca; De Marchi, Daniele; De Masi, Francesco; Kuppers, Beate; Lombardo, Francesco; Caramella, Davide; Montanaro, Domenico

2016-01-01

Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS. PMID:27626634

The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer

PubMed Central

Munkley, Jennifer; Oltean, Sebastian; Vodák, Daniel; Wilson, Brian T.; Livermore, Karen E.; Zhou, Yan; Star, Eleanor; Floros, Vasileios I.; Johannessen, Bjarne; Knight, Bridget; McCullagh, Paul; McGrath, John; Crundwell, Malcolm; Skotheim, Rolf I.; Robson, Craig N.; Leung, Hing Y.; Harries, Lorna W.; Rajan, Prabhakar; Mills, Ian G.; Elliott, David J.

2015-01-01

Patterns of glycosylation are important in cancer, but the molecular mechanisms that drive changes are often poorly understood. The androgen receptor drives prostate cancer (PCa) development and progression to lethal metastatic castration-resistant disease. Here we used RNA-Seq coupled with bioinformatic analyses of androgen-receptor (AR) binding sites and clinical PCa expression array data to identify ST6GalNAc1 as a direct and rapidly activated target gene of the AR in PCa cells. ST6GalNAc1 encodes a sialytransferase that catalyses formation of the cancer-associated sialyl-Tn antigen (sTn), which we find is also induced by androgen exposure. Androgens induce expression of a novel splice variant of the ST6GalNAc1 protein in PCa cells. This splice variant encodes a shorter protein isoform that is still fully functional as a sialyltransferase and able to induce expression of the sTn-antigen. Surprisingly, given its high expression in tumours, stable expression of ST6GalNAc1 in PCa cells reduced formation of stable tumours in mice, reduced cell adhesion and induced a switch towards a more mesenchymal-like cell phenotype in vitro. ST6GalNAc1 has a dynamic expression pattern in clinical datasets, being significantly up-regulated in primary prostate carcinoma but relatively down-regulated in established metastatic tissue. ST6GalNAc1 is frequently upregulated concurrently with another important glycosylation enzyme GCNT1 previously associated with prostate cancer progression and implicated in Sialyl Lewis X antigen synthesis. Together our data establishes an androgen-dependent mechanism for sTn antigen expression in PCa, and are consistent with a general role for the androgen receptor in driving important coordinate changes to the glycoproteome during PCa progression. PMID:26452038

Focal therapy: patients, interventions, and outcomes--a report from a consensus meeting.

PubMed

Donaldson, Ian A; Alonzi, Roberto; Barratt, Dean; Barret, Eric; Berge, Viktor; Bott, Simon; Bottomley, David; Eggener, Scott; Ehdaie, Behfar; Emberton, Mark; Hindley, Richard; Leslie, Tom; Miners, Alec; McCartan, Neil; Moore, Caroline M; Pinto, Peter; Polascik, Thomas J; Simmons, Lucy; van der Meulen, Jan; Villers, Arnauld; Willis, Sarah; Ahmed, Hashim U

2015-04-01

Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field. To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design. Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health. Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level. Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging-targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3+3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus. The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy. In this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Focal Therapy: Patients, Interventions, and Outcomes—A Report from a Consensus Meeting

PubMed Central

Donaldson, Ian A.; Alonzi, Roberto; Barratt, Dean; Barret, Eric; Berge, Viktor; Bott, Simon; Bottomley, David; Eggener, Scott; Ehdaie, Behfar; Emberton, Mark; Hindley, Richard; Leslie, Tom; Miners, Alec; McCartan, Neil; Moore, Caroline M.; Pinto, Peter; Polascik, Thomas J.; Simmons, Lucy; van der Meulen, Jan; Villers, Arnauld; Willis, Sarah; Ahmed, Hashim U.

2015-01-01

Background Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field. Objective To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design. Design, setting, and participants Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health. Outcome measurements and statistical analysis Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level. Results and limitations Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging–targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5 mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3 + 3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus. Conclusions The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy. Patient summary In this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer. PMID:25281389

Prostate-specific membrane antigen targeted imaging and therapy of prostate cancer using a PSMA inhibitor as a homing ligand.

PubMed

Kularatne, Sumith A; Wang, Kevin; Santhapuram, Hari-Krishna R; Low, Philip S

2009-01-01

Prostate cancer (PCa) is a major cause of mortality and morbidity in Western society today. Current methods for detecting PCa are limited, leaving most early malignancies undiagnosed and sites of metastasis in advanced disease undetected. Major deficiencies also exist in the treatment of PCa, especially metastatic disease. In an effort to improve both detection and therapy of PCa, we have developed a PSMA-targeted ligand that delivers attached imaging and therapeutic agents selectively to PCa cells without targeting normal cells. The PSMA-targeted radioimaging agent (DUPA-(99m)Tc) was found to bind PSMA-positive human PCa cells (LNCaP cell line) with nanomolar affinity (K(D) = 14 nM). Imaging and biodistribution studies revealed that DUPA-(99m)Tc localizes primarily to LNCaP cell tumor xenografts in nu/nu mice (% injected dose/gram = 11.3 at 4 h postinjection; tumor-to-muscle ratio = 75:1). Two PSMA-targeted optical imaging agents (DUPA-FITC and DUPA-rhodamine B) were also shown to efficiently label PCa cells and to internalize and traffic to intracellular endosomes. A PSMA-targeted chemotherapeutic agent (DUPA-TubH) was demonstrated to kill PSMA-positive LNCaP cells in culture (IC(50) = 3 nM) and to eliminate established tumor xenografts in nu/nu mice with no detectable weight loss. Blockade of tumor targeting upon administration of excess PSMA inhibitor (PMPA) and the absence of targeting to PSMA-negative tumors confirmed the specificity of each of the above targeted reagents for PSMA. Tandem use of the imaging and therapeutic agents targeted to the same receptor could allow detection, staging, monitoring, and treatment of PCa with improved accuracy and efficacy.

Statin use and risk of prostate cancer: a Danish population-based case-control study, 1997-2010.

PubMed

Jespersen, Christina G; Nørgaard, Mette; Friis, Søren; Skriver, Charlotte; Borre, Michael

2014-02-01

Conflicting evidence has suggested that statins possess chemopreventive properties against prostate cancer (PCa). Therefore, we examined the association between statin use and risk of PCa in a Denmark-based case-control study. We identified 42,480 patients diagnosed with incident PCa during 1997-2010 from a national cancer registry. Five age-matched population controls (n=212,400) were selected for each case using risk-set sampling. Statin use from 1996 to the index date was obtained from the National Prescription Registry. Odds ratios (ORs) adjusted for age, comorbidity, non-steroidal anti-inflammatory drug use, and educational level for PCa associated with statin use, were computed using conditional logistic regression. Analyses were stratified by duration of statin use (0-1, 2-4, 5-9, or ≥10 years), stage of PCa (localized or advanced), and type of statin used (lipophilic or hydrophilic). In total, 7915 patients (19%) and 39,384 controls (19%) redeemed statin prescriptions prior to the index date. Overall, statin users had a 6% lower risk of PCa compared with non-users [adjusted OR (ORa), 0.94; 95% confidence interval (CI), 0.91-0.97]. Risk estimates did not differ substantially by duration or type of statin used. Slightly larger statin use-associated risk reductions were observed for advanced PCa (ORa, 0.90; 95% CI, 0.85-0.96) and with statin use ≥10 years (ORa, 0.78; 95% CI, 0.65-0.95). Statin use was associated with a risk reduction overall (6%) and, specifically with advanced PCa (10%). Differences in diagnostic measures and residual confounding by socioeconomic parameters may have influenced our results. Copyright © 2013 Elsevier Ltd. All rights reserved.

Physical activity in relation to risk of prostate cancer: a systematic review and meta-analysis.

PubMed

Benke, I N; Leitzmann, M F; Behrens, G; Schmid, D

2018-05-01

Prostate cancer (PCa) is one of the most common cancers among men, yet little is known about its modifiable risk and protective factors. This study aims to quantitatively summarize observational studies relating physical activity (PA) to PCa incidence and mortality. Published articles pertaining to PA and PCa incidence and mortality were retrieved in July 2017 using the Medline and EMBASE databases. The literature review yielded 48 cohort studies and 24 case-control studies with a total of 151 748 PCa cases. The mean age of the study participants at baseline was 61 years. In random-effects models, comparing the highest versus the lowest level of overall PA showed a summary relative risk (RR) estimate for total PCa incidence close to the null [RR = 0.99, 95% confidence interval (CI) = 0.94-1.04]. The corresponding RRs for advanced and non-advanced PCa were 0.92 (95% CI = 0.80-1.06) and 0.95 (95% CI = 0.85-1.07), respectively. We noted a statistically significant inverse association between long-term occupational activity and total PCa (RR = 0.83, 95% CI = 0.71-0.98, n studies = 13), although that finding became statistically non-significant when individual studies were removed from the analysis. When evaluated by cancer subtype, an inverse association with long-term occupational activity was noted for non-advanced/non-aggressive PCa (RR = 0.51, 95% CI = 0.37-0.71, n studies = 2) and regular recreational activity was inversely related to advanced/aggressive PCa (RR = 0.75, 95% CI = 0.60-0.95, n studies = 2), although these observations are based on a low number of studies. Moreover, PA after diagnosis was related to reduced risk of PCa mortality among survivors of PCa (summary RR based on four studies = 0.69, 95% CI = 0.55-0.85). Whether PA protects against PCa remains elusive. Further investigation taking into account the complex clinical and pathologic nature of PCa is needed to clarify the PA and PCa incidence relation. Moreover, future studies are needed to confirm whether PA after diagnosis reduces risk of PCa mortality.

Statistical modeling of interfractional tissue deformation and its application in radiation therapy planning

NASA Astrophysics Data System (ADS)

Vile, Douglas J.

In radiation therapy, interfraction organ motion introduces a level of geometric uncertainty into the planning process. Plans, which are typically based upon a single instance of anatomy, must be robust against daily anatomical variations. For this problem, a model of the magnitude, direction, and likelihood of deformation is useful. In this thesis, principal component analysis (PCA) is used to statistically model the 3D organ motion for 19 prostate cancer patients, each with 8-13 fractional computed tomography (CT) images. Deformable image registration and the resultant displacement vector fields (DVFs) are used to quantify the interfraction systematic and random motion. By applying the PCA technique to the random DVFs, principal modes of random tissue deformation were determined for each patient, and a method for sampling synthetic random DVFs was developed. The PCA model was then extended to describe the principal modes of systematic and random organ motion for the population of patients. A leave-one-out study tested both the systematic and random motion model's ability to represent PCA training set DVFs. The random and systematic DVF PCA models allowed the reconstruction of these data with absolute mean errors between 0.5-0.9 mm and 1-2 mm, respectively. To the best of the author's knowledge, this study is the first successful effort to build a fully 3D statistical PCA model of systematic tissue deformation in a population of patients. By sampling synthetic systematic and random errors, organ occupancy maps were created for bony and prostate-centroid patient setup processes. By thresholding these maps, PCA-based planning target volume (PTV) was created and tested against conventional margin recipes (van Herk for bony alignment and 5 mm fixed [3 mm posterior] margin for centroid alignment) in a virtual clinical trial for low-risk prostate cancer. Deformably accumulated delivered dose served as a surrogate for clinical outcome. For the bony landmark setup subtrial, the PCA PTV significantly (p<0.05) reduced D30, D20, and D5 to bladder and D50 to rectum, while increasing rectal D20 and D5. For the centroid-aligned setup, the PCA PTV significantly reduced all bladder DVH metrics and trended to lower rectal toxicity metrics. All PTVs covered the prostate with the prescription dose.

Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer: Models, Mechanisms and Questions

PubMed Central

Nyquist, Michael D.; Schweizer, Michael T.; Balk, Stephen P.; Corey, Eva; Plymate, Stephen; Nelson, Peter S.; Mostaghel, Elahe A.

2017-01-01

Since Huggins defined the androgen-sensitive nature of prostate cancer (PCa), suppression of systemic testosterone (T) has remained the most effective initial therapy for advanced disease although progression inevitably occurs. From the inception of clinical efforts to suppress androgen receptor (AR) signaling by reducing AR ligands, it was also recognized that administration of T in men with castration-resistant prostate cancer (CRPC) could result in substantial clinical responses. Data from preclinical models have reproducibly shown biphasic responses to T administration, with proliferation at low androgen concentrations and growth inhibition at supraphysiological T concentrations. Many questions regarding the biphasic response of PCa to androgen treatment remain, primarily regarding the mechanisms driving these responses and how best to exploit the biphasic phenomenon clinically. Here we review the preclinical and clinical data on high dose androgen growth repression and discuss cellular pathways and mechanisms likely to be involved in mediating this response. Although meaningful clinical responses have now been observed in men with PCa treated with high dose T, not all men respond, leading to questions regarding which tumor characteristics promote response or resistance, and highlighting the need for studies designed to determine the molecular mechanism(s) driving these responses and identify predictive biomarkers. PMID:29210989

Inflammation: an important parameter in the search of prostate cancer biomarkers

PubMed Central

2014-01-01

Background A more specific and early diagnostics for prostate cancer (PCa) is highly desirable. In this study, being inflammation the focus of our effort, serum protein profiles were analyzed in order to investigate if this parameter could interfere with the search of discriminating proteins between PCa and benign prostatic hyperplasia (BPH). Methods Patients with clinical suspect of PCa and candidates for trans-rectal ultrasound guided prostate biopsy (TRUS) were enrolled. Histological specimens were examined in order to grade and classify the tumor, identify BPH and detect inflammation. Surface Enhanced Laser Desorption/Ionization-Time of Flight-Mass Spectrometry (SELDI-ToF-MS) and two-dimensional gel electrophoresis (2-DE) coupled with Liquid Chromatography-MS/MS (LC-MS/MS) were used to analyze immuno-depleted serum samples from patients with PCa and BPH. Results The comparison between PCa (with and without inflammation) and BPH (with and without inflammation) serum samples by SELDI-ToF-MS analysis did not show differences in protein expression, while changes were only observed when the concomitant presence of inflammation was taken into consideration. In fact, when samples with histological sign of inflammation were excluded, 20 significantly different protein peaks were detected. Subsequent comparisons (PCa with inflammation vs PCa without inflammation, and BPH with inflammation vs BPH without inflammation) showed that 16 proteins appeared to be modified in the presence of inflammation, while 4 protein peaks were not modified. With 2-DE analysis, comparing PCa without inflammation vs PCa with inflammation, and BPH without inflammation vs the same condition in the presence of inflammation, were identified 29 and 25 differentially expressed protein spots, respectively. Excluding samples with inflammation the comparison between PCa vs BPH showed 9 unique PCa proteins, 4 of which overlapped with those previously identified in the presence of inflammation, while other 2 were new proteins, not identified in our previous comparisons. Conclusions The present study indicates that inflammation might be a confounding parameter during the proteomic research of candidate biomarkers of PCa. These results indicate that some possible biomarker-candidate proteins are strongly influenced by the presence of inflammation, hence only a well-selected protein pattern should be considered for potential marker of PCa. PMID:24944525

Multiparametric MRI Apparent Diffusion Coefficient (ADC) Accuracy in Diagnosing Clinically Significant Prostate Cancer.

PubMed

Pepe, Pietro; D'Urso, Davide; Garufi, Antonio; Priolo, Giandomenico; Pennisi, Michele; Russo, Giorgio; Sabini, Maria Gabriella; Valastro, Lucia Maria; Galia, Antonio; Fraggetta, Filippo

2017-01-01

To evaluate the accuracy of multiparametric magnetic resonance imaging apparent diffusion coefficient (mpMRI ADC) in the diagnosis of clinically significant prostate cancer (PCa). From January 2016 to December 2016, 44 patients who underwent radical prostatectomy for PCa and mpMRI lesions suggestive of cancer were retrospectively evaluated at definitive specimen. The accuracy of suspicious mpMRI prostate imaging reporting and data system (PI-RADS ≥3) vs. ADC values in the diagnosis of Gleason score ≥7 was evaluated. Receiver operating characteristics (ROC) curve analysis gave back an ADC threshold of 0.747×10 -3 mm 2 /s to separate between Gleason Score 6 and ≥7. The diagnostic accuracy of ADC value (cut-off 0.747×10 -3 mm 2 /s) vs. PI-RADS score ≥3 in diagnosing PCa with Gleason score ≥7 was equal to 84% vs. 63.6% with an area under the curve (AUC) ROC of 0.81 vs. 0.71, respectively. ADC evaluation could support clinicians in decision making of patients with PI-RADS score <3 at risk for PCa. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Prostate cancer: computer-aided diagnosis on multiparametric MRI

NASA Astrophysics Data System (ADS)

Marin, Laura; Racoceanu, Daniel; Renard Penna, Raphaele; Ezziane, Malek

2017-11-01

Prostate cancer (PCa) is one of the most common cancers in men, being also the second most deadly cancer after lung cancer. There is increasing interest in active surveillance and minimally invasive focal therapies in PCa to avoid morbidities associated with whole gland therapy. Tumor volume represents an essential prognostic factor of PCa and the definition of index lesion volume is critical for appropriate decision making, especially for image guide focal treatment or in case of active surveillance. Multi-parametric Magnetic Resonance Imaging (mp-MRI) is the modality of choice for the detection and the localization of PCa foci. However, little has been published on mp-MRI accuracy in determining PCa volume, especially at 3T. There is insufficient evidence and no consensus to determine which of the methods for measuring volume is optimal. The objective of this study concerns the elaboration of an algorithm for automatic interpretation of mp-MRI. We determine the accuracy of the proposed method by comparing the prostate tumor volume issued from the automated volumetric mp-MRI measurements of the tumoral region, with manual and semi-automated volumetric measurements done by and respectively with radiologists. Information issued from whole mount histopathology is used to validate the whole approach.

Basic visual function and cortical thickness patterns in posterior cortical atrophy.

PubMed

Lehmann, Manja; Barnes, Josephine; Ridgway, Gerard R; Wattam-Bell, John; Warrington, Elizabeth K; Fox, Nick C; Crutch, Sebastian J

2011-09-01

Posterior cortical atrophy (PCA) is characterized by a progressive decline in higher-visual object and space processing, but the extent to which these deficits are underpinned by basic visual impairments is unknown. This study aimed to assess basic and higher-order visual deficits in 21 PCA patients. Basic visual skills including form detection and discrimination, color discrimination, motion coherence, and point localization were measured, and associations and dissociations between specific basic visual functions and measures of higher-order object and space perception were identified. All participants showed impairment in at least one aspect of basic visual processing. However, a number of dissociations between basic visual skills indicated a heterogeneous pattern of visual impairment among the PCA patients. Furthermore, basic visual impairments were associated with particular higher-order object and space perception deficits, but not with nonvisual parietal tasks, suggesting the specific involvement of visual networks in PCA. Cortical thickness analysis revealed trends toward lower cortical thickness in occipitotemporal (ventral) and occipitoparietal (dorsal) regions in patients with visuoperceptual and visuospatial deficits, respectively. However, there was also a lot of overlap in their patterns of cortical thinning. These findings suggest that different presentations of PCA represent points in a continuum of phenotypical variation.

Markerless gating for lung cancer radiotherapy based on machine learning techniques

NASA Astrophysics Data System (ADS)

Lin, Tong; Li, Ruijiang; Tang, Xiaoli; Dy, Jennifer G.; Jiang, Steve B.

2009-03-01

In lung cancer radiotherapy, radiation to a mobile target can be delivered by respiratory gating, for which we need to know whether the target is inside or outside a predefined gating window at any time point during the treatment. This can be achieved by tracking one or more fiducial markers implanted inside or near the target, either fluoroscopically or electromagnetically. However, the clinical implementation of marker tracking is limited for lung cancer radiotherapy mainly due to the risk of pneumothorax. Therefore, gating without implanted fiducial markers is a promising clinical direction. We have developed several template-matching methods for fluoroscopic marker-less gating. Recently, we have modeled the gating problem as a binary pattern classification problem, in which principal component analysis (PCA) and support vector machine (SVM) are combined to perform the classification task. Following the same framework, we investigated different combinations of dimensionality reduction techniques (PCA and four nonlinear manifold learning methods) and two machine learning classification methods (artificial neural networks—ANN and SVM). Performance was evaluated on ten fluoroscopic image sequences of nine lung cancer patients. We found that among all combinations of dimensionality reduction techniques and classification methods, PCA combined with either ANN or SVM achieved a better performance than the other nonlinear manifold learning methods. ANN when combined with PCA achieves a better performance than SVM in terms of classification accuracy and recall rate, although the target coverage is similar for the two classification methods. Furthermore, the running time for both ANN and SVM with PCA is within tolerance for real-time applications. Overall, ANN combined with PCA is a better candidate than other combinations we investigated in this work for real-time gated radiotherapy.

Liposome bupivacaine for improvement in economic outcomes and opioid burden in GI surgery: IMPROVE Study pooled analysis.

PubMed

Cohen, Stephen M; Vogel, Jon D; Marcet, Jorge E; Candiotti, Keith A

2014-01-01

Postsurgical pain management remains a significant challenge. Liposome bupivacaine, as part of a multimodal analgesic regimen, has been shown to significantly reduce postsurgical opioid consumption, hospital length of stay (LOS), and hospitalization costs in gastrointestinal (GI) surgery, compared with intravenous (IV) opioid-based patient-controlled analgesia (PCA). Pooled results from open-label studies comparing a liposome bupivacaine-based multimodal analgesic regimen with IV opioid PCA were analyzed. Patients (n=191) who underwent planned surgery and received study drug (IV opioid PCA, n=105; multimodal analgesia, n=86) were included. Liposome bupivacaine-based multimodal analgesia compared with IV opioid PCA significantly reduced mean (standard deviation [SD]) postsurgical opioid consumption (38 [55] mg versus [vs] 96 [85] mg; P<0.0001), postsurgical LOS (median 2.9 vs 4.3 days; P<0.0001), and mean hospitalization costs (US$8,271 vs US$10,726; P=0.0109). The multimodal analgesia group reported significantly fewer patients with opioid-related adverse events (AEs) than the IV opioid PCA group (P=0.0027); there were no significant between-group differences in patient satisfaction scores at 30 days. A liposome bupivacaine-based multimodal analgesic regimen was associated with significantly less opioid consumption, opioid-related AEs, and better health economic outcomes compared with an IV opioid PCA-based regimen in patients undergoing GI surgery. This pooled analysis is based on data from Phase IV clinical trials registered on the US National Institutes of Health www.ClinicalTrials.gov database under study identifiers NCT01460485, NCT01507220, NCT01507233, NCT01509638, NCT01509807, NCT01509820, NCT01461122, NCT01461135, NCT01534988, and NCT01507246.

Neoadjuvant luteinizing-hormone-releasing hormone agonist plus low-dose estramustine phosphate improves prostate-specific antigen-free survival in high-risk prostate cancer patients: a propensity score-matched analysis.

PubMed

Koie, Takuya; Mitsuzuka, Koji; Yoneyama, Takahiro; Narita, Shintaro; Kawamura, Sadafumi; Kaiho, Yasuhiro; Tsuchiya, Norihiko; Tochigi, Tatsuo; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara; Yoneyama, Tohru; Tobisawa, Yuki

2015-10-01

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with a neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). In the present study, we used a retrospective design via propensity score matching to elucidate the clinical benefit of neoadjuvant LHRH+EMP for high-risk Pca. The Michinoku Urological Cancer Study Group database contained data for 1,268 consecutive Pca patients treated with RP alone at 4 institutions between April 2000 and March 2011 (RP alone group). In the RP alone group, we identified 386 high-risk Pca patients. The neoadjuvant LHRH+EMP group included 274 patients with high-risk Pca treated between September 2005 and November 2013 at Hirosaki University. Neoadjuvant LHRH+EMP therapy included LHRH and EMP administration at a dose of 280 mg/day for 6 months before RP. The outcome measures were overall survival (OS) and BRFS. The propensity score-matched analysis indicated 210 matched pairs from both groups. The 5-year BRFS rates were 90.4 and 65.8 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P < 0.0001). The 5-year OS rates were 100 and 96.1 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P = 0.110). Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP appeared to reduce the risk of biochemical recurrence. A prospective randomized study is warranted to determine the clinical implications of the neoadjuvant therapy described here.

PI-RADS v2 and ADC values: is there room for improvement?

PubMed

Jordan, Eric J; Fiske, Charles; Zagoria, Ronald; Westphalen, Antonio C

2018-03-17

To determine the diagnostic accuracy of ADC values in combination with PI-RADS v2 for the diagnosis of clinically significant prostate cancer (CS-PCa) compared to PI-RADS v2 alone. This retrospective study included 155 men whom underwent 3-Tesla prostate MRI and subsequent MR/US fusion biopsies at a single non-academic center from 11/2014 to 3/2016. All scans were performed with a surface coil and included T2, diffusion-weighted, and dynamic contrast-enhanced sequences. Suspicious findings were classified using Prostate Imaging Reporting and Data System (PI-RADS) v2 and targeted using MR/US fusion biopsies. Mixed-effect logistic regression analyses were used to determine the ability of PIRADS v2 alone and combined with ADC values to predict CS-PCa. As ADC categories are more practical in clinical situations than numeric values, an additional model with ADC categories of ≤ 800 and > 800 was performed. A total of 243 suspicious lesions were included, 69 of which were CS-PCa, 34 were Gleason score 3+3 PCa, and 140 were negative. The overall PIRADS v2 score, ADC values, and ADC categories are independent statistically significant predictors of CS-PCa (p < 0.001). However, the area under the ROC of PIRADS v2 alone and PIRADS v2 with ADC categories are significantly different in both peripheral and transition zone lesions (p = 0.026 and p = 0.03, respectively) Further analysis of the ROC curves also shows that the main benefit of utilizing ADC values or categories is better discrimination of PI-RADS v2 4 lesions. ADC values and categories help to diagnose CS-PCa when lesions are assigned a PI-RADS v2 score of 4.

CDO1 promoter methylation is associated with gene silencing and is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients.

PubMed

Meller, Sebastian; Zipfel, Lisa; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Majores, Michael; Stein, Johannes; Sailer, Verena; Jung, Maria; Kristiansen, Glen; Dietrich, Dimo

2016-12-01

Molecular biomarkers may facilitate the distinction between aggressive and clinically insignificant prostate cancer (PCa), thereby potentially aiding individualized treatment. We analyzed cysteine dioxygenase 1 (CDO1) promoter methylation and mRNA expression in order to evaluate its potential as prognostic biomarker. CDO1 methylation and mRNA expression were determined in cell lines and formalin-fixed paraffin-embedded prostatectomy specimens from a first cohort of 300 PCa patients using methylation-specific qPCR and qRT-PCR. Univariate and multivariate Cox proportional hazards and Kaplan-Meier analyses were performed to evaluate biochemical recurrence (BCR)-free survival. Results were confirmed in an independent second cohort comprising 498 PCa cases. Methylation and mRNA expression data from the second cohort were generated by The Cancer Genome Atlas (TCGA) Research Network by means of Infinium HumanMethylation450 BeadChip and RNASeq. CDO1 was hypermethylated in PCa compared to normal adjacent tissues and benign prostatic hyperplasia (P < 0.001) and was associated with reduced gene expression (ρ = -0.91, P = 0.005). Using two different methodologies for methylation quantification, high CDO1 methylation as continuous variable was associated with BCR in univariate analysis (first cohort: HR = 1.02, P = 0.002, 95% CI [1.01-1.03]; second cohort: HR = 1.02, P = 0.032, 95% CI [1.00-1.03]) but failed to reach statistical significance in multivariate analysis. CDO1 promoter methylation is involved in gene regulation and is a potential prognostic biomarker for BCR-free survival in PCa patients following radical prostatectomy. Further studies are needed to validate CDO1 methylation assays and to evaluate the clinical utility of CDO1 methylation for the management of PCa.

Release kinetics of esterified p-coumaric acid and ferulic acid from rice straw in mild alkaline solution.

PubMed

Linh, Tran Ngoc; Fujita, Hirokata; Sakoda, Akiyoshi

2017-05-01

The release kinetics of esterified p-coumaric acid (PCA) and ferulic acid (FA) from rice straw under a mild alkaline condition were investigated to collect fundamental data for the design of a recovery process. The results showed that the straw size, NaOH concentration, and temperature were the key parameters governing release kinetics. The analysis demonstrated that FA is released considerably faster than PCA. The close relationship between lignin and the PCA dissolution indicates a reciprocal and/or simultaneous release. Moreover, PCA is broadly distributed in the lignin network but tends to be located more densely in the lignin fraction which is not easily solubilized by alkaline treatment. In contrast, the release of FA is strongly affected by removal of lignin fraction which is easily solubilized. These results suggest that the release kinetics are controlled by the accessibility of NaOH to their ester sites in the lignin/hemicellulose network, and by their localization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Epigenetic regulation of EFEMP1 in prostate cancer: biological relevance and clinical potential

PubMed Central

Almeida, Mafalda; Costa, Vera L; Costa, Natália R; Ramalho-Carvalho, João; Baptista, Tiago; Ribeiro, Franclim R; Paulo, Paula; Teixeira, Manuel R; Oliveira, Jorge; Lothe, Ragnhild A; Lind, Guro E; Henrique, Rui; Jerónimo, Carmen

2014-01-01

Epigenetic alterations are common in prostate cancer (PCa) and seem to contribute decisively to its initiation and progression. Moreover, aberrant promoter methylation is a promising biomarker for non-invasive screening. Herein, we sought to characterize EFEMP1 as biomarker for PCa, unveiling its biological relevance in prostate carcinogenesis. Microarray analyses of treated PCa cell lines and primary tissues enabled the selection of differentially methylated genes, among which EFEMP1 was further validated by MSP and bisulfite sequencing. Assessment of biomarker performance was accomplished by qMSP. Expression analysis of EFEMP1 and characterization of histone marks were performed in tissue samples and cancer cell lines to determine the impact of epigenetic mechanisms on EFEMP1 transcriptional regulation. Phenotypic assays, using transfected cell lines, permitted the evaluation of EFEMP1’s role in PCa development. EFEMP1 methylation assay discriminated PCa from normal prostate tissue (NPT; P < 0.001, Kruskall–Wallis test) and renal and bladder cancers (96% sensitivity and 98% specificity). EFEMP1 transcription levels inversely correlated with promoter methylation and histone deacetylation, suggesting that both epigenetic mechanisms are involved in gene regulation. Phenotypic assays showed that EFEMP1 de novo expression reduces malignant phenotype of PCa cells. EFEMP1 promoter methylation is prevalent in PCa and accurately discriminates PCa from non-cancerous prostate tissues and other urological neoplasms. This epigenetic alteration occurs early in prostate carcinogenesis and, in association with histone deacetylation, progressively leads to gene down-regulation, fostering cell proliferation, invasion and evasion of apoptosis. PMID:25211630

Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report.

PubMed

Francio, Vinicius T; Boesch, Ron; Tunning, Michael

2015-03-01

Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient's perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option.

[The percutaneous effect of a heparin-allantoin-dexpanthenol combination in a specific ointment base. Anti-allergic, anti-inflammatory effect in the PCA test in the rat].

PubMed

Rudolph, C; Tauschel, H D

1984-01-01

Local application of a heparin-allantoin-dexpanthenol (Hepathrombin-Adenylchemie) ointment to rats 15 min prior to induction of a passive cutaneous anaphylaxis (PCA) reaction inhibits the anaphylactic reaction as compared to the ointment base. Also, the Evans Blue content as a measure for vascular permeability and the oedema weights are reduced under the heparin containing ointment. The antiallergic/antiinflammatory effect is probably due to heparin.

Using the prostate imaging reporting and data system version 2 (PI-RIDS v2) to detect prostate cancer can prevent unnecessary biopsies and invasive treatment.

PubMed

Liu, Chang; Liu, Shi-Liang; Wang, Zhi-Xian; Yu, Kai; Feng, Chun-Xiang; Ke, Zan; Wang, Liang; Zeng, Xiao-Yong

2018-04-13

Prostate cancer (PCa) is one of the most common cancers among men globally. The authors aimed to evaluate the ability of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) to classify men with PCa, clinically significant PCa (CSPCa), or no PCa, especially among those with serum total prostate-specific antigen (tPSA) levels in the "gray zone" (4-10 ng ml -1 ). A total of 308 patients (355 lesions) were enrolled in this study. Diagnostic efficiency was determined. Univariate and multivariate analyses, receiver operating characteristic curve analysis, and decision curve analysis were performed to determine and compare the predictors of PCa and CSPCa. The results suggested that PI-RADS v2, tPSA, and prostate-specific antigen density (PSAD) were independent predictors of PCa and CSPCa. A PI-RADS v2 score ≥4 provided high negative predictive values (91.39% for PCa and 95.69% for CSPCa). A model of PI-RADS combined with PSA and PSAD helped to define a high-risk group (PI-RADS score = 5 and PSAD ≥0.15 ng ml -1 cm -3 , with tPSA in the gray zone, or PI-RADS score ≥4 with high tPSA level) with a detection rate of 96.1% for PCa and 93.0% for CSPCa while a low-risk group with a detection rate of 6.1% for PCa and 2.2% for CSPCa. It was concluded that the PI-RADS v2 could be used as a reliable and independent predictor of PCa and CSPCa. The combination of PI-RADS v2 score with PSA and PSAD could be helpful in the prediction and diagnosis of PCa and CSPCa and, thus, may help in preventing unnecessary invasive procedures.

SU-F-R-41: Regularized PCA Can Model Treatment-Related Changes in Head and Neck Patients Using Daily CBCTs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chetvertkov, M; Henry Ford Health System, Detroit, MI; Siddiqui, F

2016-06-15

Purpose: To use daily cone beam CTs (CBCTs) to develop regularized principal component analysis (PCA) models of anatomical changes in head and neck (H&N) patients, to guide replanning decisions in adaptive radiation therapy (ART). Methods: Known deformations were applied to planning CT (pCT) images of 10 H&N patients to model several different systematic anatomical changes. A Pinnacle plugin was used to interpolate systematic changes over 35 fractions, generating a set of 35 synthetic CTs for each patient. Deformation vector fields (DVFs) were acquired between the pCT and synthetic CTs and random fraction-to-fraction changes were superimposed on the DVFs. Standard non-regularizedmore » and regularized patient-specific PCA models were built using the DVFs. The ability of PCA to extract the known deformations was quantified. PCA models were also generated from clinical CBCTs, for which the deformations and DVFs were not known. It was hypothesized that resulting eigenvectors/eigenfunctions with largest eigenvalues represent the major anatomical deformations during the course of treatment. Results: As demonstrated with quantitative results in the supporting document regularized PCA is more successful than standard PCA at capturing systematic changes early in the treatment. Regularized PCA is able to detect smaller systematic changes against the background of random fraction-to-fraction changes. To be successful at guiding ART, regularized PCA should be coupled with models of when anatomical changes occur: early, late or throughout the treatment course. Conclusion: The leading eigenvector/eigenfunction from the both PCA approaches can tentatively be identified as a major systematic change during radiotherapy course when systematic changes are large enough with respect to random fraction-to-fraction changes. In all cases the regularized PCA approach appears to be more reliable at capturing systematic changes, enabling dosimetric consequences to be projected once trends are established early in the treatment course. This work is supported in part by a grant from Varian Medical Systems, Palo Alto, CA.« less

Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers-An Explorative Concept Study.

PubMed

Neuhaus, Jochen; Schiffer, Eric; Mannello, Ferdinando; Horn, Lars-Christian; Ganzer, Roman; Stolzenburg, Jens-Uwe

2017-05-04

Previously, we described prostate cancer (PCa) detection (83% sensitivity; 67% specificity) in seminal plasma by CE-MS/MS. Moreover, advanced disease was distinguished from organ-confined tumors with 80% sensitivity and 82% specificity. The discovered biomarkers were naturally occurring fragments of larger seminal proteins, predominantly semenogelin 1 and 2, representing endpoints of the ejaculate liquefaction. Here we identified proteases putatively involved in PCa specific protein cleavage, and examined gene expression and tissue protein levels, jointly with cell localization in normal prostate (nP), benign prostate hyperplasia (BPH), seminal vesicles and PCa using qPCR, Western blotting and confocal laser scanning microscopy. We found differential gene expression of chymase (CMA1), matrix metalloproteinases (MMP3, MMP7), and upregulation of MMP14 and tissue inhibitors (TIMP1 and TIMP2) in BPH. In contrast tissue protein levels of MMP14 were downregulated in PCa. MMP3/TIMP1 and MMP7/TIMP1 ratios were decreased in BPH. In seminal vesicles, we found low-level expression of most proteases and, interestingly, we also detected TIMP1 and low levels of TIMP2. We conclude that MMP3 and MMP7 activity is different in PCa compared to BPH due to fine regulation by their inhibitor TIMP1. Our findings support the concept of seminal plasma biomarkers as non-invasive tool for PCa detection and risk stratification.

Localized Principal Component Analysis based Curve Evolution: A Divide and Conquer Approach

PubMed Central

Appia, Vikram; Ganapathy, Balaji; Yezzi, Anthony; Faber, Tracy

2014-01-01

We propose a novel localized principal component analysis (PCA) based curve evolution approach which evolves the segmenting curve semi-locally within various target regions (divisions) in an image and then combines these locally accurate segmentation curves to obtain a global segmentation. The training data for our approach consists of training shapes and associated auxiliary (target) masks. The masks indicate the various regions of the shape exhibiting highly correlated variations locally which may be rather independent of the variations in the distant parts of the global shape. Thus, in a sense, we are clustering the variations exhibited in the training data set. We then use a parametric model to implicitly represent each localized segmentation curve as a combination of the local shape priors obtained by representing the training shapes and the masks as a collection of signed distance functions. We also propose a parametric model to combine the locally evolved segmentation curves into a single hybrid (global) segmentation. Finally, we combine the evolution of these semilocal and global parameters to minimize an objective energy function. The resulting algorithm thus provides a globally accurate solution, which retains the local variations in shape. We present some results to illustrate how our approach performs better than the traditional approach with fully global PCA. PMID:25520901

64Cu-PSMA-617 PET/CT Imaging of Prostate Adenocarcinoma: First In-Human Studies.

PubMed

Grubmüller, Bernhard; Baum, Richard P; Capasso, Enza; Singh, Aviral; Ahmadi, Yasaman; Knoll, Peter; Floth, Andreas; Righi, Sergio; Zandieh, Shahin; Meleddu, Carlo; Shariat, Shahrokh F; Klingler, Hans Christoph; Mirzaei, Siroos

2016-10-07

The prostate-specific membrane antigen (PSMA) is a cell surface protein, which is overexpressed in nearly all cases of prostate cancer (PCa). PET imaging with 68 Ga-PSMA-HBED-CC has recently found widespread application in the diagnosis of recurrent PCa. In this study, the diagnostic potential of 64 Cu-labeled PSMA ligand (PSMA-617) PET in patients with PCa has been investigated. The study was conducted simultaneously at two nuclear medicine centers, Austria (Vienna, Center 1) and Germany (Bad Berka, Center 2). The patients (n = 29) included in this study were referred for PET (Center 1, 21 patients) or PET/CT (Center 2, 8 patients) imaging with either a high suspicion of recurrent disease or for possible surgical or PSMA radioligand therapy planning. PET images of the whole body were performed at 1 hour p.i. and additional images of the pelvis at 2 hours p.i. In 23 of 29 patients, at least one focus of pathological tracer uptake suspicious for primary disease in the prostate lobe or recurrent disease was detected. Among healthy organs, the salivary glands, kidneys, and liver showed the highest radiotracer uptake. Lesions suspicious for PCa were detected with excellent contrast as early as 1 hour p.i. with high detection rates even at low prostate-specific antigen (PSA) levels. The preliminary results of this study demonstrate the high potential of 64 Cu-PSMA ligand PET/CT imaging in patients with recurrent disease and in the primary staging of selected patients with progressive local disease. The acquired PET images showed an excellent resolution of the detected lesions with very high lesion-to- background contrast. Furthermore, the long half-life of 64 Cu allows distribution of the tracer to clinical PET centers that lack radiochemistry facilities for the preparation of 68 Ga-PSMA ligand (satellite concept).

Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention

PubMed Central

Kumar, Nagi B.; Pow-Sang, Julio; Egan, Kathleen M.; Spiess, Philippe E.; Dickinson, Shohreh; Salup, Raoul; Helal, Mohamed; McLarty, Jerry; Williams, Christopher R.; Schreiber, Fred; Parnes, Howard L.; Sebti, Said; Kazi, Aslam; Kang, Loveleen; Quinn, Gwen; Smith, Tiffany; Yue, Binglin; Diaz, Karen; Chornokur, Ganna; Crocker, Theresa; Schell, Michael J.

2015-01-01

Preclinical, epidemiological and prior clinical trial data suggest that green tea catechins (GTCs) may reduce prostate cancer (PCa) risk. We conducted a placebo-controlled, randomized clinical trial of Polyphenon E® (PolyE), a proprietary mixture of GTCs, containing 400 mg (–)-epigallocatechin-3-gallate (EGCG) per day, in 97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP). The primary study endpoint was a comparison of the cumulative one-year PCa rates on the two study arms. No differences in the number of PCa cases were observed: 5/49 (PolyE) versus 9/48 (placebo), P=0.25. A secondary endpoint comparing the cumulative rate of PCa plus ASAP among men with HGPIN without ASAP at baseline, revealed a decrease in this composite endpoint: 3/26 (PolyE) versus 10/25 (placebo), P<0.024. This finding was driven by a decrease in ASAP diagnoses on the Poly E (0/26) compared to the placebo arm (5/25). A decrease in serum prostate specific antigen (PSA) was observed on the PolyE arm [−0.87 ng/ml (95%CI: −1.66, −0.09)]. Adverse events related to the study agent did not significantly differ between the two study groups. Daily intake of a standardized, decaffeinated catechin mixture containing 400 mg EGCG per day for 1 year accumulated in plasma and was well tolerated but did not reduce the likelihood of PCa in men with baseline HGPIN or ASAP. PMID:25873370

Novel RNA hybridization method for the in situ detection of ETV1, ETV4, and ETV5 gene fusions in prostate cancer.

PubMed

Kunju, Lakshmi P; Carskadon, Shannon; Siddiqui, Javed; Tomlins, Scott A; Chinnaiyan, Arul M; Palanisamy, Nallasivam

2014-09-01

The genetic basis of 50% to 60% of prostate cancer (PCa) is attributable to rearrangements in E26 transformation-specific (ETS) (ERG, ETV1, ETV4, and ETV5), BRAF, and RAF1 genes and overexpression of SPINK1. The development and validation of reliable detection methods are warranted to classify various molecular subtypes of PCa for diagnostic and prognostic purposes. ETS gene rearrangements are typically detected by fluorescence in situ hybridization and reverse-transcription polymerase chain reaction methods. Recently, monoclonal antibodies against ERG have been developed that detect the truncated ERG protein in immunohistochemical assays where staining levels are strongly correlated with ERG rearrangement status by fluorescence in situ hybridization. However, specific antibodies for ETV1, ETV4, and ETV5 are unavailable, challenging their clinical use. We developed a novel RNA in situ hybridization-based assay for the in situ detection of ETV1, ETV4, and ETV5 in formalin-fixed paraffin-embedded tissues from prostate needle biopsies, prostatectomy, and metastatic PCa specimens using RNA probes. Further, with combined RNA in situ hybridization and immunohistochemistry we identified a rare subset of PCa with dual ETS gene rearrangements in collisions of independent tumor foci. The high specificity and sensitivity of RNA in situ hybridization provides an alternate method enabling bright-field in situ detection of ETS gene aberrations in routine clinically available PCa specimens.

Elevated levels of circulating IL-7 and IL-15 in patients with early stage prostate cancer

PubMed Central

2011-01-01

Background Chronic inflammation has been suggested to favour prostate cancer (PCA) development. Interleukins (IL) represent essential inflammation mediators. IL-2, IL-7, IL-15 and IL-21, sharing a common receptor γ chain (c-γ), control T lymphocyte homeostasis and proliferation and play major roles in regulating cancer-immune system interactions. We evaluated local IL-2, IL-7, IL-15 and IL-21 gene expression in prostate tissues from patients with early stage PCA or benign prostatic hyperplasia (BPH). As control, we used IL-6 gene, encoding an IL involved in PCA progression. IL-6, IL-7 and IL-15 titres were also measured in patients' sera. Methods Eighty patients with BPH and 79 with early (1 to 2c) stage PCA were enrolled. Gene expression in prostate tissues was analyzed by quantitative real-time PCR (qRT-PCR). Serum IL concentrations and acute phase protein titres were evaluated by ELISA. Mann-Whitney, Wilcoxon and χ2 tests were used to compare IL gene expression and serum titers in the two groups of patients. Receiver operating characteristic (ROC) curves were constructed to evaluate the possibility to distinguish sera from different groups of patients based on IL titers. Results IL-2 and IL-21 gene expression was comparably detectable, with low frequency and at low extents, in PCA and BPH tissues. In contrast, IL-6, IL-7 and IL-15 genes were expressed more frequently (p < 0.0001, p = 0.0047 and p = 0.0085, respectively) and to significantly higher extents (p = 0.0051, p = 0.0310 and p = 0.0205, respectively) in early stage PCA than in BPH tissues. Corresponding proteins could be detected to significantly higher amounts in sera from patients with localized PCA, than in those from patients with BPH (p = 0.0153, p = 0.0174 and p = 0.0064, respectively). Analysis of ROC curves indicates that IL-7 (p = 0.0039), but not IL-6 (p = 0.2938) or IL-15 (p = 0.1804) titres were able to distinguish sera from patients with malignancy from those from patients with benign disease. Serum titres of C reactive (CRP), high mobility group B1 (HMGB1) and serum amyloid A (SAA) acute phase proteins were similar in both groups of patients. Conclusions Expression IL-7 and IL-15 genes in prostate tissues and corresponding serum titres are significantly increased in patients with early stage PCA as compared with patients with BPH. PMID:21943235

Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer.

PubMed

Martínez-Piñeiro, Luis; Schalken, Jack A; Cabri, Patrick; Maisonobe, Pascal; de la Taille, Alexandre

2014-10-01

To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics. The Triptocare study was a prospective, open-label, multicentre, single-arm, Phase III study of triptorelin 22.5 mg in men with locally advanced or metastatic prostate cancer, who were naïve to androgen-deprivation therapy (ADT). The primary objective was to model the urinary PCA3 change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse events and changes in laboratory parameters. The intent-to-treat population comprised 322 patients; 39 (12.1%) had non-assessable PCA3 scores at baseline, and 109/322 (33.9%), 215/313 (68.7%) and 232/298 (77.9%) had non-assessable PCA3 scores at 1, 3 and 6 months, respectively. Baseline Gleason score was the only variable associated with non-assessability of PCA3 score at 6 months (P = 0.017) - the hazard of having a non-assessable PCA3 score at 6 months was 1.824-fold higher (95% confidence interval 1.186-2.805) in patients with a Gleason score ≥8 vs those with a Gleason score ≤6. The median PCA3 scores at baseline were significantly higher in patients aged ≥65 years vs those aged <65 years and in patients with a serum PSA level <100 ng/mL vs those with serum PSA level of >200 ng/mL. The median PCA3 score was significantly lower in patients with metastasis than in patients with no metastasis or unknown metastasis status. TMPRSS2-ERG scores ≥35 were considered positive (n = 149 [51.6%]). Age, presence of metastasis, PSA level and Gleason score at baseline were not associated with a significant difference in the proportion of TMPRSS2-ERG-positive scores. The median serum PSA levels decreased from 45.5 ng/mL at baseline to 1.2 ng/mL after 6 months, and as expected, >90% of patients achieved castrate levels of testosterone (<50 ng/dL) at 1, 3, and 6 months during triptorelin treatment. The safety profile reported from this study is consistent with the known safety profile of triptorelin. These data from the Triptocare study suggest that urinary PCA3 or TMPRSS2-ERG score are not reliable markers of cancer stage in advanced prostate cancer. Urinary PCA3 and TMPRSS2-ERG scores do not appear to be useful in assessing response to ADT in advanced prostate cancer, with most patients having non-assessable scores after 6 months of treatment. © 2013 The Authors. BJU International © 2013 BJU International.

Effect of scalp blocks with levobupivacaine on recovery profiles after craniotomy for aneurysm clipping: a randomized, double-blind, and controlled study.

PubMed

Hwang, Jin-Young; Bang, Jae-Seung; Oh, Chang-Wan; Joo, Jin-Deok; Park, Seong-Joo; Do, Sang-Hwan; Yoo, Yong-Jae; Ryu, Jung-Hee

2015-01-01

This study was conducted to evaluate the effect of scalp blocks using levobupivacaine on recovery profiles including postoperative pain, patient-controlled analgesia (PCA) consumption, postoperative nausea and vomiting (PONV), and other adverse events in patients undergoing frontoparietal craniotomy for aneurysm clipping. Fifty-two patients scheduled for elective frontoparietal craniotomy for unruptured aneurysm clipping were enrolled. After surgery, scalp blocks were performed using normal saline (group C, n = 26) or 0.75% levobupivacaine (group L, n = 26). Postoperative pain scores and PCA consumption were recorded for 72 hours after recovery of consciousness. The time from patient recovery to the first use of PCA drug and rescue analgesics, the requirement for vasoactive agents, and adverse effects related to PCA and local anesthetics also were recorded. Postoperative pain scores and PCA consumption in group L were lower than in group C (P < .05). The time intervals from patient recovery to the first use of PCA drug (P < .001) and rescue analgesics (P = .038) was longer in group L than in group C. Additionally, less antihypertensive agent was required (P = .017), and PONV occurred less frequently (P = .039) in group L than in group C. Scalp blocks with 0.75% levobupivacaine improved recovery profiles in that it effectively lowered postoperative pain and PCA consumption without severe adverse events and also reduced the requirement for a postoperative antihypertensive agent and the incidence of PONV in patients who underwent frontoparietal craniotomy for aneurysm clipping. Copyright © 2015 Elsevier Inc. All rights reserved.

A three-gene panel on urine increases PSA specificity in the detection of prostate cancer.

PubMed

Rigau, Marina; Ortega, Israel; Mir, Maria Carmen; Ballesteros, Carlos; Garcia, Marta; Llauradó, Marta; Colás, Eva; Pedrola, Núria; Montes, Melania; Sequeiros, Tamara; Ertekin, Tugce; Majem, Blanca; Planas, Jacques; Ruiz, Anna; Abal, Miguel; Sánchez, Alex; Morote, Juan; Reventós, Jaume; Doll, Andreas

2011-12-01

Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic "gray zone" (4-10 ng/ml) on a target subset of 82 men with no prior biopsy. By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic "gray zone." Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone. Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Copyright © 2011 Wiley Periodicals, Inc.

Inhibition of prostate cancer osteoblastic progression with VEGF121/rGel, a single agent targeting osteoblasts, osteoclasts, and tumor neovasculature.

PubMed

Mohamedali, Khalid A; Li, Zhi Gang; Starbuck, Michael W; Wan, Xinhai; Yang, Jun; Kim, Sehoon; Zhang, Wendy; Rosenblum, Michael G; Navone, Nora M

2011-04-15

A hallmark of prostate cancer (PCa) progression is the development of osteoblastic bone metastases, which respond poorly to available therapies. We previously reported that VEGF(121)/rGel targets osteoclast precursors and tumor neovasculature. Here we tested the hypothesis that targeting nontumor cells expressing these receptors can inhibit tumor progression in a clinically relevant model of osteoblastic PCa. Cells from MDA PCa 118b, a PCa xenograft obtained from a bone metastasis in a patient with castrate-resistant PCa, were injected into the femurs of mice. Osteoblastic progression was monitored following systemic administration of VEGF(121)/rGel. VEGF(121)/rGel was cytotoxic in vitro to osteoblast precursor cells. This cytotoxicity was specific as VEGF(121)/rGel internalization into osteoblasts was VEGF(121) receptor driven. Furthermore, VEGF(121)/rGel significantly inhibited PCa-induced bone formation in a mouse calvaria culture assay. In vivo, VEGF(121)/rGel significantly inhibited the osteoblastic progression of PCa cells in the femurs of nude mice. Microcomputed tomographic analysis revealed that VEGF(121)/rGel restored the bone volume fraction of tumor-bearing femurs to values similar to those of the contralateral (non-tumor-bearing) femurs. VEGF(121)/rGel significantly reduced the number of tumor-associated osteoclasts but did not change the numbers of peritumoral osteoblasts. Importantly, VEGF(121)/rGel-treated mice had significantly less tumor burden than control mice. Our results thus indicate that VEGF(121)/rGel inhibits osteoblastic tumor progression by targeting angiogenesis, osteoclastogenesis, and bone formation. Targeting VEGF receptor (VEGFR)-1- or VEGFR-2-expressing cells is effective in controlling the osteoblastic progression of PCa in bone. These findings provide the basis for an effective multitargeted approach for metastatic PCa. ©2011 AACR.

Androgen receptor (AR) degradation enhancer ASC-J9® in an FDA-approved formulated solution suppresses castration resistant prostate cancer cell growth.

PubMed

Cheng, Max A; Chou, Fu-Ju; Wang, Keliang; Yang, Rachel; Ding, Jie; Zhang, Qiaoxia; Li, Gonghui; Yeh, Shuyuan; Xu, Defeng; Chang, Chawnshang

2018-03-28

ASC-J9 ® is a recently-developed androgen receptor (AR)-degradation enhancer that effectively suppresses castration resistant prostate cancer (PCa) cell proliferation and invasion. The optimal half maximum inhibitory concentrations (IC 50 ) of ASC-J9 ® at various PCa cell confluences (20%, 50%, and 100%) were assessed via both short-term MTT growth assays and long-term clonogenic proliferation assays. Our results indicate that the IC 50 values for ASC-J9 ® increased with increasing cell confluency. The IC 50 values were significantly decreased in PCa AR-positive cells compared to PCa AR-negative cells or in normal prostate cells. This suggests that ASC-J9 ® may function mainly via targeting the AR-positive PCa cells with limited unwanted side-effects to suppress the surrounding normal prostate cells. Mechanism dissection indicated that ASC-J9 ® might function via altering the apoptosis signals to suppress the PCa AR-negative PC-3 cells. Preclinical studies using multiple in vitro PCa cell lines and an in vivo mouse model with xenografted castration-resistant PCa CWR22Rv1 cells demonstrated that ASC-J9 ® has similar AR degradation effects when dissolved in FDA-approved solvents, including DMSO, PEG-400:Tween-80 (95:5), DMA:Labrasol:Tween-80 (10:45:45), and DMA:Labrasol:Tween-20 (10:45:45). Together, results from preclinical studies suggest a potential new therapy with AR-degradation enhancer ASC-J9 ® may potentially be ready to be used in human clinical trials in order to better suppress PCa at later castration resistant stages. Copyright © 2017 Elsevier B.V. All rights reserved.

The relationship between nutrition and prostate cancer: is more always better?

PubMed

Masko, Elizabeth M; Allott, Emma H; Freedland, Stephen J

2013-05-01

Prostate cancer (PCa) remains one of the most diagnosed malignancies in the world, correlating with regions where men consume more of a so-called Western-style diet. As such, there is much interest in understanding the role of lifestyle and diet on the incidence and progression of PCa. To provide a summary of published literature with regard to dietary macro- and micronutrients and PCa incidence and progression. A literature search was completed using the PubMed database for all studies published on diet and PCa in June 2012 or earlier. Primary literature and meta-analyses were given preference over other review articles when possible. The literature was reviewed on seven dietary components: carbohydrates, protein, fat and cholesterol, vegetables, vitamins and minerals, and phytochemicals. Current literature linking these nutrients to PCa is limited at best, but trends in the published data suggest consumption of carbohydrates, saturated and ω-6 fats, and certain vitamin supplements may promote PCa risk and progression. Conversely, consumption of many plant phytochemicals and ω-3 fatty acids seem to slow the risk and progression of the disease. All other nutrients seem to have no effect or data are inconclusive. A brief summary about the clinical implications of dietary interventions with respect to PCa prevention, treatment, and survivorship is provided. Due to the number and heterogeneity of published studies investigating diet and PCa, it is difficult to determine what nutrients make up the perfect diet for the primary and secondary prevention of PCa. Because diets are made of multiple macro- and micronutrients, further prospective studies are warranted, particularly those investigating the relationship between whole foods instead of a single nutritional component. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

miR-503 suppresses tumor cell proliferation and metastasis by directly targeting RNF31 in prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Jia; Liu, Xiuheng, E-mail: l_xiuheng@163.com; Wang, Min

2015-09-04

Microarray data analyses were performed to search for metastasis-associated oncogenes in prostate cancer (PCa). RNF31 mRNA expressions in tumor tissues and benign prostate tissues were evaluated. The RNF31 protein expression levels were also analyzed by western blot and immunohistochemistry. Luciferase reporter assays were used to identify miRNAs that can regulate RNF31. The effect of RNF31 on PCa progression was studied in vitro and in vivo. We found that RNF31 was significantly increased in PCa and its expression level was highly correlated with seminal vesicle invasion, clinical stage, prostate specific antigen (PSA) level, Gleason score, and BCR. Silence of RNF31 suppressed PCa cellmore » proliferation and metastasis in vitro and in vivo. miR-503 can directly regulate RNF31. Enforced expression of miR-503 inhibited the expression of RNF31 significantly and the restoration of RNF31 expression reversed the inhibitory effects of miR-503 on PCa cell proliferation and metastasis. These findings collectively indicated an oncogene role of RNF31 in PCa progression which can be regulated by miR-503, suggesting that RNF31 could serve as a potential prognostic biomarker and therapeutic target for PCa. - Highlights: • RNF31 is a potential metastasis associated gene and is associated with prostate cancer progression. • Silence of RNF31 inhibits PCa cell colony formation, migration and invasion. • RNF31 as a direct target of miR-503. • miR-503 can regulate cell proliferation, invasion and migration by targeting RNF31. • RNF31 plays an important role in PCa growth and metastasis in vivo.« less

USE OF THE PROSTATE HEALTH INDEX FOR DETECTION OF PROSTATE CANCER: RESULTS FROM A LARGE ACADEMIC PRACTICE

PubMed Central

Tosoian, Jeffrey J.; Druskin, Sasha C.; Andreas, Darian; Mullane, Patrick; Chappidi, Meera; Joo, Sarah; Ghabili, Kamyar; Agostino, Joseph; Macura, Katarzyna J.; Carter, H. Ballentine; Schaeffer, Edward M.; Partin, Alan W.; Sokoll, Lori J.; Ross, Ashley E.

2016-01-01

BACKGROUND The Prostate Health Index (phi) outperforms PSA and other PSA derivatives for the diagnosis of prostate cancer (PCa). The impact of phi testing in the real-world clinical setting has not been previously assessed. METHODS In a single, large, academic center, phi was tested in 345 patients presenting for diagnostic evaluation for PCa. Findings on prostate biopsy (including Grade Group [GG], defined as GG1: Gleason score [GS] 6, GG2: GS 3+4=7, GG3: GS 4+3=7, GG4: GS 8, and GG5: GS 9-10), magnetic resonance imaging (MRI), and radical prostatectomy (RP) were prospectively recorded. Biopsy rates and outcomes were compared to a contemporary cohort that did not undergo phi testing (n=1318). RESULTS Overall, 39% of men with phi testing underwent prostate biopsy. No men with phi<19.6 were diagnosed with PCa, and only 3 men with phi<27 had cancer of GG≥2. Phi was superior to PSA for the prediction of any PCa (AUC 0.72 vs. 0.47) and GG≥2 PCa (AUC 0.77 vs. 0.53) on prostate biopsy. Among men undergoing MRI and phi, no men with phi<27 and PI-RADS≤3 had GG≥2 cancer. For those men proceeding to RP, increasing phi was associated with higher pathologic GG (p=0.002) and stage (p=0.001). Compared to patients who did not undergo phi testing, the use of phi was associated with a 9% reduction in the rate of prostate biopsy (39% vs. 48%; p<0.001). Importantly, the reduction in biopsy among the phi population was secondary to decreased incidence of negative (8%) and GG1 (1%) biopsies, while the proportion of biopsies detecting GG≥2 cancers remained unchanged. CONCLUSIONS In this large, real-time clinical experience, phi outperformed PSA alone, was associated with high-grade PCa, and provided complementary information to MRI. Incorporation of phi into clinical practice reduced the rate of unnecessary biopsies without changing the frequency of detection of higher grade cancers. PMID:28117387

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuz'mina, L. G., E-mail: kuzmina@igic.ras.ru; Sitin, A. G.; Gulakova, E. N.

The crystal and molecular structures of five styrylheterocycles of the quinoline series are studied. All molecules are planar. The double bond in the ethylene fragment is essentially localized. In the molecule of 2-(4-methylstyryl)quinoline, the ethylene fragment is disordered by the bicycle-pedal pattern. In four of the five compounds, the crystal packings do not contain stacking dimers prearranged for the [2+2] photocycloaddition (PCA) reaction. In the crystal of 2-(3-nitrostyryl)quinoline, pairs of crystallographically independent molecules form stacking dimers. In a dimer, the ethylene fragments have a twist orientation, which is incompatible with the PCA reaction. An attempt to initiate a temperature-dependent processmore » of bicyclepedal isomerization in the crystal and, as a consequence, the PCA reaction by means of simultaneous irradiation and heating of a single crystal is unsuccessful.« less

Prostate health index and prostate cancer gene 3 score but not percent-free Prostate Specific Antigen have a predictive role in differentiating histological prostatitis from PCa and other nonneoplastic lesions (BPH and HG-PIN) at repeat biopsy.

PubMed

De Luca, Stefano; Passera, Roberto; Fiori, Cristian; Bollito, Enrico; Cappia, Susanna; Mario Scarpa, Roberto; Sottile, Antonino; Franco Randone, Donato; Porpiglia, Francesco

2015-10-01

To determine if prostate health index (PHI), prostate cancer antigen gene 3 (PCA3) score, and percentage of free prostate-specific antigen (%fPSA) may be used to differentiate asymptomatic acute and chronic prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA levels and negative findings on digital rectal examination at repeat biopsy (re-Bx). In this prospective study, 252 patients were enrolled, undergoing PHI, PCA3 score, and %fPSA assessments before re-Bx. We used 3 multivariate logistic regression models to test the PHI, PCA3 score, and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the "gray zone" of PSA (4-10ng/ml) cohort (171 individuals). Of the 252 patients, 43 (17.1%) had diagnosis of PCa. The median PHI was significantly different between men with a negative biopsy and those with a positive biopsy (34.9 vs. 48.1, P<0.001), as for the PCA3 score (24 vs. 54, P<0.001) and %fPSA (11.8% vs. 15.8%, P = 0.012). The net benefit of using PCA3 and PHI to differentiate prostatitis and PCa was moderate, although it extended to a good range of threshold probabilities (40%-100%), whereas that from using %fPSA was negligible: this pattern was reported for the whole population as for the "gray zone" PSA cohort. In front of a good diagnostic performance of all the 3 biomarkers in distinguishing negative biopsy vs. positive biopsy, the clinical benefit of using the PCA3 score and PHI to estimate prostatitis vs. PCa was comparable. PHI was the only determinant for prostatitis vs. BPH, whereas no biomarkers could differentiate prostate inflammation from HG-PIN. Copyright © 2015 Elsevier Inc. All rights reserved.

Multiparametric dynamic contrast-enhanced ultrasound imaging of prostate cancer.

PubMed

Wildeboer, Rogier R; Postema, Arnoud W; Demi, Libertario; Kuenen, Maarten P J; Wijkstra, Hessel; Mischi, Massimo

2017-08-01

The aim of this study is to improve the accuracy of dynamic contrast-enhanced ultrasound (DCE-US) for prostate cancer (PCa) localization by means of a multiparametric approach. Thirteen different parameters related to either perfusion or dispersion were extracted pixel-by-pixel from 45 DCE-US recordings in 19 patients referred for radical prostatectomy. Multiparametric maps were retrospectively produced using a Gaussian mixture model algorithm. These were subsequently evaluated on their pixel-wise performance in classifying 43 benign and 42 malignant histopathologically confirmed regions of interest, using a prostate-based leave-one-out procedure. The combination of the spatiotemporal correlation (r), mean transit time (μ), curve skewness (κ), and peak time (PT) yielded an accuracy of 81% ± 11%, which was higher than the best performing single parameters: r (73%), μ (72%), and wash-in time (72%). The negative predictive value increased to 83% ± 16% from 70%, 69% and 67%, respectively. Pixel inclusion based on the confidence level boosted these measures to 90% with half of the pixels excluded, but without disregarding any prostate or region. Our results suggest multiparametric DCE-US analysis might be a useful diagnostic tool for PCa, possibly supporting future targeting of biopsies or therapy. Application in other types of cancer can also be foreseen. • DCE-US can be used to extract both perfusion and dispersion-related parameters. • Multiparametric DCE-US performs better in detecting PCa than single-parametric DCE-US. • Multiparametric DCE-US might become a useful tool for PCa localization.

Outcome of repeated prostatic biopsy during active surveillance: implications for focal therapy.

PubMed

Barayan, Ghassan A; Aprikian, Armen G; Hanley, James; Kassouf, Wassim; Brimo, Fadi; Bégin, Louis R; Tanguay, Simon

2015-09-01

Active surveillance (AS) is commonly recommended for men with localized low-intermediate-risk prostate cancer (PCa). The aim of our study was to assess the probability that patients with PCa would develop unfavorable disease features (UDF) while under AS for the purpose of evaluating whether immediate hemiablation therapy (HAT) could bring clinical benefit to selected patients. In our cohort of AS patients, 157 were diagnosed with unilateral PCa. Using five different definitions of UDF, patients' data were used to simulate the theoretical outcome whether these patients were managed by immediate unilateral HAT or remained on AS. The mean age at the time of diagnosis was 67 years (range 47-81). The median follow-up was 5.4 years [interquartile range (IQR) 3.4-8]. Baseline characteristics included a median PSA value of 5.5 ng/ml (IQR 4.5-7), median number of biopsy taken of 10 (IQR 6-10), and maximum cancer percentage on any core of 10 (IQR 5-20). Of the 157 patients, 144 (92 %) had a Gleason score (GS) of ≤6. Using the whole range of definition for UDF, 10-47 % of patients developed UDF while under AS. Using baseline GS, maximum percentage of cancer on any core, and PSA density, we found significant trends for higher development of UDF for patients under AS. The majority of our patients did not develop UDF while under AS. Our study, thus, suggests that careful patient selection for focal therapy should be performed to avoid subjecting patients to unnecessary treatment.

Prostatitis, other genitourinary infections and prostate cancer: results from a population-based case-control study.

PubMed

Boehm, Katharina; Valdivieso, Roger; Meskawi, Malek; Larcher, Alessandro; Schiffmann, Jonas; Sun, Maxine; Graefen, Markus; Saad, Fred; Parent, Marie-Élise; Karakiewicz, Pierre I

2016-03-01

We relied on a population-based case-control study (PROtEuS) to examine a potential association between the presence of histologically confirmed prostate cancer (PCa) and history of genitourinary infections, e.g., prostatitis, urethritis, orchitis and epididymitis. Cases were 1933 men with incident PCa, diagnosed across Montreal hospitals between 2005 and 2009. Population controls were 1994 men from the same residential area and age distribution. In-person interviews collected information about socio-demographic characteristics, lifestyle and medical history, e.g., self-reported history of several genitourinary infections, as well as on PCa screening. Logistic regression analyses tested overall and grade-specific associations, including subgroup analyses with frequent PSA testing. After multivariable adjustment, prostatitis was associated with an increased risk of any PCa (OR 1.81 [1.44-2.27]), but not urethritis (OR 1.05 [0.84-1.30]), orchitis (OR 1.28 [0.92-1.78]) or epididymitis (OR 0.98 [0.57-1.68]). The association between prostatitis and PCa was more pronounced for low-grade PCa (Gleason ≤ 6: OR 2.11 [1.61-2.77]; Gleason ≥ 7: OR 1.59 [1.22-2.07]). Adjusting for frequency of physician visits, PSA testing frequency or restricting analyses to frequently screened subjects did not affect these results. Prostatitis was associated with an increased probability for detecting PCa even after adjustment for frequency of PSA testing and physician visits, but not urethritis, orchitis or epididymitis. These considerations may be helpful in clinical risk stratification of individuals in whom the risk of PCa is pertinent.

Prediction of BP reactivity to talking using hybrid soft computing approaches.

PubMed

Kaur, Gurmanik; Arora, Ajat Shatru; Jain, Vijender Kumar

2014-01-01

High blood pressure (BP) is associated with an increased risk of cardiovascular diseases. Therefore, optimal precision in measurement of BP is appropriate in clinical and research studies. In this work, anthropometric characteristics including age, height, weight, body mass index (BMI), and arm circumference (AC) were used as independent predictor variables for the prediction of BP reactivity to talking. Principal component analysis (PCA) was fused with artificial neural network (ANN), adaptive neurofuzzy inference system (ANFIS), and least square-support vector machine (LS-SVM) model to remove the multicollinearity effect among anthropometric predictor variables. The statistical tests in terms of coefficient of determination (R (2)), root mean square error (RMSE), and mean absolute percentage error (MAPE) revealed that PCA based LS-SVM (PCA-LS-SVM) model produced a more efficient prediction of BP reactivity as compared to other models. This assessment presents the importance and advantages posed by PCA fused prediction models for prediction of biological variables.

Multiresolution generalized N dimension PCA for ultrasound image denoising

PubMed Central

2014-01-01

Background Ultrasound images are usually affected by speckle noise, which is a type of random multiplicative noise. Thus, reducing speckle and improving image visual quality are vital to obtaining better diagnosis. Method In this paper, a novel noise reduction method for medical ultrasound images, called multiresolution generalized N dimension PCA (MR-GND-PCA), is presented. In this method, the Gaussian pyramid and multiscale image stacks on each level are built first. GND-PCA as a multilinear subspace learning method is used for denoising. Each level is combined to achieve the final denoised image based on Laplacian pyramids. Results The proposed method is tested with synthetically speckled and real ultrasound images, and quality evaluation metrics, including MSE, SNR and PSNR, are used to evaluate its performance. Conclusion Experimental results show that the proposed method achieved the lowest noise interference and improved image quality by reducing noise and preserving the structure. Our method is also robust for the image with a much higher level of speckle noise. For clinical images, the results show that MR-GND-PCA can reduce speckle and preserve resolvable details. PMID:25096917

Adaptive non-local means on local principle neighborhood for noise/artifacts reduction in low-dose CT images.

PubMed

Zhang, Yuanke; Lu, Hongbing; Rong, Junyan; Meng, Jing; Shang, Junliang; Ren, Pinghong; Zhang, Junying

2017-09-01

Low-dose CT (LDCT) technique can reduce the x-ray radiation exposure to patients at the cost of degraded images with severe noise and artifacts. Non-local means (NLM) filtering has shown its potential in improving LDCT image quality. However, currently most NLM-based approaches employ a weighted average operation directly on all neighbor pixels with a fixed filtering parameter throughout the NLM filtering process, ignoring the non-stationary noise nature of LDCT images. In this paper, an adaptive NLM filtering scheme on local principle neighborhoods (PC-NLM) is proposed for structure-preserving noise/artifacts reduction in LDCT images. Instead of using neighboring patches directly, in the PC-NLM scheme, the principle component analysis (PCA) is first applied on local neighboring patches of the target patch to decompose the local patches into uncorrelated principle components (PCs), then a NLM filtering is used to regularize each PC of the target patch and finally the regularized components is transformed to get the target patch in image domain. Especially, in the NLM scheme, the filtering parameter is estimated adaptively from local noise level of the neighborhood as well as the signal-to-noise ratio (SNR) of the corresponding PC, which guarantees a "weaker" NLM filtering on PCs with higher SNR and a "stronger" filtering on PCs with lower SNR. The PC-NLM procedure is iteratively performed several times for better removal of the noise and artifacts, and an adaptive iteration strategy is developed to reduce the computational load by determining whether a patch should be processed or not in next round of the PC-NLM filtering. The effectiveness of the presented PC-NLM algorithm is validated by experimental phantom studies and clinical studies. The results show that it can achieve promising gain over some state-of-the-art methods in terms of artifact suppression and structure preservation. With the use of PCA on local neighborhoods to extract principal structural components, as well as adaptive NLM filtering on PCs of the target patch using filtering parameter estimated based on the local noise level and corresponding SNR, the proposed PC-NLM method shows its efficacy in preserving fine anatomical structures and suppressing noise/artifacts in LDCT images. © 2017 American Association of Physicists in Medicine.

Under-representation of racial minorities in prostate cancer studies submitted to the US Food and Drug Administration to support potential marketing approval, 1993-2013.

PubMed

Wissing, Michel D; Kluetz, Paul G; Ning, Yang-Min; Bull, Jonca; Merenda, Christine; Murgo, Anthony J; Pazdur, Richard

2014-10-01

US Food and Drug Administration (FDA) approval of new drugs depends on results from clinical trials that must be generalized to the US population. However, racial minorities are frequently under-represented in clinical studies. The enrollment of racial minorities was compared in key clinical studies submitted to the FDA in the last 10 years in support of potential marketing approval for prostate cancer (PCa) prevention or treatment. Patient demographic data were obtained from archival data sets of large registration trials submitted to the FDA to support proposed PCa indications. Six countries/regions were analyzed: the United States, Canada, Australia, Europe, the United Kingdom, and Eastern Europe. Background racial demographics were collected from national census data. Seventeen key PCa clinical trials were analyzed. These trials were conducted in the past 20 years, comprising 39,574 patients with known racial information. Most patients were enrolled in the United States, but there appeared to be a trend toward increased non-US enrollment over time. In all countries, racial minorities were generally under-represented. There was no significant improvement in racial minority enrollment over time. The United States enrolled the largest nonwhite population (7.1%). Over the past 20 years, racial minorities were consistently under-represented in key PCa trials. There is a need for effective measures that will improve enrollment of racial minorities. With increased global enrollment, drug developers should aim to recruit a patient population that resembles the racial demographics of the patient population to which drug use will be generalized upon approval. © 2014 American Cancer Society.

Elevated hardness of peripheral gland on real-time elastography is an independent marker for high-risk prostate cancers.

PubMed

Zhang, Qi; Yao, Jing; Cai, Yehua; Zhang, Limin; Wu, Yishuo; Xiong, Jingyu; Shi, Jun; Wang, Yuanyuan; Wang, Yi

2017-12-01

To examine the role of quantitative real-time elastography (RTE) features on differentiation between high-risk prostate cancer (PCA) and non-high-risk prostatic diseases in the initial transperineal biopsy setting. We retrospectively included 103 patients with suspicious PCA who underwent both RTE and initial transperineal prostate biopsy. Patients were grouped into high-risk and non-high-risk categories according to the D'Amico's risk stratification. With computer assistance based on MATLAB programming, three features were extracted from RTE, i.e., the median hardness within peripheral gland (PG) (H med ), the ratio of the median hardness within PG to that outside PG (H ratio ), and the ratio of the hard area within PG to the total PG area (H ar ). A multiple regression model incorporating an RTE feature, age, transrectal ultrasound finding, and prostate volume was used to identify markers for high-risk PCA. Forty-seven patients (45.6%) were diagnosed with PCA and 34 (33.0%) were diagnosed with high-risk PCA. Three RTE features were all statistically higher in high-risk PCA than in non-high-risk diseases (p < 0.001), indicating that the PGs in high-risk PCA patients were harder than those in non-high-risk patients. A high H ratio , high age, and low prostate volume were found to be independent markers for PCAs (p < 0.05), among which the high H ratio was the only independent marker for high-risk PCAs (p = 0.012). When predicting high-risk PCAs, the multiple regression achieved an area under receiver operating characteristic curve of 0.755, sensitivity of 73.5%, and specificity of 71.0%. The elevated hardness of PG identified high-risk PCA and served as an independent marker of high-risk PCA. As a non-invasive imaging modality, the RTE could be potentially used in routine clinical practice for the detection of high-risk PCA to decrease unnecessary biopsies and reduce overtreatment.

Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling

PubMed Central

Deep, Gagan; Kumar, Rahul; Jain, Anil K; Agarwal, Chapla; Agarwal, Rajesh

2014-01-01

Prostate cancer (PCA) is the 2nd leading cause of cancer-related deaths among men in the United States. Preventing or inhibiting metastasis-related events through non-toxic agents could be a useful approach for lowering high mortality among PCA patients. We have earlier reported that natural flavonoid silibinin possesses strong anti-metastatic efficacy against PCA however, mechanism/s of its action still remains largely unknown. One of the major events during metastasis is the replacement of cell-cell interaction with integrins-based cell-matrix interaction that controls motility, invasiveness and survival of cancer cells. Accordingly, here we examined silibinin effect on advanced human PCA PC3 cells' interaction with extracellular matrix component fibronectin. Silibinin (50-200 μM) treatment significantly decreased the fibronectin (5 μg/ml)-induced motile morphology via targeting actin cytoskeleton organization in PC3 cells. Silibinin also decreased the fibronectin-induced cell proliferation and motility but significantly increased cell death in PC3 cells. Silibinin also inhibited the PC3 cells invasiveness in Transwell invasion assays with fibronectin or cancer associated fibroblasts (CAFs) serving as chemoattractant. Importantly, PC3-luc cells cultured on fibronectin showed rapid dissemination and localized in lungs following tail vein injection in athymic male nude mice; however, in silibinin-treated PC3-luc cells, dissemination and lung localization was largely compromised. Molecular analyses revealed that silibinin treatment modulated the fibronectin-induced expression of integrins (α5, αV, β1 and β3), actin-remodeling (FAK, Src, GTPases, ARP2 and cortactin), apoptosis (cPARP and cleaved caspase 3), EMT (E-cadherin and β-catenin), and cell survival (survivin and Akt) related signaling molecules in PC3 cells. Furthermore, PC3-xenograft tissue analyses confirmed the inhibitory effect of silibinin on fibronectin and integrins expression. Together, these results showed that silibinin targets PCA cells' interaction with fibronectin and inhibits their motility, invasiveness and survival; thus further supporting silibinin use in PCA intervention including its metastatic progression. PMID:25285031

Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling.

PubMed

Deep, Gagan; Kumar, Rahul; Jain, Anil K; Agarwal, Chapla; Agarwal, Rajesh

2014-10-01

Prostate cancer (PCA) is the 2nd leading cause of cancer-related deaths among men in the United States. Preventing or inhibiting metastasis-related events through non-toxic agents could be a useful approach for lowering high mortality among PCA patients. We have earlier reported that natural flavonoid silibinin possesses strong anti-metastatic efficacy against PCA however, mechanism/s of its action still remains largely unknown. One of the major events during metastasis is the replacement of cell-cell interaction with integrins-based cell-matrix interaction that controls motility, invasiveness and survival of cancer cells. Accordingly, here we examined silibinin effect on advanced human PCA PC3 cells' interaction with extracellular matrix component fibronectin. Silibinin (50-200 μM) treatment significantly decreased the fibronectin (5 μg/ml)-induced motile morphology via targeting actin cytoskeleton organization in PC3 cells. Silibinin also decreased the fibronectin-induced cell proliferation and motility but significantly increased cell death in PC3 cells. Silibinin also inhibited the PC3 cells invasiveness in Transwell invasion assays with fibronectin or cancer associated fibroblasts (CAFs) serving as chemoattractant. Importantly, PC3-luc cells cultured on fibronectin showed rapid dissemination and localized in lungs following tail vein injection in athymic male nude mice; however, in silibinin-treated PC3-luc cells, dissemination and lung localization was largely compromised. Molecular analyses revealed that silibinin treatment modulated the fibronectin-induced expression of integrins (α5, αV, β1 and β3), actin-remodeling (FAK, Src, GTPases, ARP2 and cortactin), apoptosis (cPARP and cleaved caspase 3), EMT (E-cadherin and β-catenin), and cell survival (survivin and Akt) related signaling molecules in PC3 cells. Furthermore, PC3-xenograft tissue analyses confirmed the inhibitory effect of silibinin on fibronectin and integrins expression. Together, these results showed that silibinin targets PCA cells' interaction with fibronectin and inhibits their motility, invasiveness and survival; thus further supporting silibinin use in PCA intervention including its metastatic progression.

Regional and local background ozone in Houston during Texas Air Quality Study 2006

NASA Astrophysics Data System (ADS)

Langford, A. O.; Senff, C. J.; Banta, R. M.; Hardesty, R. M.; Alvarez, R. J.; Sandberg, Scott P.; Darby, Lisa S.

2009-04-01

Principal Component Analysis (PCA) is used to isolate the common modes of behavior in the daily maximum 8-h average ozone mixing ratios measured at 30 Continuous Ambient Monitoring Stations in the Houston-Galveston-Brazoria area during the Second Texas Air Quality Study field intensive (1 August to 15 October 2006). Three principal components suffice to explain 93% of the total variance. Nearly 84% is explained by the first component, which is attributed to changes in the "regional background" determined primarily by the large-scale winds. The second component (6%) is attributed to changes in the "local background," that is, ozone photochemically produced in the Houston area and spatially and temporally averaged by local circulations. Finally, the third component (3.5%) is attributed to short-lived plumes containing high ozone originating from industrial areas along Galveston Bay and the Houston Ship Channel. Regional background ozone concentrations derived using the first component compare well with mean ozone concentrations measured above the Gulf of Mexico by the tunable profiler for aerosols and ozone lidar aboard the NOAA Twin Otter. The PCA regional background values also agree well with background values derived using the lowest daily 8-h maximum method of Nielsen-Gammon et al. (2005), provided the Galveston Airport data (C34) are omitted from that analysis. The differences found when Galveston is included are caused by the sea breeze, which depresses ozone at Galveston relative to sites further inland. PCA removes the effects of this and other local circulations to obtain a regional background value representative of the greater Houston area.

Dysregulated fibronectin trafficking by Hsp90 inhibition restricts prostate cancer cell invasion.

PubMed

Armstrong, Heather K; Gillis, Joanna L; Johnson, Ian R D; Nassar, Zeyad D; Moldovan, Max; Levrier, Claire; Sadowski, Martin C; Chin, Mei Yieng; Tomlinson Guns, Emma S; Tarulli, Gerard; Lynn, David J; Brooks, Douglas A; Selth, Luke A; Centenera, Margaret M; Butler, Lisa M

2018-02-01

The molecular chaperone Hsp90 is overexpressed in prostate cancer (PCa) and is responsible for the folding, stabilization and maturation of multiple oncoproteins, which are implicated in PCa progression. Compared to first-in-class Hsp90 inhibitors such as 17-allylamino-demethoxygeldanamycin (17-AAG) that were clinically ineffective, second generation inhibitor AUY922 has greater solubility and efficacy. Here, transcriptomic and proteomic analyses of patient-derived PCa explants identified cytoskeletal organization as highly enriched with AUY922 treatment. Validation in PCa cell lines revealed that AUY922 caused marked alterations to cell morphology, and suppressed cell motility and invasion compared to vehicle or 17-AAG, concomitant with dysregulation of key extracellular matrix proteins such as fibronectin (FN1). Interestingly, while the expression of FN1 was increased by AUY922, FN1 secretion was significantly decreased. This resulted in cytosolic accumulation of FN1 protein within late endosomes, suggesting that AUY922 disrupts vesicular secretory trafficking pathways. Depletion of FN1 by siRNA knockdown markedly reduced the invasive capacity of PCa cells, phenocopying AUY922. These results highlight a novel mechanism of action for AUY922 beyond its established effects on cellular mitosis and survival and, furthermore, identifies extracellular matrix cargo delivery as a potential therapeutic target for the treatment of aggressive PCa.

[Posterior cortical atrophy. Pathology, diagnosis and treatment of a rare form of dementia].

PubMed

Ortner, M; Kurz, A

2015-07-01

The syndrome of posterior cortical atrophy (PCA) is a rare clinical manifestation of several neurodegenerative diseases which affect the parieto-occipital cortex. The most frequent underlying pathology is Alzheimer's disease but some cases are caused by Lewy body disease, progressive subcortical gliosis, corticobasal degeneration or prion diseases. The most prominent clinical feature of PCA is complex visual disturbances including object agnosia, simultanagnosia, optical ataxia and oculomotor apraxia while basic visual functions remain intact. These deficits lead to multiple impairments in activities of daily living that require visual control. On progression of the disease amnestic, apraxic and dysexecutive symptoms occur so that a global dementia gradually emerges. At the core of the diagnostic work-up are a detailed patient history, accurate analysis of behavior and neuropsychological testing. Structural and functional brain imaging are suitable to demonstrate the localization of the disease process. Measurement of cerebrospinal fluid proteins (e.g. beta amyloid, tau, phospho-tau and 14-3-3) serves to confirm or exclude Alzheimer's disease or prion diseases. The mainstay of treatment are non-pharmacological interventions to support activities of daily living and personal independence. These treatments include cognitive training and compensatory strategies which can be prescribed as neuropsychological treatment or occupational therapy. If Alzheimer's disease or Lewy body disease is the likely cause, a treatment with cholinesterase inhibitor may be tried. Caregiver education and support are another essential part of the treatment regimen as with all forms of dementia.

Biomarkers in prostate cancer: what’s new?

PubMed Central

Sartori, David A.; Chan, Daniel W.

2014-01-01

Purpose of review This review is intended to provide an overview of the current state of biomarkers for prostate cancer (PCa), with a focus on biomarkers approved by the US Food and Drug Administration (FDA) as well as biomarkers available from Clinical Laboratory Improvement Amendment (CLIA)-certified clinical laboratories within the last 1–2 years. Recent findings During the past 2 years, two biomarkers have been approved by the US FDA. These include proPSA as part of the Prostate Health Index (phi) by Beckman Coulter, Inc and PCA3 as Progensa by Gen Probe, Inc. With the advances in genomic and proteomic technologies, several new CLIA-based laboratory-developed tests have become available. Examples are Oncotype DX from Genomics Health, Inc, and Prolaris from Myriad Genetics, Inc. In most cases, these new tests are based on a combination of multiple genomic or proteomic biomarkers. Summary Several new tests, as discussed in this review, have become available during the last 2 years. Although the intended use of most of these tests is to distinguish PCa from benign prostatic conditions with better sensitivity and specificity than prostate-specific antigen, studies have shown that some of them may also be useful in the differentiation of aggressive from nonaggressive forms of PCa. PMID:24626128

Clinical Features and Risk Factors of Skeletal-Related Events in Genitourinary Cancer Patients with Bone Metastasis: A Retrospective Analysis of Prostate Cancer, Renal Cell Carcinoma, and Urothelial Carcinoma.

PubMed

Owari, Takuya; Miyake, Makito; Nakai, Yasushi; Morizawa, Yosuke; Itami, Yoshitaka; Hori, Shunta; Anai, Satoshi; Tanaka, Nobumichi; Fujimoto, Kiyohide

2018-06-06

The objective of the present study was to report the incidence of skeletal-related events (SREs) and identify risk factors for SREs in patients with genitourinary cancer with newly diagnosed bone metastasis. This retrospective study included 180 patients with bone metastasis from prostate cancer (PCa; n = 111), renal cell carcinoma (RCC; n = 43), and urothelial carcinoma (UC; n = 26). Clinical factors at the time of diagnosis of bone metastasis were evaluated with Cox proportional hazards regression analysis to identify independent risk factors for SREs. During follow-up, 29 (26%) patients with PCa, 30 (70%) with RCC, and 15 (58%) with UC developed SREs. Treatment with bone-modifying agents (BMAs) before the development of SREs and within 6 months from the diagnosis of bone metastasis significantly delayed the time to first SRE as compared to nonuse of BMAs. Multivariate analysis identified type of primary cancer (PCa vs. RCC, PCa vs. UC), performance status, and bone pain as significant independent predictive risk factors for SREs. Treatment with BMAs significantly delayed the development of first SREs. The identified predictors of SREs might be useful to select patients who would benefit most from early treatment with BMAs. © 2018 S. Karger AG, Basel.

Point-of-care blood gases, electrolytes, chemistries, hemoglobin, and hematocrit measurement in venous samples from pet rabbits.

PubMed

Selleri, Paolo; Di Girolamo, Nicola

2014-01-01

Point-of-care testing is an attractive option in rabbit medicine, because it permits rapid analysis of a panel of electrolytes, chemistries, blood gases, hemoglobin, and hematocrit, requiring only 65 μL of blood. The purpose of this study was to evaluate the performance of a portable clinical analyzer for measurement of pH, partial pressure of CO2, Na, chloride, potassium, blood urea nitrogen, glucose, hematocrit, and hemoglobin in healthy and diseased rabbits. Blood samples obtained from 30 pet rabbits were analyzed immediately after collection by the portable clinical analyzer (PCA) and immediately thereafter (time <20 sec) by a reference analyzer. Bland-Altman plots and Passing-Bablok regression analysis were used to compare the results. Limits of agreement were wide for all the variables studied, with the exception of pH. Most variables presented significant proportional and/or constant bias. The current study provides sufficient evidence that the PCA presents reliability for pH, although its low agreement with a reference analyzer for the other variables does not support their interchangeability. Limits of agreement provided for each variable allow researchers to evaluate if the PCA is reliable enough for their scope. To the authors' knowledge, the present is the first report evaluating a PCA in the rabbit.

Exploring high-affinity binding properties of octamer peptides by principal component analysis of tetramer peptides.

PubMed

Kume, Akiko; Kawai, Shun; Kato, Ryuji; Iwata, Shinmei; Shimizu, Kazunori; Honda, Hiroyuki

2017-02-01

To investigate the binding properties of a peptide sequence, we conducted principal component analysis (PCA) of the physicochemical features of a tetramer peptide library comprised of 512 peptides, and the variables were reduced to two principal components. We selected IL-2 and IgG as model proteins and the binding affinity to these proteins was assayed using the 512 peptides mentioned above. PCA of binding affinity data showed that 16 and 18 variables were suitable for localizing IL-2 and IgG high-affinity binding peptides, respectively, into a restricted region of the PCA plot. We then investigated whether the binding affinity of octamer peptide libraries could be predicted using the identified region in the tetramer PCA. The results show that octamer high-affinity binding peptides were also concentrated in the tetramer high-affinity binding region of both IL-2 and IgG. The average fluorescence intensity of high-affinity binding peptides was 3.3- and 2.1-fold higher than that of low-affinity binding peptides for IL-2 and IgG, respectively. We conclude that PCA may be used to identify octamer peptides with high- or low-affinity binding properties from data from a tetramer peptide library. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Prostate Cancer Predictive Simulation Modelling, Assessing the Risk Technique (PCP-SMART): Introduction and Initial Clinical Efficacy Evaluation Data Presentation of a Simple Novel Mathematical Simulation Modelling Method, Devised to Predict the Outcome of Prostate Biopsy on an Individual Basis.

PubMed

Spyropoulos, Evangelos; Kotsiris, Dimitrios; Spyropoulos, Katherine; Panagopoulos, Aggelos; Galanakis, Ioannis; Mavrikos, Stamatios

2017-02-01

We developed a mathematical "prostate cancer (PCa) conditions simulating" predictive model (PCP-SMART), from which we derived a novel PCa predictor (prostate cancer risk determinator [PCRD] index) and a PCa risk equation. We used these to estimate the probability of finding PCa on prostate biopsy, on an individual basis. A total of 371 men who had undergone transrectal ultrasound-guided prostate biopsy were enrolled in the present study. Given that PCa risk relates to the total prostate-specific antigen (tPSA) level, age, prostate volume, free PSA (fPSA), fPSA/tPSA ratio, and PSA density and that tPSA ≥ 50 ng/mL has a 98.5% positive predictive value for a PCa diagnosis, we hypothesized that correlating 2 variables composed of 3 ratios (1, tPSA/age; 2, tPSA/prostate volume; and 3, fPSA/tPSA; 1 variable including the patient's tPSA and the other, a tPSA value of 50 ng/mL) could operate as a PCa conditions imitating/simulating model. Linear regression analysis was used to derive the coefficient of determination (R 2 ), termed the PCRD index. To estimate the PCRD index's predictive validity, we used the χ 2 test, multiple logistic regression analysis with PCa risk equation formation, calculation of test performance characteristics, and area under the receiver operating characteristic curve analysis using SPSS, version 22 (P < .05). The biopsy findings were positive for PCa in 167 patients (45.1%) and negative in 164 (44.2%). The PCRD index was positively signed in 89.82% positive PCa cases and negative in 91.46% negative PCa cases (χ 2 test; P < .001; relative risk, 8.98). The sensitivity was 89.8%, specificity was 91.5%, positive predictive value was 91.5%, negative predictive value was 89.8%, positive likelihood ratio was 10.5, negative likelihood ratio was 0.11, and accuracy was 90.6%. Multiple logistic regression revealed the PCRD index as an independent PCa predictor, and the formulated risk equation was 91% accurate in predicting the probability of finding PCa. On the receiver operating characteristic analysis, the PCRD index (area under the curve, 0.926) significantly (P < .001) outperformed other, established PCa predictors. The PCRD index effectively predicted the prostate biopsy outcome, correctly identifying 9 of 10 men who were eventually diagnosed with PCa and correctly ruling out PCa for 9 of 10 men who did not have PCa. Its predictive power significantly outperformed established PCa predictors, and the formulated risk equation accurately calculated the probability of finding cancer on biopsy, on an individual patient basis. Copyright © 2016 Elsevier Inc. All rights reserved.

The Clinical Impact of Additional Late PET/CT Imaging with 68Ga-PSMA-11 (HBED-CC) in the Diagnosis of Prostate Cancer.

PubMed

Afshar-Oromieh, Ali; Sattler, Lars Peter; Mier, Walter; Hadaschik, Boris A; Debus, Jürgen; Holland-Letz, Tim; Kopka, Klaus; Haberkorn, Uwe

2017-05-01

Although PET/CT with 68 Ga-PSMA-11 in the diagnosis of prostate cancer (PCa) is routinely performed at 1 h after injection, later scans may be beneficial because most lesions present with higher uptake and contrast. This evaluation aimed to investigate the clinical impact of additional late 68 Ga-PSMA-11 PET/CT. Methods: Between 2011 and 2016, 112 patients with PCa who underwent early (at 1 h after injection) and late (at 3 h after injection) 68 Ga-PSMA-11 PET/CT scans were retrospectively evaluated. The late scans were conducted to clarify unclear findings in early scans or to increase the probability of tumor detection in the case of negative early scans. All patients were asked to drink 1 L of water between early and late scans. In addition, 20 patients received 20 mg of furosemide before late scans. Tumor detection and radioactivity concentration within the urinary bladder were analyzed in both scans. The SUV max and contrast of 149 tumor lesions were measured in 69 patients with pathologic findings. Results: Overall, 134 lesions characteristic for PCa in 57 patients clearly presented at 1 h after injection and 147 lesions in 68 patients at 3 h after injection. Forty-three patients showed no pathologic findings. Eight patients (7.1%) showed 1 unclear finding in early scans, which could be clarified as characteristic for PCa at 3 h after injection. Four patients (3.6%) presented with 1 lesion characteristic for PCa at 3 h after injection only. Twelve patients (10.7%) presented with 12 possible PCa lesions at 1 h after injection, which, however, could not be confirmed as PCa in late scans. Two patients presented with 1 lesion characteristic for PCa at 1 h after injection, which became invisible at 3 h after injection because of low contrast. At 3 h after injection, 62.4% of the lesions demonstrated a higher SUV max and 65.1% a higher contrast than at 1 h after injection. Patients with furosemide presented with lower SUV and radioactivity concentration within the urinary bladder. Conclusion: 68 Ga-PSMA-11 PET/CT at 3 h after injection showed most lesions characteristic for PCa with a higher uptake and contrast. In addition, the radioactivity signal within the urinary bladder was lower at 3 h after injection, especially when furosemide was applied. Consequently, scans at 3 h after injection detected more tumor lesions than at 1 h after injection. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Clinical efficacy of transrectal ultrasound-guided prostate biopsy in men younger than 50 years old with an elevated prostate-specific antigen concentration (>4.0 ng/mL).

PubMed

Lu, Chin-Heng; Lin, Tzu-Ping; Shen, She Huei; Huang, Yi-Hsiu; Chung, Hsiao-Jen; Kuo, Junne-Yih; Huang, William J S; Wu, Howard H H; Chang, Yen-Hwa; Lin, Alex T L; Chen, Kuang-Kuo

2017-07-01

Prostate cancer (PCa) is not commonly found in men younger than 50 years of age. However, serum prostate-specific antigen (PSA) concentration has been examined more frequently at a younger age in Asia partially due to an increased awareness of prostate cancer. The purpose of our study was to investigate the efficacy and complication of PSA-triggered transrectal ultrasonography-guided prostate (TRUSP) biopsies. We retrospectively reviewed TRUSP biopsies in young men with elevated PSA concentration in Taipei Veterans General Hospital. We reviewed the cases of patients younger than 50 years of age with elevated PSA concentration (>4.0 ng/mL), who received 12 cores TRUSP biopsies at TPEVGH from January 2008-December 2013. The age, family history, digital rectal examination (DRE) results, PSA concentration, free/total PSA ratio, total prostate volume, PSA density, lower urinary tract symptoms and complications after the procedure were reviewed. The pathologic findings of TRUSP biopsy and clinical follow-up were reviewed and analyzed according to the Epstein criteria. A total of 77 patients were included and were divided into 2 groups: 1) the younger group consisted of 20 patients <40 years of age; and 2) the elder group had 57 patients who were 40-50 years of age. The overall detection rate of PCa was 11.69% (9/77), and all of the PCa cases were diagnosed in the elder group (group detection rate: 15.8%). There was a significant difference in the severity of lower urinary tract symptoms (LUTS) between these 2 groups. All PCa patients were clinically significant according to the Epstein criteria. Two patients experienced fever (2.60%) after TRUSP biopsy. From our patient cohort, it appears that no benefit was apparent for patients younger than 40 years old who received TRUSP biopsy, even with elevated PSA. However, PCa detected in men between 40 and 50 years of age were all clinically significant. Overall, our results supported current major practice guidelines which recommend an initial PSA checkup at 40 years of age. Copyright © 2017. Published by Elsevier Taiwan LLC.

Novel Multiplex MethyLight Protocol for Detection of DNA Methylation in Patient Tissues and Bodily Fluids

PubMed Central

Olkhov-Mitsel, Ekaterina; Zdravic, Darko; Kron, Ken; van der Kwast, Theodorus; Fleshner, Neil; Bapat, Bharati

2014-01-01

Aberrant DNA methylation is a hallmark of cancer and is an important potential biomarker. Particularly, combined analysis of a panel of hypermethylated genes shows the most promising clinical performance. Herein, we developed, optimized and standardized a multiplex MethyLight assay to simultaneously detect hypermethylation of APC, HOXD3 and TGFB2 in DNA extracted from prostate cancer (PCa) cell lines, archival tissue specimens, and urine samples. We established that the assay is capable of discriminating between fully methylated and unmethylated alleles with 100% specificity and demonstrated the assay as highly accurate and reproducible as the singleplex approach. For proof of principle, we analyzed the methylation status of these genes in tissue and urine samples of PCa patients as well as PCa-free controls. These data show that the multiplex MethyLight assay offers a significant advantage when working with limited quantities of DNA and has potential applications in research and clinical settings. PMID:24651255

[Experience in the treatment of patent ductus arteriosus closure at a mexican hospital].

PubMed

Márquez-González, Horacio; Castro-Contreras, Uriel; Cerrud-Sánchez, Carmen Emma; López-Gallegos, Diana; Yáñez-Gutiérrez, Lucelli

2016-01-01

The patent ductus arteriosus (PDA) represents one of the most prevalent diseases in hospitals which treat congenital heart diseases (CHD). Currently, in groups of more than 1 year of age percutaneous closure it is the standard therapy. The aim of this paper is to determine the frequency, characteristics and treatment of PCA in congenital heart disease service at the a Cardiology Hospital in Mexico. In clinical CHD our hospital, a descriptive study of 2010-2015 of patients who were treated with percutaneous closure PCA and surgery was performed. They were divided into the following ages: infant, preschool, children, adolescents and adults. The absolute frequencies were recorded. 187 patients of preschool and school which accounted for 60% of the total sample were obtained. Percutaneous closure catheterization was performed in 90%; 2% of complications were recorded. In this clinic, the PCA is treated mostly by interventional catheterization in most stages of the human being with minimal complications.

Arachidonate 15-Lipoxygenase 2 as an Endogenous Inhibitor of Prostate Cancer Development

DTIC Science & Technology

2006-03-01

dehydrogenase; NHP, normal human prostate epithelial cells; PCa, prostate cancer; NLS, nuclear localization signal; PPAR -, peroxisome proliferator...cloned, i.e., 15-LOX2sv-a/b/c, are mostly excluded from the nucleus. A potential bi-partite nuclear localization signal (NLS...only partially involved in the nuclear import of 15-LOX2. To elucidate the relationship between nuclear localization , enzymatic activity, and tumor

Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahara, Kiyoshi; Ii, Masaaki, E-mail: masaii@art.osaka-med.ac.jp; Inamoto, Teruo

2014-04-18

Highlights: • AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells. • AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway. • High expression of the TGF-β1 gene in AdSCs. - Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferationmore » of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.« less

Prospective Quality of Life Outcomes for Low-Risk Prostate Cancer: Active Surveillance versus Radical Prostatectomy

PubMed Central

Jeldres, Claudio; Cullen, Jennifer; Hurwitz, Lauren M.; Wolff, Erika M.; Levie, Katherine; Odem-Davis, Katherine; Johnston, Richard B.; Pham, Khanh N.; Rosner, Inger L; Brand, Timothy C.; L’Esperance, James O.; Sterbis, Joseph R.; Etzioni, Ruth B.; Porter, Christopher R.

2015-01-01

Background For low-risk prostate cancer (PCa), active surveillance (AS) may confer comparable oncological outcomes to radical prostatectomy (RP). Health-related quality of life (HRQoL) outcomes are important to consider, yet few studies have examined HRQoL for patients managed with AS. This study compared longitudinal HRQoL in a prospective, racially diverse, and contemporary cohort of patients who underwent RP or AS for low-risk PCa. Methods Beginning in 2007, HRQoL data from validated questionnaires (EPIC and SF-36) were collected by the Center for Prostate Disease Research in a multi-center national database. Patients aged ≤75 that were diagnosed with low-risk PCa and elected RP or AS for initial disease management were followed for three years. Mean scores were estimated using generalized estimating equations, adjusting for baseline HRQoL, demographic and clinical patient characteristics. Results Of the patients with low-risk PCa, 228 underwent RP and 77 underwent AS. Multivariable analysis revealed that RP patients had significantly worse sexual function, sexual bother, and urinary function at all time points compared to patients on AS. Differences in mental health between groups were below the threshold for clinical significance at one year. Conclusions This study found no differences in mental health outcomes but worse urinary and sexual HRQoL for RP patients compared to AS patients for up to three years. These data offer support for management of low risk PCa with AS as a means for postponing the morbidity associated with RP without concomitant mental health declines. PMID:25845467

Genome-wide copy number analysis reveals candidate gene loci that confer susceptibility to high-grade prostate cancer.

PubMed

Poniah, Prevathe; Mohd Zain, Shamsul; Abdul Razack, Azad Hassan; Kuppusamy, Shanggar; Karuppayah, Shankar; Sian Eng, Hooi; Mohamed, Zahurin

2017-09-01

Two key issues in prostate cancer (PCa) that demand attention currently are the need for a more precise and minimally invasive screening test owing to the inaccuracy of prostate-specific antigen and differential diagnosis to distinguish advanced vs. indolent cancers. This continues to pose a tremendous challenge in diagnosis and prognosis of PCa and could potentially lead to overdiagnosis and overtreatment complications. Copy number variations (CNVs) in the human genome have been linked to various carcinomas including PCa. Detection of these variants may improve clinical treatment as well as an understanding of the pathobiology underlying this complex disease. To this end, we undertook a pilot genome-wide CNV analysis approach in 36 subjects (18 patients with high-grade PCa and 18 controls that were matched by age and ethnicity) in search of more accurate biomarkers that could potentially explain susceptibility toward high-grade PCa. We conducted this study using the array comparative genomic hybridization technique. Array results were validated in 92 independent samples (46 high-grade PCa, 23 benign prostatic hyperplasia, and 23 healthy controls) using polymerase chain reaction-based copy number counting method. A total of 314 CNV regions were found to be unique to PCa subjects in this cohort (P<0.05). A log 2 ratio-based copy number analysis revealed 5 putative rare or novel CNV loci or both associated with susceptibility to PCa. The CNV gain regions were 1q21.3, 15q15, 7p12.1, and a novel CNV in PCa 12q23.1, harboring ARNT, THBS1, SLC5A8, and DDC genes that are crucial in the p53 and cancer pathways. A CNV loss and deletion event was observed at 8p11.21, which contains the SFRP1 gene from the Wnt signaling pathway. Cross-comparison analysis with genes associated to PCa revealed significant CNVs involved in biological processes that elicit cancer pathogenesis via cytokine production and endothelial cell proliferation. In conclusion, we postulated that the CNVs identified in this study could provide an insight into the development of advanced PCa. Copyright © 2017 Elsevier Inc. All rights reserved.

Racial Differences in the Diagnosis and Treatment of Prostate Cancer.

PubMed

Pietro, Giuliano Di; Chornokur, Ganna; Kumar, Nagi B; Davis, Chemar; Park, Jong Y

2016-11-01

Disparities between African American and Caucasian men in prostate cancer (PCa) diagnosis and treatment in the United States have been well established, with significant racial disparities documented at all stages of PCa management, from differences in the type of treatment offered to progression-free survival or death. These disparities appear to be complex in nature, involving biological determinants as well as socioeconomic and cultural aspects. We present a review of the literature on racial disparities in the diagnosis of PCa, treatment, survival, and genetic susceptibility. Significant differences were found among African Americans and whites in the incidence and mortality rates; namely, African Americans are diagnosed with PCa at younger ages than whites and usually with more advanced stages of the disease, and also undergo prostate-specific antigen testing less frequently. However, the determinants of the high rate of incidence and aggressiveness of PCa in African Americans remain unresolved. This pattern can be attributed to socioeconomic status, detection occurring at advanced stages of the disease, biological aggressiveness, family history, and differences in genetic susceptibility. Another risk factor for PCa is obesity. We found many discrepancies regarding treatment, including a tendency for more African American patients to be in watchful waiting than whites. Many factors are responsible for the higher incidence and mortality rates in African Americans. Better screening, improved access to health insurance and clinics, and more homogeneous forms of treatment will contribute to the reduction of disparities between African Americans and white men in PCa incidence and mortality.

Probability distributions of the electroencephalogram envelope of preterm infants.

PubMed

Saji, Ryoya; Hirasawa, Kyoko; Ito, Masako; Kusuda, Satoshi; Konishi, Yukuo; Taga, Gentaro

2015-06-01

To determine the stationary characteristics of electroencephalogram (EEG) envelopes for prematurely born (preterm) infants and investigate the intrinsic characteristics of early brain development in preterm infants. Twenty neurologically normal sets of EEGs recorded in infants with a post-conceptional age (PCA) range of 26-44 weeks (mean 37.5 ± 5.0 weeks) were analyzed. Hilbert transform was applied to extract the envelope. We determined the suitable probability distribution of the envelope and performed a statistical analysis. It was found that (i) the probability distributions for preterm EEG envelopes were best fitted by lognormal distributions at 38 weeks PCA or less, and by gamma distributions at 44 weeks PCA; (ii) the scale parameter of the lognormal distribution had positive correlations with PCA as well as a strong negative correlation with the percentage of low-voltage activity; (iii) the shape parameter of the lognormal distribution had significant positive correlations with PCA; (iv) the statistics of mode showed significant linear relationships with PCA, and, therefore, it was considered a useful index in PCA prediction. These statistics, including the scale parameter of the lognormal distribution and the skewness and mode derived from a suitable probability distribution, may be good indexes for estimating stationary nature in developing brain activity in preterm infants. The stationary characteristics, such as discontinuity, asymmetry, and unimodality, of preterm EEGs are well indicated by the statistics estimated from the probability distribution of the preterm EEG envelopes. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Disparities at Presentation, Diagnosis, Treatment and Survival in African American Men, Affected by Prostate Cancer

PubMed Central

Chornokur, Ganna; Dalton, Kyle; Borysova, Meghan; Kumar, Nagi

2011-01-01

Background Prostate cancer (PCa) remains the most common malignancy and the second leading cause of cancer death among men in the United States. PCa exhibits the most striking racial disparity, as African American men are at 1.4 times higher risk of being diagnosed, and two to three times higher risk of dying of PCa, compared to Caucasian men. The etiology of the disparity has not been clearly elucidated. The objective of this paper is to critically review the literature and summarize the most prominent PCa racial disparities accompanied by proposed explanations. Methods The present literature on disparities at presentation, diagnosis, treatment and survival of African American men affected by PCa was systematically reviewed. Original research as well as relevant review articles were included. Results African American men recurrently present with more advanced disease than Caucasian men, are administered different treatment regimens than Caucasian men, and have shorter progression-free survival following treatment. In addition, African American men report more treatment related side-effects that translates to the diminished quality of life. Conclusions PCa racial disparity exists at stages of presentation, diagnosis, treatment regimens and subsequent survival, and the quality of life. The disparities are complex in involving biological, socio-economic and socio-cultural determinants. These mounting results highlight an urgent need for future clinical, scientific and socio-cultural research involving transdisciplinary teams to elucidate the causes for PCa racial disparities. PMID:21541975

Extraction of prostatic lumina and automated recognition for prostatic calculus image using PCA-SVM.

PubMed

Wang, Zhuocai; Xu, Xiangmin; Ding, Xiaojun; Xiao, Hui; Huang, Yusheng; Liu, Jian; Xing, Xiaofen; Wang, Hua; Liao, D Joshua

2011-01-01

Identification of prostatic calculi is an important basis for determining the tissue origin. Computation-assistant diagnosis of prostatic calculi may have promising potential but is currently still less studied. We studied the extraction of prostatic lumina and automated recognition for calculus images. Extraction of lumina from prostate histology images was based on local entropy and Otsu threshold recognition using PCA-SVM and based on the texture features of prostatic calculus. The SVM classifier showed an average time 0.1432 second, an average training accuracy of 100%, an average test accuracy of 93.12%, a sensitivity of 87.74%, and a specificity of 94.82%. We concluded that the algorithm, based on texture features and PCA-SVM, can recognize the concentric structure and visualized features easily. Therefore, this method is effective for the automated recognition of prostatic calculi.

Low-Dimensional Feature Representation for Instrument Identification

NASA Astrophysics Data System (ADS)

Ihara, Mizuki; Maeda, Shin-Ichi; Ikeda, Kazushi; Ishii, Shin

For monophonic music instrument identification, various feature extraction and selection methods have been proposed. One of the issues toward instrument identification is that the same spectrum is not always observed even in the same instrument due to the difference of the recording condition. Therefore, it is important to find non-redundant instrument-specific features that maintain information essential for high-quality instrument identification to apply them to various instrumental music analyses. For such a dimensionality reduction method, the authors propose the utilization of linear projection methods: local Fisher discriminant analysis (LFDA) and LFDA combined with principal component analysis (PCA). After experimentally clarifying that raw power spectra are actually good for instrument classification, the authors reduced the feature dimensionality by LFDA or by PCA followed by LFDA (PCA-LFDA). The reduced features achieved reasonably high identification performance that was comparable or higher than those by the power spectra and those achieved by other existing studies. These results demonstrated that our LFDA and PCA-LFDA can successfully extract low-dimensional instrument features that maintain the characteristic information of the instruments.

Patient and provider attitudes toward genomic testing for prostate cancer susceptibility: a mixed method study.

PubMed

Birmingham, Wendy C; Agarwal, Neeraj; Kohlmann, Wendy; Aspinwall, Lisa G; Wang, Mary; Bishoff, Jay; Dechet, Christopher; Kinney, Anita Y

2013-07-20

The strong association between family history and prostate cancer (PCa) suggests a significant genetic contribution, yet specific highly penetrant PCa susceptibility genes have not been identified. Certain single-nucleotide-polymorphisms have been found to correlate with PCa risk; however uncertainty remains regarding their clinical utility and how to best incorporate this information into clinical decision-making. Genetic testing is available directly to consumers and both patients and healthcare providers are becoming more aware of this technology. Purchasing online allows patients to bypass their healthcare provider yet patients may have difficulty interpreting test results and providers may be called upon to interpret results. Determining optimal ways to educate both patients and providers, and strategies for appropriately incorporating this information into clinical decision-making are needed. A mixed-method study was conducted in Utah between October 2011 and December 2011. Eleven focus group discussions were held and surveys were administered to 23 first-degree relatives of PCa patients living in Utah and 24 primary-care physicians and urologists practicing in Utah to present specific information about these assessments and determine knowledge and attitudes regarding health implications of using these assessments. Data was independently coded by two researchers (relative Kappa = .88; provider Kappa = .77) and analyzed using a grounded theory approach. Results indicated differences in attitudes and behavioral intentions between patient and provider. Despite the test's limitations relatives indicated interest in genetic testing (52%) while most providers indicated they would not recommend the test for their patients (79%). Relatives expected providers to interpret genetic test results and use results to provide personalized healthcare recommendations while the majority of providers did not think the information would be useful in patient care (92%) and indicated low-levels of genetic self-efficacy. Although similarities exist, discordance between provider and patient attitudes may influence the effective translation of novel genomic tests into clinical practice suggesting both patient and provider perceptions and expectations be considered in development of clinical decision-support tools.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Bo, E-mail: luboufl@gmail.com; Park, Justin C.; Fan, Qiyong

Purpose: Accurately localizing lung tumor localization is essential for high-precision radiation therapy techniques such as stereotactic body radiation therapy (SBRT). Since direct monitoring of tumor motion is not always achievable due to the limitation of imaging modalities for treatment guidance, placement of fiducial markers on the patient’s body surface to act as a surrogate for tumor position prediction is a practical alternative for tracking lung tumor motion during SBRT treatments. In this work, the authors propose an innovative and robust model to solve the multimarker position optimization problem. The model is able to overcome the major drawbacks of the sparsemore » optimization approach (SOA) model. Methods: The principle-component-analysis (PCA) method was employed as the framework to build the authors’ statistical prediction model. The method can be divided into two stages. The first stage is to build the surrogate tumor matrix and calculate its eigenvalues and associated eigenvectors. The second stage is to determine the “best represented” columns of the eigenvector matrix obtained from stage one and subsequently acquire the optimal marker positions as well as numbers. Using 4-dimensional CT (4DCT) and breath hold CT imaging data, the PCA method was compared to the SOA method with respect to calculation time, average prediction accuracy, prediction stability, noise resistance, marker position consistency, and marker distribution. Results: The PCA and SOA methods which were both tested were on all 11 patients for a total of 130 cases including 4DCT and breath-hold CT scenarios. The maximum calculation time for the PCA method was less than 1 s with 64 752 surface points, whereas the average calculation time for the SOA method was over 12 min with 400 surface points. Overall, the tumor center position prediction errors were comparable between the two methods, and all were less than 1.5 mm. However, for the extreme scenarios (breath hold), the prediction errors for the PCA method were not only smaller, but were also more stable than for the SOA method. Results obtained by imposing a series of random noises to the surrogates indicated that the PCA method was much more noise resistant than the SOA method. The marker position consistency tests using various combinations of 4DCT phases to construct the surrogates suggested that the marker position predictions of the PCA method were more consistent than those of the SOA method, in spite of surrogate construction. Marker distribution tests indicated that greater than 80% of the calculated marker positions fell into the high cross correlation and high motion magnitude regions for both of the algorithms. Conclusions: The PCA model is an accurate, efficient, robust, and practical model for solving the multimarker position optimization problem to predict lung tumor motion during SBRT treatments. Due to its generality, PCA model can also be applied to other imaging guidance system whichever using surface motion as the surrogates.« less

Mapping the Similarities of Spectra: Global and Locally-biased Approaches to SDSS Galaxies

NASA Astrophysics Data System (ADS)

Lawlor, David; Budavári, Tamás; Mahoney, Michael W.

2016-12-01

We present a novel approach to studying the diversity of galaxies. It is based on a novel spectral graph technique, that of locally-biased semi-supervised eigenvectors. Our method introduces new coordinates that summarize an entire spectrum, similar to but going well beyond the widely used Principal Component Analysis (PCA). Unlike PCA, however, this technique does not assume that the Euclidean distance between galaxy spectra is a good global measure of similarity. Instead, we relax that condition to only the most similar spectra, and we show that doing so yields more reliable results for many astronomical questions of interest. The global variant of our approach can identify very finely numerous astronomical phenomena of interest. The locally-biased variants of our basic approach enable us to explore subtle trends around a set of chosen objects. The power of the method is demonstrated in the Sloan Digital Sky Survey Main Galaxy Sample, by illustrating that the derived spectral coordinates carry an unprecedented amount of information.

High Accuracy Passive Magnetic Field-Based Localization for Feedback Control Using Principal Component Analysis.

PubMed

Foong, Shaohui; Sun, Zhenglong

2016-08-12

In this paper, a novel magnetic field-based sensing system employing statistically optimized concurrent multiple sensor outputs for precise field-position association and localization is presented. This method capitalizes on the independence between simultaneous spatial field measurements at multiple locations to induce unique correspondences between field and position. This single-source-multi-sensor configuration is able to achieve accurate and precise localization and tracking of translational motion without contact over large travel distances for feedback control. Principal component analysis (PCA) is used as a pseudo-linear filter to optimally reduce the dimensions of the multi-sensor output space for computationally efficient field-position mapping with artificial neural networks (ANNs). Numerical simulations are employed to investigate the effects of geometric parameters and Gaussian noise corruption on PCA assisted ANN mapping performance. Using a 9-sensor network, the sensing accuracy and closed-loop tracking performance of the proposed optimal field-based sensing system is experimentally evaluated on a linear actuator with a significantly more expensive optical encoder as a comparison.

Multiparametric magnetic resonance imaging and frozen-section analysis efficiently predict upgrading, upstaging, and extraprostatic extension in patients undergoing nerve-sparing robotic-assisted radical prostatectomy

PubMed Central

Bianchi, Roberto; Cozzi, Gabriele; Petralia, Giuseppe; Alessi, Sarah; Renne, Giuseppe; Bottero, Danilo; Brescia, Antonio; Cioffi, Antonio; Cordima, Giovanni; Ferro, Matteo; Matei, Deliu Victor; Mazzoleni, Federica; Musi, Gennaro; Mistretta, Francesco Alessandro; Serino, Alessandro; Tringali, Valeria Maria Lucia; Coman, Ioan; De Cobelli, Ottavio

2016-01-01

Abstract To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) in predicting upgrading, upstaging, and extraprostatic extension in patients with low-risk prostate cancer (PCa). MpMRI may reduce positive surgical margins (PSM) and improve nerve-sparing during robotic-assisted radical prostatectomy (RARP) for localized prostate cancer PCa. This was a retrospective, monocentric, observational study. We retrieved the records of patients undergoing RARP from January 2012 to December 2013 at our Institution. Inclusion criteria were: PSA <10 ng/mL; clinical stage

Multiparametric magnetic resonance imaging and frozen-section analysis efficiently predict upgrading, upstaging, and extraprostatic extension in patients undergoing nerve-sparing robotic-assisted radical prostatectomy.

PubMed

Bianchi, Roberto; Cozzi, Gabriele; Petralia, Giuseppe; Alessi, Sarah; Renne, Giuseppe; Bottero, Danilo; Brescia, Antonio; Cioffi, Antonio; Cordima, Giovanni; Ferro, Matteo; Matei, Deliu Victor; Mazzoleni, Federica; Musi, Gennaro; Mistretta, Francesco Alessandro; Serino, Alessandro; Tringali, Valeria Maria Lucia; Coman, Ioan; De Cobelli, Ottavio

2016-10-01

To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) in predicting upgrading, upstaging, and extraprostatic extension in patients with low-risk prostate cancer (PCa). MpMRI may reduce positive surgical margins (PSM) and improve nerve-sparing during robotic-assisted radical prostatectomy (RARP) for localized prostate cancer PCa.This was a retrospective, monocentric, observational study. We retrieved the records of patients undergoing RARP from January 2012 to December 2013 at our Institution. Inclusion criteria were: PSA <10 ng/mL; clinical stage

Neoadjuvant docetaxel treatment for locally advanced prostate cancer: a clinicopathologic study.

PubMed

Magi-Galluzzi, Cristina; Zhou, Ming; Reuther, Alwyn M; Dreicer, Robert; Klein, Eric A

2007-09-15

The objective of the current study was to determine the histologic and molecular changes that occurred in patients with high-risk, localized prostate cancer (PCa) after neoadjuvant docetaxel chemotherapy. Patients who had locally advanced PCa (serum preoperative [initial] prostate-specific antigen [iPSA] level >or=15 ng/mL, or clinical >or=T2b disease, or biopsy Gleason score [GS] >or=8) and no evidence of metastatic disease received 6 doses of intravenous docetaxel (40 mg/m(2)) administered weekly for 6 weeks followed by radical prostatectomy (RP). The Wilcoxon signed-rank test was used to compare pretreatment and posttreatment markers. Twenty-eight patients completed chemotherapy and underwent RP at the Cleveland Clinic; none achieved a pathologic complete response. Pretreatment diagnostic prostate biopsies (PBx) were reviewed in all patients, and unstained sections of formalin-fixed tissue were available from 11 patients. The median patient age was 62 years (range, 49-72 years), and the median iPSA was 6.8 ng/mL (range, 2.5-24 ng/mL). At a median follow-up of 49.5 months (range, 23-72 months), 12 patients (43%) remained clinically and biochemically free of disease with no additional therapy, and 16 patients (57%) had biochemical failure. The pretreatment GS was 6 in 2 patients (7%), 7 in 10 patients (36%), 8 in 11 patients (39%) and 9 in 5 patients (18%). Two patients (7.1%) had organ-confined disease, and 23 patients (82.1%) had extraprostatic extension. Four patients (14.3%) had positive lymph nodes, and 11 patients (39.3%) had seminal vesicle involvement. Immunohistochemical (IHC) staining for a panel of markers involved in various cellular functions (alpha-methylacyl-coenzyme A racemase [AMACR], beta-tubulin I, beta-tubulin III, cyclin D1, p27, p21, Ki-67, p53, Bcl-2, and an apoptosis detection kit [ApopTag]) was performed on a tissue microarray that contained the posttreatment (RP) tissue specimens and on the PBx specimens, if available. When the IHC staining patterns were compared between PBx and RP specimens using the Wilcoxon signed-rank test, only p53 expression (P = .017) and Bcl-2 expression (P = .014) were found to be increased significantly after neoadjuvant docetaxel treatment. However, after performing the Bonferroni adjustment, these differences were no longer significant (P > .005). Ki-67, ApopTag, beta-tubulin I, and beta-tubulin III expression levels also were increased after treatment; however, the differences were not found to be statistically significant. The expression levels of AMACR, p27, p21, and cyclin D1 were comparable in pretreatment and posttreatment specimens. The current results indicated that, although it will require longer follow-up studies and larger numbers of patients to ascertain the value of neoadjuvant treatment, the negative findings of the current study may explain the lack of clinical response in patients who received neoadjuvant docetaxel for PCa. Although the results were subject to interpretation limits based on the study size, the increased expression of p53 and Bcl-2 that was detected after treatment using the Wilcoxon signed-rank test suggested that the apoptotic pathway may be an important target for this drug, and further investigation is warranted. (c) 2007 American Cancer Society.

The histogram analysis of diffusion-weighted intravoxel incoherent motion (IVIM) imaging for differentiating the gleason grade of prostate cancer.

PubMed

Zhang, Yu-Dong; Wang, Qing; Wu, Chen-Jiang; Wang, Xiao-Ning; Zhang, Jing; Liu, Hui; Liu, Xi-Sheng; Shi, Hai-Bin

2015-04-01

To evaluate histogram analysis of intravoxel incoherent motion (IVIM) for discriminating the Gleason grade of prostate cancer (PCa). A total of 48 patients pathologically confirmed as having clinically significant PCa (size > 0.5 cm) underwent preoperative DW-MRI (b of 0-900 s/mm(2)). Data was post-processed by monoexponential and IVIM model for quantitation of apparent diffusion coefficients (ADCs), perfusion fraction f, diffusivity D and pseudo-diffusivity D*. Histogram analysis was performed by outlining entire-tumour regions of interest (ROIs) from histological-radiological correlation. The ability of imaging indices to differentiate low-grade (LG, Gleason score (GS) ≤6) from intermediate/high-grade (HG, GS > 6) PCa was analysed by ROC regression. Eleven patients had LG tumours (18 foci) and 37 patients had HG tumours (42 foci) on pathology examination. HG tumours had significantly lower ADCs and D in terms of mean, median, 10th and 75th percentiles, combined with higher histogram kurtosis and skewness for ADCs, D and f, than LG PCa (p < 0.05). Histogram D showed relatively higher correlations (ñ = 0.641-0.668 vs. ADCs: 0.544-0.574) with ordinal GS of PCa; and its mean, median and 10th percentile performed better than ADCs did in distinguishing LG from HG PCa. It is feasible to stratify the pathological grade of PCa by IVIM with histogram metrics. D performed better in distinguishing LG from HG tumour than conventional ADCs. • GS had relatively higher correlation with tumour D than ADCs. • Difference of histogram D among two-grade tumours was statistically significant. • D yielded better individual features in demonstrating tumour grade than ADC. • D* and f failed to determine tumour grade of PCa.

Urinary MicroRNAs of Prostate Cancer: Virus-Encoded hsv1-miRH18 and hsv2-miR-H9-5p Could Be Valuable Diagnostic Markers.

PubMed

Yun, Seok Joong; Jeong, Pildu; Kang, Ho Won; Kim, Ye-Hwan; Kim, Eun-Ah; Yan, Chunri; Choi, Young-Ki; Kim, Dongho; Kim, Jung Min; Kim, Seon-Kyu; Kim, Seon-Young; Kim, Sang Tae; Kim, Won Tae; Lee, Ok-Jun; Koh, Gou-Young; Moon, Sung-Kwon; Kim, Isaac Yi; Kim, Jayoung; Choi, Yung-Hyun; Kim, Wun-Jae

2015-06-01

MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH. In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study. A urine-based miRNA microarray analysis suggested the presence of differentially expressed urinary miRNAs in patients with PCa, and these were further validated in three independent PCa cohorts, using a quantitative reverse transcriptionpolymerase chain reaction analysis. The expression levels of hsa-miR-615-3p, hsv1-miR-H18, hsv2-miR-H9-5p, and hsa-miR-4316 were significantly higher in urine samples of patients with PCa than in those of BPH controls. In particular, herpes simplex virus (hsv)-derived hsv1-miR-H18 and hsv2-miR-H9-5p showed better diagnostic performance than did the serum prostate-specific antigen (PSA) test for patients in the PSA gray zone. Furthermore, a combination of urinary hsv2-miR-H9-5p with serum PSA showed high sensitivity and specificity, providing a potential clinical benefit by reducing unnecessary biopsies. Our findings showed that hsv-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are significantly associated with PCa and can facilitate early diagnosis of PCa for patients within the serum PSA gray zone.

Urinary MicroRNAs of Prostate Cancer: Virus-Encoded hsv1-miRH18 and hsv2-miR-H9-5p Could Be Valuable Diagnostic Markers

PubMed Central

Yun, Seok Joong; Jeong, Pildu; Kang, Ho Won; Kim, Ye-Hwan; Kim, Eun-Ah; Yan, Chunri; Choi, Young-Ki; Kim, Dongho; Kim, Jung Min; Kim, Seon-Kyu; Kim, Seon-Young; Kim, Sang Tae; Kim, Won Tae; Lee, Ok-Jun; Koh, Gou-Young; Moon, Sung-Kwon; Kim, Isaac Yi; Kim, Jayoung; Choi, Yung-Hyun; Kim, Wun-Jae

2015-01-01

Purpose: MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH. Methods: In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study. A urine-based miRNA microarray analysis suggested the presence of differentially expressed urinary miRNAs in patients with PCa, and these were further validated in three independent PCa cohorts, using a quantitative reverse transcriptionpolymerase chain reaction analysis. Results: The expression levels of hsa-miR-615-3p, hsv1-miR-H18, hsv2-miR-H9-5p, and hsa-miR-4316 were significantly higher in urine samples of patients with PCa than in those of BPH controls. In particular, herpes simplex virus (hsv)-derived hsv1-miR-H18 and hsv2-miR-H9-5p showed better diagnostic performance than did the serum prostate-specific antigen (PSA) test for patients in the PSA gray zone. Furthermore, a combination of urinary hsv2-miR-H9-5p with serum PSA showed high sensitivity and specificity, providing a potential clinical benefit by reducing unnecessary biopsies. Conclusions: Our findings showed that hsv-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are significantly associated with PCa and can facilitate early diagnosis of PCa for patients within the serum PSA gray zone. PMID:26126436

Polymorphisms in carcinogen metabolism enzymes, fish intake, and risk of prostate cancer

PubMed Central

Stern, Mariana C.

2012-01-01

Cooking fish at high temperature can produce potent carcinogens such as heterocyclic amines and polycyclic aromatic hydrocarbons. The effects of these carcinogens may undergo modification by the enzymes responsible for their detoxification and/or activation. In this study, we investigated genetic polymorphisms in nine carcinogen metabolism enzymes and their modifying effects on the association between white or dark fish consumption and prostate cancer (PCA) risk. We genotyped 497 localized and 936 advanced PCA cases and 760 controls from the California Collaborative Case–Control Study of Prostate Cancer. Three polymorphisms, EPHX1 Tyr113His, CYP1B1 Leu432Val and GSTT1 null/present, were associated with localized PCA risk. The PTGS2 765 G/C polymorphism modified the association between white fish consumption and advanced PCA risk (interaction P 5 0.002), with high white fish consumption being positively associated with risk only among carriers of the C allele. This effect modification by PTGS2 genotype was stronger when restricted to consumption of well-done white fish (interaction P 5 0.021). These findings support the hypotheses that changes in white fish brought upon by high-temperature cooking methods, such as carcinogen accumulation and/or fatty acid composition changes, may contribute to prostate carcinogenesis. However, the gene–diet interactions should be interpreted with caution given the limited sample size. Thus, our findings require further validation with additional studies. Abbreviations: AA African American; BMI body mass index; CI confidence interval; CNV copy number variant; EPIC European Prospective Investigation into Cancer and Nutrition; HCA heterocyclic amine; HCFA Health Care Financing Administration; LAC Los Angeles county; MAF minor allele frequency; NHW non-Hispanic White; OR odds ratio; PAH polycyclic aromatic hydrocarbon; PCA prostate cancer; PTGS2 prostaglandin- endoperoxide synthase 2; PUFA polyunsaturated fatty acids; RDD random-digit dialing; SEER Surveillance, Epidemiology, and End Result; SES socio-economic status; SFBA San Francisco Bay Area; SNP single-nucleotide polymorphism PMID:22610071

A reversible Renilla luciferase protein complementation assay for rapid identification of protein-protein interactions reveals the existence of an interaction network involved in xyloglucan biosynthesis in the plant Golgi apparatus.

PubMed

Lund, Christian H; Bromley, Jennifer R; Stenbæk, Anne; Rasmussen, Randi E; Scheller, Henrik V; Sakuragi, Yumiko

2015-01-01

A growing body of evidence suggests that protein-protein interactions (PPIs) occur amongst glycosyltransferases (GTs) required for plant glycan biosynthesis (e.g. cell wall polysaccharides and N-glycans) in the Golgi apparatus, and may control the functions of these enzymes. However, identification of PPIs in the endomembrane system in a relatively fast and simple fashion is technically challenging, hampering the progress in understanding the functional coordination of the enzymes in Golgi glycan biosynthesis. To solve the challenges, we adapted and streamlined a reversible Renilla luciferase protein complementation assay (Rluc-PCA), originally reported for use in human cells, for transient expression in Nicotiana benthamiana. We tested Rluc-PCA and successfully identified luminescence complementation amongst Golgi-localizing GTs known to form a heterodimer (GAUT1 and GAUT7) and those which homooligomerize (ARAD1). In contrast, no interaction was shown between negative controls (e.g. GAUT7, ARAD1, IRX9). Rluc-PCA was used to investigate PPIs amongst Golgi-localizing GTs involved in biosynthesis of hemicelluloses. Although no PPI was identified among six GTs involved in xylan biosynthesis, Rluc-PCA confirmed three previously proposed interactions and identified seven novel PPIs amongst GTs involved in xyloglucan biosynthesis. Notably, three of the novel PPIs were confirmed by a yeast-based split-ubiquitin assay. Finally, Gateway-enabled expression vectors were generated, allowing rapid construction of fusion proteins to the Rluc reporters and epitope tags. Our results show that Rluc-PCA coupled with transient expression in N. benthamiana is a fast and versatile method suitable for analysis of PPIs between Golgi resident proteins in an easy and mid-throughput fashion in planta. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Intraindividual Comparison of 18F-PSMA-1007 PET/CT, Multiparametric MRI, and Radical Prostatectomy Specimens in Patients with Primary Prostate Cancer: A Retrospective, Proof-of-Concept Study.

PubMed

Kesch, Claudia; Vinsensia, Maria; Radtke, Jan P; Schlemmer, Heinz P; Heller, Martina; Ellert, Elena; Holland-Letz, Tim; Duensing, Stefan; Grabe, Nils; Afshar-Oromieh, Ali; Wieczorek, Kathrin; Schäfer, Martin; Neels, Oliver C; Cardinale, Jens; Kratochwil, Clemens; Hohenfellner, Markus; Kopka, Klaus; Haberkorn, Uwe; Hadaschik, Boris A; Giesel, Frederik L

2017-11-01

68 Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT represents an advanced method for the staging of primary prostate cancer (PCa) and diagnosis of recurrent or metastatic PCa. However, because of the narrow availability of 68 Ga the development of alternative tracers is of high interest. The objective of this study was to examine the value of the new PET tracer 18 F-PSMA-1007 for the staging of local disease by comparing it with multiparametric MRI (mpMRI) and radical prostatectomy (RP) histopathology. Methods: In 2016, 18 F-PSMA-1007 PET/CT was performed in 10 men with biopsy-confirmed high-risk PCa. Nine patients underwent mpMRI in the process of primary diagnosis. Consecutively, RP was performed in all 10 men. Agreement analysis was performed retrospectively. PSMA staining was added for representative sections in RP specimen slices. Localization and agreement analysis of 18 F-PSMA-1007 PET/CT, mpMRI, and RP specimens was performed by dividing the prostate into 38 sections as described in the prostate imaging reporting and data system (PI-RADS) (version 2). Sensitivity, specificity, positive predictive values, negative predictive values (NPVs), and accuracy were calculated for total and near-total agreement. Results: 18 F-PSMA-1007 PET/CT had an NPV of 68% and an accuracy of 75%, and mpMRI had an NPV of 88% and an accuracy of 73% for total agreement. Near-total agreement analysis resulted in an NPV of 91% and an accuracy of 93% for 18 F-PSMA-1007 PET/CT and 91% and 87% for mpMRI, respectively. Retrospective combination of mpMRI and PET/CT had an accuracy of 81% for total and 93% for near-total agreement. Conclusion: Comparison with RP histopathology demonstrates that 18 F-PSMA-1007 PET/CT is promising for accurate local staging of PCa. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Sociodemographic Disparities in Cure-Intended Treatment in Localized Prostate Cancer.

PubMed

des Bordes, Jude K A; Lopez, David S; Swartz, Michael D; Volk, Robert J

2018-02-01

Disparities in prostate cancer (PCa) morbidity and mortality occur across various populations. We investigated the sociodemographic correlates of treatment and disparities in the application of cure-intended (i.e., radical prostatectomy [RP], radiation therapy [RT]) treatment strategies in localized PCa among Texas residents diagnosed with PCa. We analyzed data from the Texas Cancer Registry on men diagnosed with stage T1 or T2 PCa between 2004 and 2009. Multinomial logistic regression analysis was used to explore independent associations between cure-intended treatment modalities and sociodemographic characteristics (age, race/ethnicity, socioeconomic status [SES], and geographic location (rural versus urban)) using patients who did not receive definitive treatment as comparison group. Of 46,971 patients with available treatment data, age-adjusted treatment rates were 39.1% RP, 30.7% RT, and 30.2% for all other non-curative modalities. Compared to patients under 60 years, those ≥60 were less likely to receive RP, patients between 60 and 80 years were more likely to undergo RT, while those 80 years or older were less likely. Non-Hispanic blacks (OR =0.55, 95% CI, 0.50-0.59) and Hispanics (OR = 0.68, 95%CI, 0.62-0.74) were less likely to receive RP compared with whites. Hispanics were significantly less likely to receive RT (OR = 0.78, 95%CI, 0.72-0.85) than blacks and whites. People of low SES were 35% (OR = 0.65, 95%CI, 0.60-0.69) and 15% (OR = 0.85, 95%CI, 0.79-0.90) less likely to receive RP and RT, respectively, compared with those of high SES. Rural-urban status was not associated with cure-intended treatment. Potential sociodemographic disparities exist in the application of cure-intended treatment in localized prostate cancer in Texas particularly in race/ethnicity and SES.

Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial.

PubMed

Johnston, Thomas J; Shaw, Greg L; Lamb, Alastair D; Parashar, Deepak; Greenberg, David; Xiong, Tengbin; Edwards, Alison L; Gnanapragasam, Vincent; Holding, Peter; Herbert, Phillipa; Davis, Michael; Mizielinsk, Elizabeth; Lane, J Athene; Oxley, Jon; Robinson, Mary; Mason, Malcolm; Staffurth, John; Bollina, Prasad; Catto, James; Doble, Andrew; Doherty, Alan; Gillatt, David; Kockelbergh, Roger; Kynaston, Howard; Prescott, Steve; Paul, Alan; Powell, Philip; Rosario, Derek; Rowe, Edward; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E

2017-03-01

Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The median PSA was 17μg/l. Treatments included radical prostatectomy (RP; n=54; 11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122; 25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38-0.83; p=0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy.

PubMed

Miller, Zachary A; Rosenberg, Lynne; Santos-Santos, Miguel A; Stephens, Melanie; Allen, Isabel E; Hubbard, H Isabel; Cantwell, Averill; Mandelli, Maria Luisa; Grinberg, Lea T; Seeley, William W; Miller, Bruce L; Rabinovici, Gil D; Gorno-Tempini, Maria Luisa

2018-06-01

Increased prevalence of language-based learning disabilities (LDs) has been previously reported in patients with primary progressive aphasia (PPA). This study hypothesized that patients with focal neurodegenerative syndromes outside the language network, such as posterior cortical atrophy (PCA), would have a higher rate of nonlanguage LDs, congruent with their mainly visuospatial presentation. To investigate the prevalence and type of LD (language and/or mathematical and visuospatial) in a large cohort of patients with PCA compared with patients with logopenic variant PPA (lvPPA) and amnestic Alzheimer disease (AD). This case-control study reviewed 279 medical records from a university-based clinic and research center for patients with neurodegenerative diseases for LD history, including patients with PCA (n = 95), patients with lvPPA (n = 84), and a matched cohort with amnestic AD (n = 100). No records were excluded. The study compared cognitive and neuroimaging features of patients with PCA with and without LDs. A review of the records of patients presenting from March 1, 1999, to August 31, 2014, revealed 95 PCA cases and 84 lvPPA cases. Then 100 patients with amnestic AD from this same period were chosen for comparison, matching against the groups for age, sex, and disease severity. Data analysis was performed from September 8, 2013, to November 6, 2017. Prevalence of total LD history and prevalence of language and mathematical or visuospatial LD history across all cohorts. A total of 179 atypical AD cases (95 with PCA and 84 with lvPPA) and 100 disease control cases (amnestic AD) were included in the study. The groups were not statistically different for mean (SD) age at first visit (PCA, 61.9 [7.0] years; lvPPA, 65.1 [8.7] years; amnestic AD, 64.0 [12.6] years; P = .08), mean (SD) age at first symptom (PCA, 57.5 [7.0] years; lvPPA, 61.1 [9.0] years; amnestic AD, 59.6 [13.7] years; P = .06), or sex (PCA, 66.3% female; lvPPA, 56.0% female; amnestic AD, 57.0% female; P = .30) but differed on non-right-hand preference (PCA, 18.3%; lvPPA, 20.2%; amnestic AD, 7.7%; P = .04), race/ethnicity (PCA, 88.3% white; lvPPA, 99.0% white; amnestic AD, 80.0% white; P < .001), and mean (SD) educational level (PCA, 15.7 [3.2] years; lvPPA, 16.2 [3.3] years; amnestic AD, 14.8 [3.5] years; P = .02). A total of 18 of the 95 patients with PCA (18.9%) reported a history of LD, which is greater than the 3 of 100 patients (3.0%) in the amnestic AD cohort (P < .001) and the 10.0% expected rate in the general population (P = .007). In the PCA cohort, 13 of 95 patients (13.7%) had a nonlanguage mathematical and/or visuospatial LD; this rate was greater than that in the amnestic AD (1 of 100 [1.0%]; P < .001) and lvPPA (2 of 84 [2.4%]; P = .006) cohorts and greater than the 6.0% expected general population rate of mathematical LD (P = .003). Compared with the patients with PCA without LDs, the group with LDs had greater preservation of global cognition and a more right-lateralized pattern of atrophy. Nonlanguage mathematical and visuospatial LDs were associated with focal, visuospatial predominant neurodegenerative clinical syndromes. This finding supports the hypothesis that neurodevelopmental differences in specific brain networks are associated with phenotypic manifestation of later-life neurodegenerative disease.

MRI Fusion-Targeted Transrectal Prostate Biopsy and the Role of Prostate-Specific Antigen Density and Prostate Health Index for the Detection of Clinically Significant Prostate Cancer in Southeast Asian Men.

PubMed

Tan, Teck Wei; Png, Keng Siang; Lee, Chau Hung; Yuwono, Arianto; Yeow, Yuyi; Chong, Kian Tai; Lee, Yee Mun; Tan, Cher Heng; Tan, Yung Khan

2017-11-01

To test the hypothesis that targeted biopsy has a higher detection rate for clinically significant prostate cancer (csPCa) than systematic biopsy. We defined csPCa as any Gleason sum ≥7 cancer. In patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, to determine if factors, such as prostate-specific antigen density (PSAD) and prostate health index (PHI), can predict csPCa and help select patients for biopsy. We report the first series of targeted biopsies in Southeast Asian men, with comparison against systematic biopsy. Consecutive patients were registered into a prospective institutional review board-approved database in our institution. We reviewed patients who underwent biopsy from May 2016 to June 2017. Inclusion criteria for our study were patients with at least one PI-RADS ≥3, and who underwent both targeted and systematic biopsies in the same sitting. There were 115 patients in the study, of whom 74 (64.3%) had a previous negative systematic biopsy. Targeted biopsies detected significantly less Gleason 6 cancers than systematic biopsies (p < 0.01), and demonstrated significantly higher sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for the detection of csPCa. For patients with PI-RADS 3 lesions, PHI and PSAD were found to be the best predictors for csPCa. PSAD <0.10 ng/mL/mL had an NPV of 93% and sensitivity of 92%, while allowing 20% of patients to avoid biopsy. PHI cutoff of <27 would allow 34% of patients to avoid biopsy, with both sensitivity and NPV of 100%. Targeted prostate biopsies were found to be significantly superior to systematic biopsies for the detection of csPCa, while detecting less Gleason 6 cancer. Usage of PSAD and PHI cutoff levels in patients with PI-RADS 3 lesions may enable a number of patients to avoid unnecessary biopsy.

Evaluation of Food Freshness and Locality by Odor Sensor

NASA Astrophysics Data System (ADS)

Koike, Takayuki; Shimada, Koji; Kamimura, Hironobu; Kaneki, Noriaki

The aim of this study was to investigate whether food freshness and locality can be classified using a food evaluation system consisting four SnO2-semiconductor gas sensors and a solid phase column, into which collecting aroma materials. The temperature of sensors was periodically changed to be in unsteady state and thus, the sensor information was increased. The parameters (in quefrency band) were extracted from sensor information using cepstrum analysis that enable to separate superimposed information on sinusoidal wave. The quefrency was used as parameters for principal component and discriminant analyses (PCA and DCA) to detect food freshness and food localities. We used three kinds of strawberries, people can perceive its odors, passed from one to three days after harvest, and kelps and Ceylon tea, people are hardly to perceive its odor, corrected from five areas as sample. Then, the deterioration of strawberries and localities of kelps and Ceylon teas were visually evaluated using the numerical analyses. While the deteriorations were classified using PCA or DCA, the localities were classified only by DCA. The findings indicate that, although odorant intensity influenced the method detecting food quality, the quefrency obtained from odorant information using cepstrum analysis were available to detect the difference in the freshness and the localities of foods.

Removal of inflammatory ascites is associated with dynamic modification of local and systemic inflammation along with prevention of acute lung injury: in vivo and in silico studies.

PubMed

Emr, Bryanna; Sadowsky, David; Azhar, Nabil; Gatto, Louis A; An, Gary; Nieman, Gary F; Vodovotz, Yoram

2014-04-01

Sepsis-induced inflammation in the gut/peritoneal compartment occurs early in sepsis and can lead to acute lung injury (ALI). We have suggested that inflammatory ascites drives the pathogenesis of ALI and that removal of ascites with an abdominal wound vacuum prevents ALI. We hypothesized that the time- and compartment-dependent changes in inflammation that determine this process can be discerned using principal component analysis (PCA) and Dynamic Bayesian Network (DBN) inference. To test this hypothesis, data from a previous study were analyzed using PCA and DBN. In that study, two groups of anesthetized, ventilated pigs were subjected to experimental sepsis via intestinal ischemia/reperfusion and placement of a peritoneal fecal clot. The control group (n = 6) had the abdomen opened at 12 h after injury (T12) with attachment of a passive drain. The peritoneal suction treatment (PST) group (n = 6) was treated in an identical fashion except that a vacuum was applied to the peritoneal cavity at T12 to remove ascites and maintained until T48. Multiple inflammatory mediators were measured in ascites and plasma and related to lung function (PaO2/FIO2 ratio and oxygen index) using PCA and DBN. Peritoneal suction treatment prevented ALI based on lung histopathology, whereas control animals developed ALI. Principal component analysis revealed that local to the insult (i.e., ascites), primary proinflammatory cytokines play a decreased role in the overall response in the treatment group as compared with control. In both groups, multiple, nested positive feedback loops were inferred from DBN, which included interrelated roles for bacterial endotoxin, interleukin 6, transforming growth factor β1, C-reactive protein, PaO2/FIO2 ratio, and oxygen index. von Willebrand factor was an output in control, but not PST, ascites. These combined in vivo and in silico studies suggest that in this clinically realistic paradigm of sepsis, endotoxin drives the inflammatory response in the ascites, interplaying with lung dysfunction in a feed-forward loop that exacerbates inflammation and leads to endothelial dysfunction, systemic spillover, and ALI; PST partially modifies this process.

Inhibition of prostate cancer osteoblastic progression with VEGF121/rGel, a single agent targeting osteoblasts, osteoclasts, and tumor neovasculature

PubMed Central

Mohamedali, Khalid A.; Li, Zhi Gang; Starbuck, Michael W.; Wan, Xinhai; Yang, Jun; Kim, Sehoon; Zhang, Wendy; Rosenblum, Michael G.; Navone, Nora M.

2011-01-01

Purpose A hallmark of prostate cancer (PCa) progression is the development of osteoblastic bone metastases, which respond poorly to available therapies. We previously reported that VEGF121/rGel targets osteoclast precursors and tumor neovasculature. Here we tested the hypothesis that targeting non-tumor cells expressing these receptors can inhibit tumor progression in a clinically relevant model of osteoblastic PCa. Experimental Design Cells from MDA PCa 118b, a PCa xenograft obtained from a bone metastasis in a patient with castrate-resistant PCa, were injected into the femurs of mice. Osteoblastic progression was monitored following systemic administration of VEGF121/rGel. Results VEGF121/rGel was cytotoxic in vitro to osteoblast precursor cells. This cytotoxicity was specific as VEGF121/rGel internalization into osteoblasts was VEGF121 receptor driven. Furthermore, VEGF121/rGel significantly inhibited PCa-induced bone formation in a mouse calvaria culture assay. In vivo, VEGF121/rGel significantly inhibited the osteoblastic progression of PCa cells in the femurs of nude mice. Microcomputed tomography analysis revealed that VEGF121/rGel restored the bone volume fraction of tumor-bearing femurs to values similar to those of the contralateral (non–tumor bearing) femurs. VEGF121/rGel significantly reduced the number of tumor-associated osteoclasts but did not change the numbers of peritumoral osteoblasts. Importantly, VEGF121/rGel-treated mice had significantly less tumor burden than control mice. Our results thus indicate that VEGF121/rGel inhibits osteoblastic tumor progression by targeting angiogenesis, osteoclastogenesis, and bone formation. Conclusions Targeting VEGFR-1 – or VEGFR-2–expressing cells is effective in controlling the osteoblastic progression of PCa in bone. These findings provide the basis for an effective multitargeted approach for metastatic PCa. PMID:21343372

Testosterone therapy in men with prostate cancer: literature review, clinical experience, and recommendations

PubMed Central

Morgentaler, Abraham; Conners III, William P

2015-01-01

For several decades any diagnosis of prostate cancer (PCa) has been considered an absolute contraindication to the use of testosterone (T) therapy in men. Yet this prohibition against T therapy has undergone recent re-examination with refinement of our understanding of the biology of androgens and PCa, and increased appreciation of the benefits of T therapy. A reassuringly low rate of negative outcomes has been reported with T therapy after radical prostatectomy (RP), radiation treatments, and in men on active surveillance. Although the number of these published reports are few and the total number of treated men is low, these experiences do provide a basis for consideration of T therapy in selected men with PCa. For clinicians considering offering this treatment, we recommend first selecting patients with low grade cancers and undetectable prostate-specific antigen following RP. Further research is required to define the safety of T therapy in men with PCa. However, many patients symptomatic from T deficiency are willing to accept the potential risk of PCa progression or recurrence in return for the opportunity to live a fuller and happier life with T therapy. PMID:25652633

Regulators of gene expression as biomarkers for prostate cancer

PubMed Central

Willard, Stacey S; Koochekpour, Shahriar

2012-01-01

Recent technological advancements in gene expression analysis have led to the discovery of a promising new group of prostate cancer (PCa) biomarkers that have the potential to influence diagnosis and the prediction of disease severity. The accumulation of deleterious changes in gene expression is a fundamental mechanism of prostate carcinogenesis. Aberrant gene expression can arise from changes in epigenetic regulation or mutation in the genome affecting either key regulatory elements or gene sequences themselves. At the epigenetic level, a myriad of abnormal histone modifications and changes in DNA methylation are found in PCa patients. In addition, many mutations in the genome have been associated with higher PCa risk. Finally, over- or underexpression of key genes involved in cell cycle regulation, apoptosis, cell adhesion and regulation of transcription has been observed. An interesting group of biomarkers are emerging from these studies which may prove more predictive than the standard prostate specific antigen (PSA) serum test. In this review, we discuss recent results in the field of gene expression analysis in PCa including the most promising biomarkers in the areas of epigenetics, genomics and the transcriptome, some of which are currently under investigation as clinical tests for early detection and better prognostic prediction of PCa. PMID:23226612

Minireview: SLCO and ABC Transporters: A Role for Steroid Transport in Prostate Cancer Progression

PubMed Central

Cho, Eunpi; Montgomery, R. Bruce

2014-01-01

Androgens play a critical role in the development and progression of prostate cancer (PCa), and androgen deprivation therapy via surgical or medical castration is front-line therapy for patients with advanced PCa. However, intratumoral testosterone levels are elevated in metastases from patients with castration-resistant disease, and residual intratumoral androgens have been implicated in mediating ligand-dependent mechanisms of androgen receptor activation. The source of residual tissue androgens present despite castration has not been fully elucidated, but proposed mechanisms include uptake and conversion of adrenal androgens, such as dehdroepiandrosterone to testosterone and dihydrotestosterone, or de novo androgen synthesis from cholesterol or progesterone precursors. In this minireview, we discuss the emerging evidence that suggests a role for specific transporters in mediating transport of steroids into or out of prostate cells, thereby influencing intratumoral androgen levels and PCa development and progression. We focus on the solute carrier and ATP binding cassette gene families, which have the most published data for a role in PCa-related steroid transport, and review the potential impact of genetic variation on steroid transport activity and PCa outcomes. Continued assessment of transport activity in PCa models and human tumor tissue is needed to better delineate the different roles these transporters play in physiologic and neoplastic settings, and in order to determine whether targeting the uptake of steroid substrates by specific transporters may be a clinically feasible therapeutic strategy. PMID:25147980

Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

PubMed Central

Olivan, M.; Rigau, M.; Colás, E.; Garcia, M.; Montes, M.; Sequeiros, T.; Regis, L.; Celma, A.; Planas, J.; Placer, J.; Reventós, J.; de Torres, I.; Doll, A.; Morote, J.

2015-01-01

Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467–0.812), P < 0.001). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068–3.155), P = 0.028) or the combination of both drugs (OR: 3.059 (95% CI: 1.894–4.939), P < 0.001) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effects in vitro are enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence. PMID:25649906

Proportion and characteristics of men with unknown risk category in the National Prostate Cancer Register of Sweden.

PubMed

Tomic, Katarina; Westerberg, Marcus; Robinson, David; Garmo, Hans; Stattin, Pär

2016-12-01

Knowledge on missing data in a clinical cancer register is important to assess the validity of research results. For analysis of prostate cancer (Pca), risk category, a composite variable based on serum levels of prostate specific antigen (PSA), stage, and Gleason score, is crucial for treatment decisions and a strong determinant of outcome. The aim of this study was to assess the proportion and characteristics of men in the National Prostate Cancer Register (NPCR) of Sweden with unknown risk category. Men diagnosed with Pca between 1998 and 2012 registered in NPCR with known or unknown risk category were compared with respect to age, socioeconomic factors, comorbidity, cancer characteristics, cancer treatment, and mortality from Pca and other causes. In total, 3315 of 129 391 (3%) men had unknown risk category. Compared to other men in NPCR, these men more often had a concomitant bladder cancer diagnosis, 19% versus 1%, diagnosis of benign prostatic hyperplasia 31% versus 5%, received unspecified Pca treatment 16% versus 3%, had higher comorbidity, Charlson Comorbidity Index 2 or higher, 34% versus 13%, and had lower Pca mortality 12% versus 30%, but similar mortality from other causes. Men with unknown risk category were rare in NPCR but distinctly different from other men in NPCR in many aspects including higher comorbidity and lower Pca mortality.

Association of THADA, FOXP4, GPRC6A/RFX6 genes and 8q24 risk alleles with prostate cancer in Northern Chinese men.

PubMed

Li, Xing-Hui; Xu, Yong; Yang, Kuo; Shi, Jian-Jian; Zhang, Xiao; Yang, Fang; Yuan, Huiping; Zhu, Xiaoquan; Zhang, Yu-Hong; Wang, Jian-Ye; Yang, Ze

2015-01-01

Prostate cancer (PCa) is one of the most common malignancies in males, and multiple genetic studies have confirmed association with susceptibility to PCa. However, the risk conferred in men living in China is unkown. We selected 6 previously identified variants as candidates to define their association with PCa in Chinese men. We genotyped 6 single nucleotide polymorphisms (SNPs) (rs1465618, rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) using high resolution melting (HRM) analysis and assessed their association with PCa risk in a case-control study of 481 patients and 480 controls in a Chinese population. In addition, the individual and cumulative contribution for the risk of PCa and clinical covariates were analysed. We found that 5 of the 6 genetic variants were associated with PCa risk. The T allele of rs339331 and the G allele of rs16901966 showed a significant association with PCa susceptibility: OR (95%CI)= 0.78 (0.64-0.94), p<0.009 and OR (95%CI)= 0.66 (0.54-0.81), p<0.0001, as well as A allele of rs1447295 (OR [95%CI]=1.46 (1.17-1.84), p<0.001) and T allele of rs10090154 (OR [95%CI]= 0.58 (0.46-0.74), p<0.0001). rs339331(T) was associated with a 0.71-fold and 1.42-fold increase of PCa risk by dominant model (p=0.007) and recessive model (p=0.007). rs16901966 (G) was associated with a 0.51-fold and 1.98-fold increase of PCa risk by dominant model (p=0.006) and recessive model (p=0.0058). rs10090154 (T) was associated with a 1.89-fold and 0.53-fold increase of PCa risk by dominant model (p=0.000006) and recessive model (p=0.000006). And, rs1983891(C) was associated with a 0.77-fold increase of PCa risk by recessive model (p=0.045). rs1447295 was associated with a 1.57-fold increase of PCa risk by dominant model (p=0.008). rs1465618 showed no significant association with PCa. The cumulative effects test of risk alleles (rs rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) showed an increasing risk to PCa in a frequency-dependent manner (ptrend=0.001), and men with more than 3 risk alleles had the most significant susceptibility to PCa (OR=1.99, p=0.001), compared with those who had one risk allele (OR=1.17, p=0.486). Our results provide further support for association of the THADA, FOXP4, GPRC6A/RFX6 and 8q24 genes with Pca in Asian populations. Further work is still required to determine the functional variations and finally clarify the underlying biological mechanisms.

Principal components analysis in clinical studies.

PubMed

Zhang, Zhongheng; Castelló, Adela

2017-09-01

In multivariate analysis, independent variables are usually correlated to each other which can introduce multicollinearity in the regression models. One approach to solve this problem is to apply principal components analysis (PCA) over these variables. This method uses orthogonal transformation to represent sets of potentially correlated variables with principal components (PC) that are linearly uncorrelated. PCs are ordered so that the first PC has the largest possible variance and only some components are selected to represent the correlated variables. As a result, the dimension of the variable space is reduced. This tutorial illustrates how to perform PCA in R environment, the example is a simulated dataset in which two PCs are responsible for the majority of the variance in the data. Furthermore, the visualization of PCA is highlighted.

Is it possible to predict low-volume and insignificant prostate cancer by core needle biopsies?

PubMed

Berg, Kasper Drimer; Toft, Birgitte Grønkaer; Røder, Martin Andreas; Brasso, Klaus; Vainer, Ben; Iversen, Peter

2013-04-01

In an attempt to minimize overtreatment of localized prostate cancer (PCa) active surveillance (AS) and minor invasive procedures have received increased attention. We investigated the accuracy of pre-operative findings in defining insignificant disease and distinguishing between unilateral/unifocal and bilateral/multifocal PCa. One-hundred and sixty patients undergoing radical prostatectomy were included. Histology reports from the biopsies and matching prostatectomies were compared. Three definitions of insignificant cancer were used: InsigE: tumour volume ≤0.5 mL; InsigW: tumour volume ≤1.3 mL; InsigM: tumour ≤5% of total prostate volume and prostate-specific antigen (PSA) ≤10 ng/mL. In all definitions, Gleason score (GS) was ≤6 and the tumour was organ confined. Biopsies alone performed poorly as a predictor of unifocal and unilateral cancer in the prostatectomy specimens with positive predictive values of 17.8% and 18.9% respectively. Inclusion of other clinical and biochemical parameters did not significantly increase the predictive value. However, the combination of GS ≤ 6, PSA ≤ 10 ng/mL and unifocal or unilateral cancer in biopsy cores resulted in a positive predictive value of 61.1%, 38.9% and 12.0%, respectively, for identifying InsigM, InsigW and InsigE in the prostate specimen. Conclusively, routine prostate biopsies cannot predict unifocal and unilateral PCa, and must be regarded insufficient to select patients for focal therapy. Although candidates for AS may be identified using standard biopsies, a considerable fraction of patients will be understaged. There is a need for more precise diagnostic tools to assess intraprostatic tumour growth. © 2012 The Authors APMIS © 2012 APMIS.

Survival outcomes of radical prostatectomy and external beam radiotherapy in clinically localized high-risk prostate cancer: a population-based, propensity score matched study

PubMed Central

Gu, Xiaobin; Gao, Xianshu; Cui, Ming; Xie, Mu; Ma, Mingwei; Qin, Shangbin; Li, Xiaoying; Qi, Xin; Bai, Yun; Wang, Dian

2018-01-01

Objective This study was aimed to compare survival outcomes in high-risk prostate cancer (PCa) patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP). Materials and methods The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCa patients with high-risk features who received RP alone or EBRT alone from 2004 to 2008. Propensity-score matching (PSM) was performed. Kaplan–Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS). Multivariate Cox regression analysis was used to identify independent prognostic factors. Results A total of 24,293 patients were identified, 14,460 patients receiving RP and 9833 patients receiving EBRT. Through PSM, 3828 patients were identified in each group. The mean CSS was 128.6 and 126.7 months for RP and EBRT groups, respectively (P<0.001). The subgroup analyses showed that CSS of the RP group was better than that of the EBRT group for patients aged <65 years (P<0.001), White race (P<0.001), and married status (P<0.001). However, there was no significant difference in CSS for patients aged ≥65 years, Black race, other race, and unmarried status. Similar trends were observed for OS. Multivariate analysis showed that EBRT treatment modality, T3–T4 stage, Gleason score 8–10, and prostate-specific antigen >20 ng/mL were significant risk factors for both CSS and OS. Conclusion This study suggested that survival outcomes might be better with RP than EBRT in high-risk PCa patients aged <65 years; however, RP and EBRT provided equivalent survival outcomes in older patients, which argues for primary radiotherapy in this older cohort.

Extraction of Prostatic Lumina and Automated Recognition for Prostatic Calculus Image Using PCA-SVM

PubMed Central

Wang, Zhuocai; Xu, Xiangmin; Ding, Xiaojun; Xiao, Hui; Huang, Yusheng; Liu, Jian; Xing, Xiaofen; Wang, Hua; Liao, D. Joshua

2011-01-01

Identification of prostatic calculi is an important basis for determining the tissue origin. Computation-assistant diagnosis of prostatic calculi may have promising potential but is currently still less studied. We studied the extraction of prostatic lumina and automated recognition for calculus images. Extraction of lumina from prostate histology images was based on local entropy and Otsu threshold recognition using PCA-SVM and based on the texture features of prostatic calculus. The SVM classifier showed an average time 0.1432 second, an average training accuracy of 100%, an average test accuracy of 93.12%, a sensitivity of 87.74%, and a specificity of 94.82%. We concluded that the algorithm, based on texture features and PCA-SVM, can recognize the concentric structure and visualized features easily. Therefore, this method is effective for the automated recognition of prostatic calculi. PMID:21461364

Prostate cancer in senior adults: over- or undertreated?

PubMed

Berger, Ingrid; Böhmer, Franz; Ponholzer, Anton; Madersbacher, Stephan

2009-01-01

Despite the widespread use of prostate specific antigen for early prostate cancer (PCa) detection in younger men, PCa is still as disease of the elderly as 2/3 of incident cases are detected in men older than 65 years and 25% are older than 75 years at diagnosis. Opportunistic screening for PCa is not recommended for men with a life expectancy of less than 10 years. The therapeutic strategy for senior adults is driven by tumour stage/aggressiveness, co-morbidity and chronological age. Elderly patients with low/intermediate risk tumours - particularly those with a life expectancy of less than 10 years - are best managed by watchful waiting. Senior adults with intermediate/high risk tumours and a life expectancy of >10 years may benefit from curative local therapy such as radical prostatectomy or combined external beam irradiation/androgen ablation therapy. For elderly patients with metastatic disease, androgen deprivation remains the mainstay of therapy, intermittent androgen ablation is a promising approach.

Optimized principal component analysis on coronagraphic images of the fomalhaut system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meshkat, Tiffany; Kenworthy, Matthew A.; Quanz, Sascha P.

We present the results of a study to optimize the principal component analysis (PCA) algorithm for planet detection, a new algorithm complementing angular differential imaging and locally optimized combination of images (LOCI) for increasing the contrast achievable next to a bright star. The stellar point spread function (PSF) is constructed by removing linear combinations of principal components, allowing the flux from an extrasolar planet to shine through. The number of principal components used determines how well the stellar PSF is globally modeled. Using more principal components may decrease the number of speckles in the final image, but also increases themore » background noise. We apply PCA to Fomalhaut Very Large Telescope NaCo images acquired at 4.05 μm with an apodized phase plate. We do not detect any companions, with a model dependent upper mass limit of 13-18 M {sub Jup} from 4-10 AU. PCA achieves greater sensitivity than the LOCI algorithm for the Fomalhaut coronagraphic data by up to 1 mag. We make several adaptations to the PCA code and determine which of these prove the most effective at maximizing the signal-to-noise from a planet very close to its parent star. We demonstrate that optimizing the number of principal components used in PCA proves most effective for pulling out a planet signal.« less

The genetics of phaeochromocytoma: using clinical features to guide genetic testing.

PubMed

Jafri, Mariam; Maher, Eamonn R

2012-02-01

Phaeochromocytoma is a rare, usually benign, tumour predominantly managed by endocrinologists. Over the last decade, major advances have been made in understanding the molecular genetic basis of adrenal and extra-adrenal phaeochromocytoma (also referred to as adrenal phaeochromocytoma (aPCA) and extra-adrenal functional paraganglioma (eFPGL)). In contrast to the previously held belief that only 10% of cases had a genetic component, currently about one-third of all aPCA/eFPGL cases are thought to be attributable to germline mutations in at least nine genes (NF1, RET, SDHA, SDHB, SDHC, SDHD, TMEM127, MAX and VHL). Recognition of inherited cases of aPCA/eFPGL is critical for optimal patient management. Thus, the identification of a germline mutation can predict risks of malignancy, recurrent disease, associated non-chromaffin tumours and risks to other family members. Mutation carriers should be offered specific surveillance programmes (according to the relevant gene). In this review, we will describe the genetics of aPCA/eFPGL and strategies for genetic testing.

Cost-effectiveness analysis comparing epidural, patient-controlled intravenous morphine, and continuous wound infiltration for postoperative pain management after open abdominal surgery.

PubMed

Tilleul, P; Aissou, M; Bocquet, F; Thiriat, N; le Grelle, O; Burke, M J; Hutton, J; Beaussier, M

2012-06-01

Continuous wound infiltration (CWI), i.v. patient-controlled analgesia (i.v.-PCA), and epidural analgesia (EDA) are analgesic techniques commonly used for pain relief after open abdominal surgery. The aim of this study was to evaluate the cost-effectiveness of these techniques. A decision analytic model was developed, including values retrieved from clinical trials and from an observational prospective cohort of 85 patients. Efficacy criteria were based on pain at rest (VAS ≤ 30/100 mm at 24 h). Resource use and costs were evaluated from medical record measurements and published data. Probabilistic sensitivity analysis (PSA) was performed. When taking into account all resources consumed, the CWI arm (€ 6460) is economically dominant when compared with i.v.-PCA (€ 7273) and EDA (€ 7500). The proportion of patients successfully controlled for their postoperative pain management are 77.4%, 53.9%, and 72.9% for CWI, i.v.-PCA, and EDA, respectively, demonstrating the CWI procedure to be both economically and clinically dominant. PSA reported that CWI remains cost saving in 70.4% of cases in comparison with EDA and in 59.2% of cases when compared with PCA. Device-related costs of using CWI for pain management after abdominal laparotomy are partly counterbalanced by a reduction in resource consumption. The cost-effectiveness analysis suggests that CWI is the dominant treatment strategy for managing postoperative pain (i.e. more effective and less costly) in comparison with i.v.-PCA. When compared with EDA, CWI is less costly with almost equivalent efficacy. This economic evaluation may be useful for clinicians to design algorithms for pain management after major abdominal surgery.

Facilitating in vivo tumor localization by principal component analysis based on dynamic fluorescence molecular imaging

NASA Astrophysics Data System (ADS)

Gao, Yang; Chen, Maomao; Wu, Junyu; Zhou, Yuan; Cai, Chuangjian; Wang, Daliang; Luo, Jianwen

2017-09-01

Fluorescence molecular imaging has been used to target tumors in mice with xenograft tumors. However, tumor imaging is largely distorted by the aggregation of fluorescent probes in the liver. A principal component analysis (PCA)-based strategy was applied on the in vivo dynamic fluorescence imaging results of three mice with xenograft tumors to facilitate tumor imaging, with the help of a tumor-specific fluorescent probe. Tumor-relevant features were extracted from the original images by PCA and represented by the principal component (PC) maps. The second principal component (PC2) map represented the tumor-related features, and the first principal component (PC1) map retained the original pharmacokinetic profiles, especially of the liver. The distribution patterns of the PC2 map of the tumor-bearing mice were in good agreement with the actual tumor location. The tumor-to-liver ratio and contrast-to-noise ratio were significantly higher on the PC2 map than on the original images, thus distinguishing the tumor from its nearby fluorescence noise of liver. The results suggest that the PC2 map could serve as a bioimaging marker to facilitate in vivo tumor localization, and dynamic fluorescence molecular imaging with PCA could be a valuable tool for future studies of in vivo tumor metabolism and progression.

Do hormone treatments for prostate cancer cause anxiety and depression?

PubMed

Sharpley, Christopher F; Christie, David R H; Bitsika, Vicki

2014-01-01

To investigate the relationship between hormone therapy (HT) and incidence of anxiety and depression among prostate cancer patients (PCa). 526 PCa patients completed a survey about their cancer status, treatment received, anxiety, and depression status. Total scores on anxiety and depression inventories, plus symptom profiles that discriminated between patients with current HT, past HT, and never having received HT, were compiled for analysis. Patients who were currently receiving HT had significantly higher total anxiety and depression scores than patients who had previously received HT or who had never received HT. Analysis of the symptoms of anxiety and depression which distinguished between these groups of patients suggested that patients who had never received HT had significantly lower scores than current or past HT patients. Although several symptoms could be directly allocated to PCa and/or HT, symptom profiles were indicative of clinically significant anxiety and/or depression in patients who were currently receiving, or who had previously received, HT. Current HT may lead to symptoms of anxiety and/or depression which require clinical attention. These effects seem to decrease after completion of HT.

Uptake of 18F-DCFPyL in Paget's Disease of Bone, an Important Potential Pitfall in Clinical Interpretation of PSMA PET Studies.

PubMed

Rowe, Steven P; Deville, Curtiland; Paller, Channing; Cho, Steve Y; Fishman, Elliot K; Pomper, Martin G; Ross, Ashley E; Gorin, Michael A

2015-12-01

Prostate-specific membrane antigen (PSMA)-targeted PET imaging is an emerging technique for evaluating patients with prostate cancer (PCa) in a variety of clinical contexts. As with any new imaging modality, there are interpretive pitfalls that are beginning to be recognized. In this image report, we describe the findings in a 63-year-old male with biochemically recurrent PCa after radical prostatectomy who was imaged with 18 F-DCFPyL, a small molecule inhibitor of PSMA. Diffuse radiotracer uptake was noted throughout the sacrum, corresponding to imaging findings on contrast-enhanced CT, bone scan, and pelvic MRI consistent with Paget's disease of bone. The uptake of 18 F-DCFPyL in Paget's disease is most likely due to hyperemia and increased radiotracer delivery. In light of the overlap in patients affected by PCa and Paget's, it is important for nuclear medicine physicians and radiologists interpreting PSMA PET/CT scans to be aware of the potential for this diagnostic pitfall. Correlation to findings on conventional imaging such as diagnostic CT and bone scan can help confirm the diagnosis.

SU-C-209-02: 3D Fluoroscopic Image Generation From Patient-Specific 4DCBCT-Based Motion Models Derived From Clinical Patient Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhou, S; Cai, W; Hurwitz, M

Purpose: We develop a method to generate time varying volumetric images (3D fluoroscopic images) using patient-specific motion models derived from four-dimensional cone-beam CT (4DCBCT). Methods: Motion models are derived by selecting one 4DCBCT phase as a reference image, and registering the remaining images to it. Principal component analysis (PCA) is performed on the resultant displacement vector fields (DVFs) to create a reduced set of PCA eigenvectors that capture the majority of respiratory motion. 3D fluoroscopic images are generated by optimizing the weights of the PCA eigenvectors iteratively through comparison of measured cone-beam projections and simulated projections generated from the motionmore » model. This method was applied to images from five lung-cancer patients. The spatial accuracy of this method is evaluated by comparing landmark positions in the 3D fluoroscopic images to manually defined ground truth positions in the patient cone-beam projections. Results: 4DCBCT motion models were shown to accurately generate 3D fluoroscopic images when the patient cone-beam projections contained clearly visible structures moving with respiration (e.g., the diaphragm). When no moving anatomical structure was clearly visible in the projections, the 3D fluoroscopic images generated did not capture breathing deformations, and reverted to the reference image. For the subset of 3D fluoroscopic images generated from projections with visibly moving anatomy, the average tumor localization error and the 95th percentile were 1.6 mm and 3.1 mm respectively. Conclusion: This study showed that 4DCBCT-based 3D fluoroscopic images can accurately capture respiratory deformations in a patient dataset, so long as the cone-beam projections used contain visible structures that move with respiration. For clinical implementation of 3D fluoroscopic imaging for treatment verification, an imaging field of view (FOV) that contains visible structures moving with respiration should be selected. If no other appropriate structures are visible, the images should include the diaphragm. This project was supported, in part, through a Master Research Agreement with Varian Medical Systems, Inc, Palo Alto, CA.« less

Post-uterine artery embolization pain and clinical outcomes for symptomatic myomas using gelfoam pledgets alone versus embospheres plus gelfoam pledgets: a comparative pilot study.

PubMed

Vilos, Angelos G; Vilos, George A; Hollett-Caines, Jackie; Garvin, Greg; Kozak, Roman; Abu-Rafea, Basim

2014-11-01

To evaluate the efficacy and post-procedural pain associated with uterine artery embolization (UAE) using Gelfoam alone versus Embospheres plus Gelfoam in women with symptomatic uterine fibroids. We conducted a prospective, non-randomized pilot study. Fluoroscopy-guided trans-femoral artery UAE was performed using Gelfoam pledgets alone or Embospheres (500 to 700 mg) plus Gelfoam under conscious sedation and local anaesthesia. This was followed by patient-controlled analgesia (PCA) using a morphine pump overnight. Post-procedural pain was assessed by the mean amount of self-administered morphine delivered by PCA pump (mL) from 0 to 19 hours in each group. The mean volumes of the uterus and the dominant fibroid were calculated by ultrasound at baseline, three months, six months, and 12 months. A total of 17 women participated in the study. Bilateral uterine artery occlusion was performed in eight women using Gelfoam alone, and in nine women using Embosphere + Gelfoam. One woman in the Embosphere + Gelfoam group developed a puncture-site hematoma requiring further intervention one week later. The mean (SD) amount of morphine self-administered by PCA pump at time 0, 1, and 2 hours was 3.4 mg (3.1), 2.9 mg (2.2), and 2.4 mg (3.3) in the Gelfoam-only group and 6.1 mg (3.0), 9.6 mg (7.1), and 5.3 mg (4.4) in the Embosphere + Gelfoam group, respectively. After three hours, the amount of morphine used was equal in both groups. The mean (SD) total dose of morphine used was 29.5 mg (18.6) in the Gelfoam group and 41.1 mg (19.3) in the Embosphere + Gelfoam group (P = 0.228). At 12 months, the reduction in median total uterine volume and median dominant fibroid volume in each group was equal. Clinical outcomes were equivalent after uterine artery embolization using Gelfoam alone versus Gelfoam + Embospheres. Although the amount of immediate post-procedure pain may be less with Gelfoam alone, we could not demonstrate this objectively using morphine use as a measure of pain.

EGFR‑associated pathways involved in traditional Chinese medicine (TCM)‑1‑induced cell growth inhibition, autophagy and apoptosis in prostate cancer.

PubMed

Wu, Zhaomeng; Zhu, Qingyi; Zhang, Yu; Yin, Yingying; Kang, Dan; Cao, Runyi; Tian, Qian; Lu, Shan; Liu, Ping

2018-06-01

Traditional Chinese medicine (TCM) has the synergistic effect of the combination of a single ingredient and a monomer, and systemic and local therapeutic effects in cancer treatment, through which TCM is able to enhance the curative effect and reduce the side effects. The present study analyzed the effect of TCM‑1 (an anti‑cancer TCM) on prostate cancer (PCa) cell lines, and studied in detail the mechanism of cell death induced by TCM‑1 in vitro and in vivo. From the present results, it was identified for the first time, to the best of our knowledge, that TCM‑1 arrested the cell cycle at the G1 phase, decreased cell viability and increased nuclear rupture in a dose‑dependent manner; these effects finally resulted in apoptosis in PCa cells. At the molecular level, the data demonstrated that TCM‑1 competitively acted on epidermal growth factor receptor (EGFR) with EGF, and suppressed the auto‑phosphorylation and activity of EGFR. Inhibition of EGFR further suppressed the downstream phosphatidylinositol 3‑kinase (PI3K)/RAC‑α serine/threonine‑protein kinase (AKT) and RAF proto‑oncogene serine/threonine‑protein kinase/extracellular signal regulated kinase signaling pathways and resulted in a decrease in the phosphorylated‑forkhead box protein O1 (at Ser256, Thr24 and Ser319) expression level, and induced cell growth inhibition and apoptosis by regulating the expression of apoptosis‑and cell cycle‑associated genes. In addition, TCM‑1 markedly inhibited the PI3K/AKT/serine/threonine‑protein kinase mTOR signaling pathway and induced cell autophagy by downregulating the phosphorylation of p70S6K and upregulating the levels of Beclin‑1 and microtubule‑associated protein light chain‑3II. In vivo, the TCM‑1‑treated group exhibited a significant decrease in tumor volume compared with the negative control group in subcutaneous xenograft nude mice by inhibiting EGFR‑associated signaling pathways. Therefore, the bio‑functions of Chinese medicine TCM‑1 in inducing PCa cell growth inhibition, autophagy and apoptosis suggested that TCM‑1 may have clinical potential for the treatment of patients with PCa.

Standardizing the definition of adverse pathology for lower risk men undergoing radical prostatectomy.

PubMed

Kozminski, Michael A; Tomlins, Scott; Cole, Adam; Singhal, Udit; Lu, Louis; Skolarus, Ted A; Palapattu, Ganesh S; Montgomery, Jeffrey S; Weizer, Alon Z; Mehra, Rohit; Hollenbeck, Brent K; Miller, David C; He, Chang; Feng, Felix Y; Morgan, Todd M

2016-09-01

Numerous definitions of adverse pathology at radical prostatectomy (RP) have been proposed and implemented for both research and clinical care, and there is tremendous variation in the specific criteria used to define adverse pathology in these settings. Given the current landscape in which magnetic resonance imaging criteria and biomarker cutoffs are validated for disparate adverse pathology definitions, we sought to identify which of these is most closely tied to biochemical recurrence (BCR) after RP. A total of 2,837 patients who underwent RP at a single institution for localized prostate cancer (PCa) were included. We evaluated the following existing definitions of adverse pathology at RP: (1) Gleason score ≥7, (2) primary Gleason pattern ≥4, (3) Gleason score ≥7 or pathologic stage T3-4, (4) pathologic stage T3-4, (5) primary Gleason pattern ≥4 or pathologic stage T3-4. The primary outcome measure was BCR. Multiple statistical techniques were used to assess BCR prediction. Of the 5 definitions assessed, 1 (primary Gleason pattern ≥4 or pathologic stage T3-4, 540 patients [19% of cohort]) consistently outperformed the other definitions across all statistical measures. Additionally, a total of only 13 (6.6%) and 34 (10.3%) men with very-low-risk and low-risk cancer per National Comprehensive Cancer Network guideline, respectively, met this definition of adverse pathology at the time of RP. Varying definitions of adverse pathology differ in their prognostic performance. The criteria defined by either primary Gleason pattern ≥4 or pT3-4 disease appears to most accurately predict BCR in this subset of patients with lower risk PCa at the time of diagnosis. Additionally, men with very-low-risk or low-risk PCa per National Comprehensive Cancer Network guidelines are relatively unlikely to have adverse pathology at the time of surgical resection. These data may help inform the use of imaging and molecular markers as well as the intensity of surveillance in men with newly diagnosed PCa. Copyright © 2016 Elsevier Inc. All rights reserved.

Differentiating malignant from benign breast tumors on acoustic radiation force impulse imaging using fuzzy-based neural networks with principle component analysis

NASA Astrophysics Data System (ADS)

Liu, Hsiao-Chuan; Chou, Yi-Hong; Tiu, Chui-Mei; Hsieh, Chi-Wen; Liu, Brent; Shung, K. Kirk

2017-03-01

Many modalities have been developed as screening tools for breast cancer. A new screening method called acoustic radiation force impulse (ARFI) imaging was created for distinguishing breast lesions based on localized tissue displacement. This displacement was quantitated by virtual touch tissue imaging (VTI). However, VTIs sometimes express reverse results to intensity information in clinical observation. In the study, a fuzzy-based neural network with principle component analysis (PCA) was proposed to differentiate texture patterns of malignant breast from benign tumors. Eighty VTIs were randomly retrospected. Thirty four patients were determined as BI-RADS category 2 or 3, and the rest of them were determined as BI-RADS category 4 or 5 by two leading radiologists. Morphological method and Boolean algebra were performed as the image preprocessing to acquire region of interests (ROIs) on VTIs. Twenty four quantitative parameters deriving from first-order statistics (FOS), fractal dimension and gray level co-occurrence matrix (GLCM) were utilized to analyze the texture pattern of breast tumors on VTIs. PCA was employed to reduce the dimension of features. Fuzzy-based neural network as a classifier to differentiate malignant from benign breast tumors. Independent samples test was used to examine the significance of the difference between benign and malignant breast tumors. The area Az under the receiver operator characteristic (ROC) curve, sensitivity, specificity and accuracy were calculated to evaluate the performance of the system. Most all of texture parameters present significant difference between malignant and benign tumors with p-value of less than 0.05 except the average of fractal dimension. For all features classified by fuzzy-based neural network, the sensitivity, specificity, accuracy and Az were 95.7%, 97.1%, 95% and 0.964, respectively. However, the sensitivity, specificity, accuracy and Az can be increased to 100%, 97.1%, 98.8% and 0.985, respectively if PCA was performed to reduce the dimension of features. Patterns of breast tumors on VTIs can effectively be recognized by quantitative texture parameters, and differentiated malignant from benign lesions by fuzzy-based neural network with PCA.

Application of Principal Component Analysis to NIR Spectra of Phyllosilicates: A Technique for Identifying Phyllosilicates on Mars

NASA Technical Reports Server (NTRS)

Rampe, E. B.; Lanza, N. L.

2012-01-01

Orbital near-infrared (NIR) reflectance spectra of the martian surface from the OMEGA and CRISM instruments have identified a variety of phyllosilicates in Noachian terrains. The types of phyllosilicates present on Mars have important implications for the aqueous environments in which they formed, and, thus, for recognizing locales that may have been habitable. Current identifications of phyllosilicates from martian NIR data are based on the positions of spectral absorptions relative to laboratory data of well-characterized samples and from spectral ratios; however, some phyllosilicates can be difficult to distinguish from one another with these methods (i.e. illite vs. muscovite). Here we employ a multivariate statistical technique, principal component analysis (PCA), to differentiate between spectrally similar phyllosilicate minerals. PCA is commonly used in a variety of industries (pharmaceutical, agricultural, viticultural) to discriminate between samples. Previous work using PCA to analyze raw NIR reflectance data from mineral mixtures has shown that this is a viable technique for identifying mineral types, abundances, and particle sizes. Here, we evaluate PCA of second-derivative NIR reflectance data as a method for classifying phyllosilicates and test whether this method can be used to identify phyllosilicates on Mars.

Analyzing brain networks with PCA and conditional Granger causality.

PubMed

Zhou, Zhenyu; Chen, Yonghong; Ding, Mingzhou; Wright, Paul; Lu, Zuhong; Liu, Yijun

2009-07-01

Identifying directional influences in anatomical and functional circuits presents one of the greatest challenges for understanding neural computations in the brain. Granger causality mapping (GCM) derived from vector autoregressive models of data has been employed for this purpose, revealing complex temporal and spatial dynamics underlying cognitive processes. However, the traditional GCM methods are computationally expensive, as signals from thousands of voxels within selected regions of interest (ROIs) are individually processed, and being based on pairwise Granger causality, they lack the ability to distinguish direct from indirect connectivity among brain regions. In this work a new algorithm called PCA based conditional GCM is proposed to overcome these problems. The algorithm implements the following two procedures: (i) dimensionality reduction in ROIs of interest with principle component analysis (PCA), and (ii) estimation of the direct causal influences in local brain networks, using conditional Granger causality. Our results show that the proposed method achieves greater accuracy in detecting network connectivity than the commonly used pairwise Granger causality method. Furthermore, the use of PCA components in conjunction with conditional GCM greatly reduces the computational cost relative to the use of individual voxel time series. Copyright 2009 Wiley-Liss, Inc

Application of principal component analysis to multispectral imaging data for evaluation of pigmented skin lesions

NASA Astrophysics Data System (ADS)

Jakovels, Dainis; Lihacova, Ilze; Kuzmina, Ilona; Spigulis, Janis

2013-11-01

Non-invasive and fast primary diagnostics of pigmented skin lesions is required due to frequent incidence of skin cancer - melanoma. Diagnostic potential of principal component analysis (PCA) for distant skin melanoma recognition is discussed. Processing of the measured clinical multi-spectral images (31 melanomas and 94 nonmalignant pigmented lesions) in the wavelength range of 450-950 nm by means of PCA resulted in 87 % sensitivity and 78 % specificity for separation between malignant melanomas and pigmented nevi.

Hetero-bivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2013-09-01

Suzuki cross-coupling reaction. The effects of solvent and base on the synthesis of 3 were studied using Pd(PPh3)4 as catalyst . DMF, ethanol, and DMSO...PSMA/hepsin for in vitro cell uptake and in vivo imaging studies . Compound 13 showed a low but detectable increased cell uptake into the developed...have been comprehensive clinical studies whether PSA testing is an efficient biomarker in diagnosing PCa and reducing PCa deaths. Two European studies

Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspicion of prostate cancer (IMPROD Trial).

PubMed

Jambor, Ivan; Boström, Peter J; Taimen, Pekka; Syvänen, Kari; Kähkönen, Esa; Kallajoki, Markku; Perez, Ileana Montoya; Kauko, Tommi; Matomäki, Jaakko; Ettala, Otto; Merisaari, Harri; Kiviniemi, Aida; Dean, Peter B; Aronen, Hannu J

2017-10-01

To evaluate the role of a 3T biparametric magnetic resonance imaging (bpMRI), T 2 -weighted imaging, and three separate diffusion-weighted imaging acquisitions combined with targeted biopsy (TB) for improving risk stratification of men with elevated prostate-specific antigen (PSA). Between March 2013 and February 2015, 175 men with a clinical suspicion of prostate cancer (PCa) were offered bpMRI (NCT01864135) based on a suspicion of PCa (two repeated PSA measurements in the range 2.5-20.0 ng/ml and/or abnormal digital rectal examination). Men with an equivocal to high suspicion of PCa had two TBs of the dominant lesion using cognitive ultrasound guidance, followed by systematic biopsy (SB). Men with a low to very low suspicion had only SB. In total, 161 (161/175, 92%) prospectively enrolled men completed the trial and were included in the final analyses. The primary endpoint of the trial was the cancer detection rate (CDR) of TB and SB. Clinically significant cancer (SPCa) was defined as Gleason score ≥3 + 4. TB compared with SB had higher CDR for SPCa (45%, 72/161 vs. 39%, 63/161, respectively; P > 0.05) and a lower CDR for Gleason score 3 + 3 (8%, 15/161 vs. 16%, 30/161; P < 0.05). Restricting biopsy to men with equivocal to highly suspicious bpMRI findings would have resulted in a 24% (38/161) reduction in the number of men undergoing biopsy, while missing 4 (2%) with SPCa. All anonymized datasets, including bpMRI reports and follow up information, are freely available on the trial server. Prebiopsy bpMRI and TB in men with a clinical suspicion of PCa improved risk stratification. 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2017;46:1089-1095. © 2017 International Society for Magnetic Resonance in Medicine.

The oncogenic role of the In1-ghrelin splicing variant in prostate cancer aggressiveness.

PubMed

Hormaechea-Agulla, Daniel; Gahete, Manuel D; Jiménez-Vacas, Juan M; Gómez-Gómez, Enrique; Ibáñez-Costa, Alejandro; L-López, Fernando; Rivero-Cortés, Esther; Sarmento-Cabral, André; Valero-Rosa, José; Carrasco-Valiente, Julia; Sánchez-Sánchez, Rafael; Ortega-Salas, Rosa; Moreno, María M; Tsomaia, Natia; Swanson, Steve M; Culler, Michael D; Requena, María J; Castaño, Justo P; Luque, Raúl M

2017-08-29

The Ghrelin-system is a complex, pleiotropic family composed of several peptides, including native-ghrelin and its In1-ghrelin splicing variant, and receptors (GHSR 1a/b), which are dysregulated in various endocrine-related tumors, where they associate to pathophysiological features, but the presence, functional role, and mechanisms of actions of In1-ghrelin splicing variant in prostate-cancer (PCa), is completely unexplored. Herein, we aimed to determine the presence of key ghrelin-system components (native-ghrelin, In1-ghrelin, GHSR1a/1b) and their potential pathophysiological role in prostate cancer (PCa). In1-ghrelin and native-ghrelin expression was evaluated by qPCR in prostate tissues from patients with high PCa-risk (n = 52; fresh-tumoral biopsies), and healthy-prostates (n = 12; from cystoprostatectomies) and correlated with clinical parameters using Spearman-test. In addition, In1-ghrelin and native-ghrelin was measured in plasma from an additional cohort of PCa-patients with different risk levels (n = 30) and control-healthy patients (n = 20). In vivo functional (proliferation/migration) and mechanistic (gene expression/signaling-pathways) assays were performed in PCa-cell lines in response to In1-ghrelin and native-ghrelin treatment, overexpression and/or silencing. Finally, tumor progression was monitored in nude-mice injected with PCa-cells overexpressing In1-ghrelin, native-ghrelin and empty vector (control). In1-ghrelin, but not native-ghrelin, was overexpressed in high-risk PCa-samples compared to normal-prostate (NP), and this expression correlated with that of PSA. Conversely, GHSR1a/1b expression was virtually absent. Remarkably, plasmatic In1-ghrelin, but not native-ghrelin, levels were also higher in PCa-patients compared to healthy-controls. Furthermore, In1-ghrelin treatment/overexpression, and to a much lesser extent native-ghrelin, increased aggressiveness features (cell-proliferation, migration and PSA secretion) of NP and PCa cells. Consistently, nude-mice injected with PC-3-cells stably-transfected with In1-ghrelin, but not native-ghrelin, presented larger tumors. These effects were likely mediated by ERK1/2-signaling activation and involved altered expression of key oncogenes/tumor suppressor genes. Finally, In1-ghrelin silencing reduced cell-proliferation and PSA secretion from PCa cells. Altogether, our results indicate that In1-ghrelin levels (in tissue) and circulating levels (in plasma) are increased in PCa where it can regulate key pathophysiological processes, thus suggesting that In1-ghrelin may represent a novel biomarker and a new therapeutic target in PCa.

Statistical analysis of aerosol species, trace gasses, and meteorology in Chicago.

PubMed

Binaku, Katrina; O'Brien, Timothy; Schmeling, Martina; Fosco, Tinamarie

2013-09-01

Both canonical correlation analysis (CCA) and principal component analysis (PCA) were applied to atmospheric aerosol and trace gas concentrations and meteorological data collected in Chicago during the summer months of 2002, 2003, and 2004. Concentrations of ammonium, calcium, nitrate, sulfate, and oxalate particulate matter, as well as, meteorological parameters temperature, wind speed, wind direction, and humidity were subjected to CCA and PCA. Ozone and nitrogen oxide mixing ratios were also included in the data set. The purpose of statistical analysis was to determine the extent of existing linear relationship(s), or lack thereof, between meteorological parameters and pollutant concentrations in addition to reducing dimensionality of the original data to determine sources of pollutants. In CCA, the first three canonical variate pairs derived were statistically significant at the 0.05 level. Canonical correlation between the first canonical variate pair was 0.821, while correlations of the second and third canonical variate pairs were 0.562 and 0.461, respectively. The first canonical variate pair indicated that increasing temperatures resulted in high ozone mixing ratios, while the second canonical variate pair showed wind speed and humidity's influence on local ammonium concentrations. No new information was uncovered in the third variate pair. Canonical loadings were also interpreted for information regarding relationships between data sets. Four principal components (PCs), expressing 77.0 % of original data variance, were derived in PCA. Interpretation of PCs suggested significant production and/or transport of secondary aerosols in the region (PC1). Furthermore, photochemical production of ozone and wind speed's influence on pollutants were expressed (PC2) along with overall measure of local meteorology (PC3). In summary, CCA and PCA results combined were successful in uncovering linear relationships between meteorology and air pollutants in Chicago and aided in determining possible pollutant sources.

Transabdominal contrast-enhanced ultrasound imaging of the prostate.

PubMed

Mischi, Massimo; Demi, Libertario; Smeenge, Martijn; Kuenen, Maarten P J; Postema, Arnoud W; de la Rosette, Jean J M C H; Wijkstra, Hessel

2015-04-01

Numerous age-related pathologies affect the prostate gland, the most menacing of which is prostate cancer (PCa). The diagnostic tools for prostate investigation are invasive, requiring biopsies when PCa is suspected. Novel dynamic contrast-enhanced ultrasound (DCE-US) imaging approaches have been proposed recently and appear promising for minimally invasive localization of PCa. Ultrasound imaging of the prostate is traditionally performed with a transrectal probe because the location of the prostate allows for high-resolution images using high-frequency transducers. However, DCE-US imaging requires lower frequencies to induce bubble resonance and, thus, improve contrast-to-tissue ratio. For this reason, in this study we investigate the feasibility of quantitative DCE-US imaging of the prostate via the abdomen. The study included 10 patients (age = 60.7 ± 5.7 y) referred for a needle biopsy study. After having given informed consent, patients underwent DCE-US with both transabdominal and transrectal probes. Time-intensity contrast curves were derived using both approaches and their model-fit quality was compared. Although further improvements are expected by optimization of the transabdominal settings, the results of transabdominal and transrectal DCE-US are closely comparable, confirming the feasibility of transabdominal DCE-US; transabdominal curve fitting revealed an average determination coefficient r(2) = 0.91 (r(2) > 0.75 for 78.6% of all prostate pixels) compared with r(2) = 0.91 (r(2) > 0.75 for 81.6% of all prostate pixels) by the transrectal approach. Replacing the transrectal approach with more acceptable transabdominal scanning for prostate investigation is feasible. This approach would improve patient comfort and represent a useful option for PCa localization and monitoring. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Local infiltration analgesia for total knee arthroplasty: should ketorolac be added?

PubMed

Andersen, K V; Nikolajsen, L; Haraldsted, V; Odgaard, A; Søballe, K

2013-08-01

Adequate postoperative analgesia with minimal side-effects is essential for early mobilization and recovery in patients undergoing total knee arthroplasty (TKA). High-volume local infiltration analgesia (LIA) with ropivacaine has been introduced, but effects of adjuvants are still debated. We tested the hypothesis that the addition of ketorolac to LIA significantly improves analgesia after TKA. Sixty patients undergoing TKA were randomized to receive intraoperative LIA (ropivacaine 300 mg and epinephrine 0.5 mg) combined with either ketorolac 30 mg (ketorolac group) or saline (control group). After surgery, eight bolus doses of ropivacaine 100 mg combined with either ketorolac 15 mg (ketorolac group) or saline (control group) were administered every 6 h via an intra-articular catheter. The primary outcome was postoperative consumption of i.v. morphine patient-controlled analgesia (PCA). Secondary outcomes were time to first request of i.v. morphine PCA, pain intensity, side-effects, and readiness for hospital discharge. Consumption of i.v. morphine PCA was lower in the ketorolac group vs control group {0-6 h: 0 (0-0) vs 5 (0-10) mg, P<0.0001; 0-48 h: 10 (0-22.5) vs 48.75 (30-82.5) mg, P<0.0001 [median (inter-quartile range, IQR)]}. Time to first request of i.v. morphine PCA was longer in the ketorolac group vs the control group [490 (248-617) vs 223 (115-319) min, P=0.02, median (IQR)]. Early postoperative pain (<48 h) and readiness for hospital discharge were also significantly reduced in the ketorolac group. LIA with ketorolac results in reduced morphine consumption, reduced pain intensity, and earlier readiness for hospital discharge.

Modeling Pair Distribution Functions of Rare-Earth Phosphate Glasses Using Principal Component Analysis.

PubMed

Cole, Jacqueline M; Cheng, Xie; Payne, Michael C

2016-11-07

The use of principal component analysis (PCA) to statistically infer features of local structure from experimental pair distribution function (PDF) data is assessed on a case study of rare-earth phosphate glasses (REPGs). Such glasses, codoped with two rare-earth ions (R and R') of different sizes and optical properties, are of interest to the laser industry. The determination of structure-property relationships in these materials is an important aspect of their technological development. Yet, realizing the local structure of codoped REPGs presents significant challenges relative to their singly doped counterparts; specifically, R and R' are difficult to distinguish in terms of establishing relative material compositions, identifying atomic pairwise correlation profiles in a PDF that are associated with each ion, and resolving peak overlap of such profiles in PDFs. This study demonstrates that PCA can be employed to help overcome these structural complications, by statistically inferring trends in PDFs that exist for a restricted set of experimental data on REPGs, and using these as training data to predict material compositions and PDF profiles in unknown codoped REPGs. The application of these PCA methods to resolve individual atomic pairwise correlations in t(r) signatures is also presented. The training methods developed for these structural predictions are prevalidated by testing their ability to reproduce known physical phenomena, such as the lanthanide contraction, on PDF signatures of the structurally simpler singly doped REPGs. The intrinsic limitations of applying PCA to analyze PDFs relative to the quality control of source data, data processing, and sample definition, are also considered. While this case study is limited to lanthanide-doped REPGs, this type of statistical inference may easily be extended to other inorganic solid-state materials and be exploited in large-scale data-mining efforts that probe many t(r) functions.

Potentiation of Inflammatory CXCL8 Signalling Sustains Cell Survival in PTEN-deficient Prostate Carcinoma

PubMed Central

Maxwell, Pamela J.; Coulter, Jonathan; Walker, Steven M.; McKechnie, Melanie; Neisen, Jessica; McCabe, Nuala; Kennedy, Richard D.; Salto-Tellez, Manuel; Albanese, Chris; Waugh, David J.J.

2014-01-01

Background: Inflammation and genetic instability are enabling characteristics of prostate carcinoma (PCa). Inactivation of the tumour suppressor gene phosphatase and tensin homolog (PTEN) is prevalent in early PCa. The relationship of PTEN deficiency to inflammatory signalling remains to be characterised. Objective: To determine how loss of PTEN functionality modulates expression and efficacy of clinically relevant, proinflammatory chemokines in PCa. Design, setting, and participants: Experiments were performed in established cell-based PCa models, supported by pathologic analysis of chemokine expression in prostate tissue harvested from PTEN heterozygous (Pten+/−) mice harbouring inactivation of one PTEN allele. Interventions: Small interfering RNA (siRNA)–or small hairpin RNA (shRNA)–directed strategies were used to repress PTEN expression and resultant interleukin-8 (CXCL8) signalling, determined under normal and hypoxic culture conditions. Outcome measurements and statistical analysis: Changes in chemokine expression in PCa cells and tissue were analysed by real-time polymerase chain reaction (PCR), immunoblotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry; effects of chemokine signalling on cell function were assessed by cell cycle analysis, apoptosis, and survival assays. Results and limitations: Transient (siRNA) or prolonged (shRNA) PTEN repression increased expression of CXCL8 and its receptors, chemokine (C-X-C motif) receptor (CXCR) 1 and CXCR2, in PCa cells. Hypoxia-induced increases in CXCL8, CXCR1, and CXCR2 expression were greater in magnitude and duration in PTEN-depleted cells. Autocrine CXCL8 signalling was more efficacious in PTEN-depleted cells, inducing hypoxia-inducible factor-1 (HIF-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription and regulating genes involved in survival and angiogenesis. Increased expression of the orthologous chemokine KC was observed in regions displaying atypical cytologic features in Pten+/− murine prostate tissue relative to normal epithelium in wild-type PTEN (PtenWT) glands. Attenuation of CXCL8 signalling decreased viability of PCa cells harbouring partial or complete PTEN loss through promotion of G1 cell cycle arrest and apoptosis. The current absence of clinical validation is a limitation of the study. Conclusions: PTEN loss induces a selective upregulation of CXCL8 signalling that sustains the growth and survival of PTEN-deficient prostate epithelium. PMID:22939387

Estrogen induces androgen-repressed SOX4 expression to promote progression of prostate cancer cells.

PubMed

Yang, Muyi; Wang, Jing; Wang, Lin; Shen, Chengwu; Su, Bo; Qi, Mei; Hu, Jing; Gao, Wei; Tan, Weiwei; Han, Bo

2015-09-01

The sex determing region Y-box 4 (SOX4) gene is a critical developmental transcriptional factor that is overexpressed in prostate cancer (PCa). While we and others have investigated the role of SOX4 overexpression in PCa, the molecular mechanism underlying its aberrant expression remains unclear. Immunohistochemistry were utilized to detect SOX4 expression and the correlation between estrogen receptor β (ERβ), androgen receptor (AR) and SOX4 in a cohort of 94 clinical specimens. Real-time quantitative PCR and Western blotting were used to study the transcript and protein expression levels. Immunofluorescence staining and co-immunoprecipitation were performed to assess the interaction and subcellular location of ERβ and AR. Chromatin immunoprecipitation (ChIP) assays and Luciferase reporter assays were performed to explore the binding and transcriptional activities of ERβ and AR to the SOX4 promoter. Cellular function was evaluated by MTS, invasion and wound healing assays. SOX4 expression is up-regulated in Castration-Resistant Prostate Cancer (CRPC) tumors compared to hormone-dependent PCa (HDPC) cases. Increased expression was also observed in PCa cells after long-term androgen-deprivation treatment (ADT). In vitro data indicated that SOX4 is an AR transcriptional target and down-regulated by dihydrotestosterone (DHT) via AR. 17β-estradiol (E2) up-regulates SOX4 expression in the absence of androgen through the formation of a protein complex between ERβ and AR. Knockdown of AR or ERβ blocks the E2-induced SOX4 expression. ChIP assays confirmed that both ERβ and AR bind to the SOX4 promoter in response to E2. Functionally, silencing SOX4 significantly attenuates the proliferative effect, as well as the capacity of migration and invasion of E2 on PCa cells. Clinically, overexpression of SOX4 is significantly associated with ERβ expression in PCa. In addition, this association is still retained in CRPC patients with poor prognosis. These findings suggest that SOX4 is a novel DHT-repressed AR-target gene. E2 could promote proliferation of PCa cells through the up-regulation of SOX4 under androgen-depleted environment. Our data provides a possible molecular basis for the overexpression of SOX4 in CRPC and may facilitate the detection and prevention of the emergence of CRPC. © 2015 Wiley Periodicals, Inc.

The synergy between ionizing radiation and immunotherapy in the treatment of prostate cancer.

PubMed

Sathianathen, Niranjan J; Krishna, Suprita; Konety, Badrinath R; Griffith, Thomas S

2017-09-01

There has been a surge in the use of immunotherapy for genitourinary malignancies. Immunotherapy is an established treatment for metastatic renal cell carcinoma and nonmuscle invasive bladder cancer, but its potential for treating prostate cancer (PCa) remains under investigation. Despite reported survival benefits, no published Phase III PCa trials using immunotherapy only as a treatment has demonstrated direct antitumor effects by reducing prostate-specific antigen levels. Subsequently, the thought of combining immunotherapy with other treatment modalities has gained traction as a way to achieving optimal results. Based on data from other malignancies, it is hypothesized that radiotherapy and immunotherapy can act synergistically to improve outcomes. We will discuss the clinical potential of combining immune-based treatments with radiotherapy as a treatment for advanced PCa.

Racial disparities: disruptive genes in prostate carcinogenesis.

PubMed

Singh, Savita; Plaga, Alexis; Shukla, Girish C

2017-06-01

Population specific studies in prostate cancer (PCa) reveal a unique heterogeneous etiology. Various factors, such as genetics, environment and dietary regimen seems to determine disease progression, therapeutic resistance and rate of mortality. Enormous disparity documented in disease incidences, aggressiveness and mortality in PCa among AAs (African Americans) and CAs (Caucasian Americans) is attributed to the variations in genetics, epigenetics and their association with metabolism. Scientific and clinical evidences have revealed the influence of variations in Androgen Receptor (AR), RNAse L, macrophage scavenger receptor 1 ( MRS1 ), androgen metabolism by cytochrome P450 3A4, differential regulation of microRNAs, epigenetic alterations and diet in racial disparity in PCa incidences and mortality. Concerted efforts are needed to identify race specific prognostic markers and treatment regimen for a better management of the disease.

Modified locally weighted--partial least squares regression improving clinical predictions from infrared spectra of human serum samples.

PubMed

Perez-Guaita, David; Kuligowski, Julia; Quintás, Guillermo; Garrigues, Salvador; Guardia, Miguel de la

2013-03-30

Locally weighted partial least squares regression (LW-PLSR) has been applied to the determination of four clinical parameters in human serum samples (total protein, triglyceride, glucose and urea contents) by Fourier transform infrared (FTIR) spectroscopy. Classical LW-PLSR models were constructed using different spectral regions. For the selection of parameters by LW-PLSR modeling, a multi-parametric study was carried out employing the minimum root-mean square error of cross validation (RMSCV) as objective function. In order to overcome the effect of strong matrix interferences on the predictive accuracy of LW-PLSR models, this work focuses on sample selection. Accordingly, a novel strategy for the development of local models is proposed. It was based on the use of: (i) principal component analysis (PCA) performed on an analyte specific spectral region for identifying most similar sample spectra and (ii) partial least squares regression (PLSR) constructed using the whole spectrum. Results found by using this strategy were compared to those provided by PLSR using the same spectral intervals as for LW-PLSR. Prediction errors found by both, classical and modified LW-PLSR improved those obtained by PLSR. Hence, both proposed approaches were useful for the determination of analytes present in a complex matrix as in the case of human serum samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Scene perception in posterior cortical atrophy: categorization, description and fixation patterns.

PubMed

Shakespeare, Timothy J; Yong, Keir X X; Frost, Chris; Kim, Lois G; Warrington, Elizabeth K; Crutch, Sebastian J

2013-01-01

Partial or complete Balint's syndrome is a core feature of the clinico-radiological syndrome of posterior cortical atrophy (PCA), in which individuals experience a progressive deterioration of cortical vision. Although multi-object arrays are frequently used to detect simultanagnosia in the clinical assessment and diagnosis of PCA, to date there have been no group studies of scene perception in patients with the syndrome. The current study involved three linked experiments conducted in PCA patients and healthy controls. Experiment 1 evaluated the accuracy and latency of complex scene perception relative to individual faces and objects (color and grayscale) using a categorization paradigm. PCA patients were both less accurate (faces < scenes < objects) and slower (scenes < objects < faces) than controls on all categories, with performance strongly associated with their level of basic visual processing impairment; patients also showed a small advantage for color over grayscale stimuli. Experiment 2 involved free description of real world scenes. PCA patients generated fewer features and more misperceptions than controls, though perceptual errors were always consistent with the patient's global understanding of the scene (whether correct or not). Experiment 3 used eye tracking measures to compare patient and control eye movements over initial and subsequent fixations of scenes. Patients' fixation patterns were significantly different to those of young and age-matched controls, with comparable group differences for both initial and subsequent fixations. Overall, these findings describe the variability in everyday scene perception exhibited by individuals with PCA, and indicate the importance of exposure duration in the perception of complex scenes.

Quantitative assessment of the mechanical properties of prostate tissue with optical coherence elastography

NASA Astrophysics Data System (ADS)

Ling, Yuting; Li, Chunhui; Zhou, Kanheng; Guan, Guangying; Lang, Stephen; McGloin, David; Nabi, Ghulam; Huang, Zhihong

2018-02-01

Prostate cancer (PCa) is a heterogeneous disease with multifocal origin. In current clinical care, the Gleason scoring system is the well-established diagnosis by microscopic evaluation of the tissue from trans-rectal ultrasound (TRUS) guided biopsies. Nevertheless, the sensitivity and specificity in detecting PCa can range from 40 to 50% for conventional TRUS B-mode imaging. Tissue elasticity is associated with the disease progression and elastography technique has recently shown promise in aiding PCa diagnosis. However, many cancer foci in the prostate gland has very small size less than 1 mm and those detected by medical elastography were larger than 2 mm. Hereby, we introduce optical coherence elastography (OCE) to quantify the prostate stiffness with high resolution in the magnitude of 10 µm. Following our feasibility study of 10 patients reported previously, we recruited 60 more patients undergoing 12-core TRUS guided biopsies for suspected PCa with a total of 720 biopsies. The stiffness of cancer tissue was approximately 57.63% higher than that of benign ones. Using histology as reference standard and cut-off threshold of 600kPa, the data analysis showed sensitivity and specificity of 89.6% and 99.8% respectively. The method also demonstrated potential in characterising different grades of PCa based on the change of tissue morphology and quantitative mechanical properties. In conclusion, quantitative OCE can be a reliable technique to identify PCa lesion and differentiate indolent from aggressive cancer.

Predicting the effectiveness of virtual reality relaxation on pain and anxiety when added to PCA morphine in patients having burns dressings changes.

PubMed

Konstantatos, A H; Angliss, M; Costello, V; Cleland, H; Stafrace, S

2009-06-01

Pain arising in burns sufferers is often severe and protracted. The prospect of a dressing change can heighten existing pain by impacting both physically and psychologically. In this trial we examined whether pre-procedural virtual reality guided relaxation added to patient controlled analgesia with morphine reduced pain severity during awake dressings changes in burns patients. We conducted a prospective randomized clinical trial in all patients with burns necessitating admission to a tertiary burns referral centre. Eligible patients requiring awake dressings changes were randomly allocated to single use virtual reality relaxation plus intravenous morphine patient controlled analgesia (PCA) infusion or to intravenous morphine patient controlled analgesia infusion alone. Patients rated their worst pain intensity during the dressing change using a visual analogue scale. The primary outcome measure was presence of 30% or greater difference in pain intensity ratings between the groups in estimation of worst pain during the dressing change. Of 88 eligible and consenting patients having awake dressings changes, 43 were assigned to virtual reality relaxation plus intravenous morphine PCA infusion and 43 to morphine PCA infusion alone. The group receiving virtual reality relaxation plus morphine PCA infusion reported significantly higher pain intensities during the dressing change (mean=7.3) compared with patients receiving morphine PCA alone (mean=5.3) (p=0.003) (95% CI 0.6-2.8). The addition of virtual reality guided relaxation to morphine PCA infusion in burns patients resulted in a significant increase in pain experienced during awake dressings changes. In the absence of a validated predictor for responsiveness to virtual reality relaxation such a therapy cannot be recommended for general use in burns patients having awake dressings changes.

Upregulation of miR-146a by YY1 depletion correlates with delayed progression of prostate cancer

PubMed Central

Huang, Yeqing; Tao, Tao; Liu, Chunhui; Guan, Han; Zhang, Guangyuan; Ling, Zhixin; Zhang, Lei; Lu, Kai; Chen, Shuqiu; Xu, Bin; Chen, Ming

2017-01-01

Previously published studies explained that the excessive expression of miR-146a influences the prostate cancer (PCa) cells in terms of apoptosis, progression, and viability. Although miR-146a acts as a tumor suppressor, current knowledge on the molecular mechanisms that controls its expression in PCa is limited. In this study, gene set enrichment analysis (GSEA) showed negatively enriched expression of miR-146a target gene sets and positively enriched expression of gene sets suppressed by the enhancer of zeste homolog 2 (EZH2) after YY1 depletion in PCa cells. The current results demonstrated that the miR-146a levels in PCa tissues with high Gleason scores (>7) are significantly lower than those in PCa tissues with low Gleason scores (≤7), which were initially observed in the clinical specimens. An inverse relationship between YY1 and miR-146a expression was also observed. Experiments indicated the decrease in cell viability, proliferation, and promoting apoptosis after YY1 depletion, while through inhibiting miR-146a could alleviate the negative effect brought by YY1 depletion. We detected the reversed adjustment of YY1 to accommodate miR-146a transcriptions. On the basis of YY1 depletion, we determined that the expression of miR-146a increased after EZH2 knockdown. We validated the combination of YY1 and its interaction with EZH2 at the miR-146a promoter binding site, thereby prohibiting the transcriptional activity of miR-146a in PCa cells. Our results suggested that YY1 depletion repressed PCa cell viability and proliferation and induced apoptosis at least in a miR-146a-assisted manner. PMID:28101571

Ketamine added to morphine or hydromorphone patient-controlled analgesia for acute postoperative pain in adults: a systematic review and meta-analysis of randomized trials.

PubMed

Wang, Li; Johnston, Bradley; Kaushal, Alka; Cheng, Davy; Zhu, Fang; Martin, Janet

2016-03-01

To determine whether ketamine added to morphine or hydromorphone patient-controlled analgesia (PCA) provides clinically relevant reductions in postoperative pain, opioid requirements, and adverse events when compared with morphine or hydromorphone PCA in adults undergoing surgery. We systematically searched six databases up to June 2, 2015 for randomized controlled trials (RCTs) comparing ketamine plus morphine/hydromorphone PCA vs morphine/hydromorphone PCA for postoperative pain in adults. Thirty-six RCTs including 2,502 patients proved eligible, and 22 of these were at low risk of bias. The addition of ketamine to morphine/hydromorphone PCA decreased postoperative pain intensity at six to 72 hr when measured at rest (weighted mean difference [WMD] on a 10-cm visual analogue scale ranged from -0.4 to -1.3 cm) and during mobilization (WMD ranged from -0.4 to -0.5 cm). Adjunctive ketamine also significantly reduced cumulative morphine consumption at 24-72 hr by approximately 5-20 mg. Predefined subgroup analyses and meta-regression did not detect significant differences across subgroups, including a dose-response relationship. There was no significant difference in patient satisfaction scores at 24 and 48 hr. Nevertheless, the addition of ketamine to morphine/hydromorphone PCA significantly reduced postoperative nausea and vomiting (relative risk, 0.71; 95% confidence interval [CI], 0.60 to 0.85; absolute risk reduction, 8.9%; 95% CI, 4.6 to 12.2). Significant effects on other adverse events (e.g., hallucinations, vivid dreams) were not detected, though only a few studies reported on them. Adding ketamine to morphine/hydromorphone PCA provides a small improvement in postoperative analgesia while reducing opioid requirements. Adjunctive ketamine also reduces postoperative nausea and vomiting without a detected increase in other adverse effects; however, adverse events were probably underreported.

Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and posterior AD.

PubMed

Carrasquillo, Minerva M; Khan, Qurat ul Ain; Murray, Melissa E; Krishnan, Siddharth; Aakre, Jeremiah; Pankratz, V Shane; Nguyen, Thuy; Ma, Li; Bisceglio, Gina; Petersen, Ronald C; Younkin, Steven G; Dickson, Dennis W; Boeve, Bradley F; Graff-Radford, Neill R; Ertekin-Taner, Nilüfer

2014-04-22

To investigate association of genetic risk factors for late-onset Alzheimer disease (LOAD) with risk of posterior cortical atrophy (PCA), a syndrome of visual impairment with predominant Alzheimer disease (AD) pathology in posterior cortical regions, and with risk of "posterior AD" neuropathology. We assessed 81 participants with PCA diagnosed clinically and 54 with neuropathologic diagnosis of posterior AD vs 2,523 controls for association with 11 significant single nucleotide polymorphisms (SNPs) from published LOAD risk genome-wide association studies. There was highly significant association with APOE ε4 and increased risk of PCA (p = 0.0003, odds ratio [OR] = 3.17) and posterior AD (p = 1.11 × 10(-17), OR = 6.43). No other locus was significant after corrections for multiple testing, although rs11136000 near CLU (p = 0.019, OR = 0.60) and rs744373 near BIN1 (p = 0.025, OR = 1. 63) associated nominally significantly with posterior AD, and rs3851179 at the PICALM locus had significant association with PCA (p = 0.0003, OR = 2.84). ABCA7 locus SNP rs3764650, which was also tested under the recessive model because of Hardy-Weinberg disequilibrium, also had nominally significant association with PCA risk. The direction of association at APOE, CLU, and BIN1 loci was the same for participants with PCA and posterior AD. The effects for all SNPs, except rs3851179, were consistent with those for LOAD risk. We identified a significant effect for APOE and nominate CLU, BIN1, and ABCA7 as additional risk loci for PCA and posterior AD. Our findings suggest that at least some of the genetic risk factors for LOAD are shared with these atypical conditions and provide effect-size estimates for their future genetic studies.

CXCR6 is expressed in human prostate cancer in vivo and is involved in the in vitro invasion of PC3 and LNCap cells.

PubMed

Hu, Weidong; Zhen, Xinming; Xiong, Bin; Wang, Bicheng; Zhang, Weibing; Zhou, Wenhui

2008-07-01

In spite of the clinical importance of prostate cancer (PCa) bone metastasis, the precise mechanisms for the directed migration of malignant cells remain unclear. In the present study, the expression of CXCR6 in human PCa and benign prostatic hyperplasia samples, and the expression of CXCL16 in human osseous tissues were determined by immunohistochemistry. It was found that the level of CXCR6 protein expression was elevated in human malignant prostate tumors, and CXCL16 was expressed positively by human osteocytes in vivo. The in vitro experiments further confirmed that the PCa cell lines PC3 and LNCap expressed CXCR6 at both the mRNA and protein levels, and exogenous CXCL16 has the potential to stimulate the invasion of PC3 and LNCap. To further elucidate the role of the CXCL16-CXCR6 axis in PCa progression, we compared the expression of CXCR6 and CXCR4 in human PCa tissues and the effects of CXCL16 and CXCL12 on the in vitro invasion of PC3 and LNCap cells. It was shown that CXCR6 and CXCR4 proteins were coexpressed and elevated in human PCa samples, and CXCL16 and CXCL12 promoted the invasion of PC3 and LNCap via their respective receptors. Furthermore, in contrast to CXCL12, which enhanced the activity of matrix metalloproteinase (MMP) 9 and MMP2 in PC3 and LNCap, CXCL16 ligation resulted in stronger MMP9 and MMP2 activity in LNCap but not in PC3. Our results suggest that besides CXCL12/CXCR4, CXCL16/CXCR6 might be another important factor involved in PCa bone metastasis.

Amino-terminal enhancer of split gene AES encodes a tumor and metastasis suppressor of prostate cancer.

PubMed

Okada, Yoshiyuki; Sonoshita, Masahiro; Kakizaki, Fumihiko; Aoyama, Naoki; Itatani, Yoshiro; Uegaki, Masayuki; Sakamoto, Hiromasa; Kobayashi, Takashi; Inoue, Takahiro; Kamba, Tomomi; Suzuki, Akira; Ogawa, Osamu; Taketo, M Mark

2017-04-01

A major cause of cancer death is its metastasis to the vital organs. Few effective therapies are available for metastatic castration-resistant prostate cancer (PCa), and progressive metastatic lesions such as lymph nodes and bones cause mortality. We recently identified AES as a metastasis suppressor for colon cancer. Here, we have studied the roles of AES in PCa progression. We analyzed the relationship between AES expression and PCa stages of progression by immunohistochemistry of human needle biopsy samples. We then performed overexpression and knockdown of AES in human PCa cell lines LNCaP, DU145 and PC3, and determined the effects on proliferation, invasion and metastasis in culture and in a xenograft model. We also compared the PCa phenotypes of Aes/Pten compound knockout mice with those of Pten simple knockout mice. Expression levels of AES were inversely correlated with clinical stages of human PCa. Exogenous expression of AES suppressed the growth of LNCaP cells, whereas the AES knockdown promoted it. We also found that AES suppressed transcriptional activities of androgen receptor and Notch signaling. Notably, AES overexpression in AR-defective DU145 and PC3 cells reduced invasion and metastasis to lymph nodes and bones without affecting proliferation in culture. Consistently, prostate epithelium-specific inactivation of Aes in Pten flox/flox mice increased expression of Snail and MMP9, and accelerated growth, invasion and lymph node metastasis of the mouse prostate tumor. These results suggest that AES plays an important role in controlling tumor growth and metastasis of PCa by regulating both AR and Notch signaling pathways. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Targeting IκB kinase β/NF-κB signaling in human prostate cancer by a novel IκB kinase β inhibitor CmpdA

PubMed Central

Zhang, Yanting; Lapidus, Rena G.; Liu, Peiyan; Choi, Eun Yong; Adediran, Samusi; Hussain, Arif; Wang, Xinghuan; Liu, Xuefeng; Dan, Han C.

2016-01-01

NF-κB plays an important role in many types of cancer, including prostate cancer (PCa), but the role of the upstream kinase of NF-κB, IKKβ, in PCa has not been fully documented, nor are there any effective IKKβ inhibitors used in clinical settings. Here, we have shown that IKKβ activity is mediated by multiple kinases including IKKα in human PCa cell lines that express activated IKKβ. Immunohistochemical analysis (IHC) of human PCa tissue microarrays (TMA) demonstrates that phosphorylation of IKKα/β within its activation loop gradually increases in low to higher stage tumors as compared to normal tissue. The expression of cell proliferation and survival markers (Ki67, Survivin), epithelial-to-mesenchymal transition (EMT) markers (Slug, Snail), as well as cancer stem cell (CSC) related transcription factors (Nanog, Sox2, Oct-4), also increase in parallel among the respective TMA samples analyzed. IKKβ, but not NF-κB, is found to regulate Nanog, which, in turn, modulates the levels of Oct4, Sox2, Snail and Slug, indicating an essential role of IKKβ in regulating cancer stem cells and EMT. The novel IKKβ inhibitor CmpdA inhibits constitutively activated IKKβ/NF-κB signaling, leading to induction of apoptosis and inhibition of proliferation, migration and stemness in these cells. CmpdA also significantly inhibits tumor growth in xenografts without causing apparent in vivo toxicity. Furthermore, CmpdA and docetaxel act synergistically to inhibit proliferation of PCa cells. These results indicate that IKKβ plays a pivotal role in PCa, and targeting IKKβ, including in combination with docetaxel, may be a potentially useful strategy for treating advanced PCa. PMID:27196761

Model Classes, Approximation, and Metrics for Dynamic Processing of Urban Terrain Data

DTIC Science & Technology

2013-01-01

Sensing,” DARPA IPTO Retreat, Annapolis, 2008. R. Baraniuk, “Compressive Sensing, Wavelets, and Sparsity,” SPIE Defense + Security (acceptance speech ... Speech and Signal Processing (ICASSP). 2011/05/22 00:00:00, Prague, Czech Republic. : , 08/31/2011 33.00 Sang-Mook Lee, Jeong Joon Im, Bo-Hee Lee... KNN ) points to define a local intrinsic coordinate system using PCA and to construct the manifold and function locally using least squares. Local

Evolutionary plasticity of plasma membrane interaction in DREPP family proteins.

PubMed

Vosolsobě, Stanislav; Petrášek, Jan; Schwarzerová, Kateřina

2017-05-01

The plant-specific DREPP protein family comprises proteins that were shown to regulate the actin and microtubular cytoskeleton in a calcium-dependent manner. Our phylogenetic analysis showed that DREPPs first appeared in ferns and that DREPPs have a rapid and plastic evolutionary history in plants. Arabidopsis DREPP paralogues called AtMDP25/PCaP1 and AtMAP18/PCaP2 are N-myristoylated, which has been reported as a key factor in plasma membrane localization. Here we show that N-myristoylation is neither conserved nor ancestral for the DREPP family. Instead, by using confocal microscopy and a new method for quantitative evaluation of protein membrane localization, we show that DREPPs rely on two mechanisms ensuring their plasma membrane localization. These include N-myristoylation and electrostatic interaction of a polybasic amino acid cluster. We propose that various plasma membrane association mechanisms resulting from the evolutionary plasticity of DREPPs are important for refining plasma membrane interaction of these signalling proteins under various conditions and in various cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Pavement thickness design for local roads in Iowa.

DOT National Transportation Integrated Search

2010-02-01

Three pavement design software packages were compared with regards to how they were different in determining design input parameters and their influences on the pavement thickness. StreetPave designs the concrete pavement thickness based on the PCA m...

Spatial Mapping of Pyocyanin in Pseudomonas aeruginosa Bacterial Communities by Surface Enhanced Raman Scattering

PubMed Central

Polisetti, Sneha; Baig, Nameera F.; Morales-Soto, Nydia; Shrout, Joshua D.; Bohn, Paul W.

2017-01-01

Surface Enhanced Raman Spectroscopy (SERS) imaging was used in conjunction with Principal Component Analysis (PCA) for the in situ spatiotemporal mapping of the virulence factor pyocyanin, in communities of the pathogenic bacterium Pseudomonas aeruginosa. The combination of SERS imaging and PCA analysis provides a robust method for characterization of heterogeneous biological systems while circumventing issues associated with interference from sample autofluorescence and low reproducibility of SERS signals. The production of pyocyanin is found to depend both on the growth carbon source and on the specific strain of P. aeruginosa studied. A cystic fibrosis lung isolate strain of P. aeruginosa synthesizes and secretes pyocyanin when grown with glucose and glutamate, while the laboratory strain exhibits detectable production of pyocyanin only when grown with glutamate as the source of carbon. Pyocyanin production in the laboratory strain grown with glucose was below the limit of detection of SERS. In addition, the combination of SERS imaging and PCA can elucidate subtle differences in the molecular composition of biofilms. PCA loading plots from the clinical isolate exhibit features corresponding to vibrational bands of carbohydrates, which represent the mucoid biofilm matrix specific to that isolate, features that are not seen in the PCA loading plots of the laboratory strain. PMID:27354400

[Development of a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse tanscription polymerase chain reaction (qRT-PCR)].

PubMed

Pavlov, K A; Shkoporov, A N; Khokhlova, E V; Korchagina, A A; Sidorenkov, A V; Grigor'ev, M É; Pushkar', D Iu; Chekhonin, V P

2013-01-01

The wide introduction of prostatic specific antigen (PSA) determination into clinical practice has resulted in a larger number of prostate biopsies, while the lower age threshold for PSA has led to a larger number of unnecessary prostate biopsies. Hence, there is a need for new biomarkers that can detect prostate cancer. PCA3 is a noncoding messenger ribonucleic acid (mRNA) that is expressed exclusively in prostate cells. The aim of the study has been to develop a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of the study, a laboratory diagnostic test system prototype has been designed, an application methodology has been developed and specificity and sensitivity data of the method has been assessed. The diagnostic system has demonstrated its ability to detect significantly elevated levels of PCA 3/KLK 3 in samples from prostate cancer (PCa) patients compared with those from healthy men. The findings have shown relatively high diagnostic sensitivity, specificity and negative-predictive values for an early non-invasive screening of prostate cancer

Lipid catabolism via CPT1 as a therapeutic target for prostate cancer

PubMed Central

Schlaepfer, Isabel R.; Rider, Leah; Rodrigues, Lindsey Ulkus; Gijón, Miguel A.; Pac, Colton T.; Romero, Lina; Cimic, Adela; Sirintrapun, S. Joseph; Glodé, L. Michael; Eckel, Robert H.; Cramer, Scott D.

2014-01-01

Prostate cancer (PCa) is the most commonly diagnosed malignancy among western men and accounts for the second leading cause of cancer-related deaths. PCa tends to grow slowly and recent studies suggest that it relies on lipid fuel more than on aerobic glycolysis. However, the biochemical mechanisms governing the relationships between lipid synthesis, lipid utilization, and cancer growth remain unknown. To address the role of lipid metabolism in PCa we have used Etomoxir and Orlistat, clinically safe drugs that block lipid oxidation and lipid synthesis/lipolysis, respectively. Etomoxir is an irreversible inhibitor of the carnitine palmitoyltransferase (CPT1) enzyme that decreases beta oxidation in the mitochondria. Combinatorial treatments using Etomoxir and Orlistat resulted in synergistic decreased viability in LNCaP, VCaP and patient-derived benign and PCa cells. These effects were associated with decreased androgen receptor (AR) expression, decreased mammalian target of Rapamycin (mTOR) signaling and increased caspase-3 activation. Knockdown of CPT1A enzyme in LNCaP cells resulted in decreased palmitate oxidation but increased sensitivity to Etomoxir, with inactivation of AKT kinase and activation of caspase-3. Systemic treatment with Etomoxir in nude nice resulted in decreased xenograft growth over 21 days, underscoring the therapeutic potential of blocking lipid catabolism to decrease PCa tumor growth. PMID:25122071

Multifunctional Envelope-Type siRNA Delivery Nanoparticle Platform for Prostate Cancer Therapy.

PubMed

Xu, Xiaoding; Wu, Jun; Liu, Yanlan; Saw, Phei Er; Tao, Wei; Yu, Mikyung; Zope, Harshal; Si, Michelle; Victorious, Amanda; Rasmussen, Jonathan; Ayyash, Dana; Farokhzad, Omid C; Shi, Jinjun

2017-03-28

With the capability of specific silencing of target gene expression, RNA interference (RNAi) technology is emerging as a promising therapeutic modality for the treatment of cancer and other diseases. One key challenge for the clinical applications of RNAi is the safe and effective delivery of RNAi agents such as small interfering RNA (siRNA) to a particular nonliver diseased tissue (e.g., tumor) and cell type with sufficient cytosolic transport. In this work, we proposed a multifunctional envelope-type nanoparticle (NP) platform for prostate cancer (PCa)-specific in vivo siRNA delivery. A library of oligoarginine-functionalized and sharp pH-responsive polymers was synthesized and used for self-assembly with siRNA into NPs with the features of long blood circulation and pH-triggered oligoarginine-mediated endosomal membrane penetration. By further modification with ACUPA, a small molecular ligand specifically recognizing prostate-specific membrane antigen (PSMA) receptor, this envelope-type nanoplatform with multifunctional properties can efficiently target PSMA-expressing PCa cells and silence target gene expression. Systemic delivery of the siRNA NPs can efficiently silence the expression of prohibitin 1 (PHB1), which is upregulated in PCa and other cancers, and significantly inhibit PCa tumor growth. These results suggest that this multifunctional envelope-type nanoplatform could become an effective tool for PCa-specific therapy.

BPH and prostate cancer risk.

PubMed

Miah, Saiful; Catto, James

2014-04-01

With the exclusion of non-melanomatous skin malignancy, prostate cancer (PCa) is the second most prevalent cancer in men globally. It has been reported that the majority of men will develop benign prostatic hyperplasia (BPH) by the time they reach their 60s. Together, these prostatic diseases have a significant morbidity and mortality affecting over a billion men throughout the world. The risk of developing prostate cancer of men suffering BPH is one that has resulted in a healthy debate amongst the urological community. Here, we try to address this conundrum with clinical and basic science evidence. Data from an online search and contemporary data presented at international urological congresses was reviewed. BPH and PCa can be linked together at a molecular and cellular level on genetic, hormonal, and inflammatory platforms suggesting that these prostatic diseases have common pathophysiological driving factors. Epidemiological studies are weighted towards the presence of BPH having a greater risk for a man to develop PCa in his lifetime; however, a conclusion of causality cannot be confidently stated. The future workload healthcare practitioners will face regarding BPH, and PCa will substantially increase. Further basic science and large epidemiological studies using a global cohort of men are required prior to the urological community confidently counseling their patients with BPH with regards to their PCa risk.

Ultra-sensitive high performance liquid chromatography-laser-induced fluorescence based proteomics for clinical applications.

PubMed

Patil, Ajeetkumar; Bhat, Sujatha; Pai, Keerthilatha M; Rai, Lavanya; Kartha, V B; Chidangil, Santhosh

2015-09-08

An ultra-sensitive high performance liquid chromatography-laser induced fluorescence (HPLC-LIF) based technique has been developed by our group at Manipal, for screening, early detection, and staging for various cancers, using protein profiling of clinical samples like, body fluids, cellular specimens, and biopsy-tissue. More than 300 protein profiles of different clinical samples (serum, saliva, cellular samples and tissue homogenates) from volunteers (normal, and different pre-malignant/malignant conditions) were recorded using this set-up. The protein profiles were analyzed using principal component analysis (PCA) to achieve objective detection and classification of malignant, premalignant and healthy conditions with high sensitivity and specificity. The HPLC-LIF protein profiling combined with PCA, as a routine method for screening, diagnosis, and staging of cervical cancer and oral cancer, is discussed in this paper. In recent years, proteomics techniques have advanced tremendously in life sciences and medical sciences for the detection and identification of proteins in body fluids, tissue homogenates and cellular samples to understand biochemical mechanisms leading to different diseases. Some of the methods include techniques like high performance liquid chromatography, 2D-gel electrophoresis, MALDI-TOF-MS, SELDI-TOF-MS, CE-MS and LC-MS techniques. We have developed an ultra-sensitive high performance liquid chromatography-laser induced fluorescence (HPLC-LIF) based technique, for screening, early detection, and staging for various cancers, using protein profiling of clinical samples like, body fluids, cellular specimens, and biopsy-tissue. More than 300 protein profiles of different clinical samples (serum, saliva, cellular samples and tissue homogenates) from healthy and volunteers with different malignant conditions were recorded by using this set-up. The protein profile data were analyzed using principal component analysis (PCA) for objective classification and detection of malignant, premalignant and healthy conditions. The method is extremely sensitive to detect proteins with limit of detection of the order of femto-moles. The HPLC-LIF combined with PCA as a potential proteomic method for the diagnosis of oral cancer and cervical cancer has been discussed in this paper. This article is part of a Special Issue entitled: Proteomics in India. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of Body Mass Index, Age, Prostate Volume, and Genetic Polymorphisms on Prostate-specific Antigen Levels in a Control Population.

PubMed

Cornu, Jean-Nicolas; Cancel-Tassin, Geraldine; Cox, David G; Roupret, Morgan; Koutlidis, Nicolas; Bigot, Pierre; Valeri, Antoine; Ondet, Valerie; Gaffory, Cécile; Fournier, Georges; Azzouzi, Abdel-Rahmene; Cormier, Luc; Cussenot, Olivier

2016-07-01

Prostate-specific antigen (PSA) is still the cornerstone of prostate cancer (PCa) screening and diagnosis in both research and current clinical practice. Inaccuracy of PSA is partly due to the influence of a number of genetic, clinical, and biological factors modifying PSA blood levels. In the present study, we detailed the respective influence of each factor among age, body mass index (BMI), prostate volume, and five single-nucleotide polymorphisms-rs10788160 (10q26), rs10993994 (10q11), rs11067228 (12q24), rs17632542 (19q13.33), and rs2928679 (8p21)-on PSA values in a cohort of 1374 men without PCa. Our results show that genetic factors, when risk variants are combined, influence PSA levels with an effect size similar to that of BMI. Taken together, the respective correlations of clinical parameters and genetic parameters would make it possible to correct and adjust PSA values more effectively in each individual. These results establish the basis to understand and implement a more personalised approach for the interpretation of PSA blood levels in the context of PCa screening and diagnosis. Prostate-specific antigen (PSA) values in an individual may vary according to genetic predisposition. The effect size of this variation can be significant, comparable with those resulting from clinical characteristics. Personalised PSA testing should take this into account. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and the prostate health index (PHI) in a Chinese hospital-based biopsy population.

PubMed

Na, Rong; Ye, Dingwei; Liu, Fang; Chen, Haitao; Qi, Jun; Wu, Yishuo; Zhang, Guiming; Wang, Meilin; Wang, Wenying; Sun, Jielin; Yu, Guopeng; Zhu, Yao; Ren, Shancheng; Zheng, S Lilly; Jiang, Haowen; Sun, Yinghao; Ding, Qiang; Xu, Jianfeng

2014-11-01

The use of serum [-2]proPSA (p2PSA) and its derivative, the prostate health index (PHI), in detecting prostate cancer (PCa) have been consistently shown to have better performance than total prostate-specific antigen (tPSA) in discriminating biopsy outcomes in western countries. However, little is known about their performance in Chinese men. Our objective is to test the performance of p2PSA and PHI and their added value to tPSA in discriminating biopsy outcomes in Chinese men. Consecutive patients who underwent prostate biopsy in three tertiary hospitals in Shanghai, China during 2012-2013 were recruited. Serum tPSA, free PSA (fPSA), and p2PSA were measured centrally using Beckman Coulter's DxI 800 Immunoassay System. The primary outcome is PCa and the secondary outcome is high-grade PCa (Gleason Score of 4 + 3 or worse). Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC), detection rate and Decision Curve Analysis (DCA). Among 636 patients who underwent prostate biopsy, PHI was a significant predictor of biopsy outcomes, independent of other clinical variables. The AUC in discriminating PCa from non-PCa was consistently higher for PHI than tPSA in the entire cohort (0.88 vs. 0.81) as well as in patients with tPSA at 2-10 ng/ml (0.73 vs. 0.53), at 10.1-20 ng/ml (0.81 vs. 0.58), and at tPSA >20 ng/ml (0.90 vs. 0.80). The differences were statistically significant in all comparisons, P < 0.01. To detect 90% of all PCa in the cohort, 362 and 457 patients would need to be biopsied based on PHI and tPSA cutoff, respectively, a 21% reduction for PHI. Similar results were found for discriminating high-grade PCa. PHI provides added value over tPSA in discriminating PCa and high-grade PCa in patients who underwent prostate biopsy in China. © 2014 Wiley Periodicals, Inc.

Tissue-scale, personalized modeling and simulation of prostate cancer growth

NASA Astrophysics Data System (ADS)

Lorenzo, Guillermo; Scott, Michael A.; Tew, Kevin; Hughes, Thomas J. R.; Zhang, Yongjie Jessica; Liu, Lei; Vilanova, Guillermo; Gomez, Hector

2016-11-01

Recently, mathematical modeling and simulation of diseases and their treatments have enabled the prediction of clinical outcomes and the design of optimal therapies on a personalized (i.e., patient-specific) basis. This new trend in medical research has been termed “predictive medicine.” Prostate cancer (PCa) is a major health problem and an ideal candidate to explore tissue-scale, personalized modeling of cancer growth for two main reasons: First, it is a small organ, and, second, tumor growth can be estimated by measuring serum prostate-specific antigen (PSA, a PCa biomarker in blood), which may enable in vivo validation. In this paper, we present a simple continuous model that reproduces the growth patterns of PCa. We use the phase-field method to account for the transformation of healthy cells to cancer cells and use diffusion-reaction equations to compute nutrient consumption and PSA production. To accurately and efficiently compute tumor growth, our simulations leverage isogeometric analysis (IGA). Our model is shown to reproduce a known shape instability from a spheroidal pattern to fingered growth. Results of our computations indicate that such shift is a tumor response to escape starvation, hypoxia, and, eventually, necrosis. Thus, branching enables the tumor to minimize the distance from inner cells to external nutrients, contributing to cancer survival and further development. We have also used our model to perform tissue-scale, personalized simulation of a PCa patient, based on prostatic anatomy extracted from computed tomography images. This simulation shows tumor progression similar to that seen in clinical practice.

Development of a Voided Urine Assay for Detecting Prostate Cancer Noninvasively: A Pilot Study

PubMed Central

Trabulsi, Edouard J.; Tripathi, Sushil K.; Gomella, Leonard; Solomides, Charalambos; Wickstrom, Eric; Thakur, Mathew L.

2017-01-01

Objective To validate a hypothesis that prostate cancer (PCa) can be detected noninvasively by a simple and reliable assay by targeting genomic VPAC receptors expressed on malignant PCa cells shed in voided urine. Materials and Methods VPAC receptors were targeted with a specific biomolecule, TP4303, developed in our laboratory. With an IRB “exempt” approval of use of de-identified discarded samples, an aliquot of urine collected as a standard of care, from patients presenting to the urology clinic, (N=207, M= 176, F= 31, 21 years or older) was cytospun. The cells were fixed and treated with TP4303 and 4, 6 Dimidino-2-phenylindole, Dihydrochloride (DAPI). The cells were then observed under a microscope and cells with TP4303 orange fluorescence around the blue (DAPI) nucleus were considered malignant and those only with blue nucleus were regarded as normal. VPAC presence was validated using receptor blocking assay and cell malignancy was confirmed by PCa gene profile examination. Results The urine specimens were labeled only with gender and presenting diagnosis, with no personal health identifiers or other clinical data. The assay detected VPAC positive cells in 98.6% of the patients having a PCa diagnosis, (N=141), and none (0%) of the males with benign prostatic hyperplasia (BPH) (N=10). Of the 56 “normal” patients, 62.5% (N=35, M=10, F=25) were negative for VPAC cells; 19.6% (N=11, M=11, F=0) had VPAC positive cells; and 17.8% (N=10, M=4, F=6) were uninterpretable due to excessive crystals in the urine. Although data are limited, the sensitivity of the assay was 99.3% with confidence interval of 96.1%–100% and the specificity was 100% with confidence interval of 69.2%–100%. Receptor blocking assay and FACS analyses demonstrated the presence of VPAC receptors and gene profiling examinations confirmed that the cells expressing VPAC receptors were malignant PCa cells. Conclusion These preliminary data are highly encouraging and warrant further evaluation of the assay to serve as a simple and reliable tool to detect PCa noninvasively. PMID:28075510

The pre-image problem in kernel methods.

PubMed

Kwok, James Tin-yau; Tsang, Ivor Wai-hung

2004-11-01

In this paper, we address the problem of finding the pre-image of a feature vector in the feature space induced by a kernel. This is of central importance in some kernel applications, such as on using kernel principal component analysis (PCA) for image denoising. Unlike the traditional method which relies on nonlinear optimization, our proposed method directly finds the location of the pre-image based on distance constraints in the feature space. It is noniterative, involves only linear algebra and does not suffer from numerical instability or local minimum problems. Evaluations on performing kernel PCA and kernel clustering on the USPS data set show much improved performance.

RankProd Combined with Genetic Algorithm Optimized Artificial Neural Network Establishes a Diagnostic and Prognostic Prediction Model that Revealed C1QTNF3 as a Biomarker for Prostate Cancer.

PubMed

Hou, Qi; Bing, Zhi-Tong; Hu, Cheng; Li, Mao-Yin; Yang, Ke-Hu; Mo, Zu; Xie, Xiang-Wei; Liao, Ji-Lin; Lu, Yan; Horie, Shigeo; Lou, Ming-Wu

2018-06-01

Prostate cancer (PCa) is the most commonly diagnosed cancer in males in the Western world. Although prostate-specific antigen (PSA) has been widely used as a biomarker for PCa diagnosis, its results can be controversial. Therefore, new biomarkers are needed to enhance the clinical management of PCa. From publicly available microarray data, differentially expressed genes (DEGs) were identified by meta-analysis with RankProd. Genetic algorithm optimized artificial neural network (GA-ANN) was introduced to establish a diagnostic prediction model and to filter candidate genes. The diagnostic and prognostic capability of the prediction model and candidate genes were investigated in both GEO and TCGA datasets. Candidate genes were further validated by qPCR, Western Blot and Tissue microarray. By RankProd meta-analyses, 2306 significantly up- and 1311 down-regulated probes were found in 133 cases and 30 controls microarray data. The overall accuracy rate of the PCa diagnostic prediction model, consisting of a 15-gene signature, reached up to 100% in both the training and test dataset. The prediction model also showed good results for the diagnosis (AUC = 0.953) and prognosis (AUC of 5 years overall survival time = 0.808) of PCa in the TCGA database. The expression levels of three genes, FABP5, C1QTNF3 and LPHN3, were validated by qPCR. C1QTNF3 high expression was further validated in PCa tissue by Western Blot and Tissue microarray. In the GEO datasets, C1QTNF3 was a good predictor for the diagnosis of PCa (GSE6956: AUC = 0.791; GSE8218: AUC = 0.868; GSE26910: AUC = 0.972). In the TCGA database, C1QTNF3 was significantly associated with PCa patient recurrence free survival (P < .001, AUC = 0.57). In this study, we have developed a diagnostic and prognostic prediction model for PCa. C1QTNF3 was revealed as a promising biomarker for PCa. This approach can be applied to other high-throughput data from different platforms for the discovery of oncogenes or biomarkers in different kinds of diseases. Copyright © 2018. Published by Elsevier B.V.

PBOV1 as a potential biomarker for more advanced prostate cancer based on protein and digital histomorphometric analysis.

PubMed

Carleton, Neil M; Zhu, Guangjing; Gorbounov, Mikhail; Miller, M Craig; Pienta, Kenneth J; Resar, Linda M S; Veltri, Robert W

2018-05-01

There are few tissue-based biomarkers that can accurately predict prostate cancer (PCa) progression and aggressiveness. We sought to evaluate the clinical utility of prostate and breast overexpressed 1 (PBOV1) as a potential PCa biomarker. Patient tumor samples were designated by Grade Groups using the 2014 Gleason grading system. Primary radical prostatectomy tumors were obtained from 48 patients and evaluated for PBOV1 levels using Western blot analysis in matched cancer and benign cancer-adjacent regions. Immunohistochemical evaluation of PBOV1 was subsequently performed in 80 cancer and 80 benign cancer-adjacent patient samples across two tissue microarrays (TMAs) to verify protein levels in epithelial tissue and to assess correlation between PBOV1 proteins and nuclear architectural changes in PCa cells. Digital histomorphometric analysis was used to track 22 parameters that characterized nuclear changes in PBOV1-stained cells. Using a training and test set for validation, multivariate logistic regression (MLR) models were used to identify significant nuclear parameters that distinguish Grade Group 3 and above PCa from Grade Group 1 and 2 PCa regions. PBOV1 protein levels were increased in tumors from Grade Group 3 and above (GS 4 + 3 and ≥ 8) regions versus Grade Groups 1 and 2 (GS 3 + 3 and 3 + 4) regions (P = 0.005) as assessed by densitometry of immunoblots. Additionally, by immunoblotting, PBOV1 protein levels differed significantly between Grade Group 2 (GS 3 + 4) and Grade Group 3 (GS 4 + 3) PCa samples (P = 0.028). In the immunohistochemical analysis, measures of PBOV1 staining intensity strongly correlated with nuclear alterations in cancer cells. An MLR model retaining eight parameters describing PBOV1 staining intensity and nuclear architecture discriminated Grade Group 3 and above PCa from Grade Group 1 and 2 PCa and benign cancer-adjacent regions with a ROC-AUC of 0.90 and 0.80, respectively, in training and test sets. Our study demonstrates that the PBOV1 protein could be used to discriminate Grade Group 3 and above PCa. Additionally, the PBOV1 protein could be involved in modulating changes to the nuclear architecture of PCa cells. Confirmatory studies are warranted in an independent population for further validation. © 2018 Wiley Periodicals, Inc.

Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study.

PubMed

Thomsen, F B; Brasso, K; Berg, K D; Gerds, T A; Johansson, J-E; Angelsen, A; Tammela, T L J; Iversen, P

2016-03-01

The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting. Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method. Two hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel ≥2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0-1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent ≤10 or >25 ng/ml. We found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values. NCT00672282. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Anthropometric Measures at Multiple Times Throughout Life and Prostate Cancer Diagnosis, Metastasis, and Death.

PubMed

Gerdtsson, Axel; Poon, Jessica B; Thorek, Daniel L; Mucci, Lorelei A; Evans, Michael J; Scardino, Peter; Abrahamsson, Per-Anders; Nilsson, Peter; Manjer, Jonas; Bjartell, Anders; Malm, Johan; Vickers, Andrew; Freedland, Stephen J; Lilja, Hans; Ulmert, David

2015-12-01

Previous studies of prostate cancer (PCa) risk and anthropometrics (ie, body measurements) were based on single measurements or obtained over limited time spans. To study the association between anthropometrics measured at multiple time points in life and their relation to later diagnosis, metastasis, or death from PCa. This case-control study includes 27 167 Swedish men enrolled in two population-based projects from 1974 to 1996. PCa diagnosis up to December 31, 2006, disease information, gestation time, and anthropometrics at birth, military conscript testing, and adulthood were collected. A total of 1355 PCa cases were matched with 5271 controls. Univariate conditional logistic regression was used to determine whether clinical diagnosis, metastasis, or PCa death was associated with low birth weight (weight <2500 g); with small size for gestational age; or with weight, length, or body mass index (BMI) at birth, adolescence (aged 16-22 yr), or early middle age (aged 44-50 yr). Apart from weight at adolescence, which was associated with an increased risk of PCa diagnosis (odds ratio [OR] per 5 kg: 1.05; 95% confidence interval [CI], 1.01-1.09; p=0.026), preadulthood measurements were not associated with any PCa end point. Adulthood parameters were not associated with diagnosis. In contrast, weight and BMI at early middle age were significantly associated with metastasis (OR per 5 kg: 1.13; 95% CI, 1.06-1.20; p<0.0001, and OR: 1.09; 95% CI, 1.05-1.14; p<0.0001) and death (OR per 5 kg: 1.11 (95% CI, 1.03-1.19; p=0.005, and OR: 1.08; 95% CI, 1.03-1.13; p=0.003), respectively. It remains unclear whether these results apply to men of nonwhite origin, to populations with active PCa screening programs, or to countries without socialized health care. The analyses of these large data sets demonstrate that significant effects of body characteristics (with links to metabolic syndrome) measured at early middle age are associated with PCa disease severity, metastatic progression, and outcome. Conversely, measurements at birth and adolescence are not associated with PCa prevalence or outcome. Increased weight and body mass index in adults is associated with a higher risk of prostate cancer metastasis and death. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Ultrasound-guided rectus sheath and transversus abdominis plane blocks for perioperative analgesia in upper abdominal surgery: A randomized controlled study.

PubMed

Abdelsalam, Khaled; Mohamdin, O W

2016-01-01

Regional anesthetic techniques can be used to alleviate postoperative pain in patients undergoing major upper abdominal surgery. Our aim was to evaluate the efficacy of bilateral ultrasound (US)-guided rectus sheath (RS) and transversus abdominis plane (TAP) blocks for better perioperative analgesia. It is a prospective, observer-blinded, randomized clinical study. 40 eligible patients undergoing elective liver resection or Whipple procedure were included. All patients received a standardized anesthetic technique. Group 1 (n = 20) received preincisional US-guided bilateral RS and TAP blocks using 20 ml volume of bupivacaine 0.25% for each, and group 2 (n = 20) received local wound infiltration at end of surgery with 40 ml of bupivacaine 0.25%. A standardized postoperative analgesic regimen composed of intravenous paracetamol and a morphine patient-controlled analgesia (PCA). The use of intraoperative fentanyl and recovery room morphine boluses, PCA-administered morphine, pain scores as well as number of patients' experienced postoperative nausea and vomiting in the ward at 6 and 24 h were recorded. Group 1 patients received a significantly lower cumulative intraoperative fentanyl, significantly lesser boluses of morphine in postanesthesia care unit, as well, significantly lower cumulative 24 h postoperative morphine dosage than the group 2 patients. Pain visual analog scale scores were significantly lower at both 6 and 24 h postoperatively in TAP group when compared with the no-TAP group. There were no complications related to the TAP block procedures. No signs or symptoms of local anesthetic systemic toxicity were detected. The combination of bilateral US-guided RS and TAP blocks provides excellent perioperative analgesia for major upper abdominal surgery.

Immunotherapy for Prostate Cancer: Lessons from Responses to Tumor-Associated Antigens

PubMed Central

Westdorp, Harm; Sköld, Annette E.; Snijer, Berit A.; Franik, Sebastian; Mulder, Sasja F.; Major, Pierre P.; Foley, Ronan; Gerritsen, Winald R.; de Vries, I. Jolanda M.

2014-01-01

Prostate cancer (PCa) is the most common cancer in men and the second most common cause of cancer-related death in men. In recent years, novel therapeutic options for PCa have been developed and studied extensively in clinical trials. Sipuleucel-T is the first cell-based immunotherapeutic vaccine for treatment of cancer. This vaccine consists of autologous mononuclear cells stimulated and loaded with an immunostimulatory fusion protein containing the prostate tumor antigen prostate acid posphatase. The choice of antigen might be key for the efficiency of cell-based immunotherapy. Depending on the treatment strategy, target antigens should be immunogenic, abundantly expressed by tumor cells, and preferably functionally important for the tumor to prevent loss of antigen expression. Autoimmune responses have been reported against several antigens expressed in the prostate, indicating that PCa is a suitable target for immunotherapy. In this review, we will discuss PCa antigens that exhibit immunogenic features and/or have been targeted in immunotherapeutic settings with promising results, and we highlight the hurdles and opportunities for cancer immunotherapy. PMID:24834066

Ionospheric total electron content anomalies due to Typhoon Nakri on 29 May 2008: A nonlinear principal component analysis

NASA Astrophysics Data System (ADS)

Lin, Jyh-Woei

2012-09-01

This paper uses Nonlinear Principal Component Analysis (NLPCA) and Principal Component Analysis (PCA) to determine Total Electron Content (TEC) anomalies in the ionosphere for the Nakri Typhoon on 29 May, 2008 (UTC). NLPCA, PCA and image processing are applied to the global ionospheric map (GIM) with transforms conducted for the time period 12:00-14:00 UT on 29 May 2008 when the wind was most intense. Results show that at a height of approximately 150-200 km the TEC anomaly using NLPCA is more localized; however its intensity increases with height and becomes more widespread. The TEC anomalies are not found by PCA. Potential causes of the results are discussed with emphasis given to vertical acoustic gravity waves. The approximate position of the typhoon's eye can be detected if the GIM is divided into fine enough maps with adequate spatial-resolution at GPS-TEC receivers. This implies that the trace of the typhoon in the regional GIM is caught using NLPCA.

Rotation of EOFs by the Independent Component Analysis: Towards A Solution of the Mixing Problem in the Decomposition of Geophysical Time Series

NASA Technical Reports Server (NTRS)

Aires, Filipe; Rossow, William B.; Chedin, Alain; Hansen, James E. (Technical Monitor)

2001-01-01

The Independent Component Analysis is a recently developed technique for component extraction. This new method requires the statistical independence of the extracted components, a stronger constraint that uses higher-order statistics, instead of the classical decorrelation, a weaker constraint that uses only second-order statistics. This technique has been used recently for the analysis of geophysical time series with the goal of investigating the causes of variability in observed data (i.e. exploratory approach). We demonstrate with a data simulation experiment that, if initialized with a Principal Component Analysis, the Independent Component Analysis performs a rotation of the classical PCA (or EOF) solution. This rotation uses no localization criterion like other Rotation Techniques (RT), only the global generalization of decorrelation by statistical independence is used. This rotation of the PCA solution seems to be able to solve the tendency of PCA to mix several physical phenomena, even when the signal is just their linear sum.

Automated high-grade prostate cancer detection and ranking on whole slide images

NASA Astrophysics Data System (ADS)

Huang, Chao-Hui; Racoceanu, Daniel

2017-03-01

Recently, digital pathology (DP) has been largely improved due to the development of computer vision and machine learning. Automated detection of high-grade prostate carcinoma (HG-PCa) is an impactful medical use-case showing the paradigm of collaboration between DP and computer science: given a field of view (FOV) from a whole slide image (WSI), the computer-aided system is able to determine the grade by classifying the FOV. Various approaches have been reported based on this approach. However, there are two reasons supporting us to conduct this work: first, there is still room for improvement in terms of detection accuracy of HG-PCa; second, a clinical practice is more complex than the operation of simple image classification. FOV ranking is also an essential step. E.g., in clinical practice, a pathologist usually evaluates a case based on a few FOVs from the given WSI. Then, makes decision based on the most severe FOV. This important ranking scenario is not yet being well discussed. In this work, we introduce an automated detection and ranking system for PCa based on Gleason pattern discrimination. Our experiments suggested that the proposed system is able to perform high-accuracy detection ( 95:57% +/- 2:1%) and excellent performance of ranking. Hence, the proposed system has a great potential to support the daily tasks in the medical routine of clinical pathology.

Genomic and epigenomic analysis of high-risk prostate cancer reveals changes in hydroxymethylation and TET1.

PubMed

Spans, Lien; Van den Broeck, Thomas; Smeets, Elien; Prekovic, Stefan; Thienpont, Bernard; Lambrechts, Diether; Karnes, R Jeffrey; Erho, Nicholas; Alshalalfa, Mohammed; Davicioni, Elai; Helsen, Christine; Gevaert, Thomas; Tosco, Lorenzo; Haustermans, Karin; Lerut, Evelyne; Joniau, Steven; Claessens, Frank

2016-04-26

The clinical heterogeneity of prostate cancer (PCa) makes it difficult to identify those patients that could benefit from more aggressive treatments. As a contribution to a better understanding of the genomic changes in the primary tumor that are associated with the development of high-risk disease, we performed exome sequencing and copy number determination of a clinically homogeneous cohort of 47 high-risk PCas. We confirmed recurrent mutations in SPOP, PTEN and TP53 among the 850 point mutations we detected. In seven cases, we discovered genomic aberrations in the TET1 (Ten-Eleven Translocation 1) gene which encodes a DNA hydroxymethylase than can modify methylated cytosines in genomic DNA and thus is linked with gene expression changes. TET1 protein levels were reduced in tumor versus non-tumor prostate tissue in 39 of 40 cases. The clinical relevance of changes in TET1 levels was demonstrated in an independent PCa cohort, in which low TET1 mRNA levels were significantly associated with worse metastases-free survival. We also demonstrate a strong reduction in hydroxymethylated DNA in tumor tissue in 27 of 41 cases. Furthermore, we report the first exploratory (h)MeDIP-Seq analyses of eight high-risk PCa samples. This reveals a large heterogeneity in hydroxymethylation changes in tumor versus non-tumor genomes which can be linked with cell polarity.

Patient-reported outcomes in randomised controlled trials of prostate cancer: methodological quality and impact on clinical decision making.

PubMed

Efficace, Fabio; Feuerstein, Michael; Fayers, Peter; Cafaro, Valentina; Eastham, James; Pusic, Andrea; Blazeby, Jane

2014-09-01

Patient-reported outcomes (PRO) data from randomised controlled trials (RCTs) are increasingly used to inform patient-centred care as well as clinical and health policy decisions. The main objective of this study was to investigate the methodological quality of PRO assessment in RCTs of prostate cancer (PCa) and to estimate the likely impact of these studies on clinical decision making. A systematic literature search of studies was undertaken on main electronic databases to retrieve articles published between January 2004 and March 2012. RCTs were evaluated on a predetermined extraction form, including (1) basic trial demographics and clinical and PRO characteristics; (2) level of PRO reporting based on the recently published recommendations by the International Society for Quality of Life Research; and (3) bias, assessed using the Cochrane Risk of Bias tool. Studies were systematically analysed to evaluate their relevance for supporting clinical decision making. Sixty-five RCTs enrolling a total of 22 071 patients were evaluated, with 31 (48%) in patients with nonmetastatic disease. When a PRO difference between treatments was found, it related in most cases to symptoms only (n=29, 58%). Although the extent of missing data was generally documented (72% of RCTs), few reported details on statistical handling of this data (18%) and reasons for dropout (35%). Improvements in key methodological aspects over time were found. Thirteen (20%) RCTs were judged as likely to be robust in informing clinical decision making. Higher-quality PRO studies were generally associated with those RCTs that had higher internal validity. Including PRO in RCTs of PCa patients is critical for better evaluating the treatment effectiveness of new therapeutic approaches. Marked improvements in PRO quality reporting over time were found, and it is estimated that at least one-fifth of PRO RCTs have provided sufficient details to allow health policy makers and physicians to make critical appraisals of results. In this report, we have investigated the methodological quality of PCa trials that have included a PRO assessment. We conclude that including PRO is critical to better evaluating the treatment effectiveness of new therapeutic approaches from the patient's perspective. Also, at least one-fifth of PRO RCTs in PCa have provided sufficient details to allow health policy makers and physicians to make a critical appraisal of results. Copyright © 2013. Published by Elsevier B.V.

Assessing EphA2 and Ephrin-A as Novel Diagnostic and Prognostic Biomarkers of Prostate Cancer

DTIC Science & Technology

2017-10-01

prostatectomy at our institution. We will correlate their levels of EphA2 and ephrin-A1 mRNA as well as staining of phosphorylated pS897-EphA2 to the...protein. These values will then be correlated to the presence or absence of PCa, the aggressiveness of PCa as determined by traditional clinical...from malignant prostate tissue and/or correlate with cancer aggressiveness. ▪ Major Task 1: Characterize EphA2 and ephrin-A expression levels in

Quantification of dose uncertainties for the bladder in prostate cancer radiotherapy based on dominant eigenmodes

NASA Astrophysics Data System (ADS)

Rios, Richard; Acosta, Oscar; Lafond, Caroline; Espinosa, Jairo; de Crevoisier, Renaud

2017-11-01

In radiotherapy for prostate cancer the dose at the treatment planning for the bladder may be a bad surrogate of the actual delivered dose as the bladder presents the largest inter-fraction shape variations during treatment. This paper presents PCA models as a virtual tool to estimate dosimetric uncertainties for the bladder produced by motion and deformation between fractions. Our goal is to propose a methodology to determine the minimum number of modes required to quantify dose uncertainties of the bladder for motion/deformation models based on PCA. We trained individual PCA models using the bladder contours available from three patients with a planning computed tomography (CT) and on-treatment cone-beam CTs (CBCTs). Based on the above models and via deformable image registration (DIR), we estimated two accumulated doses: firstly, an accumulated dose obtained by integrating the planning dose over the Gaussian probability distribution of the PCA model; and secondly, an accumulated dose obtained by simulating treatment courses via a Monte Carlo approach. We also computed a reference accumulated dose for each patient using his available images via DIR. Finally, we compared the planning dose with the three accumulated doses, and we calculated local dose variability and dose-volume histogram uncertainties.

68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients.

PubMed

Zang, Shiming; Shao, Guoqiang; Cui, Can; Li, Tian-Nv; Huang, Yue; Yao, Xiaochen; Fan, Qiu; Chen, Zejun; Du, Jin; Jia, Ruipeng; Sun, Hongbin; Hua, Zichun; Tang, Jun; Wang, Feng

2017-02-14

We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images. Only 3 patients with stable mCRPC after chemotherapy were negative for PSMA. The sensitivity, specificity and accuracy of 68Ga-PSMA-11 imaging were 97.3%, 100.0% and 97.5%, respectively. The maximum standardized uptake (SUVmax) of prostatic lesions was 17.09 ± 11.08 and 13.33 ± 12.31 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 revealed 105 metastatic lymph nodes in 15 patients; the SUVmax was 16.85 ± 9.70 and 7.54 ± 5.20 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 PET/CT also newly detected visceral metastasis in 9 patients (22.5%) and bone metastasis in 29 patients (72.5%). 68Ga-PSMA-11 PET/CT exhibits potential for staging and risk stratification in naïve PCa, as well as improved sensitivity for detection of lymph node and remote metastasis.

Increased Expression of ALDH1A1 in Prostate Cancer is Correlated With Tumor Aggressiveness: A Tissue Microarray Study of Iranian Patients.

PubMed

Kalantari, Elham; Saadi, Faezeh H; Asgari, Mojgan; Shariftabrizi, Ahmad; Roudi, Raheleh; Madjd, Zahra

2017-09-01

Subpopulations of prostate cancer (PCa) cells expressing putative stem cell markers possess the ability to promote tumor growth, maintenance, and progression. This study aimed to evaluate the expression patterns and clinical significance of putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH1A1) in prostate tumor tissues. ALDH1A1 expression was examined in a well-defined series of prostate tissues, including 105 (68%) samples of PCa, 21 (13%) samples of high-grade prostatic intraepithelial neoplasia, and 31 (19%) samples of benign prostate hyperplasia, which were embedded in tissue microarray blocks. The correlation of ALDH1A1 expression with clinicopathologic parameters was also assessed. There was a significant difference between the expression level of ALDH1A1 in PCa compared with the high-grade prostatic intraepithelial neoplasia and benign prostate hyperplasia samples (P<0.001). PCa cells expressing ALDH1A1 were more often seen in samples with advanced Gleason score (P=0.05) and high serum prostate specific antigen level (P=0.02). In addition, a positive correlation was found between ALDH1A1 expression and primary tumor stage and regional lymph node involvement (P=0.04 and 0.03, respectively). The significant association between ALDH1A1 expressions with Gleason score indicates the potential role of this protein in PCa tumorigenesis and aggressive behavior; therefore, this cancer stem cell marker can be used as a promising candidate for targeted therapy of PCa, especially those with high Gleason score.

SRC: marker or actor in prostate cancer aggressiveness.

PubMed

Vlaeminck-Guillem, Virginie; Gillet, Germain; Rimokh, Ruth

2014-01-01

A key question for urologic practitioners is whether an apparently organ-confined prostate cancer (PCa) is actually aggressive or not. The dilemma is to specifically identify among all prostate tumors the very aggressive high-grade cancers that will become life-threatening by developing extra-prostatic invasion and metastatic potential and the indolent cancers that will never modify a patient's life expectancy. A choice must be made between several therapeutic options to achieve the optimal personalized management of the disease that causes as little harm as possible to patients. Reliable clinical, biological, or pathological markers that would enable distinctions to be made between aggressive and indolent PCas in routine practice at the time of initial diagnosis are still lacking. The molecular mechanisms that explain why a PCa is aggressive or not are also poorly understood. Among the potential markers and/or actors in PCa aggressiveness, Src and other members of the Src kinase family, are valuable candidates. Activation of Src-dependent intracellular pathways is frequently observed in PCa. Indeed, Src is at the cross-roads of several pathways [including androgen receptor (AR), TGFbeta, Bcl-2, Akt/PTEN or MAPK, and ERK …], and is now known to influence some of the cellular and tissular events that accompany tumor progression: cell proliferation, cell motility, invasion, epithelial-to-mesenchymal transition, resistance to apoptosis, angiogenesis, neuroendocrine differentiation, and metastatic spread. Recent work even suggests that Src could also play a part in PCa initiation in coordination with the AR. The aim of this review is to gather data that explore the links between the Src kinase family and PCa progression and aggressiveness.

Endovascular Treatment of Posterior Cerebral Artery Aneurysms With Flow Diversion: Case Series and Systematic Review.

PubMed

Wallace, Adam N; Grossberg, Jonathan A; Almandoz, Josser E Delgado; Kamran, Mudassar; Roy, Anil K; Kayan, Yasha; Austin, Matthew J; Howard, Brian M; Moran, Christopher J; Cawley, C Michael; Cross, DeWitte T; Dion, Jacques E; Kansagra, Akash P; Osbun, Joshua W

2018-03-08

Flow diversion of posterior cerebral artery (PCA) aneurysms has not been widely reported, possibly owing to concerns regarding parent vessel size and branch vessel coverage. To examine the safety and effectiveness of PCA aneurysm flow diverter treatment. Retrospective review of PCA aneurysms treated with the Pipeline Embolization Device (PED; Medtronic Inc, Dublin, Ireland) at 3 neurovascular centers, including periprocedural complications and clinical and angiographic outcomes. Systematic review of the literature identified published reports of PCA aneurysms treated with flow diversion. Rates of aneurysm occlusion and complications were calculated, and outcomes of saccular and fusiform aneurysm treatments were compared. Ten PCA aneurysms in 9 patients were treated with the PED. There were 2 intraprocedural thromboembolic events (20%), including 1 symptomatic infarction and 1 delayed PED thrombosis. Eight of 10 patients returned to or improved from their baseline functional status. Complete aneurysm occlusion with parent vessel preservation was achieved in 75% (6/8) of cases at mean follow-up of 16.7 mo. Eleven of 12 (92%) major branch vessels covered by a PED remained patent. Including the present study, systematic review of 15 studies found a complete aneurysm occlusion rate of 88% (30/34) and complication rate of 26% (10/38), including 5 symptomatic ischemic strokes (13%; 5/38). Fusiform aneurysms more frequently completely occluded compared with saccular aneurysms (100% vs 70%; P = .03) but were associated with a higher complication rate (43% vs 9%; P = .06). The safety and effectiveness profile of flow diverter treatment of PCA aneurysms may be acceptable in select cases.

Scene perception in posterior cortical atrophy: categorization, description and fixation patterns

PubMed Central

Shakespeare, Timothy J.; Yong, Keir X. X.; Frost, Chris; Kim, Lois G.; Warrington, Elizabeth K.; Crutch, Sebastian J.

2013-01-01

Partial or complete Balint's syndrome is a core feature of the clinico-radiological syndrome of posterior cortical atrophy (PCA), in which individuals experience a progressive deterioration of cortical vision. Although multi-object arrays are frequently used to detect simultanagnosia in the clinical assessment and diagnosis of PCA, to date there have been no group studies of scene perception in patients with the syndrome. The current study involved three linked experiments conducted in PCA patients and healthy controls. Experiment 1 evaluated the accuracy and latency of complex scene perception relative to individual faces and objects (color and grayscale) using a categorization paradigm. PCA patients were both less accurate (faces < scenes < objects) and slower (scenes < objects < faces) than controls on all categories, with performance strongly associated with their level of basic visual processing impairment; patients also showed a small advantage for color over grayscale stimuli. Experiment 2 involved free description of real world scenes. PCA patients generated fewer features and more misperceptions than controls, though perceptual errors were always consistent with the patient's global understanding of the scene (whether correct or not). Experiment 3 used eye tracking measures to compare patient and control eye movements over initial and subsequent fixations of scenes. Patients' fixation patterns were significantly different to those of young and age-matched controls, with comparable group differences for both initial and subsequent fixations. Overall, these findings describe the variability in everyday scene perception exhibited by individuals with PCA, and indicate the importance of exposure duration in the perception of complex scenes. PMID:24106469

68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients

PubMed Central

Cui, Can; Li, Tian-Nv; Huang, Yue; Yao, Xiaochen; Fan, Qiu; Chen, Zejun; Du, Jin; Jia, Ruipeng; Sun, Hongbin; Hua, Zichun; Tang, Jun; Wang, Feng

2017-01-01

We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images. Only 3 patients with stable mCRPC after chemotherapy were negative for PSMA. The sensitivity, specificity and accuracy of 68Ga-PSMA-11 imaging were 97.3%, 100.0% and 97.5%, respectively. The maximum standardized uptake (SUVmax) of prostatic lesions was 17.09 ± 11.08 and 13.33 ± 12.31 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 revealed 105 metastatic lymph nodes in 15 patients; the SUVmax was 16.85 ± 9.70 and 7.54 ± 5.20 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 PET/CT also newly detected visceral metastasis in 9 patients (22.5%) and bone metastasis in 29 patients (72.5%). 68Ga-PSMA-11 PET/CT exhibits potential for staging and risk stratification in naïve PCa, as well as improved sensitivity for detection of lymph node and remote metastasis. PMID:28103574

Epidural Analgesia Versus Patient-Controlled Analgesia for Pain Relief in Uterine Artery Embolization for Uterine Fibroids: A Decision Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kooij, Sanne M. van der, E-mail: s.m.vanderkooij@amc.uva.nl; Moolenaar, Lobke M.; Ankum, Willem M.

Purpose: This study was designed to compare the costs and effects of epidural analgesia (EDA) to those of patient-controlled intravenous analgesia (PCA) for postintervention pain relief in women having uterine artery embolization (UAE) for systematic uterine fibroids. Methods: Cost-effectiveness analysis (CEA) based on data from the literature by constructing a decision tree to model the clinical pathways for estimating the effects and costs of treatment with EDA and PCA. Literature on EDA for pain-relief after UAE was missing, and therefore, data on EDA for abdominal surgery were used. Outcome measures were compared costs to reduce one point in visual analoguemore » score (VAS) or numeric rating scale (NRS) for pain 6 and 24 h after UAE and risk for complications. Results: Six hours after the intervention, the VAS was 3.56 when using PCA and 2.0 when using EDA. The costs for pain relief in women undergoing UAE with PCA and EDA were Euro-Sign 191 and Euro-Sign 355, respectively. The costs for EDA to reduce the VAS score 6 h after the intervention with one point compared with PCA were Euro-Sign 105 and Euro-Sign 179 after 24 h. The risk of having a complication was 2.45 times higher when using EDA. Conclusions: The results of this indirect comparison of EDA for abdominal surgery with PCA for UAE show that EDA would provide superior analgesia for post UAE pain at 6 and 24 h but with higher costs and an increased risk of complications.« less

Impact of PCA Strategies on Pain Intensity and Functional Assessment Measures in Adults with Sickle Cell Disease during Hospitalized Vaso-Occlusive Episodes

PubMed Central

Dampier, Carlton D.; Wager, Carrie G.; Harrison, Ryan; Hsu, Lewis L.; Minniti, Caterina P.; Smith, Wally R.

2012-01-01

Clinical trials of sickle cell disease (SCD) pain treatment usually observe only small decrements in pain intensity during the course of hospitalization. Sub-optimal analgesic management and inadequate pain assessment methods are possible explanations for these findings. In a search for better methods for assessing inpatient SCD pain in adults, we examined several pain intensity and interference measures in both arms of a randomized controlled trial comparing two different opioid PCA therapies. Based upon longitudinal analysis of pain episodes, we found that scores from daily average Visual Analogue Scales (VAS) and several other measures, especially the Brief Pain Inventory (BPI), were sensitive to change in daily improvements in pain intensity associated with resolution of vaso-occlusive pain. In this preliminary trial, the low demand, high basal infusion (LDHI) strategy demonstrated faster, larger improvements in various measures of pain than the high demand, low basal infusion (HDLI) strategy for opioid PCA dosing, however, verification in larger studies is required. The measures and statistical approaches used in this analysis may facilitate design, reduce sample size, and improve analyses of treatment response in future SCD clinical trials of vaso-occlusive episodes. PMID:22886853

Evaluation of non-negative matrix factorization of grey matter in age prediction.

PubMed

Varikuti, Deepthi P; Genon, Sarah; Sotiras, Aristeidis; Schwender, Holger; Hoffstaedter, Felix; Patil, Kaustubh R; Jockwitz, Christiane; Caspers, Svenja; Moebus, Susanne; Amunts, Katrin; Davatzikos, Christos; Eickhoff, Simon B

2018-06-01

The relationship between grey matter volume (GMV) patterns and age can be captured by multivariate pattern analysis, allowing prediction of individuals' age based on structural imaging. Raw data, voxel-wise GMV and non-sparse factorization (with Principal Component Analysis, PCA) show good performance but do not promote relatively localized brain components for post-hoc examinations. Here we evaluated a non-negative matrix factorization (NNMF) approach to provide a reduced, but also interpretable representation of GMV data in age prediction frameworks in healthy and clinical populations. This examination was performed using three datasets: a multi-site cohort of life-span healthy adults, a single site cohort of older adults and clinical samples from the ADNI dataset with healthy subjects, participants with Mild Cognitive Impairment and patients with Alzheimer's disease (AD) subsamples. T1-weighted images were preprocessed with VBM8 standard settings to compute GMV values after normalization, segmentation and modulation for non-linear transformations only. Non-negative matrix factorization was computed on the GM voxel-wise values for a range of granularities (50-690 components) and LASSO (Least Absolute Shrinkage and Selection Operator) regression were used for age prediction. First, we compared the performance of our data compression procedure (i.e., NNMF) to various other approaches (i.e., uncompressed VBM data, PCA-based factorization and parcellation-based compression). We then investigated the impact of the granularity on the accuracy of age prediction, as well as the transferability of the factorization and model generalization across datasets. We finally validated our framework by examining age prediction in ADNI samples. Our results showed that our framework favorably compares with other approaches. They also demonstrated that the NNMF based factorization derived from one dataset could be efficiently applied to compress VBM data of another dataset and that granularities between 300 and 500 components give an optimal representation for age prediction. In addition to the good performance in healthy subjects our framework provided relatively localized brain regions as the features contributing to the prediction, thereby offering further insights into structural changes due to brain aging. Finally, our validation in clinical populations showed that our framework is sensitive to deviance from normal structural variations in pathological aging. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of a Structured Reporting Template on Adherence to Prostate Imaging Reporting and Data System Version 2 and on the Diagnostic Performance of Prostate MRI for Clinically Significant Prostate Cancer.

PubMed

Shaish, Hiram; Feltus, Whitney; Steinman, Jonathan; Hecht, Elizabeth; Wenske, Sven; Ahmed, Firas

2018-05-01

The aim of this study was to assess the impact of a structured reporting template on adherence to the Prostate Imaging Reporting and Data System (PI-RADS) version 2 lexicon and on the diagnostic performance of prostate MRI to detect clinically significant prostate cancer (CS-PCa). An imaging database was searched for consecutive patients who underwent prostate MRI followed by MRI-ultrasound fusion biopsy from October 2015 through October 2017. The initial MRI reporting template used included only subheadings. In July 2016, the template was changed to a standardized PI-RADS-compliant structured template incorporating dropdown menus. Lesion, patient characteristics, pathology, and adherence to the PI-RADS lexicon were extracted from MRI reports and patient charts. Diagnostic performance of prostate MRI to detect CS-PCa using combined ultrasound-MRI fusion and systematic biopsy as a reference standard was assessed. Three hundred twenty-four lesions in 202 patients (average age, 67 years; average prostate-specific antigen level, 5.9 ng/mL) were analyzed, including 217 MRI peripheral zone (PZ) lesions, 84 MRI non-PZ lesions, and 23 additional PZ lesions found on systematic biopsy but missed on MRI. Thirty-three percent (106 of 324) were CS-PCa. Adherence to the PI-RADS lexicon improved from 32.9% (50 of 152) to 88.4% (152 of 172) (P < .0001) after introduction of the structured template. The sensitivity of prostate MRI for CS-PCa in the PZ increased from 53% to 70% (P = .011). There was no significant change in specificity (60% versus 55%, P = .458). A structured template with dropdown menus incorporating the PI-RADS lexicon and classification rules improves adherence to PI-RADS and may increase the diagnostic performance of prostate MRI for CS-PCa. Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Increased resource use in men with metastatic prostate cancer does not result in improved survival or quality of care at the end of life.

PubMed

Golan, Ron; Bernstein, Adrien N; Gu, Xiangmei; Dinerman, Brian F; Sedrakyan, Art; Hu, Jim C

2018-05-15

Cancer care and end-of-life (EOL) care contribute substantially to health care expenditures. Outside of clinical trials, to our knowledge there exists no standardized protocol to monitor disease progression in men with metastatic prostate cancer (mPCa). The objective of the current study was to evaluate the factors and outcomes associated with increased imaging and serum prostate-specific antigen use in men with mPCa. Using Surveillance, Epidemiology, and End Results-Medicare data from 2004 to 2012, the authors identified men diagnosed with mPCa with at least 6 months of follow-up. Extreme users were classified as those who had either received prostate-specific antigen testing greater than once per month, or who underwent cross-sectional imaging or bone scan more frequently than every 2 months over a 6-month period. Associations between extreme use and survival outcomes, costs, and quality of care at EOL, as measured by timing of hospice referral, frequency of emergency department visits, length of stay, and intensive care unit or hospital admissions, were examined. Overall, a total of 3026 men with mPCa were identified, 791 of whom (26%) were defined as extreme users. Extreme users were more commonly young, white/non-Hispanic, married, higher earning, and more educated (P<.001, respectively). Extreme use was not associated with improved quality of care at EOL. Yearly health care costs after diagnosis were 36.4% higher among extreme users (95% confidence interval, 27.4%-45.3%; P<.001). Increased monitoring among men with mPCa significantly increases health care costs, without a definitive improvement in survival nor quality of care at EOL noted. Monitoring for disease progression outside of clinical trials should be reserved for those in whom findings will change management. Cancer 2018;124:2212-9. © 2018 American Cancer Society. © 2018 American Cancer Society.

Real-time volumetric image reconstruction and 3D tumor localization based on a single x-ray projection image for lung cancer radiotherapy.

PubMed

Li, Ruijiang; Jia, Xun; Lewis, John H; Gu, Xuejun; Folkerts, Michael; Men, Chunhua; Jiang, Steve B

2010-06-01

To develop an algorithm for real-time volumetric image reconstruction and 3D tumor localization based on a single x-ray projection image for lung cancer radiotherapy. Given a set of volumetric images of a patient at N breathing phases as the training data, deformable image registration was performed between a reference phase and the other N-1 phases, resulting in N-1 deformation vector fields (DVFs). These DVFs can be represented efficiently by a few eigenvectors and coefficients obtained from principal component analysis (PCA). By varying the PCA coefficients, new DVFs can be generated, which, when applied on the reference image, lead to new volumetric images. A volumetric image can then be reconstructed from a single projection image by optimizing the PCA coefficients such that its computed projection matches the measured one. The 3D location of the tumor can be derived by applying the inverted DVF on its position in the reference image. The algorithm was implemented on graphics processing units (GPUs) to achieve real-time efficiency. The training data were generated using a realistic and dynamic mathematical phantom with ten breathing phases. The testing data were 360 cone beam projections corresponding to one gantry rotation, simulated using the same phantom with a 50% increase in breathing amplitude. The average relative image intensity error of the reconstructed volumetric images is 6.9% +/- 2.4%. The average 3D tumor localization error is 0.8 +/- 0.5 mm. On an NVIDIA Tesla C1060 GPU card, the average computation time for reconstructing a volumetric image from each projection is 0.24 s (range: 0.17 and 0.35 s). The authors have shown the feasibility of reconstructing volumetric images and localizing tumor positions in 3D in near real-time from a single x-ray image.

Interval to Testosterone Recovery After Hormonal Therapy for Prostate Cancer and Risk of Death

DOE Office of Scientific and Technical Information (OSTI.GOV)

D'Amico, Anthony V.; Chen, M.-H.; Renshaw, Andrew A.

Purpose: To assess whether the risk of death is associated with the time to testosterone recovery (TTR) after radiotherapy (RT) and hormonal therapy (HT) for prostate cancer (PCa). Patients and Methods: Between 1995 and 2001, 206 men with localized, unfavorable-risk PCa were randomized to receive RT or RT plus 6 months of HT. A multivariate postrandomization Cox regression analysis was used to assess whether the TTR in years was associated with the risk of death after adjusting for the known prognostic factors, age, Adult Comorbidity Evaluation-27 score, and the use of HT for recurrence. Results: Of the 102 men randomizedmore » to receive RT and HT, 57 (56%) had a TTR of >2 years, and none of these men had died of PCa after a median follow-up of 7.6 years. As the TTR increased, the risk of death decreased significantly (adjusted hazard ratio, 0.60; 95% confidence interval, 0.43-0.84; p = .003). A significant interaction was noted between the TTR and the comorbidity score (p = .002). The survival estimates were similar (p = 0.17) across the TTR values in men with moderate to severe comorbidity; however, these estimates increased significantly (p < .001) with decreasing PCa-specific mortality (p = .006) as the TTR increased in men with no or minimal comorbidity. Conclusion: The results of our study have shown that a longer TTR after RT plus 6 months of HT for unfavorable-risk PCa is associated with a lower risk of death in men with no or minimal comorbidity.« less

Prostate cancer invasion and metastasis: Insights from mining genomic data

DOE PAGES

Hudson, Bryan D.; Kulp, Kristen S.; Loots, Gabriela G.

2013-07-22

Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men in the Western world and the second leading cause of cancer-related deaths among men worldwide. Although most cancers have the potential to metastasize under appropriate conditions, PCa favors the skeleton as a primary site of metastasis, suggesting that the bone microenvironment is conducive to its growth. PCa metastasis proceeds through a complex series of molecular events that include angiogenesis at the site of the original tumor, local migration within the primary site, intravasation into the blood stream, survival within the circulation, extravasation of the tumor cells to themore » target organ and colonization of those cells within the new site. In turn, each one of these steps involves a complicated chain of events that utilize multiple protein–protein interactions, protein signaling cascades and transcriptional changes. Despite the urgent need to improve current biomarkers for diagnosis, prognosis and drug resistance, advances have been slow. Global gene expression methods such as gene microarrays and RNA sequencing enable the study of thousands of genes simultaneously and allow scientists to examine molecular pathways of cancer pathogenesis. In this review, we summarize the current literature that explored high-throughput transcriptome analysis toward the advancement of biomarker discovery for PCa. Novel biomarkers are strongly needed to enable more accurate detection of PCa, improve prediction of tumor aggressiveness and facilitate the discovery of new therapeutic targets for tailored medicine. Furthermore, promising molecular markers identified from gene expression profiling studies include HPN, CLU1, WT1, WNT5A, AURKA and SPARC.« less

Prostate cancer invasion and metastasis: Insights from mining genomic data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hudson, Bryan D.; Kulp, Kristen S.; Loots, Gabriela G.

Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men in the Western world and the second leading cause of cancer-related deaths among men worldwide. Although most cancers have the potential to metastasize under appropriate conditions, PCa favors the skeleton as a primary site of metastasis, suggesting that the bone microenvironment is conducive to its growth. PCa metastasis proceeds through a complex series of molecular events that include angiogenesis at the site of the original tumor, local migration within the primary site, intravasation into the blood stream, survival within the circulation, extravasation of the tumor cells to themore » target organ and colonization of those cells within the new site. In turn, each one of these steps involves a complicated chain of events that utilize multiple protein–protein interactions, protein signaling cascades and transcriptional changes. Despite the urgent need to improve current biomarkers for diagnosis, prognosis and drug resistance, advances have been slow. Global gene expression methods such as gene microarrays and RNA sequencing enable the study of thousands of genes simultaneously and allow scientists to examine molecular pathways of cancer pathogenesis. In this review, we summarize the current literature that explored high-throughput transcriptome analysis toward the advancement of biomarker discovery for PCa. Novel biomarkers are strongly needed to enable more accurate detection of PCa, improve prediction of tumor aggressiveness and facilitate the discovery of new therapeutic targets for tailored medicine. Furthermore, promising molecular markers identified from gene expression profiling studies include HPN, CLU1, WT1, WNT5A, AURKA and SPARC.« less

Levels of C{sub 10}-C{sub 13} polychloro-n-alkanes in marine mammals from the Arctic and the St. Lawrence River estuary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomy, G.T.; Muir, D.C.G.; Stern, G.A.

2000-05-01

Marine mammals from various regions of the Arctic and the St. Lawrence River estuary were examined for the first time for levels of C{sub 10}--C{sub 13} polychloro-n-alkanes (sPCAs). Respective mean total sPCA concentrations in the blubber of beluga whales (Delphinapterus leucas) from Saqqaq and Nuussuaq, western Greenland, were 0.23 {+-} 0.02 (n = 2) and 0.164 {+-} 0.06 {micro}g/g (n = 2), similar to that in beluga from the Mackenzie Delta in the western Canadian Arctic 0.21 {+-} 0.08 {micro}g/g (m = 3). sPCAs levels were higher in beluga blubber from the St. Lawrence River (0.37 to 1.4 {micro}g/g). Meanmore » sPCA concentrations in the blubber samples from walruses (Odobenus rosmarus) (Thule, northwest Greenland) and ringed seal (Phoca hispida) (Eureka, southwest Ellesmere Island) were 0.43 {+-} 0.06 (n = 2) and 0.53 {+-} 0.2 {micro}g/g (n = 6), respectively. Relative to commercial sPCA formulations, samples from the Arctic marine mammals showed a predominance of the shorter chain length lower percent chlorinated PCA congeners, the more volatile components of industrial formulations. This observation is consistent with long-range atmospheric transport of sPCAs to this region. The profiles of the belugas from the St. Lawrence River estuary, however, had higher proportions of the less volatile sPCA congeners, implying that contamination to this region is probably from local sources.« less

Study of ionospheric anomalies due to impact of typhoon using Principal Component Analysis and image processing

NASA Astrophysics Data System (ADS)

LIN, JYH-WOEI

2012-08-01

Principal Component Analysis (PCA) and image processing are used to determine Total Electron Content (TEC) anomalies in the F-layer of the ionosphere relating to Typhoon Nakri for 29 May, 2008 (UTC). PCA and image processing are applied to the global ionospheric map (GIM) with transforms conducted for the time period 12:00-14:00 UT on 29 May, 2008 when the wind was most intense. Results show that at a height of approximately 150-200 km the TEC anomaly is highly localized; however, it becomes more intense and widespread with height. Potential causes of these results are discussed with emphasis given to acoustic gravity waves caused by wind force.

Procrustean rotation in concert with principal component analysis of molecular dynamics trajectories: Quantifying global and local differences between conformational samples.

PubMed

Oblinsky, Daniel G; Vanschouwen, Bryan M B; Gordon, Heather L; Rothstein, Stuart M

2009-12-14

Given the principal component analysis (PCA) of a molecular dynamics (MD) conformational trajectory for a model protein, we perform orthogonal Procrustean rotation to "best fit" the PCA squared-loading matrix to that of a target matrix computed for a related but different molecular system. The sum of squared deviations of the elements of the rotated matrix from those of the target, known as the error of fit (EOF), provides a quantitative measure of the dissimilarity between the two conformational samples. To estimate precision of the EOF, we perform bootstrap resampling of the molecular conformations within the trajectories, generating a distribution of EOF values for the system and target. The average EOF per variable is determined and visualized to ascertain where, locally, system and target sample properties differ. We illustrate this approach by analyzing MD trajectories for the wild-type and four selected mutants of the beta1 domain of protein G.

Procrustean rotation in concert with principal component analysis of molecular dynamics trajectories: Quantifying global and local differences between conformational samples

NASA Astrophysics Data System (ADS)

Oblinsky, Daniel G.; VanSchouwen, Bryan M. B.; Gordon, Heather L.; Rothstein, Stuart M.

2009-12-01

Given the principal component analysis (PCA) of a molecular dynamics (MD) conformational trajectory for a model protein, we perform orthogonal Procrustean rotation to "best fit" the PCA squared-loading matrix to that of a target matrix computed for a related but different molecular system. The sum of squared deviations of the elements of the rotated matrix from those of the target, known as the error of fit (EOF), provides a quantitative measure of the dissimilarity between the two conformational samples. To estimate precision of the EOF, we perform bootstrap resampling of the molecular conformations within the trajectories, generating a distribution of EOF values for the system and target. The average EOF per variable is determined and visualized to ascertain where, locally, system and target sample properties differ. We illustrate this approach by analyzing MD trajectories for the wild-type and four selected mutants of the β1 domain of protein G.

Assessing climate change and health vulnerability at the local level: Travis County, Texas.

PubMed

Prudent, Natasha; Houghton, Adele; Luber, George

2016-10-01

We created a measure to help comprehend population vulnerability to potential flooding and excessive heat events using health, built environment and social factors. Through principal component analysis (PCA), we created non-weighted sum index scores of literature-reviewed social and built environment characteristics. We created baseline poor health measures using 1999-2005 age-adjusted cardiovascular and combined diabetes and hypertension mortality rates to correspond with social-built environment indices. We mapped US Census block groups by linked age-adjusted mortality and a PCA-created social-built environment index. The goal was to measure flooding and excessive heat event vulnerability as proxies for population vulnerability to climate change for Travis County, Texas. This assessment identified communities where baseline poor health, social marginalisation and built environmental impediments intersected. Such assessments may assist targeted interventions and improve emergency preparedness in identified vulnerable communities, while fostering resilience through the focus of climate change adaptation policies at the local level. No claim to original US government works. Journal compilation © 2016 Overseas Development Institute.

Value of PET/CT and MR Lymphography in Treatment of Prostate Cancer Patients With Lymph Node Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fortuin, Ansje S., E-mail: A.Fortuin@rad.umcn.nl; Deserno, Willem M.L.L.G.; Meijer, Hanneke J.M.

2012-11-01

Purpose: To determine the clinical value of two novel molecular imaging techniques: {sup 11}C-choline positron emission tomography (PET)/computed tomography (CT) and ferumoxtran-10 enhanced magnetic resonance imaging (magnetic resonance lymphography [MRL]) for lymph node (LN) treatment in prostate cancer (PCa) patients. Therefore, we evaluated the ability of PET/CT and MRL to assess the number, size, and location of LN metastases in patients with primary or recurrent PCa. Methods and Materials: A total of 29 patients underwent MRL and PET/CT for LN evaluation. The MRL and PET/CT data were analyzed independently. The number, size, and location of the LN metastases were determined.more » The location was described as within or outside the standard clinical target volume for elective pelvic irradiation as defined by the Radiation Therapy Oncology Group. Subsequently, the results from MRL and PET/CT were compared. Results: Of the 738 LNs visible on MRL, 151 were positive in 23 of 29 patients. Of the 132 LNs visible on PET/CT, 34 were positive in 13 of 29 patients. MRL detected significantly more positive LNs (p < 0.001) in more patients than PET/CT (p = 0.002). The mean diameter of the detected suspicious LNs on MRL was significantly smaller than those detected by PET/CT, 4.9 mm and 8.4 mm, respectively (p < 0.0001). In 14 (61%) of 23 patients, suspicious LNs were found outside the clinical target volume with MRL and in 4 (31%) of 13 patients with PET/CT. Conclusion: In patients with PCa, both molecular imaging techniques, MRL and {sup 11}C-choline PET/CT, can detect LNs suspicious for metastasis, irrespective of the existing size and shape criteria for CT and conventional magnetic resonance imaging. On MRL and PET/CT, 61% and 31% of the suspicious LNs were located outside the conventional clinical target volume. Therefore, these techniques could help to individualize treatment selection and enable image-guided radiotherapy for patients with PCa LN metastases.« less

Structured Sparse Principal Components Analysis With the TV-Elastic Net Penalty.

PubMed

de Pierrefeu, Amicie; Lofstedt, Tommy; Hadj-Selem, Fouad; Dubois, Mathieu; Jardri, Renaud; Fovet, Thomas; Ciuciu, Philippe; Frouin, Vincent; Duchesnay, Edouard

2018-02-01

Principal component analysis (PCA) is an exploratory tool widely used in data analysis to uncover the dominant patterns of variability within a population. Despite its ability to represent a data set in a low-dimensional space, PCA's interpretability remains limited. Indeed, the components produced by PCA are often noisy or exhibit no visually meaningful patterns. Furthermore, the fact that the components are usually non-sparse may also impede interpretation, unless arbitrary thresholding is applied. However, in neuroimaging, it is essential to uncover clinically interpretable phenotypic markers that would account for the main variability in the brain images of a population. Recently, some alternatives to the standard PCA approach, such as sparse PCA (SPCA), have been proposed, their aim being to limit the density of the components. Nonetheless, sparsity alone does not entirely solve the interpretability problem in neuroimaging, since it may yield scattered and unstable components. We hypothesized that the incorporation of prior information regarding the structure of the data may lead to improved relevance and interpretability of brain patterns. We therefore present a simple extension of the popular PCA framework that adds structured sparsity penalties on the loading vectors in order to identify the few stable regions in the brain images that capture most of the variability. Such structured sparsity can be obtained by combining, e.g., and total variation (TV) penalties, where the TV regularization encodes information on the underlying structure of the data. This paper presents the structured SPCA (denoted SPCA-TV) optimization framework and its resolution. We demonstrate SPCA-TV's effectiveness and versatility on three different data sets. It can be applied to any kind of structured data, such as, e.g., -dimensional array images or meshes of cortical surfaces. The gains of SPCA-TV over unstructured approaches (such as SPCA and ElasticNet PCA) or structured approach (such as GraphNet PCA) are significant, since SPCA-TV reveals the variability within a data set in the form of intelligible brain patterns that are easier to interpret and more stable across different samples.

Comparison between target magnetic resonance imaging (MRI) in-gantry and cognitively directed transperineal or transrectal-guided prostate biopsies for Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 MRI lesions.

PubMed

Yaxley, Anna J; Yaxley, John W; Thangasamy, Isaac A; Ballard, Emma; Pokorny, Morgan R

2017-11-01

To compare the detection rates of prostate cancer (PCa) in men with Prostate Imaging-Reporting and Data System (PI-RADS) 3-5 abnormalities on 3-Tesla multiparametric (mp) magnetic resonance imaging (MRI) using in-bore MRI-guided biopsy compared with cognitively directed transperineal (cTP) biopsy and transrectal ultrasonography (cTRUS) biopsy. This was a retrospective single-centre study of consecutive men attending the private practice clinic of an experienced urologist performing MRI-guided biopsy and an experienced urologist performing cTP and cTRUS biopsy techniques for PI-RADS 3-5 lesions identified on 3-Tesla mpMRI. There were 595 target mpMRI lesions from 482 men with PI-RADS 3-5 regions of interest during 483 episodes of biopsy. The abnormal mpMRI target lesion was biopsied using the MRI-guided method for 298 biopsies, the cTP method for 248 biopsies and the cTRUS method for 49 biopsies. There were no significant differences in PCa detection among the three biopsy methods in PI-RADS 3 (48.9%, 40.0% and 44.4%, respectively), PI-RADS 4 (73.2%, 81.0% and 85.0%, respectively) or PI-RADS 5 (95.2, 92.0% and 95.0%, respectively) lesions, and there was no significant difference in detection of significant PCa among the biopsy methods in PI-RADS 3 (42.2%, 30.0% and 33.3%, respectively), PI-RADS 4 (66.8%, 66.0% and 80.0%, respectively) or PI-RADS 5 (90.5%, 89.8% and 90.0%, respectively) lesions. There were also no differences in PCa or significant PCa detection based on lesion location or size among the methods. We found no significant difference in the ability to detect PCa or significant PCa using targeted MRI-guided, cTP or cTRUS biopsy methods. Identification of an abnormal area on mpMRI appears to be more important in increasing the detection of PCa than the technique used to biopsy an MRI abnormality. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Molecular profiling of ETS and non‐ETS aberrations in prostate cancer patients from northern India

PubMed Central

Kunju, Lakshmi P.; Carskadon, Shannon L.; Pandey, Swaroop K.; Singh, Geetika; Pradeep, Immanuel; Tandon, Vini; Singhai, Atin; Goel, Apul; Amit, Sonal; Agarwal, Asha; Dinda, Amit K.; Seth, Amlesh; Tsodikov, Alexander; Chinnaiyan, Arul M.; Palanisamy, Nallasivam

2015-01-01

Abstract BACKGROUND Molecular stratification of prostate cancer (PCa) based on genetic aberrations including ETS or RAF gene‐rearrangements, PTEN deletion, and SPINK1 over‐expression show clear prognostic and diagnostic utility. Gene rearrangements involving ETS transcription factors are frequent pathogenetic somatic events observed in PCa. Incidence of ETS rearrangements in Caucasian PCa patients has been reported, however, occurrence in Indian population is largely unknown. The aim of this study was to determine the prevalence of the ETS and RAF kinase gene rearrangements, SPINK1 over‐expression, and PTEN deletion in this cohort. METHODS In this multi‐center study, formalin‐fixed paraffin embedded (FFPE) PCa specimens (n = 121) were procured from four major medical institutions in India. The tissues were sectioned and molecular profiling was done using immunohistochemistry (IHC), RNA in situ hybridization (RNA‐ISH) and/or fluorescence in situ hybridization (FISH). RESULTS ERG over‐expression was detected in 48.9% (46/94) PCa specimens by IHC, which was confirmed in a subset of cases by FISH. Among other ETS family members, while ETV1 transcript was detected in one case by RNA‐ISH, no alteration in ETV4 was observed. SPINK1 over‐expression was observed in 12.5% (12/96) and PTEN deletion in 21.52% (17/79) of the total PCa cases. Interestingly, PTEN deletion was found in 30% of the ERG‐positive cases (P = 0.017) but in only one case with SPINK1 over‐expression (P = 0.67). BRAF and RAF1 gene rearrangements were detected in ∼1% and ∼4.5% of the PCa cases, respectively. CONCLUSIONS This is the first report on comprehensive molecular profiling of the major spectrum of the causal aberrations in Indian men with PCa. Our findings suggest that ETS gene rearrangement and SPINK1 over‐expression patterns in North Indian population largely resembled those observed in Caucasian population but differed from Japanese and Chinese PCa patients. The molecular profiling data presented in this study could help in clinical decision‐making for the pursuit of surgery, diagnosis, and in selection of therapeutic intervention. Prostate 75:1051–1062, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc. PMID:25809148

Localization of Pathology on Complex Architecture Building Surfaces

NASA Astrophysics Data System (ADS)

Sidiropoulos, A. A.; Lakakis, K. N.; Mouza, V. K.

2017-02-01

The technology of 3D laser scanning is considered as one of the most common methods for heritage documentation. The point clouds that are being produced provide information of high detail, both geometric and thematic. There are various studies that examine techniques of the best exploitation of this information. In this study, an algorithm of pathology localization, such as cracks and fissures, on complex building surfaces is being tested. The algorithm makes use of the points' position in the point cloud and tries to distinguish them in two groups-patterns; pathology and non-pathology. The extraction of the geometric information that is being used for recognizing the pattern of the points is being accomplished via Principal Component Analysis (PCA) in user-specified neighborhoods in the whole point cloud. The implementation of PCA leads to the definition of the normal vector at each point of the cloud. Two tests that operate separately examine both local and global geometric criteria among the points and conclude which of them should be categorized as pathology. The proposed algorithm was tested on parts of the Gazi Evrenos Baths masonry, which are located at the city of Giannitsa at Northern Greece.

Diffusion MRI noise mapping using random matrix theory

PubMed Central

Veraart, Jelle; Fieremans, Els; Novikov, Dmitry S.

2016-01-01

Purpose To estimate the spatially varying noise map using a redundant magnitude MR series. Methods We exploit redundancy in non-Gaussian multi-directional diffusion MRI data by identifying its noise-only principal components, based on the theory of noisy covariance matrices. The bulk of PCA eigenvalues, arising due to noise, is described by the universal Marchenko-Pastur distribution, parameterized by the noise level. This allows us to estimate noise level in a local neighborhood based on the singular value decomposition of a matrix combining neighborhood voxels and diffusion directions. Results We present a model-independent local noise mapping method capable of estimating noise level down to about 1% error. In contrast to current state-of-the art techniques, the resultant noise maps do not show artifactual anatomical features that often reflect physiological noise, the presence of sharp edges, or a lack of adequate a priori knowledge of the expected form of MR signal. Conclusions Simulations and experiments show that typical diffusion MRI data exhibit sufficient redundancy that enables accurate, precise, and robust estimation of the local noise level by interpreting the PCA eigenspectrum in terms of the Marchenko-Pastur distribution. PMID:26599599

Sexual Recovery Following Prostate Cancer: Recommendations From 2 Established Canadian Sexual Rehabilitation Clinics.

PubMed

Elliott, Stacy; Matthew, Andrew

2018-04-01

Supportive sexual health care is much-needed adjuvant care to oncologic management for men with prostate cancer (PCa). To inspire the initiation of biopsychosocial sexual health programming where it does not exist and to inform program enhancement in existing sexual rehabilitation clinics (SRCs). This article reviews the combined 30-year experience of 2 well-established Canadian SRCs for men and their partners after PCa treatments, interwoven with empirical evidence. To comprehensively review the biopsychosocial approach to sexual health assessment of men with PCa and their partners to direct the practicalities of running a successful and sustainable SRC. A full description of the biomedical and psychosocial approaches, inclusive of comprehensive sexual function, the penile rehabilitation controversy, and other medical and relationship issues affecting sexual adjustment, is provided to highlight the relevance of proper assessment and follow-through for sexual adaptation and adjustment. 10 recommendations for a successful SRC are discussed, including the principles behind developing a sustainable business plan, staff acquisition and training, budget, integration of treatment and research priorities, respectful and multidisciplinary approaches to care, and suggestions of visit formats, protocols, and questionnaires. We recommend a phased approach of an SRC into usual care with the option to provide accessible and equitable care to patients not within proximal access of treating institutions. Sexual rehabilitation after treatment for PCa requires a complex treatment process. Providing sustainable sexual rehabilitation programming under the financially strained environment of the Canadian medical system is a challenge; therefore, to provide Canadian patients and their partners with comprehensive cancer care, they deserve a biopsychosocial approach combined with a creative and systematic implementation strategy. Elliott S, Matthew A. Sexual Recovery Following Prostate Cancer: Recommendations From 2 Established Canadian Sexual Rehabilitation Clinics. Sex Med Rev 2018;6:279-294. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Trans-rectal ultrasound visibility of prostate lesions identified by magnetic resonance imaging increases accuracy of image-fusion targeted biopsies.

PubMed

Ukimura, Osamu; Marien, Arnaud; Palmer, Suzanne; Villers, Arnauld; Aron, Manju; de Castro Abreu, Andre Luis; Leslie, Scott; Shoji, Sunao; Matsugasumi, Toru; Gross, Mitchell; Dasgupta, Prokar; Gill, Inderbir S

2015-11-01

To compare the diagnostic yield of targeted prostate biopsy using image-fusion of multi-parametric magnetic resonance (mp-MR) with real-time trans-rectal ultrasound (TRUS) for clinically significant lesions that are suspicious only on mp-MR versus lesions that are suspicious on both mp-MR and TRUS. Pre-biopsy MRI and TRUS were each scaled on a 3-point score: highly suspicious, likely, and unlikely for clinically significant cancer (sPCa). Using an MR-TRUS elastic image-fusion system (Koelis), a 127 consecutive patients with a suspicious clinically significant index lesion on pre-biopsy mp-MR underwent systematic biopsies and MR/US-fusion targeted biopsies (01/2010-09/2013). Biopsy histological outcomes were retrospectively compared with MR suspicion level and TRUS-visibility of the MR-suspicious lesion. sPCa was defined as biopsy Gleason score ≥7 and/or maximum cancer core length ≥5 mm. Targeted biopsies outperformed systematic biopsies in overall cancer detection rate (61 vs. 41 %; p = 0.007), sPCa detection rate (43 vs. 23 %; p = 0.0013), cancer core length (7.5 vs. 3.9 mm; p = 0.0002), and cancer rate per core (56 vs. 12 %; p < 0.0001), respectively. Highly suspicious lesions on mp-MR correlated with higher positive biopsy rate (p < 0.0001), higher Gleason score (p = 0.018), and greater cancer core length (p < 0.0001). Highly suspicious lesions on TRUS in corresponding to MR-suspicious lesion had a higher biopsy yield (p < 0.0001) and higher sPCa detection rate (p < 0.0001). Since majority of MR-suspicious lesions were also suspicious on TRUS, TRUS-visibility allowed selection of the specific MR-visible lesion which should be targeted from among the multiple TRUS suspicious lesions in each prostate. MR-TRUS fusion-image-guided biopsies outperformed systematic biopsies. TRUS-visibility of a MR-suspicious lesion facilitates image-guided biopsies, resulting in higher detection of significant cancer.

Prostate-specific antigen (PSA) density in the diagnostic algorithm of prostate cancer.

PubMed

Nordström, Tobias; Akre, Olof; Aly, Markus; Grönberg, Henrik; Eklund, Martin

2018-04-01

Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early evidence on its use for biopsy decisions was conflicting and use of PSA density is not commonly recommended in guidelines. We analyzed biopsy outcomes in 5291 men in the population-based STHLM3 study with PSA ≥ 3 ng/ml and ultrasound-guided prostate volume measurements by using percentages and regression models. PSA density was calculated as total PSA (ng/ml) divided by prostate volume (ml). Main endpoint was clinically significant cancer (csPCa) defined as Gleason Score ≥ 7. The median PSA-density was 0.10 ng/ml 2 (IQR 0.075-0.14). PSA-density was associated with the risk of finding csPCa both with and without adjusting for the additional clinical information age, family history, previous biopsies, total PSA and free/total PSA (OR 1.06; 95% CI:1.05-1.07 and OR 1.07, 95% CI 1.06-1.08). Discrimination for csPCa was better when PSA density was added to a model with additional clinical information (AUC 0.75 vs. 0.73, P < 0.05). The proportion of men with Gleason Score 6 (ISUP 1) was similar across stratas of PSA-density. Omitting prostate biopsy for men with PSA-density ≤0.07 ng/ml 2 would save 19.7% of biopsy procedures, while missing 6.9% of csPCa. PSA-density cutoffs of 0.10 ng/ml 2 and 0.15 ng/ml 2 resulted in detection of 77% (729/947) and 49% (461/947) of Gleason Score ≥7 tumors. PSA-density might inform biopsy decisions, and spare some men from the morbidity associated with a prostate biopsy and diagnosis of low-grade prostate cancer.

L-dopa decarboxylase (DDC) gene expression is related to outcome in patients with prostate cancer.

PubMed

Koutalellis, Georgios; Stravodimos, Konstantinos; Avgeris, Margaritis; Mavridis, Konstantinos; Scorilas, Andreas; Lazaris, Andreas; Constantinides, Constantinos

2012-09-01

What's known on the subject? and What does the study add? L-dopa decarboxylase (DDC) has been documented as a novel co-activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH. In the present study, there was a significant association between the DDC gene expression levels and the pathological stage and Gleason score of patients with prostate cancer (PCa). Moreover, DDC expression was shown to be an unfavourable prognostic marker of biochemical recurrence and disease-free survival in patients with PCa treated by radical prostatectomy. To determine whether L-dopa decarboxylase gene (DDC) expression levels in patients with prostate cancer (PCa) correlate to biochemical recurrence and disease prognosis after radical prostatectomy (RP). The present study consisted of 56 samples with confirmed malignancy from patients with PCa who had undergone RP at a single tertiary academic centre. Total RNA was isolated from tissue specimens and a SYBR Green fluorescence-based quantitative real-time polymerase chain reaction methodology was developed for the determination of DDC mRNA expression levels of the tested tissues. Follow-up time ranged between 1.0 and 62.0 months (mean ± SE, 28.6 ± 2.1 month; median, 31.5 months). Time to biochemical recurrence was defined as the interval between the surgery and the measurement of two consecutive values of prostate-specific antigen (PSA) ≥0.2 ng/mL. DDC expression levels were found to be positively correlated with the tumour-node-metastasis stage (P = 0.021) and Gleason score (P = 0.036) of the patients with PCa. Patients with PCa with raised DDC expression levels run a significantly higher risk of biochemical recurrence after RP, as indicated by Cox proportional regression analysis (P = 0.021). Multivariate Cox proportional regression models revealed the preoperative PSA-, age- and digital rectal examination-independent prognostic value of DDC expression for the prediction of disease-free survival (DFS) among patients with PCa (P = 0.036). Kaplan-Meier survival analysis confirms the significantly shorter DFS after RP of PCa with higher DDC expression levels (P = 0.015). This is the first study indicating the potential of DDC expression as a novel prognostic biomarker in patients with PCa who have undergone RP. For further evaluation and clinical application of the findings of the present study, a direct analysis of mRNA and/or its protein expression level in preoperative biopsy, blood serum and urine should be conducted. © 2012 BJU INTERNATIONAL.

A comparison of clinicopathological features and prognosis in prostate cancer between atomic bomb survivors and control patients

PubMed Central

Shoji, Koichi; Teishima, Jun; Hayashi, Tetsutaro; Shinmei, Shunsuke; Akita, Tomoyuki; Sentani, Kazuhiro; Takeshima, Yukio; Arihiro, Koji; Tanaka, Junko; Yasui, Wataru; Matsubara, Akio

2017-01-01

An atomic bomb (A-bomb) was dropped on Hiroshima on 6th August 1945. Although numerous studies have investigated cancer incidence and mortality among A-bomb survivors, only a small number have addressed urological cancer in these survivors. The aim of the present study was to investigate the clinicopathological features of prostate cancer (PCa) in A-bomb survivors. The clinicopathological features and prognosis of PCa were retrospectively reviewed in 212 survivors and 595 control patients between November 1996 and December 2010. The histopathological and clinical outcomes of surgical treatment of PCa were also evaluated in 69 survivors and 162 control patients. Despite the higher age at diagnosis compared with the control group (P=0.0031), survivors were more likely to have been diagnosed with PCa from a health check compared with the control group (P<0.0001). As a consequence, the survivors were found to exhibit metastasis significantly less frequently (199/212, 93.9%) compared with the control patients (521/595, 87.6%; P=0.0076). Prognosis in the two groups was examined, subsequent to a mean length of follow-up of 44 months. Overall survival (OS) and PCa-specific survival (CS) were similar between the two groups (OS, P=0.2196; CS, P=0.1017). A-bomb exposure was not found to be an independent predictor for prognosis by multivariate analysis (OS, P=0.7800; CS, P=0.8688). The clinicopathological features of patients who underwent a prostatectomy were similar except for the diagnosis opportunity between the two groups. Progression-free survival rates were similar between the two groups (P=0.5630). A-bomb exposure was not a significant and independent predictor for worsening of progression-free prognosis by multivariate analysis (P=0.3763). A-bomb exposure does not appear to exert deleterious effects on the biological aggressiveness of PCa and the prognosis of patients with PCa. PMID:28693168

A comparison of clinicopathological features and prognosis in prostate cancer between atomic bomb survivors and control patients.

PubMed

Shoji, Koichi; Teishima, Jun; Hayashi, Tetsutaro; Shinmei, Shunsuke; Akita, Tomoyuki; Sentani, Kazuhiro; Takeshima, Yukio; Arihiro, Koji; Tanaka, Junko; Yasui, Wataru; Matsubara, Akio

2017-07-01

An atomic bomb (A-bomb) was dropped on Hiroshima on 6th August 1945. Although numerous studies have investigated cancer incidence and mortality among A-bomb survivors, only a small number have addressed urological cancer in these survivors. The aim of the present study was to investigate the clinicopathological features of prostate cancer (PCa) in A-bomb survivors. The clinicopathological features and prognosis of PCa were retrospectively reviewed in 212 survivors and 595 control patients between November 1996 and December 2010. The histopathological and clinical outcomes of surgical treatment of PCa were also evaluated in 69 survivors and 162 control patients. Despite the higher age at diagnosis compared with the control group (P=0.0031), survivors were more likely to have been diagnosed with PCa from a health check compared with the control group (P<0.0001). As a consequence, the survivors were found to exhibit metastasis significantly less frequently (199/212, 93.9%) compared with the control patients (521/595, 87.6%; P=0.0076). Prognosis in the two groups was examined, subsequent to a mean length of follow-up of 44 months. Overall survival (OS) and PCa-specific survival (CS) were similar between the two groups (OS, P=0.2196; CS, P=0.1017). A-bomb exposure was not found to be an independent predictor for prognosis by multivariate analysis (OS, P=0.7800; CS, P=0.8688). The clinicopathological features of patients who underwent a prostatectomy were similar except for the diagnosis opportunity between the two groups. Progression-free survival rates were similar between the two groups (P=0.5630). A-bomb exposure was not a significant and independent predictor for worsening of progression-free prognosis by multivariate analysis (P=0.3763). A-bomb exposure does not appear to exert deleterious effects on the biological aggressiveness of PCa and the prognosis of patients with PCa.

Choline Kinase Alpha as an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target

PubMed Central

Asim, Mohammad; Massie, Charles E.; Orafidiya, Folake; Pértega-Gomes, Nelma; Warren, Anne Y.; Esmaeili, Mohsen; Selth, Luke A.; Zecchini, Heather I.; Luko, Katarina; Qureshi, Arham; Baridi, Ajoeb; Menon, Suraj; Madhu, Basetti; Escriu, Carlos; Lyons, Scott; Vowler, Sarah L.; Zecchini, Vincent R.; Shaw, Greg; Hessenkemper, Wiebke; Russell, Roslin; Mohammed, Hisham; Stefanos, Niki; Lynch, Andy G.; Grigorenko, Elena; D’Santos, Clive; Taylor, Chris; Lamb, Alastair; Sriranjan, Rouchelle; Yang, Jiali; Stark, Rory; Dehm, Scott M.; Rennie, Paul S.; Carroll, Jason S.; Griffiths, John R.; Tavaré, Simon; Mills, Ian G.; McEwan, Iain J.; Baniahmad, Aria; Tilley, Wayne D.; Neal, David E.

2016-01-01

Background: The androgen receptor (AR) is a major drug target in prostate cancer (PCa). We profiled the AR-regulated kinome to identify clinically relevant and druggable effectors of AR signaling. Methods: Using genome-wide approaches, we interrogated all AR regulated kinases. Among these, choline kinase alpha (CHKA) expression was evaluated in benign (n = 195), prostatic intraepithelial neoplasia (PIN) (n = 153) and prostate cancer (PCa) lesions (n = 359). We interrogated how CHKA regulates AR signaling using biochemical assays and investigated androgen regulation of CHKA expression in men with PCa, both untreated (n = 20) and treated with an androgen biosynthesis inhibitor degarelix (n = 27). We studied the effect of CHKA inhibition on the PCa transcriptome using RNA sequencing and tested the effect of CHKA inhibition on cell growth, clonogenic survival and invasion. Tumor xenografts (n = 6 per group) were generated in mice using genetically engineered prostate cancer cells with inducible CHKA knockdown. Data were analyzed with χ2 tests, Cox regression analysis, and Kaplan-Meier methods. All statistical tests were two-sided. Results: CHKA expression was shown to be androgen regulated in cell lines, xenografts, and human tissue (log fold change from 6.75 to 6.59, P = .002) and was positively associated with tumor stage. CHKA binds directly to the ligand-binding domain (LBD) of AR, enhancing its stability. As such, CHKA is the first kinase identified as an AR chaperone. Inhibition of CHKA repressed the AR transcriptional program including pathways enriched for regulation of protein folding, decreased AR protein levels, and inhibited the growth of PCa cell lines, human PCa explants, and tumor xenografts. Conclusions: CHKA can act as an AR chaperone, providing, to our knowledge, the first evidence for kinases as molecular chaperones, making CHKA both a marker of tumor progression and a potential therapeutic target for PCa. PMID:26657335

Evaluating the performance of PI-RADS v2 in the non-academic setting.

PubMed

Jordan, Eric J; Fiske, Charles; Zagoria, Ronald J; Westphalen, Antonio C

2017-11-01

To evaluate the utility of PI-RADS v2 to diagnose clinically significant prostate cancer (CS-PCa) with magnetic resonance ultrasound (MR/US) fusion-guided prostate biopsies in the non-academic setting. Retrospective analysis of men whom underwent prostate multiparametric MRI and subsequent MR/US fusion biopsies at a single non-academic center from 11/2014 to 3/2016. Prostate MRIs were performed on a 3-Tesla scanner with a surface body coil. The Prostate Imaging Reporting and Data System (PI-RADS) v2 scoring algorithm was utilized and MR/US fusion biopsies were performed in selected cases. Mixed effect logistic regression analyses and receiver-operating characteristic (ROC) curves were performed on PI-RADS v2 alone and combined with PSA density (PSAD) to predict CS-PCa. 170 patients underwent prostate MRI with 282 PI-RADS lesions. MR/US fusion diagnosed 71 CS-PCa, 33 Gleason score 3+3, and 168 negative. PI-RADS v2 score is a statistically significant predictor of CS-PCa (P < 0.001). For each one-point increase in the overall PI-RADS v2 score, the odds of having CS-PCa increases by 4.2 (95% CI 2.2-8.3). The area under the ROC curve for PI-RADS v2 is 0.69 (95% CI 0.63-0.76) and for PI-RADS v2 + PSAD is 0.76 (95% CI 0.69-0.82), statistically higher than PI-RADS v2 alone (P < 0.001). The rate of CS-PCa was about twice higher in men with high PSAD (≥0.15) compared to men with low PSAD (<0.15) when a PI-RADS 4 or 5 lesion was detected (P = 0.005). PI-RADS v2 is a strong predictor of CS-PCa in the non-academic setting and can be further strengthened when utilized with PSA density.

Clinical significance of miRNA host gene promoter methylation in prostate cancer.

PubMed

Daniunaite, Kristina; Dubikaityte, Monika; Gibas, Povilas; Bakavicius, Arnas; Rimantas Lazutka, Juozas; Ulys, Albertas; Jankevicius, Feliksas; Jarmalaite, Sonata

2017-07-01

Only a part of prostate cancer (PCa) patients has aggressive malignancy requiring adjuvant treatment after radical prostatectomy (RP). Biomarkers capable to predict biochemical PCa recurrence (BCR) after RP would significantly improve preoperative risk stratification and treatment decisions. MicroRNA (miRNA) deregulation has recently emerged as an important phenomenon in tumor development and progression, however, the mechanisms remain largely unstudied. In the present study, based on microarray profiling of DNA methylation in 9 pairs of PCa and noncancerous prostate tissues (NPT), host genes of miR-155-5p, miR-152-3p, miR-137, miR-31-5p, and miR-642a, -b were analyzed for promoter methylation in 129 PCa, 35 NPT, and 17 benign prostatic hyperplasia samples (BPH) and compared to the expression of mature miRNAs and their selected targets (DNMT1, KDM1A, and KDM5B). The Cancer Genome Atlas dataset was utilized for validation. Methylation of mir-155, mir-152, and mir-137 host genes was PCa-specific, and downregulation of miR-155-5p significantly correlated with promoter methylation. Higher KDM5B expression was observed in samples with methylated mir-155 or mir-137 promoters, whereas upregulation of KDM1A and DNMT1 was associated with mir-155 and mir-152 methylation status, respectively. Promoter methylation of mir-155, mir-152, and mir-31 was predictive of BCR-free survival in various Cox models and increased the prognostic value of clinicopathologic factors. In conclusion, methylated mir-155, mir-152, mir-137, and mir-31 host genes are promising diagnostic and/or prognostic biomarkers of PCa. Methylation status of particular miRNA host genes as independent variables or in combinations might assist physicians in identifying poor prognosis PCa patients preoperatively. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wasser, M.N.; Schultze Kool, L.J.; Roos, A. de

Our goal was to assess the value of MRA for detecting stenoses in the celiac (CA) and superior mesenteric (SMA) arteries in patients suspected of having chronic mesenteric ischemia, using an optimized systolically gated 3D phase contrast technique. In an initial study in 24 patients who underwent conventional angiography of the abdominal vessels for different clinical indications, a 3D phase contrast MRA technique (3D-PCA) was evaluated and optimized to image the CAs and SMAs. Subsequently, a prospective study was performed to assess the value of systolically gated 3D-PCA in evaluation of the mesenteric arteries in 10 patients with signs andmore » symptoms of chronic mesenteric ischemia. Intraarterial digital subtraction angiography and surgical findings were used as the reference standard. In the initial study, systolic gating appeared to be essential in imaging the SMA on 3D-PCA. In 10 patients suspected of mesenteric ischemia, systolically gated 3D-PCA identified significant proximal disease in the two mesenteric vessels in 4 patients. These patients underwent successful reconstruction of their stenotic vessels. Cardiac-gated MRA may become a useful tool in selection of patients suspected of having mesenteric ischemia who may benefit from surgery. 16 refs., 6 figs., 4 tabs.« less

Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer.

PubMed

Nonomura, Norio; Takayama, Hitoshi; Nakayama, Masashi; Nakai, Yasutomo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Aozasa, Katsuyuki; Tsujimura, Akira

2011-06-01

• To evaluate tumour-associated macrophage (TAM) infiltration in prostate biopsy specimens as a possible prognostic factor for prostate cancer (PCa) after hormonal therapy. • Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 for 71 patients having PCa treated with hormonal therapy. • Six microscopic (×400) fields around the cancer foci were selected for TAM counting. • The median value of serum prostate-specific antigen (PSA) was 50.1 ng/mL, and the median TAM count was 22. • Recurrence-free survival was significantly better in patients with fewer TAMs (<22) than in those with higher numbers of TAMs (≥22) (P < 0.001). • TAM count was higher in those with higher serum PSA (PSA), higher Gleason score, clinical T stage or those with PSA failure. Cox multivariate analysis showed that TAM count is one of the prognostic factors for PCa treated by hormonal therapy (P < 0.0001). • TAM infiltration in prostate needle biopsy specimens is a useful predictive factor for PSA failure or progression of PCa after hormonal therapy. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

Is it time to perform only MRI targeted cores? Our experience in 1032 men submitted to prostate biopsy.

PubMed

Pepe, Pietro; Garufi, Antonio; Priolo, Gian Domenico; Galia, Antonio; Fraggetta, Filippo; Pennisi, Michele

2018-04-18

Diagnostic accuracy of mpMRI (multiparametric magnetic resonance imaging) in the diagnosis of clinically significant prostate cancer (csPCa) has been evaluated and compared with transperineal saturation prostate biopsy (SPBx). From January 2011 to Febraury 2018 1032 men (median age 63 years) with median PSA of 8.6 ng/ml underwent repeat SPBx (reference test) for the suspicion of cancer. All the patients underwent 3.0 Tesla pelvic mpMRI before SPBx and the lesions with PI-RADS (Prostate Imaging-Reporting and Data System) score ≥ 3 were submitted to additional targeted fusion prostate biopsy (TPBx). A T1c PCa was found in 372/1032 (36%) patients and 272 (73.1%) of them were classified as csPCa. SPBx vs. TPBx PI-RADS > 3 vs. TPBx PI-RADS > 4 diagnosed 95.6 vs. 83.8 vs. 60.3% (p < 0.0001) of the csPCa; in detail, SPBx missed 12/272 (4.5%) csPCa vs. 44/272 (16.2%) and 108/272 (39.7%) missed by TPBx PI-RADS > 3 and TPBx PI-RADS > 4 (p < 0.0001), respectively. The use of mpMRI as "a triage test" would have spared 49.3% vs. 73.6% using as cut-off a PI-RADS > 3 vs PI-RADS > 4, respectively. MpMRI could significantly reduce the number of unnecessary repeat prostate biopsies (about 50% of the cases using a PI-RADS score > 3); at the same time, the patients should be informed of the false-negative rate for csPCa of TPBx for PI-RADS > 3 (16.2%) or > 4 (39.7%). Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A diffusion-matched principal component analysis (DM-PCA) based two-channel denoising procedure for high-resolution diffusion-weighted MRI

PubMed Central

Chang, Hing-Chiu; Bilgin, Ali; Bernstein, Adam; Trouard, Theodore P.

2018-01-01

Over the past several years, significant efforts have been made to improve the spatial resolution of diffusion-weighted imaging (DWI), aiming at better detecting subtle lesions and more reliably resolving white-matter fiber tracts. A major concern with high-resolution DWI is the limited signal-to-noise ratio (SNR), which may significantly offset the advantages of high spatial resolution. Although the SNR of DWI data can be improved by denoising in post-processing, existing denoising procedures may potentially reduce the anatomic resolvability of high-resolution imaging data. Additionally, non-Gaussian noise induced signal bias in low-SNR DWI data may not always be corrected with existing denoising approaches. Here we report an improved denoising procedure, termed diffusion-matched principal component analysis (DM-PCA), which comprises 1) identifying a group of (not necessarily neighboring) voxels that demonstrate very similar magnitude signal variation patterns along the diffusion dimension, 2) correcting low-frequency phase variations in complex-valued DWI data, 3) performing PCA along the diffusion dimension for real- and imaginary-components (in two separate channels) of phase-corrected DWI voxels with matched diffusion properties, 4) suppressing the noisy PCA components in real- and imaginary-components, separately, of phase-corrected DWI data, and 5) combining real- and imaginary-components of denoised DWI data. Our data show that the new two-channel (i.e., for real- and imaginary-components) DM-PCA denoising procedure performs reliably without noticeably compromising anatomic resolvability. Non-Gaussian noise induced signal bias could also be reduced with the new denoising method. The DM-PCA based denoising procedure should prove highly valuable for high-resolution DWI studies in research and clinical uses. PMID:29694400

Principal component analysis of the CT density histogram to generate parametric response maps of COPD

NASA Astrophysics Data System (ADS)

Zha, N.; Capaldi, D. P. I.; Pike, D.; McCormack, D. G.; Cunningham, I. A.; Parraga, G.

2015-03-01

Pulmonary x-ray computed tomography (CT) may be used to characterize emphysema and airways disease in patients with chronic obstructive pulmonary disease (COPD). One analysis approach - parametric response mapping (PMR) utilizes registered inspiratory and expiratory CT image volumes and CT-density-histogram thresholds, but there is no consensus regarding the threshold values used, or their clinical meaning. Principal-component-analysis (PCA) of the CT density histogram can be exploited to quantify emphysema using data-driven CT-density-histogram thresholds. Thus, the objective of this proof-of-concept demonstration was to develop a PRM approach using PCA-derived thresholds in COPD patients and ex-smokers without airflow limitation. Methods: Fifteen COPD ex-smokers and 5 normal ex-smokers were evaluated. Thoracic CT images were also acquired at full inspiration and full expiration and these images were non-rigidly co-registered. PCA was performed for the CT density histograms, from which the components with the highest eigenvalues greater than one were summed. Since the values of the principal component curve correlate directly with the variability in the sample, the maximum and minimum points on the curve were used as threshold values for the PCA-adjusted PRM technique. Results: A significant correlation was determined between conventional and PCA-adjusted PRM with 3He MRI apparent diffusion coefficient (p<0.001), with CT RA950 (p<0.0001), as well as with 3He MRI ventilation defect percent, a measurement of both small airways disease (p=0.049 and p=0.06, respectively) and emphysema (p=0.02). Conclusions: PRM generated using PCA thresholds of the CT density histogram showed significant correlations with CT and 3He MRI measurements of emphysema, but not airways disease.

Prebiopsy biparametric MRI: differences of PI-RADS version 2 in patients with different PSA levels.

PubMed

Choi, M H; Lee, Y J; Jung, S E; Rha, S E; Byun, J Y

2018-06-09

To validate the diagnostic accuracy of Prostate Imaging-Reporting and Data System (PI-RADS) version 2 in detecting clinically significant prostate cancer (csPCa, Gleason score ≥7) on prebiopsy biparametric MRI (bpMRI) in patients with different prostate-specific antigen (PSA) levels. This retrospective study included 184 patients who underwent prebiopsy bpMRI followed by transrectal ultrasonography-guided biopsy between June 2015 and February 2017. Reader 1 performed a combination of systematic and targeted biopsy with cognitive fusion after reviewing bpMRI and reader 2 reviewed the bpMRIs retrospectively. PI-RADS categories 4 and 5 were considered positive, and the results of the biopsy were considered the reference standard. Diagnostic performance of PI-RADS of bpMRI was evaluated in two PSA groups with a PSA cut-off level of 10 ng/ml and compared to PSA and the PSA density using receiver operating characteristics (ROC) curve analysis. csPCa was diagnosed in 24 of 123 patients (19.5%) and 26 of 61 patients (42.6%) in the low and high PSA groups, respectively. A PI-RADS v2 category by either readers 1 or 2 had a significantly better performance to detect csPCa than PSA in both PSA groups. In the high PSA group, only one csPCa was missed by reader 2, but none by reader 1. In the low PSA group, readers 1 and 2 were unable to detect seven and five of the 24 csPCas, respectively. Prebiopsy bpMRI has good performance for detecting csPCa in the high PSA group but may miss small-volume csPCa in the low PSA group. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Modeling pair distribution functions of rare-earth phosphate glasses using principal component analysis

DOE PAGES

Cole, Jacqueline M.; Cheng, Xie; Payne, Michael C.

2016-10-18

The use of principal component analysis (PCA) to statistically infer features of local structure from experimental pair distribution function (PDF) data is assessed on a case study of rare-earth phosphate glasses (REPGs). Such glasses, co-doped with two rare-earth ions (R and R’) of different sizes and optical properties, are of interest to the laser industry. The determination of structure-property relationships in these materials is an important aspect of their technological development. Yet, realizing the local structure of co-doped REPGs presents significant challenges relative to their singly-doped counterparts; specifically, R and R’ are difficult to distinguish in terms of establishing relativemore » material compositions, identifying atomic pairwise correlation profiles in a PDF that are associated with each ion, and resolving peak overlap of such profiles in PDFs. This study demonstrates that PCA can be employed to help overcome these structural complications, by statistically inferring trends in PDFs that exist for a restricted set of experimental data on REPGs, and using these as training data to predict material compositions and PDF profiles in unknown co-doped REPGs. The application of these PCA methods to resolve individual atomic pairwise correlations in t(r) signatures is also presented. The training methods developed for these structural predictions are pre-validated by testing their ability to reproduce known physical phenomena, such as the lanthanide contraction, on PDF signatures of the structurally simpler singly-doped REPGs. The intrinsic limitations of applying PCA to analyze PDFs relative to the quality control of source data, data processing, and sample definition, are also considered. Furthermore, while this case study is limited to lanthanide-doped REPGs, this type of statistical inference may easily be extended to other inorganic solid-state materials, and be exploited in large-scale data-mining efforts that probe many t(r) functions.« less

Relationships between serum PSA levels, Gleason scores and results of 68Ga-PSMAPET/CT in patients with recurrent prostate cancer.

PubMed

Sanli, Yasemin; Kuyumcu, Serkan; Sanli, Oner; Buyukkaya, Fikret; İribaş, Ayça; Alcin, Goksel; Darendeliler, Emin; Ozluk, Yasemin; Yildiz, Sevda Ozel; Turkmen, Cüneyt

2017-11-01

To investigate the relationship between serum PSA level, Gleason score of PCa and the outcomes of Ga 68 -PSMA PET/CT in patients with recurrent PCa. A total of 109 consecutive patients (median age 71 years; range 48-89 years) who had PSA recurrence after RP and/or hormonotherapy and/or radiotherapy were included in this study. Local recurrences, lymph node metastasis (pelvic, abdominal and/or supradiaphragmatic), bone metastases (oligometastatic/multimetastatic) and other metastatic sites (lung, liver, brain, etc) were documented. In 91(83.4%) patients at least one lesion characteristic for PCa was detected by 68 Ga-PSMA PET/CT. The median serum total PSA (tPSA) was 6.5 (0.2-640) ng/ml.There was a significant difference between 68 Ga-PSMA PET/CT positive and negative patients in terms of serum total PSA value. No statistical significance was found between positive and negative 68 Ga-PSMA PET/CT findings in terms of Gleason score. Local recurrence was detected in 56 patients. whereas lymph node metastases were demonstrated in 46 patients. Pelvic nodal disease was the most frequent presentation followed by abdominal and supradiaphragmaticnodal involvement. Bone metastases [oligometastasis, (n = 20); multimetastasis, (n = 35)⦌ were also detected in 55 patients. In the ROC analysis for the study cohort, the optimal cut-off value of total serum PSA was determined as 0.67 ng/ml for distinguishing between positive and negative 68 Ga-PSMA PET/CT images, with an area under curve of 0.952 (95% CI 0.911-0.993). 68 Ga-PSMA PET/CT was found to be an effective tool for the detection of recurrent PCa. Even though no relationship was detected between the GS and 68 Ga-PSMA PET/CT findings, serum total PSA values may be used for estimating the likelihood of positive 68 Ga-PSMA PET/CT results.

Esophageal cancer detection based on tissue surface-enhanced Raman spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Chen, Weisheng; Wang, Yue; Chen, Rong; Zeng, Haishan

2013-01-01

The capability of using silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) spectroscopy combined with principal component analysis (PCA) and linear discriminate analysis (LDA) to differentiate esophageal cancer tissue from normal tissue was presented. Significant differences in Raman intensities of prominent SERS bands were observed between normal and cancer tissues. PCA-LDA multivariate analysis of the measured tissue SERS spectra achieved diagnostic sensitivity of 90.9% and specificity of 97.8%. This exploratory study demonstrated great potential for developing label-free tissue SERS analysis into a clinical tool for esophageal cancer detection.

Principal component analysis-based anatomical motion models for use in adaptive radiation therapy of head and neck cancer patients

NASA Astrophysics Data System (ADS)

Chetvertkov, Mikhail A.

Purpose: To develop standard and regularized principal component analysis (PCA) models of anatomical changes from daily cone beam CTs (CBCTs) of head and neck (H&N) patients, assess their potential use in adaptive radiation therapy (ART), and to extract quantitative information for treatment response assessment. Methods: Planning CT (pCT) images of H&N patients were artificially deformed to create "digital phantom" images, which modeled systematic anatomical changes during Radiation Therapy (RT). Artificial deformations closely mirrored patients' actual deformations, and were interpolated to generate 35 synthetic CBCTs, representing evolving anatomy over 35 fractions. Deformation vector fields (DVFs) were acquired between pCT and synthetic CBCTs (i.e., digital phantoms), and between pCT and clinical CBCTs. Patient-specific standard PCA (SPCA) and regularized PCA (RPCA) models were built from these synthetic and clinical DVF sets. Eigenvectors, or eigenDVFs (EDVFs), having the largest eigenvalues were hypothesized to capture the major anatomical deformations during treatment. Modeled anatomies were used to assess the dose deviations with respect to the planned dose distribution. Results: PCA models achieve variable results, depending on the size and location of anatomical change. Random changes prevent or degrade SPCA's ability to detect underlying systematic change. RPCA is able to detect smaller systematic changes against the background of random fraction-to-fraction changes, and is therefore more successful than SPCA at capturing systematic changes early in treatment. SPCA models were less successful at modeling systematic changes in clinical patient images, which contain a wider range of random motion than synthetic CBCTs, while the regularized approach was able to extract major modes of motion. For dose assessment it has been shown that the modeled dose distribution was different from the planned dose for the parotid glands due to their shrinkage and shift into the higher dose volumes during the radiotherapy course. Modeled DVHs still underestimated the effect of parotid shrinkage due to the large compression factor (CF) used to acquire DVFs. Conclusion: Leading EDVFs from both PCA approaches have the potential to capture systematic anatomical changes during H&N radiotherapy when systematic changes are large enough with respect to random fraction-to-fraction changes. In all cases the RPCA approach appears to be more reliable than SPCA at capturing systematic changes, enabling dosimetric consequences to be projected to the future treatment fractions based on trends established early in a treatment course, or, potentially, based on population models. This work showed that PCA has a potential in identifying the major mode of anatomical changes during the radiotherapy course and subsequent use of this information in future dose predictions is feasible. Use of smaller CF values for DVFs is preferred, otherwise anatomical motion will be underestimated.

[Role of tissue markers on diagnosis, prognosis and monitoring of prostate cancer].

PubMed

Mora, Miguel J

2015-04-01

Prostate specific antigen has maintained a key role as serum marker for prostate cancer (PCa) diagnosis and management since almost 25 years ago. However, suboptimal sensitivity and specificity, resulting in missed diagnoses, unnecessary prostate biopsies, as well as, detection of clinically indolent disease emphasize the need for new biomarkers. The purpose of this review is to examine the current status of tissue-based PCa markers, with special emphasis on recently marketed assays, and to evaluate their potential advantages to improve diagnosis, discriminate between indolent and aggressive disease, as well as, their role selecting therapeutic strategies. PubMed-based available literature provided primarily the core for this review. The more recent, larger size series, meta-analysis and frequently referred originals were prioritized. Advances in genomics, molecular technologies along with new immunohistochemical procedures have enabled the discovery and study of a growing number of PCA markers. In the past two years, these efforts have produced assays to more accurately detect and characterize the disease. We present the development and validation of tissue-based genetic tests, and discuss the challenge of incorporating the use of these new markers into clinical practice. Since prostate cancer is a heterogeneous disease, having a defined set of markers for early diagnosis, prognosis and follow-up, is clinically relevant. Some of these new markers can now be used to complement the conventional histopathologic diagnosis, as well as, to help already established parameters assessing prognosis.

Quantitative Ultrasound Using Texture Analysis of Myofascial Pain Syndrome in the Trapezius.

PubMed

Kumbhare, Dinesh A; Ahmed, Sara; Behr, Michael G; Noseworthy, Michael D

2018-01-01

Objective-The objective of this study is to assess the discriminative ability of textural analyses to assist in the differentiation of the myofascial trigger point (MTrP) region from normal regions of skeletal muscle. Also, to measure the ability to reliably differentiate between three clinically relevant groups: healthy asymptomatic, latent MTrPs, and active MTrP. Methods-18 and 19 patients were identified with having active and latent MTrPs in the trapezius muscle, respectively. We included 24 healthy volunteers. Images were obtained by research personnel, who were blinded with respect to the clinical status of the study participant. Histograms provided first-order parameters associated with image grayscale. Haralick, Galloway, and histogram-related features were used in texture analysis. Blob analysis was conducted on the regions of interest (ROIs). Principal component analysis (PCA) was performed followed by multivariate analysis of variance (MANOVA) to determine the statistical significance of the features. Results-92 texture features were analyzed for factorability using Bartlett's test of sphericity, which was significant. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.94. PCA demonstrated rotated eigenvalues of the first eight components (each comprised of multiple texture features) explained 94.92% of the cumulative variance in the ultrasound image characteristics. The 24 features identified by PCA were included in the MANOVA as dependent variables, and the presence of a latent or active MTrP or healthy muscle were independent variables. Conclusion-Texture analysis techniques can discriminate between the three clinically relevant groups.

Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter, retrospective analysis.

PubMed

Ghedini, Pietro; Bossert, I; Zanoni, L; Ceci, F; Graziani, T; Castellucci, P; Ambrosini, V; Massari, F; Nobili, E; Melotti, B; Musto, A; Zoboli, S; Antunovic, L; Kirienko, M; Chiti, A; Mosconi, C; Ardizzoni, A; Golfieri, R; Fanti, S; Nanni, C

2018-05-01

During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases. We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma). Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

Putative Prostate Cancer Risk SNP in an Androgen Receptor‐Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites

PubMed Central

Bu, Huajie; Narisu, Narisu; Schlick, Bettina; Rainer, Johannes; Manke, Thomas; Schäfer, Georg; Pasqualini, Lorenza; Chines, Peter; Schweiger, Michal R.; Fuchsberger, Christian

2015-01-01

ABSTRACT Genome‐wide association studies have identified genomic loci, whose single‐nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the mechanisms of most of these variants are largely unknown. We integrated chromatin‐immunoprecipitation‐coupled sequencing and microarray expression profiling in TMPRSS2‐ERG gene rearrangement positive DUCaP cells with the GWAS PCa risk SNPs catalog to identify disease susceptibility SNPs localized within functional androgen receptor‐binding sites (ARBSs). Among the 48 GWAS index risk SNPs and 3,917 linked SNPs, 80 were found located in ARBSs. Of these, rs11891426:T>G in an intron of the melanophilin gene (MLPH) was within a novel putative auxiliary AR‐binding motif, which is enriched in the neighborhood of canonical androgen‐responsive elements. T→G exchange attenuated the transcriptional activity of the ARBS in an AR reporter gene assay. The expression of MLPH in primary prostate tumors was significantly lower in those with the G compared with the T allele and correlated significantly with AR protein. Higher melanophilin level in prostate tissue of patients with a favorable PCa risk profile points out a tumor‐suppressive effect. These results unravel a hidden link between AR and a functional putative PCa risk SNP, whose allele alteration affects androgen regulation of its host gene MLPH. PMID:26411452

Genistein versus ICI 182, 780: an ally or enemy in metastatic progression of prostate cancer.

PubMed

Nakamura, Hisae; Wang, Yuwei; Xue, Hui; Romanish, Mark T; Mager, Dixie L; Helgason, Cheryl D; Wang, Yuzhuo

2013-12-01

Androgen signalling through the androgen receptor (AR) plays a critical role in prostate cancer (PCa) initiation and progression. Estrogen in synergy with androgen is essential for cell growth of the normal and malignant prostate. However, the exact role that estrogen and the estrogen receptor play in prostate carcinogenesis remains unclear. We have previously demonstrated the metastasis-promoting effect of an estrogen receptor beta (ERβ) agonist (genistein) in a patient-derived PCa xenograft model mimicking localized and metastatic disease. To test the hypothesis that the tumor-promoting activity of genistein was due to its estrogenic properties, we treated the xenograft-bearing mice with genistein and an anti-estrogen compound (ICI 182, 780) and compared the differential gene expression using microarrays. Using a second xenograft model which was derived from another patient, we showed that genistein promoted disease progression in vivo and ICI 182, 780 inhibited metastatic spread. The microarray analysis revealed that the metallothionein (MT) gene family was differentially expressed in tumors treated by these compounds. Using qRT-PCR, the differences in expression levels were validated in the metastatic and non-metastatic LTL313 PCa xenograft tumor lines, both of which were originally derived from the same PCa patient. Together our data provide evidence that genistein stimulates and ICI 182, 780 inhibits metastatic progression, suggesting that these effects may be mediated by ERβ signalling. © 2013 Wiley Periodicals, Inc.

Study of recognizing multiple persons' complicated hand gestures from the video sequence acquired by a moving camera

NASA Astrophysics Data System (ADS)

Dan, Luo; Ohya, Jun

2010-02-01

Recognizing hand gestures from the video sequence acquired by a dynamic camera could be a useful interface between humans and mobile robots. We develop a state based approach to extract and recognize hand gestures from moving camera images. We improved Human-Following Local Coordinate (HFLC) System, a very simple and stable method for extracting hand motion trajectories, which is obtained from the located human face, body part and hand blob changing factor. Condensation algorithm and PCA-based algorithm was performed to recognize extracted hand trajectories. In last research, this Condensation Algorithm based method only applied for one person's hand gestures. In this paper, we propose a principal component analysis (PCA) based approach to improve the recognition accuracy. For further improvement, temporal changes in the observed hand area changing factor are utilized as new image features to be stored in the database after being analyzed by PCA. Every hand gesture trajectory in the database is classified into either one hand gesture categories, two hand gesture categories, or temporal changes in hand blob changes. We demonstrate the effectiveness of the proposed method by conducting experiments on 45 kinds of sign language based Japanese and American Sign Language gestures obtained from 5 people. Our experimental recognition results show better performance is obtained by PCA based approach than the Condensation algorithm based method.

Cell cycle-coupled expansion of AR activity promotes cancer progression.

PubMed

McNair, C; Urbanucci, A; Comstock, C E S; Augello, M A; Goodwin, J F; Launchbury, R; Zhao, S G; Schiewer, M J; Ertel, A; Karnes, J; Davicioni, E; Wang, L; Wang, Q; Mills, I G; Feng, F Y; Li, W; Carroll, J S; Knudsen, K E

2017-03-23

The androgen receptor (AR) is required for prostate cancer (PCa) survival and progression, and ablation of AR activity is the first line of therapeutic intervention for disseminated disease. While initially effective, recurrent tumors ultimately arise for which there is no durable cure. Despite the dependence of PCa on AR activity throughout the course of disease, delineation of the AR-dependent transcriptional network that governs disease progression remains elusive, and the function of AR in mitotically active cells is not well understood. Analyzing AR activity as a function of cell cycle revealed an unexpected and highly expanded repertoire of AR-regulated gene networks in actively cycling cells. New AR functions segregated into two major clusters: those that are specific to cycling cells and retained throughout the mitotic cell cycle ('Cell Cycle Common'), versus those that were specifically enriched in a subset of cell cycle phases ('Phase Restricted'). Further analyses identified previously unrecognized AR functions in major pathways associated with clinical PCa progression. Illustrating the impact of these unmasked AR-driven pathways, dihydroceramide desaturase 1 was identified as an AR-regulated gene in mitotically active cells that promoted pro-metastatic phenotypes, and in advanced PCa proved to be highly associated with development of metastases, recurrence after therapeutic intervention and reduced overall survival. Taken together, these findings delineate AR function in mitotically active tumor cells, thus providing critical insight into the molecular basis by which AR promotes development of lethal PCa and nominate new avenues for therapeutic intervention.

Cohort Profile: the National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0.

PubMed

Van Hemelrijck, Mieke; Wigertz, Annette; Sandin, Fredrik; Garmo, Hans; Hellström, Karin; Fransson, Per; Widmark, Anders; Lambe, Mats; Adolfsson, Jan; Varenhorst, Eberhard; Johansson, Jan-Erik; Stattin, Pär

2013-08-01

In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case-control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.

Smoking increased the risk of prostate cancer with grade group ≥ 4 and intraductal carcinoma in a prospective biopsy cohort.

PubMed

Tang, Bo; Han, Cheng-Tao; Gan, Hua-Lei; Zhang, Gui-Ming; Zhang, Cui-Zhu; Yang, Wei-Yi; Shen, Ying; Zhu, Yao; Ye, Ding-Wei

2017-06-01

To investigate the association between smoking and different prostate cancer (PCa) pathological subtypes incidence in Chinese men. We prospectively included 1795 patients who underwent prostate biopsies in one tertiary center between March 2013 and April 2016. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the association between cigarette smoking and PCa incidence. A total of 737 men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade group ≥ 4 as accepted by the 2014 ISUP) and intraductal carcinoma of the prostate (IDC-P), respectively. Current smokers had a significantly higher risk of HGPCa than never smokers (OR = 1.89, 95%CI: 1.44-2.48). No such association was observed for low-grade disease and cigarette smoking (OR = 0.84, 95%CI: 0.61-1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher risk of HGPCa, compared with men who had smoked fewer than 30 years (OR = 1.50, 95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never smokers (OR = 2.29, 95%CI: 1.14-4.59). Among men in this Chinese biopsy cohort, current smoking was associated with highly malignant PCa incidence, such as HGPCa and IDC-P. The duration of smoking may be associated with HGPCa. © 2017 Wiley Periodicals, Inc.

Kernel-PCA data integration with enhanced interpretability

PubMed Central

2014-01-01

Background Nowadays, combining the different sources of information to improve the biological knowledge available is a challenge in bioinformatics. One of the most powerful methods for integrating heterogeneous data types are kernel-based methods. Kernel-based data integration approaches consist of two basic steps: firstly the right kernel is chosen for each data set; secondly the kernels from the different data sources are combined to give a complete representation of the available data for a given statistical task. Results We analyze the integration of data from several sources of information using kernel PCA, from the point of view of reducing dimensionality. Moreover, we improve the interpretability of kernel PCA by adding to the plot the representation of the input variables that belong to any dataset. In particular, for each input variable or linear combination of input variables, we can represent the direction of maximum growth locally, which allows us to identify those samples with higher/lower values of the variables analyzed. Conclusions The integration of different datasets and the simultaneous representation of samples and variables together give us a better understanding of biological knowledge. PMID:25032747

Standardized processing of MALDI imaging raw data for enhancement of weak analyte signals in mouse models of gastric cancer and Alzheimer's disease.

PubMed

Schwartz, Matthias; Meyer, Björn; Wirnitzer, Bernhard; Hopf, Carsten

2015-03-01

Conventional mass spectrometry image preprocessing methods used for denoising, such as the Savitzky-Golay smoothing or discrete wavelet transformation, typically do not only remove noise but also weak signals. Recently, memory-efficient principal component analysis (PCA) in conjunction with random projections (RP) has been proposed for reversible compression and analysis of large mass spectrometry imaging datasets. It considers single-pixel spectra in their local context and consequently offers the prospect of using information from the spectra of adjacent pixels for denoising or signal enhancement. However, little systematic analysis of key RP-PCA parameters has been reported so far, and the utility and validity of this method for context-dependent enhancement of known medically or pharmacologically relevant weak analyte signals in linear-mode matrix-assisted laser desorption/ionization (MALDI) mass spectra has not been explored yet. Here, we investigate MALDI imaging datasets from mouse models of Alzheimer's disease and gastric cancer to systematically assess the importance of selecting the right number of random projections k and of principal components (PCs) L for reconstructing reproducibly denoised images after compression. We provide detailed quantitative data for comparison of RP-PCA-denoising with the Savitzky-Golay and wavelet-based denoising in these mouse models as a resource for the mass spectrometry imaging community. Most importantly, we demonstrate that RP-PCA preprocessing can enhance signals of low-intensity amyloid-β peptide isoforms such as Aβ1-26 even in sparsely distributed Alzheimer's β-amyloid plaques and that it enables enhanced imaging of multiply acetylated histone H4 isoforms in response to pharmacological histone deacetylase inhibition in vivo. We conclude that RP-PCA denoising may be a useful preprocessing step in biomarker discovery workflows.

Local Ancestry Inference in a Large US-Based Hispanic/Latino Study: Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

PubMed Central

Browning, Sharon R.; Grinde, Kelsey; Plantinga, Anna; Gogarten, Stephanie M.; Stilp, Adrienne M.; Kaplan, Robert C.; Avilés-Santa, M. Larissa; Browning, Brian L.; Laurie, Cathy C.

2016-01-01

We estimated local ancestry on the autosomes and X chromosome in a large US-based study of 12,793 Hispanic/Latino individuals using the RFMix method, and we compared different reference panels and approaches to local ancestry estimation on the X chromosome by means of Mendelian inconsistency rates as a proxy for accuracy. We developed a novel and straightforward approach to performing ancestry-specific PCA after finding artifactual behavior in the results from an existing approach. Using the ancestry-specific PCA, we found significant population structure within African, European, and Amerindian ancestries in the Hispanic/Latino individuals in our study. In the African ancestral component of the admixed individuals, individuals whose grandparents were from Central America clustered separately from individuals whose grandparents were from the Caribbean, and also from reference Yoruba and Mandenka West African individuals. In the European component, individuals whose grandparents were from Puerto Rico diverged partially from other background groups. In the Amerindian ancestral component, individuals clustered into multiple different groups depending on the grandparental country of origin. Therefore, local ancestry estimation provides further insight into the complex genetic structure of US Hispanic/Latino populations, which must be properly accounted for in genotype-phenotype association studies. It also provides a basis for admixture mapping and ancestry-specific allele frequency estimation, which are useful in the identification of risk factors for disease. PMID:27172203