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Sample records for aggressive prostate cancers

  1. Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer?

    MedlinePlus

    ... html Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer? Study also suggests that cholesterol-lowering ... fatty beef and cheese was linked with more aggressive prostate cancer, the researchers found. A diet high ...

  2. Low Vitamin D Levels May Signal More Aggressive Prostate Cancer

    MedlinePlus

    ... html Low Vitamin D Levels May Signal More Aggressive Prostate Cancer But men should not expect supplements ... 2016 (HealthDay News) -- Prostate cancer may be more aggressive in men who are deficient in vitamin D, ...

  3. Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer?

    MedlinePlus

    ... Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer? Study also suggests that cholesterol-lowering drugs may ... meats and cheese -- may affect how quickly their prostate cancer progresses, a new study suggests. "We show that ...

  4. Characterization of aggressive prostate cancer using ultrasound RF time series

    NASA Astrophysics Data System (ADS)

    Khojaste, Amir; Imani, Farhad; Moradi, Mehdi; Berman, David; Siemens, D. Robert; Sauerberi, Eric E.; Boag, Alexander H.; Abolmaesumi, Purang; Mousavi, Parvin

    2015-03-01

    Prostate cancer is the most prevalently diagnosed and the second cause of cancer-related death in North American men. Several approaches have been proposed to augment detection of prostate cancer using different imaging modalities. Due to advantages of ultrasound imaging, these approaches have been the subject of several recent studies. This paper presents the results of a feasibility study on differentiating between lower and higher grade prostate cancer using ultrasound RF time series data. We also propose new spectral features of RF time series to highlight aggressive prostate cancer in small ROIs of size 1 mm × 1 mm in a cohort of 19 ex vivo specimens of human prostate tissue. In leave-one-patient-out cross-validation strategy, an area under accumulated ROC curve of 0.8 has been achieved with overall sensitivity and specificity of 81% and 80%, respectively. The current method shows promising results on differentiating between lower and higher grade of prostate cancer using ultrasound RF time series.

  5. Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods.

    PubMed

    Moyad, Mark A

    2015-01-01

    Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Risk factors for prostate cancer have primarily mirrored risk proven risk factors for CVD, especially aggressive disease. Obesity, dyslipidemia, glucose intolerance, metabolic syndrome, unhealthy dietary habits or caloric excess, lack of physical activity, and inflammation are just some of these shared risk factors. The evidence also suggests proven CVD preventive measures are identical to prostate cancer preventive measures, especially in regard to aggressive disease. Thus, apart from lifestyle measures that can encourage optimal heart and prostate health there are potentially several dietary supplements that need to be avoided in healthy men because they may also increase the risk of prostate cancer. However, there are also several low-cost, generic, safe in the appropriate individuals, and naturally derived agents that could reduce prostate cancer risk, and these can be discussed and remembered utilizing the acronym S.A.M. (statins, aspirin, and/or metformin). PMID:26112486

  6. PBX3 is a putative biomarker of aggressive prostate cancer.

    PubMed

    Ramberg, Håkon; Grytli, Helene Hartvedt; Nygård, Ståle; Wang, Wanzhong; Ögren, Olov; Zhao, Sen; Løvf, Marthe; Katz, Betina; Skotheim, Rolf I; Bjartell, Anders; Eri, Lars Magne; Berge, Viktor; Svindland, Aud; Taskén, Kristin Austlid

    2016-10-15

    There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis. Furthermore, the expression of PBX3 transcript variants was analyzed by RT-PCR, NanoString Technologies®, and by analyzing RNA sequence data. The potential of PBX3 to predict prognosis, either at mRNA or protein level, was studied in four independent cohorts. PBX3 was mainly expressed in the nucleus of normal prostate basal cells, while it showed cytosolic expression in prostatic intraepithelial neoplasia and cancer cells. We detected four PBX3 transcript variants in prostate tissue. Competing risk regression analysis revealed that high PBX3 expression was associated with slower progression to castration resistant prostate cancer (sub-hazard ratio (SHR) 0.18, 95% CI: 0.081-0.42, p values < 0.001). PBX3 expression had a high predictive accuracy (area under the curve (AUC) = 0.82) when combined with Gleason score and age. Patients undergoing radical prostatectomy, with high levels of PBX3 mRNA, had improved prostate cancer specific survival compared to patients expressing low levels (SHR 0.21, 95% CI: 0.46-0.93, p values < 0.001, and AUC = 0.75). Our findings strongly indicate that PBX3 has potential as a biomarker, both as part of a larger gene panel and as an immunohistochemical marker, for aggressive prostate cancer. PMID:27273830

  7. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    SciTech Connect

    Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul; Taussky, Daniel

    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 prostate 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.

  8. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

    PubMed Central

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

    2016-01-01

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

  9. Apolipoprotein E gene polymorphism influences aggressive behavior in prostate cancer cells by deregulating cholesterol homeostasis

    PubMed Central

    IFERE, GODWIN O.; DESMOND, RENEE; DEMARK-WAHNEFRIED, WENDY; NAGY, TIM R.

    High circulating cholesterol and its deregulated homeostasis may facilitate prostate cancer progression. Genetic polymorphism in Apolipoprotein (Apo) E, a key cholesterol regulatory protein may effect changes in systemic cholesterol levels. In this investigation, we determined whether variants of the Apo E gene can trigger defective intracellular cholesterol efflux, which could promote aggressive prostate cancer. ApoE genotypes of weakly (non-aggressive), moderate and highly tumorigenic (aggressive) prostate cancer cell lines were characterized, and we explored whether the ApoE variants were associated with tumor aggressiveness generated by intra cellular cholesterol imbalance, using the expression of caveolin-1 (cav-1), a pro-malignancy surrogate of cholesterol overload. Restriction isotyping of ApoE isoforms revealed that the non-aggressive cell lines carried ApoE ε3/ε3 or ε3/ε4 alleles, while the aggressive cell lines carried the Apoε2/ε4 alleles. Our data suggest a contrast between the non-aggressive and the aggressive prostate cancer cell lines in the pattern of cholesterol efflux and cav-1 expression. Our exploratory results suggest a relationship between prostate aggressiveness, ApoE isoforms and cholesterol imbalance. Further investigation of this relationship may elucidate the molecular basis for considering cholesterol as a risk factor of aggressive prostate tumors, and underscore the potential of the dysfunctional ApoE2/E4 isoform as a biomarker of aggressive disease. PMID:23934233

  10. Prostate Cancer Prevention

    MedlinePlus

    ... finasteride who did have prostate cancer had more aggressive tumors . The number of deaths from prostate cancer ... men that did not. The number of less aggressive prostate cancers was lower, but the number of ...

  11. Intake of grains and dietary fiber and prostate cancer aggressiveness by race.

    PubMed

    Tabung, Fred; Steck, Susan E; Su, L Joseph; Mohler, James L; Fontham, Elizabeth T H; Bensen, Jeannette T; Hebert, James R; Zhang, Hongmei; Arab, Lenore

    2012-01-01

    Purpose. To examine the associations among intake of refined grains, whole grains and dietary fiber and aggressiveness of prostate cancer in African Americans (AA, n = 930) and European Americans (EA, n = 993) in a population-based, case-only study (The North Carolina-Louisiana Prostate Cancer Project, PCaP). Methods. Prostate cancer aggressiveness was categorized as high, intermediate or low based on Gleason grade, PSA level and clinical stage. Dietary intake was assessed utilizing the NCI Diet History Questionnaire. Logistic regression (comparing high to intermediate/low aggressive cancers) and polytomous regression with adjustment for potential confounders were used to determine odds of high prostate cancer aggressiveness with intake of refined grains, whole grains and dietary fiber from all sources. Results. An inverse association with aggressive prostate cancer was observed in the 2nd and 3rd tertiles of total fiber intake (OR = 0.70; 95% CI, 0.50-0.97 and OR = 0.61; 95% CI, 0.40-0.93, resp.) as compared to the lowest tertile of intake. In the race-stratified analyses, inverse associations were observed in the 3rd tertile of total fiber intake for EA (OR = 0.44; 95% CI, 0.23-0.87) and the 2nd tertile of intake for AA (OR = 0.57; 95% CI, 0.35-0.95). Conclusions. Dietary fiber intake was inversely associated with aggressive prostate cancer among both AA and EA men. PMID:23213538

  12. Intake of Grains and Dietary Fiber and Prostate Cancer Aggressiveness by Race

    PubMed Central

    Tabung, Fred; Steck, Susan E.; Su, L. Joseph; Mohler, James L.; Fontham, Elizabeth T. H.; Bensen, Jeannette T.; Hebert, James R.; Zhang, Hongmei; Arab, Lenore

    2012-01-01

    Purpose. To examine the associations among intake of refined grains, whole grains and dietary fiber and aggressiveness of prostate cancer in African Americans (AA, n = 930) and European Americans (EA, n = 993) in a population-based, case-only study (The North Carolina-Louisiana Prostate Cancer Project, PCaP). Methods. Prostate cancer aggressiveness was categorized as high, intermediate or low based on Gleason grade, PSA level and clinical stage. Dietary intake was assessed utilizing the NCI Diet History Questionnaire. Logistic regression (comparing high to intermediate/low aggressive cancers) and polytomous regression with adjustment for potential confounders were used to determine odds of high prostate cancer aggressiveness with intake of refined grains, whole grains and dietary fiber from all sources. Results. An inverse association with aggressive prostate cancer was observed in the 2nd and 3rd tertiles of total fiber intake (OR = 0.70; 95% CI, 0.50–0.97 and OR = 0.61; 95% CI, 0.40–0.93, resp.) as compared to the lowest tertile of intake. In the race-stratified analyses, inverse associations were observed in the 3rd tertile of total fiber intake for EA (OR = 0.44; 95% CI, 0.23–0.87) and the 2nd tertile of intake for AA (OR = 0.57; 95% CI, 0.35–0.95). Conclusions. Dietary fiber intake was inversely associated with aggressive prostate cancer among both AA and EA men. PMID:23213538

  13. Vasectomy: potential links to an increased risk of aggressive prostate cancer?

    PubMed

    Gaines, Alexis R; Vidal, Adriana C; Freedland, Stephen J

    2015-01-01

    Several studies have found associations between aggressive prostate cancer (PC) and having a vasectomy. However, findings from two very recent meta-analyses have found that this is not the case. Therefore, the data are mixed. Herein, we detail the controversy between vasectomy and PC risk, particularly aggressive PC, by shedding some light on the molecular pathways, potential risk factors and suggested links for those considering vasectomy and medical professionals who perform it. We conclude by supporting the American Urological Association's position that there is no need to discuss potential prostate cancer risks with patients considering vasectomy given reasonably strong data finding no link between vasectomy and prostate cancer risk. PMID:26402245

  14. Single-nucleotide polymorphisms within the antioxidant defence system and associations with aggressive prostate cancer

    PubMed Central

    Abe, Miyako; Xie, Wanling; Regan, Meredith M.; King, Irena B.; Stampfer, Meir J.; Kantoff, Philip W.; Oh, William K.; Chan, June M.

    2010-01-01

    Objective To study the effects of oxidative stress on prostate cancer development as the exact biological mechanisms behind the relationship remain uncertain. We previously reported a statistically significant interaction between circulating selenium levels, variants in the superoxide dismutase 2 gene (SOD2; rs4880), and risk of developing prostate cancer and presenting with aggressive prostate cancer. Patients and methods We genotyped men with localized/regional prostate cancer for 26 loci across eight genes that are central to cellular antioxidant defence: glutathione peroxidase (GPX1, GPX4), peroxisome proliferator-activated receptor γ coactivator (PPARGC1A, PPARGC1B), SOD1, SOD2, and SOD3, and ‘X-ray repair complementing defective repair in Chinese hamster cell 1’ (XRCC1). Among 489 men, we examined the relationships between genotypes, circulating selenium levels, and risk of presenting with aggressive prostate cancer at diagnosis, as defined by stage, grade and prostate-specific antigen (PSA) level (213 aggressive cases). Results Two variants in SOD2 were significantly associated with the risk of aggressive prostate cancer (rs17884057, odds ratio 0.83, 95% confidence interval 0.70–0.99; and rs4816407, 1.27, 1.02–1.57); men with A alleles at rs2842958 in SOD2 had lower plasma selenium levels (median 116 vs 121.8 μg/L, P = 0.03); and the association between plasma selenium levels and risk of aggressive prostate cancer was modified by SOD1 (rs10432782) and SOD2 (rs2758330). Conclusion While this study was cross-sectional and these associations might be due to chance, further research is warranted on the potential important role of antioxidant defence in prostate cancer. PMID:20477822

  15. Risk of Total and Aggressive Prostate Cancer and Pesticide Use in the Agricultural Health Study

    PubMed Central

    Koutros, Stella; Beane Freeman, Laura E.; Lubin, Jay H.; Heltshe, Sonya L.; Andreotti, Gabriella; Barry, Kathryn Hughes; DellaValle, Curt T.; Hoppin, Jane A.; Sandler, Dale P.; Lynch, Charles F.; Blair, Aaron; Alavanja, Michael C. R.

    2013-01-01

    Because pesticides may operate through different mechanisms, the authors studied the risk of prostate cancer associated with specific pesticides in the Agricultural Health Study (1993–2007). With 1,962 incident cases, including 919 aggressive prostate cancers among 54,412 applicators, this is the largest study to date. Rate ratios and 95% confidence intervals were calculated by using Poisson regression to evaluate lifetime use of 48 pesticides and prostate cancer incidence. Three organophosphate insecticides were significantly associated with aggressive prostate cancer: fonofos (rate ratio (RR) for the highest quartile of exposure (Q4) vs. nonexposed = 1.63, 95% confidence interval (CI): 1.22, 2.17; Ptrend < 0.001); malathion (RR for Q4 vs. nonexposed = 1.43, 95% CI: 1.08, 1.88; Ptrend = 0.04); and terbufos (RR for Q4 vs. nonexposed = 1.29, 95% CI: 1.02, 1.64; Ptrend = 0.03). The organochlorine insecticide aldrin was also associated with increased risk of aggressive prostate cancer (RR for Q4 vs. nonexposed = 1.49, 95% CI: 1.03, 2.18; Ptrend = 0.02). This analysis has overcome several limitations of previous studies with the inclusion of a large number of cases with relevant exposure and detailed information on use of specific pesticides at 2 points in time. Furthermore, this is the first time specific pesticides are implicated as risk factors for aggressive prostate cancer. PMID:23171882

  16. Nuclear Kaiso Indicates Aggressive Prostate Cancers and Promotes Migration and Invasiveness of Prostate Cancer Cells

    PubMed Central

    Jones, Jacqueline; Wang, Honghe; Zhou, Jianjun; Hardy, Shana; Turner, Timothy; Austin, David; He, Qinghua; Wells, Alan; Grizzle, William E.; Yates, Clayton

    2013-01-01

    Kaiso, a p120 catenin-binding protein, is expressed in the cytoplasmic and nuclear compartments of cells; however, the biological consequences and clinical implications of a shift between these compartments have yet to be established. Herein, we report an enrichment of nuclear Kaiso expression in cells of primary and metastatic prostate tumors relative to the normal prostate epithelium. Nuclear expression of Kaiso correlates with Gleason score (P < 0.001) and tumor grade (P < 0.001). There is higher nuclear expression of Kaiso in primary tumor/normal matched samples and in primary tumors from African American men (P < 0.0001). We further found that epidermal growth factor (EGF) receptor up-regulates Kaiso at the RNA and protein levels in prostate cancer cell lines, but more interestingly causes a shift of cytoplasmic Kaiso to the nucleus that is reversed by the EGF receptor–specific kinase inhibitor, PD153035. In both DU-145 and PC-3 prostate cancer cell lines, Kaiso inhibition (short hairpin RNA-Kaiso) decreased cell migration and invasion even in the presence of EGF. Further, Kaiso directly binds to the E-cadherin promoter, and inhibition of Kaiso in PC-3 cells results in increased E-cadherin expression, as well as re-establishment of cell–cell contacts. In addition, Kaiso-depleted cells show more epithelial morphology and a reversal of the mesenchymal markers N-cadherin and fibronectin. Our findings establish a defined oncogenic role of Kaiso in promoting the progression of prostate cancer. PMID:22974583

  17. Paper Highlight: Biomarker Identified for Predicting Early Prostate Cancer Aggressiveness — Site

    Cancer.gov

    A team led by Cory Abate-Shen, Michael Shen, and Andrea Califano at Columbia University found that measuring the expression levels of three genes associated with aging can be used to predict the aggressiveness of seemingly low-risk prostate cancer.

  18. Spermine and citrate as metabolic biomarkers for assessing prostate cancer aggressiveness.

    PubMed

    Giskeødegård, Guro F; Bertilsson, Helena; Selnæs, Kirsten M; Wright, Alan J; Bathen, Tone F; Viset, Trond; Halgunset, Jostein; Angelsen, Anders; Gribbestad, Ingrid S; Tessem, May-Britt

    2013-01-01

    Separating indolent from aggressive prostate cancer is an important clinical challenge for identifying patients eligible for active surveillance, thereby reducing the risk of overtreatment. The purpose of this study was to assess prostate cancer aggressiveness by metabolic profiling of prostatectomy tissue and to identify specific metabolites as biomarkers for aggressiveness. Prostate tissue samples (n = 158, 48 patients) with a high cancer content (mean: 61.8%) were obtained using a new harvesting method, and metabolic profiles of samples representing different Gleason scores (GS) were acquired by high resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS). Multivariate analysis (PLS, PLS-DA) and absolute quantification (LCModel) were used to examine the ability to predict cancer aggressiveness by comparing low grade (GS = 6, n = 30) and high grade (GS≥7, n = 81) cancer with normal adjacent tissue (n = 47). High grade cancer tissue was distinguished from low grade cancer tissue by decreased concentrations of spermine (p = 0.0044) and citrate (p = 7.73·10(-4)), and an increase in the clinically applied (total choline+creatine+polyamines)/citrate (CCP/C) ratio (p = 2.17·10(-4)). The metabolic profiles were significantly correlated to the GS obtained from each tissue sample (r = 0.71), and cancer tissue could be distinguished from normal tissue with sensitivity 86.9% and specificity 85.2%. Overall, our findings show that metabolic profiling can separate aggressive from indolent prostate cancer. This holds promise for the benefit of applying in vivo magnetic resonance spectroscopy (MRS) within clinical MR imaging investigations, and HR-MAS analysis of transrectal ultrasound-guided biopsies has a potential as an additional diagnostic tool. PMID:23626811

  19. A Systems Genetics Approach Identifies CXCL14, ITGAX, and LPCAT2 as Novel Aggressive Prostate Cancer Susceptibility Genes

    PubMed Central

    Andreas, Jonathan; Patel, Shashank J.; Zhang, Suiyuan; Chines, Peter; Elkahloun, Abdel; Chandrasekharappa, Settara; Gutkind, J. Silvio; Molinolo, Alfredo A.; Crawford, Nigel P. S.

    2014-01-01

    Although prostate cancer typically runs an indolent course, a subset of men develop aggressive, fatal forms of this disease. We hypothesize that germline variation modulates susceptibility to aggressive prostate cancer. The goal of this work is to identify susceptibility genes using the C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP) mouse model of neuroendocrine prostate cancer. Quantitative trait locus (QTL) mapping was performed in transgene-positive (TRAMPxNOD/ShiLtJ) F2 intercross males (n = 228), which facilitated identification of 11 loci associated with aggressive disease development. Microarray data derived from 126 (TRAMPxNOD/ShiLtJ) F2 primary tumors were used to prioritize candidate genes within QTLs, with candidate genes deemed as being high priority when possessing both high levels of expression-trait correlation and a proximal expression QTL. This process enabled the identification of 35 aggressive prostate tumorigenesis candidate genes. The role of these genes in aggressive forms of human prostate cancer was investigated using two concurrent approaches. First, logistic regression analysis in two human prostate gene expression datasets revealed that expression levels of five genes (CXCL14, ITGAX, LPCAT2, RNASEH2A, and ZNF322) were positively correlated with aggressive prostate cancer and two genes (CCL19 and HIST1H1A) were protective for aggressive prostate cancer. Higher than average levels of expression of the five genes that were positively correlated with aggressive disease were consistently associated with patient outcome in both human prostate cancer tumor gene expression datasets. Second, three of these five genes (CXCL14, ITGAX, and LPCAT2) harbored polymorphisms associated with aggressive disease development in a human GWAS cohort consisting of 1,172 prostate cancer patients. This study is the first example of using a systems genetics approach to successfully identify novel susceptibility genes for aggressive prostate cancer. Such approaches will

  20. Coordinate loss of MAP3K7 and CHD1 promotes aggressive prostate cancer.

    PubMed

    Rodrigues, Lindsey Ulkus; Rider, Leah; Nieto, Cera; Romero, Lina; Karimpour-Fard, Anis; Loda, Massimo; Lucia, M Scott; Wu, Min; Shi, Lihong; Cimic, Adela; Sirintrapun, S Joseph; Nolley, Rosalie; Pac, Colton; Chen, Haitao; Peehl, Donna M; Xu, Jianfeng; Liu, Wennuan; Costello, James C; Cramer, Scott D

    2015-03-15

    Prostate cancer subtypes are poorly defined and functional validation of drivers of ETS rearrangement-negative prostate cancer has not been conducted. Here, we identified an ETS(-) subtype of aggressive prostate cancer (ERG(-)MAP3K7(del)CHD1(del)) and used a novel developmental model and a cell line xenograft model to show that cosuppression of MAP3K7 and CHD1 expression promotes aggressive disease. Analyses of publicly available prostate cancer datasets revealed that MAP3K7 and CHD1 were significantly codeleted in 10% to 20% of localized tumors and combined loss correlated with poor disease-free survival. To evaluate the functional impact of dual MAP3K7-CHD1 loss, we suppressed Map3k7 and/or Chd1 expression in mouse prostate epithelial progenitor/stem cells (PrP/SC) and performed tissue recombination experiments in vivo. Dual shMap3k7-shChd1 PrP/SC recombinants displayed massive glandular atypia with regions of prostatic intraepithelial neoplasia and carcinoma apparent. Combined Map3k7-Chd1 suppression greatly disrupted normal prostatic lineage differentiation; dual recombinants displayed significant androgen receptor loss, increased neuroendocrine differentiation, and increased neural differentiation. Clinical samples with dual MAP3K7-CHD1 loss also displayed neuroendocrine and neural characteristics. In addition, dual Map3k7-Chd1 suppression promoted E-cadherin loss and mucin production in recombinants. MAP3K7 and CHD1 protein loss also correlated with Gleason grade and E-cadherin loss in clinical samples. To further validate the phenotype observed in the PrP/SC model, we suppressed MAP3K7 and/or CHD1 expression in LNCaP prostate cancer cells. Dual shMAP3K7-shCHD1 LNCaP xenografts displayed increased tumor growth and decreased survival compared with shControl, shMAP3K7, and shCHD1 xenografts. Collectively, these data identify coordinate loss of MAP3K7 and CHD1 as a unique driver of aggressive prostate cancer development. PMID:25770290

  1. Relationship Between Male Pattern Baldness and the Risk of Aggressive Prostate Cancer: An Analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    PubMed Central

    Zhou, Cindy Ke; Pfeiffer, Ruth M.; Cleary, Sean D.; Hoffman, Heather J.; Levine, Paul H.; Chu, Lisa W.; Hsing, Ann W.; Cook, Michael B.

    2015-01-01

    Purpose Male pattern baldness and prostate cancer appear to share common pathophysiologic mechanisms. However, results from previous studies that assess their relationship have been inconsistent. Therefore, we investigated the association of male pattern baldness at age 45 years with risks of overall and subtypes of prostate cancer in a large, prospective cohort—the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Methods We included 39,070 men from the usual care and screening arms of the trial cohort who had no cancer diagnosis (excluding nonmelanoma skin cancer) at the start of follow-up and recalled their hair-loss patterns at age 45 years. Hazard ratios (HRs) and 95% CIs were estimated by using Cox proportional hazards regression models with age as the time metric. Results During follow-up (median, 2.78 years), 1,138 incident prostate cancer cases were diagnosed, 571 of which were aggressive (biopsy Gleason score ≥ 7, and/or clinical stage III or greater, and/or fatal). Compared with no baldness, frontal plus moderate vertex baldness at age 45 years was not significantly associated with overall (HR, 1.19; 95% CI, 0.98 to 1.45) or nonaggressive (HR, 0.97; 95% CI, 0.72 to 1.30) prostate cancer risk but was significantly associated with increased risk of aggressive prostate cancer (HR, 1.39; 95% CI, 1.07 to 1.80). Adjustment for covariates did not substantially alter these estimates. Other classes of baldness were not significantly associated with overall or subtypes of prostate cancer. Conclusion Our analysis indicates that frontal plus moderate vertex baldness at age 45 years is associated with an increased risk of aggressive prostate cancer and supports the possibility of common pathophysiologic mechanisms. PMID:25225425

  2. The tumour hypoxia marker pimonidazole reflects a transcriptional programme associated with aggressive prostate cancer

    PubMed Central

    Ragnum, H B; Vlatkovic, L; Lie, A K; Axcrona, K; Julin, C H; Frikstad, K M; Hole, K H; Seierstad, T; Lyng, H

    2015-01-01

    Background: The hypoxia marker pimonidazole is a candidate biomarker of cancer aggressiveness. We investigated the transcriptional programme associated with pimonidazole staining in prostate cancer. Methods: Index tumour biopsies were taken by image guidance from an investigation cohort of 52 patients, where 43 patients received pimonidazole before prostatectomy. Biopsy location within the index tumour was verified for 46 (88%) patients, who were included for gene expression profiling and immunohistochemistry. Two independent cohorts of 59 and 281 patients were used for validation. Results: Expression of genes in proliferation, DNA repair and hypoxia response was a major part of the transcriptional programme associated with pimonidazole staining. A signature of 32 essential genes was constructed and showed positive correlation to Ki67 staining, confirming the increased proliferation in hypoxic tumours as suggested from the gene data. Positive correlations were also found to tumour stage and lymph node status, but not to blood prostate-specific antigen level, consistent with the findings for pimonidazole staining. The association with aggressiveness was confirmed in validation cohorts, where the signature correlated with Gleason score and had independent prognostic impact, respectively. Conclusions: Pimonidazole staining reflects an aggressive hypoxic phenotype of prostate cancer characterised by upregulation of proliferation, DNA repair and hypoxia response genes. PMID:25461803

  3. Prostate cancer staging

    MedlinePlus

    ... test. A faster increase could show a more aggressive tumor. A prostate biopsy is done in your ... suggest the cancer is slow growing and not aggressive. Higher numbers indicate a faster growing cancer that ...

  4. Prostate Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Prostate Cancer What is Prostate Cancer? How Tumors Form The body is made up ... the Escape (Esc) button on your keyboard.) How Prostate Cancer Occurs Prostate cancer occurs when a tumor forms ...

  5. Impact of consumption of vegetable, fruit, grain, and high glycemic index foods on aggressive prostate cancer risk

    PubMed Central

    Hardin, Jill; Cheng, Iona; Witte, John S.

    2011-01-01

    Prostate cancer is a common but complex disease, and distinguishing modifiable risk factors such as diet for more aggressive disease is extremely important. Previous work has detected intriguing associations between vegetable, fruit, and grains and more aggressive prostate cancer, although these remain somewhat unclear. Here we further investigate such potential relationships with a case-control study of 982 men (470 more aggressive prostate cancer cases and 512 control subjects). Comparing the highest to lowest quartiles of intake, we found that increasing intakes of leafy vegetables were inversely associated with risk of aggressive prostate cancer (adjusted odds ratio (OR) =0.66, 95% CI: 0.46, 0.96, P-trend=0.02), as was higher consumption of high carotenoid vegetables (OR=0.71, 95% CI: 0.48, 1.04; P-trend=0.04). Conversely, increased consumption of high glycemic index foods were positively associated with risk of aggressive disease (OR=1.64, 95% CI: 1.05, 2.57; P-trend=0.02). These results were driven by a number of specific foods within the food groups. Our findings support the hypothesis that diets high in vegetables and low in high glycemic index foods decrease risk of aggressive prostate cancer. PMID:21774611

  6. Mitochondrial oncobioenergetic index: A potential biomarker to predict progression from indolent to aggressive prostate cancer

    PubMed Central

    Vayalil, Praveen K.; Landar, Aimee

    2015-01-01

    Mitochondrial function is influenced by alterations in oncogenes and tumor suppressor genes and changes in the microenvironment occurring during tumorigenesis. Therefore, we hypothesized that mitochondrial function will be stably and dynamically altered at each stage of the prostate tumor development. We tested this hypothesis in RWPE-1 cells and its tumorigenic clones with progressive malignant characteristics (RWPE-1 < WPE-NA22 < WPE-NB14 < WPE-NB11 < WPE-NB26) using high-throughput respirometry. Our studies demonstrate that mitochondrial content do not change with increasing malignancy. In premalignant cells (WPE-NA22 and WPE-NB14), OXPHOS is elevated in presence of glucose or glutamine alone or in combination compared to RWPE-1 cells and decreases with increasing malignancy. Glutamine maintained higher OXPHOS than glucose and suggests that it may be an important substrate for the growth and proliferation of prostate epithelial cells. Glycolysis significantly increases with malignancy and follow a classical Warburg phenomenon. Fatty acid oxidation (FAO) is significantly lower in tumorigenic clones and invasive WPE-NB26 does not utilize FAO at all. In this paper, we introduce for the first time the mitochondrial oncobioenergetic index (MOBI), a mathematical representation of oncobioenergetic profile of a cancer cell, which increases significantly upon transformation into localized premalignant form and rapidly falls below the normal as they become aggressive in prostate tumorigenesis. We have validated this in five prostate cancer cell lines and MOBI appears to be not related to androgen dependence or mitochondrial content, but rather dependent on the stage of the cancer. Altogether, we propose that MOBI could be a potential biomarker to distinguish aggressive cancer from that of indolent disease. PMID:26515588

  7. Dietary Total Antioxidant Capacity is Inversely Associated with Prostate Cancer Aggressiveness in a Population-Based Study.

    PubMed

    Vance, Terrence M; Wang, Ying; Su, L Joseph; Fontham, Elizabeth T H; Steck, Susan E; Arab, Lenore; Bensen, Jeannette T; Mohler, James L; Chen, Ming-Hui; Chun, Ock K

    2016-01-01

    The purpose of this study was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire. EA reported greater dietary TAC from diet and supplements combined (P < 0.0001). In both minimally and fully adjusted logistic regression models, TAC from diet and supplements combined was associated with a reduced odds of high aggressive prostate cancer in all men, AA and EA: odds ratios for highest vs. lowest level (>1500 vs. <500 mg vitamin C equivalent/day): 0.31 [95% confidence interval (CI): 0.15, 0.67; P-trend < 0.01], 0.28 (95% CI: 0.08, 0.96; P-trend < 0.001), and 0.36 (95% CI: 0.15, 0.86; P-trend = 0.58), respectively. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer. Additional research is needed to confirm these results and determine the underlying mechanisms. PMID:26847416

  8. Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer.

    PubMed

    Wu, Chunxiao; Wyatt, Alexander W; Lapuk, Anna V; McPherson, Andrew; McConeghy, Brian J; Bell, Robert H; Anderson, Shawn; Haegert, Anne; Brahmbhatt, Sonal; Shukin, Robert; Mo, Fan; Li, Estelle; Fazli, Ladan; Hurtado-Coll, Antonio; Jones, Edward C; Butterfield, Yaron S; Hach, Faraz; Hormozdiari, Fereydoun; Hajirasouliha, Iman; Boutros, Paul C; Bristow, Robert G; Jones, Steven Jm; Hirst, Martin; Marra, Marco A; Maher, Christopher A; Chinnaiyan, Arul M; Sahinalp, S Cenk; Gleave, Martin E; Volik, Stanislav V; Collins, Colin C

    2012-05-01

    Next-generation sequencing is making sequence-based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology-pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora. Despite a homogeneous cell type, our transcriptome analysis revealed signatures of both luminal and neuroendocrine cell types. Remarkably, the repertoire of expressed but apparently private gene fusions, including C15orf21:MYC, recapitulated this biology. We hypothesize that the amplification and over-expression of the stem cell gene MSI2 may have contributed to the stable hybrid cellular identity. This hybrid luminal-neuroendocrine tumour appears to represent a novel and highly aggressive case of prostate cancer with unique biological features and, conceivably, a propensity for rapid progression to castrate-resistance. Overall, this work highlights the importance of integrated analyses of genome, exome and transcriptome sequences for basic tumour biology, sequence-based molecular pathology and personalized oncology. PMID:22294438

  9. Prostate cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000380.htm Prostate cancer To use the sharing features on this page, please enable JavaScript. Prostate cancer is cancer that starts in the prostate gland. ...

  10. Association of genetic polymorphisms in the telomerase reverse transcriptase gene with prostate cancer aggressiveness.

    PubMed

    Wu, Dapeng; Yu, Hongjie; Sun, Jielin; Qi, Jun; Liu, Qiang; Li, Ruipeng; Zheng, Siqun Lily; Xu, Jianfeng; Kang, Jian

    2015-07-01

    Telomerase reverse transcriptase (TERT), encoded by the TERT gene, is an essential component of telomerase, essential for the maintenance of telomere DNA length, chromosomal stability and cellular immortality. The aim of the present study was to evaluate the association between common genetic variations across the TERT gene region and prostate cancer (PCa) aggressiveness in a Chinese population. A total of 12 TERT tagging single-nucleotide polymorphisms (SNPs) were genotyped on the Sequenom Mass-ARRAY iPLEX® platform in a case-case study with 1,210 Chinese patients with PCa. Unconditional logistic regression was used to investigate the association of genotypes with PCa aggressiveness, Gleason grade and risk of developing early-onset PCa. It was observed that the C allele of the TERT intron 2 SNP (rs2736100) was significantly associated with reduced risk of PCa aggressiveness [odds ratio (OR)=0.81; 95% confidence interval (CI): 0.66-0.99; P=0.037]. This allele was also significantly correlated with a reduced risk of developing a tumor with a high Gleason score (>7; OR=0.83; 95% CI: 0.70-0.99; P=0.039). The T allele of the intron 4 SNP (rs10069690) was found to be significantly associated with a decreased risk for an aggressive form of PCa (OR=0.76; 95% CI: 0.59-0.97; P=0.030). In addition, the A allele of rs10078761 located at the 3' end of the TERT gene exhibited a statistically significant association with the reduced risk of developing a higher grade disease (OR=0.48; 95% CI: 0.28-0.81; P=0.006). However, no association between TERT polymorphisms and age at diagnosis was observed in the present study. The present findings demonstrated for the first time, to the best of our knowledge, that genetic variations across the TERT gene are associated with PCa aggressiveness in a Chinese Han population. PMID:25738283

  11. PVT1 Exon 9: A Potential Biomarker of Aggressive Prostate Cancer?

    PubMed Central

    Ilboudo, Adeodat; Chouhan, Jyoti; McNeil, Brian K.; Osborne, Joseph R.; Ogunwobi, Olorunseun O.

    2015-01-01

    Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). Interestingly, this has been shown to be associated with single nucleotide polymorphisms around regions 2 and 3 of the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is overexpressed in PCa and, therefore, is also a candidate biomarker to explain the well-known disparity in this group. PVT1 has at least 12 exons that make separate transcripts which may have different functions, all of which are at present unknown in PCa. Our aim was to determine if any PVT1 transcripts play a role in aggressiveness and racial disparity in PCa. We used a panel of seven PCa cell lines including three derived from MoAA. Ribonucleic acid extraction, complementary deoxyribonucleic acid synthesis, and quantitative polymerase chain reaction (qPCR) were performed to evaluate expression of all 12 PVT1 exons. Each qPCR was performed in quadruplicates. At least four separate qPCR experiments were performed. Expression of PVT1 exons was inconsistent except for exon 9. There was no significant difference in exon 9 expression between cell lines derived from Caucasian males (CM), and an indolent cell line derived from MoAA. However, exon 9 expression in the aggressive MDA PCa 2b and E006AA-hT cell lines derived from MoAA was significantly higher than in other cell lines. Consequently, we observed differential expression of exon 9 of PVT1 in a manner that suggests that PVT1 exon 9 may be associated with aggressive PCa in MoAA. PMID:26703666

  12. Glycoprotein Biomarkers for the Early Detection of Aggressive Prostate Cancer — EDRN Public Portal

    Cancer.gov

    The Early Detection Research Network of the NCI is charged with the discovery, development and validation of biomarkers for early detection and prognosis related to neoplastic disease. Our laboratory is an NCI EDRN (U01CA152813) working on "Glycoprotein biomarkers for the early detection of aggressive prostate cancer". This EDRN administratiVE! supplement is a collaboration with Robert Veltri on his project to identify men with very low risk (indolent) prostate cancer (CaP) at the diagnostic biopsy at selection for active surveillance (AS). We will assess biopsy tissue using quantitative nuclear histomorphometric measurements and molecular biomarkers to predict an unexpected catastrophic CaP in such men with indolent CaP. At Johns Hopkins Hospital w1e use the Epstein criteria that includes; PSA density (PSAD) <0.15 ng/mVcm3, Gleason score SS, S2 cons involved with cancer, and ::;;SO% of any core involved with cancer to select AS. Our approach will study 140 AS men (70 with a expected outcome and 70 with a disastrous outcome) using nuclear histomorphometry and pre-qualified biomarkers quantified by digital microscopy. Previously, our laboratory combined measurements of DNA content and (-2)pPSA in the serum and (-5,-?)pPSA in biopsy tissue to identify 7/10 men that would fail surveillance based on the primary diagnostic biopsy. We now will devHiop a clinical, morphological and biomarker 'signature' for identifying severe aggressive disease from a AS diagnostic biopsy. Our approach will combine nuclear morphometry measured by digital microscopy with a unique biopsy tissue biomarker profile (DNA content, Ki67, Her2neu, CACND1 and periostin). Fc•r the molecular targets we will us•e a multiplex tissue blot (MTB) immunohistochemistry method. The Aims o'f our work include 1) to utilize retrospective archival biopsy material from 70 AS cases where the outcome was unexpected and disastrous and collect an equal number of AS cases (n=140) and perform assays for morphology

  13. Prostate cancer

    SciTech Connect

    Murphy, G.P.; Kuss, R., Khoury, S.; Chatelain, C.; Denis, L.

    1987-01-01

    This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results.

  14. [Prostate cancer].

    PubMed

    Morote, Joan; Maldonado, Xavier; Morales-Bárrera, Rafael

    2016-02-01

    The Vall d'Hebron multidisciplinary prostate cancer (PC) team reviews recent advances in the management of this neoplasm. Screening studies with long follow-up show a reduction in mortality, whereas active surveillance is emerging as a therapeutic approach of non-aggressive cancers. New markers increase the specificity of PSA and also allow targeting suspected aggressive cancers. Multiparametric magnetic resonance (mMRI) has emerged as the most effective method in the selection of patients for biopsy and also for local tumor staging. The paradigm of random prostatic biopsy is changing through the fusion techniques that allow guiding ultrasonography-driven biopsy of suspicious areas detected in mMRI. Radical prostatectomy (RP) and radiotherapy (RT) are curative treatments of localized PC and both have experienced significant technological improvements. RP is highly effective and the incorporation of robotic surgery is reducing morbidity. Modern RT allows the possibility of high tumor dose with minimal adjacent dose reducing its toxicity. Androgen deprivation therapy with LHRH analogues remains the treatment of choice for advanced PC, but should be limited to this indication. The loss of bone mass and adverse metabolic effects increases the frequency of fractures and cardiovascular morbimortality. After castration resistance in metastatic disease, new hormone-based drugs have demonstrated efficacy even after chemotherapy resistance. PMID:25727526

  15. Prostate Cancer

    MedlinePlus

    ... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  16. Prostate Cancer

    MedlinePlus

    ... a man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... men younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  17. Genetic deletion of osteopontin in TRAMP mice skews prostate carcinogenesis from adenocarcinoma to aggressive human-like neuroendocrine cancers

    PubMed Central

    Mauri, Giorgio; Jachetti, Elena; Comuzzi, Barbara; Dugo, Matteo; Arioli, Ivano; Miotti, Silvia; Sangaletti, Sabina; Di Carlo, Emma; Tripodo, Claudio; Colombo, Mario P.

    2016-01-01

    Osteopontin (OPN) is a secreted glycoprotein, that belongs to the non-structural extracellular matrix (ECM), and its over expression in human prostate cancer has been associated with disease progression, androgen independence and metastatic ability. Nevertheless, the pathophysiology of OPN in prostate tumorigenesis has never been studied. We crossed TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice with OPN deficient (OPN−/−) mice and followed tumor onset and progression in these double mutants. Ultrasound examination detected the early onset of a rapidly growing, homogeneous and spherical tumor in about 60% of OPN−/− TRAMP mice. Such neoplasms seldom occurred in parental TRAMP mice otherwise prone to adenocarcinomas and were characterized for being androgen receptor negative, highly proliferative and endowed with neuroendocrine (NE) features. Gene expression profiling showed up-regulation of genes involved in tumor progression, cell cycle and neuronal differentiation in OPN-deficient versus wild type TRAMP tumors. Down-regulated genes included key genes of TGFa pathway, including SMAD3 and Filamin, which were confirmed at the protein level. Furthermore, NE genes and particularly those characterizing early prostatic lesions of OPN-deficient mice were found to correlate with those of human prostate NE tumours. These data underscore a novel role of OPN in the early stages of prostate cancer growth, protecting against the development of aggressive NE tumors. PMID:26700622

  18. Genetic deletion of osteopontin in TRAMP mice skews prostate carcinogenesis from adenocarcinoma to aggressive human-like neuroendocrine cancers.

    PubMed

    Mauri, Giorgio; Jachetti, Elena; Comuzzi, Barbara; Dugo, Matteo; Arioli, Ivano; Miotti, Silvia; Sangaletti, Sabina; Di Carlo, Emma; Tripodo, Claudio; Colombo, Mario P

    2016-01-26

    Osteopontin (OPN) is a secreted glycoprotein, that belongs to the non-structural extracellular matrix (ECM), and its over expression in human prostate cancer has been associated with disease progression, androgen independence and metastatic ability. Nevertheless, the pathophysiology of OPN in prostate tumorigenesis has never been studied. We crossed TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice with OPN deficient (OPN-/-) mice and followed tumor onset and progression in these double mutants. Ultrasound examination detected the early onset of a rapidly growing, homogeneous and spherical tumor in about 60% of OPN-/- TRAMP mice. Such neoplasms seldom occurred in parental TRAMP mice otherwise prone to adenocarcinomas and were characterized for being androgen receptor negative, highly proliferative and endowed with neuroendocrine (NE) features. Gene expression profiling showed up-regulation of genes involved in tumor progression, cell cycle and neuronal differentiation in OPN-deficient versus wild type TRAMP tumors. Down-regulated genes included key genes of TGFa pathway, including SMAD3 and Filamin, which were confirmed at the protein level. Furthermore, NE genes and particularly those characterizing early prostatic lesions of OPN-deficient mice were found to correlate with those of human prostate NE tumours. These data underscore a novel role of OPN in the early stages of prostate cancer growth, protecting against the development of aggressive NE tumors. PMID:26700622

  19. What is Prostate Cancer?

    MedlinePlus

    ... Topic Key statistics for prostate cancer What is prostate cancer? Cancer starts when cells in the body begin ... through the center of the prostate. Types of prostate cancer Almost all prostate cancers are adenocarcinomas . These cancers ...

  20. Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer.

    PubMed

    Yin, Bo; Zhang, Mo; Zeng, Yu; Li, Youqiang; Zhang, Chao; Song, Yongsheng

    2016-04-01

    Paclitaxel frequently serves as the first-line chemotherapeutic agent for castration-resistant prostate cancer (PCa) patients. However, acquired paclitaxel-resistance almost always occurs after initial responses, and the mechanisms by which this occurs remain largely unknown. The goal of the present study was to identify differentially expressed protein(s) associated with paclitaxel-resistance and further explore the potential mechanisms involved in drug resistance. By comparing the nuclear matrix protein (NMP) patterns of DU145-TxR cells, the previously established stable paclitaxel-resistant PCa cells, with that of the parental DU145 cells using two-dimensional electrophoresis, we found that cytokeratin 18 (CK18) is downregulated in DU145-TxR cells. The downregulation of CK18 in DU145-TxR cells at mRNA, NMP and total cellular protein levels was validated by real-time RT-PCR, immunoblotting and immunofluorescence, indicating that the downregulation of CK18 was a global effect in DU145-TxR cells due to paclitaxel-resistance. Furthermore, in vivo assay of xenograft transplantation confirmed the higher tumorigenicity of DU145-TxR cells, suggesting that these paclitaxel-resistant PCa cells possessed potent cancer stem cell (CSC)-like properties and eventually developed paclitaxel-resistance. Moreover, we determined by immunohistochemistry that CK18 expression in PCa tissues was inversely correlated with tumor grade in a statistically significant fashion, indicating a potential association of the downregulation of CK18 with tumor aggressiveness. Therefore, further study to define the potential role of CK18 may lead to novel therapy strategies as well as clinically useful biomarker for PCa patients. PMID:26892177

  1. Prostate cancer.

    PubMed

    Castillejos-Molina, Ricardo Alonso; Gabilondo-Navarro, Fernando Bernardo

    2016-04-01

    Prostate cancer is the most frequent tumor found in men worldwide and in Mexico in particular. Age and family history are the main risk factors. The diagnosis is made by prostate biopsy in patients with abnormalities detected in their prostate-specific antigen (PSA) levels or digital rectal exam (DRE). This article reviews screening and diagnostic methods as well as treatment options for patients diagnosed with prostate cancer. PMID:27557386

  2. The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer

    PubMed Central

    Sharma, Naomi L.; Massie, Charlie E.; Butter, Falk; Mann, Matthias; Bon, Helene; Ramos-Montoya, Antonio; Menon, Suraj; Stark, Rory; Lamb, Alastair D.; Scott, Helen E.; Warren, Anne Y.; Neal, David E.; Mills, Ian G.

    2014-01-01

    In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. GABPα has a transcriptional role that dissects the overlapping cistromes of the two most common ETS gene fusions in PC: overlapping significantly with ETV1 but not with ERG target genes. GABPα bound predominantly to gene promoters, regulated the expression of one-third of AR target genes and modulated sensitivity to AR antagonists in hormone responsive and castrate resistant PC models. This study supports a critical role for GABPα in CRPC and reveals potential targets for therapeutic intervention. PMID:24753418

  3. Texture features on T2-weighted magnetic resonance imaging: new potential biomarkers for prostate cancer aggressiveness

    NASA Astrophysics Data System (ADS)

    Vignati, A.; Mazzetti, S.; Giannini, V.; Russo, F.; Bollito, E.; Porpiglia, F.; Stasi, M.; Regge, D.

    2015-04-01

    To explore contrast (C) and homogeneity (H) gray-level co-occurrence matrix texture features on T2-weighted (T2w) Magnetic Resonance (MR) images and apparent diffusion coefficient (ADC) maps for predicting prostate cancer (PCa) aggressiveness, and to compare them with traditional ADC metrics for differentiating low- from intermediate/high-grade PCas. The local Ethics Committee approved this prospective study of 93 patients (median age, 65 years), who underwent 1.5 T multiparametric endorectal MR imaging before prostatectomy. Clinically significant (volume ≥0.5 ml) peripheral tumours were outlined on histological sections, contoured on T2w and ADC images, and their pathological Gleason Score (pGS) was recorded. C, H, and traditional ADC metrics (mean, median, 10th and 25th percentile) were calculated on the largest lesion slice, and correlated with the pGS through the Spearman correlation coefficient. The area under the receiver operating characteristic curve (AUC) assessed how parameters differentiate pGS = 6 from pGS ≥ 7. The dataset included 49 clinically significant PCas with a balanced distribution of pGS. The Spearman ρ and AUC values on ADC were: -0.489, 0.823 (mean) -0.522, 0.821 (median) -0.569, 0.854 (10th percentile) -0.556, 0.854 (25th percentile) -0.386, 0.871 (C); 0.533, 0.923 (H); while on T2w they were: -0.654, 0.945 (C); 0.645, 0.962 (H). AUC of H on ADC and T2w, and C on T2w were significantly higher than that of the mean ADC (p = 0.05). H and C calculated on T2w images outperform ADC parameters in correlating with pGS and differentiating low- from intermediate/high-risk PCas, supporting the role of T2w MR imaging in assessing PCa biological aggressiveness.

  4. Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer.

    PubMed

    Kirk, Jason S; Schaarschuch, Kevin; Dalimov, Zafardjan; Lasorsa, Elena; Ku, ShengYu; Ramakrishnan, Swathi; Hu, Qiang; Azabdaftari, Gissou; Wang, Jianmin; Pili, Roberto; Ellis, Leigh

    2015-02-20

    Progression of aggressive prostate cancers (PCa) with androgen receptor splice variants or neuroendrocrine features is currently untreatable in the clinic. Therefore novel therapies are urgently required. We conducted RNA-seq using tumors from a unique murine transplant mouse model which spontaneously progresses to metastatic disease. Differential gene expression analysis revealed a significant increase of topoisomerase IIα, Top2a (Top2a) in metastatic tumors. Interrogation of human data revealed that increased Top2a expression in primary tumors selected patients with more aggressive disease. Further, significant positive correlation was observed between Top2a and the histone methyltransferase, Ezh2. Combination of the Top2 poison etoposide with the Ezh2 inhibitor GSK126 or DZNep significantly increased cell death in vitro in murine and human prostate cancer cell lines. Additionally, combination therapy extended time to progression and increased therapeutic efficacy in vivo. Overall, our studies demonstrate that patients screened for Top2a and Ezh2 expression would exhibit significant response to a combinational treatment involving low dose etoposide combined with Ezh2 inhibition. In addition, our data suggests that this combination therapeutic strategy is beneficial against aggressive PCa, and provides strong rationale for continued clinical development. PMID:25605014

  5. Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer

    PubMed Central

    Lasorsa, Elena; Ku, ShengYu; Ramakrishnan, Swathi; Hu, Qiang; Azabdaftari, Gissou; Wang, Jianmin; Pili, Roberto; Ellis, Leigh

    2015-01-01

    Progression of aggressive prostate cancers (PCa) with androgen receptor splice variants or neuroendrocrine features is currently untreatable in the clinic. Therefore novel therapies are urgently required. We conducted RNA-seq using tumors from a unique murine transplant mouse model which spontaneously progresses to metastatic disease. Differential gene expression analysis revealed a significant increase of topoisomerase IIα, Top2a (Top2a) in metastatic tumors. Interrogation of human data revealed that increased Top2a expression in primary tumors selected patients with more aggressive disease. Further, significant positive correlation was observed between Top2a and the histone methyltransferase, Ezh2. Combination of the Top2 poison etoposide with the Ezh2 inhibitor GSK126 or DZNep significantly increased cell death in vitro in murine and human prostate cancer cell lines. Additionally, combination therapy extended time to progression and increased therapeutic efficacy in vivo. Overall, our studies demonstrate that patients screened for Top2a and Ezh2 expression would exhibit significant response to a combinational treatment involving low dose etoposide combined with Ezh2 inhibition. In addition, our data suggests that this combination therapeutic strategy is beneficial against aggressive PCa, and provides strong rationale for continued clinical development. PMID:25605014

  6. Prostate cancer is not breast cancer

    PubMed Central

    Venniyoor, Ajit

    2016-01-01

    Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach. PMID:27051149

  7. Prostate cancer.

    PubMed

    Attard, Gerhardt; Parker, Chris; Eeles, Ros A; Schröder, Fritz; Tomlins, Scott A; Tannock, Ian; Drake, Charles G; de Bono, Johann S

    2016-01-01

    Much progress has been made in research for prostate cancer in the past decade. There is now greater understanding for the genetic basis of familial prostate cancer with identification of rare but high-risk mutations (eg, BRCA2, HOXB13) and low-risk but common alleles (77 identified so far by genome-wide association studies) that could lead to targeted screening of patients at risk. This is especially important because screening for prostate cancer based on prostate-specific antigen remains controversial due to the high rate of overdiagnosis and unnecessary prostate biopsies, despite evidence that it reduces mortality. Classification of prostate cancer into distinct molecular subtypes, including mutually exclusive ETS-gene-fusion-positive and SPINK1-overexpressing, CHD1-loss cancers, could allow stratification of patients for different management strategies. Presently, men with localised disease can have very different prognoses and treatment options, ranging from observation alone through to radical surgery, with few good-quality randomised trials to inform on the best approach for an individual patient. The survival of patients with metastatic prostate cancer progressing on androgen-deprivation therapy (castration-resistant prostate cancer) has improved substantially. In addition to docetaxel, which has been used for more than a decade, in the past 4 years five new drugs have shown efficacy with improvements in overall survival leading to licensing for the treatment of metastatic castration-resistant prostate cancer. Because of this rapid change in the therapeutic landscape, no robust data exist to inform on the selection of patients for a specific treatment for castration-resistant prostate cancer or the best sequence of administration. Moreover, the high cost of the newer drugs limits their widespread use in several countries. Data from continuing clinical and translational research are urgently needed to improve, and, crucially, to personalise management. PMID

  8. Assessment of apparent diffusion coefficient values as predictor of aggressiveness in peripheral zone prostate cancer: comparison with Gleason score.

    PubMed

    Anwar, Shayan Sirat Maheen; Anwar Khan, Zahid; Shoaib Hamid, Rana; Haroon, Fahd; Sayani, Raza; Beg, Madiha; Khattak, Yasir Jamil

    2014-01-01

    Purpose. To determine association between apparent diffusion coefficient value on diffusion-weighted imaging and Gleason score in patients with prostate cancer. Methods. This retrospective case series was conducted at Radiology Department of Aga Khan University between June 2009 and June 2011. 28 patients with biopsy-proven prostate cancer were included who underwent ultrasound guided sextant prostate biopsy and MRI. MRI images were analyzed on diagnostic console and regions of interest were drawn. Data were entered and analyzed on SPSS 20.0. ADC values were compared with Gleason score using one-way ANOVA test. Results. In 28 patients, 168 quadrants were biopsied and 106 quadrants were positive for malignancy. 89 lesions with proven malignancy showed diffusion restriction. The mean ADC value for disease with a Gleason score of 6 was 935 mm(2)/s (SD = 248.4 mm(2)/s); Gleason score of 7 was 837 mm(2)/s (SD = 208.5 mm(2)/s); Gleason score of 8 was 614 mm(2)/s (SD = 108 mm(2)/s); and Gleason score of 9 was 571 mm(2)/s (SD = 82 mm(2)/s). Inverse relationship was observed between Gleason score and mean ADC values. Conclusion. DWI and specifically quantitative ADC values may help differentiate between low-risk (Gleason score, 6), intermediate-risk (Gleason score, 7), and high-risk (Gleason score 8 and 9) prostate cancers, indirectly determining the aggressiveness of the disease. PMID:24967293

  9. A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men

    PubMed Central

    Petrovics, Gyorgy; Li, Hua; Stümpel, Tanja; Tan, Shyh-Han; Young, Denise; Katta, Shilpa; Li, Qiyuan; Ying, Kai; Klocke, Bernward; Ravindranath, Lakshmi; Kohaar, Indu; Chen, Yongmei; Ribli, Dezső; Grote, Korbinian; Zou, Hua; Cheng, Joseph; Dalgard, Clifton L.; Zhang, Shimin; Csabai, István; Kagan, Jacob; Takeda, David; Loda, Massimo; Srivastava, Sudhir; Scherf, Matthias; Seifert, Martin; Gaiser, Timo; McLeod, David G.; Szallasi, Zoltan; Ebner, Reinhard; Werner, Thomas; Sesterhenn, Isabell A.; Freedman, Matthew; Dobi, Albert; Srivastava, Shiv

    2015-01-01

    Evaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP) incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA) and Caucasian American (CA) CaP genomes. We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients). Notably, carriers of this deletion experienced more rapid disease progression. In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somatic mutations in CaP across ancestral groups, which have implications for precision medicine strategies. PMID:26844274

  10. A meta-analysis of genome-wide association studies to identify prostate cancer susceptibility loci associated with aggressive and non-aggressive disease

    PubMed Central

    Amin Al Olama, Ali; Kote-Jarai, Zsofia; Schumacher, Fredrick R.; Wiklund, Fredrik; Berndt, Sonja I.; Benlloch, Sara; Giles, Graham G.; Severi, Gianluca; Neal, David E.; Hamdy, Freddie C.; Donovan, Jenny L.; Hunter, David J.; Henderson, Brian E.; Thun, Michael J.; Gaziano, Michael; Giovannucci, Edward L.; Siddiq, Afshan; Travis, Ruth C.; Cox, David G.; Canzian, Federico; Riboli, Elio; Key, Timothy J.; Andriole, Gerald; Albanes, Demetrius; Hayes, Richard B.; Schleutker, Johanna; Auvinen, Anssi; Tammela, Teuvo L.J.; Weischer, Maren; Stanford, Janet L.; Ostrander, Elaine A.; Cybulski, Cezary; Lubinski, Jan; Thibodeau, Stephen N.; Schaid, Daniel J.; Sorensen, Karina D.; Batra, Jyotsna; Clements, Judith A.; Chambers, Suzanne; Aitken, Joanne; Gardiner, Robert A.; Maier, Christiane; Vogel, Walther; Dörk, Thilo; Brenner, Hermann; Habuchi, Tomonori; Ingles, Sue; John, Esther M.; Dickinson, Joanne L.; Cannon-Albright, Lisa; Teixeira, Manuel R.; Kaneva, Radka; Zhang, Hong-Wei; Lu, Yong-Jie; Park, Jong Y.; Cooney, Kathleen A.; Muir, Kenneth R.; Leongamornlert, Daniel A.; Saunders, Edward; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Guy, Michelle; Govindasami, Koveela; O'Brien, Lynne T.; Wilkinson, Rosemary A.; Hall, Amanda L.; Sawyer, Emma J.; Dadaev, Tokhir; Morrison, Jonathan; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Van As, Nicholas; Woodhouse, Christopher J.; Thompson, Alan; Dudderidge, Tim; Ogden, Chris; Cooper, Colin S.; Lophatonanon, Artitaya; Southey, Melissa C.; Hopper, John L.; English, Dallas; Virtamo, Jarmo; Le Marchand, Loic; Campa, Daniele; Kaaks, Rudolf; Lindstrom, Sara; Diver, W. Ryan; Gapstur, Susan; Yeager, Meredith; Cox, Angela; Stern, Mariana C.; Corral, Roman; Aly, Markus; Isaacs, William; Adolfsson, Jan; Xu, Jianfeng; Zheng, S. Lilly; Wahlfors, Tiina; Taari, Kimmo; Kujala, Paula; Klarskov, Peter; Nordestgaard, Børge G.; Røder, M. Andreas; Frikke-Schmidt, Ruth; Bojesen, Stig E.; FitzGerald, Liesel M.; Kolb, Suzanne; Kwon, Erika M.; Karyadi, Danielle M.; Orntoft, Torben Falck; Borre, Michael; Rinckleb, Antje; Luedeke, Manuel; Herkommer, Kathleen; Meyer, Andreas; Serth, Jürgen; Marthick, James R.; Patterson, Briony; Wokolorczyk, Dominika; Spurdle, Amanda; Lose, Felicity; McDonnell, Shannon K.; Joshi, Amit D.; Shahabi, Ahva; Pinto, Pedro; Santos, Joana; Ray, Ana; Sellers, Thomas A.; Lin, Hui-Yi; Stephenson, Robert A.; Teerlink, Craig; Muller, Heiko; Rothenbacher, Dietrich; Tsuchiya, Norihiko; Narita, Shintaro; Cao, Guang-Wen; Slavov, Chavdar; Mitev, Vanio; Chanock, Stephen; Gronberg, Henrik; Haiman, Christopher A.; Kraft, Peter; Easton, Douglas F.; Eeles, Rosalind A.

    2013-01-01

    Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of prostate cancer (PrCa), but these explain less than one-third of the heritability. To identify further susceptibility alleles, we conducted a meta-analysis of four GWAS including 5953 cases of aggressive PrCa and 11 463 controls (men without PrCa). We computed association tests for approximately 2.6 million SNPs and followed up the most significant SNPs by genotyping 49 121 samples in 29 studies through the international PRACTICAL and BPC3 consortia. We not only confirmed the association of a PrCa susceptibility locus, rs11672691 on chromosome 19, but also showed an association with aggressive PrCa [odds ratio = 1.12 (95% confidence interval 1.03–1.21), P = 1.4 × 10−8]. This report describes a genetic variant which is associated with aggressive PrCa, which is a type of PrCa associated with a poorer prognosis. PMID:23065704

  11. Prostate Cancer Screening (Beyond the Basics)

    MedlinePlus

    ... complications of advanced disease. ● For men with an aggressive prostate cancer, the best chance for curing it ... body. However, many early-stage cancers are not aggressive, and the five-year survival will be nearly ...

  12. Chemoprevention of prostate cancer.

    PubMed

    Rittmaster, Roger S

    2011-06-01

    Over the past two decades, many more men are diagnosed with prostate cancer then die of the disease. This increase in diagnosis has led to aggressive treatment of indolent disease in many individuals and has been the impetus for finding a means of reducing the risk of prostate cancer. In the past decade, there have been eight large trials of prostate cancer risk reduction using dietary supplements, 5α-reductase inhibitors, or anti-estrogens. The only two trials which have demonstrated efficacy are those involving 5α-reductase inhibitors: the PCPT (finasteride) and REDUCE (dutasteride). This review examines prostate cancer risk reduction, with emphasis on conclusions that can be drawn from these two landmark studies. PMID:21604953

  13. Decreased expression of SLC 39A14 is associated with tumor aggressiveness and biochemical recurrence of human prostate cancer

    PubMed Central

    Xu, Xiao-Ming; Wang, Cheng-Gong; Zhu, Yu-Di; Chen, Wei-Hua; Shao, Si-Liang; Jiang, Fu-Neng; Liao, Qian-De

    2016-01-01

    Objective Solute carrier family 39, member 14 (SLC39A14), has been identified as a potential biomarker for various cancers. However, its roles in prostate cancer (PCa) are still unclear. The aim of this study was to investigate the clinical significance of SLC39A14 in patients with PCa and its functions in malignant phenotypes of PCa cells. Patients and methods Subcellular localization and expression pattern of SLC39A14 protein were examined by immunohistochemistry. Then, the associations of SLC39A14 expression with various clinicopathological features and clinical outcome of patients with PCa were statistically evaluated. Subsequently, the effects of SLC39A14 overexpression and knockdown on PCa cell proliferation and motility were, respectively, examined by Cell Counting Kit-8, transwell, and wound-healing assays. Results The immunoreactive scores of SLC39A14 protein in human PCa tissues were significantly lower than those in normal prostate tissues. Based on the Taylor dataset, SLC39A14 downregulation occurred more frequently in patients with PCa with a higher Gleason score (P<0.001), advanced clinical stage (P=0.008), presence of metastasis (P=0.009), and prostate-specific antigen failure (P=0.006). More interestingly, the survival analysis identified SLC39A14 as an independent factor for predicting the biochemical recurrence-free survival of patients with PCa (P=0.017). Functionally, the enforced expression of SLC39A14 could suppress cell proliferation, invasion, and migration of PCa cell lines in vitro, which could be reversed by the knockdown of SLC39A14. Conclusion Decreased expression of SLC39A14 may lead to malignant phenotypes of PCa cells and aggressive tumor progression in patients with PCa. Importantly, SLC39A14 may function as a tumor suppressor and a biomarker for screening patients with biochemical recurrence following radical prostatectomy. PMID:27471394

  14. MYC and Prostate Cancer

    PubMed Central

    Koh, Cheryl M.; Bieberich, Charles J.; Dang, Chi V.; Nelson, William G.; Yegnasubramanian, Srinivasan; De Marzo, Angelo M.

    2010-01-01

    Prostate cancer, the majority of which is adenocarcinoma, is the most common epithelial cancer affecting a majority of elderly men in Western nations. Its manifestation, however, varies from clinically asymptomatic insidious neoplasms that progress slowly and do not threaten life to one that is highly aggressive with a propensity for metastatic spread and lethality if not treated in time. A number of somatic genetic and epigenetic alterations occur in prostate cancer cells. Some of these changes, such as loss of the tumor suppressors PTEN and p53, are linked to disease progression. Others, such as ETS gene fusions, appear to be linked more with early phases of the disease, such as invasion. Alterations in chromosome 8q24 in the region of MYC have also been linked to disease aggressiveness for many years. However, a number of recent studies in human tissues have indicated that MYC appears to be activated at the earliest phases of prostate cancer (e.g., in tumor-initiating cells) in prostatic intraepithelial neoplasia, a key precursor lesion to invasive prostatic adenocarcinoma. The initiation and early progression of prostate cancer can be recapitulated in genetically engineered mouse models, permitting a richer understanding of the cause and effects of loss of tumor suppressors and activation of MYC. The combination of studies using human tissues and mouse models paints an emerging molecular picture of prostate cancer development and early progression. This picture reveals that MYC contributes to disease initiation and progression by stimulating an embryonic stem cell–like signature characterized by an enrichment of genes involved in ribosome biogenesis and by repressing differentiation. These insights pave the way to potential novel therapeutic concepts based on MYC biology. PMID:21779461

  15. Glycoproteomic Analysis of Prostate Cancer Tissues by SWATH Mass Spectrometry Discovers N-acylethanolamine Acid Amidase and Protein Tyrosine Kinase 7 as Signatures for Tumor Aggressiveness*

    PubMed Central

    Liu, Yansheng; Chen, Jing; Sethi, Atul; Li, Qing K.; Chen, Lijun; Collins, Ben; Gillet, Ludovic C. J.; Wollscheid, Bernd; Zhang, Hui; Aebersold, Ruedi

    2014-01-01

    The identification of biomarkers indicating the level of aggressiveness of prostate cancer (PCa) will address the urgent clinical need to minimize the general overtreatment of patients with non-aggressive PCa, who account for the majority of PCa cases. Here, we isolated formerly N-linked glycopeptides from normal prostate (n = 10) and from non-aggressive (n = 24), aggressive (n = 16), and metastatic (n = 25) PCa tumor tissues and analyzed the samples using SWATH mass spectrometry, an emerging data-independent acquisition method that generates a single file containing fragment ion spectra of all ionized species of a sample. The resulting datasets were searched using a targeted data analysis strategy in which an a priori spectral reference library representing known N-glycosites of the human proteome was used to identify groups of signals in the SWATH mass spectrometry data. On average we identified 1430 N-glycosites from each sample. Out of those, 220 glycoproteins showed significant quantitative changes associated with diverse biological processes involved in PCa aggressiveness and metastasis and indicated functional relationships. Two glycoproteins, N-acylethanolamine acid amidase and protein tyrosine kinase 7, that were significantly associated with aggressive PCa in the initial sample cohort were further validated in an independent set of patient tissues using tissue microarray analysis. The results suggest that N-acylethanolamine acid amidase and protein tyrosine kinase 7 may be used as potential tissue biomarkers to avoid overtreatment of non-aggressive PCa. PMID:24741114

  16. Prostate cancer - resources

    MedlinePlus

    Resources - prostate cancer ... The following organizations are good resources for information on prostate cancer : American Cancer Society -- www.cancer.org/cancer/prostatecancer/index National Cancer Institute -- www.cancer.gov/cancertopics/ ...

  17. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    PubMed Central

    Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  18. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer.

    PubMed

    Dal Pra, Alan; Locke, Jennifer A; Borst, Gerben; Supiot, Stephane; Bristow, Robert G

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  19. 6 Common Cancers - Prostate Cancer

    MedlinePlus

    ... Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... for early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

  20. 6 Common Cancers - Prostate Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

  1. Prevention and early detection of prostate cancer.

    PubMed

    Cuzick, Jack; Thorat, Mangesh A; Andriole, Gerald; Brawley, Otis W; Brown, Powel H; Culig, Zoran; Eeles, Rosalind A; Ford, Leslie G; Hamdy, Freddie C; Holmberg, Lars; Ilic, Dragan; Key, Timothy J; La Vecchia, Carlo; Lilja, Hans; Marberger, Michael; Meyskens, Frank L; Minasian, Lori M; Parker, Chris; Parnes, Howard L; Perner, Sven; Rittenhouse, Harry; Schalken, Jack; Schmid, Hans-Peter; Schmitz-Dräger, Bernd J; Schröder, Fritz H; Stenzl, Arnulf; Tombal, Bertrand; Wilt, Timothy J; Wolk, Alicja

    2014-10-01

    Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer. PMID:25281467

  2. The Quantitative Criteria Based on the Fractal Dimensions, Entropy, and Lacunarity for the Spatial Distribution of Cancer Cell Nuclei Enable Identification of Low or High Aggressive Prostate Carcinomas

    PubMed Central

    Waliszewski, Przemyslaw

    2016-01-01

    Background: Tumor grading, PSA concentration, and stage determine a risk of prostate cancer patients with accuracy of about 70%. An approach based on the fractal geometrical model was proposed to eliminate subjectivity from the evaluation of tumor aggressiveness and to improve the prediction. This study was undertaken to validate classes of equivalence for the spatial distribution of cancer cell nuclei in a larger, independent set of prostate carcinomas. Methods: The global fractal capacity D0, information D1 and correlation D2 dimension, the local fractal dimension (LFD) and the local connected fractal dimension (LCFD), Shannon entropy H and lacunarity λ were measured using computer algorithms in digitalized images of both the reference set (n = 60) and the test set (n = 208) of prostate carcinomas. Results: Prostate carcinomas were re-stratified into seven classes of equivalence. The cut-off D0-values 1.5450, 1.5820, 1.6270, 1.6490, 1.6980, 1.7640 defined the classes from C1 to C7, respectively. The other measures but the D1 failed to define the same classes of equivalence. The pairs (D0, LFD), (D0, H), (D0, λ), (D1, LFD), (D1, H), (D1, λ) characterized the spatial distribution of cancer cell nuclei in each class. The co-application of those measures enabled the subordination of prostate carcinomas to one out of three clusters associated with different tumor aggressiveness. For D0 < 1.5820, LFD < 1.3, LCFD > 1.5, H < 0.7, and λ > 0.8, the class C1 or C2 contains low complexity low aggressive carcinomas exclusively. For D0 > 1.6980, LFD > 1.7644, LCFD > 1.7051, H > 0.9, and λ < 0.7, the class C6 or C7 contains high complexity high aggressive carcinomas. Conclusions: The cut-off D0-values defining the classes of equivalence were validated in this study. The cluster analysis suggested that the number of the subjective Gleason grades and the number of the objective classes of equivalence could be decreased from seven to three without a loss of clinically

  3. Semi supervised multi kernel (SeSMiK) graph embedding: identifying aggressive prostate cancer via magnetic resonance imaging and spectroscopy.

    PubMed

    Tiwari, Pallavi; Kurhanewicz, John; Rosen, Mark; Madabhushi, Anant

    2010-01-01

    With the wide array of multi scale, multi-modal data now available for disease characterization, the major challenge in integrated disease diagnostics is to able to represent the different data streams in a common framework while overcoming differences in scale and dimensionality. This common knowledge representation framework is an important pre-requisite to develop integrated meta-classifiers for disease classification. In this paper, we present a unified data fusion framework, Semi Supervised Multi Kernel Graph Embedding (SeSMiK-GE). Our method allows for representation of individual data modalities via a combined multi-kernel framework followed by semi- supervised dimensionality reduction, where partial label information is incorporated to embed high dimensional data in a reduced space. In this work we evaluate SeSMiK-GE for distinguishing (a) benign from cancerous (CaP) areas, and (b) aggressive high-grade prostate cancer from indolent low-grade by integrating information from 1.5 Tesla in vivo Magnetic Resonance Imaging (anatomic) and Spectroscopy (metabolic). Comparing SeSMiK-GE with unimodal T2w, MRS classifiers and a previous published non-linear dimensionality reduction driven combination scheme (ScEPTre) yielded classification accuracies of (a) 91.3% (SeSMiK), 66.1% (MRI), 82.6% (MRS) and 86.8% (ScEPTre) for distinguishing benign from CaP regions, and (b) 87.5% (SeSMiK), 79.8% (MRI), 83.7% (MRS) and 83.9% (ScEPTre) for distinguishing high and low grade CaP over a total of 19 multi-modal MRI patient studies. PMID:20879458

  4. Localized Prostate Cancer

    MedlinePlus

    ... a decision aid for men with clinically localized prostate cancer (available at http://effectivehealthcare.ahrq.gov/prostate_da) ... A Decision Aid for Men With Clinically Localized Prostate Cancer Page 1 of 24 Introduction Men with clinically ...

  5. Molecular Imaging of Prostate Cancer.

    PubMed

    Wibmer, Andreas G; Burger, Irene A; Sala, Evis; Hricak, Hedvig; Weber, Wolfgang A; Vargas, Hebert Alberto

    2016-01-01

    Prostate cancer is the most common noncutaneous malignancy among men in the Western world. The natural history and clinical course of prostate cancer are markedly diverse, ranging from small indolent intraprostatic lesions to highly aggressive disseminated disease. An understanding of this biologic heterogeneity is considered a necessary requisite in the quest for the adoption of precise and personalized management strategies. Molecular imaging offers the potential for noninvasive assessment of the biologic interactions underpinning prostate carcinogenesis. Currently, numerous molecular imaging probes are in clinical use or undergoing preclinical or clinical evaluation. These probes can be divided into those that image increased cell metabolism, those that target prostate cancer-specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to bone. The increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. The androgen receptor, prostate-specific membrane antigen, and gastrin-releasing peptide receptor (ie, bombesin) are overexpressed in prostate cancer and can be targeted by specific radiolabeled imaging probes. Because metastatic prostate cancer cells induce osteoblastic signaling pathways of adjacent bone tissue, bone-seeking radiotracers are sensitive tools for the detection of metastases to bone. Knowledge about the underlying biologic processes responsible for the phenotypes associated with the different stages of prostate cancer allows an appropriate choice of methods and helps avoid pitfalls. PMID:26587888

  6. Role of Serum Cholesterol and Statin Use in the Risk of Prostate Cancer Detection and Tumor Aggressiveness

    PubMed Central

    Morote, Juan; Celma, Anna; Planas, Jacques; Placer, José; de Torres, Inés; Olivan, Mireia; Carles, Juan; Reventós, Jaume; Doll, Andreas

    2014-01-01

    The aim of this study was to analyze the relationship between statin use along with serum cholesterol levels and prostate cancer (PCa) detection and aggressiveness. Statin users of three years or more and serum cholesterol levels (SC) were assessed in 2408 men scheduled for prostate biopsy. SC was classified as normal (NSC: <200 mg/dL) or high (HSC: >200 mg/dL). High-grade PCa (HGPCa) was considered if the Gleason score was greater than 7. Statin users comprised 30.9% of those studied. The PCa detection rate was 31.2% of men on statins and 37% of non-statin users (p < 0.006). The PCa detection rate was 26.3% in men with NSC and 40.6% in those with HSC (p < 0.001). In the subset of NSC men, the PCa rate was 26.5% for statin users and 26.2% for non-users (p = 0.939), while in men with HSC, the PCa rate was 36.4% for statin users and 42.0% for non-statin users (p = 0.063). The HGPCa rate was 41.8% for statin users and 32.5% for non-users (p = 0.012). NSC men had a 53.8% rate of HGPCa, while the rate was only 27.6% in HSC men (p < 0.001). NSC men on statins had an HGPCa rate of 70.2%, while non-statin users had a rate of 41.2% (p < 0.001). The HGPCa rate for HSC men on statins was 18.8%, while the rate was 30.0% (p = 0.011) for non-users. Logistic regression analysis suggested that serum cholesterol levels could serve as an independent predictor of PCa risk, OR 1.87 (95% CI 1.56–2.24) and HGPCa risk, OR 0.31 (95% CI 0.23–0.44), while statin usage could not. Statin treatment may prevent PCa detection through serum cholesterol-mediated mechanisms. A disturbing increase in the HGPCa rate was observed in statin users who normalized their serum cholesterol. PMID:25101846

  7. Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP

    PubMed Central

    Steck, Susan E.; Arab, Lenore; Zhang, Hongmei; Bensen, Jeannette T.; Fontham, Elizabeth T. H.; Johnson, Candace S.; Mohler, James L.; Smith, Gary J.; Su, Joseph L.; Trump, Donald L.; Woloszynska-Read, Anna

    2015-01-01

    Background African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs). Methods Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either ‘high’ or ‘low’ aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3. Results AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT3vs.T1: 2.23, 95%CI: 1.26–3.95 among men with low calcium intake, and ORT3vs.T1: 0.19, 95%CI: 0.05–0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null. Conclusions Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study. PMID:25919866

  8. Endothelial NOS, estrogen receptor β, and HIFs cooperate in the activation of a prognostic transcriptional pattern in aggressive human prostate cancer

    PubMed Central

    Nanni, Simona; Benvenuti, Valentina; Grasselli, Annalisa; Priolo, Carmen; Aiello, Aurora; Mattiussi, Stefania; Colussi, Claudia; Lirangi, Vittoria; Illi, Barbara; D’Eletto, Manuela; Cianciulli, Anna Maria; Gallucci, Michele; De Carli, Piero; Sentinelli, Steno; Mottolese, Marcella; Carlini, Paolo; Strigari, Lidia; Finn, Stephen; Mueller, Elke; Arcangeli, Giorgio; Gaetano, Carlo; Capogrossi, Maurizio C.; Donnorso, Raffaele Perrone; Bacchetti, Silvia; Sacchi, Ada; Pontecorvi, Alfredo; Loda, Massimo; Farsetti, Antonella

    2009-01-01

    The identification of biomarkers that distinguish between aggressive and indolent forms of prostate cancer (PCa) is crucial for diagnosis and treatment. In this study, we used cultured cells derived from prostate tissue from patients with PCa to define a molecular mechanism underlying the most aggressive form of PCa that involves the functional activation of eNOS and HIFs in association with estrogen receptor β (ERβ). Cells from patients with poor prognosis exhibited a constitutively hypoxic phenotype and increased NO production. Upon estrogen treatment, formation of ERβ/eNOS, ERβ/HIF-1α, or ERβ/HIF-2α combinatorial complexes led to chromatin remodeling and transcriptional induction of prognostic genes. Tissue microarray analysis, using an independent cohort of patients, established a hierarchical predictive power for these proteins, with expression of eNOS plus ERβ and nuclear eNOS plus HIF-2α being the most relevant indicators of adverse clinical outcome. Genetic or pharmacologic modulation of eNOS expression and activity resulted in reciprocal conversion of the transcriptional signature in cells from patients with bad or good outcome, respectively, highlighting the relevance of eNOS in PCa progression. Our work has considerable clinical relevance, since it may enable the earlier diagnosis of aggressive PCa through routine biopsy assessment of eNOS, ERβ, and HIF-2α expression. Furthermore, proposing eNOS as a therapeutic target fosters innovative therapies for PCa with NO inhibitors, which are employed in preclinical trials in non-oncological diseases. PMID:19363294

  9. Mutational Landscape of Aggressive Prostate Tumors in African American Men.

    PubMed

    Lindquist, Karla J; Paris, Pamela L; Hoffmann, Thomas J; Cardin, Niall J; Kazma, Rémi; Mefford, Joel A; Simko, Jeffrey P; Ngo, Vy; Chen, Yalei; Levin, Albert M; Chitale, Dhananjay; Helfand, Brian T; Catalona, William J; Rybicki, Benjamin A; Witte, John S

    2016-04-01

    Prostate cancer is the most frequently diagnosed and second most fatal nonskin cancer among men in the United States. African American men are two times more likely to develop and die of prostate cancer compared with men of other ancestries. Previous whole genome or exome tumor-sequencing studies of prostate cancer have primarily focused on men of European ancestry. In this study, we sequenced and characterized somatic mutations in aggressive (Gleason ≥7, stage ≥T2b) prostate tumors from 24 African American patients. We describe the locations and prevalence of small somatic mutations (up to 50 bases in length), copy number aberrations, and structural rearrangements in the tumor genomes compared with patient-matched normal genomes. We observed several mutation patterns consistent with previous studies, such as large copy number aberrations in chromosome 8 and complex rearrangement chains. However, TMPRSS2-ERG gene fusions and PTEN losses occurred in only 21% and 8% of the African American patients, respectively, far less common than in patients of European ancestry. We also identified mutations that appeared specific to or more common in African American patients, including a novel CDC27-OAT gene fusion occurring in 17% of patients. The genomic aberrations reported in this study warrant further investigation of their biologic significant role in the incidence and clinical outcomes of prostate cancer in African Americans. Cancer Res; 76(7); 1860-8. ©2016 AACR. PMID:26921337

  10. Screening for Prostate Cancer

    MedlinePlus

    ... of Internal Medicine Summaries for Patients Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ... Physicians The full report is titled “Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ...

  11. Prostate cancer screenings

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000846.htm Prostate cancer screenings To use the sharing features on this ... present it is not clear if screening for prostate cancer is helpful for most men. For this reason, ...

  12. Prostate Cancer Foundation

    MedlinePlus

    ... PCF Spotlight Prostate Cancer Foundation and Major League Baseball Step Up To The Plate To Raise Awareness ... Foundation News Prostate Cancer Foundation and Major League Baseball Step Up To The Plate To Raise Awareness ...

  13. Prostate Cancer Screening

    MedlinePlus

    ... treat. There is no standard screening test for prostate cancer. Researchers are studying different tests to find those ... PSA level may be high if you have prostate cancer. It can also be high if you have ...

  14. Prostate Cancer Research Trial Helps John Spencer Treat His Cancer

    MedlinePlus

    ... please turn Javascript on. Feature: Prostate Cancer Prostate Cancer Research Trial Helps John Spencer Treat His Cancer Past ... Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His Cancer / Prostate ...

  15. Cancer of the prostate.

    PubMed Central

    Dearnaley, D. P.

    1994-01-01

    Prostate cancer presents a growing health problem in Western societies as longevity increases. It is characteristically a disease of elderly men associated with the development of osteoblastic bone metastases and initial hormone responsiveness to androgen deprivation. Previously regarded as a Cinderella of cancers, there is currently more controversy concerning the detection and management of both localised and metastatic disease than for any other common malignancy. A balance needs to be drawn between the potential gains of more aggressive management and the disadvantages in terms of increased treatment side effects and cost, taking into account both the natural course of the disease and the life expectancy of patients. Images FIG 1 FIG 2 PMID:8142838

  16. Cryotherapy for prostate cancer

    MedlinePlus

    Cryotherapy uses very cold temperatures to freeze and kill prostate cancer cells. The goal of cryosurgery is ... Possible short-term side effects of cryotherapy for prostate ... of the penis or scrotum Problems controlling your bladder (more ...

  17. Screening for prostate cancer

    NASA Technical Reports Server (NTRS)

    Weirich, Stephen A.

    1993-01-01

    Despite recent advances in both the survival and cure rates for many forms of cancer, unfortunately the same has not been true for prostate cancer. In fact, the age-adjusted death rate from prostate cancer has not significantly improved since 1949, and prostate cancer remains the most common cancer in American men, causing the second highest cancer mortality rate. Topics discussed include the following: serum testosterone levels; diagnosis; mortality statistics; prostate-sppecific antigen (PSA) tests; and the Occupational Medicine Services policy at LeRC.

  18. Annexin A1 is involved in the acquisition and maintenance of a stem cell-like/aggressive phenotype in prostate cancer cells with acquired resistance to zoledronic acid

    PubMed Central

    Bizzarro, Valentina; Belvedere, Raffaella; Milone, Maria Rita; Pucci, Biagio; Lombardi, Rita; Bruzzese, Francesca; Popolo, Ada; Parente, Luca; Budillon, Alfredo; Petrella, Antonello

    2015-01-01

    In this study, we have characterized the role of annexin A1 (ANXA1) in the acquisition and maintenance of stem-like/aggressive features in prostate cancer (PCa) cells comparing zoledronic acid (ZA)-resistant DU145R80 with their parental DU145 cells. ANXA1 is over-expressed in DU145R80 cells and its down-regulation abolishes their resistance to ZA. Moreover, ANXA1 induces DU145 and DU145R80 invasiveness acting through formyl peptide receptors (FPRs). Also, ANXA1 knockdown is able to inhibit epithelial to mesenchymal transition (EMT) and to reduce focal adhesion kinase (FAK) and metalloproteases (MMP)-2/9 expression in PCa cells. DU145R80 show a cancer stem cell (CSC)-like signature with a high expression of CSC markers including CD44, CD133, NANOG, Snail, Oct4 and ALDH7A1 and CSC-related genes as STAT3. Interestingly, ANXA1 knockdown induces these cells to revert from a putative prostate CSC to a more differentiated phenotype resembling DU145 PCa cell signature. Similar results are obtained concerning some drug resistance-related genes such as ATP Binding Cassette G2 (ABCG2) and Lung Resistant Protein (LRP). Our study provides new insights on the role of ANXA1 protein in PCa onset and progression.

  19. Annexin A1 is involved in the acquisition and maintenance of a stem cell-like/aggressive phenotype in prostate cancer cells with acquired resistance to zoledronic acid.

    PubMed

    Bizzarro, Valentina; Belvedere, Raffaella; Milone, Maria Rita; Pucci, Biagio; Lombardi, Rita; Bruzzese, Francesca; Popolo, Ada; Parente, Luca; Budillon, Alfredo; Petrella, Antonello

    2015-09-22

    In this study, we have characterized the role of annexin A1 (ANXA1) in the acquisition and maintenance of stem-like/aggressive features in prostate cancer (PCa) cells comparing zoledronic acid (ZA)-resistant DU145R80 with their parental DU145 cells. ANXA1 is over-expressed in DU145R80 cells and its down-regulation abolishes their resistance to ZA. Moreover, ANXA1 induces DU145 and DU145R80 invasiveness acting through formyl peptide receptors (FPRs). Also, ANXA1 knockdown is able to inhibit epithelial to mesenchymal transition (EMT) and to reduce focal adhesion kinase (FAK) and metalloproteases (MMP)-2/9 expression in PCa cells. DU145R80 show a cancer stem cell (CSC)-like signature with a high expression of CSC markers including CD44, CD133, NANOG, Snail, Oct4 and ALDH7A1 and CSC-related genes as STAT3. Interestingly, ANXA1 knockdown induces these cells to revert from a putative prostate CSC to a more differentiated phenotype resembling DU145 PCa cell signature. Similar results are obtained concerning some drug resistance-related genes such as ATP Binding Cassette G2 (ABCG2) and Lung Resistant Protein (LRP). Our study provides new insights on the role of ANXA1 protein in PCa onset and progression. PMID:26312765

  20. Vaccine Treatment for Prostate Cancer

    MedlinePlus

    ... Preventing and treating prostate cancer spread to bones Vaccine treatment for prostate cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  1. Hormone therapy for prostate cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000908.htm Hormone therapy for prostate cancer To use the sharing ... helps slow the growth of prostate cancer. Male Hormones and Prostate Cancer Androgens are male sex hormones. ...

  2. Down-regulation of both p21/Cip1 and p27/Kip1 produces a more aggressive prostate cancer phenotype

    PubMed Central

    Roy, Srirupa; Singh, Rana P.; Agarwal, Chapla; Siriwardana, Sunitha; Sclafani, Robert; Agarwal, Rajesh

    2009-01-01

    Roles of cyclin dependent kinase inhibitors, p21/Cip1 (p21) and p27/Kip1 (p27) in prostate cancer (PCa) progression is still not clear. Lower p27 protein expression in PCa tissues is often associated with poor prognosis, but prognostic significance of p21 is still controversial. Herein, we investigated the role of these molecules in determining PCa growth characteristics. We generated human PCa DU145 cell variants with knocked down levels of p21 (DU-p21) or p27 (DU-p27), or both (DU-p21+p27) via retroviral transduction of respective shRNAs and compared their various characteristics with empty vector-transduced DU145 (DU-EV) cells in vitro as well as in vivo. Knocking down either p21 or p27 did not show any significant change in doubling time, clonogenicity and cell cycle progression in DU145 cells, but simultaneous knock-down of both p21 and p27 significantly enhanced these parameters. In athymic mice, DU-p21+p27 tumors showed higher growth rate than the comparable growth of DU-EV, DU-p21 and DU-p27 tumors. Concurrently, DU-p21+p27 tumors had significantly higher proliferation rate, showing 54% and 48% increase in proliferating cell nuclear antigen (PCNA) and Ki-67-positive cells, respectively, compared to DU-EV tumors. DU-p21+p27 tumors also showed higher microvessel density and increased expression of vascular endothelial growth factor (VEGF). Proliferation and angiogenic status of DU-p21 and DU-p27 tumors was comparable to DU-EV tumors. Both in vitro and in vivo results implicate that p21 and p27 have compensatory roles in advanced prostate cancer cells, and ablation or down-modulation of both these molecules essentially enhances the aggressive prostate carcinoma phenotype. PMID:18583941

  3. PSA Screening Has Led to Overtreatment of Many Prostate Cancers

    Cancer.gov

    Screening for prostate cancer with the prostate-specific antigen (PSA) test has led to overtreatment of many prostate cancers, including aggressive treatments in older men considered to be at low risk for progression of the disease according to a study published in the July 26, 2010 Archives of Internal Medicine.

  4. Prostate cancer staging

    MedlinePlus

    ... effects of treatment The chance that treatment can cure your cancer or help you in other ways With stage ... III prostate cancer, the main goal is to cure the cancer by treating it and keeping it from coming ...

  5. A Genome-wide Pleiotropy Scan for Prostate Cancer Risk

    PubMed Central

    Panagiotou, Orestis A; Travis, Ruth C; Campa, Daniele; Berndt, Sonja I.; Lindstrom, Sara; Kraft, Peter; Schumacher, Fredrick R.; Siddiq, Afshan; Papatheodorou, Stefania I.; Stanford, Janet L.; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie J.; Diver, W. Ryan; Gapstur, Susan M.; Stevens, Victoria L.; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Gurrea, Aurelio Barricarte; Kaaks, Rudolf; Khaw, Kay-Tee; Krogh, Vittorio; Overvad, Kim; Riboli, Elio; Trichopoulos, Dimitrios; Giovannucci, Edward; Stampfer, Meir; Haiman, Christopher; Henderson, Brian; Le Marchand, Loic; Gaziano, J. Michael; Hunter, DavidJ.; Koutros, Stella; Yeager, Meredith; Hoover, Robert N.; Chanock, Stephen J.; Wacholder, Sholom; Key, Timothy J.; Tsilidis, Konstantinos K

    2014-01-01

    Background No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). Objective To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. Design, setting, and participants SNPs implicated in any phenotype other than prostate cancer (p ≤ 10−7) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24 534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Outcome measurements and statistical analysis Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated. Results and limitations A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p = 1.6 × 10-6), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95%CI 1.16–1.27; p = 3.22 × 10−18). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86–0.94; p = 2.5 × 10−6). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12,95% CI 1.06–1.19; p = 4.67 × 10−5); it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. Conclusions We did

  6. Hormone therapy for prostate cancer

    MedlinePlus

    Androgen deprivation therapy; ADT; Androgen suppression therapy; Combined androgen blockade ... Androgens cause prostate cancer cells to grow. Hormone therapy for prostate cancer lowers the effect level of ...

  7. Prostate cancer screenings

    MedlinePlus

    Prostate-specific antigen (PSA) test is a blood test that checks the level of PSA in your blood. In some cases, a high level of PSA could mean you have prostate cancer. But other conditions can also cause a high level, such as infection in the prostate or ...

  8. Height and Prostate Cancer Risk

    PubMed Central

    Zuccolo, Luisa; Harris, Ross; Gunnell, David; Oliver, Steven; Lane, Jane Athene; Davis, Michael; Donovan, Jenny; Neal, David; Hamdy, Freddie; Beynon, Rebecca; Savovic, Jelena; Martin, Richard Michael

    2008-01-01

    Background Height, a marker of childhood environmental exposures, is positively associated with prostate cancer risk, perhaps through the insulin-like growth factor system. We investigated the relationship of prostate cancer with height and its components (leg and trunk length) in a nested case-control study and with height in a dose-response meta-analysis. Methods We nested a case-control study within a population-based randomized controlled trial evaluating treatments for localized prostate cancer in British men ages 50 to 69 years, including 1,357 cases detected through prostate-specific antigen testing and 7,990 controls (matched on age, general practice, assessment date). Nine bibliographic databases were searched systematically for studies on the height-prostate cancer association that were pooled in a meta-analysis. Results Based on the nested case-control, the odds ratio (OR) of prostate-specific antigen-detected prostate cancer per 10 cm increase in height was 1.06 [95% confidence interval (95% CI): 0.97-1.16; ptrend = 0.2]. There was stronger evidence of an association of height with high-grade prostate cancer (OR: 1.23; 95% CI: 1.06-1.43), mainly due to the leg component, but not with low-grade disease (OR: 0.99; 95% CI: 0.90-1.10). In general, associations with leg or trunk length were similar. A meta-analysis of 58 studies found evidence that height is positively associated with prostate cancer (random-effects OR per 10 cm: 1.06; 95% CI: 1.03-1.09), with a stronger effect for prospective studies of more advanced/aggressive cancers (random-effects OR: 1.12; 95% CI: 1.05-1.19). Conclusion These data indicate a limited role for childhood environmental exposures—as indexed by adult height—on prostate cancer incidence, while suggesting a greater role for progression, through mechanisms requiring further investigation. PMID:18768501

  9. What Is Prostate Cancer?

    MedlinePlus Videos and Cool Tools

    ... the more likely he is to develop the disease. Physician: Come on back, first room. Narrator: Most ... cancer. Prostate cancer is really a spectrum of diseases where on one end of the spectrum there ...

  10. Prostate cancer - treatment

    MedlinePlus

    ... when cancer has spread to the bone. External beam radiation therapy uses high-powered x-rays pointed ... radiation therapy used to treat prostate cancer. Proton beams target the tumor precisely, so there is less ...

  11. Detecting Prostate Cancer

    MedlinePlus Videos and Cool Tools

    ... abnormal and raises the index of suspicion that cancer may be present. Narrator: While the use of ... examination does not mean that they have prostate cancer. It means that we're concerned about it ...

  12. Prostate cancer (image)

    MedlinePlus

    Treatment of prostate cancer varies depending on the stage of the cancer (i.e., spread) and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

  13. siRNA Knockdown of Ribosomal Protein Gene RPL19 Abrogates the Aggressive Phenotype of Human Prostate Cancer

    PubMed Central

    Bee, Alix; Brewer, Daniel; Beesley, Carol; Dodson, Andrew; Forootan, Shiva; Dickinson, Timothy; Gerard, Patricia; Lane, Brian; Yao, Sheng; Cooper, Colin S.; Djamgoz, Mustafa B. A.; Gosden, Christine M.; Ke, Youqiang; Foster, Christopher S.

    2011-01-01

    We provide novel functional data that posttranscriptional silencing of gene RPL19 using RNAi not only abrogates the malignant phenotype of PC-3M prostate cancer cells but is selective with respect to transcription and translation of other genes. Reducing RPL19 transcription modulates a subset of genes, evidenced by gene expression array analysis and Western blotting, but does not compromise cell proliferation or apoptosis in-vitro. However, growth of xenografted tumors containing the knocked-down RPL19 in-vivo is significantly reduced. Analysis of the modulated genes reveals induction of the non-malignant phenotype principally to involve perturbation of networks of transcription factors and cellular adhesion genes. The data provide evidence that extra-ribosomal regulatory functions of RPL19, beyond protein synthesis, are critical regulators of cellular phenotype. Targeting key members of affected networks identified by gene expression analysis raises the possibility of therapeutically stabilizing a benign phenotype generated by modulating the expression of an individual gene and thereafter constraining a malignant phenotype while leaving non-malignant tissues unaffected. PMID:21799931

  14. An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality

    PubMed Central

    Sullivan, J; Kopp, R; Stratton, K; Manschreck, C; Corines, M; Rau-Murthy, R; Hayes, J; Lincon, A; Ashraf, A; Thomas, T; Schrader, K; Gallagher, D; Hamilton, R; Scher, H; Lilja, H; Scardino, P; Eastham, J; Offit, K; Vijai, J; Klein, R J

    2015-01-01

    Background: Genome-wide association studies have identified multiple single-nucleotide polymorphsims (SNPs) associated with prostate cancer (PCa). Although these SNPs have been clearly associated with disease risk, their relationship with clinical outcomes is less clear. Our aim was to assess the frequency of known PCa susceptibility alleles within a single institution ascertainment and to correlate risk alleles with disease-specific outcomes. Methods: We genotyped 1354 individuals treated for localised PCa between June 1988 and December 2007. Blood samples were prospectively collected and de-identified before being genotyped and matched to phenotypic data. We investigated associations between 61 SNPs and disease-specific end points using multivariable analysis and also determined if SNPs were associated with PSA at diagnosis. Results: Seven SNPs showed associations on multivariable analysis (P<0.05), rs13385191 with both biochemical recurrence (BR) and castrate metastasis (CM), rs339331 (BR), rs1894292, rs17178655 and rs11067228 (CM), and rs11902236 and rs4857841 PCa-specific mortality. After applying a Bonferroni correction for number of SNPs (P<0.0008), the only persistent significant association was between rs17632542 (KLK3) and PSA levels at diagnosis (P=1.4 × 10−5). Conclusions: We confirmed that rs17632542 in KLK3 is associated with PSA at diagnosis. No significant association was seen between loci and disease-specific end points when accounting for multiple testing. This provides further evidence that known PCa risk SNPs do not predict likelihood of disease progression. PMID:26068399

  15. Prevention and Early Detection of Prostate Cancer

    PubMed Central

    Cuzick, Jack; Thorat, Mangesh A.; Andriole, Gerald; Brawley, Otis W.; Brown, Powel H.; Culig, Zoran; Eeles, Rosalind A.; Ford, Leslie G.; Hamdy, Freddie C.; Holmberg, Lars; Ilic, Dragan; Key, Timothy J.; La Vecchia, Carlo; Lilja, Hans; Marberger, Michael; Meyskens, Frank L.; Minasian, Lori M.; Parker, Chris; Parnes, Howard L.; Perner, Sven; Rittenhouse, Harry; Schalken, Jack; Schmid, Hans-Peter; Schmitz-Dräger, Bernd J.; Schröder, Fritz H.; Stenzl, Arnulf; Tombal, Bertrand; Wilt, Timothy J.; Wolk, Alicja

    2014-01-01

    Prostate cancer is one of the most common cancers in men and the global burden of this disease is rising. Lifestyle modifications like smoking cessation, exercise and weight control offer opportunities to decrease the risk of developing prostate cancer. Early detection of prostate cancer by PSA screening remains controversial; yet, changes in PSA threshold, frequency of screening, and addition of other biomarkers have potential to minimise overdiagnosis associated with PSA screening. Several new biomarkers appear promising in individuals with elevated PSA levels or those diagnosed with prostate cancer, these are likely to guide in separating individuals who can be spared of aggressive treatment from those who need it. Several pharmacological agents like 5α-reductase inhibitors, aspirin etc. have a potential to prevent development of prostate cancer. In this review, we discuss the current evidence and research questions regarding prevention, early detection of prostate cancer and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer. PMID:25281467

  16. Chemoprevention of prostate cancer.

    PubMed

    Vemana, Goutham; Hamilton, Robert J; Andriole, Gerald L; Freedland, Stephen J

    2014-01-01

    Large prospective randomized trials, such as the Prostate Cancer Prevention Trial (PCPT), Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, and Selenium and Vitamin E Cancer Prevention Trial (SELECT), have provided practitioners with considerable data regarding methods of treatment and prevention of prostate cancer. The best-studied medications for prevention are 5 alpha-reductase inhibitors. Their efficacy and side effects are well characterized. Other medications, dietary nutrients, and supplements have not been as well studied and generally do not demonstrate efficacy for disease prevention with an acceptable level of evidence. PMID:24188663

  17. PSA and beyond: alternative prostate cancer biomarkers

    PubMed Central

    2016-01-01

    Background The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions. Methods A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected. Conclusions With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine. PMID:26790878

  18. Cancer of the Prostate

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 180,890 % of All New Cancer Cases 10.7% Estimated Deaths in 2016 26,120 % of All Cancer ... of This Cancer : In 2013, there were an estimated 2,850,139 men living with prostate cancer ...

  19. Magnetic resonance imaging of prostate cancer.

    PubMed

    Guneyli, Serkan; Erdem, Cemile Zuhal; Erdem, Lutfi Oktay

    2016-01-01

    Prostate cancer is one of the causes of cancer-related deaths. Multiparametric magnetic resonance imaging (MRI) provides the best soft tissue resolution and plays an important role in the management of prostate cancer patients. It is the recommended imaging modality for patients with prostate cancer, and it is clinically indicated for diagnosis, staging, tumor localization, detection of tumor aggressiveness, follow-up, and MRI-guided interventions. Multiparametric MRI includes T1- and high-resolution T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced MRI. We evaluated MR images of patients with prostate cancer who underwent multiparametric endorectal MRI on a 3.0-T scanner and presented demonstrative images. PMID:27317204

  20. The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence

    PubMed Central

    2013-01-01

    Background Although a previous meta-analysis reported no association between metabolic syndrome (MetS) and prostate cancer risk, a number of studies suggest that MetS may be associated with the aggressiveness and progression of prostate cancer. However, these results have been inconsistent. This systematic review and meta-analysis investigated the nature of this association. Methods We systematically searched MEDLINE, EMBASE and bibliographies of retrieved studies up to January 2013 using the keywords “metabolic syndrome” and “prostate cancer”. We assessed relative risks (RRs) of the prostate cancer, several parameters of prostate cancer aggressiveness and progression associated with MetS using 95% confidence intervals (95% CIs). Results The literature search produced 547 hits from which 19 papers were extracted for the meta-analysis. In cancer-free population with and without MetS, the combined adjusted RR (95% CI) of prostate cancer risk and prostate cancer-specific mortality in longitudinal cohort studies is 0.96 (0.85 ~ 1.09) and 1.12 (1.02 ~ 1.23) respectively. In the prostate cancer patients with and without MetS, the combined unadjusted OR (95% CI) of high grade Gleason prostate cancer is 1.44 (1.20 ~ 1.72), the OR of advanced prostate cancer is 1.37 (1.12 ~ 1.68) and the OR of biochemical recurrence is 2.06 (1.43 ~ 2.96). Conclusions The overall analyses revealed no association between MetS and prostate cancer risk, although men with MetS appear more likely to have high-grade prostate cancer and more advanced disease, were at greater risk of progression after radical prostatectomy and were more likely to suffer prostate cancer-specific death. Further primary studies with adjustment for appropriate confounders and larger, prospective, multicenter investigations are required. PMID:23406686

  1. Chemoprevention of prostate cancer.

    PubMed

    Stephenson, Andrew J; Abouassaly, Robert; Klein, Eric A

    2010-02-01

    Prostate cancer is an appropriate target for primary chemoprevention because of its ubiquity, disease-related mortality, treatment-related morbidity, and long latency period. The PCPT and REDUCE trials demonstrate that this cancer can be prevented by a relatively nontoxic oral pharmacologic agent (5alpha-reductase inhibitors). Evidence from the SELECT trial argues against the recommendation of the use of vitamins and micronutrients as chemoprevention of prostate cancer. Dietary modification may substantially alter a man's risk of prostate cancer, but the specific dietary manipulations that are necessary are poorly defined and these may need to be instituted in early adulthood to be successful. 5alpha-reductase inhibitors represent an effective primary prevention strategy, and these agents should be used more liberally for the prevention of prostate cancer, particularly in high-risk patients. PMID:20152515

  2. Drugs Approved for Prostate Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Prostate Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Prostate Cancer Abiraterone Acetate Bicalutamide Cabazitaxel Casodex (Bicalutamide) Degarelix Docetaxel ...

  3. β-Adrenergic Receptor Signaling in Prostate Cancer

    PubMed Central

    Braadland, Peder Rustøen; Ramberg, Håkon; Grytli, Helene Hartvedt; Taskén, Kristin Austlid

    2015-01-01

    Enhanced sympathetic signaling, often associated with obesity and chronic stress, is increasingly acknowledged as a contributor to cancer aggressiveness. In prostate cancer, intact sympathetic nerves are critical for tumor formation, and sympathectomy induces apoptosis and blocks tumor growth. Perineural invasion, involving enrichment of intra-prostatic nerves, is frequently observed in prostate cancer and is associated with poor prognosis. β2-adrenergic receptor (ADRB2), the most abundant receptor for sympathetic signals in prostate luminal cells, has been shown to regulate trans-differentiation of cancer cells to neuroendocrine-like cells and to affect apoptosis, angiogenesis, epithelial–mesenchymal transition, migration, and metastasis. Epidemiologic studies have shown that use of β-blockers, inhibiting β-adrenergic receptor activity, is associated with reduced prostate cancer-specific mortality. In this review, we aim to present an overview on how β-adrenergic receptor and its downstream signaling cascade influence the development of aggressive prostate cancer, primarily through regulating neuroendocrine differentiation. PMID:25629002

  4. Screening for prostate cancer.

    PubMed Central

    Cher, M L; Carroll, P R

    1995-01-01

    Prostate cancer is a serious health care problem in the United States. Whether or not to screen for it has become a timely issue. Although a large number of men have clinically important, asymptomatic, undetected prostate cancer, an even larger number have clinically unimportant cancer. To justify screening programs, not only must we avoid detecting biologically unimportant cancers, we must also detect and effectively treat that subset of tumors that, if undiagnosed, would progress, produce symptoms, and reduce life expectancy. Serum prostate-specific antigen (PSA) assay, or its variations such as PSA density, PSA velocity, and age-specific reference ranges, and the digital rectal examination are the best tests for detecting clinically important, asymptomatic, curable tumors. Recent data suggest that using serum PSA levels does not result in an overdetection of unimportant tumors. Highly effective, curative treatment of localized prostate cancer is available. These factors promote optimism that screening for prostate cancer will ultimately prove beneficial. Nonetheless, men should be informed regarding the benefits and possible risks before being screened for prostate cancer. PMID:7536993

  5. Immunotherapy in prostate cancer.

    PubMed

    Sobol, Ilya; Thompson, R H; Dong, Haidong; Krco, Christopher; Kwon, Eugene D

    2015-06-01

    Immunotherapy for the treatment of malignant neoplasms has made significant progress over the last 20 years. Multiple molecular targets and clinical agents have been developed recently, particularly in the field of metastatic adenocarcinoma of the prostate. Sipuleucel-T is currently the only FDA approved immunotherapy for prostate cancer. PSA-TRICOM (Prostvac) currently has a phase III randomized trial underway after a phase II trial showed an improvement in overall survival. Interestingly, both these agents showed improvement in overall survival with no measurable change in disease state, leading to significant controversy as the utility of these agents in prostate cancer. Ipilimumab revealed a benefit for a sub-cohort of men in a post-docetaxel group and is currently undergoing investigation in a pre-docetaxel group. There are a number of other targets such as PD-1 which have shown effectiveness in other neoplasms that will likely be investigated in the future for use in prostate cancer. PMID:25894495

  6. Understanding Prostate Cancer: Newly Diagnosed

    MedlinePlus

    ... Wellness PCF Spotlight Glossary African American Men Understanding Prostate Cancer Newly Diagnosed Newly Diagnosed Staging the Disease Issues ... you care about has recently been diagnosed with prostate cancer, this section will help guide you through the ...

  7. New Prostate Cancer Treatment Target

    Cancer.gov

    Researchers have identified a potential alternative approach to blocking a key molecular driver of an advanced form of prostate cancer, called androgen-independent or castration-resistant prostate cancer.

  8. Clinical Perspective of Prostate Cancer.

    PubMed

    Patil, Nilesh; Gaitonde, Krishnanath

    2016-06-01

    Prostate cancer is the most common noncutaneous cancer affecting men today. It largely affects men in the fifth and sixth decade of life. Screening for prostate cancer, though controversial, is still the only way to detect early prostate cancer. Multiple newer options such as blood tests and genetic markers are being used in the clinical domain today to improve cancer detection and avoid unnecessary biopsies. To date, biopsy of the prostate remains the only modality to stratify the grade of cancer. Significant improvements in the imaging technology have improved localizing and detecting the disease. Treatment of prostate cancer is stratified on the basis of the grade and volume of the disease. There are multiple treatment options involved in the management of prostate cancer. Treatment of localized prostate cancer still continues to have very high cure rates and long-term cancer-specific survival rates. PMID:27187167

  9. Evolving Recommendations on Prostate Cancer Screening.

    PubMed

    Brawley, Otis W; Thompson, Ian M; Grönberg, Henrik

    2016-01-01

    Results of a number of studies demonstrate that the serum prostate-specific antigen (PSA) in and of itself is an inadequate screening test. Today, one of the most pressing questions in prostate cancer medicine is how can screening be honed to identify those who have life-threatening disease and need aggressive treatment. A number of efforts are underway. One such effort is the assessment of men in the landmark Prostate Cancer Prevention Trial that has led to a prostate cancer risk calculator (PCPTRC), which is available online. PCPTRC version 2.0 predicts the probability of the diagnosis of no cancer, low-grade cancer, or high-grade cancer when variables such as PSA, age, race, family history, and physical findings are input. Modern biomarker development promises to provide tests with fewer false positives and improved ability to find high-grade cancers. Stockholm III (STHLM3) is a prospective, population-based, paired, screen-positive, prostate cancer diagnostic study assessing a combination of plasma protein biomarkers along with age, family history, previous biopsy, and prostate examination for prediction of prostate cancer. Multiparametric MRI incorporates anatomic and functional imaging to better characterize and predict future behavior of tumors within the prostate. After diagnosis of cancer, several genomic tests promise to better distinguish the cancers that need treatment versus those that need observation. Although the new technologies are promising, there is an urgent need for evaluation of these new tests in high-quality, large population-based studies. Until these technologies are proven, most professional organizations have evolved to a recommendation of informed or shared decision making in which there is a discussion between the doctor and patient. PMID:27249774

  10. Prostate Cancer Support Groups

    PubMed Central

    Chambers, Suzanne; Garrett, Bernie; Bottorff, Joan L.; McKenzie, Michael; Han, Christina S.; Ogrodniczuk, John S.

    2015-01-01

    To understand prostate cancer (PCa) specialists’ views about prostate cancer support groups (PCSGs), a volunteer sample of Canada-based PCa specialists (n = 150), including urologists (n = 100), radiation oncologists (n = 40), and medical oncologists (n = 10) were surveyed. The 56-item questionnaire used in this study included six sets of attitudinal items to measure prostate cancer specialists’ beliefs about positive and negative influences of PCSGs, reasons for attending PCSGs, the attributes of effective PCSGs, and the value of face-to-face and web-based PCSGs. In addition, an open-ended question was included to invite additional input from participants. Results showed that PCSGs were positively valued, particularly for information sharing, education and psychosocial support. Inclusivity, privacy, and accessibility were identified as potential barriers, and recommendations were made for better marketing PCSGs to increase engagement. Findings suggest prostate cancer specialists highly valued the role and potential benefits of face-to-face PCSGs. Information provision and an educational role were perceived as key benefits. Some concerns were expressed about the ability of web-based PCSGs to effectively engage and educate men who experience prostate cancer. PMID:25061087

  11. Radioimmunoscintigraphy of prostate cancer

    SciTech Connect

    Babaian, R.J.; Lamki, L.M. )

    1989-10-01

    The development of hybridoma technology has increased research efforts and clinical applications in the area of radioimmunodetection. Despite the many investigative antibodies directed against prostatic tissue or prostate cancer cell lines, only two have been tested in clinical trials. A 111In-labeled antibody directed against prostate-specific antigen, the best available serum tumor marker for prostate cancer, has shown poor sensitivity in limited clinical radioimmunoimaging trials. Monoclonal antibodies against prostatic acid phosphatase have shown better imaging results, particularly at higher antibody doses (greater than or equal to 40 mg). The limitations of this antibody include the poor results in detecting soft tissue lesions, including the primary lesion; the development of human antimouse antibodies in 50% of the patients at doses greater than or equal to 40 mg; the expense of the antibody; and the fact that better results are currently attainable by other less expensive imaging modalities. If and when a more suitable antibody or fragment is developed, the prospect of improved staging and new treatments using immunologic conjugates carrying therapeutic agents may become realities. Until such time, prostatic cancer will be staged with other currently available imaging modalities and conventional therapies with their limitations will remain state of the art. 56 references.

  12. A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy

    PubMed Central

    Pertega-Gomes, Nelma; Felisbino, Sergio; Massie, Charlie E; Vizcaino, Jose R; Coelho, Ricardo; Sandi, Chiranjeevi; Simoes-Sousa, Susana; Jurmeister, Sarah; Ramos-Montoya, Antonio; Asim, Mohammad; Tran, Maxine; Oliveira, Elsa; Lobo da Cunha, Alexandre; Maximo, Valdemar; Baltazar, Fatima; Neal, David E; Fryer, Lee GD

    2015-01-01

    Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia-inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors. © 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:25875424

  13. Chemotherapy in Prostate Cancer.

    PubMed

    Hurwitz, Michael

    2015-10-01

    For approximately a decade, chemotherapy has been shown to prolong life in patients with metastatic castration-resistant prostate cancer (mCRPC). Since that time, however, only two agents have proven to prolong life (docetaxel and cabazitaxel). However, in the last year, the addition of chemotherapy to primary hormonal therapy became a standard of care for high-volume castration-sensitive metastatic disease. Here I will review current prostate cancer chemotherapies, mechanisms of resistance to those therapies, and ongoing clinical studies of chemotherapy combinations and novel chemotherapeutics. PMID:26216506

  14. Acquired resistance to zoledronic acid and the parallel acquisition of an aggressive phenotype are mediated by p38-MAP kinase activation in prostate cancer cells

    PubMed Central

    Milone, M R; Pucci, B; Bruzzese, F; Carbone, C; Piro, G; Costantini, S; Capone, F; Leone, A; Di Gennaro, E; Caraglia, M; Budillon, A

    2013-01-01

    The nitrogen-containing bisphosphonates (N-BP) zoledronic acid (ZOL) inhibits osteoclast-mediated bone resorption, and it is used to prevent skeletal complications from bone metastases. ZOL has also demonstrated anticancer activities in preclinical models and, recently, in cancer patients, highlighting the interest in determining eventual mechanisms of resistance against this agent. In our study, we selected and characterised a resistant subline of prostate cancer (PCa) cells to better understand the mechanisms, by which tumour cells can escape the antitumour effect of ZOL. DU145R80-resistant cells were selected in about 5 months using stepwise increasing concentrations of ZOL from DU145 parental cells. DU145R80 cells showed a resistance index value of 5.5 and cross-resistance to another N-BP, pamidronate, but not to the non-nitrogen containing BP clodronate. Notably, compared with DU145 parental cells, DU145R80 developed resistance to apoptosis and anoikis, as well as overexpressed the anti-apoptotic protein Bcl-2 and oncoprotein c-Myc. Moreover, DU145R80 cells underwent epithelial to mesenchymal transition (EMT) and showed increased expression of the metalloproteases MMP-2/9, as well as increased invading capability. Interestingly, compared with DU145, DU145R80 cells also increased the gene expression and protein secretion of VEGF and the cytokines Eotaxin-1 and IL-12. At the molecular level, DU145R80 cells showed strong activation of the p38-MAPK-dependent survival pathway compared with parental sensitive cells. Moreover, using the p38-inhibitor SB203580, we completely reversed the resistance to ZOL, as well as EMT marker expression and invasion. Furthermore, SB203580 treatment reduced the expression of VEGF, Eotaxin-1, IL-12, MMP-9, Bcl-2 and c-Myc. Thus, for the first time, we demonstrate that the p38-MAPK pathway can be activated under continuous extensive exposure to ZOL in PCa cells and that the p38-MAPK pathway has a critical role in the induction of

  15. Prostate Cancer: Take Time to Decide

    MedlinePlus

    ... printing [PDF-983KB] Cancer Home Prostate Cancer: Take Time to Decide Infographic Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Prostate Cancer: Take Time to Decide Most prostate cancers grow slowly, and ...

  16. SU-E-J-95: Predicting Treatment Outcomes for Prostate Cancer: Irradiation Responses of Prostate Cancer Stem Cells

    SciTech Connect

    Wang, K

    2014-06-01

    Purpose: Most prostate cancers are slow-growing diseases but normally require much higher doses (80Gy) with conventional fractionation radiotherapy, comparing to other more aggressive cancers. This study is to disclose the radiobiological basis of this discrepancy by proposing the concept of prostate cancer stem cells (CSCs) and examining their specific irradiation responses. Methods: There are overwhelming evidences that CSC may keep their stemness, e.g. the competency of cell differentiation, in hypoxic microenvironments and hence become radiation resistive, though the probability is tiny for aggressiveness cancers. Tumor hypoxia used to be considered as an independent reason for poor treatment outcomes, and recent evidences showed that even prostate cancers were also hypoxic though they are very slow-growing. In addition, to achieve comparable outcomes to other much more aggressive cancers, much higher doses (rather than lower doses) are always needed for prostate cancers, regardless of its non-aggressiveness. All these abnormal facts can only be possibly interpreted by the irradiation responses characteristics of prostate CSCs. Results: Both normal cancer cells (NCCs) and CSCs exiting in tumors, in which NCCs are mainly for symptoms whereas killing all CSCs achieves disease-free. Since prostate cancers are slow-growing, the hypoxia in prostate cancers cannot possibly from NCCs, thus it is caused by hypoxic CSCs. However, single hypoxic cell cannot be imaged due to limitation of imaging techniques, unless a large group of hypoxic cells exist together, thus most of CSCs in prostate cancers are virtually hypoxic, i.e. not in working mode because CSCs in proliferating mode have to be normoxic, and this explains why prostate cancers are unaggressive. Conclusion: The fractional dose in conventional radiotherapy (∼2Gy) could only kill NCCs and CSCs in proliferating modes, whereas most CSCs survived fractional treatments since they were hypoxic, thus to eliminate all

  17. [Grading of prostate cancer].

    PubMed

    Kristiansen, G; Roth, W; Helpap, B

    2016-07-01

    The current grading of prostate cancer is based on the classification system of the International Society of Urological Pathology (ISUP) following a consensus conference in Chicago in 2014. The foundations are based on the frequently modified grading system of Gleason. This article presents a brief description of the development to the current ISUP grading system. PMID:27393141

  18. Prostate cancer markers: An update

    PubMed Central

    PENTYALA, SRINIVAS; WHYARD, TERRY; PENTYALA, SAHANA; MULLER, JOHN; PFAIL, JOHN; PARMAR, SUNJIT; HELGUERO, CARLOS G.; KHAN, SARDAR

    2016-01-01

    As the most common noncutaneous malignancy in American men, prostate cancer currently accounts for 29% of all diagnosed cancers, and ranks second as the cause of cancer fatality in American men. Prostatic cancer is rarely symptomatic early in its course and therefore disease presentation often implies local extension or even metastatic disease. Thus, it is extremely critical to detect and diagnose prostate cancer in its earliest stages, often prior to the presentation of symptoms. Three of the most common techniques used to detect prostate cancer are the digital rectal exam, the transrectal ultrasound, and the use of biomarkers. This review presents an update regarding the field of prostate cancer biomarkers and comments on future biomarkers. Although there is not a lack of research in the field of prostate cancer biomarkers, the discovery of a novel biomarker that may have the advantage of being more specific and effective warrants future scientific inquiry. PMID:26998261

  19. Vitamin E and Prostate Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin E, its metabolites or its analogs, might help prevent prostate cancer initiation or progression. Prostate cancer is the most common non-skin malignancy and the second leading cause of cancer deaths among men in the United States, exceeded only by lung cancer. About 218,890 new cases of prost...

  20. What Tests Can Detect Prostate Cancer?

    MedlinePlus

    ... prostate cancer early detection What tests can detect prostate cancer early? The tests discussed below are used to ... also found in the blood. Most men without prostate cancer have PSA levels under 4 nanograms per milliliter ( ...

  1. Survival in prostate cancer prevention trial detailed

    Cancer.gov

    In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

  2. Quantitative Analysis of Prostate Multiparametric MR Images for Detection of Aggressive Prostate Cancer in the Peripheral Zone: A Multiple Imager Study.

    PubMed

    Hoang Dinh, Au; Melodelima, Christelle; Souchon, Rémi; Lehaire, Jérôme; Bratan, Flavie; Mège-Lechevallier, Florence; Ruffion, Alain; Crouzet, Sébastien; Colombel, Marc; Rouvière, Olivier

    2016-07-01

    Purpose To assess the intermanufacturer variability of quantitative models in discriminating cancers with a Gleason score of at least 7 among peripheral zone (PZ) lesions seen at 3-T multiparametric magnetic resonance (MR) imaging. Materials and Methods An institutional review board-approved prospective database of 257 patients who gave written consent and underwent T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced imaging before prostatectomy was retrospectively reviewed. It contained outlined lesions found to be suspicious for malignancy by two independent radiologists and classified as malignant or benign after correlation with prostatectomy whole-mount specimens. One hundred six patients who underwent imaging with 3-T MR systems from two manufacturers were selected (data set A, n = 72; data set B, n = 34). Eleven parameters were calculated in PZ lesions: normalized T2-weighted signal intensity, skewness and kurtosis of T2-weighted signal intensity, T2 value, wash-in rate, washout rate, time to peak (TTP), mean apparent diffusion coefficient (ADC), 10th percentile of the ADC, and skewness and kurtosis of the histogram of the ADC values. Parameters were selected on the basis of their specificity for a sensitivity of 0.95 in diagnosing cancers with a Gleason score of at least 7, and the area under the receiver operating characteristic curve (AUC) for the models was calculated. Results The model of the 10th percentile of the ADC with TTP yielded the highest AUC in both data sets. In data set A, the AUC was 0.90 (95% confidence interval [CI]: 0.85, 0.95) or 0.89 (95% CI: 0.82, 0.94) when it was trained in data set A or B, respectively. In data set B, the AUC was 0.84 (95% CI: 0.74, 0.94) or 0.86 (95% CI: 0.76, 0.95) when it was trained in data set A or B, respectively. No third variable added significantly independent information in any data set. Conclusion The model of the 10th percentile of the ADC with TTP yielded accurate results in

  3. Dutasteride May Slow the Growth of Early-Stage Prostate Cancer | Division of Cancer Prevention

    Cancer.gov

    For men who are undergoing active surveillance for early-stage prostate cancer, the drug dutasteride (Avodart) could help control the disease and prevent the need for more aggressive treatments. |

  4. Metastatic Prostate Cancer to the Duodenum: A Rare Case

    PubMed Central

    Kaswala, Dharmesh H.; Patel, Nitin; Jadallah, Sana; Wang, Weizheng

    2014-01-01

    Prostate cancer is the third most common cancer in man. About 1 in 6 males developed prostate cancer and 1 in 35 males die of this disease. Prostate cancer behavior ranges from microscopic tumors to aggressive cancer with metastatic potential. While metastasis to bone is relatively common, prostate cancer rarely metastasizes to the cecum, pituitary gland, small bowel, maxillary sinus and skin. Our case report presents a rare presentation of metastatic prostate cancer to the duodenum. Our search of the literature found only 2 cases of prostate metastases to duodenum published from 1966 to the present. To our knowledge this is the third case of metastatic prostate cancer presenting with duodenal metastasis. Although it is rare but in symptomatic patients small intestine metastasis should not be ignored with advanced prostate cancer. The case demonstrates a novel presentation of a common malignancy, and should raise awareness in clinicians and radiologists that prostate cancer can present with distant metastases in absence of any local lymphadenopathy. PMID:25161979

  5. Tumor microenvironment and metabolism in prostate cancer.

    PubMed

    Chiarugi, Paola; Paoli, Paolo; Cirri, Paolo

    2014-04-01

    Prostate cancer is no longer viewed mostly as a disease of abnormally proliferating epithelial cells, but rather as a disease affecting the complex interactions between the cells of the prostate epithelial compartment and the surrounding stromal compartment in which they live. Indeed, the microenvironment in which tumor cells evolve towards an aggressive phenotype is highly heterogeneous, as it is composed of different cell populations such as endothelial cells, fibroblasts, macrophages, and lymphocytes, either resident or trans-differentiated by bone marrow-derived mesenchymal stem cells recruited at the tumor site. Cancer-associated fibroblasts, the most abundant population within this microenvironment, exert a mandatory role in prostate cancer progression as they metabolically sustain cancer cell survival and growth, recruit inflammatory and immune cells, and promote cancer cells stemness and epithelial mesenchymal transition, thereby favoring metastatic dissemination of aggressive cancers. The interruption of this two-compartment crosstalk, together with the idea that stromal cells are mostly vulnerable, being drug-sensitive, could lead to the development of anticancer therapies that target tumor stromal elements. PMID:24787298

  6. Prospective evaluation of serum sarcosine and risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

    PubMed Central

    Koutros, Stella; Hsing, Ann W.; Berndt, Sonja I.

    2013-01-01

    Metabolomic profiling has identified, sarcosine, a derivative of the amino acid glycine, as an important metabolite involved in the etiology or natural history of prostate cancer. We examined the association between serum sarcosine levels and risk of prostate cancer in 1122 cases (813 non-aggressive and 309 aggressive) and 1112 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Sarcosine was quantified using high-throughput liquid chromatography–mass spectrometry. A significantly increased risk of prostate cancer was observed with increasing levels of sarcosine (odds ratio [OR] for the highest quartile of exposure [Q4] versus the lowest quartile [Q1] = 1.30, 95% confidence interval [CI]: 1.02, 1.65; P-trend 0.03). When stratified by disease aggressiveness, we observed a stronger association for non-aggressive cases (OR for Q4 versus Q1 = 1.44, 95% CI: 1.11, 1.88; P-trend 0.006) but no association for aggressive prostate cancer (OR for Q4 versus Q1 = 1.03, 95% CI: 0.73, 1.47; P-trend 0.89). Although not statistically significant, temporal analyses showed a stronger association between sarcosine and prostate cancer for serum collected closer to diagnosis, suggesting that sarcosine may be an early biomarker of disease. Interestingly, the association between sarcosine and prostate cancer risk was stronger among men with diabetes (OR = 2.66, 95% CI: 1.04, 6.84) compared with those without reported diabetes (OR = 1.23, 95% CI: 0.95–1.59, P-interaction = 0.01). This study found that elevated levels of serum sarcosine are associated with an increased prostate cancer risk and evidence to suggest that sarcosine may be an early biomarker for this disease. PMID:23698636

  7. Hepcidin regulation in prostate and its disruption in prostate cancer

    PubMed Central

    Tesfay, Lia; Clausen, Kathryn A.; Kim, Jin W.; Hegde, Poornima; Wang, Xiaohong; Miller, Lance D.; Deng, Zhiyong; Blanchette, Nicole; Arvedson, Tara; Miranti, Cindy K.; Babitt, Jodie L.; Lin, Herbert Y.; Peehl, Donna M.; Torti, Frank M.; Torti, Suzy V.

    2015-01-01

    Hepcidin is a circulating peptide hormone made by the liver that is a central regulator of systemic iron uptake and recycling. Here we report that prostate epithelial cells also synthesize hepcidin, and that synthesis and secretion of hepcidin are markedly increased in prostate cancer cells and tissue. Prostatic hepcidin functions as an autocrine hormone, decreasing cell surface ferroportin, an iron exporter, increasing intracellular iron retention, and promoting prostate cancer cell survival. Synthesis of hepcidin in prostate cancer is controlled by a unique intersection of pathways that involves BMP4/7, IL6, Wnt, and the dual BMP and Wnt antagonist, SOSTDC1. Epigenetic silencing of SOSTDC1 through methylation is increased in prostate cancer, and is associated with accelerated disease progression in prostate cancer patients. These results establish a new connection between iron metabolism and prostate cancer, and suggest that prostatic dysregulation of hepcidin contributes to prostate cancer growth and progression. PMID:25858146

  8. Biomarkers in Prostate Cancer Epidemiology

    PubMed Central

    Verma, Mukesh; Patel, Payal; Verma, Mudit

    2011-01-01

    Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person's genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed. PMID:24213111

  9. Biomarkers for prostate cancer.

    PubMed

    Schiffer, Eric

    2007-12-01

    Novel biomarkers for prostate cancer (PCa) are currently being assessed for utility in PCa diagnosis. This article aims to provide concise information on the current findings that impact prostate cancer research. Results of enzyme-linked immunosorbent assays (ELISA) for single biomarkers, quantitative polymerase chain reaction (PCR)-based assays for DNA/RNA markers will be reviewed in addition to high-throughput proteomic profiling of PCa specimens. The advantages/disadvantages of tissue, blood, urine or seminal plasma as sources for potential biomarkers are discussed emphasizing the consequences for PCa diagnosis. In summary, the majority of promising marker candidates available today needs further validation. Some of the identified markers have the potential to yield novel prognostic tools for PCa, provide novel insights into its pathophysiology, and contribute to the establishment of novel treatment strategies. PMID:17690889

  10. [Screening for prostate cancer].

    PubMed

    Koch, Klaus; Büchter, Roland; Lange, Stefan

    2013-04-01

    Prostate cancer screening has been a controversial for decades. The recently published findings of large trials have further intensified the debate. The prospect of reducing mortality from prostate cancer is measured against the risk of over-diagnosing the disease. In individual cases, the trade-off between possible benefits and harms is possible to ascertain, so general recommendations in favor of or against PSA tests for individuals cannot be made. The majority of men, however, are not well-informed on the possible advantages and drawbacks of screening. This situation urgently needs to be corrected. The PSA test is promoted to healthy men, who need to be provided with especially detailed information. If not provided with clear and unbiased information on the risks associated with the test (above all over-diagnosis and over-treatment), these men cannot be considered to be fully informed. PMID:23535548

  11. Prostate Cancer MR Imaging

    NASA Astrophysics Data System (ADS)

    Fütterer, Jurgen J.

    With a total of 192,280 new cases predicted for 2009, prostate cancer (PC) now accounts for 25% of all new male cancers diagnosed in the United States [1]. Furthermore, in their lifetime, one in six men will be clinically diagnosed with having PC, although many more men are found to have histological evidence of PC at autopsy [2,3,4]. Presently, approximately 1 in 10 men will die of PC [5,6]. The ever-aging population and wider spread use of the blood prostate-specific antigen (PSA) test [7,8], as well as the tendency to apply lower cut-off levels for this test [9], will further increase the diagnosis of this disease [10].

  12. Biochip analysis of prostate cancer.

    PubMed

    Fan, M Q; Wang, P X; Feng, J Y; Xiao, Y; Huang, C B

    2014-01-01

    Microarray expression analysis was used to forecast the roles of differentially co-expressed genes (DCG) and DCG and links in the pathogenesis of prostate cancer. In addition, we demonstrate that the relationship between transcriptional factors (TFs) and their targets can be considered a key factor in determining the difference between primary and metastatic prostate cancer. Regulatory impact factors were adopted to calculate the impact of TF. We identified 5 TFs and 29 target genes important in the transition between normal prostate and primary prostate cancer and 2 TFs and 7 target genes important in the transition between primary and metastatic prostate cancer. These results suggest that it may be possible to predict the clinical behavior of prostate cancer based on gene expression analysis. PMID:24446298

  13. Cabazitaxel Plus Prednisone With Octreotide For Castration-Resistant Prostate Cancer (CRPC) Previously Treated With Docetaxel

    ClinicalTrials.gov

    2014-11-21

    Diarrhea; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

  14. Clinical variability and molecular heterogeneity in prostate cancer.

    PubMed

    Shoag, Jonathan; Barbieri, Christopher E

    2016-01-01

    Prostate cancer is a clinically heterogeneous disease, with some men having indolent disease that can safely be observed, while others have aggressive, lethal disease. Over the past decade, researchers have begun to unravel some of the genomic heterogeneity that contributes to these varying clinical phenotypes. Distinct molecular sub-classes of prostate cancer have been identified, and the uniqueness of these sub-classes has been leveraged to predict clinical outcomes, design novel biomarkers for prostate cancer diagnosis, and develop novel therapeutics. Recent work has also elucidated the temporal and spatial heterogeneity of prostate cancer, helping us understand disease pathogenesis, response to therapy, and progression. New genomic techniques have provided us with a window into the remarkable clinical and genomic heterogeneity of prostate cancer, and this new perspective will increasingly impact patient care. PMID:27080479

  15. Clinical variability and molecular heterogeneity in prostate cancer

    PubMed Central

    Shoag, Jonathan; Barbieri, Christopher E

    2016-01-01

    Prostate cancer is a clinically heterogeneous disease, with some men having indolent disease that can safely be observed, while others have aggressive, lethal disease. Over the past decade, researchers have begun to unravel some of the genomic heterogeneity that contributes to these varying clinical phenotypes. Distinct molecular sub-classes of prostate cancer have been identified, and the uniqueness of these sub-classes has been leveraged to predict clinical outcomes, design novel biomarkers for prostate cancer diagnosis, and develop novel therapeutics. Recent work has also elucidated the temporal and spatial heterogeneity of prostate cancer, helping us understand disease pathogenesis, response to therapy, and progression. New genomic techniques have provided us with a window into the remarkable clinical and genomic heterogeneity of prostate cancer, and this new perspective will increasingly impact patient care. PMID:27080479

  16. Active surveillance for prostate cancer: patient selection and management

    PubMed Central

    Klotz, L.

    2010-01-01

    Screening for prostate cancer using prostate-specific antigen (psa) has been appealing. However, the significant associated decline in prostate cancer mortality comes at the cost of a very high rate of diagnosis, and many patients with indolent, non-life-threatening cancer are exposed to the risk of significant side effects from radical treatment. Most men with favourable-risk prostate cancer are not destined to die of their disease, even in the absence of treatment. The challenge is to identify the subset that harbour more aggressive disease early enough that curative therapy is still a possibility, thereby allowing the others to enjoy improved quality of life, free from the side effects of treatment. This article reviews current research into active surveillance in favourable-risk disease and some of the issues that arise when prostate cancer is monitored rather than being treated immediately. PMID:20882126

  17. CXCL5 Promotes Prostate Cancer Progression1

    PubMed Central

    Begley, Lesa A; Kasina, Sathish; Mehra, Rohit; Adsule, Shreelekha; Admon, Andrew J; Lonigro, Robert J; Chinnaiyan, Arul M; Macoska, Jill A

    2008-01-01

    CXCL5 is a proangiogenic CXC-type chemokine that is an inflammatory mediator and a powerful attractant for granulocytic immune cells. Unlike many other chemokines, CXCL5 is secreted by both immune (neutrophil, monocyte, and macrophage) and nonimmune (epithelial, endothelial, and fibroblastic) cell types. The current study was intended to determine which of these cell types express CXCL5 in normal and malignant human prostatic tissues, whether expression levels correlated with malignancy and whether CXCL5 stimulated biologic effects consistent with a benign or malignant prostate epithelial phenotype. The results of these studies show that CXCL5 protein expression levels are concordant with prostate tumor progression, are highly associated with inflammatory infiltrate, and are frequently detected in the lumens of both benign and malignant prostate glands. Exogenous administration of CXCL5 stimulates cellular proliferation and gene transcription in both nontransformed and transformed prostate epithelial cells and induces highly aggressive prostate cancer cells to invade through synthetic basement membrane in vitro. These findings suggest that the inflammatory mediator, CXCL5, may play multiple roles in the etiology of both benign and malignant proliferative diseases in the prostate. PMID:18320069

  18. Whole Pelvic Radiotherapy Versus Prostate Only Radiotherapy in the Management of Locally Advanced or Aggressive Prostate Adenocarcinoma

    SciTech Connect

    Aizer, Ayal A.; Yu, James B.; McKeon, Anne M.; Decker, Roy H.; Colberg, John W.; Peschel, Richard E.

    2009-12-01

    Purpose: To determine whether whole pelvic radiotherapy (WPRT) or prostate-only radiotherapy (PORT) yields improved biochemical disease-free survival (BDFS) in patients with advanced or aggressive prostate adenocarcinoma. Methods and Materials: Between 2000 and 2007, a consecutive sample of 277 patients with prostate adenocarcinoma and at least a 15% likelihood of lymph node involvement who had undergone WPRT (n = 68) or PORT (n = 209) at two referral centers was analyzed. The median radiation dose in both arms was 75.6 Gy. The outcome measure was BDFS, as determined using the prostate-specific antigen nadir + 2 ng/mL definition of failure. BDFS was calculated using the Kaplan-Meier method and compared with the log-rank test. A multivariate analysis was performed to assess for confounding. Treatment-related toxicity was assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events guidelines. The median follow-up was 30 months. Results: WPRT patients had more advanced and aggressive disease at baseline (p < .001). The 4-year BDFS rate was 69.4% in the PORT cohort and 86.3% in the WPRT cohort (p = .02). Within the entire cohort, after adjustment for confounding variables, the pretreatment prostate-specific antigen (p < .001), Gleason score (p < .001), use of hormonal therapy (p = .002), and use of WPRT (vs. PORT, p = .006) predicted for BDFS. Patients undergoing WPRT had increased acute gastrointestinal toxicity (p = .048), but no significant difference in acute genitourinary toxicity was seen (p = .09). No difference in late toxicity was found. Conclusion: WPRT may yield improved BDFS in patients with advanced or aggressive prostate adenocarcinoma, but results in a greater incidence of acute toxicity.

  19. VEGF/neuropilin-2 regulation of Bmi-1 and consequent repression of IGF-IR define a novel mechanism of aggressive prostate cancer.

    PubMed

    Goel, Hira Lal; Chang, Cheng; Pursell, Bryan; Leav, Irwin; Lyle, Stephen; Xi, Hualin Simon; Hsieh, Chung-Cheng; Adisetiyo, Helty; Roy-Burman, Pradip; Coleman, Ilsa M; Nelson, Peter S; Vessella, Robert L; Davis, Roger J; Plymate, Stephen R; Mercurio, Arthur M

    2012-10-01

    We show that the VEGF receptor neuropilin-2 (NRP2) is associated with high-grade, PTEN-null prostate cancer and that its expression in tumor cells is induced by PTEN loss as a consequence of c-Jun activation. VEGF/NRP2 signaling represses insulin-like growth factor-1 receptor (IGF-IR) expression and signaling, and the mechanism involves Bmi-1-mediated transcriptional repression of the IGF-IR. This mechanism has significant functional and therapeutic implications that were evaluated. IGF-IR expression positively correlates with PTEN and inversely correlates with NRP2 in prostate tumors. NRP2 is a robust biomarker for predicting response to IGF-IR therapy because prostate carcinomas that express NRP2 exhibit low levels of IGF-IR. Conversely, targeting NRP2 is only modestly effective because NRP2 inhibition induces compensatory IGF-IR signaling. Inhibition of both NRP2 and IGF-IR, however, completely blocks tumor growth in vivo. PMID:22777769

  20. Prostate Cancer and Sexual Function

    PubMed Central

    2012-01-01

    Prostate cancer is now ranked fifth in incidence among cancers in Korean adult males. This is attributable to the more Westernized dietary style which increases the morbidity of prostate cancer and the development of cancer diagnostic technologies, such as prostate-specific antigen and advanced medical systems, increasing the rate of prostate cancer diagnosis. Prostate cancer effects include not only erectile dysfunction caused by the disease itself, but also by psychiatric disorders caused by prostate cancer or its treatments. Prostate cancer by itself reduces sexual desire and the frequency of sexual intercourse. Additionally, surgery or hormonal therapy to block testosterone further increases the frequency of erectile dysfunction. Erectile dysfunction following radical prostatectomy is primarily attributable to nerve injury caused by intraoperative nerve traction, thermal injury, ischemic injury, and local inflammatory reactions. Additionally, the absence of nocturnal penile tumescence causes persistent hypoxia of the corpus cavernosum, which, secondarily, causes anatomical and functional changes in the corpus cavernosum. Preservation of erectile function is one of the most significant issues for patients with local prostate cancer. Erectile dysfunction following radical prostatectomy is known to have various prognoses, depending on preservation of the neurovascular bundle, patient age, and preoperative erectile status. Intracavernosal injections, PDE5 inhibitors, and penile rehabilitation therapy using a vacuum constriction device after radical prostatectomy are known to improve the recovery of erectile function. Recently, testosterone replacement therapy has also drawn attention as a treatment method. PMID:23596596

  1. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  2. Androgen Control in Prostate Cancer.

    PubMed

    Pelekanou, Vasiliki; Castanas, Elias

    2016-10-01

    Research on prostate cancer has extensively advanced in the past decade, through an improved understanding for its genetic basis and risk-stratification. Molecular classification of prostate cancer into distinct subtypes and the recognition of new histologic entities promise the development of tailored-made management strategies of patients. Nowadays, various alternatives are available for clinical management of localized disease ranging from observation alone through radical prostatectomy. In patients with castration-resistant prostate cancer, the approval of new drugs for the management of metastatic disease has offered promising results improving the survival of these patients. In this context, androgen receptors (AR) remain at the epicenter of prostate cancer research holding a prominent role in the biology and therapeutic regimens of prostate cancer. As many of castration-resistant tumors retain hormone-responsiveness, AR is a clinical relevant, druggable target. However, AR paradoxically remains neglected as a prostate cancer biomarker. The great advancements in prostate cancer preclinical and clinical research, imply further improvement in clinical and translational data, for patient selection and treatment optimization. For a precision medicine-guided clinical management of prostate cancer, AR evaluation has to be implemented in companion and complementary diagnostics, as discussed here. J. Cell. Biochem. 117: 2224-2234, 2016. © 2016 Wiley Periodicals, Inc. PMID:27104784

  3. The Genomic Landscape of Prostate Cancer

    PubMed Central

    Spans, Lien; Clinckemalie, Liesbeth; Helsen, Christine; Vanderschueren, Dirk; Boonen, Steven; Lerut, Evelyne; Joniau, Steven; Claessens, Frank

    2013-01-01

    By the age of 80, approximately 80% of men will manifest some cancerous cells within their prostate, indicating that prostate cancer constitutes a major health burden. While this disease is clinically insignificant in most men, it can become lethal in others. The most challenging task for clinicians is developing a patient-tailored treatment in the knowledge that this disease is highly heterogeneous and that relatively little adequate prognostic tools are available to distinguish aggressive from indolent disease. Next-generation sequencing allows a description of the cancer at an unprecedented level of detail and at different levels, going from whole genome or exome sequencing to transcriptome analysis and methylation-specific immunoprecipitation, followed by sequencing. Integration of all these data is leading to a better understanding of the initiation, progression and metastatic processes of prostate cancer. Ultimately, these insights will result in a better and more personalized treatment of patients suffering from prostate cancer. The present review summarizes current knowledge on copy number changes, gene fusions, single nucleotide mutations and polymorphisms, methylation, microRNAs and long non-coding RNAs obtained from high-throughput studies. PMID:23708091

  4. New drugs in prostate cancer.

    PubMed

    Yoo, Sangjun; Choi, Se Young; You, Dalsan; Kim, Choung-Soo

    2016-06-01

    The standard primary treatment for advanced prostate cancer has been hormonal therapy since the 1940s. However, prostate cancer inevitably progresses to castration-resistant prostate cancer (CRPC) after a median duration of 18 months of androgen deprivation therapy. In patients with CRPC, docetaxel has been regarded as the standard treatment. However, survival advantages of docetaxel over other treatments are slim, and the need for new agents persists. In recent years, novel agents, including abiraterone, enzalutamide, cabazitaxel, radium-223, and sipuleucel-T, have been approved for the treatment of CRPC, and more such agents based on diverse mechanisms are under investigation or evaluation. In this article, the authors reviewed the current literature on recent advances in medical treatment of prostate cancer, especially CRPC. In addition, the authors elaborated on novel drugs for prostate cancer currently undergoing investigation and their mechanisms. PMID:27358841

  5. American Cancer Society Recommendations for Prostate Cancer Early Detection

    MedlinePlus

    ... Research Get Involved Find Local ACS Learn About Cancer » Prostate Cancer » More Information » Prostate Cancer Early Detection » American ... Causes Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News ...

  6. The link between benign prostatic hyperplasia and prostate cancer.

    PubMed

    Ørsted, David D; Bojesen, Stig E

    2013-01-01

    Benign prostatic hyperplasia (BPH) and prostate cancer are among the most common diseases of the prostate gland and represent significant burdens for patients and health-care systems in many countries. The two diseases share traits such as hormone-dependent growth and response to antiandrogen therapy. Furthermore, risk factors such as prostate inflammation and metabolic disruption have key roles in the development of both diseases. Despite these commonalities, BPH and prostate cancer exhibit important differences in terms of histology and localization. Although large-scale epidemiological studies have shown that men with BPH have an increased risk of prostate cancer and prostate-cancer-related mortality, it remains unclear whether this association reflects a causal link, shared risk factors or pathophysiological mechanisms, or detection bias upon statistical analysis. Establishing BPH as a causal factor for prostate cancer development could improve the accuracy of prognostication and expedite intervention, potentially reducing the number of men who die from prostate cancer. PMID:23165396

  7. Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate-cancer associated SNPs for familial disease

    PubMed Central

    Teerlink, Craig C.; Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; Rinckleb, Antje; Maier, Christiane; Vogel, Walther; Cancel-Tassin, Geraldine; Egrot, Christophe; Cussenot, Olivier; Foulkes, William D.; Giles, Graham G.; Hopper, John L.; Severi, Gianluca; Eeles, Ros; Easton, Douglas; Kote-Jarai, Zsofia; Guy, Michelle; Cooney, Kathleen A.; Ray, Anna M.; Zuhlke, Kimberly A.; Lange, Ethan M.; FitzGerald, Liesel M.; Stanford, Janet L.; Ostrander, Elaine A.; Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.; Wahlfors, Tiina; Tammela, Teuvo; Schleutker, Johanna; Wiklund, Fredrik; Grönberg, Henrik; Emanuelsson, Monica; Carpten, John; Bailey-Wilson, Joan; Whittemore, Alice S.; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Catalona, William J.; Zheng, S. Lilly; Jin, Guangfu; Lu, Lingyi; Xu, Jianfeng; Camp, Nicola J.; Cannon-Albright, Lisa A.

    2013-01-01

    Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p≤1E−3) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may be contribute risk to aggressive disease. PMID:24162621

  8. Human Prostate Cancer Hallmarks Map.

    PubMed

    Datta, Dipamoy; Aftabuddin, Md; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-01-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

  9. Human Prostate Cancer Hallmarks Map

    PubMed Central

    Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-01-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

  10. Prostate Cancer for the Internist

    PubMed Central

    Jaiswal, Shikha; Sarmad, Rehan; Arora, Sumant; Dasaraju, Radhikha; Sarmad, Komal

    2015-01-01

    In the United States, approximately 240,000 men are diagnosed annually with prostate cancer. Although effective treatment options are available for clinically localized cancer, the potential burdensome co-morbidities and attendant healthcare costs from over diagnosis and over treatment have escalated the discussion and controversy regarding appropriate screening, diagnosis, and optimal management of prostate cancer. Although the lifetime risk of developing prostate cancer is approximately 1 in 6 (~16%), the risk of dying from the disease is only ~2%. The discrepancy between the cancer incidence and lethality has led to widespread scrutiny of prostate cancer patient management, particularly for low-grade, low-stage (indolent) disease. The vast majority of men diagnosed with clinically localized prostate cancer are treated with interventional therapies despite studies demonstrating that even without treatment, prostate cancer-specific mortality is low. A MedLine/PubMed search was performed using PICO format (Patient, Intervention, Comparison and Outcome) identifying all relevant articles. No restrictions were used for publication dates. The terms “Prostate Cancer”, “Screening”, “Mortality”, “Morbidity” yielded 307 results. “Diagnosis”, “Prognosis” and “Survival” yielded 1504 results. Further filters were applied to narrow down the results using keywords “Prostate cancer screening guidelines 2014”, “Beyond PSA”, “NCCN Guidelines prostate”, “MRI guided Prostate biopsy” yielding 72, 274, 54 and 568 results respectively. Of these, approximately 137 articles were found relevant and were reviewed. References from the reviewed articles were included in the final article. PMID:26713287

  11. Impact of Candidate Genetic Polymorphisms in Prostate Cancer: An Overview.

    PubMed

    Salvi, S; Conteduca, V; Gurioli, G; Calistri, D; Casadio, V; De Giorgi, U

    2016-02-01

    In the last few years, the presence of single nucleotide polymorphisms (SNPs) has been investigated in many tumors as predictor of disease aggressiveness and clinical outcome. We searched for relevant articles from 1998 to 2015 about the impact of SNPs in prostate cancer. Particularly, in this article, we review the pathogenetic, prognostic and predictive significance of gene polymorphisms in prostate tumor, providing a brief overview of studies in which the possible role of genetic variants was investigated in clinical settings. Because conflicting results often emerge about the impact of gene polymorphisms in prostate cancer, further larger studies are warranted in order to introduce gene polymorphism into clinical practice as biomarkers. PMID:26518421

  12. IGFBP-3 is a Metastasis Suppression Gene in Prostate Cancer

    PubMed Central

    Mehta, Hemal H.; Gao, Qinglei; Galet, Colette; Paharkova, Vladislava; Wan, Junxiang; Said, Jonathan; Sohn, Joanne J.; Lawson, Gregory; Cohen, Pinchas; Cobb, Laura J.; Lee, Kuk-Wha

    2011-01-01

    The insulin-like growth factor binding protein IGFBP-3 is a pro-apoptotic and anti-angiogenic protein in prostate cancer (CaP). Epidemiological studies suggest that low IGFBP-3 is associated with greater risk of aggressive, metastatic prostate cancers, but in vivo functional data are lacking. Here we show that mice that are genetically deficient in IGFBP-3 exhibit weaker growth of primary prostate tumors growth but higher incidence of metastatic disease. Prostates in IGFBP-3 knockout mice (IGFBP-3KO mice) failed to undergo apoptosis after castration. Spontaneous prostate tumors did not develop in IGFBP-3KO mice, but splenic lymphomas occured in 23% of female IGFBP-3KO mice by 80 weeks of age. To assess the effects of IGFBP-3 deficiency on prostate cancer development, we crossed IGFBP-3KO mice with a c-Myc-driven model of CaP that develops slow-growing, non-metastatic tumors. By 24 weeks of age, well-differentiated prostate cancers were observed in all mice regardless of IGFBP-3 status. However, by 80 weeks of age IGFBP-3KO mice tended to exhibit larger prostate tumors than control mice. More strikingly, lung metastases were observed at this time in 55% of the IGFBP-3KO mice but none of the control animals. Cell lines established from Myc:IGFBP-3KO tumors displayed more aggressive phenotypes in proliferation, invasion and colony formation assays, relative to control Myc tumor cell lines. In addition, Myc:IGFBP-3KO cells exhibited evidence of epithelial-mesenchymal transition (EMT). Our findings establish a function for IGFBP-3 in suppressing metastasis in prostate cancer, and they also offer the first reported transgenic model of spontaneous metastatic prostate cancer for studies of this advanced stage of disease. PMID:21697285

  13. Rat Prostate Tumor Cells Progress in the Bone Microenvironment to a Highly Aggressive Phenotype1

    PubMed Central

    Bergström, Sofia Halin; Rudolfsson, Stina H; Bergh, Anders

    2016-01-01

    Prostate cancer generally metastasizes to bone, and most patients have tumor cells in their bone marrow already at diagnosis. Tumor cells at the metastatic site may therefore progress in parallel with those in the primary tumor. Androgen deprivation therapy is often the first-line treatment for clinically detectable prostate cancer bone metastases. Although the treatment is effective, most metastases progress to a castration-resistant and lethal state. To examine metastatic progression in the bone microenvironment, we implanted androgen-sensitive, androgen receptor–positive, and relatively slow-growing Dunning G (G) rat prostate tumor cells into the tibial bone marrow of fully immune-competent Copenhagen rats. We show that tumor establishment in the bone marrow was reduced compared with the prostate, and whereas androgen deprivation did not affect tumor establishment or growth in the bone, this was markedly reduced in the prostate. Moreover, we found that, with time, G tumor cells in the bone microenvironment progress to a more aggressive phenotype with increased growth rate, reduced androgen sensitivity, and increased metastatic capacity. Tumor cells in the bone marrow encounter lower androgen levels and a higher degree of hypoxia than at the primary site, which may cause high selective pressures and eventually contribute to the development of a new and highly aggressive tumor cell phenotype. It is therefore important to specifically study progression in bone metastases. This tumor model could be used to increase our understanding of how tumor cells adapt in the bone microenvironment and may subsequently improve therapy strategies for prostate metastases in bone. PMID:26992916

  14. [Reducing the side effects of aggressive chemotherapy (cisplatin and epirubicin) with xenogenic peptides (factor AF2) in patients with hormone refractory metastatic prostate cancer. A prospective, randomized study].

    PubMed

    Papadopoulos, I; Wand, H

    1989-06-01

    The indication of a chemotherapy is advisable with patients who are suffering from a progressively metastasised, secondarily hormone refractory carcinoma of the prostate. In search of efficient chemotherapy protocols we combined cisplatin with epirubicin (PE scheme) in our clinic. Massive side effects of that aggressive chemotherapy scheme like gastro-intestinal trouble and myelotoxicity are the limiting factors of the scheme. With measures like reducing the dosage, delaying the next cycle, or breaking off the therapy the effective dosage can often not be achieved. The anti-emetics which are usually used today exclusively give anti-emetic protection. The additional administration of xenogenic peptides (Factor AF2) had additionally myeloprotective effect in former studies. In this study we examined whether, by additionally giving Factor AF2, the patients' subjective condition, and above all their hemogram, could be stabilised in order to achieve the effective dosage or dosage intensity. For that, the patients were prospectively randomised in two groups by means of a random selection board. The analysis of the data gained in the protocol showed that the additional administration of Factor AF2 improves the patients' subjective conditions significantly. Apart from that, we noticed a considerable reduction of the vomiting frequency. Concerning the objective measured parameters of the leukocytes, thrombocytes, erythrocytes, and the hemoglobin level, the significantly myeloprotective effect of Factor AF2 could be proved. Due to the fact that in the verum group there were considerably fewer cases of breaking off or delays of the treatment than in the control group, the effective dosage intensity could be achieved with a higher number of patients in that group. PMID:2691943

  15. Contemporary Management of Prostate Cancer

    PubMed Central

    Cotter, Katherine; Konety, Badrinath; Ordonez, Maria A.

    2016-01-01

    Prostate cancer represents a spectrum ranging from low-grade, localized tumors to devastating metastatic disease. We discuss the general options for treatment and recent developments in the field. PMID:26949522

  16. Contemporary Management of Prostate Cancer.

    PubMed

    Cotter, Katherine; Konety, Badrinath; Ordonez, Maria A

    2016-01-01

    Prostate cancer represents a spectrum ranging from low-grade, localized tumors to devastating metastatic disease. We discuss the general options for treatment and recent developments in the field. PMID:26949522

  17. Breast Cancers Between Mammograms Have Aggressive Features

    Cancer.gov

    Breast cancers that are discovered in the period between regular screening mammograms—known as interval cancers—are more likely to have features associated with aggressive behavior and a poor prognosis than cancers found via screening mammograms.

  18. The hallmarks of castration-resistant prostate cancers.

    PubMed

    Katsogiannou, Maria; Ziouziou, Hajer; Karaki, Sara; Andrieu, Claudia; Henry de Villeneuve, Marie; Rocchi, Palma

    2015-07-01

    Prostate cancer has become a real public health issue in industrialized countries, mainly due to patients' relapse by castration-refractory disease after androgen ablation. Castration-resistant prostate cancer is an incurable and highly aggressive terminal stage of prostate cancer, seriously jeopardizing the patient's quality of life and lifespan. The management of castration-resistant prostate cancer is complex and has opened new fields of research during the last decade leading to an improved understanding of the biology of the disease and the development of new therapies. Most advanced tumors resistant to therapy still maintain the androgen receptor-pathway, which plays a central role for survival and growth of most castration-resistant prostate cancers. Many mechanisms induce the emergence of the castration resistant phenotype through this pathway. However some non-related AR pathways like neuroendocrine cells or overexpression of anti-apoptotic proteins like Hsp27 are described to be involved in CRPC progression. More recently, loss of expression of tumor suppressor gene, post-transcriptional modification using miRNA, epigenetic alterations, alternatif splicing and gene fusion became also hallmarks of castration-resistant prostate cancer. This review presents an up-to-date overview of the androgen receptor-related mechanisms as well as the latest evidence of the non-AR-related mechanisms underlying castration-resistant prostate cancer progression. PMID:25981454

  19. Molecular Imaging of Prostate Cancer

    PubMed Central

    Fox, Josef J.; Schöder, Heiko; Larson, Steven M.

    2015-01-01

    Purpose of review Prostate cancer is a complex and biologically heterogeneous disease that is not adequately assessed with conventional imaging alone. Molecular imaging with positron emission tomography (PET) is poised to fill this unmet need through noninvasive probing of the multiple molecular and cellular processes that are active in prostate cancer patients. Recent findings Several PET tracers are active in early and late stage prostate cancer in humans. F18-FDG, C11/F18-choline and F18-sodium fluoride (NaF) have been studied most extensively. There is a growing body of literature supporting to the utility of choline in early stage prostate cancer. FDG and NaF are more valuable in advanced disease, especially for assessing bone metastases, the prevalent form of metastases in this patient population. F18-Fluoro-dihydrotestosterone is active in castrate disease and is emerging as a valuable pharmacodynamic marker in the development of novel AR-targeted therapies. Anti-PSMA PET tracers are in the early stages of clinical development. Summary Multiple PET tracers are currently available to aid in the detection and management of prostate cancer across the clinical spectrum of the disease. Prospective, rigorously controlled, clinical imaging trials are needed to establish the optimal role of PET in prostate cancer. PMID:22617062

  20. Cryotherapy for prostate cancer

    MedlinePlus

    ... the needles to the prostate gland. Then, very cold gas passes through the needles, creating ice balls that destroy the prostate gland. Warm salt water will flow through the catheter to keep your urethra (the tube from the bladder to ...

  1. Lycopene: Redress for Prostate Cancer

    PubMed Central

    Pisipati, Sai Venkata Vedavyas; Pathapati, Harshavardhan; Bhukya, Ganesh; Nuthakki, Suresh; Chandu, Baburao; Nama, SreeKanth; Adeps, RajDev

    2012-01-01

    Lycopene, a carotenoid is what that gives red colour to some fruits like pomegranate, tomato, papaya etc... People with a sound diet of lycopene may have a less risk of cancers especially prostate cancer which is most impedent for the males of age 40-50 years. So, in countries of north America and Europe food contains much of the lycopene supplements. In accordance with the American journal of epidemiology 2002 studies implies that men with crushed serum lycopene levels are more divulged to prostate cancer and those with sound diet of lycopene have a less risk of prostate cancer. In a care study conveyed by The British journal of urology, men with prostate cancer are subjected to surgery and the tumour is detonated. Amongst the men half a set were supplemented with lycopene supplements and half were not. Those subjected with lycopene supplements have less bone pains and live longer than those not supplemented. This paints a picture about importance of lycopene in treatment of prostate cancer. This article evokes the importance of lycopene and its way of destroying the cancer. Lycopene reduces the risk of cancer by diverging its effect on the plasma Insulin like growth factor, on Connexins , and the most acceptable one, by quench of free radicals. PMID:24826034

  2. Lycopene: redress for prostate cancer.

    PubMed

    Pisipati, Sai Venkata Vedavyas; Pathapati, Harshavardhan; Bhukya, Ganesh; Nuthakki, Suresh; Chandu, Baburao; Nama, SreeKanth; Adeps, RajDev

    2012-03-01

    Lycopene, a carotenoid is what that gives red colour to some fruits like pomegranate, tomato, papaya etc... People with a sound diet of lycopene may have a less risk of cancers especially prostate cancer which is most impedent for the males of age 40-50 years. So, in countries of north America and Europe food contains much of the lycopene supplements. In accordance with the American journal of epidemiology 2002 studies implies that men with crushed serum lycopene levels are more divulged to prostate cancer and those with sound diet of lycopene have a less risk of prostate cancer. In a care study conveyed by The British journal of urology, men with prostate cancer are subjected to surgery and the tumour is detonated. Amongst the men half a set were supplemented with lycopene supplements and half were not. Those subjected with lycopene supplements have less bone pains and live longer than those not supplemented. This paints a picture about importance of lycopene in treatment of prostate cancer. This article evokes the importance of lycopene and its way of destroying the cancer. Lycopene reduces the risk of cancer by diverging its effect on the plasma Insulin like growth factor, on Connexins , and the most acceptable one, by quench of free radicals. PMID:24826034

  3. Prostate Cancer Severity Associations with Neighborhood Deprivation

    PubMed Central

    Zeigler-Johnson, Charnita M.; Tierney, Ann; Rebbeck, Timothy R.; Rundle, Andrew

    2011-01-01

    Background. The goal of this paper was to examine neighborhood deprivation and prostate cancer severity. Methods. We studied African American and Caucasian prostate cancer cases from the Pennsylvania State Cancer Registry. Census tract-level variables and deprivation scores were examined in relation to diagnosis stage, grade, and tumor aggressiveness. Results. We observed associations of low SES with high Gleason score among African Americans residing in neighborhoods with low educational attainment (OR = 1.34, 95% CI = 1.13–1.60), high poverty (OR = 1.39, 95% CI = 1.15–1.67), low car ownership (OR = 1.46, 95% CI = 1.20–1.78), and higher percentage of residents on public assistance (OR = 1.32, 95% = 1.08–1.62). The highest quartile of neighborhood deprivation was also associated with high Gleason score. For both Caucasians and African Americans, the highest quartile of neighborhood deprivation was associated with high Gleason score at diagnosis (OR = 1.34, 95% CI = 1.19–1.52; OR = 1.71, 95% CI = 1.21–2.40, resp.). Conclusion. Using a neighborhood deprivation index, we observed associations between high-grade prostate cancer and neighborhood deprivation in Caucasians and African-Americans. PMID:22111000

  4. Lipid metabolism in prostate cancer

    PubMed Central

    Wu, Xinyu; Daniels, Garrett; Lee, Peng; Monaco, Marie E

    2014-01-01

    The malignant transformation of cells requires adaptations across multiple metabolic processes to satisfy the energy required for their increased rate of proliferation. Dysregulation of lipid metabolism has been a hallmark of the malignant phenotype; increased lipid accumulation secondary to changes in the levels of a variety of lipid metabolic enzymes has been documented in a variety of tumors, including prostate. Alterations in prostate lipid metabolism include upregulation of several lipogenic enzymes as well as of enzymes that function to oxidize fatty acids as an energy source. Cholesterol metabolism and phospholipid metabolism are also affected. With respect to lipogenesis, most studies have concentrated on increased expression and activity ofthe de novo fatty acid synthesis enzyme, fatty acid synthase (FASN), with suggestions that FASN might function as an oncogene. A central role for fatty acid oxidation in supplying energy to the prostate cancer cell is supported by the observation that the peroxisomal enzyme, α-methylacyl-CoA racemase (AMACR), which facilitates the transformation of branched chain fatty acids to a form suitable for β-oxidation, is highly overexpressed in prostate cancer compared with normal prostate. Exploitation of the alterations in lipid metabolic pathways in prostate cancer could result in the development of new therapeutic modalities as well as provide candidates for new prognostic and predictive biomarkers. AMACR has already proven to be a valuable biomarker in distinguishing normal from malignant prostate tissue, and is used routinely in clinical practice. PMID:25374912

  5. Overexpression of ribosomal L1 domain containing 1 is associated with an aggressive phenotype and a poor prognosis in patients with prostate cancer

    PubMed Central

    LI, XIAO-PING; JIAO, JU; LU, LI; ZOU, QIONG; ZHU, SHU; ZHANG, YONG

    2016-01-01

    The aim of the present study was to investigate the overexpression and significance of ribosomal L1 domain containing 1 (RSL1D1) in prostate cancer (PCA). The present study performed immunohistochemical analysis on the tissues of 138 patients with pathologically confirmed PCA. The patients were followed up for a median of 87 months. In addition, 50 patients with benign prostatic hyperplasia (BPH) were enrolled in the present study as a control group. Of the 138 PCA tissue samples, 124 (89.9%) expressed RSL1D1, while 4 out of the 50 (8.0%) BPH tissues expressed RSL1D1. The present study defined a high RSL1D1 expression level as the relative gene expression that was equal to or higher than the median, and low expression as the gene expression lower than the median. The pathological stage of patients with PCA (≥pT3a vs. pT2c) and the Gleason scores of patients (≥7 vs. <7) were associated with RSL1D1 expression (χ2=4.809 and 14.703; P=0.028 and P<0.0001, respectively) and a high expression of RSL1D1 (χ2=10.294 and 17.520; P=0.001 and P<0.0001, respectively). Kaplan-Meier curve analysis demonstrated that the biochemical recurrence (BCR)-free survival rate of the patients was increased in patients without RSL1D1 expression (P=0.0046), in those with low RSL1D1 expression (P<0.0001) and in those without RSL1D1 expression in the mesenchyme (P=0.006) compared with those patients with no expression, low expression and no mesenchymal expression, respectively. A high expression level of RSL1D1 was demonstrated to be an independent prognostic factor of BCR in patients with PCA using Cox regression analysis. Overall, the present study demonstrated that RSL1D1 expression was associated with PCA, and that it may aid in the improvement of diagnosis, prognosis and risk stratification of patients with PCA. PMID:27073561

  6. Circumcision and the risk of prostate cancer

    PubMed Central

    Wright, Jonathan L; Lin, Daniel W; Stanford, Janet L

    2011-01-01

    Background Several lines of evidence support a role for infectious agents in the development of prostate cancer (PCa). In particular, sexually transmitted infections (STIs) have been implicated in PCa etiology, and studies have found that the risk of acquiring a STI can be reduced with circumcision. Therefore, circumcision may reduce PCa risk. Methods Participant data collected as part of two population-based case-control studies of PCa were analyzed. Self-reported circumcision status, age at circumcision and age at first sexual intercourse were recorded along with a history of STIs or prostatitis. Multivariate logistic regression was used to estimate the relative risk of PCa by circumcision status. Results Data from 1,754 cases and 1,645 controls were available. Circumcision before first sexual intercourse was associated with a 15% reduction in risk of PCa compared to uncircumcised men (95% CI 0.73 – 0.99). This risk reduction was observed for cases with both less aggressive (OR 0.88, 95% CI 0.74 – 1.04) and more aggressive (OR 0.82, 95% CI 0.66 – 1.00) PCa features. Conclusions Circumcision before first sexual intercourse is associated with a reduction in the relative risk of PCa in this study population. These findings are consistent with research supporting the infectious/inflammation pathway in prostate carcinogenesis. PMID:22411189

  7. African American Men and Prostate Cancer

    MedlinePlus Videos and Cool Tools

    ... have one of the highest incidences of prostate cancer in the world, and in this country the ... an epidemic. Winston Dyer: My introduction to prostate cancer started with the death of my 46-year- ...

  8. Vitamin D in Prostate Cancer.

    PubMed

    Ahn, Jungmi; Park, Sulgi; Zuniga, Baltazar; Bera, Alakesh; Song, Chung Seog; Chatterjee, Bandana

    2016-01-01

    Metastatic castration-resistant prostate cancer (mCRPC) is a progressive, noncurable disease induced by androgen receptor (AR) upon its activation by tumor tissue androgen, which is generated from adrenal steroid dehydroepiandrosterone (DHEA) through intracrine androgen biosynthesis. Inhibition of mCRPC and early-stage, androgen-dependent prostate cancer by calcitriol, the bioactive vitamin D3 metabolite, is amply documented in cell culture and animal studies. However, clinical trials of calcitriol or synthetic analogs are inconclusive, although encouraging results have recently emerged from pilot studies showing efficacy of a safe-dose vitamin D3 supplementation in reducing tumor tissue inflammation and progression of low-grade prostate cancer. Vitamin D-mediated inhibition of normal and malignant prostate cells is caused by diverse mechanisms including G1/S cell cycle arrest, apoptosis, prodifferentiation gene expression changes, and suppressed angiogenesis and cell migration. Biological effects of vitamin D are mediated by altered expression of a gene network regulated by the vitamin D receptor (VDR), which is a multidomain, ligand-inducible transcription factor similar to AR and other nuclear receptors. AR-VDR cross talk modulates androgen metabolism in prostate cancer cells. Androgen inhibits vitamin D-mediated induction of CYP24A1, the calcitriol-degrading enzyme, while vitamin D promotes androgen inactivation by inducing phase I monooxygenases (e.g., CYP3A4) and phase II transferases (e.g., SULT2B1b, a DHEA-sulfotransferase). CYP3A4 and SULT2B1b levels are markedly reduced and CYP24A1 is overexpressed in advanced prostate cancer. In future trials, combining low-calcemic, potent next-generation calcitriol analogs with CYP24A1 inhibition or androgen supplementation, or cancer stem cell suppression by a phytonutrient such as sulfarophane, may prove fruitful in prostate cancer prevention and treatment. PMID:26827958

  9. Multiparametric magnetic resonance imaging: Current role in prostate cancer management.

    PubMed

    Ueno, Yoshiko; Tamada, Tsutomu; Bist, Vipul; Reinhold, Caroline; Miyake, Hideaki; Tanaka, Utaru; Kitajima, Kazuhiro; Sugimura, Kazuro; Takahashi, Satoru

    2016-07-01

    Digital rectal examination, serum prostate-specific antigen screening and transrectal ultrasound-guided biopsy are conventionally used as screening, diagnostic and surveillance tools for prostate cancer. However, they have limited sensitivity and specificity. In recent years, the role of multiparametric magnetic resonance imaging has steadily grown, and is now part of the standard clinical management in many institutions. In multiparametric magnetic resonance imaging, the morphological assessment of T2-weighted imaging is correlated with diffusion-weighted imaging, dynamic contrast-enhanced imaging perfusion and/or magnetic resonance spectroscopic imaging. Multiparametric magnetic resonance imaging is currently regarded as the most sensitive and specific imaging technique for the evaluation of prostate cancer, including detection, staging, localization and aggressiveness evaluation. This article presents an overview of multiparametric magnetic resonance imaging, and discusses the current role of multiparametric magnetic resonance imaging in the different fields of prostate cancer management. PMID:27184019

  10. Prevention strategies for prostate cancer.

    PubMed

    Schmitz-Dräger, B J; Lümmen, G; Bismarck, E; Fischer, C

    2012-12-01

    Through the last decade consideration of the role of vitamins and minerals in primary prevention of genitourinary tumors has dramatically changed. Despite all efforts efficacy of a specific compound has not been proven, so far. In consequence, recommendations for a use of vitamins or other supplements with the intention of prostate cancer prevention should be avoided today. In contrast, there is some evidence that life style modification might be helpful: recent investigations suggest that smoking may be involved in prostate cancer carcinogenesis. In addition, there is evidence that moderate food consumption, reduction of dairy products and an Asian or Mediterranean diet might not only prevent prostate cancer but also harbors additional beneficial effects on general health. This move from single compounds to more complex diets can be considered as a change of paradigm in prostate cancer prevention and could be the starting point of future epidemiological research. Disappointing findings with regards to nutritional cancer prevention contrast with a solid evidence concerning the efficacy of chemoprevention using 5a-reductase inhibitors: Long-term use of Finasteride and Dutasteride significantly reduces prostate cancer detection. Further candidate drugs are under investigation. However, translation of these findings into urological practice remains a matter of controversial discussion. PMID:23288209

  11. Active surveillance for prostate cancer.

    PubMed

    Romero-Otero, Javier; García-Gómez, Borja; Duarte-Ojeda, José M; Rodríguez-Antolín, Alfredo; Vilaseca, Antoni; Carlsson, Sigrid V; Touijer, Karim A

    2016-03-01

    It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low-risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low-risk prostate cancer without compromising cancer-specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side-effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized. PMID:26621054

  12. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.

    PubMed

    Lee, John K; Phillips, John W; Smith, Bryan A; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M; Shokat, Kevan M; Gustafson, W Clay; Huang, Jiaoti; Witte, Owen N

    2016-04-11

    MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. PMID:27050099

  13. Prostate-specific antigen-negative prostate cancer recurrence?

    PubMed

    Froehner, Michael; Abolmaali, Nasreddin; Wirth, Manfred P

    2013-02-01

    We describe a patient with bone metastases occurring shortly after radical prostatectomy for organ-confined prostate cancer. The medical history and immunohistochemical findings suggested prostate cancer recurrence to the skeleton. Undetectable serum prostate-specific antigen levels, however, raised doubts about this diagnosis. A whole body (18)F-fluorodeoxyglucose positron emission tomography-computed tomography scan was obtained and revealed a right-sided breast cancer as the primary site of metastatic spread. PMID:23374851

  14. Prostate Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  15. Counseling the Client with Prostate Cancer.

    ERIC Educational Resources Information Center

    Curtis, Russell C.; Juhnke, Gerald A.

    2003-01-01

    Prostate cancer is prevalent in the United States and has a far-reaching effect on men and their relationships. Being diagnosed with and treated for prostate cancer often causes men to experience side effects that induce physical, emotional, and social change. Counselors need to be aware of prostate cancer's impact on men and their families.…

  16. Prostate Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  17. Prostate cancer in the elderly.

    PubMed

    Konstantinos, Hatzimouratidis

    2005-01-01

    Prostate cancer is the second leading cause of cancer deaths among men. Despite earlier diagnosis due to prostate specific antigen (PSA) screening, it is still a disease of the elderly. Diagnosis is based on digital rectal examination (DRE) and PSA assessment. Refinements in PSA testing (age-specific reference ranges, free PSA, PSA density and velocity) increased specificity and limited unnecessary prostate biopsies. Diagnosis in earlier stages (T1 and T2) commonly leads to cure with current treatment modalities. These include radical prostatectomy, external beam radiotherapy and brachytherapy. Other treatment options under development include cryotherapy and high-intensity focused ultrasound. Metastatic prostate cancer is incurable and treatment is based on hormonal therapy. Cytotoxic chemotherapy has only limited role in hormone-independent prostate cancer. Radioisotopes and biphosphonates may alleviate bone pain and prevent osteoporosis and pathological fractures. Follow-up is based on PSA. Prognostic factors for recurrence include stage, Gleason score, pre- and posttreatment PSA. Quality of life issues play an important role in selecting treatment, especially in the elderly due to comorbidities that may negatively affect the overall quality of life. A holistic approach is recommended addressing all quality of life issues without focus only in cancer control. PMID:16362603

  18. [Prostate cancer and chemotherapy].

    PubMed

    Gravis, Gwenaelle; Salem, Naji; Bladou, Franck; Viens, Patrice

    2007-07-01

    Androgen deprivation in patients with metastatic prostate cancer produces palliation of symptoms, PSA decrease and tumoral regression in most patients. After a brief period of disease regression lasting 18 to 24 months nearly all pts will progress to androgen independence disease (HRPC) with progressive clinical deterioration and ultimately death. Chemotherapy with mitoxantrone has been shown to palliate symptoms but did not extend survival. Two large randomized trials showed a survival benefit for pts with HRPC treated with docetaxel with a reduction risk of death by 21-24%, and significant improvement in palliation of symptoms and quality of life. New agents targeting angiogenesis, apoptosis, signal transduction pathway, used alone or in combination with docetaxel currently are under trial in an attempt to provide much needed improvements in outcome. Questions remains in suspend when and who need to be treated, earlier, in high risk as in adjuvant setting? Current data have demonstrated that neoadjuvant or adjuvant chemotherapy is relatively safe and feasible. Further investigation through prospective randomize trials is critical to define the precise role of this modality in high risk populations. PMID:17845990

  19. Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk.

    PubMed

    Bonn, Stephanie E; Sjölander, Arvid; Tillander, Annika; Wiklund, Fredrik; Grönberg, Henrik; Bälter, Katarina

    2016-07-01

    High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010-2012. During follow-up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high-grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log-PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer-free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: -2.1 to -1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI-categories of 25 < 30, 30 < 35 and ≥35 kg/m(2) , respectively, compared to the reference (18.5 < 25 kg/m(2) ). No statistically significant associations were seen between BMI and prostate cancer risk although results were indicative of a positive association to incidence rates of high-grade disease and an inverse association to incidence of low-grade disease. However, findings regarding risk are limited by the short follow-up time. In conclusion, BMI was inversely associated to PSA-levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA-levels. PMID:26914149

  20. Signaling lansdscape of prostate cancer.

    PubMed

    Lin, X; Aslam, A; Attar, R; Yaylim, I; Qureshi, M Z; Hasnain, S; Qadir, M I; Farooqi, A A

    2016-01-01

    Research over the decades has gradually and sequentially shown that both intratumor heterogeneity and multifocality make prostate cancer difficult to target. Different challenges associated with generation of risk-stratification tools that correlate genomic landscape with clinical outcomes severely influence clinical efficacy of therapeutic strategies. Androgen receptor mediated signaling has gained great appreciation and rewiring of AR induced signaling cascade in absence of androgen, structural variants of AR have provided near complete resolution of genomic landscape and underlying mechanisms of prostate cancer. In this review we have attempted to provide an overview of most recent advancements in our knowledge related to different signaling cascades including TGF, SHH, Notch, JAK-STAT in prostate cancer progression and development. PMID:26828986

  1. Gene therapy for prostate cancer.

    PubMed

    Tangney, Mark; Ahmad, Sarfraz; Collins, Sara A; O'Sullivan, Gerald C

    2010-05-01

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor's vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

  2. The Prostate Health Index Selectively Identifies Clinically Significant Prostate Cancer

    PubMed Central

    Loeb, Stacy; Sanda, Martin G.; Broyles, Dennis L.; Shin, Sanghyuk S.; Bangma, Chris H.; Wei, John T.; Partin, Alan W.; Klee, George G.; Slawin, Kevin M.; Marks, Leonard S.; van Schaik, Ron H. N.; Chan, Daniel W.; Sokoll, Lori J.; Cruz, Amabelle B.; Mizrahi, Isaac A.; Catalona, William J.

    2015-01-01

    Purpose The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting clinically significant prostate cancer and can help reduce prostate cancer over diagnosis. Materials and Methods From a multicenter prospective trial we identified 658 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml and normal digital rectal examination who underwent prostate biopsy. In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, [-2]proPSA and phi to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. Results The Prostate Health Index was significantly higher in men with Gleason 7 or greater and “Epstein significant” cancer. On receiver operating characteristic analysis phi had the highest AUC for overall cancer (AUCs phi 0.708, percent free prostate specific antigen 0.648, [-2]proPSA 0.550 and prostate specific antigen 0.516), Gleason 7 or greater (AUCs phi 0.707, percent free prostate specific antigen 0.661, [-2]proPSA 0.558, prostate specific antigen 0.551) and significant cancer (AUCs phi 0.698, percent free prostate specific antigen 0.654, [-2]proPSA 0.550, prostate specific antigen 0.549). At the 90% sensitivity cut point for phi (a score less than 28.6) 30.1% of patients could have been spared an unnecessary biopsy for benign disease or insignificant prostate cancer compared to 21.7% using percent free prostate specific antigen. Conclusions The new phi test outperforms its individual components of total, free and [-2]proPSA for the identification of clinically significant prostate cancer. Phi may be useful as part of a multivariable approach to reduce prostate biopsies and over diagnosis. PMID:25463993

  3. ERBB2 increases metastatic potentials specifically in androgen-insensitive prostate cancer cells.

    PubMed

    Tome-Garcia, Jessica; Li, Dan; Ghazaryan, Seda; Shu, Limin; Wu, Lizhao

    2014-01-01

    Despite all the blood-based biomarkers used to monitor prostate cancer patients, prostate cancer remains as the second common cause of cancer mortality in men in the United States. This is largely due to a lack of understanding of the molecular pathways that are responsible for the aggressive forms of prostate cancers, the castrate-resistant prostate cancer and the metastatic prostate cancer. Cell signaling pathways activated by the ERBB2 oncogene or the RAS oncogene are frequently found to be altered in metastatic prostate cancers. To evaluate and define the role of the ERBB2/RAS pathway in prostate cancer metastasis, we have evaluated the impact of ERBB2- or RAS-overexpression on the metastatic potentials for four prostate cancer cell lines derived from tumors with different androgen sensitivities. To do so, we transfected the human DU145, LnCaP, and PC3 prostate cancer cells and the murine Myc-CaP prostate cancer cells with the activated form of ERBB2 or H-RAS and assessed their metastatic potentials by three complementary assays, a wound healing assay, a transwell motility assay, and a transwell invasion assay. We showed that while overexpression of ERBB2 increased the metastatic potential of the androgen-insensitive prostate cancer cells (i.e. PC3 and DU145), it did not affect metastatic potentials of the androgen-sensitive prostate cancer cells (i.e. LnCaP and Myc-CaP). In contrast, overexpression of H-RAS only increased the cell motility of Myc-CaP cells, which overexpress the human c-MYC oncogene. Our data suggest that ERBB2 collaborates with androgen signaling to promote prostate cancer metastasis, and that although RAS is one of the critical downstream effectors of ERBB2, it does not phenocopy ERBB2 for its impact on the metastatic potentials of prostate cancer cell lines. PMID:24937171

  4. Long noncoding RNAs in prostate cancer: overview and clinical implications.

    PubMed

    Malik, Bhavna; Feng, Felix Y

    2016-01-01

    Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer (CRPC), which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs (lncRNAs) have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding (not translated into proteins). They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of lncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of lncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets. PMID:27072044

  5. Long noncoding RNAs in prostate cancer: overview and clinical implications

    PubMed Central

    Malik, Bhavna; Feng, Felix Y

    2016-01-01

    Prostate cancer is the second most common cause of cancer mortality among men in the United States. While many prostate cancers are indolent, an important subset of patients experiences disease recurrence after conventional therapy and progresses to castration-resistant prostate cancer (CRPC), which is currently incurable. Thus, there is a critical need to identify biomarkers that will distinguish indolent from aggressive disease, as well as novel therapeutic targets for the prevention or treatment of CRPC. In recent years, long noncoding RNAs (lncRNAs) have emerged as an important class of biological molecules. LncRNAs are polyadenylated RNA species that share many similarities with protein-coding genes despite the fact that they are noncoding (not translated into proteins). They are usually transcribed by RNA polymerase II and exhibit the same epigenetic signatures as protein-coding genes. LncRNAs have also been implicated in the development and progression of variety of cancers, including prostate cancer. While a large number of lncRNAs exhibit tissue- and cancer-specific expression, their utility as diagnostic and prognostic biomarkers is just starting to be explored. In this review, we highlight recent findings on the functional role and molecular mechanisms of lncRNAs in the progression of prostate cancer and evaluate their use as potential biomarkers and therapeutic targets. PMID:27072044

  6. Prostate cancer immunotherapy: beyond immunity to curability.

    PubMed

    Simons, Jonathan W

    2014-11-01

    Metastatic prostate cancer is the second leading cause of death from cancer in the United States. It is the first prevalent cancer in which overall survival in advanced disease is modestly, but objectively, improved with outpatient delivered dendritic cell-based immunotherapy. More prostate cancer patients have enrolled through Facebook and trusted-site Internet searches in clinical trials for prostate cancer vaccine-based immunotherapy than in immunotherapy trials for lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7 years. Exceptional responses to anti-CTLA-4 treatment have been documented in clinics, and prostate cancer neoantigen characterization and T-cell clonotyping are in their research ascendancy. The prostate is an accessory organ; it is not required for fertility, erectile function, or urinary continence. The true evolutionary advantage of having a prostate for male mammalian physiology is a topic of speculation in seminar rooms and on bar stools, but it remains unknown. Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000 normal human prostate lineage-unique open reading frames that can be targeted for immunologic ablation of PLUP(+) prostate cancer cells by prostate-specific autoimmunity. This bioengineered graft-versus-prostate disease is a powerful strategy that can eliminate deaths from prostate cancer. Immunologic tolerance to prostate cancer can be overcome at every clinical stage of presentation. This Cancer Immunology at the Crossroads article aims to present advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials. PMID:25367978

  7. Living with Prostate Cancer

    MedlinePlus

    ... pork, lamb, and processed meat (such as hot dogs, sausage, and bacon); and low in high-fat ... ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects Cancer ...

  8. Prevention strategies in prostate cancer

    PubMed Central

    Trottier, Greg; Lawrentschuk, N.; Fleshner, N.E.

    2010-01-01

    Prostate cancer (pca) prevention has been an exciting and controversial topic since the results of the Prostate Cancer Prevention Trial (pcpt) were published. With the recently published results of the reduce (Reduction by Dutasteride of Prostate Cancer Events) trial, interest in this topic is at a peak. Primary pca prevention will be unlikely to affect mortality significantly, but the reduction in overtreatment and the effect on quality of life from the avoidance of a cancer diagnosis are important factors to consider. This review provides a comparative update on the reduce and pcpt trials and some clinical recommendations. Other potential primary preventive strategies with statins, selective estrogen response modulators, and nutraceutical compounds—including current evidence for these agents and their roles in clinical practice—are discussed. Many substances that have been examined in the primary prevention of pca and for which clinical data are either negative or particularly weak are not covered. The future of pca prevention continues to expand, with several ongoing clinical trials and much interest in tertiary prostate cancer prevention. PMID:20882132

  9. DNA microarrays in prostate cancer.

    PubMed

    Ho, Shuk-Mei; Lau, Kin-Mang

    2002-02-01

    DNA microarray technology provides a means to examine large numbers of molecular changes related to a biological process in a high throughput manner. This review discusses plausible utilities of this technology in prostate cancer research, including definition of prostate cancer predisposition, global profiling of gene expression patterns associated with cancer initiation and progression, identification of new diagnostic and prognostic markers, and discovery of novel patient classification schemes. The technology, at present, has only been explored in a limited fashion in prostate cancer research. Some hurdles to be overcome are the high cost of the technology, insufficient sample size and repeated experiments, and the inadequate use of bioinformatics. With the completion of the Human Genome Project and the advance of several highly complementary technologies, such as laser capture microdissection, unbiased RNA amplification, customized functional arrays (eg, single-nucleotide polymorphism chips), and amenable bioinformatics software, this technology will become widely used by investigators in the field. The large amount of novel, unbiased hypotheses and insights generated by this technology is expected to have a significant impact on the diagnosis, treatment, and prevention of prostate cancer. Finally, this review emphasizes existing, but currently underutilized, data-mining tools, such as multivariate statistical analyses, neural networking, and machine learning techniques, to stimulate wider usage. PMID:12084220

  10. Prevention strategies in prostate cancer.

    PubMed

    Trottier, Greg; Lawrentschuk, N; Fleshner, N E

    2010-09-01

    Prostate cancer (PCa) prevention has been an exciting and controversial topic since the results of the Prostate Cancer Prevention Trial (PCPT) were published. With the recently published results of the reduce (Reduction by Dutasteride of Prostate Cancer Events) trial, interest in this topic is at a peak. Primary pca prevention will be unlikely to affect mortality significantly, but the reduction in overtreatment and the effect on quality of life from the avoidance of a cancer diagnosis are important factors to consider.This review provides a comparative update on the REDUCE and PCPT trials and some clinical recommendations. Other potential primary preventive strategies with statins, selective estrogen response modulators, and nutraceutical compounds-including current evidence for these agents and their roles in clinical practice-are discussed. Many substances that have been examined in the primary prevention of pca and for which clinical data are either negative or particularly weak are not covered.The future of PCa prevention continues to expand, with several ongoing clinical trials and much interest in tertiary prostate cancer prevention. PMID:20882132

  11. Circulating Levels of 25-hydroxyvitamin D and Prostate Cancer Prognosis

    PubMed Central

    Holt, Sarah K.; Kolb, Suzanne; Fu, Rong; Horst, Ronald; Feng, Ziding; Stanford, Janet L.

    2013-01-01

    Objectives Ecological, in vitro, and in vivo studies demonstrate a link between vitamin D and prostate tumor growth and aggressiveness. The goal of this study was to investigate whether plasma concentration of vitamin D is associated with survivorship and disease progression in men diagnosed with prostate cancer. Methods and Materials We conducted a population-based cohort study of 1,476 prostate cancer patients to assess disease recurrence/progression and prostate cancer-specific mortality (PCSM) risks associated with serum levels of 25(OH) vitamin D [25(OH)D]. Results There were 325 recurrence/progression and 95 PCSM events during an average of 10.8 years of follow-up. Serum levels of 25(OH)D were not associated with risk of recurrence/ progression or mortality. Clinically deficient vitamin D levels were associated with an increased risk of death from other causes. Conclusions We did not find evidence that serum vitamin D levels measured after diagnosis affect prostate cancer prognosis. Lower levels of vitamin D were associated with risk of non-prostate cancer mortality. PMID:23972671

  12. MicroRNAs and drug resistance in prostate cancers.

    PubMed

    Li, Feng; Mahato, Ram I

    2014-08-01

    Prostate cancer is the second leading cause of cancer related death in American men. Androgen deprivation therapy (ADT) is used to treat patients with aggressive prostate cancers. After androgen deprivation therapy, prostate cancers slowly progress to an androgen-independent status. Taxanes (e.g., docetaxel) are used as standard treatments for androgen-independent prostate cancers. However, these chemotherapeutic agents will eventually become ineffective due to the development of drug resistance. A microRNA (miRNA) is a small noncoding RNA molecule, which can regulate gene expression at the post-transcription level. miRNAs elicit their effects by binding to the 3'-untranslated region (3'-UTR) of their target mRNAs, leading to the inhibition of translation or the degradation of the mRNAs. miRNAs have received increasing attention as targets for cancer therapy, as they can target multiple signaling pathways related to tumor progression, metastasis, invasion, and chemoresistance. Emerging evidence suggests that aberrant expression of miRNAs can lead to the development of resistant prostate cancers. Here, we discuss the roles of miRNAs in the development of resistant prostate cancers and their involvement in various drug resistant mechanisms including androgen signaling, apoptosis avoidance, multiple drug resistance (MDR) transporters, epithelialmesenchymal transition (EMT), and cancer stem cells (CSCs). In addition, we also discuss strategies for treating resistant prostate cancers by targeting specific miRNAs. Different delivery strategies are also discussed with focus on those that have been successfully used in human clinical trials. PMID:24742219

  13. Screening spectroscopy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Yermolenko, S. B.; Voloshynskyy, D. I.; Fedoruk, O. S.

    2015-11-01

    The aim of the study was to establish objective parameters of the field of laser and incoherent radiation of different spectral ranges (UV, visible, IR) as a non-invasive optical method of interaction with different samples of biological tissues and fluids of patients to determine the state of prostate cancer and choosing the best personal treatment. The objects of study were selected venous blood plasma of patient with prostate cancer, histological sections of rat prostate gland in the postoperative period. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5-25 microns) dry residue of plasma by spectral diagnostic technique of thin histological sections of biological tissues.

  14. Common Gene Rearrangements in Prostate Cancer

    PubMed Central

    Rubin, Mark A.; Maher, Christopher A.; Chinnaiyan, Arul M.

    2011-01-01

    Prostate cancer is a common heterogeneous disease, and most patients diagnosed in the post prostate-specific antigen (PSA) era present with clinically localized disease, the majority of which do well regardless of treatment regimen undertaken. Overall, those with advanced prostate cancer at time of diagnosis do poorly after androgen withdrawal therapy. Understanding the biologic underpinning of prostate cancer is necessary to best determine the risk of disease progression and would be advantageous for the development of novel therapeutic approaches to impede or prevent disease. This review focuses on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer. Although multiple molecular alterations have been detected in prostate cancer, a detailed understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity, providing a rationale for a molecular subclassification of the disease. PMID:21859993

  15. Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer.

    PubMed

    Rybicki, Benjamin A; Rundle, Andrew; Kryvenko, Oleksandr N; Mitrache, Nicoleta; Do, Kieu C; Jankowski, Michelle; Chitale, Dhananjay A; Trudeau, Sheri; Belinsky, Steven A; Tang, Deliang

    2016-06-15

    In DNA from prostate tumors, methylation patterns in gene promoter regions can be a biomarker for disease progression. It remains unclear whether methylation patterns in benign prostate tissue--prior to malignant transformation--may provide similar prognostic information. To determine whether early methylation events predict prostate cancer outcomes, we evaluated histologically benign prostate specimens from 353 men who eventually developed prostate cancer and received "definitive" treatment [radical prostatectomy (58%) or radiation therapy (42%)]. Cases were drawn from a large hospital-based cohort of men with benign prostate biopsy specimens collected between 1990 and 2002. Risk of disease progression associated with methylation was estimated using time-to-event analyses. Average follow-up was over 5 years; biochemical recurrence (BCR) occurred in 91 cases (26%). In White men, methylation of the APC gene was associated with increased risk of BCR, even after adjusting for standard clinical risk factors for prostate cancer progression (adjusted hazard ratio (aHR) = 2.26; 95%CI 1.23-4.16). APC methylation was most strongly associated with a significant increased risk of BCR in White men with low prostate specific antigen at cohort entry (HR = 3.66; 95%CI 1.51-8.85). In additional stratified analyses, we found that methylation of the RARB gene significantly increased risk of BCR in African American cases who demonstrated methylation of at least one of the other four genes under study (HR = 3.80; 95%CI 1.07-13.53). These findings may have implications in the early identification of aggressive prostate cancer as well as reducing unnecessary medical procedures and emotional distress for men who present with markers of indolent disease. PMID:26860439

  16. Immunotherapy for metastatic prostate cancer

    PubMed Central

    Drake, Charles G.

    2016-01-01

    Chemotherapy with docetaxel is the standard treatment for men with metastatic prostate cancer, and results in statistically significant improvements in survival, as well as in quality of life. However, the response rate to single-agent docetaxel is approximately 40% to 45%, emphasizing a need for alternative approaches. More significantly, with the onset of early, PSA-based detection of prostate cancer and closer follow-up, many men present with metastatic disease that remains asymptomatic. For such patients, the side effects of chemotherapy would compromise their current performance status and, thus, a nontoxic, early treatment option that could improve overall survival would be highly desirable. Immunotherapy represents one such approach; a number of clinical trials have suggested a survival benefit for immunotherapy in metastatic prostate cancer and confirmed that these agents are generally well-tolerated. As is the case for chemotherapy, it is doubtful that maximal survival benefit will be achieved with single-agent immunotherapy; experimental treatments in which mechanistically distinct immunotherapy approaches are combined, as well as approaches in which immunotherapy is combined with chemotherapy or hormonal therapy are currently under investigation. This review will discuss the mechanisms of action of several immunotherapy approaches for metastatic prostate cancer, focusing on active immunotherapy as opposed to administration of anti-tumor antibodies. The relative advantages and disadvantages of current approaches will be noted, and ongoing clinical trials will be highlighted. PMID:18593624

  17. Prostate and Urologic Cancer | Division of Cancer Prevention

    Cancer.gov

    Conducts and supports research on the prevention and early detection of prostate and bladder cancer. | Conducts and supports research on the prevention and early detection of prostate, bladder, and skin cancers.

  18. Proteomics in diagnosis of prostate cancer.

    PubMed

    Davalieva, K; Polenakovic, M

    2015-01-01

    Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. The introduction of prostate specific antigen (PSA) has greatly increased the number of men diagnosed with PCa but at the same time, as a result of the low specificity, led to overdiagnosis, resulting to unnecessary biopsies and high medical cost treatments. The primary goal in PCa research today is to find a biomarker or biomarker set for clear and effecttive diagnosis of PCa as well as for distinction between aggressive and indolent cancers. Different proteomic technologies such as 2-D PAGE, 2-D DIGE, MALDI MS profiling, shotgun proteomics with label-based (ICAT, iTRAQ) and label-free (SWATH) quantification, MudPIT, CE-MS have been applied to the study of PCa in the past 15 years. Various biological samples, including tumor tissue, serum, plasma, urine, seminal plasma, prostatic secretions and prostatic-derived exosomes were analyzed with the aim of identifying diagnostic and prognostic biomarkers and developing a deeper understanding of the disease at the molecular level. This review is focused on the overall analysis of expression proteomics studies in the PCa field investigating all types of human samples in the search for diagnostics biomarkers. Emphasis is given on proteomics platforms used in biomarker discovery and characterization, explored sources for PCa biomarkers, proposed candidate biomarkers by comparative proteomics studies and the possible future clinical application of those candidate biomarkers in PCa screening and diagnosis. In addition, we review the specificity of the putative markers and existing challenges in the proteomics research of PCa. PMID:26076772

  19. Current role of multiparametric magnetic resonance imaging for prostate cancer

    PubMed Central

    Chevallier, Olivier; Moulin, Morgan; Favelier, Sylvain; Genson, Pierre-Yves; Pottecher, Pierre; Crehange, Gilles; Cochet, Alexandre; Cormier, Luc

    2015-01-01

    Multiparametric magnetic resonance imaging (mp-MRI) has shown promising results in diagnosis, localization, risk stratification and staging of clinically significant prostate cancer, and targeting or guiding prostate biopsy. mp-MRI consists of T2-weighted imaging (T2WI) combined with several functional sequences including diffusion-weighted imaging (DWI), perfusion or dynamic contrast-enhanced imaging (DCEI) and spectroscopic imaging. Recently, mp-MRI has been used to assess prostate cancer aggressiveness and to identify anteriorly located tumors before and during active surveillance. Moreover, recent studies have reported that mp-MRI is a reliable imaging modality for detecting local recurrence after radical prostatectomy or external beam radiation therapy. Because assessment on mp-MRI can be subjective, use of the newly developed standardized reporting Prostate Imaging and Reporting Archiving Data System (PI-RADS) scoring system and education of specialist radiologists are essential for accurate interpretation. This review focuses on the current place of mp-MRI in prostate cancer and its evolving role in the management of prostate cancer. PMID:26682144

  20. A role for STEAP2 in prostate cancer progression.

    PubMed

    Whiteland, Helen; Spencer-Harty, Samantha; Morgan, Claire; Kynaston, Howard; Thomas, David Hywel; Bose, Pradeep; Fenn, Neil; Lewis, Paul; Jenkins, Spencer; Doak, Shareen H

    2014-12-01

    Prostate adenocarcinoma is the second most frequent cancer worldwide and is one of the leading causes of male cancer-related deaths. However, it varies greatly in its behaviour, from indolent non-progressive disease to metastatic cancers with high associated mortality. The aim of this study was to identify predictive biomarkers for patients with localised prostate tumours most likely to progress to aggressive disease, to facilitate future tailored clinical treatment and identify novel therapeutic targets. The expression of 602 genes was profiled using oligoarrays, across three prostate cancer cell lines: CA-HPV-10, LNCaP and PC3, qualitatively identifying several potential prognostic biomarkers. Of particular interest was six transmembrane epithelial antigen of the prostate (STEAP) 1 and STEAP 2 which was subsequently analysed further in prostate cancer tissue samples following optimisation of an RNA extraction method from laser captured cells isolated from formalin-fixed paraffin-embedded biopsy samples. Quantitative analysis of STEAP1 and 2 gene expression were statistically significantly associated with the metastatic cell lines DU145 and PC3 as compared to the normal prostate epithelial cell line, PNT2. This expression pattern was also mirrored at the protein level in the cells. Furthermore, STEAP2 up-regulation was observed within a small patient cohort and was associated with those that had locally advanced disease. Subsequent mechanistic studies in the PNT2 cell line demonstrated that an over-expression of STEAP2 resulted in these normal prostate cells gaining an ability to migrate and invade, suggesting that STEAP2 expression may be a crucial molecule in driving the invasive ability of prostate cancer cells. PMID:25248617

  1. Spectrum of mitochondrial genomic variation and associated clinical presentation of prostate cancer in South African men

    PubMed Central

    McCrow, John P.; Petersen, Desiree C.; Louw, Melanie; Chan, Eva K. F.; Harmeyer, Katherine; Vecchiarelli, Stefano; Lyons, Ruth J.; Bornman, M. S. Riana

    2015-01-01

    BACKGROUND Prostate cancer incidence and mortality rates are significantly increased in African–American men, but limited studies have been performed within Sub–Saharan African populations. As mitochondria control energy metabolism and apoptosis we speculate that somatic mutations within mitochondrial genomes are candidate drivers of aggressive prostate carcinogenesis. METHODS We used matched blood and prostate tissue samples from 87 South African men (77 with African ancestry) to perform deep sequencing of complete mitochondrial genomes. Clinical presentation was biased toward aggressive disease (Gleason score >7, 64%), and compared with men without prostate cancer either with or without benign prostatic hyperplasia. RESULTS We identified 144 somatic mtDNA single nucleotide variants (SNVs), of which 80 were observed in 39 men presenting with aggressive disease. Both the number and frequency of somatic mtDNA SNVs were associated with higher pathological stage. CONCLUSIONS Besides doubling the total number of somatic PCa‐associated mitochondrial genome mutations identified to date, we associate mutational load with aggressive prostate cancer status in men of African ancestry. Prostate 76:349–358, 2016. © 2015 The Authors. The Prostate published by Wiley Periodicals, Inc. PMID:26660354

  2. What's New in Prostate Cancer Research and Treatment?

    MedlinePlus

    ... Next Topic Additional resources for prostate cancer What’s new in prostate cancer research? Research into the causes , ... in many medical centers throughout the world. Genetics New research on gene changes linked to prostate cancer ...

  3. Progress Against Prostate Cancer | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Prostate Cancer Progress Against Prostate Cancer Past Issues / Winter 2010 Table of Contents Click ... This can narrow the urethra, decreasing urine flow. Prostate cancer is made up of cells the body does ...

  4. Androgen receptors in prostate cancer.

    PubMed

    Culig, Z; Klocker, H; Bartsch, G; Hobisch, A

    2002-09-01

    The androgen receptor (AR), a transcription factor that mediates the action of androgens in target tissues, is expressed in nearly all prostate cancers. Carcinoma of the prostate is the most frequently diagnosed neoplasm in men in industrialized countries. Palliative treatment for non-organ-confined prostate cancer aims to down-regulate the concentration of circulating androgen or to block the transcription activation function of the AR. AR function during endocrine therapy was studied in tumor cells LNCaP subjected to long-term steroid depletion; newly generated sublines could be stimulated by lower concentrations of androgen than parental cells and showed up-regulation of AR expression and activity as well as resistance to apoptosis. Androgenic hormones regulate the expression of key cell cycle regulators, cyclin-dependent kinase 2 and 4, and that of the cell cycle inhibitor p27. Inhibition of AR expression could be achieved by potential chemopreventive agents flufenamic acid, resveratrol, quercetin, polyunsaturated fatty acids and interleukin-1beta, and by the application of AR antisense oligonucleotides. In the clinical situation, AR gene amplification and point mutations were reported in patients with metastatic disease. These mutations generate receptors which could be activated by other steroid hormones and non-steroidal antiandrogens. In the absence of androgen, the AR could be activated by various growth-promoting (growth factors, epidermal growth factor receptor-related oncogene HER-2/neu) and pleiotropic (protein kinase A activators, interleukin-6) compounds as well as by inducers of differentiation (phenylbutyrate). AR function is modulated by a number of coactivators and corepressors. The three coactivators, TIF-2, SRC-1 and RAC3, are up-regulated in relapsed prostate cancer. New experimental therapies for prostate cancer are aimed to down-regulate AR expression and to overcome difficulties which occur because of the acquisition of agonistic properties

  5. Adipocyte Secreted Factors Enhance Aggressiveness of Prostate Carcinoma Cells

    PubMed Central

    Moreira, Ângela; Pereira, Sofia S.; Costa, Madalena; Morais, Tiago; Pinto, Ana; Fernandes, Rúben; Monteiro, Mariana P.

    2015-01-01

    Obesity has been associated with increased incidence and risk of mortality of prostate cancer. One of the proposed mechanisms underlying this risk association is the change in adipokines expression that could promote the development and progression of the prostate tumor cells. The main goal of this study was to evaluate the effect of preadipocyte and adipocyte secretome in the proliferation, migration and invasion of androgen independent prostate carcinoma cells (RM1) and to assess cell proliferation in the presence of the adiposity signals leptin and insulin. RM1 cells were co-cultured in with preadipocytes, adipocytes or cultured in their respective conditioned medium. Cell proliferation was assessed by flow cytometry and XTT viability test. Cell migration was evaluated using a wound healing injury assay of RM1 cells cultured with conditioned media. Cellular invasion of RM1 cells co-cultured with adipocytes and preadipocytes was assessed using matrigel membranes. Preadipocyte conditioned medium was associated with a small increase in RM1 proliferation, while adipocytes conditioned media significantly increased RM1 cell proliferation (p<0.01). Adipocytes also significantly increased the RM1 cells proliferation in co-culture (p <0.01). Cell migration was higher in RM1 cells cultured with preadipocyte and adipocyte conditioned medium. RM1 cell invasion was significantly increased after co-culture with preadipocytes and adipocytes (p <0.05). Insulin also increased significantly the cell proliferation in contrast to leptin, which showed no effect. In conclusion, prostate carcinoma cells seem to be influenced by factors secreted by adipocytes that are able to increase their ability to proliferate, migrate and invade. PMID:25928422

  6. Myopodin, a synaptopodin homologue, is frequently deleted in invasive prostate cancers.

    PubMed

    Lin, F; Yu, Y P; Woods, J; Cieply, K; Gooding, B; Finkelstein, P; Dhir, R; Krill, D; Becich, M J; Michalopoulos, G; Finkelstein, S; Luo, J H

    2001-11-01

    Prostate cancer is one of the leading causes of cancer-related deaths for men in the United States. Like other malignancies, prostate cancer is underscored by a variety of aberrant genetic alterations during its development. Although loss of heterozygosity or allelic loss is frequently identified among prostate cancers, few genes have been identified thus far as critical to the development of invasive prostate cancers. In this report, we used the recently developed technology, the "differential subtraction chain," to perform a genome-wide search for sequences that are deleted in an aggressive prostate cancer. Among the deleted sequences, we found that one sequence was deleted in >50% of prostate cancers we tested. We mapped this sequence to chromosome 4q25 by screening the Genebridge 4 hamster radiation panel with primers specific to this probe, and subsequently identify a 54-kb minimal common deletion region that contains the sequence encoding myopodin. Sequence analysis indicates that myopodin shares significant homology with synaptopodin, a protein closely associated with podocyte and neuron differentiation. Further study shows that frequent complete or partial deletions of the myopodin gene occurred among invasive prostate cancer cases (25 of 31 cases, or 80%). Statistical analysis indicates that deletion of myopodin is highly correlated with the invasiveness of prostate cancers, and thus may hold promise as an important prognostic marker for prostate cancers. PMID:11696420

  7. Periprostatic adipocytes act as a driving force for prostate cancer progression in obesity.

    PubMed

    Laurent, Victor; Guérard, Adrien; Mazerolles, Catherine; Le Gonidec, Sophie; Toulet, Aurélie; Nieto, Laurence; Zaidi, Falek; Majed, Bilal; Garandeau, David; Socrier, Youri; Golzio, Muriel; Cadoudal, Thomas; Chaoui, Karima; Dray, Cedric; Monsarrat, Bernard; Schiltz, Odile; Wang, Yuan Yuan; Couderc, Bettina; Valet, Philippe; Malavaud, Bernard; Muller, Catherine

    2016-01-01

    Obesity favours the occurrence of locally disseminated prostate cancer in the periprostatic adipose tissue (PPAT) surrounding the prostate gland. Here we show that adipocytes from PPAT support the directed migration of prostate cancer cells and that this event is strongly promoted by obesity. This process is dependent on the secretion of the chemokine CCL7 by adipocytes, which diffuses from PPAT to the peripheral zone of the prostate, stimulating the migration of CCR3 expressing tumour cells. In obesity, higher secretion of CCL7 by adipocytes facilitates extraprostatic extension. The observed increase in migration associated with obesity is totally abrogated when the CCR3/CCL7 axis is inhibited. In human prostate cancer tumours, expression of the CCR3 receptor is associated with the occurrence of aggressive disease with extended local dissemination and a higher risk of biochemical recurrence, highlighting the potential benefit of CCR3 antagonists in the treatment of prostate cancer. PMID:26756352

  8. Periprostatic adipocytes act as a driving force for prostate cancer progression in obesity

    PubMed Central

    Laurent, Victor; Guérard, Adrien; Mazerolles, Catherine; Le Gonidec, Sophie; Toulet, Aurélie; Nieto, Laurence; Zaidi, Falek; Majed, Bilal; Garandeau, David; Socrier, Youri; Golzio, Muriel; Cadoudal, Thomas; Chaoui, Karima; Dray, Cedric; Monsarrat, Bernard; Schiltz, Odile; Wang, Yuan Yuan; Couderc, Bettina; Valet, Philippe; Malavaud, Bernard; Muller, Catherine

    2016-01-01

    Obesity favours the occurrence of locally disseminated prostate cancer in the periprostatic adipose tissue (PPAT) surrounding the prostate gland. Here we show that adipocytes from PPAT support the directed migration of prostate cancer cells and that this event is strongly promoted by obesity. This process is dependent on the secretion of the chemokine CCL7 by adipocytes, which diffuses from PPAT to the peripheral zone of the prostate, stimulating the migration of CCR3 expressing tumour cells. In obesity, higher secretion of CCL7 by adipocytes facilitates extraprostatic extension. The observed increase in migration associated with obesity is totally abrogated when the CCR3/CCL7 axis is inhibited. In human prostate cancer tumours, expression of the CCR3 receptor is associated with the occurrence of aggressive disease with extended local dissemination and a higher risk of biochemical recurrence, highlighting the potential benefit of CCR3 antagonists in the treatment of prostate cancer. PMID:26756352

  9. Decision making and prostate cancer screening.

    PubMed

    Knight, Sara J

    2014-05-01

    This article presents an overview of the challenges that men encounter in making decisions about prostate cancer screening, including complex affective and cognitive factors and controversies in the interpretation of the evidence on prostate cancer screening. Shared decision making involving patient decision aids are discussed as approaches that can be used to improve the quality of prostate cancer screening decisions, including a close alignment between a man's values, goals, and preferences and his choice about screening. PMID:24725488

  10. Molecular Imaging of Prostate Cancer: PET Radiotracers

    PubMed Central

    Jadvar, Hossein

    2012-01-01

    OBJECTIVE Recent advances in the fundamental understanding of the complex biology of prostate cancer have provided an increasing number of potential targets for imaging and treatment. The imaging evaluation of prostate cancer needs to be tailored to the various phases of this remarkably heterogeneous disease. CONCLUSION In this article, I review the current state of affairs on a range of PET radiotracers for potential use in the imaging evaluation of men with prostate cancer. PMID:22826388

  11. Testosterone Replacement Therapy and Prostate Cancer Incidence

    PubMed Central

    2015-01-01

    While early studies demonstrated a positive association between testosterone and prostate cancer, evidence on the nature of the relationship has evolved with time and newer data. Studies examining links between baseline testosterone levels as well as testosterone therapy and incident prostate cancer, reveal a more complex relationship. Moreover, investigators have reported their initial experiences with supplementing testosterone in men with a history of both treated and untreated prostate cancer. PMID:26770932

  12. When Prostate Cancer Circulates in the Bloodstream

    PubMed Central

    Vlaeminck-Guillem, Virginie

    2015-01-01

    Management of patients with prostate cancer is currently based on imperfect clinical, biological, radiological and pathological evaluation. Prostate cancer aggressiveness, including metastatic potential, remains difficult to accurately estimate. In an attempt to better adapt therapeutics to an individual (personalized medicine), reliable evaluation of the intrinsic molecular biology of the tumor is warranted, and particularly for all tumor sites (primary tumors and secondary sites) at any time of the disease progression. As a consequence of their natural tendency to grow (passive invasion) or as a consequence of an active blood vessel invasion by metastase-initiating cells, tumors shed various materials into the bloodstream. Major efforts have been recently made to develop powerful and accurate methods able to detect, quantify and/or analyze all these circulating tumor materials: circulating tumors cells, disseminating tumor cells, extracellular vesicles (including exosomes), nucleic acids, etc. The aim of this review is to summarize current knowledge about these circulating tumor materials and their applications in translational research. PMID:26854164

  13. Bone imaging in prostate cancer.

    PubMed

    Dotan, Zohar A

    2008-08-01

    Bone metastases of solid tumors are common, and about 80% of them occur in patients with breast, lung or prostate cancer. Bone metastases can be suspected clinically and by laboratory tests; however, a final diagnosis relies on radiographic evidence. Bone metastases of prostate cancer usually have osteoblastic characteristics, manifested by pathological bone resorption and formation. Conventional bone scans (e.g. with (99m)Tc-labeled methylene diphosphonate) are preferred to plain-film radiography for surveillance of the entire skeleton. Radiologic diagnosis of bone metastases, particularly in patients with low burden of disease, is difficult because noncancerous bone lesions that mimic cancer are common. Conventional bone scans are limited by their low sensitivity and high false-negative rate (up to 40%) compared with advanced bone-imaging modalities such as PET, PET-CT and MRI, which might assist or replace conventional scanning methods. The correct diagnosis of bone involvement in prostate cancer is crucial to assess the effects of therapy on the primary tumor, the patient's prognosis, and the efficacy of bone-specific treatments that can reduce future bone-associated morbidity. In addition, predictive tools such as nomograms enable the identification of patients at risk of bone involvement during the course of their disease. Such tools may limit treatment costs by avoidance of unnecessary tests and might reduce both short-term and long-term complication rates. PMID:18682719

  14. Antisense approaches in prostate cancer.

    PubMed

    Chi, Kim N; Gleave, Martin E

    2004-06-01

    Patients with hormone refractory prostate cancer have limited treatment options and new therapies are urgently needed. Advances in the understanding of the molecular mechanisms implicated in prostate cancer progression have identified many potential therapeutic gene targets that are involved in apoptosis, growth factors, cell signalling and the androgen receptor (AR). Antisense oligonucleotides are short sequences of synthetic modified DNA that are designed to be complimentary to a selected gene's mRNA and thereby specifically inhibit expression of that gene. The antisense approach continues to hold promise as a therapeutic modality to target genes involved in cancer progression, especially those in which the gene products are not amenable to small molecule inhibition or antibodies. The current status and future direction of a number of antisense oligonucleotides targeting several genes, including BCL-2, BCL-XL, clusterin, the inhibitors of apoptosis (IAP) family, MDM2, protein kinase C-alpha, c-raf, insulin-like growth factor binding proteins and the AR, that have potential clinical use in prostate cancer are reviewed. PMID:15174974

  15. Molecularly targeted radiosensitization chances towards gene aberration-due organ confined/regionally advanced prostate cancer radioresistance

    PubMed Central

    ALBERTI, C.

    2015-01-01

    Considering that the prostate cancer radioresistance occurs in a significant percentage – as 20–40% of prostate cancer (PCa) patients undergone external beam radiation therapy developing, within ten years, recurrent and more aggressive tumor – the resort to customized radiosensitizer measures, focusly targeting PCa radioresistance-linked individual molecular aberrations, can increase the successful outcomes of PCa radiotherapy. PMID:26188759

  16. Blood lipids and prostate cancer: a Mendelian randomization analysis.

    PubMed

    Bull, Caroline J; Bonilla, Carolina; Holly, Jeff M P; Perks, Claire M; Davies, Neil; Haycock, Philip; Yu, Oriana Hoi Yun; Richards, J Brent; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; MacInnis, Robert J; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Neal, David; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Micheal, Agnieszka; Pandha, Hardev; Smith, George Davey; Lewis, Sarah J; Martin, Richard M

    2016-06-01

    Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high- (≥7 Gleason score) versus low-grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy. PMID:26992435

  17. Prostate Cancer and Li-Fraumeni Syndrome: Implications for Screening and Therapy.

    PubMed

    Spees, Colleen K; Kelleher, Kelly J; Abaza, Ronney; Clinton, Steven K

    2015-03-01

    Li-Fraumeni Syndrome (LFS) is an autosomal dominant genetic disorder associated with mutations in the TP53 gene and characterized by a propensity to develop a variety of malignancies resulting in a shortened lifespan. We report a case of prostate cancer in a 50 year old male with LFS. Experimental studies suggest that TP53 mutations in prostate cancer are associated with therapeutic resistance to radiation, chemotherapy, and anti-androgens, implying that LFS men may experience more aggressive cancer biology with implications for therapeutic decisions. The potential of prostate cancer to develop earlier in LFS favors institution of screening at earlier ages. PMID:26793489

  18. Prostate Cancer and Li-Fraumeni Syndrome: Implications for Screening and Therapy

    PubMed Central

    Spees, Colleen K.; Kelleher, Kelly J.; Abaza, Ronney; Clinton, Steven K.

    2015-01-01

    Li-Fraumeni Syndrome (LFS) is an autosomal dominant genetic disorder associated with mutations in the TP53 gene and characterized by a propensity to develop a variety of malignancies resulting in a shortened lifespan. We report a case of prostate cancer in a 50 year old male with LFS. Experimental studies suggest that TP53 mutations in prostate cancer are associated with therapeutic resistance to radiation, chemotherapy, and anti-androgens, implying that LFS men may experience more aggressive cancer biology with implications for therapeutic decisions. The potential of prostate cancer to develop earlier in LFS favors institution of screening at earlier ages. PMID:26793489

  19. Metabolic Syndrome and Prostate Cancer: a Review of Complex Interplay Amongst Various Endocrine Factors in the Pathophysiology and Progression of Prostate Cancer.

    PubMed

    Rhee, Handoo; Vela, Ian; Chung, Eric

    2016-04-01

    The human prostate gland is an endocrine organ where dysregulation of various hormonal factors may play a pivotal role in the pathogenesis of prostate cancer. There is emerging epidemiological data to support the role of components of metabolic syndrome, namely, obesity, hypercholesterolaemia, diabetes and hyperinsulinaemia on the development and/or the progression of prostate cancer. Although the exact mechanisms behind the relationship between metabolic syndrome and prostate cancer remain largely unknown, various in vitro and animal experiments of metabolic syndrome models have been shown to promote survival, mitogenesis, metastasis and treatment resistance pathways, through various adaptive responses such as intracellular steroidogenesis and lipogenesis. Also, in a large proportion of men with metabolic syndrome, alteration in levels of hormones such as testosterone, leptin and adiponectin has been shown to contribute towards the aggression of prostate cancer. Whilst the exact bio-pathophysiological mechanisms between metabolic syndrome and prostate cancer are yet to be fully elucidated, medications that target specific components of metabolic syndrome have further provided evidence for the inter-relationship between metabolic syndrome, its components and prostate cancer. Emerging in vitro and molecular data is likely to bring us closer to utilizing this knowledge to target particular cancer survival pathways and improving outcomes for men with prostate cancer. PMID:26546071

  20. Simulated prostate biopsy: prostate cancer distribution and clinical correlation

    NASA Astrophysics Data System (ADS)

    Bauer, John J.; Zeng, Jianchao; Zhang, Wei; Sesterhenn, Isabell A.; Dean, Robert; Moul, Judd W.; Mun, Seong K.

    2000-04-01

    Our group has recently obtained data based upon whole- mounted step-sectioned radical prostatectomy specimens using a 3D computer assisted prostate biopsy simulator that suggests an increased detection rate is possible using laterally placed biopsies. A new 10-core biopsy pattern was demonstrated to be superior to the traditional sextant biopsy. This patter includes the traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland. The objective of this study is to confirm the higher prostate cancer defection rate obtained using our simulated 10-core biopsy pattern in a small clinical trial. We retrospectively reviewed 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent of patients were diagnosed solely with the laterally placed biopsies. Our results suggest that biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern.

  1. Identification of differentially expressed proteins in direct expressed prostatic secretions of men with organ-confined versus extracapsular prostate cancer.

    PubMed

    Kim, Yunee; Ignatchenko, Vladimir; Yao, Cindy Q; Kalatskaya, Irina; Nyalwidhe, Julius O; Lance, Raymond S; Gramolini, Anthony O; Troyer, Dean A; Stein, Lincoln D; Boutros, Paul C; Medin, Jeffrey A; Semmes, O John; Drake, Richard R; Kislinger, Thomas

    2012-12-01

    Current protocols for the screening of prostate cancer cannot accurately discriminate clinically indolent tumors from more aggressive ones. One reliable indicator of outcome has been the determination of organ-confined versus nonorgan-confined disease but even this determination is often only made following prostatectomy. This underscores the need to explore alternate avenues to enhance outcome prediction of prostate cancer patients. Fluids that are proximal to the prostate, such as expressed prostatic secretions (EPS), are attractive sources of potential prostate cancer biomarkers as these fluids likely bathe the tumor. Direct-EPS samples from 16 individuals with extracapsular (n = 8) or organ-confined (n = 8) prostate cancer were used as a discovery cohort, and were analyzed in duplicate by a nine-step MudPIT on a LTQ-Orbitrap XL mass spectrometer. A total of 624 unique proteins were identified by at least two unique peptides with a 0.2% false discovery rate. A semiquantitative spectral counting algorithm identified 133 significantly differentially expressed proteins in the discovery cohort. Integrative data mining prioritized 14 candidates, including two known prostate cancer biomarkers: prostate-specific antigen and prostatic acid phosphatase, which were significantly elevated in the direct-EPS from the organ-confined cancer group. These and five other candidates (SFN, MME, PARK7, TIMP1, and TGM4) were verified by Western blotting in an independent set of direct-EPS from patients with biochemically recurrent disease (n = 5) versus patients with no evidence of recurrence upon follow-up (n = 10). Lastly, we performed proof-of-concept SRM-MS-based relative quantification of the five candidates using unpurified heavy isotope-labeled synthetic peptides spiked into pools of EPS-urines from men with extracapsular and organ-confined prostate tumors. This study represents the first efforts to define the direct-EPS proteome from two major subclasses of prostate cancer

  2. Prostate Cancer, Version 1.2016.

    PubMed

    Mohler, James L; Armstrong, Andrew J; Bahnson, Robert R; D'Amico, Anthony Victor; Davis, Brian J; Eastham, James A; Enke, Charles A; Farrington, Thomas A; Higano, Celestia S; Horwitz, Eric M; Hurwitz, Michael; Kane, Christopher J; Kawachi, Mark H; Kuettel, Michael; Lee, Richard J; Meeks, Joshua J; Penson, David F; Plimack, Elizabeth R; Pow-Sang, Julio M; Raben, David; Richey, Sylvia; Roach, Mack; Rosenfeld, Stan; Schaeffer, Edward; Skolarus, Ted A; Small, Eric J; Sonpavde, Guru; Srinivas, Sandy; Strope, Seth A; Tward, Jonathan; Shead, Dorothy A; Freedman-Cass, Deborah A

    2016-01-01

    The NCCN Guidelines for Prostate Cancer address staging and risk assessment after an initial diagnosis of prostate cancer and management options for localized, regional, and metastatic disease. Recommendations for disease monitoring, treatment of recurrent disease, and systemic therapy for metastatic castration-recurrent prostate cancer also are included. This article summarizes the NCCN Prostate Cancer Panel's most significant discussions for the 2016 update of the guidelines, which include refinement of risk stratification methods and new options for the treatment of men with high-risk and very-high-risk disease and progressive castration-naïve disease. PMID:26733552

  3. Shear Wave Elastography for Detection of Prostate Cancer: A Preliminary Study

    PubMed Central

    Woo, Sungmin; Cho, Jeong Yeon; Kim, Seung Hyup

    2014-01-01

    Objective To assess the diagnostic value of shear wave elastography (SWE) for prostate cancer detection. Materials and Methods In this retrospective study, 87 patients with the suspicion of prostate cancer (prostate-specific antigen > 4 ng/mL and abnormal digital rectal examination) underwent a protocol-based systematic 12-core biopsy followed by targeted biopsy at hypoechoic areas on grey-scale ultrasound. Prior to biopsy, SWE was performed by placing two circular 5 mm-sized regions of interest (ROIs) along the estimated biopsy tract in each sector and one ROI for hypoechoic lesions. SWE parameters, S (mean stiffness) and R (mean stiffness ratio), were calculated and compared regarding different histopathologic tissues and their accuracy for diagnosing prostate cancer was analyzed. SWE parameters were correlated with Gleason score and were compared between indolent (< 8) and aggressive (≥ 8) tissues in prostate cancer patients. Results Prostate cancer was detected in 7.5% of 1058 cores in 29.9% of 87 patients. Seven (43.8%) of 16 hypoechoic lesions were confirmed as prostate cancer. SWE parameters were significantly different among the histopathologic entities (p < 0.001). Prostate cancer was stiffer than benign tissues (p ≤ 0.003). Sensitivity, specificity and receiver operating characteristic curve area for diagnosing cancer were 43%, 80.8%, and 0.599, respectively, for a cutoff of S > 43.9 kPa and 60.8%, 66.4%, and 0.653, respectively, for R > 3. Both, S and R showed a significant correlation with Gleason score (r ≥ 0.296, p ≤ 0.008) and were significantly different between indolent and aggressive prostate cancer (p ≤ 0.006). Conclusion Shear wave elastographic parameters are significantly different between prostate cancer and benign prostate tissue and correlate with Gleason score. PMID:24843239

  4. Toll-Like Receptors and Prostate Cancer

    PubMed Central

    Zhao, Shu; Zhang, Yifan; Zhang, Qingyuan; Wang, Fen; Zhang, Dekai

    2014-01-01

    Prostate cancer is the second leading cause of cancer-related death in men after lung cancer. Immune responses clearly play a critical role in the tumorigenesis and in the efficacy of radiation therapy and chemotherapy in prostate cancer; however, the underlying molecular mechanisms are still poorly understood. Toll-like receptors (TLRs) are a well-known family of pattern recognition receptors that play a key role in host immune system. Recent studies demonstrate that there are links between TLRs and cancer; however, the function and biological importance of TLRs in prostate cancer seems complex. To elucidate the role of TLRs and innate immunity in prostate cancer might provide us with a better understanding of the molecular mechanisms of this disease. Moreover, utilizing the agonists or antagonists of TLRs might represent a promising new strategy against prostate cancer. In this review, we summarize recent advances on the studies of association between TLR signaling and prostate cancer, TLR polymorphisms and prostate cancer risk, and provide some insights about TLRs as potential targets for prostate cancer immunotherapy. PMID:25101092

  5. Oxidative stress in prostate cancer.

    PubMed

    Khandrika, Lakshmipathi; Kumar, Binod; Koul, Sweaty; Maroni, Paul; Koul, Hari K

    2009-09-18

    As prostate cancer and aberrant changes in reactive oxygen species (ROS) become more common with aging, ROS signaling may play an important role in the development and progression of this malignancy. Increased ROS, otherwise known as oxidative stress, is a result of either increased ROS generation or a loss of antioxidant defense mechanisms. Oxidative stress is associated with several pathological conditions including inflammation and infection. ROS are products of normal cellular metabolism and play vital roles in stimulation of signaling pathways in response to changing intra- and extracellular environmental conditions. Chronic increases in ROS over time are known to induce somatic mutations and neoplastic transformation. In this review we summarize the causes for increased ROS generation and its potential role in etiology and progression of prostate cancer. PMID:19185987

  6. [Medical treatment of prostate cancer].

    PubMed

    Lobel, B; Cipolla, B; Labrador, J

    1994-03-01

    Hormone dependence of prostate cancer is well known. In 80% of cases with metastases, hormone suppression leads to the reduction of tumour volume and related disorders. However the treatment is generally palliative because malignant process recurs after about around 16 months. Mean survival is less than 3 years in these forms. Lack of response come always together with a poor prognosis, and there is 90% mortality at 2 years. Advanced prostatic cancer should not be treated with hormones if the patient has few symptoms and his quality of life is satisfactory. Symptomatic forms require hormone manipulation. Orchidectomy or LH-RH are recommended. Total androgen ablation (combined treatment) leads rapidly to more relief of symptoms, but its drawbacks and especially high cost indicate that its use should be weighed individually. Estramustine is not a first-lune treatment. Presently, there is no criteria to predict response to treatment. PMID:8066398

  7. [Novel treatment for prostate cancer targeting prostaglandins].

    PubMed

    Terada, Naoki; Inoue, Takahiro; Kamba, Tomomi; Ogawa, Osamu

    2014-12-01

    PGE2 is highly expressed in the prostate, associating with prostate cancer progression. Targeting downstream signaling pathways of PGE2 may represent an attractive new strategy for the treatment of prostate cancer. We have established a novel prostate cancer xenograft model, KUCaP-2. The expression of EP4, one of PGE2 receptors, was significantly up-regulated during the development of castration resistance. A specific EP4 antagonist, ONO-AE3-208, decelerated castration-resistant growth of KUCaP-2 tumors in vivo. Moreover, ONO-AE3-208 could in vitro inhibit the cell invasion and in vivo suppress the bone metastasis of prostate cancer cells. These results indicated that EP4 is a novel target for the treatment of metastatic castration resistant prostate cancer. PMID:25518348

  8. Prostate cancer - treatment

    MedlinePlus

    ... blood in the urine There are reports of secondary cancers arising from the radiation as well. Proton therapy ... Chemotherapy and immunotherapy (medicine that helps the body's immune system fight the cancer) may be used to ...

  9. Environmental exposures and prostate cancer.

    PubMed

    Mullins, Jeffrey K; Loeb, Stacy

    2012-01-01

    Many malignancies have been linked to specific environmental exposures. Several environmental and occupational factors have been studied for an association to prostate cancer (CaP) risk. These include Agent Orange exposure, farming and pesticides, sunlight/ultraviolet radiation, as well as trace minerals used in tire and battery manufacturing. This manuscript reviews the literature on these environmental exposures and CaP. PMID:22385992

  10. 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.

  11. [Roles of folate metabolism in prostate cancer].

    PubMed

    Sun, Fei-vu; Hu, Qing-feng; Xia, Guo-wei

    2015-07-01

    Epidemiological surveys show that folic acid can prevent prostate cancer, but fortified folic acid may increase the risk of the malignancy. The physician data queries from the National Cancer Institute of the USA describe folate as protective against prostate cancer, whereas its synthetic analog, folic acid, is considered to increase prostate cancer risk when taken at levels easily achievable by eating fortified food or taking over-the-counter supplements. We review the current literature to examine the effects of folate and folic acid on prostate cancer, help interpret previous epidemiologic data, and provide a clarification regarding the apparently opposing roles of folate for patients with prostate cancer. A literature search was conducted in Medline to identify studies investigating the effect of nutrition and specifically folate and folic acid on prostate carcinogenesis and progression. In addition, the National Health and Nutrition Examination Survey database was analyzed for the trends in serum folate levels before and after mandatory fortification. Folate likely plays a dual role in prostate carcinogenesis. There remains some conflicting epidemiologic evidence regarding folate and prostate cancer risk. However, there is growing experimental evidence that higher circulating folate levels can contribute to prostate cancer progression. Further research is needed to clarify these complex relationships. PMID:26333231

  12. Precision medicine for advanced prostate cancer

    PubMed Central

    Mullane, Stephanie A.; Van Allen, Eliezer M.

    2016-01-01

    Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

  13. THE ROLE OF ALPHA-BLOCKERS IN THE MANAGEMENT OF PROSTATE CANCER

    PubMed Central

    Tahmatzopoulos, Anastasios; Rowland, Randall G.; Kyprianou, Natasha

    2008-01-01

    Prostate cancer is the second most common cause of cancer death in men in the United States. Patients with prostate cancer are initially treated with surgical resection, radiation or antiandrogen therapy. After an initial remission however, the majority of prostate tumors evolve into a highly aggressive, metastatic androgen-independent state for which successful therapy has not yet been established. During recent years, new perspectives have emerged towards the development of preventive and therapeutic approaches for prostate cancer. The quinazoline-based α1-blockers have been shown to have antitumor efficacy against prostate cancer cells via their potency to induce apoptosis and anoikis via an α1-adrenoceptor-independent mechanism. Specifically, doxazosin and terazosin can induce apoptosis, inhibit invasion and migration of prostate cancer cells and endothelial cells and reduce their adhesion potential to extracellular matrix components (ECM), thus enhancing their susceptibility to anoikis. In this review we discuss recent evidence suggesting the apoptotic efficacy of quinazoline-based α1 adrenoceptor antagonists, doxazosin and terazosin and we speculate on the therapeutic promise of these drugs as novel antitumor agents against prostate cancer. From a drug discovery perspective, separation of the effect of doxazosin on apoptosis in prostate cancer cells from its original pharmacological activity in normal prostate cells, will provide a molecular basis to develop a novel class of apoptosis-inducing agents through lead optimization. PMID:15163273

  14. Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer

    PubMed Central

    Zhang, Liangfen; Rimando, Agnes M.; Lage, Janice M.; Lewin, Jack R.; Atfi, Azeddine; Zhang, Xu; Levenson, Anait S.

    2016-01-01

    Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1- targeted chemopreventive and therapeutic efficacy of pterostilbene, a natural potent analog of resveratrol, in pre-clinical models of prostate cancer. Here, we show that high levels of MTA1 expression in Pten-loss prostate cooperate with key oncogenes, including c-Myc and Akt among others, to promote prostate cancer progression. Loss-of-function studies using human prostate cancer cells indicated direct involvement of MTA1 in inducing inflammation and epithelial-to-mesenchymal transition. Importantly, pharmacological inhibition of MTA1 by pterostilbene resulted in decreased proliferation and angiogenesis and increased apoptosis. This restrained prostatic intraepithelial neoplasia (PIN) formation in prostate-specific Pten heterozygous mice and reduced tumor development and progression in prostate-specific Pten-null mice. Our findings highlight MTA1 as a key upstream regulator of prostate tumorigenesis and cancer progression. More significantly, it offers pre-clinical proof for pterostilbene as a promising lead natural agent for MTA1-targeted chemopreventive and therapeutic strategy to curb prostate cancer. PMID:26943043

  15. Approach to Oligometastatic Prostate Cancer.

    PubMed

    Bernard, Brandon; Gershman, Boris; Karnes, R Jeffrey; Sweeney, Christopher J; Vapiwala, Neha

    2016-01-01

    Oligometastatic prostate cancer has increasingly been recognized as a unique clinical state with therapeutic implications. It has been proposed that patients with oligometastases may have a more indolent course and that outcome may be further improved with metastasis-directed local ablative therapy. In addition, there are differing schools of thoughts regarding whether oligometastases represent isolated lesions-where targeted therapy may render a patient disease free-or whether they coexist with micrometastases, where targeted therapy in addition to systemic therapy is required for maximal clinical impact. As such, the approach to the patient with oligometastatic prostate cancer requires multidisciplinary consideration, with surgery, radiotherapy, and systemic therapy potentially of benefit either singularly or in combination. Indeed, mounting evidence suggests durable disease-free intervals and, in some cases, possibly cure, may be achieved with such a multimodal strategy. However, selecting patients that may benefit most from treatment of oligometastases is an ongoing challenge. Moreover, with the advent of new, highly sensitive imaging technologies, the spectrum based on CT of the abdomen and pelvis and technetium bone scan of localized to oligometastatic to widespread disease has become increasingly blurred. As such, new MRI- and PET-based modalities require validation. As some clinical guidelines advise against routine prostate-specific antigen screening, the possibility of more men presenting with locally advanced or de novo oligometastatic prostate cancer exists; thus, knowing how best to treat these patients may become more relevant at a population level. Ultimately, the arrival of prospective clinical data and better understanding of biology will hopefully further inform how best to treat men with this disease. PMID:27249693

  16. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  17. Development of New Treatments for Prostate Cancer

    SciTech Connect

    DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

    2005-02-01

    The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center of excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention

  18. Dietary Antioxidants and Prostate Cancer: A Review

    PubMed Central

    Vance, Terrence M.; Su, Joseph; Fontham, Elizabeth T. H.; Koo, Sung I.; Chun, Ock K.

    2013-01-01

    Prostate cancer is the most common non-cutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, while lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms. PMID:23909722

  19. Functional Imaging for Prostate Cancer: Therapeutic Implications

    PubMed Central

    Aparici, Carina Mari; Seo, Youngho

    2012-01-01

    Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities CT or MRI (SPECT/CT, PET/CT, and PET/MRI) are promising tools for the management of prostate cancer particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection, to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regards to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, while the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects. PMID:22840598

  20. Prostate Cancer Prevention: Concepts and Clinical Trials.

    PubMed

    Hamilton, Zachary; Parsons, J Kellogg

    2016-04-01

    Prevention is an important treatment strategy for diminishing prostate cancer morbidity and mortality and is applicable to both early- and late-stage disease. There are three basic classifications of cancer prevention: primary (prevention of incident disease), secondary (identification and treatment of preclinical disease), and tertiary (prevention of progression or recurrence). Based on level I evidence, 5-alpha reductase inhibitors (5-ARIs) should be considered in selected men to prevent incident prostate cancer. Level I evidence also supports the consideration of dutasteride, a 5-ARI, for tertiary prevention in active surveillance and biochemical recurrence patients. Vitamins and supplements, including selenium or vitamin E, have not been proven in clinical trials to prevent prostate cancer and in the case of Vitamin E has been found to increase the risk of incident prostate cancer. Ongoing and future trials may further elucidate the role of diet and immunotherapy for prevention of prostate cancer. PMID:26957512

  1. Review of selenium and prostate cancer prevention.

    PubMed

    Yang, Lei; Pascal, Mouracade; Wu, Xiao-Hou

    2013-01-01

    Prostate cancer is the most common malignancy in men in the United States. Surgery or radiation are sometimes unsatisfactory treatments because of the complications such as incontinence or erectile dysfunction. Selenium was found to be effective to prevent prostate cancer in the Nutritional Prevention of Cancer Trial (NPC), which motivated two other clinical trials: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and a Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia. However, these two trials failed to confirm the results of the NPC trial and indicated that the selenium may not be preventive of prostate cancer. In this article we review the three clinical trials and discuss some different points which might be potential factors underlying variation in results obtained. PMID:23725109

  2. AB012. Brachytherapy for localized prostate cancer

    PubMed Central

    Xu, Yong; Yang, Yong

    2016-01-01

    Background To evaluate the security and effect of brachytherapy for localized prostate cancer. Methods Forty five patients with Tl–T2 prostate cancer were treated with real-time transperineal ultrasound-guide 125I seeds prostate implantation. Results The median operation time was 90 min, the median number of I seeds used was 56. The follow up time was 12–48 months, the cases of PSA <1 µg/L were 29, PSA 1–2 µg/L were 11 and PSA ≥2 µg/L were 5. Conclusions Brachytherapy for localized prostate cancer is safe and effective.

  3. Detection of DNA viruses in prostate cancer

    PubMed Central

    Smelov, Vitaly; Bzhalava, Davit; Arroyo Mühr, Laila Sara; Eklund, Carina; Komyakov, Boris; Gorelov, Andrey; Dillner, Joakim; Hultin, Emilie

    2016-01-01

    We tested prostatic secretions from men with and without prostate cancer (13 cases and 13 matched controls) or prostatitis (18 cases and 18 matched controls) with metagenomic sequencing. A large number (>200) of viral reads was only detected among four prostate cancer cases (1 patient each positive for Merkel cell polyomavirus, JC polyomavirus and Human Papillomavirus types 89 or 40, respectively). Lower numbers of reads from a large variety of viruses were detected in all patient groups. Our knowledge of the biology of the prostate may be furthered by the fact that DNA viruses are commonly shed from the prostate and can be readily detected by metagenomic sequencing of expressed prostate secretions. PMID:27121729

  4. Primary Care of the Prostate Cancer Survivor.

    PubMed

    Noonan, Erika M; Farrell, Timothy W

    2016-05-01

    This summary of the American Cancer Society Prostate Cancer Survivorship Care Guidelines targets primary care physicians who coordinate care of prostate cancer survivors with subspecialists. Prostate cancer survivors should undergo prostate-specific antigen screening every six to 12 months and digital rectal examination annually. Surveillance of patients who choose watchful waiting for their prostate cancer should be conducted by a subspecialist. Any hematuria or rectal bleeding must be thoroughly evaluated. Prostate cancer survivors should be screened regularly for urinary incontinence and sexual dysfunction. Patients with predominant urge incontinence symptoms, which can occur after surgical and radiation treatments, may benefit from an anticholinergic agent. If there is difficulty with bladder emptying, a trial of an alpha blocker may be considered. A phosphodiesterase type 5 inhibitor can effectively treat sexual dysfunction following treatment for prostate cancer. Osteoporosis screening should occur before initiation of androgen deprivation therapy, and patients treated with androgen deprivation therapy should be monitored for anemia, metabolic syndrome, and vasomotor symptoms. Healthy lifestyle choices should be encouraged, including weight management, regular physical activity, proper nutrition, and smoking cessation. Primary care physicians should be vigilant for psychosocial distress, including depression, among prostate cancer survivors, as well as the potential impact of this distress on patients' family members and partners. PMID:27175954

  5. MedlinePlus: Prostate Cancer Screening

    MedlinePlus

    ... Cancer (U.S. Preventive Services Task Force) - PDF Specifics Digital Rectal Exam (DRE) (American Society of Clinical Oncology) Prostate Cancer Screening: Should You Get a PSA Test? (Mayo Foundation for Medical Education and Research) Prostate-Specific Antigen (PSA) Test (National ...

  6. A history of prostate cancer treatment

    PubMed Central

    Denmeade, Samuel R.; Isaacs, John T.

    2014-01-01

    The increased incidence of prostate cancer has led to remarkable changes in diagnosis and treatment over the past century. What were the first ways in which prostate cancer was treated, and how did these evolve into the variety of therapeutic strategies from which patients have to choose today? PMID:12044015

  7. Imaging Active Urokinase Plasminogen Activator in Prostate Cancer

    PubMed Central

    LeBeau, Aaron M.; Sevillano, Natalia; Markham, Kate; Winter, Michael B.; Murphy, Stephanie T.; Hostetter, Daniel R.; West, James; Lowman, Henry; Craik, Charles S.; VanBrocklin, Henry F.

    2015-01-01

    The increased proteolytic activity of membrane-bound and secreted proteases on the surface of cancer cells and in the transformed stroma is a common characteristic of aggressive metastatic prostate cancer. We describe here the development of an active site-specific probe for detecting a secreted peritumoral protease expressed by cancer cells and the surrounding tumor microenvironment. Using a human fragment antigen binding phage display library, we identified a human antibody termed U33 that selectively inhibited the active form of the protease urokinase plasminogen activator (uPA, PLAU). In the full-length immunoglobulin form, U33 IgG labeled with near-infrared fluorophores or radionuclides allowed us to non-invasively detect active uPA in prostate cancer xenograft models using optical and single-photon emission computed tomography (SPECT) imaging modalities. U33 IgG labeled with 111In had a remarkable tumor uptake of 43.2% injected dose per gram (%ID/g) 72hr post tail vein injection of the radiolabeled probe in subcutaneous xenografts. Additionally, U33 was able to image active uPA in small soft-tissue and osseous metastatic lesions using a cardiac dissemination prostate cancer model that recapitulated metastatic human cancer. The favorable imaging properties were the direct result of U33 IgG internalization through an uPA receptor mediated mechanism where U33 mimicked the function of the endogenous inhibitor of uPA to gain entry into the cancer cell. Overall, our imaging probe targets a prostate cancer-associated protease, through a unique mechanism, allowing for the non-invasive preclinical imaging of prostate cancer lesions. PMID:25672980

  8. Dysregulation of cholesterol homeostasis in human prostate cancer through loss of ABCA1

    PubMed Central

    Lee, Byron H.; Taylor, Margaret G.; Robinet, Peggy; Smith, Jonathan D.; Schweitzer, Jessica; Sehayek, Ephraim; Falzarano, Sara M.; Magi-Galluzzi, Cristina; Klein, Eric A.; Ting, Angela H.

    2012-01-01

    Recent epidemiologic data show that low serum cholesterol level as well as statin use is associated with a decreased risk of developing aggressive or advanced prostate cancer, suggesting a role for cholesterol in aggressive prostate cancer development. Intracellular cholesterol promotes prostate cancer progression as a substrate for de novo androgen synthesis and through regulation of AKT signaling. By performing next-generation sequencing-based DNA methylome analysis, we have discovered marked hypermethylation at the promoter of the major cellular cholesterol efflux transporter, ABCA1, in LNCaP prostate cancer cells. ABCA1 promoter hypermethylation renders the promoter unresponsive to trans-activation and leads to elevated cholesterol levels in LNCaP. ABCA1 promoter hypermethylation is enriched in intermediate to high grade prostate cancers and not detectable in benign prostate. Remarkably, ABCA1 down-regulation is evident in all prostate cancers examined, and expression levels are inversely correlated with Gleason grade. Our results suggest cancer-specific ABCA1 hypermethylation and loss of protein expression direct high intracellular cholesterol levels and hence contribute to an environment conducive to tumor progression. PMID:23233737

  9. The molecular and cellular origin of human prostate cancer.

    PubMed

    Packer, John R; Maitland, Norman J

    2016-06-01

    Prostate cancer is the most commonly diagnosed male malignancy. Despite compelling epidemiology, there are no definitive aetiological clues linking development to frequency. Pre-malignancies such as proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) yield insights into the initiating events of prostate cancer, as they supply a background "field" for further transformation. An inflammatory aetiology, linked to recurrent prostatitis, and heterologous signalling from reactive stroma and infiltrating immune cells may result in cytokine addiction of cancer cells, including a tumour-initiating population also known as cancer stem cells (CSCs). In prostate tumours, the background mutational rate is rarely exceeded, but genetic change via profound sporadic chromosomal rearrangements results in copy number variations and aberrant gene expression. In cancer, dysfunctional differentiation is imposed upon the normal epithelial lineage, with disruption/disappearance of the basement membrane, loss of the contiguous basal cell layer and expansion of the luminal population. An initiating role for androgen receptor (AR) is attractive, due to the luminal phenotype of the tumours, but alternatively a pool of CSCs, which express little or no AR, has also been demonstrated. Indolent and aggressive tumours may also arise from different stem or progenitor cells. Castrate resistant prostate cancer (CRPC) remains the inevitable final stage of disease following treatment. Time-limited effectiveness of second-generation anti-androgens, and the appearance of an AR-neuroendocrine phenotype imply that metastatic disease is reliant upon the plasticity of the CSC population, and indeed CSC gene expression profiles are most closely related to those identified in CRPCs. PMID:26921821

  10. Bone-targeting agents in prostate cancer

    PubMed Central

    Suzman, Daniel L.; Boikos, Sosipatros A.; Carducci, Michael A.

    2014-01-01

    Bone metastases are present in the vast majority of men with advanced prostate cancer, representing the main cause for morbidity and mortality. Recurrent or metastatic disease is managed initially with androgen deprivation but the majority of the patients eventually will progress to castration-resistant prostate cancer, with patients developing bone metastases in most of the cases. Survival and growth of the metastatic prostate cancer cells is dependent on a complex microenvironment (onco-niche) that includes the osteoblasts, the osteoclasts, the endothelium, and the stroma. This review summarizes agents that target the pathways involved in this complex interaction between prostate cancer and bone micro-environment and aim to transform lethal metastatic prostate cancer into a chronic disease. PMID:24398856

  11. Metabolomic Imaging for Human Prostate Cancer Detection

    PubMed Central

    Wu, Chin-Lee; Jordan, Kate W.; Ratai, Eva M.; Sheng, Jinhua; Adkins, Christen B.; DeFeo, Elita M; Jenkins, Bruce G.; Ying, Leslie; McDougal, W. Scott; Cheng, Leo L.

    2010-01-01

    As current radiological approaches cannot accurately localize prostate cancer in vivo, biopsies are conducted at random within prostates for at-risk patients, leading to high false-negative rates. Metabolomic imaging can map cancer-specific biomolecular profile values onto anatomical structures to direct biopsy. In this preliminary study, we evaluated five prostatectomy-removed whole prostates from biopsy-proven cancer patients on a 7 Tesla human, whole-body magnetic resonance scanner. Localized, multi-cross-sectional, multi-voxel magnetic resonance spectra were used to construct a malignancy index based on prostate cancer metabolomic profiles obtained from previous, intact tissue analyses by a 14 Tesla spectrometer. This calculated Malignancy Index shows linear correlation with lesion size (p<0.013) and demonstrates a 93–97% overall accuracy for detecting the presence of prostate cancer lesions. PMID:20371475

  12. Epidemiology of Prostate and Testicular Cancer.

    PubMed

    Filippou, Pauline; Ferguson, James E; Nielsen, Matthew E

    2016-09-01

    Prostate and testicular cancers account for a large percentage of cancer morbidity in men in the United States and worldwide due to high prevalence rates that continue to grow. Patterns of incidence and mortality vary greatly in both cancers among men of different age groups, ethnicities, and geographic locations. This article summarizes the incidence, prognosis, and risk factors of both prostate and testicular cancers, globally and in the United States. PMID:27582605

  13. Prostate cancer progression. Implications of histopathology.

    PubMed Central

    Ware, J. L.

    1994-01-01

    This review examines selected areas of contemporary prostate cancer research in terms of the impact of prostatic cellular and histopathological heterogeneity. Prostate tumor progression is accompanied by dysregulation of multiple growth factor networks as well as disruption of normal patterns of cell-cell interactions. Molecular and cytogenetic studies demonstrate that prostate cancer results from the accumulation of several different genetic defects. No single event predominates, but modifications in tumor suppressor genes or functional elimination of the suppressor gene product are more common than activation of known oncogenes. Intratumor heterogeneity is also detectable at the genetic level. This further complicates efforts to correlate modifications at specific loci with progression or outcome. The development of new in vitro and in vivo systems for the study of human prostate cancer should increase our understanding of this complex disease. In each approach, knowledge of the histopathology of the normal and neoplastic prostate is essential. PMID:7977655

  14. Detection of antibodies directed at M. hyorhinis p37 in the serum of men with newly diagnosed prostate cancer

    PubMed Central

    2011-01-01

    Background Recent epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including cancers of the prostate. Over the past several years, our group has been studying how mycoplasmas could possibly initiate and propagate cancers of the prostate. Specifically, Mycoplasma hyorhinis encoded protein p37 was found to promote invasion of prostate cancer cells and cause changes in growth, morphology and gene expression of these cells to a more aggressive phenotype. Moreover, we found that chronic exposure of benign human prostate cells to M. hyorhinis resulted in significant phenotypic and karyotypic changes that ultimately resulted in the malignant transformation of the benign cells. In this study, we set out to investigate another potential link between mycoplasma and human prostate cancer. Methods We report the incidence of men with prostate cancer and benign prostatic hyperplasia (BPH) being seropositive for M. hyorhinis. Antibodies to M. hyorhinis were surveyed by a novel indirect enzyme-linked immunosorbent assay (ELISA) in serum samples collected from men presenting to an outpatient Urology clinic for BPH (N = 105) or prostate cancer (N = 114) from 2006-2009. Results A seropositive rate of 36% in men with BPH and 52% in men with prostate cancer was reported, thus leading us to speculate a possible connection between M. hyorhinis exposure with prostate cancer. Conclusions These results further support a potential exacerbating role for mycoplasma in the development of prostate cancer. PMID:21663671

  15. Screening for familial and hereditary prostate cancer.

    PubMed

    Lynch, Henry T; Kosoko-Lasaki, Omofolasade; Leslie, Stephen W; Rendell, Marc; Shaw, Trudy; Snyder, Carrie; D'Amico, Anthony V; Buxbaum, Sarah; Isaacs, William B; Loeb, Stacy; Moul, Judd W; Powell, Isaac

    2016-06-01

    Prostate cancer (PC) has the highest degree of genetic transmission of any form of malignancy. In some families, the hereditary pattern is so strong as to mimic an autosomal dominance trait. We reviewed the known predisposing genetic markers to assess possible strategies for screening of families at risk. We carried out a systematic literature search using the Pubmed service of the National Center for Biotechnology Information (NCBI) and several gene libraries, including the NCBI SNP Library, the Online Mendelian Inheritance in Man® Catalog of Human Genes and Genetic Disorders (OMIM) and SNPedia to obtain known gene loci, SNPs and satellite markers associated with PC. We further cross referenced information on identified loci comparing data from different articles and gene reference sites. Whenever possible, we recorded the odds ratio (OR) for the allele associated with PC. In multiple different linkage studies, many independent PC associated loci have been identified on separate chromosomes. Genome-wide association studies have added many more markers to the set derived from linkage investigations. A subset of the alleles is associated with early onset and aggressive cancer. Due to the great heterogeneity, the OR for any one allele predicting future development of this malignancy is low. The strongest predictors are the BRCA2 mutations, and the highly penetrant G84E mutation in HOXB13. The presence of multiple risk alleles is more highly predictive than a single allele. Technical limitations on screening large panels of alleles are being overcome. It is appropriate to begin supplementing prostate specific antigen testing with alleles, such as BRCA2 and HOXB13, disclosed by targeted genomic analysis in families with an unfavorable family cancer history. Future population studies of PC should include genomic sequencing protocols, particularly in families with a history of PC and other malignancies. PMID:26638190

  16. Dietary Pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary nutrients with ability to reverse adverse epigenetic events have great potential for cancer chemoprevention. Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1-d...

  17. Computer-Aided Image Analysis and Fractal Synthesis in the Quantitative Evaluation of Tumor Aggressiveness in Prostate Carcinomas

    PubMed Central

    Waliszewski, Przemyslaw

    2016-01-01

    The subjective evaluation of tumor aggressiveness is a cornerstone of the contemporary tumor pathology. A large intra- and interobserver variability is a known limiting factor of this approach. This fundamental weakness influences the statistical deterministic models of progression risk assessment. It is unlikely that the recent modification of tumor grading according to Gleason criteria for prostate carcinoma will cause a qualitative change and improve significantly the accuracy. The Gleason system does not allow the identification of low aggressive carcinomas by some precise criteria. The ontological dichotomy implies the application of an objective, quantitative approach for the evaluation of tumor aggressiveness as an alternative. That novel approach must be developed and validated in a manner that is independent of the results of any subjective evaluation. For example, computer-aided image analysis can provide information about geometry of the spatial distribution of cancer cell nuclei. A series of the interrelated complexity measures characterizes unequivocally the complex tumor images. Using those measures, carcinomas can be classified into the classes of equivalence and compared with each other. Furthermore, those measures define the quantitative criteria for the identification of low- and high-aggressive prostate carcinomas, the information that the subjective approach is not able to provide. The co-application of those complexity measures in cluster analysis leads to the conclusion that either the subjective or objective classification of tumor aggressiveness for prostate carcinomas should comprise maximal three grades (or classes). Finally, this set of the global fractal dimensions enables a look into dynamics of the underlying cellular system of interacting cells and the reconstruction of the temporal-spatial attractor based on the Taken’s embedding theorem. Both computer-aided image analysis and the subsequent fractal synthesis could be performed

  18. Computer-Aided Image Analysis and Fractal Synthesis in the Quantitative Evaluation of Tumor Aggressiveness in Prostate Carcinomas.

    PubMed

    Waliszewski, Przemyslaw

    2016-01-01

    The subjective evaluation of tumor aggressiveness is a cornerstone of the contemporary tumor pathology. A large intra- and interobserver variability is a known limiting factor of this approach. This fundamental weakness influences the statistical deterministic models of progression risk assessment. It is unlikely that the recent modification of tumor grading according to Gleason criteria for prostate carcinoma will cause a qualitative change and improve significantly the accuracy. The Gleason system does not allow the identification of low aggressive carcinomas by some precise criteria. The ontological dichotomy implies the application of an objective, quantitative approach for the evaluation of tumor aggressiveness as an alternative. That novel approach must be developed and validated in a manner that is independent of the results of any subjective evaluation. For example, computer-aided image analysis can provide information about geometry of the spatial distribution of cancer cell nuclei. A series of the interrelated complexity measures characterizes unequivocally the complex tumor images. Using those measures, carcinomas can be classified into the classes of equivalence and compared with each other. Furthermore, those measures define the quantitative criteria for the identification of low- and high-aggressive prostate carcinomas, the information that the subjective approach is not able to provide. The co-application of those complexity measures in cluster analysis leads to the conclusion that either the subjective or objective classification of tumor aggressiveness for prostate carcinomas should comprise maximal three grades (or classes). Finally, this set of the global fractal dimensions enables a look into dynamics of the underlying cellular system of interacting cells and the reconstruction of the temporal-spatial attractor based on the Taken's embedding theorem. Both computer-aided image analysis and the subsequent fractal synthesis could be performed

  19. Opposing roles of folate in prostate cancer.

    PubMed

    Rycyna, Kevin J; Bacich, Dean J; O'Keefe, Denise S

    2013-12-01

    The US diet has been fortified with folic acid to prevent neural tube defects since 1998. The Physician Data Queries from the National Cancer Institute describe folate as protective against prostate cancer, whereas its synthetic analog, folic acid, is considered to increase prostate cancer risk when taken at levels easily achievable by eating fortified food or taking over-the-counter supplements. We review the present literature to examine the effects of folate and folic acid on prostate cancer, help interpret previous epidemiologic data, and provide clarification regarding the apparently opposing roles of folate for patients with prostate cancer. A literature search was conducted in Medline to identify studies investigating the effect of nutrition and specifically folate and folic acid on prostate carcinogenesis and progression. In addition, the National Health and Nutrition Examination Survey database was analyzed for trends in serum folate levels before and after mandatory fortification. Folate likely plays a dual role in prostate carcinogenesis. There remains conflicting epidemiologic evidence regarding folate and prostate cancer risk; however, there is growing experimental evidence that higher circulating folate levels can contribute to prostate cancer progression. Further research is needed to clarify these complex relationships. PMID:23992971

  20. The Japanese guideline for prostate cancer screening.

    PubMed

    Hamashima, Chisato; Nakayama, Tomio; Sagawa, Motoyasu; Saito, Hiroshi; Sobue, Tomotaka

    2009-06-01

    In 2005, there were 9264 deaths from prostate cancer, accounting for 4.7% of the total number of cancer deaths in Japan. As the population continues to age, interest in prostate cancer screening has increased, and opportunistic screening for prostate cancer has been conducted worldwide. The guideline for prostate cancer screening was developed based on the established method. The efficacies of prostate-specific antigen (PSA) and digital rectal examination (DRE) were evaluated. Based on the balance of the benefits and harms, recommendations for population-based and opportunistic screening were formulated. Two methods of prostate cancer screening were evaluated. Based on the analytic framework involving key questions, 1186 articles published from January 1985 to October 2006 were selected using MEDLINE and other methods. After the systematic literature review, 28 articles were identified as providing evidence of mortality reduction from prostate cancer, including 5 observational studies for DRE screening, 1 meta-analysis, 3 randomized controlled trials and 19 observational studies for PSA screening. Although several studies showed that PSA screening had a beneficial effect, the results of the selected studies were inconsistent. Overall, the evidence that screening reduced mortality from prostate cancer was insufficient. Furthermore, prostate cancer screening is associated with serious harms, including overdiagnosis, adverse effects of needle biopsy and adverse effects of local prostatectomy. At present, the evidence for the effect of prostate cancer screening is insufficient. Both PSA and DRE were not recommended for population-based screening programs, but they could be conducted as individual-based screening if basic requirements were met. PMID:19346535

  1. Imaging and Markers as Novel Diagnostic Tools in Detecting Insignificant Prostate Cancer: A Critical Overview

    PubMed Central

    Nosov, Alexander; Novikov, Roman; Petrov, Sergey

    2014-01-01

    Recent therapeutic advances for managing low-risk prostate cancer include the active surveillance and focal treatment. However, locating a tumor and detecting its volume by adequate sampling is still problematic. Development of predictive biomarkers guiding individual therapeutic choices remains an ongoing challenge. At the same time, prostate cancer magnetic resonance imaging is gaining increasing importance for prostate diagnostics. The high morphological resolution of T2-weighted imaging and functional MRI methods may increase the specificity and sensitivity of diagnostics. Also, recent studies founded an ability of novel biomarkers to identify clinically insignificant prostate cancer, risk of progression, and association with poor differentiation and, therefore, with clinical significance. Probably, the above mentioned methods would improve tumor characterization in terms of its volume, aggressiveness, and focality. In this review, we attempted to evaluate the applications of novel imaging techniques and biomarkers in assessing the significance of the prostate cancer. PMID:27351008

  2. Efficacy of targeted AKT inhibition in genetically engineered mouse models of PTEN-deficient prostate cancer

    PubMed Central

    De Velasco, Marco A.; Kura, Yurie; Yoshikawa, Kazuhiro; Nishio, Kazuto; Davies, Barry R.; Uemura, Hirotsugu

    2016-01-01

    The PI3K/AKT pathway is frequently altered in advanced human prostate cancer mainly through the loss of functional PTEN, and presents as potential target for personalized therapy. Our aim was to determine the therapeutic potential of the pan-AKT inhibitor, AZD5363, in PTEN-deficient prostate cancer. Here we used a genetically engineered mouse (GEM) model of PTEN-deficient prostate cancer to evaluate the in vivo pharmacodynamic and antitumor activity of AZD5363 in castration-naïve and castration-resistant prostate cancer. An additional GEM model, based on the concomitant inactivation of PTEN and Trp53 (P53), was established as an aggressive model of advanced prostate cancer and was used to further evaluate clinically relevant endpoints after treatment with AZD5363. In vivo pharmacodynamic studies demonstrated that AZD5363 effectively inhibited downstream targets of AKT. AZD5363 monotherapy significantly reduced growth of tumors in castration-naïve and castration-resistant models of PTEN-deficient prostate cancer. More importantly, AZD5363 significantly delayed tumor growth and improved overall survival and progression-free survival in PTEN/P53 double knockout mice. Our findings demonstrate that AZD5363 is effective against GEM models of PTEN-deficient prostate cancer and provide lines of evidence to support further investigation into the development of treatment strategies targeting AKT for the treatment of PTEN-deficient prostate cancer. PMID:26910118

  3. Diagnosis of prostate cancer via nanotechnological approach

    PubMed Central

    Kang, Benedict J; Jeun, Minhong; Jang, Gun Hyuk; Song, Sang Hoon; Jeong, In Gab; Kim, Choung-Soo; Searson, Peter C; Lee, Kwan Hyi

    2015-01-01

    Prostate cancer is one of the leading causes of cancer-related deaths among the Caucasian adult males in Europe and the USA. Currently available diagnostic strategies for patients with prostate cancer are invasive and unpleasant and have poor accuracy. Many patients have been overly or underly treated resulting in a controversy regarding the reliability of current conventional diagnostic approaches. This review discusses the state-of-the-art research in the development of novel noninvasive prostate cancer diagnostics using nanotechnology coupled with suggested diagnostic strategies for their clinical implication. PMID:26527873

  4. Multiparametric magnetic resonance imaging of prostate cancer.

    PubMed

    Hedgire, Sandeep S; Oei, Tamara N; McDermott, Shaunagh; Cao, Kai; Patel M, Zena; Harisinghani, Mukesh G

    2012-07-01

    In India, prostate cancer has an incidence rate of 3.9 per 100,000 men and is responsible for 9% of cancer-related mortality. It is the only malignancy that is diagnosed with an apparently blind technique, i.e., transrectal sextant biopsy. With increasing numbers of high-Tesla magnetic resonance imaging (MRI) equipment being installed in India, the radiologist needs to be cognizant about endorectal MRI and multiparametric imaging for prostate cancer. In this review article, we aim to highlight the utility of multiparamteric MRI in prostate cancer. It plays a crucial role, mainly in initial staging, restaging, and post-treatment follow-up. PMID:23599562

  5. [Prostate cancer and metabolic syndrome].

    PubMed

    Nagamatsu, Hirotaka; Teishima, Jun; Inoue, Shogo; Hayashi, Tetsutaro; Matsubara, Akio

    2016-01-01

    The prevalence of metabolic syndrome (MS) is increasing in Japan because of westernization of diet and lifestyle. Previous epidemiological studies have demonstrated MS to relate with the malignant potential of prostate cancer (PCa) while its relationship to the risk of PCa has been still controversial. Several pathologies involved in MS, such as insulin resistance, abnormality of secreted adipokines, chronic inflammation, alteration of sex hormones, have been reported to affect the progression of PCa. Based on these evidences, clinical studies for PCa patients have been tried for suppressing the progression of PCa through the management of MS. PMID:26793896

  6. Is prostate cancer screening responsible for the negative results of prostate cancer treatment trials?

    PubMed

    Prasad, Vinay

    2016-08-01

    Clinical guidelines continue to move away from routine prostate specific antigen screening (PSA), once a widespread medical practice. A curious difference exists between early prostate cancer and early breast cancer. While randomized trials of therapy in early breast cancer continue to show overall survival benefit, this is not the case in prostate cancer, where prostatectomy was no better than observation in a recent trial, and where early androgen deprivation is no better than late androgen deprivation. Here, I make the case that prostate cancer screening contributes so greatly to over diagnosis that even treatment trials yield null results due to contamination with non-life threatening disease. PMID:27372859

  7. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer

    PubMed Central

    Malik, Arshi; Afaq, Farrukh; Sarfaraz, Sami; Adhami, Vaqar M.; Syed, Deeba N.; Mukhtar, Hasan

    2005-01-01

    Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among U.S. males, with a similar trend in many Western countries. One approach to control this malignancy is its prevention through the use of agents present in diet consumed by humans. Pomegranate from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting effects in mouse skin. In this study, employing human prostate cancer cells, we evaluated the antiproliferative and proapoptotic properties of PFE. PFE (10-100 μg/ml; 48 h) treatment of highly aggressive human prostate cancer PC3 cells resulted in a dose-dependent inhibition of cell growth/cell viability and induction of apoptosis. Immunoblot analysis revealed that PFE treatment of PC3 cells resulted in (i) induction of Bax and Bak (proapoptotic); (ii) down-regulation of Bcl-XL and Bcl-2 (antiapoptotic); (iii) induction of WAF1/p21 and KIP1/p27; (iv) a decrease in cyclins D1, D2, and E; and (v) a decrease in cyclin-dependent kinase (cdk) 2, cdk4, and cdk6 expression. These data establish the involvement of the cyclin kinase inhibitor-cyclin-cdk network during the antiproliferative effects of PFE. Oral administration of PFE (0.1% and 0.2%, wt/vol) to athymic nude mice implanted with androgen-sensitive CWR22Rν1 cells resulted in a significant inhibition in tumor growth concomitant with a significant decrease in serum prostate-specific antigen levels. We suggest that pomegranate juice may have cancer-chemopreventive as well as cancer-chemotherapeutic effects against prostate cancer in humans. PMID:16192356

  8. Triple orbital metastases from prostate cancer.

    PubMed

    Tun, Kagan; Bulut, Turgay

    2016-01-01

    Prostate carcinoma, when metastatic, typically involves bone and produces both osteoblastic and osteolytic changes. A 73-year-old man was admitted to our department because of unilateral progressive proptosis and visual blurriness for 3 months. The patient had a history of prostate adenocarcinoma diagnosis 5 years ago. We report a case of orbital involvement presented that intraorbital mass (including periocular structures), temporal bone and temporal muscle from prostate cancer. The mass was removed with total excision. Despite the frequency of bone metastasis in prostatic carcinoma, triple orbital metastases are extremely rare. The best of our knowledge, prostate adenocarcinoma and its triple (temporal bone, temporal muscle and intraorbital mass) orbital metastases have not been published previously. Metastatic orbital tumor secondary to prostate cancer should be considered in patients who have varying degrees of eye symptoms. PMID:27591068

  9. Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer.

    PubMed

    Queisser, Angela; Hagedorn, Susanne A; Braun, Martin; Vogel, Wenzel; Duensing, Stefan; Perner, Sven

    2015-01-01

    Prostate cancer is mostly diagnosed at an early stage; however, some tumors are diagnosed in a metastatic stage as cancer of unknown primary origin. In order to allow specific treatment in the case of prostate cancer presenting as cancer of unknown primary origin, it is important to determine the tumor origin. Prostate-specific antigen is used as a diagnostic marker for prostate cancer but the expression declines with progression to castration-resistant prostate cancer. Aim of this study was to identify the most informative marker constellation, which is able to detect metastatic prostate cancer at high sensitivity. The widely used prostate cancer markers such as prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene were investigated for their sensitivity to detect prostatic origin of metastases. Expression of prostate-specific antigen, prostate-specific acid phosphatase, androgen receptor, prostate-specific membrane antigen, prostein, and ETS-related gene was determined on archived tissue specimens consisting of benign prostatic tissue (n=9), primary prostate cancer (n=79), lymph node metastases (n=58), and distant metastases (n=39) using immunohistochemistry. The staining intensity was categorized as negative (0), weak (1), moderate (2), and strong (3). All markers except ETS-related gene were able to detect at least 70% of lymph node metastases and distant metastases, with prostate-specific antigen, androgen receptor, and prostate-specific membrane antigen having the highest sensitivity (97%, 91%, and 94%, respectively). A further increase of the sensitivity up to 98% and 100% could be achieved by the combination of prostate-specific antigen, prostate-specific membrane antigen, or androgen receptor for lymph node metastases and for distant metastases, respectively. The same sensitivity could be reached by combining prostate-specific membrane antigen and prostein. Our

  10. Statin Use in Prostate Cancer: An Update.

    PubMed

    Babcook, Melissa A; Joshi, Aditya; Montellano, Jeniece A; Shankar, Eswar; Gupta, Sanjay

    2016-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are commonly prescribed for the treatment of hypercholesterolemia and cardiovascular disease. A systematic review was conducted using the keywords "statin and prostate cancer" within the title search engines including PubMed, Web of Science, and the Cochrane Library for relevant research work published between 2004 and December 2015. Although still premature, accumulating clinical evidence suggests that statin use may be beneficial in the prevention and/or treatment of prostate cancer. These human studies consist of meta-analyses of secondary endpoints obtained from randomized, controlled cardiovascular disease clinical trials of statins, patient database, observational studies, and a few, small case-control studies, directly addressing statin use on prostate cancer pathology and recurrence. This review summarizes and discusses the recent clinical literature on statins and prostate cancer with a recommendation to move forward with randomized, placebo-controlled clinical trials, investigating the use of statins. Additional preclinical testing of statins on prostate cancer cell lines and in vivo models is needed to elucidate pathways and determine its efficacy for prevention and/or treatment of prostate cancer, more specifically, the difference in the effectiveness of lipophilic versus hydrophilic statins in prostate cancer. PMID:27441003

  11. [Treatment strategies for advanced prostate cancer].

    PubMed

    Küronya, Zsófia; Bíró, Krisztina; Géczi, Lajos; Németh, Hajnalka

    2015-09-01

    There has been dramatic improvement in the diagnosis and treatment of prostate cancer recently. The treatment of localized disease became more successful with the application of new, sophisticated techniques available for urologic surgeons and radiotherapists. Nevertheless a significant proportion of patients relapses after the initial local treatment or is diagnosed with metastatic disease at the beginning. In the past five years, six new drugs became registered for the treatment of metastatic, castration-resistant prostate cancer, such as sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, the α-emitting radionuclide alpharadin and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab. The availability of these new treatment options raises numerous questions. In this review we present the standard of care of metastatic prostate cancer by disease stage (hormone naive/ hormone sensitive metastatic prostate cancer, non-metastatic castration-resistant prostate cancer, oligometastatic/multimetastatic castration-resistant prostate cancer) and the emerging treatment modalities presently assessed in clinical trials. We would also like to give advice on debatable aspects of the management of metastatic prostate cancer. PMID:26339912

  12. The Gordon Wilson Lecture. Natural history and treatment of early stage prostate cancer.

    PubMed Central

    Scardino, P. T.

    2000-01-01

    Prostate cancer poses a challenge to society and to physicians. It is a remarkably prevalent tumor, perhaps the most common cancer in the world in its histologic manifestation. In its clinically apparent form, it is notably heterogeneous. Some patients live out their lives with a prostate cancer that remains stable for decades without treatment. In other cases, the cancer grows aggressively, responds poorly to therapy, and causes death within a few years. The median loss-of-life expectancy for men diagnosed with prostate cancer has been estimated at 9 years. Important advances have been made in the past two decades in the treatment of prostate cancer. Further progress will require more accurate characterization of the primary tumor in each individual patient to tailor treatment--whether conservative or aggressive, surgery or radiation--more accurately to the nature of the individual cancer. Imaging studies in particular must be improved if we are to have better, noninvasive ways to identify the presence of a cancer and to define its volume, location, and extent. Substantial progress against this disease will require major breakthroughs in our understanding of the etiology of prostate cancer, the development of effective chemopreventive agents, more accurate ways to assess the biological potential of the tumor, and more effective systemic agents to treat metastatic cancer. Images Fig. 1 PMID:10881343

  13. Nanotherapies for treating prostate cancer

    NASA Astrophysics Data System (ADS)

    Danquah, Michael

    Current prostate cancer treatment remains ineffective primarily due to ineffectual therapeutic strategies and numerous tumor-associated physiological barriers which hinder efficacy of anticancer agents. Therefore, the focus of this study was to investigate a new combination therapy approach for treating prostate cancer and develop polymeric nanocarriers to facilitate anticancer drug and nucleic acid delivery. It was hypothesized that simultaneously targeting androgen-androgen receptor (AR) and X-linked inhibitor of apoptosis protein (XIAP) signaling pathways would be effective in treating prostate cancer. The effect of bicalutamide (antiandrogen) and embelin (XIAP inhibitor) on the growth of prostate cancer cells in vitro and in vivo was first examined. Embelin induced caspase 3 and 9 activation in LNCaP and C4-2 cells by decreasing XIAP expression and was more potent than bicalutamide in killing prostate tumor cells irrespective of their androgen status. Using a combination of MTT assay and isobologram analyses, combination of bicalutamide and embelin was observed to be cell line and schedule dependent. Since bicalutamide and embelin are extremely hydrophobic, polymeric micelles were fabricated using polyethylene glycol-b-polylactic acid (PEG-b-PLA) copolymer to improve drug solubility. Micellar formulations were found to result in at least 60-fold increase in the aqueous solubility of bicalutamide and embelin. Tumor growth was also effectively regressed upon treatment with bicalutamide, but the extent of tumor regression was significantly higher when bicalutamide was formulated in micelles. To further improve bicalutamide aqueous solubility, a series of novel biodegradable copolymers for the systematic micellar delivery of bicalutamide was designed and synthesized. Flory-Huggins interaction parameter (χFH) was used to assess compatibility between bicalutamide and poly (L-lactide) or poly (carbonate-co-lactide) polymer pairs. Polyethylene glycol-b-poly (carbonate

  14. Researchers Find 8 Immune Genes in Aggressive Brain Cancer

    MedlinePlus

    ... 159031.html Researchers Find 8 Immune Genes in Aggressive Brain Cancer Discovery might eventually lead to better ... tissue samples from 170 people with a less aggressive type of brain tumor. This led to the ...

  15. Extensive Surgery Best for an Aggressive Brain Cancer

    MedlinePlus

    ... 159415.html Extensive Surgery Best for an Aggressive Brain Cancer: Study Although larger procedure carries more risk, ... comes to battling a particularly aggressive form of brain tumor, more extensive surgeries may be best to ...

  16. Extensive Surgery Best for an Aggressive Brain Cancer

    MedlinePlus

    ... fullstory_159415.html Extensive Surgery Best for an Aggressive Brain Cancer: Study Although larger procedure carries more ... News) -- When it comes to battling a particularly aggressive form of brain tumor, more extensive surgeries may ...

  17. Novel Fusion Transcripts Associate with Progressive Prostate Cancer

    PubMed Central

    Yu, Yan P.; Ding, Ying; Chen, Zhanghui; Liu, Silvia; Michalopoulos, Amantha; Chen, Rui; Gulzar, Zulfiqar G.; Yang, Bing; Cieply, Kathleen M.; Luvison, Alyssa; Ren, Bao-Guo; Brooks, James D.; Jarrard, David; Nelson, Joel B.; Michalopoulos, George K.; Tseng, George C.; Luo, Jian-Hua

    2015-01-01

    The mechanisms underlying the potential for aggressive behavior of prostate cancer (PCa) remain elusive. In this study, whole genome and/or transcriptome sequencing was performed on 19 specimens of PCa, matched adjacent benign prostate tissues, matched blood specimens, and organ donor prostates. A set of novel fusion transcripts was discovered in PCa. Eight of these fusion transcripts were validated through multiple approaches. The occurrence of these fusion transcripts was then analyzed in 289 prostate samples from three institutes, with clinical follow-up ranging from 1 to 15 years. The analyses indicated that most patients [69 (91%) of 76] positive for any of these fusion transcripts (TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017, TMEM135-CCDC67, KDM4-AC011523.2, MAN2A1-FER, and CCNH-C5orf30) experienced PCa recurrence, metastases, and/or PCa-specific death after radical prostatectomy. These outcomes occurred in only 37% (58/157) of patients without carrying those fusion transcripts. Three fusion transcripts occurred exclusively in PCa samples from patients who experienced recurrence or PCa–related death. The formation of these fusion transcripts may be the result of genome recombination. A combination of these fusion transcripts in PCa with Gleason's grading or with nomogram significantly improves the prediction rate of PCa recurrence. Our analyses suggest that formation of these fusion transcripts may underlie the aggressive behavior of PCa. PMID:25238935

  18. Prognostic DNA Methylation Markers for Prostate Cancer

    PubMed Central

    Strand, Siri H.; Orntoft, Torben F.; Sorensen, Karina D.

    2014-01-01

    Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

  19. Prognostic DNA methylation markers for prostate cancer.

    PubMed

    Strand, Siri H; Orntoft, Torben F; Sorensen, Karina D

    2014-01-01

    Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC. PMID:25238417

  20. Endocrine disruptors and prostate cancer risk

    PubMed Central

    Prins, Gail S

    2010-01-01

    There is increasing evidence both from epidemiology studies and animal models that specific endocrine-disrupting compounds may influence the development or progression of prostate cancer. In large part, these effects appear to be linked to interference with estrogen signaling, either through interacting with ERs or by influencing steroid metabolism and altering estrogen levels within the body. In humans, epidemiologic evidence links specific pesticides, PCBs and inorganic arsenic exposures to elevated prostate cancer risk. Studies in animal models also show augmentation of prostate carcinogenesis with several other environmental estrogenic compounds including cadmium, UV filters and BPA. Importantly, there appears to be heightened sensitivity of the prostate to these endocrine disruptors during the critical developmental windows including in utero and neonatal time points as well as during puberty. Thus infants and children may be considered a highly susceptible population for ED exposures and increased risk of prostate cancers with aging. PMID:18524946

  1. Recurrent Gene Fusions in Prostate Cancer

    PubMed Central

    Kumar-Sinha, Chandan; Tomlins, Scott A.; Chinnaiyan, Arul M.

    2009-01-01

    The discovery of recurrent gene fusions in a majority of prostate cancers has important clinical and biological implications in the study of common epithelial tumors. Gene fusion and chromosomal rearrangements were previously thought to be the primary oncogenic mechanism of hematological malignancies and sarcomas. The prostate cancer gene fusions that have been identified thus far are characterized by 5’ genomic regulatory elements, most commonly controlled by androgen, fused to members of the ETS family of transcription factors, leading to the over-expression of oncogenic transcription factors. ETS gene fusions likely define a distinct class of prostate cancer which may have a bearing on diagnosis, prognosis and rational therapeutic targeting. PMID:18563191

  2. Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness

    PubMed Central

    Adamo, Hanibal Hani; Strömvall, Kerstin; Nilsson, Maria; Halin Bergström, Sofia; Bergh, Anders

    2015-01-01

    In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues. PMID:26536349

  3. Statin Use in Prostate Cancer: An Update

    PubMed Central

    Babcook, Melissa A.; Joshi, Aditya; Montellano, Jeniece A.; Shankar, Eswar; Gupta, Sanjay

    2016-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are commonly prescribed for the treatment of hypercholesterolemia and cardiovascular disease. A systematic review was conducted using the keywords “statin and prostate cancer” within the title search engines including PubMed, Web of Science, and the Cochrane Library for relevant research work published between 2004 and December 2015. Although still premature, accumulating clinical evidence suggests that statin use may be beneficial in the prevention and/or treatment of prostate cancer. These human studies consist of meta-analyses of secondary endpoints obtained from randomized, controlled cardiovascular disease clinical trials of statins, patient database, observational studies, and a few, small case–control studies, directly addressing statin use on prostate cancer pathology and recurrence. This review summarizes and discusses the recent clinical literature on statins and prostate cancer with a recommendation to move forward with randomized, placebo-controlled clinical trials, investigating the use of statins. Additional preclinical testing of statins on prostate cancer cell lines and in vivo models is needed to elucidate pathways and determine its efficacy for prevention and/or treatment of prostate cancer, more specifically, the difference in the effectiveness of lipophilic versus hydrophilic statins in prostate cancer. PMID:27441003

  4. PET/CT in prostate cancer: non-choline radiopharmaceuticals

    PubMed Central

    CASTELLUCCI, P.; JADVAR, H.

    2012-01-01

    In this brief review, the major potential clinical applications of 18F-FDG, 11C-acetate, 18F-FDHT, 18F-FLT, 18F-FMAU, and anti-18F-FACBC in the imaging evaluation of men with prostate cancer are discussed. 18F-FDG has a limited role in primary diagnosis and staging but it may be able to reflect tumour aggressiveness, detect sites of recurrence in some men with high serum PSA after biochemical failure and assess response to chemo- and hormonal treatment in metastatic disease. 11C-acetate has been investigated for intra-prostatic primary tumour detection and staging as well as for re-staging in case of biochemical relapse with results that are overall similar to those with 18F- and 11C-labeled choline. 18F-FDHT targets the androgen receptor and may be particularly useful in the assessment of the pharmacodynamics of the androgen signalling pathway. PET in conjunction with 18F-FLT or 18F-FMAU that track the thymidine salvage pathway of DNA synthesis has also been investigated for imaging cellular proliferation in prostate cancer. Initial exprience with the radiolabeked synthetic amino acid, anti-18F-FACBC, which displays slow urinary excretion has been encouraging but further studies will be needed to decipher its exact role in the imaging management of men with prostate cancer. PMID:23013666

  5. Detection rates of high-grade prostate cancer during subsequent screening visits. Results of the European Randomized Screening Study for Prostate Cancer.

    PubMed

    van der Kwast, Theodorus H; Ciatto, Stefano; Martikainen, Paula M; Hoedemaeker, Robert; Laurila, Marita; Pihl, Carl-Gustaph; Hugosson, Jonas; Neetens, Ingrid; Nelen, Vera; Di Lollo, Simonetta; Roobol, Monique J; Määtänen, Liisa; Santonja, Carlos; Moss, Sue; Schröder, Fritz H

    2006-05-15

    Screening for prostate cancer using prostate-specific antigen (PSA) tests has led to a stage and grade shift as compared to the pre-PSA era. Effectiveness of screening for prostate cancer should be manifested by a reduction in detection rate of aggressive cancers during subsequent screening. In 6 centers of the European Randomized Screening study for Prostate Cancer, a total of 58,710 men were tested for prostate cancer. Screening centers differed with regard to age-range, screening interval and biopsy indications. During the 2nd visit, the proportion of Gleason score 6 cancers increased from 62.5 to 75%, mainly at the expense of Gleason score 7 cancers. High-grade (Gleason score 8-10) cancer detection rates varied per screening center during the 1st visit from 5.1 to 41.1, and during the 2nd visit from 6.4 to 29.3/10,000 men. The overall detection rate of high-grade cancers showed a reduction during the 2nd visit from 26 to 12/10,000 men, an effect mainly attributable to the screening center with the highest cancer detection rate (i.e. 507/10,000 men). Variations in detection rates among screening centers related among others to biopsy compliance and age range. PMID:16353141

  6. Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

    PubMed Central

    Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A.; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

    2016-01-01

    Background Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Methods Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Results Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT

  7. Molecular aspects of prostate cancer with neuroendocrine differentiation

    PubMed Central

    Li, Qi; Zhang, Connie S.

    2016-01-01

    Neuroendocrine differentiation (NED), which is not uncommon in prostate cancer, is increases in prostate cancer after androgen-deprivation therapy (ADT) and generally appears in castration-resistant prostate cancer (CRPC). Neuroendocrine cells, which are found in normal prostate tissue, are a small subset of cells and have unique function in regulating the growth of prostate cells. Prostate cancer with NED includes different types of tumor, including focal NED, pure neuroendocrine tumor or mixed neuroendocrine-adenocarcinoma. Although more and more studies are carried out on NED in prostate cancer, the molecular components that are involved in NED are still poorly elucidated. We review neuroendocrine cells in normal prostate tissue, NED in prostate cancer, terminology of NED and biomarkers used for detecting NED in routine pathological practice. Some recently reported molecular components which drive NED in prostate cancer are listed in the review. PMID:27041934

  8. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

    ClinicalTrials.gov

    2016-06-22

    Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  9. Farming, reported pesticide use, and prostate cancer.

    PubMed

    Ragin, Camille; Davis-Reyes, Brionna; Tadesse, Helina; Daniels, Dennis; Bunker, Clareann H; Jackson, Maria; Ferguson, Trevor S; Patrick, Alan L; Tulloch-Reid, Marshall K; Taioli, Emanuela

    2013-03-01

    Prostate cancer is the leading cancer type diagnosed in American men and is the second leading cancer diagnosed in men worldwide. Although studies have been conducted to investigate the association between prostate cancer and exposure to pesticides and/or farming, the results have been inconsistent. We performed a meta-analysis to summarize the association of farming and prostate cancer. The PubMed database was searched to identify all published case-control studies that evaluated farming as an occupational exposure by questionnaire or interview and prostate cancer. Ten published and two unpublished studies were included in this analysis, yielding 3,978 cases and 7,393 controls. Prostate cancer cases were almost four times more likely to be farmers compared with controls with benign prostate hyperplasia (BPH; meta odds ratio [OR], crude = 3.83, 95% confidence interval [CI] = 1.96-7.48, Q-test p value = .352; two studies); similar results were obtained when non-BPH controls were considered, but with moderate heterogeneity between studies (meta OR crude = 1.38, 95% CI = 1.16-1.64, Q-test p value = .216, I (2) = 31% [95% CI = 0-73]; five studies). Reported pesticide exposure was inversely associated with prostate cancer (meta OR crude = 0.68, 95% CI = 0.49-0.96, Q-test p value = .331; four studies), whereas no association with exposure to fertilizers was observed. Our findings confirm that farming is a risk factor for prostate cancer, but this increased risk may not be due to exposure to pesticides. PMID:22948300

  10. Molecular pathways and targets in prostate cancer

    PubMed Central

    Shtivelman, Emma; Beer, Tomasz M.; Evans, Christopher P.

    2014-01-01

    Prostate cancer co-opts a unique set of cellular pathways in its initiation and progression. The heterogeneity of prostate cancers is evident at earlier stages, and has led to rigorous efforts to stratify the localized prostate cancers, so that progression to advanced stages could be predicted based upon salient features of the early disease. The deregulated androgen receptor signaling is undeniably most important in the progression of the majority of prostate tumors. It is perhaps because of the primacy of the androgen receptor governed transcriptional program in prostate epithelium cells that once this program is corrupted, the consequences of the ensuing changes in activity are pleotropic and could contribute to malignancy in multiple ways. Following localized surgical and radiation therapies, 20-40% of patients will relapse and progress, and will be treated with androgen deprivation therapies. The successful development of the new agents that inhibit androgen signaling has changed the progression free survival in hormone resistant disease, but this has not changed the almost ubiquitous development of truly resistant phenotypes in advanced prostate cancer. This review summarizes the current understanding of the molecular pathways involved in localized and metastatic prostate cancer, with an emphasis on the clinical implications of the new knowledge. PMID:25277175

  11. Role of hormonal and other factors in human prostate cancer.

    PubMed

    Wigle, Donald T; Turner, Michelle C; Gomes, James; Parent, Marie-Elise

    2008-03-01

    American men have a lifetime risk of about 18% for prostate cancer diagnosis. Large international variations in prostate cancer risks and increased risks among migrants from low- to high-risk countries indicate important roles for environmental factors. Major known risk factors include age, family history, and country/ethnicity. Type 2 diabetes appears to reduce risk, while high birth weight and adult height are linked to increased risk of aggressive prostate cancer. Limited evidence supports an association with a history of sexually transmitted infections. A previous meta-analysis of eight cohort studies indicated no associations with plasma androgen, estrogen, or sex hormone binding globulin (SHBG) levels. However, there were dose-response relationships with baseline plasma testosterone levels in two studies that adjusted for other serum hormones and obesity. Finasteride (a drug that blocks testosterone activation) reduced prostate cancer risk by 25%. Low-frequency genes linked to familial prostate cancer only explain a small fraction of all cases. Sporadic cases were linked to relatively common polymorphisms of genes involved in (1) androgen synthesis, activation, inactivation and excretion, (2) hormone and vitamin D receptors, (3) carcinogen metabolism, and (4) DNA repair. Epidemiologic evidence supports protective roles for dietary selenium, vitamin E, pulses, tomatoes/lycopene, and soy foods, and high plasma 1,25-dihydroxyvitamin D levels. There is inadequate evidence that vegetables, fruit, carotenoids, and vitamins A and C reduce risk and that animal fat, alpha-linoleic acid, meat, coffee, and tea increase risk. Two major cohort studies found dose-response relationships with dietary calcium intake. Total dietary energy intake may enhance risk. Limited evidence supports a protective role for physical activity and elevated risk for farmers and other men with occupational pesticide exposure, particularly to organochlorine compounds and phenoxy herbicides

  12. Molecular Targeted Therapies of Aggressive Thyroid Cancer

    PubMed Central

    Ferrari, Silvia Martina; Fallahi, Poupak; Politti, Ugo; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro

    2015-01-01

    Differentiated thyroid carcinomas (DTCs) that arise from follicular cells account >90% of thyroid cancer (TC) [papillary thyroid cancer (PTC) 90%, follicular thyroid cancer (FTC) 10%], while medullary thyroid cancer (MTC) accounts <5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC, and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts toward the development of new drugs. Several genetic alterations in different molecular pathways in TC have been shown in the past few decades, associated with TC development and progression. Rearranged during transfection (RET)/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs) are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the aforementioned molecular pathways involved in growth, angiogenesis, local, and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC, and anaplastic thyroid cancer, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds and to personalize the therapy in

  13. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  14. Regular Exercise May Boost Prostate Cancer Survival

    MedlinePlus

    ... nih.gov/medlineplus/news/fullstory_158374.html Regular Exercise May Boost Prostate Cancer Survival Study found that ... HealthDay News) -- Sticking to a moderate or intense exercise regimen may improve a man's odds of surviving ...

  15. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Cancer.gov

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  16. Shorter, Intensive Radiation Works for Prostate Cancer

    MedlinePlus

    ... April 4, 2016 (HealthDay News) -- A slightly higher dose of radiation therapy for early stage prostate cancer may reduce treatment time without compromising effectiveness, researchers report. The ...

  17. Radium-223 for Advanced Prostate Cancer

    Cancer.gov

    A summary of results from a phase III trial that compared radium-223 dichloride plus the best standard of care versus a placebo plus the best standard of care in men with metastatic, castration-resistant prostate cancer.

  18. Finasteride Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial

    PubMed Central

    Till, Cathee; Goodman, Phyllis J.; Chen, Xiaohong; Leach, Robin J.; Johnson-Pais, Teresa L.; Hsing, Ann W.; Hoque, Ashraful; Tangen, Catherine M.; Chu, Lisa; Parnes, Howard L.; Schenk, Jeannette M.; Reichardt, Juergen K. V.; Thompson, Ian M.; Figg, William D.

    2015-01-01

    Objective In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations. Methods Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression. Results and Conclusions Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and CYP3A5 (rs15524; rs776746) were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway. Trial Registration ClinicalTrials.gov NCT00288106 PMID:25955319

  19. Medical hospitalizations in prostate cancer survivors.

    PubMed

    Gnanaraj, Jerome; Balakrishnan, Shobana; Umar, Zarish; Antonarakis, Emmanuel S; Pavlovich, Christian P; Wright, Scott M; Khaliq, Waseem

    2016-07-01

    The objectives of the study were to explore the context and reasons for medical hospitalizations among prostate cancer survivors and to study their relationship with obesity and the type of prostate cancer treatment. A retrospective review of medical records was performed at an academic institution for male patients aged 40 years and older who were diagnosed and/or treated for prostate cancer 2 years prior to the study's observation period from January 2008 to December 2010. Unpaired t test, ANOVA, and Chi-square tests were used to compare patients' characteristics, admission types, and medical comorbidities by body mass index (BMI) and prostate cancer treatment. Mean age for the study population was 76 years (SD = 9.2). Two hundred and forty-five prostate cancer survivors were stratified into two groups: non-obese (BMI < 30 kg/m(2)) and obese (BMI ≥ 30 kg/m(2)). The study population's characteristics analyzed by BMI were similar including Gleason score, presence of metastatic disease and genitourinary-related side effects. Only 13 % of admissions were for complaints related to their genitourinary system. Neither the specific treatment that the patients had received for their prostate cancer, nor obesity was associated with the reasons for their medical admission. Survivorship after having a diagnosis of prostate cancer is often lengthy, and these men are at risk of being hospitalized, as they get older. From this inquiry, it has become clear that neither body mass index nor prior therapy is associated with specific admission characteristics, and only a minority of such admissions was directly related to prostate cancer or the genitourinary tract. PMID:27324503

  20. Engineering chemically modified viruses for prostate cancer cell recognition.

    PubMed

    Mohan, K; Weiss, G A

    2015-12-01

    Specific detection of circulating tumor cells and characterization of their aggressiveness could improve cancer diagnostics and treatment. Metastasis results from such tumor cells, and causes the majority of cancer deaths. Chemically modified viruses could provide an inexpensive and efficient approach to detect tumor cells and quantitate their cell surface biomarkers. However, non-specific adhesion between the cell surface receptors and the virus surface presents a challenge. This report describes wrapping the virus surface with different PEG architectures, including as fusions to oligolysine, linkers, spacers and scaffolded ligands. The reported PEG wrappers can reduce by >75% the non-specific adhesion of phage to cell surfaces. Dynamic light scattering verified the non-covalent attachment by the reported wrappers as increased sizes of the virus particles. Further modifications resulted in specific detection of prostate cancer cells expressing PSMA, a key prostate cancer biomarker. The approach allowed quantification of PSMA levels on the cell surface, and could distinguish more aggressive forms of the disease. PMID:26463253

  1. Immune Infiltration and Prostate Cancer

    PubMed Central

    Strasner, Amy; Karin, Michael

    2015-01-01

    It is becoming increasingly clear that inflammation influences prostate cancer (PCa) development and that immune cells are among the primary drivers of this effect. This information has launched numerous clinical trials testing immunotherapy drugs in PCa patients. The results of these studies are promising but have yet to generate a complete response. Importantly, the precise immune profile that determines clinical outcome remains unresolved. Individual immune cell types are divided into various functional subsets whose effects on tumor development may differ depending on their particular phenotype and functional status, which is often shaped by the tumor microenvironment. Thus, this review aims to examine the current knowledge regarding the role of inflammation and specific immune cell types in mediating PCa progression to assist in directing and optimizing immunotherapy targets, regimens, and responses and to uncover areas in which further research is needed. Finally, a summary of ongoing immunotherapy clinical trials in PCa is provided. PMID:26217583

  2. Role of miRNA Let-7 and Its Major Targets in Prostate Cancer

    PubMed Central

    2014-01-01

    Prostate cancer is worldwide the sixth leading cause of cancer related death in men thus early detection and successful treatment are still of major interest. The commonly performed screening of the prostate-specific antigen (PSA) is controversially discussed, as in many patients the prostate-specific antigen levels are chronically elevated in the absence of cancer. Due to the unsatisfying efficiency of available prostate cancer screening markers and the current treatment outcome of the aggressive hormone refractory prostate cancer, the evaluation of novel molecular markers and targets is considered an issue of high importance. MicroRNAs are relatively stable in body fluids orchestrating simultaneously the expression of many genes. These molecules are currently discussed to bear a greater diagnostic potential than protein-coding genes, being additionally promising therapeutic drugs and/or targets. Herein we review the potential impact of the microRNA let-7 family on prostate cancer and show how deregulation of several of its target genes could influence the cellular equilibrium in the prostate gland, promoting cancer development as they do in a variety of other human malignant neoplasias. PMID:25276782

  3. New agents for prostate cancer.

    PubMed

    Agarwal, N; Di Lorenzo, G; Sonpavde, G; Bellmunt, J

    2014-09-01

    The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging androgen pathway inhibitors include androgen synthesis inhibitors (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone). Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor (ipilimumab). Biologic agents targeting the molecular drivers of disease are also being investigated as single agents, including cabozantinib (Met and VEGFR2 inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite the disappointing results seen from studies evaluating docetaxel in combination with other agents, including GVAX, anti-angiogentic agents (bevacizumab, aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101), the results from the trial evaluating docetaxel in combination with the clusterin antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of discovering new targets, understanding resistance mechanisms, the optimal sequencing and combinations of available agents, as well as biomarkers predictive for benefit. Novel agents targeting bone metastases are being developed following the success of zoledronic acid

  4. [Optimization of prostate biopsy strategy in diagnosis of prostate cancer].

    PubMed

    Kimura, Go

    2016-01-01

    The prostate gland is the sole organ that uses not targeted but systematic biopsy in the pathological diagnosis of prostate cancer due to its anatomical location and lack of adequate imaging modality to depict cancer nodules clearly. The U.S. Preventive Services Task Force published that the harms of PSA based screening outweigh the benefits, yielding a grade D recommendation against screening. In this current situation, what we need is to optimize a biopsy template that maximizes the detection rate of clinically significant cancer and provides adequate pathological information for a treatment plan while minimizing the detection of indolent cancers and has good cost-effectiveness and safety. In this manuscript, optimal systematic biopsy templates and possible role of MRI-guided biopsy are reviewed. PMID:26793884

  5. MOLECULAR IMAGING OF PROSTATE CANCER: translating molecular biology approaches into the clinical realm

    PubMed Central

    Vargas, Hebert Alberto; Grimm, Jan; Donati, Olivio F.; Sala, Evis; Hricak, Hedvig

    2016-01-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980’s. Most prostate cancers today are detected at early stages of the disease and are considered “indolent”, however some patients’ prostate cancers demonstrate a more aggressive behavior which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterizes this disease has lead to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumor detection alone to distinguishing patients with indolent tumors that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumors that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualization of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. PMID:25693661

  6. sEphB4-HSA Before Surgery in Treating Patients With Bladder Cancer, Prostate Cancer, or Kidney Cancer

    ClinicalTrials.gov

    2016-05-06

    Infiltrating Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Prostate Cancer; Stage I Renal Cell Cancer; Stage II Bladder Urothelial Carcinoma; Stage II Renal Cell Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer

  7. Focal therapy for prostate cancer: current status and future perspectives.

    PubMed

    Miano, R; Asimakopoulos, A; Da Silva, R; Bove, P; Jones, S; De La Rosette, J; Kim, F

    2015-09-01

    Focal therapy is a relatively new and extremely attractive option of treatment for prostate cancer. It has been described as the "middle approach" between active surveillance and radical treatment, aiming to destroy the tumor itself or the region containing the tumor in order to preserve surrounding non-cancerous tissue. The goal is to maintain disease control at acceptable levels, while preserving erectile, urinary, and rectal function. While a lot of technologies have been described for delivering targeted therapy to the prostate, such as cryoablation, high intensity focused ultrasound, photodynamic therapy, irreversible electroporation and laser, the key point is the patient selection. Recent advances in mpMRI and the introduction of new biopsy techniques that use MR images as a guidance, have significantly improved localization of the tumor lesions and the detection rate, evolving prostate biopsy toward targeted rather than systematic biopsies. The future challenge to clinicians is to precisely risk-stratify patients to differentiate between those who would profit from focal treatment and who would not. Forthcoming research efforts should pursue to identify molecular, genetic, and imaging characteristics that distinguish aggressive prostate tumors from indolent lesions. PMID:26013953

  8. Prostate cancer outcome and tissue levels of metal ions

    USGS Publications Warehouse

    Sarafanov, A.G.; Todorov, T.I.; Centeno, J.A.; MacIas, V.; Gao, W.; Liang, W.-M.; Beam, C.; Gray, Michael A.; Kajdacsy-Balla, A.

    2011-01-01

    BACKGROUND There are several studies examining prostate cancer and exposure to cadmium, iron, selenium, and zinc. Less data are available on the possible influence of these metal ions on prostate cancer outcome. This study measured levels of these ions in prostatectomy samples in order to examine possible associations between metal concentrations and disease outcome. METHODS We obtained formalin fixed paraffin embedded tissue blocks of prostatectomy samples of 40 patients with PSA recurrence, matched 1:1 (for year of surgery, race, age, Gleason grading, and pathology TNM classification) with tissue blocks from 40 patients without recurrence (n = 80). Case-control pairs were compared for the levels of metals in areas adjacent to tumors. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for quantification of Cd, Fe, Zn, and Se. RESULTS Patients with biochemical (PSA) recurrence of disease had 12% lower median iron (95 ??g/g vs. 111 ??g/g; P = 0.04) and 21% lower zinc (279 ??g/g vs. 346 ??g/g; P = 0.04) concentrations in the normal-appearing tissue immediately adjacent to cancer areas. Differences in cadmium (0.489 ??g/g vs. 0.439 ??g/g; 4% higher) and selenium (1.68 ??g/g vs. 1.58 ??g/g; 5% higher) levels were not statistically significant in recurrence cases, when compared to non-recurrences (P = 0.40 and 0.21, respectively). CONCLUSIONS There is an association between low zinc and low iron prostate tissue levels and biochemical recurrence in prostate cancer. Whether these novel findings are a cause or effect of more aggressive tumors, or whether low zinc and iron prostatic levels raise implications for therapy, remains to be investigated. Copyright ?? 2011 Wiley-Liss, Inc.

  9. Update: immunological strategies for prostate cancer.

    PubMed

    Drake, Charles G; Antonarakis, Emmanuel S

    2010-05-01

    Prostate cancer is the second most common cause of cancer-related death in US men. Along with initial therapy using surgery, radiotherapy, or cryotherapy, hormonal therapy is the mainstay of treatment. For men with advanced (metastatic) disease, docetaxel-based chemotherapy is US Food and Drug Administration (FDA)-approved, and provides a significant survival advantage. This relative paucity of treatment options drives an ongoing quest for additional treatment modalities; among these is immunotherapy. The concept that prostate cancer is a malignancy that can be targeted by the immune system may seem counterintuitive; certainly kidney cancer and melanoma are more traditionally thought of as immune responsive cancers. However, prostate cancer arises in a relatively unique organ and may express a number of proteins (antigens) against which an immune response can be generated. More importantly, several of these agents have now demonstrated a significant survival benefit in randomized controlled clinical trials, and one agent in particular (Sipuleucel-T, Dendreon Corporation, Seattle, WA) could be FDA-approved in 2010. This update summarizes recent clinical developments in the field of prostate cancer immunotherapy, with a focus on dendritic cell vaccines, virus-based vaccines, DNA-based vaccines, and cell-based vaccines. In addition, the notion of agents that target immune checkpoints is introduced. Enthusiasm for prostate cancer immunotherapy is founded upon its potential to mediate targeted, specific, tumor cell destruction without significant systemic toxicity; however, this has yet to be fully realized in the clinical arena. PMID:20425628

  10. Genetics of Prostate Cancer (PDQ®)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the genetics of prostate cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for prostate cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary prostate cancer syndrome are also discussed.

  11. Shared gene expression alterations in prostate cancer and histologically benign prostate from patients with prostate cancer.

    PubMed

    Kosari, Farhad; Cheville, John C; Ida, Cristiane M; Karnes, R Jeffrey; Leontovich, Alexey A; Sebo, Thomas J; Erdogan, Sibel; Rodriguez, Erika; Murphy, Stephen J; Vasmatzis, George

    2012-07-01

    Prostate cancer (PCa) field effect alterations provide important clues regarding the initiation of these tumors and suggest targets for prevention or biomarkers for early detection. However, biomarkers of PCa field effects that have passed independent validation are lacking, largely because these alterations are subtle and difficult to distinguish from unrelated small changes in gene expression. We hypothesized that shared expression alterations in PCa and benign prostates containing PCa (BPCs) would have a higher potential for independent validation than alterations identified in BPCs alone. Expression analyses were performed on 37 PCas and 36 unmatched BPCs and were contrasted with 28 benign prostates (BPs) from patients free of PCa. Most of the protein-coding genes and nonexonic RNAs selected according to the hypothesis were validated by quantitative RT-PCR in an independent set of 51 BPCs and BPs. A statistical model based on two markers distinguished BPCs from BPs in the RT-PCR set and in an external microarray (area under the curve = 0.84 and 0.90, respectively). In addition, genes with predominant expression in stroma were identified by expression profiling of pure stroma and epithelial cells. Pathway analysis identified dysregulated platelet-derived growth factor receptor signaling in BPC stroma. These results validate our approach for finding PCa field effect alterations and demonstrate a PCa transcriptome fingerprint in nonneoplastic cells in prostates containing cancer. PMID:22640805

  12. FDG PET/CT in Peritoneal Metastasis From Prostate Cancer.

    PubMed

    Gungor, Serkan; Asa, Sertac; Kupik, Osman

    2016-09-01

    Prostate cancer is one of the leading causes of cancer death in men. The prognosis in prostate cancer is greatly worsened by the presence of metastases, which are most commonly found in bone, lung, liver, and brain. The peritoneum is an extremely uncommon metastatic site for prostate cancer, even in autopsy series. We present a case of FDG PET/CT demonstration of peritoneal metastasis from prostate cancer. PMID:27187732

  13. Prostatic Fatty Acids and Cancer Recurrence Following Radical Prostatectomy for Early-Stage Prostate Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Results from some observational studies suggest that diet and energy balance influence the clinical course of early-stage prostate cancer. To evaluate possible mechanisms, we prospectively examined the relation between prostatic concentrations of fatty acids at diagnosis and cancer recurr...

  14. Chemotherapy of prostate cancer: present and future.

    PubMed

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved. PMID:12756087

  15. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols.

    PubMed

    Atawodi, Sunday Eneojo

    2011-09-23

    Dietary polyphenols are antioxidants that can scavenge biological free radicals, and chemoprevent diseases with biological oxidation as their main etiological factor. In this paper, we review our laboratory data vis-ὰ-vis available literature on prostate cancer chemopreventive substances in Nigerian foodstuffs. Dacryodes edulis fruit, Moringa oleifera and Syzygium aromaticum contained prostate active polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and their derivatives. Also Canarium schweinfurthii Engl oil contained ten phenolic compounds and lignans, namely; catechol, p-hydroxybenzaldehyde, dihydroxyphenylacetic acid, tyrosol, p-hydroxybenzoic acid, dihydroxybenzoic acid, vanillic acid, phloretic acid, pinoresinol, secoisolariciresinol. In addition, tomatoes (Lycopersicon esculentum Mill) which contains the powerful antioxidant and anti-prostate cancer agent, lycopene; cabbage (Brassica oleracea) containing indole-3-carbinol; citrus fruits containing pectin; Soursop (Annona muricata) containing annonaceous acetogenins; soya beans (Glycine max) containing isoflavones; chilli pepper (Capsicum annuum) containing capsaicin, and green tea (Camellia sinensis) containing (-) epigallocatechin gallate (EGCG), (-) epicatechin, (-) epicatechin-3-gallate and (-) epigallocatechin -3-gallate which are widely reported to posses prostate cancer chemopreventive compounds are also grown in Nigeria and other African countries. Thus, the high incidence of prostate cancer among males of African extraction can be dramatically reduced, and the age of onset drastically increased, if the population at risk consumes the right kinds of foods in the right proportion, beginning early in life, especially as prostate cancer has a latency period of about 50 years. PMID:21992488

  16. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols

    PubMed Central

    2011-01-01

    Dietary polyphenols are antioxidants that can scavenge biological free radicals, and chemoprevent diseases with biological oxidation as their main etiological factor. In this paper, we review our laboratory data vis-ὰ-vis available literature on prostate cancer chemopreventive substances in Nigerian foodstuffs. Dacryodes edulis fruit, Moringa oleifera and Syzygium aromaticum contained prostate active polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and their derivatives. Also Canarium schweinfurthii Engl oil contained ten phenolic compounds and lignans, namely; catechol, p-hydroxybenzaldehyde, dihydroxyphenylacetic acid, tyrosol, p-hydroxybenzoic acid, dihydroxybenzoic acid, vanillic acid, phloretic acid, pinoresinol, secoisolariciresinol. In addition, tomatoes (Lycopersicon esculentum Mill) which contains the powerful antioxidant and anti-prostate cancer agent, lycopene; cabbage (Brassica oleracea) containing indole-3-carbinol; citrus fruits containing pectin; Soursop (Annona muricata) containing annonaceous acetogenins; soya beans (Glycine max) containing isoflavones; chilli pepper (Capsicum annuum) containing capsaicin, and green tea (Camellia sinensis) containing (-) epigallocatechin gallate (EGCG), (-) epicatechin, (-) epicatechin-3-gallate and (-) epigallocatechin -3-gallate which are widely reported to posses prostate cancer chemopreventive compounds are also grown in Nigeria and other African countries. Thus, the high incidence of prostate cancer among males of African extraction can be dramatically reduced, and the age of onset drastically increased, if the population at risk consumes the right kinds of foods in the right proportion, beginning early in life, especially as prostate cancer has a latency period of about 50 years. PMID:21992488

  17. Residential Exposure to Road and Railway Noise and Risk of Prostate Cancer: A Prospective Cohort Study

    PubMed Central

    Roswall, Nina; Eriksen, Kirsten T.; Hjortebjerg, Dorrit; Jensen, Steen S.; Overvad, Kim; Tjønneland, Anne; Raaschou-Nielsen, Ole; Sørensen, Mette

    2015-01-01

    Background Few modifiable risk factors for prostate cancer are known. Recently, disruption of the circadian system has been proposed to affect risk, as it entails an inhibited melatonin production, and melatonin has demonstrated beneficial effects on cancer inhibition. This suggests a potential role of traffic noise in prostate cancer. Methods Road traffic and railway noise was calculated for all present and historical addresses from 1987–2010 for a cohort of 24,473 middle-aged, Danish men. During follow-up, 1,457 prostate cancer cases were identified. We used Cox Proportional Hazards Models to calculate the association between noise exposure and incident prostate cancer. Incidence Rate Ratios (IRR) were calculated as crude and adjusted for smoking status, education, socioeconomic position, BMI, waist circumference, physical activity, calendar year, and traffic noise from other sources than the one investigated. Results There was no association between residential road traffic noise and risk of prostate cancer for any of the three exposure windows: 1, 5 or 10-year mean noise exposure before prostate cancer diagnosis. This result persisted when stratifying cases by aggressiveness. For railway noise, there was no association with overall prostate cancer. There was no statistically significant effect modification by age, education, smoking status, waist circumference or railway noise, on the association between road traffic noise and prostate cancer, although there seemed to be a suggestion of an association among never smokers (IRR: 1.16; 95% CI: 1.00–1.36). Conclusion The present study does not support an overall association between either railway or road traffic noise and overall prostate cancer. PMID:26305219

  18. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

    PubMed Central

    Liang, Yayun; Mafuvadze, Benford; Aebi, Johannes D; Hyder, Salman M

    2016-01-01

    Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration); however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4′-[6-(allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071) (RO), which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway), on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ) protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the growth of aggressive castration-resistant human prostate cancer cell xenografts in vivo without any signs of toxicity to experimental animals. Importantly, RO did not reduce the viability of normal prostate cells in vitro. Our study is the first to demonstrate that the cholesterol biosynthesis inhibitor RO effectively suppresses growth of human prostate cancer cells

  19. Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Breast Cancer, Non-small Cell Lung Cancer, or Prostate Cancer

    ClinicalTrials.gov

    2016-06-17

    Male Breast Carcinoma; Prostate Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Prostate Carcinoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Prostate Cancer

  20. Genomic Copy Number Variations in the Genomes of Leukocytes Predict Prostate Cancer Clinical Outcomes

    PubMed Central

    Huo, Zhiguang; Martin, Amantha; Nelson, Joel B.; Tseng, George C.; Luo, Jian-Hua

    2015-01-01

    Accurate prediction of prostate cancer clinical courses remains elusive. In this study, we performed whole genome copy number analysis on leukocytes of 273 prostate cancer patients using Affymetrix SNP6.0 chip. Copy number variations (CNV) were found across all chromosomes of the human genome. An average of 152 CNV fragments per genome was identified in the leukocytes from prostate cancer patients. The size distributions of CNV in the genome of leukocytes were highly correlative with prostate cancer aggressiveness. A prostate cancer outcome prediction model was developed based on large size ratio of CNV from the leukocyte genomes. This prediction model generated an average prediction rate of 75.2%, with sensitivity of 77.3% and specificity of 69.0% for prostate cancer recurrence. When combined with Nomogram and the status of fusion transcripts, the average prediction rate was improved to 82.5% with sensitivity of 84.8% and specificity of 78.2%. In addition, the leukocyte prediction model was 62.6% accurate in predicting short prostate specific antigen doubling time. When combined with Gleason’s grade, Nomogram and the status of fusion transcripts, the prediction model generated a correct prediction rate of 77.5% with 73.7% sensitivity and 80.1% specificity. To our knowledge, this is the first study showing that CNVs in leukocyte genomes are predictive of clinical outcomes of a human malignancy. PMID:26295840

  1. Protease-Activated Pore-Forming Peptides for the Treatment and Imaging of Prostate Cancer

    PubMed Central

    LeBeau, Aaron M.; Denmeade, Samuel R.

    2015-01-01

    A common hallmark of cancers with highly aggressive phenotypes is increased proteolysis in the tumor and the surrounding microenvironment. Prostate cancer has a number of proteases uniquely associated with it that may play various important roles in disease progression. In this report, we utilize the peritumoral proteolytic activity of prostate cancer to activate engineered peptide constructs for the treatment and noninvasive imaging of prostate cancer. Using a modular "propeptide" approach, a cationic diastereomeric pore-forming peptide domain was linked to an inactivating acidic peptide domain. The inactivating acidic peptide domain was engineered to be a cleavable substrate for the secreted serine protease prostate-specific antigen (PSA) or the transmembrane metalloprotease prostate-specific membrane antigen (PSMA). The propeptides were then evaluated in a direct comparison study. Both the PSA and PSMA activated propeptides were found to be cytotoxic to prostate cancer cells in vitro. In vivo, however, treatment of LNCaP and CWR22Rv1 xenografts with the PSMA propeptide resulted in a pronounced cytostatic effect when compared with xenografts treated with the PSA propeptide or the cationic diastereomeric peptide alone. The PSMA activated propeptide also proved to be an effective optical imaging probe in vivo when labeled with a near-infrared fluorophore. These data suggest that protease-activated pore-forming peptides could potentially be used for both imaging and treating prostate cancer. PMID:25537662

  2. PSA, PSA derivatives, proPSA and prostate health index in the diagnosis of prostate cancer

    PubMed Central

    Ayyıldız, Sema Nur; Ayyıldız, Ali

    2014-01-01

    Currently, prostate- specific antigen (PSA) is the most common oncological marker used for prostate cancer screening. However, high levels of PSA in benign prostatic hyperplasia and prostatitis decrease the specificity of PSA as a cancer marker. To increase the specificity of PSA, PSA derivatives and PSA kinetics have been used. However, these new techniques were not able to increase the diagnostic specificity for prostate cancer. Therefore, the search for new molecules and derivatives of PSA continues. With the aim of increasing the specificity of prostate cancer diagnosis, proPSA and the Prostate Health Index have been introduced. In this review, the roles of PSA, PSA derivatives, proPSA and the Prostate Health Index in Prostate Cancer diagnosis are examined. PMID:26328156

  3. Cholesterol Metabolism and Prostate Cancer Lethality.

    PubMed

    Stopsack, Konrad H; Gerke, Travis A; Sinnott, Jennifer A; Penney, Kathryn L; Tyekucheva, Svitlana; Sesso, Howard D; Andersson, Swen-Olof; Andrén, Ove; Cerhan, James R; Giovannucci, Edward L; Mucci, Lorelei A; Rider, Jennifer R

    2016-08-15

    Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease. Cancer Res; 76(16); 4785-90. ©2016 AACR. PMID:27325648

  4. Radiation Therapy for Prostate Cancer May Carry Certain Risks

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_157587.html Radiation Therapy for Prostate Cancer May Carry Certain Risks ... 3, 2016 THURSDAY, March 3, 2016 (HealthDay News) -- Radiation treatment for prostate cancer may put men at ...

  5. Breast and Prostate Cancer Cohort Consortium (BPC3)

    Cancer.gov

    Breast and Prostate Cancer Cohort Consortium collaborates with three genomic facilities, epidemiologists, population geneticists, and biostatisticians from multiple institutions to study hormone-related gene variants and environmental factors in breast and prostate cancers.

  6. Prostate cancer incidence in men with self-reported prostatitis after 15 years of follow-up

    PubMed Central

    Vaarala, Markku H.; Mehik, Aare; Ohtonen, Pasi; Hellström, Pekka A.

    2016-01-01

    Controversy exists regarding a possible association between prostatitis and prostate cancer. To further evaluate the incidence of prostate cancer following prostatitis, a study of prostate cancer incidence in a cohort of Finnish men was performed. The original survey evaluating self-reported prostatitis was conducted in 1996–1997. A database review was conducted focusing on prostate cancer diagnoses in the cohort. In 2012, there were 13 (5.2%) and 27 (1.8%) prostate cancer cases among men with (n=251) and without (n=1,521) prostatitis symptoms, respectively. There were no significant differences in age, primary therapy distribution, prostate-specific antigen levels, Gleason score, clinical T-class at the time of prostate cancer diagnosis, or time lag between the original survey and prostate cancer diagnosis. The standardized incidence ratio (SIR) of prostate cancer was 1.16 [95% confidence interval (CI), 0.62–1.99] and 0.44 (95% CI, 0.29–0.64) among men with and without prostatitis symptoms, respectively. After 15 years of follow-up subsequent to self-reported prostatitis, no evident increase in incidence of prostate cancer was detected among Finnish men with prostatitis symptoms. The higher percentage of prostate cancer among men with prostatitis symptoms appears to be due to coincidentally low SIR of prostate cancer among men without prostatitis symptoms, and may additionally be due to increased diagnostic examinations. Further research is required to confirm this speculation.

  7. Prostate cancer epigenetics and its clinical implications.

    PubMed

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy. PMID:27212125

  8. Prostate cancer epigenetics and its clinical implications

    PubMed Central

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy. PMID:27212125

  9. Epidermal growth factor increases LRF/Pokemon expression in human prostate cancer cells.

    PubMed

    Aggarwal, Himanshu; Aggarwal, Anshu; Agrawal, Devendra K

    2011-10-01

    Leukemia/lymphoma related factor/POK erythroid myeloid ontogenic factor (LRF/Pokemon) is a member of the POK family of proteins that promotes oncogenesis in several forms of cancer. Recently, we found higher LRF expression in human breast and prostate carcinomas compared to the corresponding normal tissues. The aim of this study was to examine the regulation of LRF expression in human prostate cells. Epidermal growth factor (EGF) and its receptors mediate several tumorigenic cascades that regulate cell differentiation, proliferation, migration and survival of prostate cancer cells. There was significantly higher level of LRF expression in the nucleus of LNCaP and PC-3 cells than RWPE-1 cells. A significant increase in LRF expression was observed with increasing doses of EGF in more aggressive and androgen-sensitive prostate cancer cells suggesting that EGF signaling pathway is critical in upregulating the expression of LRF/Pokemon to promote oncogenesis. PMID:21640721

  10. Extremely Early Diagnostic Test for Prostate Cancer

    SciTech Connect

    James, Veronica Jean

    2011-11-17

    This article reports the results of a blinded fiber diffraction study of skin samples taken from TRAMP mice and age-matched controls to determine whether changes noted in fiber diffraction studies of human skin were present in these TRAMP mice studies. These mice are bred to progress to Gleeson Type 3 to Type 5 prostate cancer. Small strips, 1 mm x 5 mm, cut from the mouse skin samples were loaded into cells in the same way as human samples and slightly stretched to remove the crimp. They remained fully hydrated throughout exposure to the synchrotron beam. The added change that was reported for prostate cancer in 2009 was obtained for all TRAMP mice samples, indicating that this change can be read as High Grade Cancer in human diagnostic tests. These changes were evident for all 3 and 7 week old TRAMP mice samples but not for any of the control samples. This indicates that the changes in the fibre diffraction patterns appear much earlier than in any other available prostate cancer diagnostic test, as none of these can verify the presence of prostate cancer in the TRAMP mice before 10 weeks of age. The fiber diffraction test is therefore the most accurate and earliest test for high grade prostate cancer.

  11. Prostate cancer radiation therapy: A physician's perspective.

    PubMed

    Dal Pra, Alan; Souhami, Luis

    2016-03-01

    Prostate cancer is the second most common cancer in men and a major cause of cancer deaths worldwide. Ionizing radiation has played a substantial role in the curative treatment of this disease. The historical evolution of radiotherapy techniques through 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT) has allowed more accurate and precise treatments toward significant improvements in the therapeutic ratio. The addition of androgen deprivation therapy has significantly improved overall survival becoming the standard therapy for intermediate- and high-risk disease. Many randomized controlled trials have shown improved local control with dose escalation, and hypofractionated RT has been consolidated with proven efficacy and safe clinical results. However, several questions remain open in the radiotherapeutic management of prostate cancer patients and hopefully ongoing studies will shed light on these uncertainties. More individualized approaches are essential through better prognostic and novel predictive biomarkers of prostate radiotherapy response. Clinicians should critically interpret the evolving technologies in prostate cancer radiotherapy with important optimism but balancing the costs and the actual magnitude of clinical benefit. This article provides an overview of the basic aspects of radiotherapy treatment in localized prostate cancer from a physician's perspective. PMID:27056435

  12. Recent Advances in Metabolic Profiling And Imaging of Prostate Cancer

    PubMed Central

    Thapar, Roopa; Titus, Mark A

    2015-01-01

    Cancer is a metabolic disease. Cancer cells, being highly proliferative, show significant alterations in metabolic pathways such as glycolysis, respiration, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, lipid metabolism, and amino acid metabolism. Metabolites like peptides, nucleotides, products of glycolysis, the TCA cycle, fatty acids, and steroids can be an important read out of disease when characterized in biological samples such as tissues and body fluids like urine, serum, etc. The cancer metabolome has been studied since the 1960s by analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Current research is focused on the identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients and distinguish between benign and advanced metastatic forms of the disease. In this review, we discuss the current state of prostate cancer metabolomics, the biomarkers that show promise in distinguishing indolent from aggressive forms of the disease, the strengths and limitations of the analytical techniques being employed, and future applications of metabolomics in diagnostic imaging and personalized medicine of prostate cancer. PMID:25632377

  13. Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers.

    PubMed

    Mimeault, M; Hauke, R; Mehta, P P; Batra, S K

    2007-01-01

    Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. This review summarizes recent advances in our understanding of the cellular origin and molecular mechanisms at the basis of cancer initiation and progression as well as the heterogeneity of cancers arising from the malignant transformation of adult stem/progenitor cells. We describe the critical functions provided by several growth factor cascades, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF) receptor (KIT), hedgehog and Wnt/beta-catenin signalling pathways that are frequently activated in cancer progenitor cells and are involved in their sustained growth, survival, invasion and drug resistance. Of therapeutic interest, we also discuss recent progress in the development of new drug combinations to treat the highly aggressive and metastatic cancers including refractory/relapsed leukaemias, melanoma and head and neck, brain, lung, breast, ovary, prostate, pancreas and gastrointestinal cancers which remain incurable in the clinics. The emphasis is on new therapeutic strategies consisting of molecular targeting of distinct oncogenic signalling elements activated in the cancer progenitor cells and their local microenvironment during cancer progression. These new targeted therapies should improve the efficacy of current therapeutic treatments against aggressive cancers, and thereby preventing disease relapse and enhancing patient survival. PMID:17979879

  14. Biallelic BRCA2 Mutations Shape the Somatic Mutational Landscape of Aggressive Prostate Tumors.

    PubMed

    Decker, Brennan; Karyadi, Danielle M; Davis, Brian W; Karlins, Eric; Tillmans, Lori S; Stanford, Janet L; Thibodeau, Stephen N; Ostrander, Elaine A

    2016-05-01

    To identify clinically important molecular subtypes of prostate cancer (PCa), we characterized the somatic landscape of aggressive tumors via deep, whole-genome sequencing. In our discovery set of ten tumor/normal subject pairs with Gleason scores of 8-10 at diagnosis, coordinated analysis of germline and somatic variants, including single-nucleotide variants, indels, and structural variants, revealed biallelic BRCA2 disruptions in a subset of samples. Compared to the other samples, the PCa BRCA2-deficient tumors exhibited a complex and highly specific mutation signature, featuring a 2.88-fold increased somatic mutation rate, depletion of context-specific C>T substitutions, and an enrichment for deletions, especially those longer than 10 bp. We next performed a BRCA2 deficiency-targeted reanalysis of 150 metastatic PCa tumors, and each of the 18 BRCA2-mutated samples recapitulated the BRCA2 deficiency-associated mutation signature, underscoring the potent influence of these lesions on somatic mutagenesis and tumor evolution. Among all 21 individuals with BRCA2-deficient tumors, only about half carried deleterious germline alleles. Importantly, the somatic mutation signature in tumors with one germline and one somatic risk allele was indistinguishable from those with purely somatic mutations. Our observations clearly demonstrate that BRCA2-disrupted tumors represent a unique and clinically relevant molecular subtype of aggressive PCa, highlighting both the promise and utility of this mutation signature as a prognostic and treatment-selection biomarker. Further, any test designed to leverage BRCA2 status as a biomarker for PCa must consider both germline and somatic mutations and all types of deleterious mutations. PMID:27087322

  15. Development of PROSTVAC immunotherapy in prostate cancer.

    PubMed

    Singh, Parminder; Pal, Sumanta K; Alex, Anitha; Agarwal, Neeraj

    2015-01-01

    PROSTVAC immunotherapy is a heterologous prime-boost regimen of two different recombinant pox-virus vectors; vaccinia as the primary immunotherapy, followed by boosters employing fowlpox, to provoke immune responses against prostate-specific antigen. Both vectors contain transgenes for prostate-specific antigen and a triad of T-cell costimulatory molecules (TRICOM). In a placebo-controlled Phase II trial of men with minimally symptomatic, chemotherapy-naive metastatic castration-resistant prostate cancer, PROSTVAC was well tolerated and associated with a 44% reduction in death. With a novel mechanism of action, and excellent tolerability, PROSTVAC has the potential to dramatically alter the treatment landscape of prostate cancer, not only as a monotherapy, but also in combination with other novel agents, such as immune check point inhibitors and novel androgen receptor blockers. A Phase III trial recently completed accrual. PMID:26235179

  16. Development of PROSTVAC immunotherapy in prostate cancer

    PubMed Central

    Singh, Parminder; Pal, Sumanta K; Alex, Anitha; Agarwal, Neeraj

    2015-01-01

    PROSTVAC immunotherapy is a heterologous prime-boost regimen of two different recombinant pox-virus vectors; vaccinia as the primary immunotherapy, followed by boosters employing fowlpox, to provoke immune responses against prostate-specific antigen. Both vectors contain transgenes for prostate-specific antigen and a triad of T-cell costimulatory molecules (TRICOM). In a placebo-controlled Phase II trial of men with minimally symptomatic, chemotherapy-naive metastatic castration-resistant prostate cancer, PROSTVAC was well tolerated and associated with a 44% reduction in death. With a novel mechanism of action, and excellent tolerability, PROSTVAC has the potential to dramatically alter the treatment landscape of prostate cancer, not only as a monotherapy, but also in combination with other novel agents, such as immune check point inhibitors and novel androgen receptor blockers. A Phase III trial recently completed accrual. PMID:26235179

  17. [Sharing uncertainties of prostate cancer screening].

    PubMed

    Selby, Kevin; Auer, Reto; Valerio, Massimo; Jichlinski, Patrice; Cornuz, Jacques

    2015-11-25

    The decision of whether our patients should undergo prostate cancer screening with the prostate specifc antigen (PSA) test remains daunting. The role of the primary care doctor is to help men decide between a potential decrease in mortality from a slow evolving but sometimes lethal cancer, and the risk of diagnosing and treating cancers that would have otherwise been indolent and asymptomatic. We can structure our discussions with three steps: choice, option, and decision making. A decision aid, such as the one that we have adapted and simplifed from the Collège des médecins du Québec, can help with this complex decision. PMID:26742351

  18. SPARCL1 suppresses metastasis in prostate cancer

    PubMed Central

    Xiang, Yuzhu; Qiu, Qingchao; Jiang, Ming; Jin, Renjie; Lehmann, Brian D; Strand, Douglas W; Jovanovic, Bojana; DeGraff, David J; Zheng, Yi; Yousif, Dina A; Case, Thomas C; Yi, Jia; Cates, Justin M; Virostko, John; He, Xiusheng; Jin, Xunbo; Hayward, Simon W; Matusik, Robert J; George, Alfred L; Yi, Yajun

    2013-01-01

    Purpose Metastasis, the main cause of death from cancer, remains poorly understood at the molecular level. Experimental design Based on a pattern of reduced expression in human prostate cancer tissues and tumor cell lines, a candidate suppressor gene (SPARCL1) was identified. We used in vitro approaches to determine whether overexpression of SPARCL1 affects cell growth, migration, and invasiveness. We then employed xenograft mouse models to analyze the impact of SPARCL1 on prostate cancer cell growth and metastasis in vivo. Results SPARCL1 expression did not inhibit tumor cell proliferation in vitro. By contrast, SPARCL1 did suppress tumor cell migration and invasiveness in vitro and tumor metastatic growth in vivo, conferring improved survival in xenograft mouse models. Conclusions We present the first in vivo data suggesting that SPARCL1 suppresses metastasis of prostate cancer. PMID:23916135

  19. New Players for Advanced Prostate Cancer and the Rationalisation of Insulin-Sensitising Medication

    PubMed Central

    Gunter, Jennifer H.; Sarkar, Phoebe L.; Lubik, Amy A.; Nelson, Colleen C.

    2013-01-01

    Obesity and type 2 diabetes are recognised risk factors for the development of some cancers and, increasingly, predict more aggressive disease, treatment failure, and cancer-specific mortality. Many factors may contribute to this clinical observation. Hyperinsulinaemia, dyslipidaemia, hypoxia, ER stress, and inflammation associated with expanded adipose tissue are thought to be among the main culprits driving malignant growth and cancer advancement. This observation has led to the proposal of the potential utility of “old players” for the treatment of type 2 diabetes and metabolic syndrome as new cancer adjuvant therapeutics. Androgen-regulated pathways drive proliferation, differentiation, and survival of benign and malignant prostate tissue. Androgen deprivation therapy (ADT) exploits this dependence to systemically treat advanced prostate cancer resulting in anticancer response and improvement of cancer symptoms. However, the initial therapeutic response from ADT eventually progresses to castrate resistant prostate cancer (CRPC) which is currently incurable. ADT rapidly induces hyperinsulinaemia which is associated with more rapid treatment failure. We discuss current observations of cancer in the context of obesity, diabetes, and insulin-lowering medication. We provide an update on current treatments for advanced prostate cancer and discuss whether metabolic dysfunction, developed during ADT, provides a unique therapeutic window for rapid translation of insulin-sensitising medication as combination therapy with antiandrogen targeting agents for the management of advanced prostate cancer. PMID:23573093

  20. Outcome of radical prostatectomy in primary circulating prostate cell negative prostate cancer

    PubMed Central

    Murray, Nigel P; Aedo, Sócrates; Reyes, Eduardo; Fuentealba, Cynthia; Jacob, Omar

    2016-01-01

    Introduction Around 90% of prostate cancers detected using the serum prostate specific antigen (PSA) as a screening test are considered to be localised. However, 20–30% of men treated by radical prostatectomy experience biochemical failure within two years of treatment. The presence of primary circulating prostate cells (CPCs) in the blood of these men implies a dissemination of the tumour and could indicate a greater risk of treatment failure. Objective To evaluate the use of the number of primary CPCs detected before surgery in the prediction of biochemical failure at ten years. Hypothesis The dissemination of cancer cells to distant sites will determine the patient’s prognosis. The absence of primary CPCs in men undergoing radical prostatectomy for prostate cancer may imply a less aggressive disease and therefore could be utilised as a prognostic factor to predict biochemical failure after surgery. Methods and patients A single-centre observational study of a cohort of 285 men who underwent radical prostatectomy as monotherapy for prostate cancer, in whom the number of CPCs prior to treatment was determined, and who were followed up for ten years to determine biochemical failure. A Cox proportional risks with polynomial fractions analysis was used to predict biochemical failure based on the number of primary CPCs detected. A decision curve analysis was performed for the model obtained. Results Kaplan–Meier curves for biochemical free survival at ten years was 47.34% (95% CI 38.71–55.48%). It is important to note that in CPC negative men, the ten years Kaplan–Meier biochemical-free survival was 90.35% (95% CI 75.0–96.27) whereas in men who were primary CPC positive, the biochemical free survival rate was 30.00% (95% CI 20.34–40.60%). The Coxs´model to predict biochemical failure using transformed data with a power of minus one for the number of primary CPCs detected, showed a Harrell´s C concordance index of 0.74 and a decision analysis curve

  1. Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance

    PubMed Central

    Vos, Larissa J; Janoski, Michele; Wachowicz, Keith; Yahya, Atiyah; Boychak, Oleksandr; Amanie, John; Pervez, Nadeem; Parliament, Matthew B; Pituskin, Edith; Fallone, B Gino; Usmani, Nawaid

    2016-01-01

    AIM: To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer. METHODS: Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated. RESULTS: During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity). CONCLUSION: Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods. PMID:27158428

  2. The evolving biology and treatment of prostate cancer

    PubMed Central

    Taichman, Russel S.; Loberg, Robert D.; Mehra, Rohit; Pienta, Kenneth J.

    2007-01-01

    Since the effectiveness of androgen deprivation for treatment of advanced prostate cancer was first demonstrated, prevention strategies and medical therapies for prostate cancer have been based on understanding the biologic underpinnings of the disease. Prostate cancer treatment is one of the best examples of a systematic therapeutic approach to target not only the cancer cells themselves, but the microenvironment in which they are proliferating. As the population ages and prostate cancer prevalence increases, challenges remain in the diagnosis of clinically relevant prostate cancer as well as the management of the metastatic and androgen-independent metastatic disease states. PMID:17786228

  3. Measurement of quality of life in men with prostate cancer.

    PubMed

    Albaugh, Jeffrey; Hacker, Eileen Danaher

    2008-02-01

    Prostate cancer continues to be one of the most common cancers diagnosed in men. In light of the excellent survival rates for prostate cancer, quality of life is a primary concern during and following prostate cancer treatment. Quality of life is defined and determined in multiple ways. This article explores quality of life in men with prostate cancer. Quality-of-life dimensions, measurement tools, and implications of quality of life with prostate cancer on clinical practice for oncology nurses will be presented. PMID:18258577

  4. Risks of Prostate Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  5. Penile Rehabilitation Strategies Among Prostate Cancer Survivors

    PubMed Central

    Aoun, Fouad; Peltier, Alexandre; van Velthoven, Roland

    2015-01-01

    Despite advances in technical and surgical approaches, erectile dysfunction (ED) remains the most common complication among prostate cancer survivors, adversely impacting quality of life. This article analyzes the concept and rationale of ED rehabilitation programs in prostate cancer patients. Emphasis is placed on the pathophysiology of ED after diagnosis and treatment of prostate cancer to understand the efficacy of rehabilitation programs in clinical practice. Available evidence shows that ED is a transient complication following prostate biopsy and cancer diagnosis, with no evidence to support rehabilitation programs in these patients. A small increase in ED and in the use of phosphodiesterase type 5 (PDE5) inhibitors was reported in patients under active surveillance. Patients should be advised that active surveillance is unlikely to severely affect erectile function, but clinically significant changes in sexual function are possible. Focal therapy could be an intermediate option for patients demanding treatment/refusing active surveillance and invested in maintaining sexual activity. Unlike radical prostatectomy, there is no support for PDE5 inhibitor use to prevent ED after highly conformal external radiotherapy or low-dose rate brachytherapy. Despite progress in the understanding of the pathophysiologic mechanisms responsible for ED in prostate cancer patients, the success rates of rehabilitation programs remain low in clinical practice. Alternative strategies to prevent ED appear warranted, with attention toward neuromodulation, nerve grafting, nerve preservation, stem cell therapy, investigation of neuroprotective interventions, and further refinements of radiotherapy dosing and delivery methods. PMID:27222641

  6. Penile Rehabilitation Strategies Among Prostate Cancer Survivors.

    PubMed

    Aoun, Fouad; Peltier, Alexandre; van Velthoven, Roland

    2015-01-01

    Despite advances in technical and surgical approaches, erectile dysfunction (ED) remains the most common complication among prostate cancer survivors, adversely impacting quality of life. This article analyzes the concept and rationale of ED rehabilitation programs in prostate cancer patients. Emphasis is placed on the pathophysiology of ED after diagnosis and treatment of prostate cancer to understand the efficacy of rehabilitation programs in clinical practice. Available evidence shows that ED is a transient complication following prostate biopsy and cancer diagnosis, with no evidence to support rehabilitation programs in these patients. A small increase in ED and in the use of phosphodiesterase type 5 (PDE5) inhibitors was reported in patients under active surveillance. Patients should be advised that active surveillance is unlikely to severely affect erectile function, but clinically significant changes in sexual function are possible. Focal therapy could be an intermediate option for patients demanding treatment/refusing active surveillance and invested in maintaining sexual activity. Unlike radical prostatectomy, there is no support for PDE5 inhibitor use to prevent ED after highly conformal external radiotherapy or low-dose rate brachytherapy. Despite progress in the understanding of the pathophysiologic mechanisms responsible for ED in prostate cancer patients, the success rates of rehabilitation programs remain low in clinical practice. Alternative strategies to prevent ED appear warranted, with attention toward neuromodulation, nerve grafting, nerve preservation, stem cell therapy, investigation of neuroprotective interventions, and further refinements of radiotherapy dosing and delivery methods. PMID:27222641

  7. Quality of Prostate Cancer Treatment Information on Cancer Center Websites

    PubMed Central

    Barrett, Olivia Claire; Rais-Bahrami, Soroush; Wakefield, Daniel; Fiveash, John; Dobelbower, Michael

    2016-01-01

    Introduction Cancer center websites are trusted sources of internet information about treatment options for prostate cancer. The quality of information on these websites is unknown. The objective of this study was to evaluate the quality of information on cancer center websites addressing prostate cancer treatment options, outcomes, and toxicity. Materials and methods We evaluated the websites of all National Cancer Institute-designated cancer centers to determine if sufficient information was provided to address eleven decision-specific knowledge questions from the validated Early Prostate Cancer Treatment Decision Quality Instrument. We recorded the number of questions addressed, the number of clicks to reach the prostate cancer-specific webpage, evaluation time, and Spanish and mobile accessibility. Correlation between evaluation time and questions addressed were calculated using the Pearson coefficient. Results Sixty-three websites were reviewed. Eighty percent had a prostate cancer-specific webpage reached in a median of three clicks. The average evaluation time was 6.5 minutes. Information was available in Spanish on 24% of sites and 59% were mobile friendly. Websites provided sufficient information to address, on average, 19% of questions. No website addressed all questions. Evaluation time correlated with the number of questions addressed (R2 = 0.42, p < 0.001). Conclusions Cancer center websites provide insufficient information for men with localized prostate cancer due to a lack of information about and direct comparison of specific treatment outcomes and toxicities. Information is also less accessible in Spanish and on mobile devices. These data can be used to improve the quality and accessibility of prostate cancer treatment information on cancer center websites. PMID:27226941

  8. Smoking, alcohol, coffee, tea, caffeine, and theobromine: risk of prostate cancer in Utah (United States).

    PubMed

    Slattery, M L; West, D W

    1993-11-01

    Data from a population-based study of newly diagnosed cases of prostate cancer (n = 362) and age-matched controls (n = 685) conducted in Utah (United States) between 1983 and 1986 were used to determine if cigarette smoking, alcohol, coffee, tea, caffeine, and theobromine were associated with prostate cancer risk. These factors were examined since their use differs in the Utah population, which is comprised predominantly of members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormon), from most other populations. Pack-years of cigarettes smoked, alcohol intake, and consumption of alcohol, coffee, tea, and caffeine were not associated with prostate cancer risk. Compared with men with very low levels of theobromine intake, older men consuming 11 to 20 and over 20 mg of theobromine per day were at increased risk of prostate cancer (odds ratio [OR] for all tumors = 2.06, 95 percent confidence interval [CI] = 1.33-3.20, and OR = 1.47, CI = 0.99-2.19, respectively; OR for aggressive tumors = 1.90, CI = 0.90-3.97, and OR = 1.74, CI = 0.91-3.32, respectively). We present biological mechanisms for a possible association between prostate cancer and theobromine. This finding needs further exploration in studies with a wider range of theobromine exposures and more men with aggressive tumors. PMID:8280834

  9. SOST Inhibits Prostate Cancer Invasion

    PubMed Central

    Hudson, Bryan D.; Hum, Nicholas R.; Thomas, Cynthia B.; Kohlgruber, Ayano; Sebastian, Aimy; Collette, Nicole M.; Coleman, Matthew A.; Christiansen, Blaine A.; Loots, Gabriela G.

    2015-01-01

    Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. We found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings. PMID:26545120

  10. Current clinical challenges in prostate cancer

    PubMed Central

    Silberstein, Jonathan L.; Pal, Sumanta Kumar; Lewis, Brian

    2013-01-01

    Prostate cancer is the most common malignancy and the second leading cause of cancer death in men in the United States. Close to $12 billion are spent annually on the treatment of prostate cancer in the US alone. Yet still there remain tremendous controversies and challenges that exist in all facets of the disease. This review and discussion will focus on issues and challenges for clinicians and patients diagnosed with the disease. Appropriate risk stratification for men with newly diagnosed prostate cancer is an appropriate first step for all patients. Once risk-stratified, for those with low-risk of death, it is increasingly recognized that overtreatment creates an unnecessary burden for many patients. This is particularly evident when put in the context of competing comorbidities in an elderly population. For those with advanced or high-risk localized disease, under-treatment remains too common. For those with a high-risk of recurrence or failure following primary treatment, adjuvant or salvage therapies are an option, but how and when to best deploy these treatments are controversial. Recently, tremendous progress has been made for those with advanced disease, in particular those with metastatic castrate-resistant prostate cancer (mCRPC). Within the last 4 years, five novel FDA approved agents, acting through distinct mechanisms have been FDA approved for mCRPC. With the introduction of these new agents a host of new challenges have arisen. Timing, sequencing and combinations of these novel agents are welcomed challenges when compared with the lack of available therapies just a few years ago. In this summary of current clinical challenges in prostate cancer we review critical recent studies that have created or shifted the current paradigms of treatment for prostate cancer. We will also highlight ongoing issues that continue to challenge our field. PMID:26816735

  11. Cytoskeleton targeting value in prostate cancer treatment

    PubMed Central

    Martin, Sarah K; Kamelgarn, Marisa; Kyprianou, Natasha

    2014-01-01

    Prostate cancer is a disease that affects hundreds of thousands of men in the United States each year. In the early stages of advanced prostate cancer, the disease can be suppressed by androgen deprivation therapy (ADT). Eventually, however, most patients experience resistance to androgen deprivation, and their treatment transitions to alternative targeting of the androgen axis with abiraterone and enzalutamide, as well as taxane-based chemotherapy. Development of advanced castration-resistant prostate cancer (CRPC) is a consequence of lack of an apoptotic response by the tumor cells to treatment. Understanding the mechanisms contributing to prostate tumor therapeutic resistance and progression to metastasis requires dissection of the signaling mechanisms navigating tumor invasion and metastasis as mediated by cell-matrix interactions engaging components of the extracellular matrix (ECM), to form adhesion complexes. For a tumor call to metastasize from the primary tumor, it requires disruption of cell-cell interactions from the surrounding cells, as well as detachment from the ECM and resistance to anoikis (apoptosis upon cell detachment from ECM). Attachment, movement and invasion of cancer cells are functionally facilitated by the actin cytoskeleton and tubulin as the structural component of microtubules. Transforming growth factor (TGF)-β has tumor-inhibitory activity in the early stages of tumorigenesis, but it promotes tumor invasive characteristics in metastatic disease. Recent evidence implicates active (dephosphorylated) cofilin, an F-actin severing protein required for cytoskeleton reorganization, as an important contributor to switching TGF-β characteristics from a growth suppressor to a promoter of prostate cancer invasion and metastasis. Cancer cells eventually lose the ability to adhere to adjacent neighboring cells as well as ECM proteins, and via epithelial-mesenchymal transition (EMT), acquire invasive and metastatic characteristics. Microtubule

  12. Dietary acrylamide and risk of prostate cancer.

    PubMed

    Wilson, Kathryn M; Giovannucci, Edward; Stampfer, Meir J; Mucci, Lorelei A

    2012-07-15

    Acrylamide has been designated by IARC as a "probable human carcinogen." High levels are formed during cooking of many commonly consumed foods including French fries, potato chips, breakfast cereal and coffee. Two prospective cohort studies and two case-control studies in Europe found no association between acrylamide intake and prostate cancer. We examined this association in a large prospective cohort of 47,896 US men in the Health Professionals' Follow-up Study, using updated dietary acrylamide intake from food frequency questionnaires in 1986, 1990, 1994, 1998 and 2002. From 1986 through 2006, we documented 5025 cases of prostate cancer, and 642 lethal cancers. We used Cox proportional hazards models to assess the association between acrylamide intake from diet and prostate cancer risk overall as well as risk of advanced or lethal cancer. Acrylamide intake ranged from a mean of 10.5 mcg/day in the lowest quintile to 40.1 mcg/day in the highest quintile; coffee and potato products were largest contributors to intake. The multivariate-adjusted relative risk of prostate cancer was 1.02 (95% confidence interval: 0.92-1.13) for the highest versus lowest quintile of acrylamide intake (p-value for trend = 0.90). Results were similar when restricted to never smokers and to men who had prostate-specific antigen (PSA) tests. There was no significant association for dietary acrylamide and risk of lethal, advanced or high-grade disease, or for different latency periods ranging from 0-4 years to 12-16 years. We found no evidence that acrylamide intake, within the range of US diets, is associated with increased risk of prostate cancer. PMID:21866549

  13. Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer.

    PubMed

    Landau, Kevin S; Na, Insung; Schenck, Ryan O; Uversky, Vladimir N

    2016-01-01

    Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease. PMID:27453073

  14. Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer

    PubMed Central

    Landau, Kevin S; Na, Insung; Schenck, Ryan O; Uversky, Vladimir N

    2016-01-01

    Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease. PMID:27453073

  15. State-of-the-art imaging of prostate cancer.

    PubMed

    Marko, Jamie; Gould, C Frank; Bonavia, Grant H; Wolfman, Darcy J

    2016-03-01

    Prostate cancer is the most common cancer in men. Modern medical imaging is intimately involved in the diagnosis and management of prostate cancer. Ultrasound is primarily used to guide prostate biopsy to establish the diagnosis of prostate carcinoma. Prostate magnetic resonance imaging uses a multiparametric approach, including anatomic and functional imaging sequences. Multiparametric magnetic resonance imaging can be used for detection and localization of prostate cancer and to evaluate for disease recurrence. Computed tomography and scintigraphic imaging are primarily used to detect regional lymph node spread and distant metastases. Recent advancements in ultrasound, multiparametric magnetic resonance imaging, and scintigraphic imaging have the potential to change the way prostate cancer is diagnosed and managed. This article addresses the major imaging modalities involved in the evaluation of prostate cancer and updates the reader on the state of the art for each modality. PMID:26087969

  16. Role of PARP-1 in prostate cancer

    PubMed Central

    Deshmukh, Dhanraj; Qiu, Yun

    2015-01-01

    Poly (ADP-ribose) polymerase-1 (PARP-1) is an enzyme that catalyzes the covalent attachment of polymers of ADP-ribose (PAR) moieties on itself and its target proteins. PARP1 activity is frequently deregulated in various cancers and therefore it has emerged as a new drug target for cancer therapy. The role of PARP-1 in DNA repair has been well documented and BRCA mutations are implicated for determining the sensitivity to PARP inhibitors. Recent studies also point to a role of PARP-1 in transcription regulation which may contribute to oncogenic signaling and cancer progression. Given that efficacy of PARP inhibitors are also seen in patients not harboring BRCA mutations, some other mechanisms might also be involved. In the present review, we highlight the mechanisms by which PARP-1 regulates gene expression in prostate cancer and provide an overview of the ongoing clinical trials using PARP inhibitors in various cancers including prostate cancer. PMID:26069882

  17. Stereotactic body radiotherapy for prostate cancer.

    PubMed

    Henderson, D R; Tree, A C; van As, N J

    2015-05-01

    The use of stereotactic body radiotherapy (SBRT) for localised prostate cancer is now supported by a substantial body of non-randomised data, with medium-term outcomes consistent with current standard radiotherapy. The ability to deliver profoundly hypofractionated treatment, combined with the relatively low α/β ratio of prostate cancer, may result in a more favourable therapeutic ratio, presenting an opportunity for isotoxic dose escalation. Furthermore, as treatment can be given in five attendances, SBRT has the potential both to reduce costs and improve patient quality of life. However, in a treatment landscape with many competing options of broadly similar efficacy, randomised trials are essential to define the relative benefits of this approach. SBRT also has an emerging application in oligometastatic prostate cancer, with promising early outcomes for delaying disease progression and deferring the need for androgen deprivation therapy. PMID:25707911

  18. CYP17 inhibitors for prostate cancer therapy.

    PubMed

    Vasaitis, Tadas S; Bruno, Robert D; Njar, Vincent C O

    2011-05-01

    Prostate cancer (PC) is now the second most prevalent cause of death in men in the USA and Europe. At present, the major treatment options include surgical or medical castration. These strategies cause ablation of the production of testosterone (T), dihydrotestosterone (DHT) and related androgens by the testes. However, because these procedures do not affect adrenal, prostate and other tissues' androgen production, they are often combined with androgen receptor antagonists to block their action. Indeed, recent studies have unequivocally established that in castration-resistant prostate cancer (CRPC) many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels. Clearly, inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, 17α-hydroxy/17,20-lyase (hereafter referred to as CYP17) could prevent androgen production from all sources. Thus, total ablation of androgen production by potent CYP17 inhibitors may provide effective treatment of prostate cancer patients. This review highlights the role of androgen biosynthesis in the progression of prostate cancer and the impact of CYP17 inhibitors, such as ketoconazole, abiraterone acetate, VN/124-1 (TOK-001) and TAK-700 in the clinic and in clinical development. Article from the special issue on Targeted Inhibitors. PMID:21092758

  19. CYP17 inhibitors for prostate cancer therapy

    PubMed Central

    Vasaitis, Tadas S.; Bruno, Robert D.; Njar, Vincent C. O.

    2010-01-01

    Prostate cancer (PC) is now the second most prevalent cause of death in men in the USA and Europe. At present, the major treatment options include surgical or medical castration. These strategies cause ablation of the production of testosterone (T), dihydrotestosterone (DHT) and related androgens by the testes. However, because these procedures do not affect adrenal, prostate and other tissues androgen production, they are often combined with androgen receptor antagonists to block their action. Indeed, recent studies have unequivocally established that in castration-resistant prostate cancer (CRPC) many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels. Clearly, inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, 17α-hydroxy/17,20-lyase (hereafter referred to as CYP17) could prevent androgen production from all sources. Thus, total ablation of androgen production by potent CYP17 inhibitors may provide effective treatment of prostate cancer patients. This review highlights the role of androgen biosynthesis in the progression of prostate cancer and the impact of CYP17 inhibitors, such as ketoconazole, abiraterone acetate, VN/124-1 (TOK-001) and TAK-700 in the clinic and in clinical development. PMID:21092758

  20. [THE EVOLUTION OF MARKERS OF PROSTATE CANCER].

    PubMed

    Peshkov, M N; Generozov, E V; Kostryukova, E S

    2016-03-01

    The implementation of biochemical laboratory tests in oncology practice increased exponentially during last decades and continues to be in progress nowadays. The application of modern molecular genetic technologies permits using diagnostic systems with greater diagnostic sensitivity and specificity. The new tests are actively implemented permitting to diagnose physical presence of tumor systemic manifestations of malignant neoplasm (cachexia, pyrexia), paraneoplastic syndromes and also to detect tumor markers. The oncomarker permits to differentiate malignant from benign tumor on the basis of quantitative differences in content of corresponding antigene-tumor marker in blood serum independently of localization of tumor nidus. The prostate cancer is a medical social problem of male population. On initial stages, this disease can take its course asymptomatically or with symptomatic conditioned by such concomitant and more prevalent pathologies as chronic prostatitis and prostate benign hyperplasia. The early diagnostic ofprostate cancer permits implementing timely radical treatment frequently contributing to total recovery of patients. The article presents detailed description of evolutionary conception of markers using in diagnostic, staging and prognostication of course of prostate cancer. The acid phosphatase was applied for the first time in early diagnostic of staging of prostate cancer in 1974. Nowadays, in century of "OMX"-technologies, in common clinical practice detection of RNA in urine of patient is used for staging diagnostic and prognostication of progression of process of tissue neotransformation. PMID:27506103

  1. Translational Molecular Imaging of Prostate Cancer

    PubMed Central

    Kiess, Ana P.; Cho, Steve Y.; Pomper, Martin G.

    2013-01-01

    Prostate cancer is a heterogeneous disease, and its management is now evolving to become more personalized and to incorporate new targeted therapies. With these new changes comes a demand for molecular imaging techniques that can not only detect disease but also assess biology and treatment response. This review article summarizes current molecular imaging approaches in prostate cancer (e.g. 99mTc bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography) and highlights emerging clinical and preclinical imaging agents, with an emphasis on mechanism and clinical application. Emerging agents at various stages of clinical translation include radiolabeled analogs of lipid, amino acid, and nucleoside metabolism, as well as agents more specifically targeting prostate cancer biomarkers including androgen receptor, prostate-specific membrane antigen and others. We also highlight new techniques and targeted contrast agents for magnetic resonance imaging and spectroscopy. For all these imaging techniques, a growing and important unmet need is for well-designed prospective clinical trials to establish clear indications with clinical benefit in prostate cancer. PMID:24159427

  2. Applications of transrectal ultrasound in prostate cancer

    PubMed Central

    Harvey, C J; Pilcher, J; Richenberg, J; Patel, U; Frauscher, F

    2012-01-01

    Transrectal ultrasound (TRUS) was first developed in the 1970s. TRUS-guided biopsy, under local anaesthetic and prophylactic antibiotics, is now the most widely accepted method to diagnose prostate cancer. However, the sensitivity and specificity of greyscale TRUS in the detection of prostate cancer is low. Prostate cancer most commonly appears as a hypoechoic focal lesion in the peripheral zone on TRUS but the appearances are variable with considerable overlap with benign lesions. Because of the low accuracy of greyscale TRUS, TRUS-guided biopsies have become established in the acquisition of systematic biopsies from standard locations. The number of systematic biopsies has increased over the years, with 10–12 cores currently accepted as the minimum standard. This article describes the technique of TRUS and biopsy and its complications. Novel modalities including contrast-enhanced modes and elastography as well as fusion techniques for increasing the sensitivity of TRUS-guided prostate-targeted biopsies are discussed along with their role in the diagnosis and management of prostate cancer. PMID:22844031

  3. 5-Alpha reductase inhibitor use and prostate cancer survival in the Finnish Prostate Cancer Screening Trial.

    PubMed

    Murtola, Teemu J; Karppa, Elina K; Taari, Kimmo; Talala, Kirsi; Tammela, Teuvo Lj; Auvinen, Anssi

    2016-06-15

    Randomized clinical trials have shown that use of 5α-reductase inhibitors (5-ARIs) lowers overall prostate cancer (PCa) risk compared to placebo, while the proportion of Gleason 8-10 tumors is elevated. It is unknown whether this affects PCa-specific survival. We studied disease-specific survival by 5-ARI usage in a cohort of 6,537 prostate cancer cases diagnosed in the Finnish Prostate Cancer Screening Trial and linked to the national prescription database for information on medication use. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for prostate cancer-specific deaths. For comparison, survival among alpha-blocker users was also evaluated. During the median follow-up of 7.5 years after diagnosis a total of 2,478 men died; 617 due to prostate cancer and 1,861 due to other causes. The risk of prostate cancer death did not differ between 5-ARI users and nonusers (multivariable adjusted HR 0.94, 95% CI 0.72-1.24 and HR 0.98, 95% CI 0.69-1.41 for usage before and after the diagnosis, respectively). Alpha-blocker usage both before and after diagnosis was associated with increased risk of prostate cancer death (HR 1.29, 95% CI 1.08-1.54 and HR 1.56, 95% CI 1.30-1.86, respectively). The risk increase vanished in long-term alpha-blocker usage. Use of 5-ARIs does not appear to affect prostate cancer mortality when used in management of benign prostatic hyperplasia. Increased risk associated with alpha-blocker usage should prompt further exploration on the prognostic role of lower urinary tract symptoms. PMID:26804670

  4. The role of glycans in the development and progression of prostate cancer.

    PubMed

    Munkley, Jennifer; Mills, Ian G; Elliott, David J

    2016-06-01

    Prostate cancer is a unique and heterogeneous disease. Currently, a major unmet clinical need exists to develop biomarkers that enable indolent disease to be distinguished from aggressive disease. The prostate is an abundant secretor of glycoproteins of all types, and alterations in glycans are, therefore, attractive as potential biomarkers and therapeutic targets. Despite progress over the past decade in profiling the genome and proteome, the prostate cancer glycoproteome remains relatively understudied. A wide range of alterations in the glycoproteins on prostate cancer cells can occur, including increased sialylation and fucosylation, increased O-β-N-acetylglucosamine (GlcNAc) conjugation, the emergence of cryptic and high-mannose N-glycans and alterations to proteoglycans. Glycosylation can alter protein function and has a key role in many important biological processes in cancer including cell adhesion, migration, interactions with the cell matrix, immune surveillance, cell signalling and cellular metabolism; altered glycosylation in prostate cancer might modify some, or all of these processes. In the past three years, powerful tools such as glycosylation-specific antibodies and glycosylation gene signatures have been developed, which enable detailed analyses of changes in glycosylation. Thus, emerging data on these often overlooked modifications have the potential to improve risk stratification and therapeutic strategies in patients with prostate cancer. PMID:27091662

  5. Overcoming Drug Resistance and Treating Advanced Prostate Cancer

    PubMed Central

    Semenas, Julius; Allegrucci, Cinzia; Boorjian, Stephen A; Mongan, Nigel P; Persson, Jenny Liao

    2012-01-01

    Most of the prostate cancers (PCa) in advanced stage will progress to castration-resistant prostate cancer (CRPC). Within CRPC group, 50-70% of the patients will develop bone metastasis in axial and other regions of the skeleton. Once PCa cells spread to the bone, currently, no treatment regimens are available to eradicate the metastasis, and cancer-related death becomes inevitable. In 2012, it is estimated that there will be 28,170 PCa deaths in the United States. Thus, PCa bone metastasis-associated clinical complications and treatment resistance pose major clinical challenges. In this review, we will present recent findings on the molecular and cellular pathways that are responsible for bone metastasis of PCa. We will address several novel mechanisms with a focus on the role of bone and bone marrow microenvironment in promoting PCa metastasis, and will further discuss why prostate cancer cells preferentially metastasize to the bone. Additionally, we will discuss novel roles of several key pathways, including angiogenesis and extracellular matrix remodeling in bone marrow and stem cell niches with their relationship to PCa bone metastasis and poor treatment response. We will evaluate how various chemotherapeutic drugs and radiation therapies may allow aggressive PCa cells to gain advantageous mutations leading to increased survival and rendering the cancer cells to become resistant to treatment. The novel concept relating several key survival and invasion signaling pathways to stem cell niches and treatment resistance will be reviewed. Lastly, we will provide an update of several recently developed novel drug candidates that target metastatic cancer microenvironments or niches, and discuss the advantages and significance provided by such therapeutic approaches in pursuit of overcoming drug resistance and treating advanced PCa. PMID:22746994

  6. Increased Expression of Serglycin in Specific Carcinomas and Aggressive Cancer Cell Lines

    PubMed Central

    Korpetinou, Angeliki; Papachristou, Dionysios J.; Lampropoulou, Angeliki; Bouris, Panagiotis; Labropoulou, Vassiliki T.; Noulas, Argyrios; Karamanos, Nikos K.; Theocharis, Achilleas D.

    2015-01-01

    In the present pilot study, we examined the presence of serglycin in lung, breast, prostate, and colon cancer and evaluated its expression in cell lines and tissues. We found that serglycin was expressed and constitutively secreted in culture medium in high levels in more aggressive cancer cells. It is worth noticing that aggressive cancer cells that harbor KRAS or EGFR mutations secreted serglycin constitutively in elevated levels. Furthermore, we detected the transcription of an alternative splice variant of serglycin lacking exon 2 in specific cell lines. In a limited number of tissue samples analyzed, serglycin was detected in normal epithelium but was also expressed in higher levels in advanced grade tumors as shown by immunohistochemistry. Serglycin staining was diffuse, granular, and mainly cytoplasmic. In some cancer cells serglycin also exhibited membrane and/or nuclear immunolocalization. Interestingly, the stromal cells of the reactive tumor stroma were positive for serglycin, suggesting an enhanced biosynthesis for this proteoglycan in activated tumor microenvironment. Our study investigated for first time the distribution of serglycin in normal epithelial and cancerous lesions in most common cancer types. The elevated levels of serglycin in aggressive cancer and stromal cells may suggest a key role for serglycin in disease progression. PMID:26581653

  7. Stroma–epithelium crosstalk in prostate cancer

    PubMed Central

    Niu, Yi-Nong; Xia, Shu-Jie

    2009-01-01

    The critical role played by stroma–epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized. These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells. In human prostate cancer, reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis. Permanent genetic mutations have been reported in stromal cells as well as in tumour cells. Transforming growth factor-β, vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis, whereas hepatocyte growth factor, insulin-like growth factor-1, epidermal growth factor, CXC12 and Interleukin-6 play active roles in the progression, androgen-independent conversion and distal metastasis of prostate cancer. Some soluble factors have reciprocal interactions with androgens and the androgen receptor (AR), and can even activate AR in the absence of the androgen ligand. In this article, we review the complex interactions between cancer cells and the surrounding microenvironment, and discuss the potential therapeutic targets in the stromal compartment of prostate cancer. PMID:19098934

  8. Changing trends of prostate cancer in Asia.

    PubMed

    Pu, Y S; Chiang, H S; Lin, C C; Huang, C Y; Huang, K H; Chen, J

    2004-06-01

    Although Asian people have the lowest incidence and mortality rates of prostate cancer in the world, these rates have risen rapidly in the past two decades in most Asian countries. Prostate cancer has become one of the leading male cancers in some Asian countries. In 2000, the age-adjusted incidence was over 10 per 100000 men in Japan, Taiwan, Singapore, Malaysia, the Philippines and Israel. Although some of the increases may result from enhanced detection, much of the increased incidence may be associated with westernization of the lifestyle, with increasing obesity and increased consumption of fat. The differences in incidences between native Americans and Asian immigrants are getting smaller, reflecting a possible improvement of diagnostic efforts and changes of environmental risk factors in Asian immigrants. Nevertheless, the huge variations in incidences among ethnic groups imply that there are important genetic risk factors. The stage distributions of prostate cancer in Asian populations are still unfavorable compared to those of Western developed countries. However, a trend towards diagnosing cancer with more favorable prognosis is seen in most Asian countries. Both genetic and environmental risk factors responsible for elevated risks in Asian people are being identified, which may help to reduce prostate cancer incidence in a chemopreventive setting. PMID:15672937

  9. Do evolutionary life-history trade-offs influence prostate cancer risk? a review of population variation in testosterone levels and prostate cancer disparities

    PubMed Central

    Alvarado, Louis Calistro

    2013-01-01

    An accumulation of evidence suggests that increased exposure to androgens is associated with prostate cancer risk. The unrestricted energy budget that is typical of Western diets represents a novel departure from the conditions in which men's steroid physiology evolved and is capable of supporting distinctly elevated testosterone levels. Although nutritional constraints likely underlie divergent patterns of testosterone secretion between Westernized and non-Western men, considerable variability exists in men's testosterone levels and prostate cancer rates within Westernized populations. Here, I use evolutionary life history theory as a framework to examine prostate cancer risk. Life history theory posits trade-offs between investment in early reproduction and long-term survival. One corollary of life history theory is the ‘challenge hypothesis’, which predicts that males augment testosterone levels in response to intrasexual competition occurring within reproductive contexts. Understanding men's evolved steroid physiology may contribute toward understanding susceptibility to prostate cancer. Among well-nourished populations of Westerners, men's testosterone levels already represent an outlier of cross-cultural variation. I hypothesize that Westernized men in aggressive social environments, characterized by intense male–male competition, will further augment testosterone production aggravating prostate cancer risk. PMID:23396824

  10. [Prostate-rectum spacers: optimization of prostate cancer irradiation].

    PubMed

    Zilli, T; Benz, E; Miralbell, R

    2014-06-01

    In the curative radiotherapy of localized prostate cancer, improvements in biochemical control observed with dose escalation have been counterbalanced by an increase in radiation-induced toxicity. The injection of biodegradable spacers between prostate and rectum represents a new frontier in the optimization of radiotherapy treatments for patients with localized disease. Transperineal injection of different types of spacers under transrectal ultrasound guidance allows creating a 7-to-20 mm additional space between the prostate and the anterior rectal wall lasting 3 to 12 months. Dosimetrically, a relative reduction in the rectal volume receiving at least 70 Gy (V70) in the order of 43% to 84% is observed with all types of spacers, regardless of the radiotherapy technique used. Preliminary clinical results show for all spacers a good tolerance and a possible reduction in the acute side effects rate. The aim of the present systematic review of the literature is to report on indications as well as dosimetric and clinical advantages of the different types of prostate-rectum spacers commercially available (hydrogel, hyaluronic acid, collagen, biodegradable balloon). PMID:24746454

  11. Diet, Supplement Use, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

    PubMed Central

    Kristal, Alan R.; Arnold, Kathryn B.; Neuhouser, Marian L.; Goodman, Phyllis; Platz, Elizabeth A.; Albanes, Demetrius; Thompson, Ian M.

    2010-01-01

    The authors examined nutritional risk factors for prostate cancer among 9,559 participants in the Prostate Cancer Prevention Trial (United States and Canada, 1994–2003). The presence or absence of cancer was determined by prostate biopsy, which was recommended during the trial because of an elevated prostate-specific antigen level or an abnormal digital rectal examination and was offered to all men at the trial's end. Nutrient intake was assessed using a food frequency questionnaire and a structured supplement-use questionnaire. Cancer was detected in 1,703 men; 127 cancers were high-grade (Gleason score 8–10). There were no associations of any nutrient or supplement with prostate cancer risk overall. Risk of high-grade cancer was associated with high intake of polyunsaturated fats (quartile 4 vs. quartile 1: odds ratio = 2.41, 95% confidence interval (CI): 1.33, 4.38). Dietary calcium was positively associated with low-grade cancer but inversely associated with high-grade cancer (for quartile 4 vs. quartile 1, odds ratios were 1.27 (95% CI: 1.02, 1.57) and 0.43 (95% CI: 0.21, 0.89), respectively). Neither dietary nor supplemental intakes of nutrients often suggested for prostate cancer prevention, including lycopene, long-chain n-3 fatty acids, vitamin D, vitamin E, and selenium, were significantly associated with cancer risk. High intake of n-6 fatty acids, through their effects on inflammation and oxidative stress, may increase prostate cancer risk. PMID:20693267

  12. The expanding landscape of diffusion-weighted MRI in prostate cancer.

    PubMed

    Wibmer, Andreas G; Sala, Evis; Hricak, Hedvig; Vargas, Hebert Alberto

    2016-05-01

    The added value of diffusion-weighted magnetic resonance imaging (DW-MRI) for the detection, localization, and staging of primary prostate cancer has been extensively reported in original studies and meta-analyses. More recently, DW-MRI and related techniques have been used to noninvasively assess prostate cancer aggressiveness and estimate its biological behavior. The present article aims to summarize the potential applications of DW-MRI for noninvasive optimization of pretherapeutic risk assessment, patient management decisions, and evaluation of treatment response. PMID:26814501

  13. MMP inhibition in prostate cancer.

    PubMed

    Lokeshwar, B L

    1999-06-30

    Matrix metalloproteinases (MMPs) play a significant role during the development and metastasis of prostate cancer (CaP). CaP cells secrete high levels of MMPs and low levels of endogenous MMP inhibitors (TIMPs), thus creating an excess balance of MMPs. Established CaP cell lines that express high levels of MMPs frequently metastasize to the bone and the lungs. Drugs such as Taxol and alendronate that reduce cell motility and calcium metabolism reduce bony metastasis of xenografted CaP tumors. We tested several synthetic, nontoxic inhibitors of MMPs that can be administered orally, including doxycycline (DC) and chemically modified tetracyclines (CMTs) on CaP cells in vitro and on a rat CaP model in vivo. Among several anti-MMP agents tested, CMT-3 (6-deoxy, 6-demethyl,4-de-dimethylamino tetracycline) showed highest activity against CaP cell invasion and cell proliferation. Micromolar concentration of CMT-3 and DC inhibited both the secretion and activity of MMPs by CaP cells. When tested for in vivo efficacy in the Dunning rat CaP model by daily oral gavage, CMT-3 and DC both reduced the lung metastases (> 50%). CMT-3, but not DC, inhibited tumor incidence (55 +/- 9%) and also reduced the tumor growth rate (27 +/- 9.3%). More significantly, the drugs showed minimum systemic toxicity. Ongoing studies indicate that CMT-3 may inhibit the skeletal metastases of CaP cells and delay the onset of paraplegia due to lumbar metastases. These preclinical studies provide the basis for clinical trials of CMT-3 for the treatment of metastatic disease. PMID:10415736

  14. Reduction in the risk of prostate cancer: future directions after the Prostate Cancer Prevention Trial.

    PubMed

    Crawford, E David; Andriole, Gerald L; Marberger, Michael; Rittmaster, Roger S

    2010-03-01

    The landmark Prostate Cancer Prevention Trial (PCPT) generated interest in the potential health benefits and cost of reducing prostate cancer risk--specifically, the potential role of 5alpha-reductase inhibitors. However, the PCPT raised several unanswered questions, including the cause and significance of the increased incidence of high-grade tumors associated with finasteride. In the present study, we review the PCPT findings and unanswered questions, next steps in this field, and ongoing prostate cancer prevention trials addressing these unanswered questions. Particular emphasis is placed on the design of the second large-scale trial of a 5alpha-reductase inhibitor, the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. PMID:20035983

  15. [Prostate cancer external beam radiotherapy].

    PubMed

    de Crevoisier, R; Pommier, P; Latorzeff, I; Chapet, O; Chauvet, B; Hennequin, C

    2016-09-01

    The prostate external beam radiotherapy techniques are described, when irradiating the prostate or after prostatectomy, with and without pelvic lymph nodes. The following parts are presented: indications of radiotherapy, total dose and fractionation, planning CT image acquisition, volume of interest delineation (target volumes and organs at risk) and margins, Intensity modulated radiotherapy planning and corresponding dose-volume constraints, and finally Image guided radiotherapy. PMID:27516051

  16. Automatic computer-aided detection of prostate cancer based on multiparametric magnetic resonance image analysis

    NASA Astrophysics Data System (ADS)

    Vos, P. C.; Barentsz, J. O.; Karssemeijer, N.; Huisman, H. J.

    2012-03-01

    In this paper, a fully automatic computer-aided detection (CAD) method is proposed for the detection of prostate cancer. The CAD method consists of multiple sequential steps in order to detect locations that are suspicious for prostate cancer. In the initial stage, a voxel classification is performed using a Hessian-based blob detection algorithm at multiple scales on an apparent diffusion coefficient map. Next, a parametric multi-object segmentation method is applied and the resulting segmentation is used as a mask to restrict the candidate detection to the prostate. The remaining candidates are characterized by performing histogram analysis on multiparametric MR images. The resulting feature set is summarized into a malignancy likelihood by a supervised classifier in a two-stage classification approach. The detection performance for prostate cancer was tested on a screening population of 200 consecutive patients and evaluated using the free response operating characteristic methodology. The results show that the CAD method obtained sensitivities of 0.41, 0.65 and 0.74 at false positive (FP) levels of 1, 3 and 5 per patient, respectively. In conclusion, this study showed that it is feasible to automatically detect prostate cancer at a FP rate lower than systematic biopsy. The CAD method may assist the radiologist to detect prostate cancer locations and could potentially guide biopsy towards the most aggressive part of the tumour.

  17. Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer.

    PubMed

    Wen, Simeng; Chang, Hong-Chiang; Tian, Jing; Shang, Zhiqun; Niu, Yuanjie; Chang, Chawnshang

    2015-02-01

    The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa, much more attention has been focused on epithelial AR roles. However, accumulating evidence indicates that stromal AR is also irreplaceable and plays critical roles in prostate disease progression. Herein, we summarize the roles of stromal AR in the development of normal prostate, BPH, and PCa, with evidence from the recent results of in vitro cell line studies, tissue recombination experiments, and AR knockout animal models. Current evidence suggests that stromal AR may play positive roles to promote BPH and PCa progression, and targeting stromal AR selectively with AR degradation enhancer, ASC-J9, may allow development of better therapies with fewer adverse effects to battle BPH and PCa. PMID:25432062

  18. Stromal Androgen Receptor Roles in the Development of Normal Prostate, Benign Prostate Hyperplasia, and Prostate Cancer

    PubMed Central

    Wen, Simeng; Chang, Hong-Chiang; Tian, Jing; Shang, Zhiqun; Niu, Yuanjie; Chang, Chawnshang

    2016-01-01

    The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa, much more attention has been focused on epithelial AR roles. However, accumulating evidence indicates that stromal AR is also irreplaceable and plays critical roles in prostate disease progression. Herein, we summarize the roles of stromal AR in the development of normal prostate, BPH, and PCa, with evidence from the recent results of in vitro cell line studies, tissue recombination experiments, and AR knockout animal models. Current evidence suggests that stromal AR may play positive roles to promote BPH and PCa progression, and targeting stromal AR selectively with AR degradation enhancer, ASC-J9, may allow development of better therapies with fewer adverse effects to battle BPH and PCa. PMID:25432062

  19. [Recent advances in diagnosis of prostate cancer].

    PubMed

    Hara, Isao

    2016-01-01

    Most valuable tool for diagnosis of prostate cancer is PSA. Although PSA is highly specific for organ, it is not so specific for disease. Therefore, about 70% of patients whose PSA value is 4-10 ng/mL are forced to undergo unnecessary prostate biopsy. In order to discriminate the unnecessary biopsies, several markers such as free/total PSA ratio, PSA density, and PSA velocity have been developed. However, none of these markers were widely approved in daily clinical settings. Prostate cancer antigen 3 (PCA3) is thought to be a useful marker for necessity of repeat biopsy. Functional MR imaging such as dynamic contrast enhancement (DCE), diffusion weighted imaging(DWI), MR spectroscopy (MRS) have been developed. Recently MRI-TRUS fusion biopsy is gathering attention. In terms of pathology, atypical glands but not high grade PIN require repeat biopsy after 3 to 6 months from initial biopsy. PMID:26793874

  20. What's wrong with chemoprevention of prostate cancer?

    PubMed

    Justman, Stewart

    2011-12-01

    When prostate-specific antigen (PSA) testing was introduced, proponents expected it to cut prostate-cancer mortality and did not expect it to unleash an epidemic of unnecessary treatments. Now that evidence of a mortality benefit remains unclear while evidence of overtreatment in undeniable, there is understandable interest in reducing the human costs of the PSA system. Two related drugs, finasteride and dutasteride, both proven to reduce the incidence of prostate cancer and the "risk of diagnosis," are being promoted accordingly. However, if not for the flaws of the PSA system the use of these drugs for purposes of prevention would lose its rationale. Not only are the drugs in this sense dependent on a faulty system, but their own mortality benefits are as speculative as PSA's-in addition to which, they introduce new risks. PMID:22146025

  1. Benign Prostatic Hyperplasia and the Risk of Prostate Cancer and Bladder Cancer

    PubMed Central

    Dai, Xiaoyu; Fang, Xiangming; Ma, Ying; Xianyu, Jianbo

    2016-01-01

    Abstract Benign prostatic hyperplasia (BPH) has been suggested to be a risk factor for certain urologic cancers, but the current evidence is inconsistent. The aim of this study was to investigate the association between BPH and urologic cancers. MEDLINE, EMBASE, Cochrane Library, and Web of Science were searched for potential eligible studies. We included case-control studies or cohort studies, which evaluated the association between BPH and urologic cancers (including prostate cancer, bladder cancer, kidney cancer, testicular cancer, or penile cancer). Overall effect estimates were calculated using the DerSimonian–Laird method for a random-effects model. Summary effect-size was calculated as risk ratio (RR), together with the 95% confidence interval (CI). This systematic review included 16 case-control studies and 10 cohort studies evaluating the association of BPH and prostate or bladder cancer; we did not identify any study about other urologic cancers. Meta-analyses demonstrated that BPH was associated with an increased incidence of prostate cancer (case-control study: RR = 3.93, 95% CI = 2.18–7.08; cohort-study: RR = 1.41, 95% CI = 1.00–1.99) and bladder cancer (case-control study: RR = 2.50, 95% CI = 1.63–3.84; cohort-study: RR = 1.58, 95% CI = 1.28–1.95). Subgroup analysis by ethnicity suggested that the association between BPH and prostate cancer was much stronger in Asians (RR = 6.09, 95% CI = 2.96–12.54) than in Caucasians (RR = 1.54, 95% CI = 1.19–2.01). Egger's tests indicated low risk of publication bias (prostate cancer: P = 0.11; bladder cancer: P = 0.95). BPH is associated with an increased risk of prostate cancer and bladder cancer. The risk of prostate cancer is particularly high in Asian BPH patients. Given the limitations of included studies, additional prospective studies with strict design are needed to confirm our findings. PMID:27149447

  2. Intake of dietary antioxidants is inversely associated with biomarkers of oxidative stress among men with prostate cancer.

    PubMed

    Vance, Terrence M; Azabdaftari, Gissou; Pop, Elena A; Lee, Sang Gil; Su, L Joseph; Fontham, Elizabeth T H; Bensen, Jeannette T; Steck, Susan E; Arab, Lenore; Mohler, James L; Chen, Ming-Hui; Koo, Sung I; Chun, Ock K

    2016-01-14

    Prostate cancer is the most common non-cutaneous cancer and the second leading cause of cancer-related mortality among men in the USA. Growing evidence suggests that oxidative stress is involved in the development and progression of prostate cancer. In this study, the association between antioxidants from diet and supplements and biomarkers of oxidative stress in blood (n 278), urine (n 298) and prostate tissue (n 55) were determined among men from the North Carolina-Louisiana Prostate Cancer Project. The association between antioxidant intake and oxidative stress biomarkers in blood and urine was determined using linear regression, adjusting for age, race, prostate cancer aggressiveness and smoking status. Greater antioxidant intake was found to be associated with lower urinary 8-isoprostane concentrations, with a 10% increase in antioxidant intake corresponding to an unadjusted 1·1% decrease in urinary 8-isoprostane levels (95% CI -1·7, -0·3%; P value<0·01) and an adjusted 0·6% decrease (95% CI -1·4, 0·2%; P value=0·16). In benign prostate tissue, thioredoxin 1 was inversely associated with antioxidant intake (P=0·02). No significant associations were found for other blood or urinary biomarkers or for malignant prostate tissue. These results indicate that antioxidant intake may be associated with less oxidative stress among men diagnosed with prostate cancer. PMID:26521663

  3. The Prostate

    MedlinePlus

    ... Renal Cell) Cancer Leukemia Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ... Publications Reports What You Need To Know About™ Prostate Cancer This booklet is about prostate cancer. Learning about ...

  4. 4-Kallikrein Test and Kallikrein Markers in Prostate Cancer Screening.

    PubMed

    McDonald, Michelle L; Parsons, J Kellogg

    2016-02-01

    A preponderance of clinical evidence supports a significant public health benefit for prostate-specific antigen (PSA)-based screening and early detection of prostate cancer in appropriately counseled and selected men. Population-based screening with PSA decreases prostate cancer mortality; however, because of relatively poor specificity, PSA-based screening may also increase the detection of clinically insignificant cancers that would otherwise never require treatment. Use of newer biomarkers that increase the specificity for prostate cancer detection may aid in risk stratification and the appropriate identification of men for prostate biopsy. The authors review the 4-kallikrein panel and 4K probability score. PMID:26614027

  5. NOTCH3 IS ACTIVATED BY CHRONIC HYPOXIA AND CONTRIBUTES TO THE PROGRESSION OF HUMAN PROSTATE CANCER

    PubMed Central

    Danza, Giovanna; Di Serio, Claudia; Ambrosio, Maria Raffaella; Sturli, Niccolò; Lonetto, Giuseppe; Rosati, Fabiana; Rocca, Bruno Jim; Ventimiglia, Giuseppina; del Vecchio, Maria Teresa; Prudovsky, Igor; Marchionni, Niccolò; Tarantini, Francesca

    2013-01-01

    Prostate cancer is still the second cause of cancer-related death among men. Although patients with metastatic presentation have an ominous outcome, the vast majority of PCs are diagnosed at an early stage. Nonetheless, even among patients with clinically localized disease the outcome may vary considerably. Other than androgen sensitivity, little is known about which other signaling pathways are deranged in aggressive, localized cancers. The elucidation of such pathways may help to develop innovative therapies aimed at specific molecular targets. We report that in a hormone-sensitive prostate cancer cell line, LNCaP, Notch3 was activated by hypoxia and sustained cell proliferation and colony formation in soft agar. Hypoxia also modulated cellular cholesterol content and the number and size of lipid rafts, causing a coalescence of small rafts into bigger clusters; under this experimental condition Notch3 migrated from the non-raft into the raft compartment where it co-localized with the γ-secretase complex. We also looked at human prostate cancer biopsies and found that expression of Notch3 positively correlated with Gleason score and with expression of carbonic anhydrase IX, a marker of hypoxia. In conclusion, hypoxia triggers the activation of Notch3 which, in turn, sustains proliferation of prostate cancer cells. Notch3 pathway represents a promising target for adjuvant therapy in patients with prostate cancer. PMID:23729168

  6. Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling

    PubMed Central

    DU, YUEFENG; LONG, QINGZHI; ZHANG, LIN; SHI, YING; LIU, XIOAGANG; LI, XUDONG; GUAN, BIN; TIAN, YANCHAO; WANG, XINYANG; LI, LEI; HE, DALIN

    2015-01-01

    Cancer-associated fibroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial to mesenchymal transition (EMT) in tumor cells and their achievement of stem cell traits. Curcumin has recently been found to possess anticancer activities via its effect on a variety of biological pathways involved in cancer progression. In this study, we found that CAFs could induce prostate cancer cell EMT and invasion through a monoamine oxidase A (MAOA)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway, which exploits reactive oxygen species (ROS) to drive a migratory and aggressive phenotype of prostate carcinoma cells. Moreover, CAFs was able to increase CXC chemokine receptor 4 (CXCR4) and interleukin-6 (IL-6) receptor expression in prostate cancer cells. However, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells through inhibiting MAOA/mTOR/HIF-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer. PMID:26499200

  7. Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling.

    PubMed

    Du, Yuefeng; Long, Qingzhi; Zhang, Lin; Shi, Ying; Liu, Xioagang; Li, Xudong; Guan, Bin; Tian, Yanchao; Wang, Xinyang; Li, Lei; He, Dalin

    2015-12-01

    Cancer-associated fibroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial to mesenchymal transition (EMT) in tumor cells and their achievement of stem cell traits. Curcumin has recently been found to possess anticancer activities via its effect on a variety of biological pathways involved in cancer progression. In this study, we found that CAFs could induce prostate cancer cell EMT and invasion through a monoamine oxidase A (MAOA)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway, which exploits reactive oxygen species (ROS) to drive a migratory and aggressive phenotype of prostate carcinoma cells. Moreover, CAFs was able to increase CXC chemokine receptor 4 (CXCR4) and interleukin-6 (IL-6) receptor expression in prostate cancer cells. However, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells through inhibiting MAOA/mTOR/HIF-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer. PMID:26499200

  8. Hypofractionated Radiotherapy for Favorable Risk Prostate Cancer

    SciTech Connect

    Rene, Nicholas; Faria, Sergio; Cury, Fabio; David, Marc; Duclos, Marie; Shenouda, George; Souhami, Luis

    2010-07-01

    Purpose: Since the recognition that prostate cancer probably has a low {alpha}/{beta} ratio, hypofractionated radiotherapy has become an attractive treatment option for localized prostate cancer. However, there is little experience with the use of hypofractionation delivering a high biologically equivalent dose. We report our experience with high-dose hypofractionated radiotherapy. Material and Methods: A total of 129 patients with favorable risk prostate cancer were treated with three-dimensional conformal radiotherapy treatment plans to the dose of 66 Gy in 22 fractions, prescribed at the isocenter. Planning target volume consisted of the prostate plus a uniform 7-mm margin, including the rectal margin. No patient received hormonal therapy. Toxicity was prospectively graded by the Common Toxicity Criteria version3. Biochemical relapse was defined as postradiotherapy nadir prostate-specific antigen + 2 ng/mL. Results: With a median follow-up of 51 months, the 5-year actuarial biochemical control rate is 98%. The only 3 cases with biochemical failure did not have a clinical local relapse. More than 50% of patients did not develop acute toxicity. For late toxicity, the worst crude rate of Grade {>=}2 genitourinary (GU) and gastrointestinal (GI) toxicity seen at any time during follow-up were 32% and 25%, respectively. There was no Grade 4 or 5 toxicity. At the last follow-up, persistent Grade {>=}2 late GU and GI toxicity were 2% and 1.5%, respectively. Conclusions: This hypofractionated regimen provides excellent biochemical control in favorable risk prostate cancer with an acceptable rate of late toxicity. Further studies exploring this hypofractionation regimen are warranted.

  9. Magnetic resonance imaging for prostate cancer radiotherapy.

    PubMed

    Dinh, Cuong V; Steenbergen, Peter; Ghobadi, Ghazaleh; Heijmink, Stijn W T J P; Pos, Floris J; Haustermans, Karin; van der Heide, Uulke A

    2016-03-01

    For radiotherapy of prostate cancer, MRI is used increasingly for delineation of the prostate gland. For focal treatment of low-risk prostate cancer or focal dose escalation for intermediate and high-risk cancer, delineation of the tumor is also required. While multi-parametric MRI is well established for detection of tumors and for staging of the disease, delineation of the tumor inside the prostate is not common practice. Guidelines, such as the PI-RADS classification, exist for tumor detection and staging, but no such guidelines are available for tumor delineation. Indeed, interobserver studies show substantial variation in tumor contours. Computer-aided tumor detection and delineation may help improve the robustness of the interpretation of multi-parametric MRI data. Comparing the performance of an earlier developed model for tumor segmentation with expert delineations, we found a significant correlation between tumor probability in a voxel and the number of experts identifying this voxel as tumor. This suggests that the model agrees with 'the wisdom of the crowd', and thus could serve as a reference for individual physicians in their decision making. With multi-parametric MRI it becomes feasible to revisit the GTV-CTV concept in radiotherapy of prostate cancer. While detection of index lesions is quite reliable, contouring variability and the low sensitivity to small lesions suggest that the remainder of the prostate should be treated as CTV. Clinical trials that investigate the options for dose differentiation, for example with dose escalation to the visible tumor or dose reduction to the CTV, are therefore warranted. PMID:26858164

  10. Expression and Localization of Aquaporins in Benign Prostate Hyperplasia and Prostate Cancer

    PubMed Central

    Hwang, Insang; Hwang, Eu-Chang; Song, Seung Hee; Lee, Hyun-Suk; Kim, Sun-Ouck; Kang, Taek-Won; Kwon, Dongdeuk; Park, Kwangsung

    2012-01-01

    The aquaporin (AQP) families of water channels are intrinsic membrane proteins that facilitate selective water and small solute movement across the plasma membrane. The purposes of this study were to determine the expression and localization of AQPs in benign prostatic hyperplasia and prostate cancer. Prostatic tissue was collected from patients with benign prostatic hyperplasia or prostate cancer by transurethral resection of the prostate. The expression and cellular localization of the AQPs were determined in the human prostate by Western blot and immunohistochemistry. AQP1, 3, and 9 were expressed in the human prostate. Western blot analysis revealed bands at 28-36 kDa for the AQP1, 3, and 9 proteins. Of these proteins, AQP3 and 9 were expressed in the epithelium. Immunolabeling showed that AQP1 was mainly expressed in the capillaries and venules of the prostate, AQP9 was expressed in the cytoplasm of the epithelium, and AQP3 was mainly associated with the plasma membrane of the prostatic epithelium. Only AQP3 expression was localized in the cell membrane, and expressed AQP3 was translocated to the cytoplasm in prostate cancer. The epithelium in the human prostate expresses AQP3 and 9 proteins, and the capillaries and venules of the prostate express AQP1. Characterizing or modifying the expression of AQP3 may lead to an understanding of the role of the AQPs in human prostatic disease. PMID:23323224

  11. Dietary Lycopene, Angiogenesis, and Prostate Cancer: A Prospective Study in the Prostate-Specific Antigen Era

    PubMed Central

    2014-01-01

    Background The role of lycopene in prostate cancer prevention remains controversial. We examined the associations between dietary lycopene intake and prostate cancer, paying particular attention to the influence of prostate-specific antigen screening, and evaluated tissue biomarkers in prostate cancers in relation to lycopene intake. Methods Among 49898 male health professionals, we obtained dietary information through questionnaires and ascertained total and lethal prostate cancer cases from 1986 through January 31, 2010. Cox regression was used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). Tissue microarrays and immunohistochemistry were used to assess tumor biomarker expression in a subset of men. Two-sided χ2 tests were used to calculate the P values. Results Higher lycopene intake was inversely associated with total prostate cancer and more strongly with lethal prostate cancer (top vs bottom quintile: HR = 0.72; 95% CI = 0.56 to 0.94; P trend = .04). In a restricted population of screened participants, the inverse associations became markedly stronger (for lethal prostate cancer: HR = 0.47; 95% CI = 0.29 to 0.75; P trend = .009). Comparing different measures of dietary lycopene, early intake, but not recent intake, was inversely associated with prostate cancer. Higher lycopene intake was associated with biomarkers in the cancer indicative of less angiogenic potential. Conclusions Dietary intake of lycopene was associated with reduced risk of lethal prostate cancer and with a lesser degree of angiogenesis in the tumor. Because angiogenesis is a strong progression factor, an endpoint of lethal prostate cancer may be more relevant than an endpoint of indolent prostate cancer for lycopene in the era of highly prevalent prostate-specific antigen screening. PMID:24463248

  12. Targeting Aggressive Cancer Stem Cells in Glioblastoma

    PubMed Central

    Seymour, Tracy; Nowak, Anna; Kakulas, Foteini

    2015-01-01

    Glioblastoma (GBM) is the most common and fatal type of primary brain tumor. Gliosarcoma (GSM) is a rarer and more aggressive variant of GBM that has recently been considered a potentially different disease. Current clinical treatment for both GBM and GSM includes maximal surgical resection followed by post-operative radiotherapy and concomitant and adjuvant chemotherapy. Despite recent advances in treating other solid tumors, treatment for GBM and GSM still remains palliative, with a very poor prognosis and a median survival rate of 12–15 months. Treatment failure is a result of a number of causes, including resistance to radiotherapy and chemotherapy. Recent research has applied the cancer stem cells theory of carcinogenesis to these tumors, suggesting the existence of a small subpopulation of glioma stem-like cells (GSCs) within these tumors. GSCs are thought to contribute to tumor progression, treatment resistance, and tumor recapitulation post-treatment and have become the focus of novel therapy strategies. Their isolation and investigation suggest that GSCs share critical signaling pathways with normal embryonic and somatic stem cells, but with distinct alterations. Research must focus on identifying these variations as they may present novel therapeutic targets. Targeting pluripotency transcription factors, SOX2, OCT4, and Nanog homeobox, demonstrates promising therapeutic potential that if applied in isolation or together with current treatments may improve overall survival, reduce tumor relapse, and achieve a cure for these patients. PMID:26258069

  13. PSA Velocity Does Not Improve Prostate Cancer Detection

    Cancer.gov

    A rapid increase in prostate-specific antigen (PSA) levels is not grounds for automatically recommending a prostate biopsy, according to a study published online February 24, 2011, in the Journal of the National Cancer Institute.

  14. Metastatic Sites Predict Prostate Cancer Survival.

    PubMed

    2016-05-01

    A new meta-analysis of clinical trial data from patients with metastatic castration-resistant prostate cancer indicates that overall survival is strongly influenced by where the disease spreads. Men with visceral disease-liver or lung metastases-fare worse than those with bone or lymph node involvement. PMID:27001152

  15. [Primary prevention of urologic tumors: prostate cancer].

    PubMed

    Schmitz-Dräger, B J; Lümmen, G; Bismarck, E; Fischer, C

    2011-10-01

    Assessment of the role of vitamins and micronutrients in the primary prevention of prostate cancer has changed dramatically in the past 10 years. Efforts to confirm the efficacy of a single substance have not yet succeeded. Therefore, such recommendations should at present no longer be given. Consideration could even be given to discussing whether additional large-scale interventional studies are expedient in this regard. There is still solid evidence that a well-balanced moderate diet, reduced consumption of milk products, and an Asian or Mediterranean diet are not only beneficial for general good health but can also prevent the development of prostate cancer. This should be the focus of further epidemiological studies. Thus, one can certainly speak of a paradigm shift in the prevention of prostate cancer. In contrast, available data on chemoprevention with 5α-reductase inhibitors is unequivocal: intake of finasteride as well as dutasteride correlates with significantly decreased evidence for prostate cancer. Converting this result into urologic practice remains the topic of extensive controversy. PMID:21927877

  16. The Molecular Taxonomy of Primary Prostate Cancer.

    PubMed

    2015-11-01

    There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects. PMID:26544944

  17. New genetic variants associated with prostate cancer

    Cancer.gov

    Researchers have newly identified 23 common genetic variants -- one-letter changes in DNA known as single-nucleotide polymorphisms or SNPs -- that are associated with risk of prostate cancer. These results come from an analysis of more than 10 million SNP

  18. 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

  19. Altered Endosome Biogenesis in Prostate Cancer has Biomarker Potential

    PubMed Central

    Johnson, Ian R D; Parkinson-Lawrence, Emma J; Shandala, Tetyana; Weigert, Roberto; Butler, Lisa M; Brooks, Doug A

    2016-01-01

    Prostate cancer is the second most common form of cancer in males, affecting one in eight men by the time they reach the age of 70. Current diagnostic tests for prostate cancer have significant problems with both false negatives and false positives, necessitating the search for new molecular markers. A recent investigation of endosomal and lysosomal proteins revealed that the critical process of endosomal biogenesis might be altered in prostate cancer. Here, a panel of endosomal markers was evaluated in prostate cancer and non-malignant cells and a significant increase in gene and protein expression was found for early, but not late endosomal proteins. There was also a differential distribution of early endosomes, and altered endosomal traffic and signalling of the transferrin receptors (TFRC and TFR2) in prostate cancer cells. These findings support the concept that endosome biogenesis and function is altered in prostate cancer. Microarray analysis of a clinical cohort confirmed the altered endosomal gene expression observed in cultured prostate cancer cells. Furthermore, in prostate cancer patient tissue specimens, the early endosomal marker and adaptor protein APPL1 showed consistently altered basement membrane histology in the vicinity of tumours and concentrated staining within tumour masses. These novel observations on altered early endosome biogenesis provide a new avenue for prostate cancer biomarker investigation and suggest new methods for the early diagnosis and accurate prognosis of prostate cancer. PMID:25080433

  20. Researchers Find 8 Immune Genes in Aggressive Brain Cancer

    MedlinePlus

    ... news/fullstory_159031.html Researchers Find 8 Immune Genes in Aggressive Brain Cancer Discovery might eventually lead ... 25, 2016 (HealthDay News) -- Researchers have identified immune genes that may affect how long people live after ...

  1. MicroRNA expression and function in prostate cancer: a review of current knowledge and opportunities for discovery

    PubMed Central

    Kumar, Binod; Lupold, Shawn E

    2016-01-01

    MicroRNAs (miRNAs) are well-conserved noncoding RNAs that broadly regulate gene expression through posttranscriptional silencing of coding genes. Dysregulated miRNA expression in prostate and other cancers implicates their role in cancer biology. Moreover, functional studies provide support for the contribution of miRNAs to several key pathways in cancer initiation and progression. Comparative analyses of miRNA gene expression between malignant and nonmalignant prostate tissues, healthy controls and prostate cancer (PCa) patients, as well as less aggressive versus more aggressive disease indicate that miRNAs may be future diagnostic or prognostic biomarkers in tumor tissue, blood, or urine. Further, miRNAs may be future therapeutics or therapeutic targets. In this review, we examine the miRNAs most commonly observed to be de-regulated in PCa gene expression analyses and review the potential contribution of these miRNAs to important pathways in PCa initiation and progression. PMID:27056344

  2. MicroRNA expression and function in prostate cancer: a review of current knowledge and opportunities for discovery.

    PubMed

    Kumar, Binod; Lupold, Shawn E

    2016-01-01

    MicroRNAs (miRNAs) are well-conserved noncoding RNAs that broadly regulate gene expression through posttranscriptional silencing of coding genes. Dysregulated miRNA expression in prostate and other cancers implicates their role in cancer biology. Moreover, functional studies provide support for the contribution of miRNAs to several key pathways in cancer initiation and progression. Comparative analyses of miRNA gene expression between malignant and nonmalignant prostate tissues, healthy controls and prostate cancer (PCa) patients, as well as less aggressive versus more aggressive disease indicate that miRNAs may be future diagnostic or prognostic biomarkers in tumor tissue, blood, or urine. Further, miRNAs may be future therapeutics or therapeutic targets. In this review, we examine the miRNAs most commonly observed to be de-regulated in PCa gene expression analyses and review the potential contribution of these miRNAs to important pathways in PCa initiation and progression. PMID:27056344

  3. Olaparib Targets Some Advanced Prostate Cancers.

    PubMed

    2016-01-01

    In the phase II TOPARP-A clinical trial, patients with metastatic castrate-resistant prostate cancer who were treated with the PARP inhibitor olaparib lived nearly three times longer without their cancer worsening if their tumors had mutations in at least one of 12 DNA repair genes. However, physicians say that a larger trial is needed to confirm olaparib's effectiveness against the disease before they start routinely sequencing tumors and prescribing the drug. PMID:26658963

  4. Radical treatment of localised prostate cancer in the elderly.

    PubMed

    Everaerts, Wouter; Van Rij, Simon; Reeves, Fairleigh; Costello, Anthony

    2015-12-01

    Elderly men are more likely to be diagnosed with aggressive cancer, but are often inappropriately denied curative treatment. Biological rather than chronological age should be used to decide if a patient will profit from radical treatment. Therefore, every man aged >70 years should undergo a health assessment using a validated tool before making treatment decisions. Fit elderly men with intermediate- or high-risk disease should be offered standard curative local treatment in keeping with guidelines for younger men. Vulnerable and frail elderly men warrant geriatric intervention before treatment. In the case of vulnerable patients, this intervention may render them suitable for standard care. When considering radical prostatectomy outcomes a 'bifecta' of oncological control and continence is appropriate, as erectile dysfunction (although prevalent) has a much smaller impact on quality of life than in younger patients. Radiotherapy is an alternative to radical prostatectomy in men with a life expectancy of <10 years. Primary androgen-deprivation therapy is not associated with improved survival in localised prostate cancer and should only be used for symptom palliation. Further elderly-specific research is needed to guide prostate cancer care. PMID:25810141

  5. Evolving Paradigm of Radiotherapy for High-Risk Prostate Cancer: Current Consensus and Continuing Controversies

    PubMed Central

    Juloori, Aditya; Shah, Chirag; Stephans, Kevin; Vassil, Andrew; Tendulkar, Rahul

    2016-01-01

    High-risk prostate cancer is an aggressive form of the disease with an increased risk of distant metastasis and subsequent mortality. Multiple randomized trials have established that the combination of radiation therapy and long-term androgen deprivation therapy improves overall survival compared to either treatment alone. Standard of care for men with high-risk prostate cancer in the modern setting is dose-escalated radiotherapy along with 2-3 years of androgen deprivation therapy (ADT). There are research efforts directed towards assessing the efficacy of shorter ADT duration. Current research has been focused on assessing hypofractionated and stereotactic body radiation therapy (SBRT) techniques. Ongoing randomized trials will help assess the utility of pelvic lymph node irradiation. Research is also focused on multimodality therapy with addition of a brachytherapy boost to external beam radiation to help improve outcomes in men with high-risk prostate cancer. PMID:27313896

  6. [Epidemiological situation of prostate cancer in Spain].

    PubMed

    Granado de la Orden, S; Saá Requejo, C; Quintás Viqueira, A

    2006-06-01

    Prostate cancer is the third most frequent neoplasms in Spanish men and the third cause of cancer death. Incidence grows up with the increase of age. 90% of cases are diagnostic in people over 65 years old. Etiology is quite unknown and has been associated with environmental exposure, life style, family sign and genetic factors. In 2002 mortality rate was 21.5/ 100.000 (situated among the lowest in Europe), with more than 5.000 deaths. Trend of mortality has grown up until 1998, from this year it has decreased due to improve on diagnostic and treatment. In order to study prostate cancer incidence we find a difficulty due to shortage of population cancer register. Estimations have found incidence rates of 45.33/100.000 which are among the lowest in Europe. Annual incidence of prostatic cancer has grown up in all Spanish registers, not only improve in register systems explains it, but also the development of diagnosis tests with a higher survival from the beginning of 90s (86% the first year after diagnosis and 65,5% five years after diagnosis), similar to other European countries. Blow up the cancer register system is necessary to know the incidence and prevalence, to assess survival and effectiveness of screening programs and to improve the knowledge of risk factors. PMID:16921834

  7. The essential role of methylthioadenosine phosphorylase in prostate cancer

    PubMed Central

    Foster, Barbara A.; Karasik, Ellen; Gillard, Bryan; Morrison, Carl; Mohler, James; Phillips, James G.; Smiraglia, Dominic J.

    2016-01-01

    Prostatic epithelial cells secrete high levels of acetylated polyamines into the prostatic lumen. This distinctive characteristic places added strain on the connected pathways, which are forced to increase metabolite production to maintain pools. The methionine salvage pathway recycles the one-carbon unit lost to polyamine biosynthesis back to the methionine cycle, allowing for replenishment of SAM pools providing a mechanism to help mitigate metabolic stress associated with high flux through these pathways. The rate-limiting enzyme involved in this process is methylthioadenosine phosphorylase (MTAP), which, although commonly deleted in many cancers, is protected in prostate cancer. We report near universal retention of MTAP expression in a panel of human prostate cancer cell lines as well as patient samples. Upon metabolic perturbation, prostate cancer cell lines upregulate MTAP and this correlates with recovery of SAM levels. Furthermore, in a mouse model of prostate cancer we find that both normal prostate and diseased prostate maintain higher SAM levels than other tissues, even under increased metabolic stress. Finally, we show that knockdown of MTAP, both genetically and pharmacologically, blocks androgen sensitive prostate cancer growth in vivo. Our findings strongly suggest that the methionine salvage pathway is a major player in homeostatic regulation of metabolite pools in prostate cancer due to their high level of flux through the polyamine biosynthetic pathway. Therefore, this pathway, and specifically the MTAP enzyme, is an attractive therapeutic target for prostate cancer. PMID:26910893

  8. A Molecular Signature Predictive of Indolent Prostate Cancer

    PubMed Central

    Irshad, Shazia; Bansal, Mukesh; Castillo-Martin, Mireia; Zheng, Tian; Aytes, Alvaro; Wenske, Sven; Le Magnen, Clémentine; Guarnieri, Paolo; Sumazin, Pavel; Benson, Mitchell C.; Shen, Michael M.; Califano, Andrea; Abate-Shen, Cory

    2014-01-01

    Many newly diagnosed prostate cancers present as low Gleason score tumors that require no treatment intervention. Distinguishing the many indolent tumors from the minority of lethal ones remains a major clinical challenge. We now show that low Gleason score prostate tumors can be distinguished as indolent and aggressive subgroups on the basis of their expression of genes associated with aging and senescence. Using gene set enrichment analysis, we identified a 19-gene signature enriched in indolent prostate tumors. We then further classified this signature with a decision tree learning model to identify three genes—FGFR1, PMP22, and CDKN1A—that together accurately predicted outcome of low Gleason score tumors. Validation of this three-gene panel on independent cohorts confirmed its independent prognostic value as well as its ability to improve prognosis with currently used clinical nomograms. Furthermore, protein expression of this three-gene panel in biopsy samples distinguished Gleason 6 patients who failed surveillance over a 10-year period. We propose that this signature may be incorporated into prognostic assays for monitoring patients on active surveillance to facilitate appropriate courses of treatment. PMID:24027026

  9. Defining young in the context of prostate cancer.

    PubMed

    Chambers, Suzanne K; Lowe, Anthony; Hyde, Melissa K; Zajdlewicz, Leah; Gardiner, Robert A; Sandoe, David; Dunn, Jeff

    2015-03-01

    The experience of prostate cancer is for most men a major life stress with the psychological burden of this disease falling more heavily on those who are younger. Despite this, being young as it applies to prostate cancer is not yet clearly defined with varied chronological approaches applied. However, men's responses to health crises are closely bound to life course and masculinities from which social roles emerge. This paper applied qualitative methodology (structured focus groups and semistructured interviews with expert informants) using interpretative phenomenological analysis to define what it means to be young and have prostate cancer. Structured focus groups were held with 26 consumer advisors (men diagnosed with prostate cancer who provide support to other men with prostate cancer or raise community awareness) and health professionals. As well, 15 men diagnosed with prostate cancer and in their 40s, 50s, or 60s participated in semi-structured interviews. Participants discussed the attributes that describe a young man with prostate cancer and the experience of being young and diagnosed with prostate cancer. Chronological definitions of a young man were absent or inconsistent. Masculine constructions of what it means to be a young man and life course characteristics appear more relevant to defining young as it applies to prostate cancer compared with chronological age. These findings have implications for better understanding the morbidities associated with this illness, and in designing interventions that are oriented to life course and helping young men reconstruct their identities after prostate cancer. PMID:24780936

  10. Defining Young in the Context of Prostate Cancer

    PubMed Central

    Lowe, Anthony; Hyde, Melissa K.; Zajdlewicz, Leah; Gardiner, Robert A.; Sandoe, David; Dunn, Jeff

    2015-01-01

    The experience of prostate cancer is for most men a major life stress with the psychological burden of this disease falling more heavily on those who are younger. Despite this, being young as it applies to prostate cancer is not yet clearly defined with varied chronological approaches applied. However, men’s responses to health crises are closely bound to life course and masculinities from which social roles emerge. This paper applied qualitative methodology (structured focus groups and semistructured interviews with expert informants) using interpretative phenomenological analysis to define what it means to be young and have prostate cancer. Structured focus groups were held with 26 consumer advisors (men diagnosed with prostate cancer who provide support to other men with prostate cancer or raise community awareness) and health professionals. As well, 15 men diagnosed with prostate cancer and in their 40s, 50s, or 60s participated in semi-structured interviews. Participants discussed the attributes that describe a young man with prostate cancer and the experience of being young and diagnosed with prostate cancer. Chronological definitions of a young man were absent or inconsistent. Masculine constructions of what it means to be a young man and life course characteristics appear more relevant to defining young as it applies to prostate cancer compared with chronological age. These findings have implications for better understanding the morbidities associated with this illness, and in designing interventions that are oriented to life course and helping young men reconstruct their identities after prostate cancer. PMID:24780936

  11. Atg7 cooperates with Pten loss to drive prostate cancer tumor growth.

    PubMed

    Santanam, Urmila; Banach-Petrosky, Whitney; Abate-Shen, Cory; Shen, Michael M; White, Eileen; DiPaola, Robert S

    2016-02-15

    Understanding new therapeutic paradigms for both castrate-sensitive and more aggressive castrate-resistant prostate cancer is essential to improve clinical outcomes. As a critically important cellular process, autophagy promotes stress tolerance by recycling intracellular components to sustain metabolism important for tumor survival. To assess the importance of autophagy in prostate cancer, we generated a new autochthonous genetically engineered mouse model (GEMM) with inducible prostate-specific deficiency in the Pten tumor suppressor and autophagy-related-7 (Atg7) genes. Atg7 deficiency produced an autophagy-deficient phenotype and delayed Pten-deficient prostate tumor progression in both castrate-naïve and castrate-resistant cancers. Atg7-deficient tumors display evidence of endoplasmic reticulum (ER) stress, suggesting that autophagy may promote prostate tumorigenesis through management of protein homeostasis. Taken together, these data support the importance of autophagy for both castrate-naïve and castrate-resistant growth in a newly developed GEMM, suggesting a new paradigm and model to study approaches to inhibit autophagy in combination with known and new therapies for advanced prostate cancer. PMID:26883359

  12. Is there a link between BPH and prostate cancer?

    PubMed

    Chang, R T M; Kirby, Roger; Challacombe, B J

    2012-04-01

    BPH is one of the most common diseases of older men, with more than 70% of men over 70 years affected, and prostate cancer is the most common cancer in men in the UK. Prostate cancer generally presents in one of three ways: asymptomatic patients who are screened (usually by a PSA test); men with LUTS who are investigated and undergo prostate biopsy; or patients with symptoms of metastasis such as bone pain. Men can be reassured that the main cause of LUTS is BPH. Only a small proportion of men have LUTS that are directly attributable to prostate cancer. Digital rectal examination (DRE) gives an evaluation of prostate size, which is relevant in particular to BPH management, and along with PSA testing it is one of the only ways of differentiating clinically between BPH and prostate cancer. If a nodular abnormality is present there is around a 50% chance of a diagnosis of prostate cancer being made on biopsy. Raised levels of serum PSA may be suggestive of prostate cancer, but diagnosis requires histological confirmation in almost every case. A normal PSA, PSA density and DRE can give reasonable confidence with regards to excluding clinically significant prostate cancer. BPH is not a known risk factor for prostate cancer, although the two frequently coexist. Age is the strongest predictor of prostate cancer risk, along with family history. BPH is not considered to be a precursor of prostate cancer. It is likely that although BPH may not make prostate cancer more likely to occur, it may increase the chance of diagnosing an incidental cancer. PMID:22792684

  13. New Developments in the Medical Management of Prostate Cancer

    PubMed Central

    Kohli, Manish; Tindall, Donald J.

    2010-01-01

    Prostate cancer is a substantial public health burden and a leading cause of cancer—related morbidity and mortality in the United States despite the observation that annual prostate cancer—specific mortality rates have been declining during the previous decade. Although the reasons for this positive development are unclear, a combination of factors may have contributed. This update will review ongoing developments and summarize therapeutic advances in prostate cancer treatment on the basis of the current understanding of prostate cancer biology. Literature for this review was selected in 2009 by searching PubMed for the following keywords: prostatic neoplasms, castration, androgen receptor, hormonal, and chemotherapy. Emphasis is placed on published clinical studies in advanced prostate cancer therapeutics in the past 5 to 10 years. Also included in the review are novel hormonal agents targeting the androgen receptor currently in development for the treatment of advanced prostate cancer. PMID:20042563

  14. Oligometastatic prostate cancer: Metastases-directed therapy?

    PubMed

    Van Poppel, Hein; De Meerleer, Gert; Joniau, Steven

    2016-09-01

    Since the introduction of anatomical and functional imaging with multiparametric magnetic resonance imaging and choline or prostate-specific membrane antigen positron emission tomography-computed tomography, we are able to diagnose a previously unknown disease, the oligometastatic prostate cancer after local therapy. Reports on surgical and radiation treatment for low-volume metastatic recurrence have shown promising results, with definitive cure in few but a relevant delay of androgen-deprivation therapy with both treatment methods. Obviously, these results need to be validated with prospective randomised data. PMID:27547457

  15. PET Imaging in Prostate Cancer: Focus on Prostate-Specific Membrane Antigen

    PubMed Central

    Mease, Ronnie C.; Foss, Catherine A.; Pomper, Martin G.

    2014-01-01

    Prostate cancer (PCa) is the second leading cause of cancer-related death in American men. Positron emission tomography/computed tomography (PET/CT) with emerging radiopharmaceuticals promises accurate staging of primary disease, restaging of recurrent disease, detection of metastatic lesions and, ultimately, for predicting the aggressiveness of disease. Prostate-specific membrane antigen (PSMA) is a well-characterized imaging biomarker of PCa. Because PSMA levels are directly related to androgen independence, metastasis and progression, PSMA could prove an important target for the development of new radiopharmaceuticals for PET. Preclinical data for new PSMA-based radiotracers are discussed and include new 89Zr- and 64Cu-labeled anti-PSMA antibodies and antibody fragments, 64Cu-labeled aptamers, and 11C-, 18F-, 68Ga-, 64Cu-, and 86Y-labeled low molecular weight inhibitors of PSMA. Several of these agents, namely 68Ga-HBED-CC conjugate 15, 18F-DCFBC 8, and BAY1075553 are particularly promising, each having detected sites of PCa in initial clinical studies. These early clinical results suggest that PET/CT using PSMA-targeted agents, especially with compounds of low molecular weight, will make valuable contributions to the management of PCa. PMID:23590171

  16. Challenges in Clinical Prostate Cancer: Role of Imaging

    PubMed Central

    Kelloff, Gary J.; Choyke, Peter; Coffey, Donald S.

    2010-01-01

    Objective This article reviews a recent 2-day workshop on prostate cancer and imaging technology that was conducted by the Cancer Imaging Program of the National Cancer Institute. The workshop dealt with research trends and avenues for improving imaging and applications across the clinical spectrum of the disease. Conclusion After a summary of prostate cancer incidence and mortality, four main clinical challenges in prostate cancer treatment and management—diagnostic accuracy; risk stratification, initial staging, active surveillance, and focal therapy; prostate-specific antigen relapse after radiation therapy or radical prostatectomy; and assessing response to therapy in advanced disease—were discussed by the 55-member panel. The overarching issue in prostate cancer is distinguishing lethal from nonlethal disease. New technologies and fresh uses for established procedures make imaging effective in both assessing and treating prostate cancer. PMID:19457806

  17. Whole-exome sequencing of over 4100 men of African ancestry and prostate cancer risk.

    PubMed

    Rand, Kristin A; Rohland, Nadin; Tandon, Arti; Stram, Alex; Sheng, Xin; Do, Ron; Pasaniuc, Bogdan; Allen, Alex; Quinque, Dominique; Mallick, Swapan; Le Marchand, Loic; Kaggwa, Sam; Lubwama, Alex; Stram, Daniel O; Watya, Stephen; Henderson, Brian E; Conti, David V; Reich, David; Haiman, Christopher A

    2016-01-15

    Prostate cancer is the most common non-skin cancer in males, with a ∼1.5-2-fold higher incidence in African American men when compared with whites. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. We identified 395 220 coding variants down to 0.05% frequency [57% non-synonymous (NS), 42% synonymous and 1% gain or loss of stop codon or splice site variant] in 16 751 genes with the strongest associations observed in SPARCL1 on 4q22.1 (rs13051, Ala49Asp, OR = 0.78, P = 1.8 × 10(-6)) and PTPRR on 12q15 (rs73341069, Val239Ile, OR = 1.62, P = 2.5 × 10(-5)). In gene-level testing, the two most significant genes were C1orf100 (P = 2.2 × 10(-4)) and GORAB (P = 2.3 × 10(-4)). We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case-control or case-case analyses of disease aggressiveness. In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5-1.0% frequency have large effects on prostate cancer risk in men of African ancestry. Higher-coverage sequencing efforts in larger samples will be needed to study rarer variants with smaller effect sizes associated with prostate cancer risk. PMID:26604137

  18. Gene regulatory mechanisms underpinning prostate cancer susceptibility.

    PubMed

    Whitington, Thomas; Gao, Ping; Song, Wei; Ross-Adams, Helen; Lamb, Alastair D; Yang, Yuehong; Svezia, Ilaria; Klevebring, Daniel; Mills, Ian G; Karlsson, Robert; Halim, Silvia; Dunning, Mark J; Egevad, Lars; Warren, Anne Y; Neal, David E; Grönberg, Henrik; Lindberg, Johan; Wei, Gong-Hong; Wiklund, Fredrik

    2016-04-01

    Molecular characterization of genome-wide association study (GWAS) loci can uncover key genes and biological mechanisms underpinning complex traits and diseases. Here we present deep, high-throughput characterization of gene regulatory mechanisms underlying prostate cancer risk loci. Our methodology integrates data from 295 prostate cancer chromatin immunoprecipitation and sequencing experiments with genotype and gene expression data from 602 prostate tumor samples. The analysis identifies new gene regulatory mechanisms affected by risk locus SNPs, including widespread disruption of ternary androgen receptor (AR)-FOXA1 and AR-HOXB13 complexes and competitive binding mechanisms. We identify 57 expression quantitative trait loci at 35 risk loci, which we validate through analysis of allele-specific expression. We further validate predicted regulatory SNPs and target genes in prostate cancer cell line models. Finally, our integrated analysis can be accessed through an interactive visualization tool. This analysis elucidates how genome sequence variation affects disease predisposition via gene regulatory mechanisms and identifies relevant genes for downstream biomarker and drug development. PMID:26950096

  19. African Americans' Perceptions of Prostate-Specific Antigen Prostate Cancer Screening

    ERIC Educational Resources Information Center

    Hunter, Jaimie C.; Vines, Anissa I.; Carlisle, Veronica

    2015-01-01

    Background: In 2012, the U.S. Preventive Services Task Force released a hotly debated recommendation against prostate-specific antigen testing for all men. The present research examines African Americans' beliefs about their susceptibility to prostate cancer (PCa) and the effectiveness of prostate-specific antigen testing in the context of the…

  20. African American Men and Prostate Cancer: Be Your Own Advocate and Understand Screening

    MedlinePlus

    ... the benefits of prostate cancer screening outweigh the harms. Some doctors screen some men for prostate cancer ... find prostate cancers that never would have caused harm in a man’s lifetime. In either case, screening ...

  1. Prostate Cancer: Symptoms, Diagnosis and Treatment | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Javascript on. Feature: Prostate Cancer Prostate Cancer: Symptoms, Diagnosis and Treatment Past Issues / Winter 2010 Table of ... thighs Difficulty having an erection Pain with ejaculation Diagnosis Your healthcare provider can check for prostate cancer ...

  2. Finasteride Reduces the Risk of Low-Grade Prostate Cancer in Men 55 and Older

    MedlinePlus

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Finasteride Reduces the Risk of Low-Grade Prostate Cancer ... PCPT) continue to show that regular use of finasteride (Proscar®) for up to 7 years decreased the ...

  3. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

  4. An unusual case of retrovesical ectopic prostate tissue accompanied by primary prostate cancer.

    PubMed

    Tan, Fu-Qing; Xu, Xin; Shen, Bo-Hua; Qin, Jie; Sun, Ke; You, Qihan; Shang, De-Sheng; Zheng, Xiang-Yi

    2012-01-01

    We report an unusual case of retrovesical ectopic prostate tissue in a 73-year-old man with primary prostate cancer. The man's prostate-specific antigen was 24.66 ng/ml.Transabdominal ultrasonography, pelvic computed tomography,and pelvic magnetic resonance imaging demonstrated a heterogeneous 8.5 × 8.0 × 7.0 cm mass in contact with the posterior wall of the urinary bladder. The patient underwent a retropubic radical prostatectomy and resection of tumor. Pathological examination of prostate revealed a prostatic adenocarcinoma, Gleason score of 4 + 5 = 9, and the retrovesical tumor was confirmed to be a benign prostate tissue. PMID:22966979

  5. Acid ceramidase as a therapeutic target in metastatic prostate cancer[S

    PubMed Central

    Camacho, Luz; Meca-Cortés, Óscar; Abad, José Luis; García, Simón; Rubio, Nuria; Díaz, Alba; Celià-Terrassa, Toni; Cingolani, Francesca; Bermudo, Raquel; Fernández, Pedro L.; Blanco, Jerónimo; Delgado, Antonio; Casas, Josefina; Fabriàs, Gemma; Thomson, Timothy M.

    2013-01-01

    Acid ceramidase (AC) catalyzes the hydrolysis of ceramide into sphingosine, in turn a substrate of sphingosine kinases that catalyze its conversion into the mitogenic sphingosine-1-phosphate. AC is expressed at high levels in several tumor types and has been proposed as a cancer therapeutic target. Using a model derived from PC-3 prostate cancer cells, the highly tumorigenic, metastatic, and chemoresistant clone PC-3/Mc expressed higher levels of the AC ASAH1 than the nonmetastatic clone PC-3/S. Stable knockdown of ASAH1 in PC-3/Mc cells caused an accumulation of ceramides, inhibition of clonogenic potential, increased requirement for growth factors, and inhibition of tumorigenesis and lung metastases. We developed de novo ASAH1 inhibitors, which also caused a dose-dependent accumulation of ceramides in PC-3/Mc cells and inhibited their growth and clonogenicity. Finally, immunohistochemical analysis of primary prostate cancer samples showed that higher levels of ASAH1 were associated with more advanced stages of this neoplasia. These observations confirm ASAH1 as a therapeutic target in advanced and chemoresistant forms of prostate cancer and suggest that our new potent and specific AC inhibitors could act by counteracting critical growth properties of these highly aggressive tumor cells. PMID:23423838

  6. EXAFS studies of prostate cancer cell lines

    NASA Astrophysics Data System (ADS)

    Czapla, J.; Kwiatek, W. M.; Lekki, J.; Kisiel, A.; Steininger, R.; Goettlicher, J.

    2013-04-01

    Sulphur plays a vital role in every human organism. It is known, that sulphur-bearing compounds, such as for example cysteine and glutathione, play critical roles in development and progression of many diseases. Any alteration in sulphur's biochemistry could become a precursor of serious pathological conditions. One of such condition is prostate cancer, the most frequently diagnosed malignancy in the western world and the second leading cause of cancer related death in men. The purpose of presented studies was to examine what changes occur in the nearest chemical environment of sulphur in prostate cancer cell lines in comparison to healthy cells. The Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy was used, followed by theoretical calculations. The results of preliminary analysis is presented.

  7. Prospective Evaluation of Operating Characteristics of Prostate Cancer Detection Biomarkers

    PubMed Central

    Liang, Yuanyuan; Ankerst, Donna P.; Ketchum, Norma S.; Ercole, Barbara; Shah, Girish; Shaughnessy, John D.; Leach, Robin J.; Thompson, Ian M.

    2016-01-01

    Purpose We assessed the independent predictive values of the serum markers free prostate specific antigen, proenzyme prostate specific antigen, neuroendocrine marker and Dickkopf-1 compared to serum prostate specific antigen and other standard risk factors for early prostate cancer detection. Materials and Methods From the prospectively collected SABOR cohort 250 prostate cancer cases, and 250 mean age matched and proportion of African-American race/ethnicity matched controls were selected who had a prior available prostate specific antigen and digital rectal examination. Serum samples were obtained, and free prostate specific antigen, [−2]proenzyme prostate specific antigen, Dickkopf-1 and neuroendocrine marker were measured. AUC, sensitivities and specificities were calculated, and multivariable logistic regression was used to assess the independent predictive value compared to prostate specific antigen, digital rectal examination, family history, prior biopsy history, race/ethnicity and age. Results The AUCs (95% CI) were 0.76 (0.71, 0.8) for free prostate specific antigen, 0.72 (0.67, 0.76) for [−2]proenzyme prostate specific antigen, 0.76 (0.72, 0.8) for %free prostate specific antigen, 0.61 (0.56, 0.66) for %[−2]proenzyme prostate specific antigen, 0.73 (0.68, 0.77) for prostate health index, 0.53 (0.48, 0.58) for Dickkopf-1 and 0.53 (0.48, 0.59) for neuroendocrine marker. In the 2 to 10 ng/ml prostate specific antigen range the AUCs (95% CI) were 0.58 (0.49, 0.67) for free prostate specific antigen, 0.53 (0.44, 0.62) for [−2]proenzyme prostate specific antigen, 0.67 (0.59, 0.75) for %free prostate specific antigen, 0.57 (0.49, 0.65) for %[−2]proenzyme prostate specific antigen and 0.59 (0.51, 0.67) for phi. Only %free prostate specific antigen retained independent predictive value compared to the traditional risk factors. Conclusions Free prostate specific antigen retained independent diagnostic usefulness for prostate cancers detected through

  8. Prostate cancer: a serious disease suitable for prevention.

    PubMed

    Fitzpatrick, John M; Schulman, Claude; Zlotta, Alexandre R; Schröder, Fritz H

    2009-04-01

    Prostate cancer is among the most common causes of death from cancer in men, and accounts for 10% of all new male cancers worldwide. The diagnosis and treatment of prostate cancer place a substantial physical and emotional burden on patients and their families, and have considerable financial implications for healthcare providers and society. Given that the risk of prostate cancer continues to increase with age, the burden of the disease is likely to increase in line with population life-expectancy. Reducing the risk of prostate cancer has gained increasing coverage in recent years, with proof of principle shown in the Prostate Cancer Prevention Trial with the type 2 5alpha-reductase (5AR) inhibitor, finasteride. The long latency period, high disease prevalence, and significant associated morbidity and mortality make prostate cancer a suitable target for a risk-reduction approach. Several agents are under investigation for reducing the risk of prostate cancer, including selenium/vitamin E and selective oestrogen receptors modulators (e.g. toremifene). In addition, the Reduction by Dutasteride of Prostate Cancer Events trial, involving >8000 men, is evaluating the effect of the dual 5AR inhibitor, dutasteride, on the risk of developing prostate cancer. A successful risk-reduction strategy might decrease the incidence of the disease, as well as the anxiety, cost and morbidity associated with its diagnosis and treatment. PMID:19302133

  9. The predictive value of 2-year posttreatment biopsy after prostate cancer radiotherapy for eventual biochemical outcome

    SciTech Connect

    Vance, Waseet; Tucker, Susan L.; Crevoisier, Renaud de; Kuban, Deborah A.; Cheung, M. Rex . E-mail: mrcheung@mdanderson.org

    2007-03-01

    Purpose: To determine the value of a 2-year post-radiotherapy (RT) prostate biopsy for predicting eventual biochemical failure in patients who were treated for localized prostate cancer. Methods and Materials: This study comprised 164 patients who underwent a planned 2-year post-RT prostate biopsy. The independent prognostic value of the biopsy results for forecasting eventual biochemical outcome and overall survival was tested with other factors (the Gleason score, 1992 American Joint Committee on Cancer tumor stage, pretreatment prostate-specific antigen level, risk group, and RT dose) in a multivariate analysis. The current nadir + 2 (CN + 2) definition of biochemical failure was used. Patients with rising prostate-specific antigen (PSA) or suspicious digital rectal examination before the biopsy were excluded. Results: The biopsy results were normal in 78 patients, scant atypical and malignant cells in 30, carcinoma with treatment effect in 43, and carcinoma without treatment effect in 13. Using the CN + 2 definition, we found a significant association between biopsy results and eventual biochemical failure. We also found that the biopsy status provides predictive information independent of the PSA status at the time of biopsy. Conclusion: A 2-year post-RT prostate biopsy may be useful for forecasting CN + 2 biochemical failure. Posttreatment prostate biopsy may be useful for identifying patients for aggressive salvage therapy.

  10. What can proteomic analyses contribute to understanding the molecular biology and clinical behavior of prostate cancer?

    PubMed

    Ware, Joy L

    2004-12-01

    Identifying the proteins and their complex interactions that promote and/or sustain the aggressive malignant phenotype is essential for understanding key effectors of the molecular biology of prostate cancer. This is also essential for development of new clinical applications. A variety of proteomic techniques, ranging from mass spectrometry to new methods of multiplexing protein identification, have great potential for rapidly achieving these goals. However, in order to obtain meaningful results, these techniques must be applied within the context of our knowledge of the heterogeneity of prostate tissues and tumors, the impact of specimen processing on both the quality and quantity of proteins detected and a thorough understanding of prostate cell biology. Collaboration between the protein chemist and the prostate cell biologist will expedite progress in this important field. PMID:15966843

  11. Optimization of Radiation Therapy Techniques for Prostate Cancer With Prostate-Rectum Spacers: A Systematic Review

    SciTech Connect

    Mok, Gary; Benz, Eileen; Vallee, Jean-Paul; Miralbell, Raymond; Zilli, Thomas

    2014-10-01

    Dose-escalated radiation therapy for localized prostate cancer improves disease control but is also associated with worse rectal toxicity. A spacer placed between the prostate and rectum can be used to displace the anterior rectal wall outside of the high-dose radiation regions and potentially minimize radiation-induced rectal toxicity. This systematic review focuses on the published data regarding the different types of commercially available prostate-rectum spacers. Dosimetric results and preliminary clinical data using prostate-rectum spacers in patients with localized prostate cancer treated by curative radiation therapy are compared and discussed.

  12. Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

    PubMed Central

    Buczek, M E; Miles, A K; Green, W; Johnson, C; Boocock, D J; Pockley, A G; Rees, R C; Hulman, G; van Schalkwyk, G; Parkinson, R; Hulman, J; Powe, D G; Regad, T

    2016-01-01

    Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit. PMID:26549027

  13. Epidemiological study of prostate cancer (EPICAP): a population-based case–control study in France

    PubMed Central

    2014-01-01

    factors through a detailed questionnaire, (4) role of individual genetic susceptibility of genes involved in biological pathways of interest. The EPICAP study will also allow us to study prognostic factors and tumor aggressiveness. Taken together, the EPICAP study will provide a comprehensive framework to go further in the understanding of prostate cancer occurrence and its prognosis. PMID:24552491

  14. New serum biomarkers for prostate cancer diagnosis

    PubMed Central

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

    2014-01-01

    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  15. Demography and disease characteristics of prostate cancer in India

    PubMed Central

    Hariharan, Krishnamoorthy; Padmanabha, Venugopal

    2016-01-01

    Introduction: The incidence of prostate cancer has shown significant variation across the globe. Though the prevalence and characteristics of this disease have been extensively studied in many countries, data regarding the true incidence of prostate cancer in India is limited. Materials and Methods: MEDLINE publications from 1990 to 2014 were searched and reviewed and compiled to assess the demographic profile of prostate cancer in India and characteristics unique to this disease in India. Results: The limited data available on prostate cancer showed significant differences in incidence, precipitating factors, and disease characteristics of prostate cancer in India. Conclusions: Since India would be having more number of cases of prostate cancer than most others in the years to come, adequate population-based data regarding the demography and disease characteristics of this disease are of paramount importance in this country. PMID:27127351

  16. Laser Illumination Modality of Photoacoustic Imaging Technique for Prostate Cancer

    NASA Astrophysics Data System (ADS)

    Peng, Dong-qing; Peng, Yuan-yuan; Guo, Jian; Li, Hui

    2016-02-01

    Photoacoustic imaging (PAI) has recently emerged as a promising imaging technique for prostate cancer. But there was still a lot of challenge in the PAI for prostate cancer detection, such as laser illumination modality. Knowledge of absorbed light distribution in prostate tissue was essential since the distribution characteristic of absorbed light energy would influence the imaging depth and range of PAI. In order to make a comparison of different laser illumination modality of photoacoustic imaging technique for prostate cancer, optical model of human prostate was established and combined with Monte Carlo simulation method to calculate the light absorption distribution in the prostate tissue. Characteristic of light absorption distribution of transurethral and trans-rectal illumination case, and of tumor at different location was compared with each other.The relevant conclusions would be significant for optimizing the light illumination in a PAI system for prostate cancer detection.

  17. Optimal management of prostate cancer with lethal biology--state-of-the-art local therapy.

    PubMed

    Chapin, Brian F

    2015-01-01

    Defining prostate cancer with lethal biology based upon clinical criteria is challenging. Locally advanced/High-Grade prostate cancer can be downstaged or even downgraded with cure in up to 60% of patients with primary therapy. However, what is known is that high-grade prostate cancers have a greater potential for recurrence and progression to metastatic disease, which can ultimately result in a patient's death. Patients with clinical features of "high-risk" prostate cancer (cT2c, PSA >20, ≥ Gl 8 on biopsy) are more likely to harbor more aggressive pathologic findings. The optimal management of high-risk prostate cancer is not known as there are not prospective studies comparing surgery to radiation therapy (RT). Retrospective and population-based studies are subject to many biases and attempts to compare surgery and radiation have demonstrated mixed results. Some show equivalent survival outcomes while others showing an advantage of surgery over RT. Local therapy for high-risk disease does appear to be beneficial. Improved outcomes realized with local therapy have been clearly demonstrated by several prospective studies evaluating androgen deprivation therapy (ADT) alone versus ADT plus RT. The combination of local with systemic treatment showed improved disease-specific and overall survival outcomes. Unfortunately, primary ADT for N0M0 prostate cancer is still inappropriately applied in general practice. While the surgical literature is largely retrospective, it too demonstrates that surgery in the setting of high-risk prostate cancer is effective in providing durable disease-specific and overall survivals. [ PMID:26178396

  18. Perineural invasion associated with increased cancer-specific mortality after external beam radiation therapy for men with low- and intermediate-risk prostate cancer

    SciTech Connect

    Beard, Clair . E-mail: cbeard@lroc.harvard.edu; Schultz, Delray; Loffredo, Marian; Cote, Kerri; Renshaw, Andrew A.; Hurwitz, Mark D.; D'Amico, Anthony V.

    2006-10-01

    Purpose: To identify an association between perineural invasion (PNI) and cancer-specific survival in patients with prostate cancer after standard-dose external beam radiation therapy (RT). Methods and Materials: A total of 517 consecutive patients who underwent RT (median dose, 70.5 Gy) between 1989 and 2003 for low-risk or intermediate-risk prostate cancer were studied. A genitourinary pathologist (AAR) scored presence or absence of PNI on all prostate needle-biopsy specimens. A Cox regression multivariable analysis was performed to assess whether the presence of PNI was associated with risk of prostate cancer-specific mortality after RT when the recognized risk-group variables were factored into the model. Estimates of cancer-specific mortality were made using a cumulative incidence method. Comparisons of survival were made using a two-tailed log-rank test. Results: At a median follow-up of 4.5 years, 84 patients (16%) have died, 15 of 84 (18%) from prostate cancer. PNI was the only significant predictor of prostate cancer-specific mortality after RT (p = 0.012). The estimated prostate cancer-specific mortality was 14% at 8 years for PNI+ patients vs. 5% for PNI- patients (p = 0.0008). Conclusions: Patients with low- or intermediate-risk prostate cancer who have PNI on prostate needle biopsy have a significantly higher rate of prostate cancer-specific mortality after standard-dose radiation therapy than patients without PNI. Although this analysis is retrospective, this association argues for consideration of the use of more aggressive therapy, such as hormonal therapy with RT or dose escalation, in these select patients.

  19. Hypofractionated External-Beam Radiotherapy for Prostate Cancer

    PubMed Central

    Cho, L. Chinsoo; Timmerman, Robert; Kavanagh, Brian

    2013-01-01

    There are radiobiological rationales supporting hypofractionated radiotherapy for prostate cancer. The recent advancements in treatment planning and delivery allow sophisticated radiation treatments to take advantage of the differences in radiobiology of prostate cancer and the surrounding normal tissues. The preliminary results from clinical studies indicate that abbreviated fractionation programs can result in successful treatment of localized prostate cancer without escalation of late toxicity. PMID:23533777

  20. Port site metastasis in prostate cancer.

    PubMed

    De Bruyne, Peter; Schatteman, Peter; De Naeyer, Geert; Carpentier, Paul; Mottrie, Alex

    2015-01-01

    Port-site metastasis of prostatic adenocarcinoma is rare and usually associated with poor prognosis. We report a case of a young man with a rising prostate-specific antigen (PSA) 4.5 years after robot-assisted laparoscopic prostatectomy (RALP) and extended pelvic lymphadenectomy (ePLND) for a Gleason 7 (4+3) prostate cancer (pT3b pN0 cM0). Choline positron emission tomography-computed tomography (PET-CT) demonstrated a PET positive subcutaneous recurrence in a previous trocar site accompanied by a PET positive ipsilateral inguinal lymph node. Excision of both lesions was performed, confirming the diagnosis of metastatic prostate cancer. The patient's PSA dropped significantly postoperatively enabling postponement of androgen deprivation treatment up to this date. The etiology of port-site metastasis is multifactorial, including patient and surgery related factors. Such metastases have been scarcely reported following ePLND with or without RALP. Certain surgical precautions can be made to prevent the occurrence. We summarize previously reported mechanisms of development and possible precautionary measures. PMID:26225184

  1. Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer.

    PubMed

    Ahmad, Imran; Mui, Ernest; Galbraith, Laura; Patel, Rachana; Tan, Ee Hong; Salji, Mark; Rust, Alistair G; Repiscak, Peter; Hedley, Ann; Markert, Elke; Loveridge, Carolyn; van der Weyden, Louise; Edwards, Joanne; Sansom, Owen J; Adams, David J; Leung, Hing Y

    2016-07-19

    Prostate cancer (CaP) is the most common adult male cancer in the developed world. The paucity of biomarkers to predict prostate tumor biology makes it important to identify key pathways that confer poor prognosis and guide potential targeted therapy. Using a murine forward mutagenesis screen in a Pten-null background, we identified peroxisome proliferator-activated receptor gamma (Pparg), encoding a ligand-activated transcription factor, as a promoter of metastatic CaP through activation of lipid signaling pathways, including up-regulation of lipid synthesis enzymes [fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACLY)]. Importantly, inhibition of PPARG suppressed tumor growth in vivo, with down-regulation of the lipid synthesis program. We show that elevated levels of PPARG strongly correlate with elevation of FASN in human CaP and that high levels of PPARG/FASN and PI3K/pAKT pathway activation confer a poor prognosis. These data suggest that CaP patients could be stratified in terms of PPARG/FASN and PTEN levels to identify patients with aggressive CaP who may respond favorably to PPARG/FASN inhibition. PMID:27357679

  2. Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer

    PubMed Central

    Ahmad, Imran; Mui, Ernest; Galbraith, Laura; Patel, Rachana; Tan, Ee Hong; Salji, Mark; Rust, Alistair G.; Repiscak, Peter; Hedley, Ann; Markert, Elke; Loveridge, Carolyn; van der Weyden, Louise; Edwards, Joanne; Sansom, Owen J.; Adams, David J.; Leung, Hing Y.

    2016-01-01

    Prostate cancer (CaP) is the most common adult male cancer in the developed world. The paucity of biomarkers to predict prostate tumor biology makes it important to identify key pathways that confer poor prognosis and guide potential targeted therapy. Using a murine forward mutagenesis screen in a Pten-null background, we identified peroxisome proliferator-activated receptor gamma (Pparg), encoding a ligand-activated transcription factor, as a promoter of metastatic CaP through activation of lipid signaling pathways, including up-regulation of lipid synthesis enzymes [fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACLY)]. Importantly, inhibition of PPARG suppressed tumor growth in vivo, with down-regulation of the lipid synthesis program. We show that elevated levels of PPARG strongly correlate with elevation of FASN in human CaP and that high levels of PPARG/FASN and PI3K/pAKT pathway activation confer a poor prognosis. These data suggest that CaP patients could be stratified in terms of PPARG/FASN and PTEN levels to identify patients with aggressive CaP who may respond favorably to PPARG/FASN inhibition. PMID:27357679

  3. Integrative clinical genomics of advanced prostate cancer.

    PubMed

    Robinson, Dan; Van Allen, Eliezer M; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim; Bradley, Robert K; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P; Hussain, Maha; Feng, Felix Y; Tomlins, Scott A; Cooney, Kathleen A; Smith, David C; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E; Morris, Michael J; Solomon, Stephen B; Durack, Jeremy C; Reuter, Victor E; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T; Bowden, Michaela; Balk, Stephen P; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y; Mostaghel, Elahe A; Cheng, Heather H; Mulcahy, Hyojeong; True, Lawrence D; Plymate, Stephen R; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Perez-Lopez, Raquel; Demichelis, Francesca; Robinson, Brian D; Schiffman, Marc; Nanus, David M; Tagawa, Scott T; Sigaras, Alexandros; Eng, Kenneth W; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I; Scher, Howard I; Pienta, Kenneth J; Kantoff, Philip; de Bono, Johann S; Rubin, Mark A; Nelson, Peter S; Garraway, Levi A; Sawyers, Charles L; Chinnaiyan, Arul M

    2015-05-21

    Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals. PMID:26000489

  4. Integrative clinical genomics of advanced prostate cancer

    PubMed Central

    Dan, Robinson; Van Allen, Eliezer M.; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J.; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim M.; Bradley, Robert K.; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P.; Hussain, Maha; Feng, Felix Y.; Tomlins, Scott A.; Cooney, Kathleen A.; Smith, David C.; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E.; Morris, Michael J.; Solomon, Stephen B.; Durack, Jeremy C.; Reuter, Victor E.; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T.; Bowden, Michaela; Balk, Stephen P.; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y.; Mostaghel, Elahe A.; Cheng, Heather H.; Mulcahy, Hyojeong; True, Lawrence D.; Plymate, Stephen R.; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Lopez, Raquel Perez; Demichelis, Francesca; Robinson, Brian D.; Schiffman, Marc A.; Nanus, David M.; Tagawa, Scott T.; Sigaras, Alexandros; Eng, Kenneth W.; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I.; Scher, Howard I.; Pienta, Kenneth J.; Kantoff, Philip; de Bono, Johann S.; Rubin, Mark A.; Nelson, Peter S.; Garraway, Levi A.; Sawyers, Charles L.; Chinnaiyan, Arul M.

    2015-01-01

    SUMMARY Toward development of a precision medicine framework for metastatic, castration resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53 and PTEN were frequent (40–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified novel genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin and ZBTB16/PLZF. Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies (19.3% overall) than seen in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides evidence that clinical sequencing in mCRPC is feasible and could impact treatment decisions in significant numbers of affected individuals. PMID:26000489

  5. 75 FR 54453 - National Prostate Cancer Awareness Month, 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-07

    .... (Presidential Sig.) [FR Doc. 2010-22429 Filed 9-3-10; 11:15 am] Billing code 3195-W0-P ... Documents#0;#0; ] Proclamation 8552 of August 31, 2010 National Prostate Cancer Awareness Month, 2010 By the... the last decade, prostate cancer is still the second leading cause of cancer deaths among men in...

  6. (-)-Gossypol reduces invasiveness in metastatic prostate cancer cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. (-)-Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferation and pro-apoptotic effects in various cancer cells. In this study, the differences betwee...

  7. The Distinct Gene Regulatory Network of Myoglobin in Prostate and Breast Cancer

    PubMed Central

    Bicker, Anne; Brahmer, Alexandra M.; Meller, Sebastian; Kristiansen, Glen; Gorr, Thomas A.; Hankeln, Thomas

    2015-01-01

    Myoglobin (MB) is not only strongly expressed in myocytes, but also at much lower levels in different cancer entities. 40% of breast tumors are MB-positive, with the globin being co-expressed with markers of tumor hypoxia in a proportion of cases. In breast cancer, MB expression is associated with a positive hormone receptor status and patient prognosis. In prostate cancer, another hormone-dependent cancer type, 53% of tumors were recently shown to express MB. Especially in more aggressive prostate cancer specimen MB expression also correlates with increased patient survival rates. Both findings might be due to tumor-suppressing properties of MB in cancer cells. In contrast to muscle, MB transcription in breast and prostate cancer mainly depends on a novel, alternative promoter site. We show here that its associated transcripts can be upregulated by hypoxia and downregulated by estrogens and androgens in MCF7 breast and LNCaP prostate cancer cells, respectively. Bioinformatic data mining of epigenetic histone marks and experimental verification reveal a hitherto uncharacterized transcriptional network that drives the regulation of the MB gene in cancer cells. We identified candidate hormone-receptor binding elements that may interact with the cancer-associated MB promoter to decrease its activity in breast and prostate cancer cells. Additionally, a regulatory element, 250 kb downstream of the promoter, acts as a hypoxia-inducible site within the transcriptional machinery. Understanding the distinct regulation of MB in tumors will improve unraveling the respiratory protein’s function in the cancer context and may provide new starting points for developing therapeutic strategies. PMID:26559958

  8. Ethnicity and Prostate Cancer in Southern Nigeria: A Preliminary Report

    PubMed Central

    Sapira, Monday K; Eke, Ndubuisi; Nwofor, Alexander ME

    2015-01-01

    Introduction: The natural history of prostate cancer varies among patients. The aim of this study is to detect any variations in clinical and pathological characteristics of the tumor in patients from different ethnic groups in Southern Nigeria. Patients and Methods: Consecutive patients who presented with features of prostatic diseases at the Urology Units of University of Port Harcourt Teaching Hospital, Port Harcourt and Nnamdi Azikiwe University Teaching Hospital, Nnewi, were evaluated prospectively with history, physical examination, and relevant investigations using a proforma. Data obtained were collated and analyzed statistically using the Chi-square test and Microsoft Excel. Results: Of 187 patients studied, 169 were analyzed. Eighty-six were Ibos, 31 Ijaws, 25 Ikwerres, and 12 Ogonis. Two were from each Etche, Urhobo, Opobo, and Effik; 4 from Andoni, and 3 Ibibio. Fifty-seven (66.3%) Ibos presented with the disease at higher ages (70–80 years) than 19 (61.3%) Ijaws and 11 (91.7%) Ogonis. These age differences were statistically significant with 95% and 99.9% confidence, respectively. All cases were adenocarcinomas. Clinical features, pattern of serum prostate-specific antigen levels, grades of the tumors, tumor metastases, and complications were similar for all ethnic groups. Although more Ibos had tumors with relatively more aggressive metastatic features, there was no statistical significance. Conclusion: Clinical and pathological features of adenocarcinoma of the prostate in Ibos, Ikwerres, Ijaws, and Ogonis were found to be similar. However, Ibos presented with the disease at older ages than Ijaws and Ogonis. PMID:26425060

  9. [Laser microdissection in the molecular oncology of prostate cancer].

    PubMed

    Wernert, N

    2004-06-01

    Nearly all diseases, including prostate cancer (PCA), occur in mixed tissues with different cell types interconnected by multiple interactions. Laser microdissection permits a separate analysis of specific cell types necessary to understand tumorigenesis. Microdissection can be combined with different molecular methods for analyses at the levels of the genome, the transcriptome or the proteome. With respect to the molecular pathogenesis of PCA, normal glands can be compared to preneoplasias, and these in turn to the carcinoma. Different malignancy grades, as well as intra- and extraprostatic tumor parts, can be specifically analysed and molecular markers of aggressiveness can be identified. The molecular signatures obtained provide the basis for functional studies. New prognostic markers and therapeutic targets can be expected from such approaches in the near future. A far reaching goal is the computer representation of multiple molecular components and their interactions, "E-cell in cyberspace", in which prognostic behaviour and therapeutic responsiveness can be approximately predicted. PMID:15098090

  10. Epigenetics in Breast and Prostate Cancer

    PubMed Central

    Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V.

    2015-01-01

    SUMMARY Most recent investigations into cancer etiology have identified a key role played by epigenetics. Specifically, aberrant DNA and histone modifications which silence tumor suppressor genes or promote oncogenes have been demonstrated in multiple cancer models. While the role of epigenetics in several solid tumor cancers such as colorectal cancer are well established, there is emerging evidence that epigenetics also plays a critical role in breast and prostate cancer. In breast cancer, DNA methylation profiles have been linked to hormone receptor status and tumor progression. Similarly in prostate cancer, epigenetic patterns have been associated with androgen receptor status and response to therapy. The regulation of key receptor pathways and activities which affect clinical therapy treatment options by epigenetics renders this field high priority for elucidating mechanisms and potential targets. A new set of methylation arrays are now available to screen epigenetic changes and provide the cuttingedge tools needed to perform such investigations. The role of nutritional interventions affecting epigenetic changes particularly holds promise. Ultimately, determining the causes and outcomes from epigenetic changes will inform translational applications for utilization as biomarkers for risk and prognosis as well as candidates for therapy. PMID:25421674

  11. Resveratrol–zinc combination for prostate cancer management

    PubMed Central

    Singh, Chandra K; Pitschmann, Anna; Ahmad, Nihal

    2014-01-01

    Zinc, an essential trace element, plays a critical role in cell signaling, and defect(s) in zinc homeostasis may contribute to adverse physiological and pathological conditions, including cancer. Zinc is present in healthy prostate at a very high concentration, where it is required for important prostatic functions. However, zinc levels are significantly diminished in cancerous tissue, and intracellular zinc level is inversely correlated with prostate cancer progression. During neoplastic transformation, zinc-accumulating, citrate-producing normal prostate cells are metabolically transformed to citrate oxidizing cells that lose the ability to accumulate zinc. Interestingly, zinc has been shown to function as chemopreventive agent against prostate cancer, albeit at high doses, which may lead to many adverse effects. Therefore, novel means to enhance bioaccumulation of sufficient zinc in prostate cells via increasing zinc transport could be useful against prostate cancer. On the basis of available evidence, we present a possibility that the grape antioxidant resveratrol, when given with zinc, may lead to retuning the zinc homeostasis in prostate, thereby abolishing or reversing malignancy. If experimentally verified in in vivo model(s) of prostate cancer, such as transgenic mouse models, this may lead to novel means toward management of prostate cancer and other conditions with compromised zinc homeostasis. PMID:24866157

  12. PET/CT AND RADIOIMMUNOTHERAPY OF PROSTATE CANCER

    PubMed Central

    Bouchelouche, Kirsten; Capala, Jacek; Oehr, Peter

    2009-01-01

    Purpose of review Traditional morphologically based imaging modalities are now being complemented by positron emission tomography (PET)/computerized tomography (CT) in prostate cancer. Metastatic prostate cancer is an attractive target for radioimmunotherapy (RIT) since no effective therapies are available. This review highlights the most important achievements within the last year in PET/CT and RIT of prostate cancer. Recent findings Conflicting results exist on the use of choline for detection of malignant disease in the prostate gland. The role of PET/CT in N-staging remains to be elucidated further. However, 18F-choline and 11C-choline PET/CT have been demonstrated to be useful for detection of recurrence. 18F-choline and 18F-fluoride PET/CT are useful for detection of bone metastases. Prostate tumor antigens may be used as targets for RIT. Prostate specific membrane antigen (PSMA) is currently under focus of a number of diagnostic and therapeutic strategies. J591, a monoclonal antibody, that targets the extracellular domain of PSMA, shows promising results. HER2 receptors may also have a potential as target for PET/CT imaging and RIT of advanced prostate cancer. Summary PET/CT in prostate cancer has proven to play a significant role, in particular for detection of prostate cancer recurrence and bone metastases. Radioimmunotherapy of metastatic prostate cancer warrant further investigations. PMID:19535981

  13. Resveratrol-zinc combination for prostate cancer management.

    PubMed

    Singh, Chandra K; Pitschmann, Anna; Ahmad, Nihal

    2014-01-01

    Zinc, an essential trace element, plays a critical role in cell signaling, and defect(s) in zinc homeostasis may contribute to adverse physiological and pathological conditions, including cancer. Zinc is present in healthy prostate at a very high concentration, where it is required for important prostatic functions. However, zinc levels are significantly diminished in cancerous tissue, and intracellular zinc level is inversely correlated with prostate cancer progression. During neoplastic transformation, zinc-accumulating, citrate-producing normal prostate cells are metabolically transformed to citrate oxidizing cells that lose the ability to accumulate zinc. Interestingly, zinc has been shown to function as chemopreventive agent against prostate cancer, albeit at high doses, which may lead to many adverse effects. Therefore, novel means to enhance bioaccumulation of sufficient zinc in prostate cells via increasing zinc transport could be useful against prostate cancer. On the basis of available evidence, we present a possibility that the grape antioxidant resveratrol, when given with zinc, may lead to retuning the zinc homeostasis in prostate, thereby abolishing or reversing malignancy. If experimentally verified in in vivo model(s) of prostate cancer, such as transgenic mouse models, this may lead to novel means toward management of prostate cancer and other conditions with compromised zinc homeostasis. PMID:24866157

  14. Chronic Chlorpyrifos Exposure Does Not Promote Prostate Cancer in Prostate Specific PTEN Mutant Mice

    PubMed Central

    Svensson, Robert U.; Bannick, Nadine L.; Marin, Maximo J.; Robertson, Larry W.; Lynch, Charles F.; Henry, Michael D.

    2014-01-01

    Environmental factors are likely to interact with genetic determinants to influence prostate cancer progression. The Agricultural Health Study has identified an association between exposure to organophosphorous pesticides including chlorpyrifos, and increased prostate cancer risk in pesticide applicators with a first-degree family history of this disease. Exploration of this potential gene-environment interaction would benefit from the development of a suitable animal model. Utilizing a previously described mouse model that is genetically predisposed to prostate cancer through a prostate-specific heterozygous PTEN deletion, termed C57/Luc/Ptenp+/−, we used bioluminescence imaging and histopathological analyses to test whether chronic exposure to chlorpyrifos in a grain-based diet for 32 weeks was able to promote prostate cancer development. Chronic exposure to chlorpyrifos in the diet did not promote prostate cancer development in C57/Luc/Ptenp+/− mice despite achieving sufficient levels to inhibit acetylcholinesterase activity in plasma. We found no significant differences in numbers of murine prostatic intraepithelial neoplasia lesions or disease progression in chlorpyrifos versus control treated animals up to 32 weeks. The mechanistic basis of pesticide-induced prostate cancer may be complex and may involve other genetic variants, multiple genes, or nongenetic factors that might alter prostate cancer risk during pesticide exposure in agricultural workers. PMID:23758150

  15. From Inflammation to Prostate Cancer: The Role of Inflammasomes

    PubMed Central

    Dubey, Seema

    2016-01-01

    Inflammation-associated studies entice specific attention due to inflammation's role in multiple stages of prostate cancer development. However, mechanistic regulation of inflammation inciting prostate cancer remains largely uncharacterized. A focused class of inflammatory regulators known as inflammasomes has recently gained attention in cancer development. Inflammasomes are a multiprotein complex that drives a cascade of proinflammatory cytokines regulating various cellular activities. Inflammasomes activation is linked with infection, stress, or danger signals, which are common events within the prostate gland. In this study, we review the potential of inflammasomes in understanding the role of inflammation in prostate cancer. PMID:27429614

  16. Coffee and tea consumption in relation to prostate cancer prognosis

    PubMed Central

    Geybels, Milan S.; Neuhouser, Marian L.; Wright, Jonathan L.; Stott-Miller, Marni; Stanford, Janet L.

    2013-01-01

    Background Bioactive compounds found in coffee and tea may delay the progression of prostate cancer. Methods We investigated associations of pre-diagnostic coffee and tea consumption with risk of prostate cancer recurrence/progression. Study participants were men diagnosed with prostate cancer in 2002–2005 in King County, Washington, USA. We assessed the usual pattern of coffee and tea consumption two years before diagnosis date. Prostate cancer outcome events were identified using a detailed follow-up survey. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results The analysis of coffee intake in relation to prostate cancer recurrence/progression included 630 patients with a median follow-up of 6.4 years, during which 140 prostate cancer recurrence/progression events were recorded. Approximately 61% of patients consumed at least one cup of coffee per day. Coffee consumption was associated with a reduced risk of prostate cancer recurrence/progression; the adjusted HR for ≥4 cups/day versus ≤1 cup/week was 0.41 (95% CI: 0.20, 0.81; P for trend = 0.01). Approximately 14% of patients consumed one or more cups of tea per day, and tea consumption was unrelated to prostate cancer recurrence/progression. Conclusion Results indicate that pre-diagnostic coffee consumption is associated with a lower risk of prostate cancer recurrence/progression. This finding will require replication in larger studies. PMID:23907772

  17. Fortifying the Treatment of Prostate Cancer with Physical Activity

    PubMed Central

    Champ, Colin E.; Francis, Lanie; Klement, Rainer J.; Dickerman, Roger; Smith, Ryan P.

    2016-01-01

    Over the past decade, significant data have shown that obese men experience a survival detriment after treatment for prostate cancer. While methods to combat obesity are of utmost importance for the prostate cancer patient, newer data reveal the overall metabolic improvements that accompany increased activity levels and intense exercise beyond weight loss. Along these lines, a plethora of data have shown improvement in prostate cancer-specific outcomes after treatment accompanied with these activity levels. This review discusses the metabolic mechanisms in which increased activity levels and exercise can help improve both outcomes for men treated for prostate cancer while lowering the side effects of treatment. PMID:26977321

  18. Fortifying the Treatment of Prostate Cancer with Physical Activity.

    PubMed

    Champ, Colin E; Francis, Lanie; Klement, Rainer J; Dickerman, Roger; Smith, Ryan P

    2016-01-01

    Over the past decade, significant data have shown that obese men experience a survival detriment after treatment for prostate cancer. While methods to combat obesity are of utmost importance for the prostate cancer patient, newer data reveal the overall metabolic improvements that accompany increased activity levels and intense exercise beyond weight loss. Along these lines, a plethora of data have shown improvement in prostate cancer-specific outcomes after treatment accompanied with these activity levels. This review discusses the metabolic mechanisms in which increased activity levels and exercise can help improve both outcomes for men treated for prostate cancer while lowering the side effects of treatment. PMID:26977321

  19. Targeting 5α-reductase for prostate cancer prevention and treatment.

    PubMed

    Nacusi, Lucas P; Tindall, Donald J

    2011-07-01

    Testosterone is the most abundant circulating androgen, and can be converted to dihydrotestosterone (DHT), a more potent androgen, by the 5α-reductase enzymes in target tissues. Current treatments for prostate cancer consist of reducing androgen levels by chemical or surgical castration or pure antiandrogen therapy that directly targets the androgen receptor (AR). Although these therapies reduce tumor burden and AR activity, the cancer inevitably recurs within 18-30 months. An approach targeting the androgen-AR axis at different levels could, therefore, improve the efficacy of prostate cancer therapy. Inhibition of 5α-reductase is one such approach; however, the two largest trials to investigate the use of the 5α-reductase inhibitors (5ARIs) finasteride and dutasteride in patients with prostate cancer have shown that, although the incidence of cancer was reduced by 5ARI treatment, those cancers that were detected were more aggressive than in patients treated with placebo. Thus, the best practice for using these drugs to prevent and treat prostate cancer remains unclear. PMID:21629218

  20. Targeting 5α-reductase for prostate cancer prevention and treatment

    PubMed Central

    Nacusi, Lucas P.; Tindall, Donald J.

    2014-01-01

    Testosterone is the most abundant circulating androgen, and can be converted to dihydrotestosterone (DHT), a more potent androgen, by the 5α-reductase enzymes in target tissues. Current treatments for prostate cancer consist of reducing androgen levels by chemical or surgical castration or pure antiandrogen therapy that directly targets the androgen receptor (AR). Although these therapies reduce tumor burden and AR activity, the cancer inevitably recurs within 18–30 months. An approach targeting the androgen–AR axis at different levels could, therefore, improve the efficacy of prostate cancer therapy. Inhibition of 5α-reductase is one such approach; however, the two largest trials to investigate the use of the 5α-reductase inhibitors (5ARIs) finasteride and dutasteride in patients with prostate cancer have shown that, although the incidence of cancer was reduced by 5ARI treatment, those cancers that were detected were more aggressive than in patients treated with placebo. Thus, the best practice for using these drugs to prevent and treat prostate cancer remains unclear. PMID:21629218

  1. Prostate cancer and glutathione S-transferase deletions

    PubMed Central

    Malik, Saima Shakil; Masood, Nosheen; Yasmin, Azra

    2015-01-01

    GSTM1 and GSTT1 gene polymorphisms have been studied in many populations to evaluate their association with prostate cancer risk with contrasting results. The current study was aimed to find out the association of GSTM1 and GSTT1 gene polymorphisms with prostate cancer in Pakistani men. This case control study included pathologically confirmed prostate cancer patients and age matched male controls. Epidemiological data was collected by a standard questionnaire and presence or absence of GSTM1 and GSTT1 gene was observed by multiplex PCR using CYP1A1 as housekeeping gene. Prostate cancer was more prevalent in age of >60 years and most of the patients were at stage IV (70 %) and have undergone surgery. Family history of cancer, smoking, metastasis and surgery were found to be significant (P<0.05) risk factors in prostate cancer development. Gleason score 7 was most prevalent (40.5 %) in prostate cancer patients. Source of drinking water, residential area, occupation, eating habits and number of family members had no association (P>0.05) with prostate cancer risk. No significant association was found when comparing GSTM1 (OR=0.78) and GSTT1 (OR=0.89) gene deletions with prostate cancer risk. Smoking and TNM staging were also not associated with deletion of GSTM1 and GSTT1 genes. Comparison of dual null deletion of both genes with prostate cancer also showed non-significant associations. Deletion of GSTM1 gene at stage IV prostate cancer patients was significantly higher compared with other stages of cancer while no significance was shown by GSTT1 gene deletion. GSTM1, GSTT1 and deletion of both GSTM1 and GSTT1 genes do not contribute towards increased risk of prostate cancer in Pakistani population. PMID:26600754

  2. Genomic approaches to outcome prediction in prostate cancer.

    PubMed

    Febbo, Phillip G

    2009-07-01

    Prostate cancer remains a common cause of cancer death in men. Applications of emerging genomic technologies to high-quality prostate cancer models and patient samples in multiple contexts have made significant contributions to our molecular understanding of the development and progression of prostate cancer. Genomic analysis of DNA, RNA, and protein alterations allows for the global assessment of this disease and provides the molecular framework to improve risk classification, outcome prediction, and development of targeted therapies. In this review, the author focused on highlighting recent work in genomics and its role in evaluating molecular modifiers of prostate cancer risk and behavior and the development of predictive models that anticipate the risk of developing prostate cancer, prostate cancer progression, and the response of prostate cancer to therapy. This framework has the exciting potential to be predictive and to provide personalized and individual treatment to the large number of men diagnosed with prostate cancer each year. Cancer 2009;115(13 suppl):3046-57. (c) 2009 American Cancer Society. PMID:19544546

  3. Europa Uomo: the European Prostate Cancer Coalition.

    PubMed

    Hudson, Tom; Denis, Louis J

    2007-01-01

    Europa Uomo is a patient-led, non-governmental association (NGO), launched formally in Milan in 2004 with a legal base in Antwerp. As a coalition of prostate cancer patient groups with representation in 18 European countries, the NGO focusses on awareness, early detection, optimal treatment, multi-professional care and, above all, quality of life and patient advocacy. In the majority of European countries prostate cancer is the most commonly diagnosed cancer affecting men beyond middle age. The incidence and substantial mortality rises with age, peaking in the seventh decade. Standards of diagnosis and treatment vary across Europe and attitudes differ. Information about the early detection and awareness of prostate cancer available to the public leaves much to be desired. Since 2002, involved individuals, patient support groups, patients, family members, physicians, urologists, oncologists and nurses joined in the formation of an independent, international, non-profit association of patient-led prostate cancer support groups from European countries known as Europa Uomo, the European Prostate Cancer Coalition. This Coalition was legally established as an NGO in June 2004 in Milan with the headquarters and secretariat in Antwerp, Belgium. Its membership represents 18 countries by the national or regional groups listed in Table 16.1 with their respective contact persons. The coalition is led by a steering committee under the control of the annual general assembly. The steering committee members and their co-ordinates are listed in Table 16.2. Scientific advice is given by a scientific committee chaired by Prof. H. Van Poppel as the liaison officer with the European Association of Urology (EAU). The support for EAU guidelines appears on the Web site and will be linked to all members in their own language (www.cancerworld.org/europauomo). The goals and activities of Europa Uomo have been condensed in a series of slides at the request of the Eurocan+Plus collaboration to

  4. [Chemoprevention of prostate cancer - a plea].

    PubMed

    Schmitz-Dräger, B J; Bismarck, E; Schöffski, O; Fischer, C

    2012-05-01

    The high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make the diagnosis of and therapy for prostate cancer a special challenge for urologists. Effective prevention of the disease may help to improve some of the problems mentioned above. Two randomised, controlled studies have proved that effective chemoprevention of prostate cancer is viable using 5α-reductase inhibitors (finasteride, dutasteride). Furthermore, there is increasing evidence that other compounds, e. g., selective oestrogen receptor modulators (SERMs), NSAIDs and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economical aspects. The authors conclude that the options of chemoprevention should be investigated in an open and unbiased way. PMID:22639024

  5. Heart healthy equals prostate healthy and statins, aspirin, and/or metformin (S.A.M.) are the ideal recommendations for prostate cancer prevention.

    PubMed

    Moyad, Mark A; Vogelzang, Nicholas J

    2015-01-01

    Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Lifestyle factors that promote CVD also appear to increase prostate cancer risk and those that reduce CVD risk also appear to reduce the risk of prostate cancer. The largest randomized trials utilizing dietary supplements or pharmacologic agents for prostate cancer prevention (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) have also shed light on the problems and future solutions in this area. Dietary supplements that have not been found to be CVD protective, such as selenium and Vitamin E have not been found to be prostate protective. In addition, over exposure to specific anti-oxidants in nutritionally replete populations may be encouraging cancer growth. Future trials of dietary supplements to prevent prostate cancer could be problematic because by the time a definitive trial is initiated the participants will no longer be "deficient" in the nutrient being tested, which arguably occurred in the SELECT trial. It is also interesting that statins, aspirin, and/or metformin (S.A.M.) are 3 generic, low-cost, heart healthy agents derived from natural sources with separate mechanism of actions, which all appear to have the best benefit to risk ratio compared to any other agent available for prostate cancer prevention, especially aggressive disease, or as an ancillary agent (s) to conventional cancer treatment. It is time to focus on the forest over the trees and recommend proven CVD protective measures for men concerned about their risk of prostate cancer. PMID:25657084

  6. Heart healthy equals prostate healthy and statins, aspirin, and/or metformin (S.A.M.) are the ideal recommendations for prostate cancer prevention

    PubMed Central

    Moyad, Mark A; Vogelzang, Nicholas J

    2015-01-01

    Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Lifestyle factors that promote CVD also appear to increase prostate cancer risk and those that reduce CVD risk also appear to reduce the risk of prostate cancer. The largest randomized trials utilizing dietary supplements or pharmacologic agents for prostate cancer prevention (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) have also shed light on the problems and future solutions in this area. Dietary supplements that have not been found to be CVD protective, such as selenium and Vitamin E have not been found to be prostate protective. In addition, over exposure to specific anti-oxidants in nutritionally replete populations may be encouraging cancer growth. Future trials of dietary supplements to prevent prostate cancer could be problematic because by the time a definitive trial is initiated the participants will no longer be “deficient” in the nutrient being tested, which arguably occurred in the SELECT trial. It is also interesting that statins, aspirin, and/or metformin (S.A.M.) are 3 generic, low-cost, heart healthy agents derived from natural sources with separate mechanism of actions, which all appear to have the best benefit to risk ratio compared to any other agent available for prostate cancer prevention, especially aggressive disease, or as an ancillary agent (s) to conventional cancer treatment. It is time to focus on the forest over the trees and recommend proven CVD protective measures for men concerned about their risk of prostate cancer. PMID:25657084

  7. Ureteral Metastasis Secondary to Prostate Cancer: A Case Report.

    PubMed

    Morales, I; Bassa, C; Pavlovic, A; Morales, C

    2016-03-01

    Prostate cancer is very frequent, but secondary ureteral metastasis are extremely rare. We present a 55 year old man with a 2 month history of right flank pain and lower urinary tract symptoms. Prostatic specific antigen of 11.3 ng/mL. Computed tomography showed right hydroureteronephrosis, a developing urinoma and right iliac adenopathies. He underwent right ureteronephrectomy, iliac lymphadenectomy and prostate biopsy. Pathology revealed prostatic carcinoma infiltrating the ureteral muscularis propria, without mucosal involvement. There are 46 reported cases of prostate cancer with ureteral metastases. Ureteral metastasis are a rare cause of renal colic and need of a high index of suspicion. PMID:26793587

  8. Ureteral Metastasis Secondary to Prostate Cancer: A Case Report

    PubMed Central

    Morales, I.; Bassa, C.; Pavlovic, A.; Morales, C.

    2015-01-01

    Prostate cancer is very frequent, but secondary ureteral metastasis are extremely rare. We present a 55 year old man with a 2 month history of right flank pain and lower urinary tract symptoms. Prostatic specific antigen of 11.3 ng/mL. Computed tomography showed right hydroureteronephrosis, a developing urinoma and right iliac adenopathies. He underwent right ureteronephrectomy, iliac lymphadenectomy and prostate biopsy. Pathology revealed prostatic carcinoma infiltrating the ureteral muscularis propria, without mucosal involvement. There are 46 reported cases of prostate cancer with ureteral metastases. Ureteral metastasis are a rare cause of renal colic and need of a high index of suspicion. PMID:26793587

  9. A recommender system for prostate cancer websites.

    PubMed

    Witteman, Holly; Chignell, Mark; Krahn, Murray

    2008-01-01

    One of the challenges for people seeking health information online is the difficulty in locating health Websites that are personally relevant, credible and useful. We developed a Web-based recommender system in order to help address this problem in the context of prostate cancer. We are conducting an online randomized controlled trial to evaluate the accuracy of its recommendations and to compare the efficacy of content-based and collaborative filtering. PMID:18999034

  10. 12-HETER1/GPR31, a high-affinity 12(S)-hydroxyeicosatetraenoic acid receptor, is significantly up-regulated in prostate cancer and plays a critical role in prostate cancer progression.

    PubMed

    Honn, Kenneth V; Guo, Yande; Cai, Yinlong; Lee, Menq-Jer; Dyson, Gregory; Zhang, Wenliang; Tucker, Stephanie C

    2016-06-01

    Previously we identified and deorphaned G-protein-coupled receptor 31 (GPR31) as the high-affinity 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] receptor (12-HETER1). Here we have determined its distribution in prostate cancer tissue and its role in prostate tumorigenesis using in vitro and in vivo assays. Data-mining studies strongly suggest that 12-HETER1 expression positively correlates with the aggressiveness and progression of prostate tumors. This was corroborated with real-time PCR analysis of human prostate tumor tissue arrays that revealed the expression of 12-HETER1 positively correlates with the clinical stages of prostate cancers and Gleason scores. Immunohistochemistry analysis also proved that the expression of 12-HETER1 is positively correlated with the grades of prostate cancer. Knockdown of 12-HETER1 in prostate cancer cells markedly reduced colony formation and inhibited tumor growth in animals. To discover the regulatory factors, 5 candidate 12-HETER1 promoter cis elements were assayed as luciferase reporter fusions in Chinese hamster ovary (CHO) cells, where the putative cis element required for gene regulation was mapped 2 kb upstream of the 12-HETER1 transcriptional start site. The data implicate 12-HETER1 in a critical new role in the regulation of prostate cancer progression and offer a novel alternative target for therapeutic intervention.-Honn, K. V., Guo, Y., Cai, Y., Lee, M.-J., Dyson, G., Zhang, W., Tucker, S. C. 12-HETER1/GPR31, a high-affinity 12(S)-hydroxyeicosatetraenoic acid receptor, is significantly up-regulated in prostate cancer and plays a critical role in prostate cancer progression. PMID:26965684

  11. Prostate epithelial cell of origin determines cancer differentiation state in an organoid transformation assay

    PubMed Central

    Park, Jung Wook; Lee, John K.; Phillips, John W.; Huang, Patrick; Cheng, Donghui; Huang, Jiaoti; Witte, Owen N.

    2016-01-01

    The cell of origin for prostate cancer remains a subject of debate. Genetically engineered mouse models have demonstrated that both basal and luminal cells can serve as cells of origin for prostate cancer. Using a human prostate regeneration and transformation assay, our group previously demonstrated that basal cells can serve as efficient targets for transformation. Recently, a subpopulation of multipotent human luminal cells defined by CD26 expression that retains progenitor activity in a defined organoid culture was identified. We transduced primary human prostate basal and luminal cells with lentiviruses expressing c-Myc and activated AKT1 (myristoylated AKT1 or myrAKT1) to mimic the MYC amplification and PTEN loss commonly detected in human prostate cancer. These cells were propagated in organoid culture before being transplanted into immunodeficient mice. We found that c-Myc/myrAKT1–transduced luminal xenografts exhibited histological features of well-differentiated acinar adenocarcinoma, with strong androgen receptor (AR) and prostate-specific antigen (PSA) expression. In contrast, c-Myc/myrAKT1–transduced basal xenografts were histologically more aggressive, with a loss of acinar structures and low/absent AR and PSA expression. Our findings imply that distinct subtypes of prostate cancer may arise from luminal and basal epithelial cell types subjected to the same oncogenic insults. This study provides a platform for the functional evaluation of oncogenes in basal and luminal epithelial populations of the human prostate. Tumors derived in this fashion with defined genetics can be used in the preclinical development of targeted therapeutics. PMID:27044116

  12. Prostate Cancer Induced by Loss of Apc Is Restrained by TGFβ Signaling

    PubMed Central

    Bjerke, Glen A.; Pietrzak, Karolina; Melhuish, Tiffany A.; Frierson Jr., Henry F.; Paschal, Bryce M.; Wotton, David

    2014-01-01

    Recent work with mouse models of prostate cancer (CaP) has shown that inactivation of TGFβ signaling in prostate epithelium can cooperate with deletion of the Pten tumor suppressor to drive locally aggressive cancer and metastatic disease. Here, we show that inactivating the TGFβ pathway by deleting the gene encoding the TGFβ type II receptor (Tgfbr2) in combination with a deletion of the Apc tumor suppressor gene specifically in mouse prostate epithelium, results in the rapid onset of invasive CaP. Micro-metastases were observed in the lymph nodes and lungs of a proportion of the double mutant mice, whereas no metastases were observed in Apc single mutant mice. Prostate-specific Apc;Tgfbr2 mutants had a lower frequency of metastasis and survived significantly longer than Pten;Tgfbr2 double mutants. However, all Apc;Tgfbr2 mutants developed invasive cancer by 30 weeks of age, whereas invasive cancer was rarely observed in Apc single mutant animals, even by one year of age. Further comparison of the Pten and Apc models of CaP revealed additional differences, including adenosquamous carcinoma in the Apc;Tgfbr2 mutants that was not seen in the Pten model, and a lack of robust induction of the TGFβ pathway in Apc null prostate. In addition to causing high-grade prostate intra-epithelial neoplasia (HGPIN), deletion of either Pten or Apc induced senescence in affected prostate ducts, and this restraint was overcome by loss of Tgfbr2. In summary, this work demonstrates that TGFβ signaling restrains the progression of CaP induced by different tumor suppressor mutations, suggesting that TGFβ signaling exerts a general tumor suppressive effect in prostate. PMID:24651496

  13. Metabolomic Imaging of Prostate Cancer with Magnetic Resonance Spectroscopy and Mass Spectrometry

    PubMed Central

    Spur, Eva-Margarete; Decelle, Emily A.; Cheng, Leo L.

    2013-01-01

    Metabolomic imaging of prostate cancer (PCa) aims to improve in vivo imaging capability so that PCa tumors can be localized non-invasively to guide biopsy and evaluated for aggressiveness prior to prostatectomy, as well as to assess and monitor PCa growth for newly biopsy-diagnosed, asymptomatic PCa patients. Metabolomics studies global variations of metabolites with which malignancy conditions can be evaluated by profiling the entire measurable metabolome, instead of focusing only on certain metabolites or isolated metabolic pathways. At present, the study of PCa metabolomics is mainly accomplished utilizing magnetic resonance spectroscopy (MRS) and mass spectrometry (MS). With MRS imaging, the anatomic image, obtained from magnetic resonance imaging, is mapped with values of disease condition-specific metabolomic profiles calculated from MRS of each location. For example, imaging of removed whole prostates demonstrated the ability of metabolomic profiles to differentiate cancerous foci from histologically benign regions. Additionally, MS metabolomic imaging of prostate biopsies uncovered metabolomic expression patterns that could discriminate between PCa and benign tissue. Metabolomic imaging offers the potential to identify cancer lesions to guide prostate biopsy and evaluate PCa aggressiveness non-invasively in vivo, or ex vivo to increase the power of pathology analysis. Potentially, this imaging ability could be possible not only with PCa, but applied to different tissues and organs to evaluate other human malignancies or metabolic diseases. PMID:23549758

  14. [Metastatic hormone-sensitive prostate cancer].

    PubMed

    Gravis, Gwenaelle; Salem, Naji; Walz, Jochen

    2015-01-01

    The prostate cancer in its hormone-sensitive metastatic presentation is infrequent, it is either an initial presentation of the disease or an evolution after local treatment, without castration of the biological relapse. The surgical or biological castration remains the cornerstone of the treatment. The deadline of castration initiation and its modalities of administration, intermittent or continuous rest debated but consensual on the initiation is the appearance of the symptomatic disease. The chemotherapy by docetaxel in association with the castration increases significantly the survival of the patients having a high tumoral volume. The efficacy on the whole metastatic population requires additional analyses. Clinical prognostic factors as the bone localizations (axial or appendicular), the visceral involvement (liver, lung) are determining for the survival of these patients. Biological prognostic factors are in evaluation. Except the clodronate acid, which showed a survival improvement in the hormone-sensitive metastatic prostate cancer (HSMPC), the other treatments targeting the bone (zoledronic acid, rank-ligand inhibitor) demonstrated a benefit only in castrate resistant metastatic prostate cancer (MCRPC). The management of local disease lets suggest a benefit to at least symptomatic disease, but it requires to be estimated prospectively in clinical trials. The new hormonal treatments targeting the androgen receptor in CPMRC are in evaluation in CPMHS. The objective is to increase the survival and the quality of life of the CPMHS and to delay the evolution towards the castration resistant metastatic disease. PMID:25609491

  15. Upfront Chemotherapy for Metastatic Prostate Cancer.

    PubMed

    Lam, Elaine T; Flaig, Thomas W

    2015-12-01

    Traditionally, androgen deprivation therapy (ADT) has been the standard initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC), with chemotherapy utilized in the castration-resistant setting. Data reported from three recent clinical trials shed new light on the role of upfront docetaxel in advanced or mHSPC. Two of these studies-CHAARTED and STAMPEDE-showed significant improvement in overall survival, while the third study, GETUG-AFU 15, showed no statistical difference. The CHAARTED study showed a 13.6-month survival improvement and the STAMPEDE study showed a 10-month survival improvement with ADT plus docetaxel, compared with ADT alone, in the hormone-sensitive setting. These numbers are remarkable when compared with the 2.9-month survival benefit from docetaxel in the metastatic castration-resistant setting, which has been the standard setting for the use of docetaxel in advanced prostate cancer. In this review, we describe the historical data for chemotherapy in the perioperative and metastatic prostate cancer settings, and the recent trials that are changing the paradigm in support of docetaxel in the upfront setting. PMID:26676900

  16. Insights into Chemoresistance of Prostate Cancer

    PubMed Central

    Zhang, Wei; Meng, Yan; Liu, Na; Wen, Xiao-Fei; Yang, Tao

    2015-01-01

    Prostate cancer (PCa) remains the most prevalent malignancy among males in the western world. Though hormonal therapies through chemical or surgical castration have been proposed many years ago, heretofore, such mainstay for the treatment on advanced PCa has not fundamentally changed. These therapeutic responses are temporary and most cases will eventually undergo PCa recurrence and metastasis, or even progress to castration-resistant prostate cancer (CRPC) due to persistent development of drug resistance. Prostate cancer stem cells (PCSCs) are a small population of cells, which possess unlimited self-renewal capacities, and can regenerate tumorigenic progenies, and play an essential role in PCa therapy resistance, metastasis and recurrence. Nowadays advanced progresses have been made in understanding of PCSC properties, roles of androgen receptor signaling and ATP-binding cassette sub-family G member 2 (ABCG2), as well as roles of genomic non-coding microRNAs and key signaling pathways, which have led to the development of novel therapies which are active against chemoresistant PCa and CRPC. Based on these progresses, this review is dedicated to address mechanisms underlying PCa chemoresistance, unveil crosstalks among pivotal signaling pathways, explore novel biotherapeutic agents, and elaborate functional properties and specific roles of chemoresistant PCSCs, which may act as a promising target for novel therapies against chemoresistant PCa. PMID:26327810

  17. Controversies in proton therapy for prostate cancer.

    PubMed

    Bryant, Curtis; Henderson, Randal H; Hoppe, Bradford S; Mendenhall, William M; Nichols, R Charles; Su, Zhong; Li, Zuofeng; Mendenhall, Nancy P

    2016-08-01

    Proton therapy (PT) for prostate cancer has been a subject of controversy over the past two decades. Because of its dosimetric advantages when compared to conventional radiation, PT has the potential to improve the therapeutic ratio in the management of prostate cancer by decreasing toxicity and improving disease control. Nevertheless, its higher costs and the current lack of level I evidence documenting improved clinical outcomes have led some to question its cost-effectiveness. A number of new PT centers have been built over the past decade, leading many stakeholders, including patients, physicians, and insurers, to demand comparative effectiveness data to support its current use. In this review, we summarize the results of recently published studies that support the safety and efficacy of PT in the treatment of prostate cancer. We also review the available cost-effectiveness data for PT and discuss the future of PT, including the current randomized trial comparing PT to intensity-modulated radiation therapy and the need for additional research that may help to establish the relative benefit of PT when compared to photon-based radiation therapy. PMID:27558255

  18. Palliative Radiofrequency Ablation for Recurrent Prostate Cancer

    SciTech Connect

    Jindal, Gaurav; Friedman, Marc; Locklin, Julia Wood, Bradford J.

    2006-06-15

    Percutaneous radiofrequency ablation (RFA) is a minimally invasive local therapy for cancer. Its efficacy is now becoming well documented in many different organs, including liver, kidney, and lung. The goal of RFA is typically complete eradication of a tumor in lieu of an invasive surgical procedure. However, RFA can also play an important role in the palliative care of cancer patients. Tumors which are surgically unresectable and incompatible for complete ablation present the opportunity for RFA to be used in a new paradigm. Cancer pain runs the gamut from minor discomfort relieved with mild pain medication to unrelenting suffering for the patient, poorly controlled by conventional means. RFA is a tool which can potentially palliate intractable cancer pain. We present here a case in which RFA provided pain relief in a patient with metastatic prostate cancer with pain uncontrolled by conventional methods.

  19. Targeted prostate biopsy and MR-guided therapy for prostate cancer.

    PubMed

    Woodrum, David A; Kawashima, Akira; Gorny, Krzysztof R; Mynderse, Lance A

    2016-05-01

    Prostate cancer is the most commonly diagnosed noncutaneous cancer and second-leading cause of death in men. Many patients with clinically organ-confined prostate cancer undergo definitive treatment of the whole gland including radical prostatectomy, radiation therapy, and cryosurgery. Active surveillance is a growing alternative option for patients with documented low-volume, low-grade prostate cancer. With recent advances in software and hardware of MRI, multiparametric MRI of the prostate has been shown to improve the accuracy in detecting and characterizing clinically significant prostate cancer. Targeted biopsy is increasingly utilized to improve the yield of MR-detected, clinically significant prostate cancer and to decrease in detection of indolent prostate cancer. MR-guided targeted biopsy techniques include cognitive MR fusion TRUS biopsy, in-bore transrectal targeted biopsy using robotic transrectal device, and in-bore direct MR-guided transperineal biopsy with a software-based transperineal grid template. In addition, advances in MR compatible thermal ablation technology allow accurate focal or regional delivery of optimal thermal energy to the biopsy-proved, MRI-detected tumor, utilizing cryoablation, laser ablation, high-intensity focused ultrasound ablation under MR guidance and real-time or near simultaneous monitoring of the ablation zone. Herein we present a contemporary review of MR-guided targeted biopsy techniques of MR-detected lesions as well as MR-guided focal or regional thermal ablative therapies for localized naïve and recurrent cancerous foci of the prostate. PMID:26907717

  20. Molecular Alterations in Primary Prostate Cancer After Androgen Ablation Therapy

    PubMed Central

    Best, Carolyn J. M.; Gillespie, John W.; Yi, Yajun; Chandramouli, G.V. R.; Perlmutter, Mark A.; Gathright, Yvonne; Erickson, Heidi S.; Georgevich, Lauren; Tangrea, Michael A.; Duray, Paul H.; González, Sergio; Velasco, Alfredo; Linehan, W. Marston; Matusik, Robert J.; Price, Douglas K.; Figg, William D.; Emmert-Buck, Michael R.; Chuaqui, Rodrigo F.

    2005-01-01

    PURPOSE After an initial response to androgen ablation, most prostate tumors recur, ultimately progressing to highly aggressive androgen independent (AI) cancer. The molecular mechanisms underlying progression are not well known, in part due to the rarity of AI samples from primary and metastatic sites. EXPERIMENTAL DESIGN We compared the gene expression profiles of ten AI primary prostate tumor biopsies with ten primary, untreated androgen-dependent (AD) tumors. Samples were laser capture microdissected, the RNA was amplified, and gene expression was assessed using Affymetrix Human Genome U133A Gene Chips. Differential expression was examined with principle component analysis (PCA) and Student t testing. Analysis of gene ontology was performed with Expression Analysis Systematic Explorer (EASE) and gene expression data were integrated with genomic alterations with DIfferential Gene locus MAPping (DIGMAP). RESULTS Unsupervised PCA showed that the AD and AI tumors segregated from one another. After filtering the data, 239 differentially expressed genes were identified. Two main gene ontologies were found discordant between AI and AD tumors: macromolecule biosynthesis was down-regulated and cell adhesion up-regulated in AI tumors. Other differentially expressed genes were related to IL-6 signaling, as well as angiogenesis, cell adhesion, apoptosis, oxidative stress, and hormone response. The DIGMAP analysis identified nine regions of potential chromosomal deletion in the AI tumors including 1p36, 3p21, 6p21, 8p21, 11p15, 11q12, 12q23, 16q12, and 16q21. CONCLUSIONS Taken together, these data identify several unique characteristics of AI prostate cancer that may hold potential for the development of targeted therapeutic intervention. PMID:16203770

  1. Prostate cancer, Hu antibodies and paraneoplastic neurological syndromes.

    PubMed

    Storstein, A; Raspotnig, M; Vitaliani, R; Giometto, B; Graus, F; Grisold, W; Honnorat, J; Vedeler, C A

    2016-05-01

    Prostate cancer is the most common cancer among American and European men. Nervous system affection caused by local tumor growth or osseous metastases are the main causes of neurological symptoms in prostate cancer patients. Prostate cancer is rarely reported in association with paraneoplastic neurological syndromes (PNS). We have, therefore, studied clinical and paraclinical findings of a series of patients with prostate cancer and PNS, and reviewed cases reported in the literature. Case histories of 14 patients with definite PNS from the PNS Euronetwork database and from the authors' databases were reviewed. A PubMed literature search identified 23 patients with prostate cancer and PNS. Thus, a total of 37 case histories were reviewed with respect to syndrome type, cancer evolution, paraclinical investigations, antibody status, treatment and outcome. The three most frequent isolated PNS were paraneoplastic cerebellar degeneration, paraneoplastic encephalomyelitis (PEM)/limbic encephalitis and subacute sensory neuronopathy (SSN). Onconeural antibodies were detected in 23 patients, in most cases the Hu antibody (17 patients, 74 % of all antibody-positive cases). Other well-characterized onconeural antibodies (Yo, CV2/CRMP5, amphiphysin, VGCC antibodies) were found in a minority. PNS was diagnosed prior to prostate cancer diagnosis in 50 % of the cases. The association of PNS with prostate cancer is quite infrequent, but clinically important. PNS often heralds prostate cancer diagnosis. Syndromes associated with Hu antibodies predominate. Another tumor more prone to associate with PNS should always be excluded. PMID:27007485

  2. The role of SPINK1 in ETS rearrangement-negative prostate cancers.

    PubMed

    Tomlins, Scott A; Rhodes, Daniel R; Yu, Jianjun; Varambally, Sooryanarayana; Mehra, Rohit; Perner, Sven; Demichelis, Francesca; Helgeson, Beth E; Laxman, Bharathi; Morris, David S; Cao, Qi; Cao, Xuhong; Andrén, Ove; Fall, Katja; Johnson, Laura; Wei, John T; Shah, Rajal B; Al-Ahmadie, Hikmat; Eastham, James A; Eggener, Scott E; Fine, Samson W; Hotakainen, Kristina; Stenman, Ulf-Håkan; Tsodikov, Alex; Gerald, William L; Lilja, Hans; Reuter, Victor E; Kantoff, Phillip W; Scardino, Peter T; Rubin, Mark A; Bjartell, Anders S; Chinnaiyan, Arul M

    2008-06-01

    ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers ( approximately 10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers. PMID:18538735

  3. Proteomic Profiling of Serum-Derived Exosomes from Ethnically Diverse Prostate Cancer Patients

    PubMed Central

    Turay, David; Khan, Salma; Osterman, Carlos J. Diaz; Curtis, Matthew P.; Khaira, Balreet; Neidigh, Jonathan W.; Mirshahidi, Saied; Casiano, Carlos A.; Wall, Nathan R.

    2015-01-01

    Prostate cancer (PCa) remains the most frequently diagnosed male malignancy in Western countries and the second most common cause of male cancer death in the United States. The relatively elevated PCa incidence and mortality among African American men makes this cancer type a challenging health disparity disease. To increase the chance for successful trea tment, earlier detection and prediction of tumor aggress iveness will be important and need to be resolved. This study demonstrates that small membrane-bound vesicles shed from the tumor called exosomes contain ethnically and tumor-specific biomarkers, and could be exploited for their diagnostic and therapeutic potential. PMID:26536157

  4. DNA damage response and prostate cancer: defects, regulation and therapeutic implications.

    PubMed

    Karanika, S; Karantanos, T; Li, L; Corn, P G; Thompson, T C

    2015-05-28

    DNA damage response (DDR) includes the activation of numerous cellular activities that prevent duplication of DNA lesions and maintain genomic integrity, which is critical for the survival of normal and cancer cells. Specific genes involved in the DDR such as BRCA1/2 and P53 are mutated during prostate cancer progression, while various oncogenic signaling such as Akt and c-Myc are activated, enhancing the replication stress and increasing the genomic instability of cancer cells. These events may render prostate cancer cells particularly sensitive to inhibition of specific DDR pathways, such as PARP in homologous recombination DNA repair and Chk1 in cell cycle checkpoint and DNA repair, creating opportunities for synthetic lethality or synergistic cytotoxicity. Recent reports highlight the critical role of androgen receptor (AR) as a regulator of DDR genes, providing a rationale for combining DNA-damaging agents or targeted DDR inhibitors with hormonal manipulation or AR inhibition as treatment for aggressive disease. The aims of this review are to discuss specific DDR defects in prostate cancer that occur during disease progression, to summarize recent advances in understanding the regulation of DDR in prostate cancer, and to present potential therapeutic opportunities through combinational targeting of the intact components of DDR signaling pathways. PMID:25132269

  5. Expression profiling of prostate cancer tissue delineates genes associated with recurrence after prostatectomy

    PubMed Central

    Mortensen, Martin Mørck; Høyer, Søren; Lynnerup, Anne-Sophie; Ørntoft, Torben Falck; Sørensen, Karina Dalsgaard; Borre, Michael; Dyrskjøt, Lars

    2015-01-01

    Prostate cancer is a leading cause of cancer death amongst males. The main clinical dilemma in treating prostate cancer is the high number of indolent cases that confer a significant risk of overtreatment. In this study, we have performed gene expression profiling of tumor tissue specimens from 36 patients with prostate cancer to identify transcripts that delineate aggressive and indolent cancer. Key genes were validated using previously published data and by tissue microarray analysis. Two molecular subgroups were identified with a significant overrepresentation of tumors from patients with biochemical recurrence in one of the groups. We successfully validated key transcripts association with recurrence using two publically available datasets totaling 669 patients. Twelve genes were found to be independent predictors of recurrence in multivariate logistical regression analysis. SFRP4 gene expression was consistently up regulated in patients with recurrence in all three datasets. Using an independent cohort of 536 prostate cancer patients we showed SFRP4 expression to be an independent predictor of recurrence after prostatectomy (HR = 1.35; p = 0.009). We identified SFRP4 to be associated with disease recurrence. Prospective studies are needed in order to assess the clinical usefulness of the identified key markers in this study. PMID:26522007

  6. DNA damage response and prostate cancer: defects, regulation and therapeutic implications

    PubMed Central

    Karanika, Styliani; Karantanos, Theodoros; Li, Likun; Corn, Paul G.; Thompson, Timothy C.

    2014-01-01

    DNA damage response (DDR) includes the activation of numerous cellular activities that prevent duplication of DNA lesions and maintain genomic integrity, which is critical for the survival of normal and cancer cells. Specific genes involved in the DDR such as BRCA1/2 and P53 are mutated during prostate cancer progression, while various oncogenic signaling such as Akt and c-Myc are activated, enhancing the replication stress and increasing the genomic instability of cancer cells. These events may render prostate cancer cells particularly sensitive to inhibition of specific DDR pathways, such as PARP in homologous recombination (HR) DNA repair and Chk1 in cell cycle checkpoint and DNA repair, creating opportunities for synthetic lethality or synergistic cytotoxicity. Recent reports highlight the critical role of androgen receptor (AR) as a regulator of DDR genes, providing a rationale for combining DNA-damaging agents or targeted DDR inhibitors with hormonal manipulation or AR inhibition as treatment for aggressive disease. The aims of this review are to discuss specific DDR defects in prostate cancer that occur during disease progression, to summarize recent advances in understanding the regulation of DDR in prostate cancer, and to present potential therapeutic opportunities through combinational targeting of the intact components of DDR signaling pathways. PMID:25132269

  7. Detection of Alpha-Methylacyl-CoA Racemase (AMACR), a Biomarker of Prostate Cancer, in Patient Blood Samples Using a Nanoparticle Electrochemical Biosensor.

    PubMed

    Lin, Po-Yuan; Cheng, Kai-Lun; McGuffin-Cawley, James D; Shieu, Fuh-Sheng; Samia, Anna C; Gupta, Sanjay; Cooney, Matthew; Thompson, Cheryl L; Liu, Chung Chiun

    2012-01-01

    Although still commonly used in clinical practice to screen and diagnose prostate cancer, there are numerous weaknesses of prostate-specific antigen (PSA) testing, including lack of specificity and the inability to distinguish between aggressive and indolent cancers. A promising prostate cancer biomarker, alpha-methylacyl-CoA racemase (AMACR), has been previously demonstrated to distinguish cancer from healthy and benign prostate cells with high sensitivity and specificity. However, no accurate clinically useful assay has been developed. This study reports the development of a single use, disposable biosensor for AMACR detection. Human blood samples were used to verify its validity, reproducibility and reliability. Plasma samples from 9 healthy males, 10 patients with high grade prostatic intraepithelial neoplasia (HGPIN), and 5 prostate cancer patients were measured for AMACR levels. The average AMACR levels in the prostate cancer patients was 10 fold higher (mean(SD) = 0.077 (0.10)) than either the controls (mean(SD) = 0.005 (0.001)) or HGPIN patients (mean(SD) = 0.004 (0.0005)). At a cutoff of between 0.08 and 0.9, we are able to achieve 100% accuracy in separating prostate cancer patients from controls. Our results provide strong evidence demonstrating that this biosensor can perform as a reliable assay for prostate cancer detection and diagnosis. PMID:25586028

  8. Germline Mutations in HOXB13 and Prostate-Cancer Risk

    PubMed Central

    Ewing, Charles M.; Ray, Anna M.; Lange, Ethan M.; Zuhlke, Kimberly A.; Robbins, Christiane M.; Tembe, Waibhav D.; Wiley, Kathleen E.; Isaacs, Sarah D.; Johng, Dorhyun; Wang, Yunfei; Bizon, Chris; Yan, Guifang; Gielzak, Marta; Partin, Alan W.; Shanmugam, Vijayalakshmi; Izatt, Tyler; Sinari, Shripad; Craig, David W.; Zheng, S. Lilly; Walsh, Patrick C.; Montie, James E.; Xu, Jianfeng; Carpten, John D.; Isaacs, William B.; Cooney, Kathleen A.

    2013-01-01

    BACKGROUND Family history is a significant risk factor for prostate cancer, although the molecular basis for this association is poorly understood. Linkage studies have implicated chromosome 17q21-22 as a possible location of a prostate-cancer susceptibility gene. METHODS We screened more than 200 genes in the 17q21-22 region by sequencing germline DNA from 94 unrelated patients with prostate cancer from families selected for linkage to the candidate region. We tested family members, additional case subjects, and control subjects to characterize the frequency of the identified mutations. RESULTS Probands from four families were discovered to have a rare but recurrent mutation (G84E) in HOXB13 (rs138213197), a homeobox transcription factor gene that is important in prostate development. All 18 men with prostate cancer and available DNA in these four families carried the mutation. The carrier rate of the G84E mutation was increased by a factor of approximately 20 in 5083 unrelated subjects of European descent who had prostate cancer, with the mutation found in 72 subjects (1.4%), as compared with 1 in 1401 control subjects (0.1%) (P = 8.5×10−7). The mutation was significantly more common in men with early-onset, familial prostate cancer (3.1%) than in those with late-onset, nonfamilial prostate cancer (0.6%) (P = 2.0×10−6). CONCLUSIONS The novel HOXB13 G84E variant is associated with a significantly increased risk of hereditary prostate cancer. Although the variant accounts for a small fraction of all prostate cancers, this finding has implications for prostate-cancer risk assessment and may provide new mechanistic insights into this common cancer. (Fund