Analysis of the learning curve for transurethral resection of the prostate. Is there any influence of musical instrument and video game skills on surgical performance?

PubMed

Yamaçake, Kleiton Gabriel Ribeiro; Nakano, Elcio Tadashi; Soares, Iva Barbosa; Cordeiro, Paulo; Srougi, Miguel; Antunes, Alberto Azoubel

2015-09-01

To evaluate the learning curve for transurethral resection of the prostate (TURP) among urology residents and study the impact of video game and musical instrument playing abilities on its performance. A prospective study was performed from July 2009 to January 2013 with patients submitted to TURP for benign prostatic hyperplasia. Fourteen residents operated on 324 patients. The following parameters were analyzed: age, prostate-specific antigen levels, prostate weight on ultrasound, pre- and postoperative serum sodium and hemoglobin levels, weight of resected tissue, operation time, speed of resection, and incidence of capsular lesions. Gender, handedness, and prior musical instrument and video game playing experience were recorded using survey responses. The mean resection speed in the first 10 procedures was 0.36 g/min and reached a mean of 0.51 g/min after the 20(th) procedure. The incidence of capsular lesions decreased progressively. The operation time decreased progressively for each subgroup regardless of the difference in the weight of tissue resected. Those experienced in playing video games presented superior resection speed (0.45 g/min) when compared with the novice (0.35 g/min) and intermediate (0.38 g/min) groups (p=0.112). Musical instrument playing abilities did not affect the surgical performance. Speed of resection, weight of resected tissue, and percentage of resected tissue improve significantly and the incidence of capsular lesions reduces after the performance of 10 TURP procedures. Experience in playing video games or musical instruments does not have a significant effect on outcomes.

Robotic Assisted Simple Prostatectomy versus Holmium Laser Enucleation of the Prostate for Lower Urinary Tract Symptoms in Patients with Large Volume Prostate: A Comparative Analysis from a High Volume Center.

PubMed

Umari, Paolo; Fossati, Nicola; Gandaglia, Giorgio; Pokorny, Morgan; De Groote, Ruben; Geurts, Nicolas; Goossens, Marijn; Schatterman, Peter; De Naeyer, Geert; Mottrie, Alexandre

2017-04-01

We report a comparative analysis of robotic assisted simple prostatectomy vs holmium laser enucleation of the prostate in patients who had benign prostatic hyperplasia with a large volume prostate (greater than 100 ml). A total of 81 patients underwent robotic assisted simple prostatectomy and 45 underwent holmium laser enucleation of the prostate in a 7-year period. Patients were preoperatively assessed with transrectal ultrasound and uroflowmetry. Functional parameters were assessed postoperatively during followup. Perioperative outcomes included operative time, postoperative hemoglobin, catheterization time and hospitalization. Complications were reported according to the Clavien-Dindo classification. Compared to the holmium laser enucleation group, patients treated with prostatectomy were significantly younger (median age 69 vs 74 years, p = 0.032) and less healthy (Charlson comorbidity index 2 or greater in 62% vs 29%, p = 0.0003), and had a lower rate of suprapubic catheterization (23% vs 42%, p = 0.028) and a higher preoperative I-PSS (International Prostate Symptom Score) (25 vs 21, p = 0.049). Both groups showed an improvement in the maximum flow rate (15 vs 11 ml per second, p = 0.7), and a significant reduction in post-void residual urine (-73 vs -100 ml, p = 0.4) and I-PSS (-20 vs -18, p = 0.8). Median operative time (105 vs 105 minutes, p = 0.9) and postoperative hemoglobin (13.2 vs 13.8 gm/dl, p = 0.08) were similar for robotic assisted prostatectomy and holmium laser enucleation, respectively. Median catheterization time (3 vs 2 days, p = 0.005) and median hospitalization (4 vs 2 days, p = 0.0001) were slightly shorter in the holmium laser group. Complication rates were similar with no Clavien grade greater than 3 in either group. Our results from a single center suggest comparable outcomes for robotic assisted simple prostatectomy and holmium laser enucleation of the prostate in patients with a large volume prostate. These findings require external validation at other high volume centers. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Thulium laser VapoResection of the prostate versus traditional transurethral resection of the prostate or transurethral plasmakinetic resection of prostate for benign prostatic obstruction: a systematic review and meta-analysis.

PubMed

Deng, Zheng; Sun, Menghao; Zhu, Yiping; Zhuo, Jian; Zhao, Fujun; Xia, Shujie; Han, Bangmin; Herrmann, Thomas R W

2018-04-12

To compare the efficacy and safety of thulium laser VapoResection of the prostate (ThuVaRP) versus standard traditional transurethral resection of the prostate (TURP) or plasmakinetic resection of prostate (PKRP) for benign prostatic obstruction. Systematic searches were performed in the Medline, EMBASE, the Cochrane Library, Web of Science, and CNKI in December 2017. The outcomes of demographic and clinical characteristics, perioperative variables, complications, and postoperative efficacy including International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), and postvoid residual (PVR) were assessed. 16 studies were selected in the meta-analysis including nine randomized controlled trials (RCTs) and seven non-RCTs. Among of them, nine studies compared ThuVaRP with PKRP, while seven studies compared ThuVaRP with TURP. It seemed that ThuVaRP needed longer operation time than TURP (WMD = 6.41, 95% CI 1.38-11.44, p = 0.01) and PKRP (WMD = 10.15, 95% CI 5.20-15.10, p < 0.0001). ThuVaRP was associated with less serum hemoglobin decreased, catheterization time, and the length of hospital stay compared with TURP (WMD = - 0.58, 95% CI - 0.77 to 0.38, p < 0.00001; WMD = - 1.89, 95% CI - 2.67 to 1.11, p < 0.00001; WMD = - 2.25, 95% CI - 2.91 to 1.60, p < 0.00001) and PKRP (WMD = - 0.28, 95% CI - 0.46 to 0.10, p = 0.002; WMD = - 1.88, 95% CI - 2.87 to 0.89, p = 0.0002; WMD = - 2.08, 95% CI - 2.63 to 1.54, p<0.00001). According to our assessment, there was no significantly difference in postoperative efficacy. The pooled data indicated that ThuVaRP had a nearly efficacy to TURP and PKRP based on IPSS, QoL, Qmax, and PVR. Although ThuVaRP was associated with longer operation time, it got distinct superiority on serum hemoglobin decreased, catheterization time, and hospital stay.

The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men

PubMed Central

Basaria, Shehzad; Collins, Lauren; Dillon, E. Lichar; Orwoll, Katie; Storer, Thomas W.; Miciek, Renee; Ulloor, Jagadish; Zhang, Anqi; Eder, Richard; Zientek, Heather; Gordon, Gilad; Kazmi, Syed; Sheffield-Moore, Melinda

2013-01-01

Background. Concerns about potential adverse effects of testosterone on prostate have motivated the development of selective androgen receptor modulators that display tissue-selective activation of androgenic signaling. LGD-4033, a novel nonsteroidal, oral selective androgen receptor modulator, binds androgen receptor with high affinity and selectivity. Objectives. To evaluate the safety, tolerability, pharmacokinetics, and effects of ascending doses of LGD-4033 administered daily for 21 days on lean body mass, muscle strength, stair-climbing power, and sex hormones. Methods. In this placebo-controlled study, 76 healthy men (21–50 years) were randomized to placebo or 0.1, 0.3, or 1.0 mg LGD-4033 daily for 21 days. Blood counts, chemistries, lipids, prostate-specific antigen, electrocardiogram, hormones, lean and fat mass, and muscle strength were measured during and for 5 weeks after intervention. Results. LGD-4033 was well tolerated. There were no drug-related serious adverse events. Frequency of adverse events was similar between active and placebo groups. Hemoglobin, prostate-specific antigen, aspartate aminotransferase, alanine aminotransferase, or QT intervals did not change significantly at any dose. LGD-4033 had a long elimination half-life and dose-proportional accumulation upon multiple dosing. LGD-4033 administration was associated with dose-dependent suppression of total testosterone, sex hormone–binding globulin, high density lipoprotein cholesterol, and triglyceride levels. follicle-stimulating hormone and free testosterone showed significant suppression at 1.0-mg dose only. Lean body mass increased dose dependently, but fat mass did not change significantly. Hormone levels and lipids returned to baseline after treatment discontinuation. Conclusions. LGD-4033 was safe, had favorable pharmacokinetic profile, and increased lean body mass even during this short period without change in prostate-specific antigen. Longer randomized trials should evaluate its efficacy in improving physical function and health outcomes in select populations. PMID:22459616

Holmium laser enucleation for prostate adenoma greater than 100 gm.: comparison to open prostatectomy.

PubMed

Moody, J A; Lingeman, J E

2001-02-01

Options for treatment of large (greater than 100 gm.) prostatic adenomas have until now been limited to open surgery or transurethral resection by skilled resectionists. Considerable blood loss, morbidity, extended hospital stay and prolonged recovery occur with open surgery for large prostatic adenomas. Endoscopic surgery for benign prostatic hyperplasia has evolved during the last decade to offer the patient and surgeon significant advantages of transurethral removal of prostatic adenomas. Holmium laser enucleation of the prostate with transurethral tissue morcellation provides significant reductions in morbidity, bleeding and hospital stay for patients with large prostate adenomas. A retrospective review of data on 10 cases of holmium laser enucleation and 10 open prostatectomies for greater than 100 gm. prostatic adenomas was performed from 1998 to 1999 at our institution. Patient demographics, indication for surgery, preoperative and postoperative American Urological Association (AUA) symptom scores, operating time, serum hemoglobin, resected prostatic weight, pathological diagnosis, length of stay and complications were compared. Patient age, indications for surgery (retention, failed medical therapy, high post-void residual, bladder calculi, bladder diverticula and azotemia) and preoperative AUA symptom scores were similar in both groups. Postoperative AUA symptom scores were significantly decreased (p <0.004) in both groups. Operating times were not significantly different. Serum sodium was unchanged by holmium laser enucleation (not significant), and postoperative hemoglobin was not significantly reduced in the holmium laser enucleation group but decreased significantly in the open prostatectomy group (mean decrease 2.9 +/- 0.7 gm., p = 0.0003). Resected weight was greater in the holmium laser enucleation group (151 versus 106 gm., p = 0.07). Length of stay was significantly shorter in the holmium laser enucleation group (2.1 versus 6.1 days, p <0.001). Complications in the holmium laser enucleation group included stress urinary incontinence in 4 cases, prostatic perforation in 1 and urinary retention in 1. No patient treated with holmium laser enucleation was discharged home with an indwelling catheter. Complications in the open prostatectomy group included bladder neck contractures in 2 cases, stress incontinence in 1 and urge incontinence in 1. All patients treated with open prostatectomy were discharged home with an indwelling catheter. Holmium laser enucleation is an effective, safe procedure for large prostatic adenomas with significantly lower morbidity, catheterization duration and length of stay. Performing holmium laser enucleation for large adenomas requires experience. Stress incontinence was seen frequently with laser but was short-term and self-limited. Holmium laser enucleation is a new procedure, and as experience and expertise increase, it may become an attractive alternative to open prostatectomy for patients with large prostate adenomas.

Analysis of the learning curve for transurethral resection of the prostate. Is there any influence of musical instrument and video game skills on surgical performance?

PubMed Central

Yamaçake, Kleiton Gabriel Ribeiro; Nakano, Elcio Tadashi; Soares, Iva Barbosa; Cordeiro, Paulo; Srougi, Miguel; Antunes, Alberto Azoubel

2015-01-01

Objective To evaluate the learning curve for transurethral resection of the prostate (TURP) among urology residents and study the impact of video game and musical instrument playing abilities on its performance. Material and methods A prospective study was performed from July 2009 to January 2013 with patients submitted to TURP for benign prostatic hyperplasia. Fourteen residents operated on 324 patients. The following parameters were analyzed: age, prostate-specific antigen levels, prostate weight on ultrasound, pre- and postoperative serum sodium and hemoglobin levels, weight of resected tissue, operation time, speed of resection, and incidence of capsular lesions. Gender, handedness, and prior musical instrument and video game playing experience were recorded using survey responses. Results The mean resection speed in the first 10 procedures was 0.36 g/min and reached a mean of 0.51 g/min after the 20th procedure. The incidence of capsular lesions decreased progressively. The operation time decreased progressively for each subgroup regardless of the difference in the weight of tissue resected. Those experienced in playing video games presented superior resection speed (0.45 g/min) when compared with the novice (0.35 g/min) and intermediate (0.38 g/min) groups (p=0.112). Musical instrument playing abilities did not affect the surgical performance. Conclusion Speed of resection, weight of resected tissue, and percentage of resected tissue improve significantly and the incidence of capsular lesions reduces after the performance of 10 TURP procedures. Experience in playing video games or musical instruments does not have a significant effect on outcomes. PMID:26516596

Predictive value of different prostate-specific antigen-based markers in men with baseline total prostate-specific antigen <2.0 ng/mL.

PubMed

Fujizuka, Yuji; Ito, Kazuto; Oki, Ryo; Suzuki, Rie; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro

2017-08-01

To investigate the predictive value of various molecular forms of prostate-specific antigen in men with baseline prostate-specific antigen <2.0 ng/mL. The case cohort comprised 150 men with a baseline prostate-specific antigen level <2.0 ng/mL, and who developed prostate cancer within 10 years. The control cohort was 300 baseline prostate-specific antigen- and age-adjusted men who did not develop prostate cancer. Serum prostate-specific antigen, free prostate-specific antigen, and [-2] proenzyme prostate-specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate-specific antigen- and [-2] proenzyme prostate-specific antigen-related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated. The baseline free to total prostate-specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate-specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [-2] proenzyme prostate-specific antigen/free prostate-specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores. Free to total prostate-specific antigen ratio in men with low baseline prostate-specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [-2] proenzyme prostate-specific antigen-related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance. © 2017 The Japanese Urological Association.

Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume.

PubMed

Choi, Woo Suk; Heo, Nam Ju; Paick, Jae-Seung; Son, Hwancheol

2016-04-01

To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume. We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen × plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 ± 0.91 vs 1.15 ± 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 ± 0.084 vs 0.115 ± 0.071 μg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046). Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume. © 2016 The Japanese Urological Association.

Effectiveness of the combined evaluation of KLK3 genetics and free-to-total prostate specific antigen ratio for prostate cancer diagnosis.

PubMed

Zambon, Carlo-Federico; Prayer-Galetti, Tommaso; Basso, Daniela; Padoan, Andrea; Rossi, Elisa; Secco, Silvia; Pelloso, Michela; Fogar, Paola; Navaglia, Filippo; Moz, Stefania; Zattoni, Filiberto; Plebani, Mario

2012-10-01

Of serum prostate specific antigen variability 40% depends on inherited factors. We ascertained whether the knowledge of KLK3 genetics would enhance prostate specific antigen diagnostic performance in patients with clinical suspicion of prostate cancer. We studied 1,058 men who consecutively underwent prostate biopsy for clinical suspicion of prostate cancer. At histology prostate cancer was present in 401 cases and absent in 657. Serum total prostate specific antigen and the free-to-total prostate specific antigen ratio were determined. Four polymorphisms of the KLK3 gene (rs2569733, rs2739448, rs925013 and rs2735839) and 1 polymorphism of the SRD5A2 gene (rs523349) were studied. The influence of genetics on prostate specific antigen variability was evaluated by multivariate linear regression analysis. The performance of total prostate specific antigen and the free-to-total prostate specific antigen ratio alone or combined with a genetically based patient classification were defined by ROC curve analyses. For prostate cancer diagnosis the free-to-total prostate specific antigen ratio index alone (cutoff 11%) was superior to total prostate specific antigen (cutoff 4 ng/ml) and to free-to-total prostate specific antigen ratio reflex testing (positive predictive value 61%, 43% and 54%, respectively). Prostate specific antigen correlated with KLK3 genetics (rs2735839 polymorphism p = 0.001, and rs2569733, rs2739448 and rs925013 haplotype combination p = 0.003). In patients with different KLK3 genetics 2 optimal free-to-total prostate specific antigen ratio cutoffs (11% and 14.5%) were found. For free-to-total prostate specific antigen ratio values between 11% and 14.5% the prostate cancer probability ranged from 30.0% to 47.4% according to patient genetics. The free-to-total prostate specific antigen ratio is superior to total prostate specific antigen for prostate cancer diagnosis, independent of total prostate specific antigen results. Free-to-total prostate specific antigen ratio findings below 11% are positively associated with prostate cancer and those above 14.5% are negatively associated with prostate cancer, while the interpretation of those between 11% and 14.5% is improved by patient KLK3 genetic analysis. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in active surveillance patients.

PubMed

Iremashvili, Viacheslav; Barney, Shane L; Manoharan, Murugesan; Kava, Bruce R; Parekh, Dipen J; Punnen, Sanoj

2016-04-01

To analyze the association between prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in prostate cancer patients on active surveillance, and to study the effect of prediagnostic prostate-specific antigen values on the predictive performance of prostate-specific antigen velocity and prostate-specific antigen doubling time. The study included 137 active surveillance patients with two or more prediagnostic prostate-specific antigen levels measured over a period of at least 3 months. Two sets of analyses were carried out. First, the association between prostate-specific antigen kinetics calculated using only the prediagnostic prostate-specific antigen values and the risk of biopsy progression was studied. Second, using the same cohort of patients, the predictive value of prostate-specific antigen kinetics calculated using only post-diagnostic prostate-specific antigens and compared with that of prostate-specific antigen kinetics based on both pre- and post-diagnostic prostate-specific antigen levels was analyzed. Of 137 patients included in the analysis, 37 (27%) had biopsy progression over a median follow-up period of 3.2 years. Prediagnostic prostate-specific antigen velocity of more than 2 ng/mL/year and 3 ng/mL/year was statistically significantly associated with the risk of future biopsy progression. However, after adjustment for baseline prostate-specific antigen density, these associations were no longer significant. None of the tested prostate-specific antigen kinetics based on combined pre- and post-diagnostic prostate-specific antigen values were statistically significantly associated with the risk of biopsy progression. Historical prediagnostic prostate-specific antigens seems to be not clinically useful in patients diagnosed with low-risk prostate cancer on active surveillance. © 2016 The Japanese Urological Association.

Prostate specific antigen density to predict prostate cancer upgrading in a contemporary radical prostatectomy series: a single center experience.

PubMed

Magheli, Ahmed; Hinz, Stefan; Hege, Claudia; Stephan, Carsten; Jung, Klaus; Miller, Kurt; Lein, Michael

2010-01-01

We investigated the value of pretreatment prostate specific antigen density to predict Gleason score upgrading in light of significant changes in grading routine in the last 2 decades. Of 1,061 consecutive men who underwent radical prostatectomy between 1999 and 2004, 843 were eligible for study. Prostate specific antigen density was calculated and a cutoff for highest accuracy to predict Gleason upgrading was determined using ROC curve analysis. The predictive accuracy of prostate specific antigen and prostate specific antigen density to predict Gleason upgrading was evaluated using ROC curve analysis based on predicted probabilities from logistic regression models. Prostate specific antigen and prostate specific antigen density predicted Gleason upgrading on univariate analysis (as continuous variables OR 1.07 and 7.21, each p <0.001) and on multivariate analysis (as continuous variables with prostate specific antigen density adjusted for prostate specific antigen OR 1.07, p <0.001 and OR 4.89, p = 0.037, respectively). When prostate specific antigen density was added to the model including prostate specific antigen and other Gleason upgrading predictors, prostate specific antigen lost its predictive value (OR 1.02, p = 0.423), while prostate specific antigen density remained an independent predictor (OR 4.89, p = 0.037). Prostate specific antigen density was more accurate than prostate specific antigen to predict Gleason upgrading (AUC 0.61 vs 0.57, p = 0.030). Prostate specific antigen density is a significant independent predictor of Gleason upgrading even when accounting for prostate specific antigen. This could be especially important in patients with low risk prostate cancer who seek less invasive therapy such as active surveillance since potentially life threatening disease may be underestimated. Further studies are warranted to help evaluate the role of prostate specific antigen density in Gleason upgrading and its significance for biochemical outcome.

Bioimaging techniques for subcellular localization of plant hemoglobins and measurement of hemoglobin-dependent nitric oxide scavenging in planta.

PubMed

Hebelstrup, Kim H; Østergaard-Jensen, Erik; Hill, Robert D

2008-01-01

Plant hemoglobins are ubiquitous in all plant families. They are expressed at low levels in specific tissues. Several studies have established that plant hemoglobins are scavengers of nitric oxide (NO) and that varying the endogenous level of hemoglobin in plant cells negatively modulates bioactivity of NO generated under hypoxic conditions or during cellular signaling. Earlier methods for determination of hemoglobin-dependent scavenging in planta were based on measuring activity in whole plants or organs. Plant hemoglobins do not contain specific organelle localization signals; however, earlier reports on plant hemoglobin have demonstrated either cytosolic or nuclear localization, depending on the method or cell type investigated. We have developed two bioimaging techniques: one for visualization of hemoglobin-catalyzed scavenging of NO in specific cells and another for visualization of subcellular localization of green fluorescent protein-tagged plant hemoglobins in transformed Arabidopsis thaliana plants.

Development of a Nomogram for Predicting Severe Neutropenia Associated With Docetaxel-Based Chemotherapy in Patients With Castration-Resistant Prostate Cancer.

PubMed

Hirasawa, Yosuke; Nakashima, Jun; Sugihara, Toru; Takizawa, Issei; Gondo, Tatsuo; Nakagami, Yoshihiro; Horiguchi, Yutaka; Ohno, Yoshio; Namiki, Kazunori; Ohori, Makoto; Tachibana, Masaaki

2017-02-01

Neutropenia is a major adverse event of docetaxel-based chemotherapy. The present study was undertaken to evaluate the incidence of neutropenia and to develop a nomogram for predicting Grade 4 neutropenia during the first cycle of docetaxel-based chemotherapy in patients with castration-resistant prostate cancer (CRPC). This study included 112 patients with CRPC treated with docetaxel-based systemic chemotherapy. We evaluated the incidence and risk factors for Grade 4 neutropenia in the first cycle of chemotherapy. Sixty-two of 112 patients (55.4%) developed Grade 4 neutropenia in the first cycle of docetaxel-based chemotherapy. There were significant differences in age, baseline white blood cell count, and baseline neutrophil count between patients with non-Grade 4 neutropenia and those with Grade 4 neutropenia in univariate analyses. The serum prostate-specific antigen level, hemoglobin level, creatinine, albumin, Eastern Cooperative Oncology Group performance status, metastatic sites, extent of disease, and history of external beam radiotherapy to the prostate were not significantly different between the 2 groups. Multivariate logistic regression analysis showed that age (odds ratio [OR], 1.08; P = .019) and baseline neutrophil counts (OR, 0.79; P = .045) were significant independent risk factors for severe neutropenia. A nomogram and a calibration plot on the basis of these results were developed from a multivariate logistic regression analysis to predict the probability of Grade 4 neutropenia. Age and baseline neutrophil counts were significant independent risk factors for Grade 4 neutropenia. The nomogram to predict it provides useful information for the management of patients with CRPC treated with docetaxel chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

African-American Men with Gleason Score 3+3=6 Prostate Cancer Produce Less Prostate Specific Antigen than Caucasian Men: A Potential Impact on Active Surveillance.

PubMed

Kryvenko, Oleksandr N; Balise, Raymond; Soodana Prakash, Nachiketh; Epstein, Jonathan I

2016-02-01

We assess the difference in prostate specific antigen production between African-American and Caucasian men with Gleason score 3+3=6 prostate cancer. We measured tumor volume in 414 consecutive radical prostatectomies from men with National Comprehensive Cancer Network(®) low risk prostate cancer (348 Caucasian, 66 African-American) who had Gleason score 3+3=6 disease at radical prostatectomy. We then compared clinical presentation, pathological findings, prostate specific antigen, prostate specific antigen density and prostate specific antigen mass (an absolute amount of prostate specific antigen in patient's circulation) between African-American and Caucasian men. The t-test and Wilcoxon rank sum were used for comparison of means. African-American and Caucasian men had similar clinical findings based on age, body mass index and prostate specific antigen. There were no statistically significant differences between the dominant tumor nodule volume and total tumor volume (mean 0.712 vs 0.665 cm(3), p=0.695) between African-American and Caucasian men. Prostates were heavier in African-American men (mean 55.4 vs 46.3 gm, p <0.03). Despite the significantly greater weight of benign prostate tissue contributing to prostate specific antigen in African-American men, prostate specific antigen mass was not different from that of Caucasian men (mean 0.55 vs 0.558 μg, p=0.95). Prostate specific antigen density was significantly less in African-American men due to larger prostates (mean 0.09 vs 0.105, p <0.02). African-American men with Gleason score 3+3=6 prostate cancer produce less prostate specific antigen than Caucasian men. African-American and Caucasian men had equal serum prostate specific antigen and prostate specific antigen mass despite significantly larger prostates in African-American men with all other parameters, particularly total tumor volume, being the same. This finding has practical implications in T1c cases diagnosed with prostate cancer due to prostate specific antigen screening. Lowering the prostate specific antigen density threshold in African-American men may account for this disparity, particularly in selecting patients for active surveillance programs. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate specific antigen velocity does not aid prostate cancer detection in men with prior negative biopsy.

PubMed

Vickers, Andrew J; Wolters, Tineke; Savage, Caroline J; Cronin, Angel M; O'Brien, M Frank; Roobol, Monique J; Aus, Gunnar; Scardino, Peter T; Hugosson, Jonas; Schröder, Fritz H; Lilja, Hans

2010-09-01

Prostate specific antigen velocity has been proposed as a marker to aid in prostate cancer detection. We determined whether prostate specific antigen velocity could predict repeat biopsy results in men with persistently increased prostate specific antigen after initial negative biopsy. We identified 1,837 men who participated in the Göteborg or Rotterdam section of the European Randomized Screening study of Prostate Cancer and who underwent 1 or more subsequent prostate biopsies after an initial negative finding. We evaluated whether prostate specific antigen velocity improved predictive accuracy beyond that of prostate specific antigen alone. Of the 2,579 repeat biopsies 363 (14%) were positive for prostate cancer, of which 44 (1.7%) were high grade (Gleason score 7 or greater). Prostate specific antigen velocity was statistically associated with cancer risk but had low predictive accuracy (AUC 0.55, p <0.001). There was some evidence that prostate specific antigen velocity improved AUC compared to prostate specific antigen for high grade cancer. However, the small increase in risk associated with high prostate specific antigen velocity (from 1.7% to 2.8% as velocity increased from 0 to 1 ng/ml per year) had questionable clinical relevance. Men with prior negative biopsy are at lower risk for prostate cancer at subsequent biopsies with high grade disease particularly rare. We found little evidence to support prostate specific antigen velocity to aid in decisions about repeat biopsy for prostate cancer. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Statin use and survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide after docetaxel failure: the international retrospective observational STABEN study.

PubMed

Gordon, Jacob A; Buonerba, Carlo; Pond, Gregory; Crona, Daniel; Gillessen, Silke; Lucarelli, Giuseppe; Rossetti, Sabrina; Dorff, Tanya; Artale, Salvatore; Locke, Jennifer A; Bosso, Davide; Milowsky, Matthew Ivan; Witek, Mira Sofie; Battaglia, Michele; Pignata, Sandro; Cherhroudi, Cyrus; Cox, Michael E; De Placido, Pietro; Ribera, Dario; Omlin, Aurelius; Buonocore, Gaetano; Chi, Kim; Kollmannsberger, Christian; Khalaf, Daniel; Facchini, Gaetano; Sonpavde, Guru; De Placido, Sabino; Eigl, Bernhard J; Di Lorenzo, Giuseppe

2018-04-13

Statins may potentiate the effects of anti-hormonal agents for metastatic castration-resistant prostate cancer (mCRPC) through further disruption of essential steroidogenic processes. We investigated the effects of statin use on clinical outcomes in patients with mCRPC receiving abiraterone or enzalutamide. This was a retrospective multicenter study including patients that received abiraterone or enzalutamide for mCRPC. The effect of concurrent statin use on outcomes was evaluated. The associations of statins with early (≤12 weeks) prostate-specific antigen (PSA) declines (> 30%), cancer-specific survival and overall survival (OS) were evaluated after controlling for known prognostic factors. Five hundred and ninety-eight patients treated with second-line abiraterone or enzalutamide after docetaxel for mCRPC were included. A total of 199 men (33.3%) received statins during abiraterone/enzalutamide treatment. Median OS was 20.8 months (95% CI = 18.3-23.2) for patients who received statins, versus 12.9 months (95% CI = 11.4-14.6) for patients who did not receive statins ( P < 0.001). After adjusting for age, alkaline phosphatase, PSA, neutrophil-to-lymphocytes ratio, Charlson comorbidity score, Gleason score, visceral disease, hemoglobin, opiate use and abiraterone versus enzalutamide treatment, the use of statin therapy was associated with a 53% reduction in the overall risk of death (hazard ratio [HR] = 0.47; 95% CI = 0.35-0.63; P < 0.001). Statin use was also associated with a 63% increased odds of a > 30% PSA decline within the first 12 weeks of treatment (OR = 1.63; 95% CI = 1.03-2.60; P = 0.039). In this retrospective cohort, statin use was significantly associated with both prolonged OS and cancer-specific survival and increased early > 30% PSA declines. Prospective validation is warranted.

Prostate-specific antigen velocity is not better than total prostate-specific antigen in predicting prostate biopsy diagnosis.

PubMed

Gorday, William; Sadrzadeh, Hossein; de Koning, Lawrence; Naugler, Christopher T

2015-12-01

1.) Identify whether prostate-specific antigen velocity improves the ability to predict prostate biopsy diagnosis. 2.) Test whether there is an increase in the predictive capability of models when Gleason 7 prostate cancers are separated into a 3+4 and a 4+3 group. Calgary Laboratory Services' Clinical Laboratory Information System was searched for prostate biopsies reported between January 1, 2009 and December 31, 2013. Total prostate-specific antigen tests were recorded for each patient from January 1, 2007 to the most recent test before their recorded prostate biopsy. The data set was divided into the following three groups for comparison; benign, all prostate cancer and Gleason 7-10. The Gleason grade 7-10 group was further divided into 4+3 and 3+4 Gleason 7 prostate cancers. Prostate-specific antigen velocity was calculated using four different methods found in the literature. Receiver operator curves were used to assess operational characteristics of the tests. 4622 men between the ages of 40-89 with a prostate biopsy were included for analysis. Combining prostate-specific antigen velocity with total prostate-specific antigen (AUC=0.570-0.712) resulted in small non-statistically significant changes to the area under the curve compared to the area under the curve of total prostate-specific antigen alone (AUC=0.572-0.699). There were marked increases in the area under curves when 3+4 and 4+3 Gleason 7 cancers were separated. Prostate-specific antigen velocity does not add predictive value for prostate biopsy diagnosis. The clinical significance of the prostate specific antigen test can be improved by separating Gleason 7 prostate cancers into a 3+4 and 4+3 group. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The impact of irrigating fluid absorption on blood coagulation in patients undergoing transurethral resection of the prostate

PubMed Central

Shin, Hyun-Jung; Na, Hyo-Seok; Jeon, Young-Tae; Park, Hee-Pyoung; Nam, Sun-Woo; Hwang, Jung-Won

2017-01-01

Abstract Although endoscopic transurethral resection of the prostate (TURP) is a well-established procedure as a treatment for benign prostatic hyperplasia, its complications remain a concern. Among these, coagulopathy may be caused by the absorption of irrigating fluid. This study aimed to evaluate such phenomenon using a rotational thromboelastometry (ROTEM). A total of 20 patients undergoing TURP participated in this study. A mixture of 2.7% sorbitol–0.54% mannitol solution and 1% ethanol was used as an irrigating fluid, and fluid absorption was measured via the ethanol concentration in expired breath. The effects on coagulation were assessed by pre- and postoperative laboratory blood tests, including hemoglobin, hematocrit, platelet count, international normalized ratio of prothrombin time (PT-INR), activated partial thromboplastin time, electrolyte, and ROTEM. INTEM-clotting time (INTEM-CT) was significantly lengthened by 14% (P = 0.001). INTEM-α-angle was significantly decreased by 3% (P = 0.011). EXTEM-clot formation time was significantly prolonged by 18% (P = 0.008), and EXTEM-maximum clot firmness (EXTEM-MCF) was significantly decreased by 4% (P = 0.010). FIBTEM-MCF was also significantly decreased by 13% (P = 0.015). Moreover, hemoglobin (P < 0.001), hematocrit (P < 0.001), platelet counts (P < 0.001), potassium (P = 0.024), and ionized calcium (P = 0.004) were significantly decreased, while PT-INR (P = 0.001) was significantly increased after surgery. The amount of irrigating fluid absorbed was significantly associated with the weight of resected prostatic tissue (P = 0.001) and change of INTEM-CT (P < 0.001). As shown by the ROTEM analysis, the irrigating fluid absorbed during TURP impaired the blood coagulation cascade by creating a disruption in the coagulation factor activity or by lowering the coagulation factor concentration via dilution. PMID:28079789

The impact of irrigating fluid absorption on blood coagulation in patients undergoing transurethral resection of the prostate: A prospective observational study using rotational thromboelastometry.

PubMed

Shin, Hyun-Jung; Na, Hyo-Seok; Jeon, Young-Tae; Park, Hee-Pyoung; Nam, Sun-Woo; Hwang, Jung-Won

2017-01-01

Although endoscopic transurethral resection of the prostate (TURP) is a well-established procedure as a treatment for benign prostatic hyperplasia, its complications remain a concern. Among these, coagulopathy may be caused by the absorption of irrigating fluid. This study aimed to evaluate such phenomenon using a rotational thromboelastometry (ROTEM).A total of 20 patients undergoing TURP participated in this study. A mixture of 2.7% sorbitol-0.54% mannitol solution and 1% ethanol was used as an irrigating fluid, and fluid absorption was measured via the ethanol concentration in expired breath. The effects on coagulation were assessed by pre- and postoperative laboratory blood tests, including hemoglobin, hematocrit, platelet count, international normalized ratio of prothrombin time (PT-INR), activated partial thromboplastin time, electrolyte, and ROTEM.INTEM-clotting time (INTEM-CT) was significantly lengthened by 14% (P = 0.001). INTEM-α-angle was significantly decreased by 3% (P = 0.011). EXTEM-clot formation time was significantly prolonged by 18% (P = 0.008), and EXTEM-maximum clot firmness (EXTEM-MCF) was significantly decreased by 4% (P = 0.010). FIBTEM-MCF was also significantly decreased by 13% (P = 0.015). Moreover, hemoglobin (P < 0.001), hematocrit (P < 0.001), platelet counts (P < 0.001), potassium (P = 0.024), and ionized calcium (P = 0.004) were significantly decreased, while PT-INR (P = 0.001) was significantly increased after surgery. The amount of irrigating fluid absorbed was significantly associated with the weight of resected prostatic tissue (P = 0.001) and change of INTEM-CT (P < 0.001).As shown by the ROTEM analysis, the irrigating fluid absorbed during TURP impaired the blood coagulation cascade by creating a disruption in the coagulation factor activity or by lowering the coagulation factor concentration via dilution.

Feasibility of interstitial near-infrared radiance spectroscopy platform for ex vivo canine prostate studies: optical properties extraction, hemoglobin and water concentration, and gold nanoparticles detection

NASA Astrophysics Data System (ADS)

Grabtchak, Serge; Montgomery, Logan G.; Whelan, William M.

2014-05-01

The canine prostate is a close match for the human prostate and is used in research of prostate cancers. Determining accurately optical absorption and scattering properties of the gland in a wide spectral range (preferably in a minimally invasive way), linking optical properties to concentrations of major endogenous chromophores, and detecting the presence of localized optical inhomogeneities like inclusions of gold nanoparticles for therapeutic and diagnostic purposes, are among the major challenges for researchers. The goal of the article is to demonstrate a feasibility of the multifunctional radiance spectroscopy platform in providing the required information. For ex vivo canine prostate, extraction of the effective attenuation and diffusion coefficients using relative cw radiance measurements was demonstrated in the 650- to 900-nm range. The derived absorption coefficient was decomposed to contributions from 9.0 μM HbO2, 29.6 μM Hb, and 0.47 fractional volume of H2O. Detection of a localized inclusion containing ˜1.5.1010 gold nanorods (0.8 μg Au) at 10 mm distance from the urethra was achieved with the detector in the urethra and the light source in a virtual rectum position. The platform offers the framework for a systematic study of various chromophores in the prostate that can be used as comprehensive diagnostic markers.

Feasibility of interstitial near-infrared radiance spectroscopy platform for ex vivo canine prostate studies: optical properties extraction, hemoglobin and water concentration, and gold nanoparticles detection.

PubMed

Grabtchak, Serge; Montgomery, Logan G; Whelan, William M

2014-05-01

The canine prostate is a close match for the human prostate and is used in research of prostate cancers. Determining accurately optical absorption and scattering properties of the gland in a wide spectral range (preferably in a minimally invasive way), linking optical properties to concentrations of major endogenous chromophores, and detecting the presence of localized optical inhomogeneities like inclusions of gold nanoparticles for therapeutic and diagnostic purposes, are among the major challenges for researchers. The goal of the article is to demonstrate a feasibility of the multifunctional radiance spectroscopy platform in providing the required information. For ex vivo canine prostate, extraction of the effective attenuation and diffusion coefficients using relative cw radiance measurements was demonstrated in the 650- to 900-nm range. The derived absorption coefficient was decomposed to contributions from 9.0 μM HbO₂, 29.6 μM Hb, and 0.47 fractional volume of H₂O. Detection of a localized inclusion containing ∼1.5·1010 gold nanorods (0.8 μg Au) at 10 mm distance from the urethra was achieved with the detector in the urethra and the light source in a virtual rectum position. The platform offers the framework for a systematic study of various chromophores in the prostate that can be used as comprehensive diagnostic markers.

Impact of obesity on the predictive accuracy of prostate-specific antigen density and prostate-specific antigen in native Korean men undergoing prostate biopsy.

PubMed

Kim, Jae Heon; Doo, Seung Whan; Yang, Won Jae; Lee, Kwang Woo; Lee, Chang Ho; Song, Yun Seob; Jeon, Yoon Su; Kim, Min Eui; Kwon, Soon-Sun

2014-10-01

To evaluate the impact of obesity on the biopsy detection of prostate cancer. We retrospectively reviewed data of 1182 consecutive Korean patients (≥50 years) with serum prostate-specific antigen levels of 3-10 ng/mL who underwent initial extended 12-cores biopsy from September 2009 to March 2013. Patients who took medications that were likely to influence the prostate-specific antigen level were excluded. Receiver operating characteristic curves were plotted for prostate-specific antigen and prostate-specific antigen density predicting cancer status among non-obese and obese men. A total of 1062 patients (mean age 67.1 years) were enrolled in the analysis. A total of 230 men (21.7%) had a positive biopsy. In the overall study sample, the area under the receiver operator characteristic curve of serum prostate-specific antigen for predicting prostate cancer on biopsy were 0.584 and 0.633 for non-obese and obese men, respectively (P = 0.234). However, the area under the curve for prostate-specific antigen density in predicting cancer status showed a significant difference (non-obese 0.696, obese 0.784; P = 0.017). There seems to be a significant difference in the ability of prostate-specific antigen density to predict biopsy results between non-obese and obese men. Obesity positively influenced the overall ability of prostate-specific antigen density to predict prostate cancer. © 2014 The Japanese Urological Association.

Prostate-specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer.

PubMed

Hashimoto, Takeshi; Ohori, Makoto; Shimodaira, Kenji; Kaburaki, Naoto; Hirasawa, Yosuke; Satake, Naoya; Gondo, Tatsuo; Nakagami, Yoshihiro; Namiki, Kazunori; Ohno, Yoshio

2018-06-01

To clarify the impact of prostate-specific antigen screening on surgical outcomes of prostate cancer. Patients who underwent radical prostatectomy were divided into two groups according to prostate-specific antigen testing opportunity (group 1, prostate-specific antigen screening; group 2, non-prostate-specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank-sum and χ 2 -tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence-free survival. In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate-specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5-year biochemical recurrence-free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate-specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate-specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate-specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study. Detection by screening results in favorable outcomes after surgery. Prostate-specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer. © 2018 The Japanese Urological Association.

Prostate Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0595 TITLE: Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate Cancer...Sep 2016 - 14 Sep 2017 4. TITLE AND SUBTITLE Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate

Prognostic Significance of Digital Rectal Examination and Prostate Specific Antigen in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Arm.

PubMed

Halpern, Joshua A; Shoag, Jonathan E; Mittal, Sameer; Oromendia, Clara; Ballman, Karla V; Hershman, Dawn L; Wright, Jason D; Shih, Ya-Chen Tina; Nguyen, Paul L; Hu, Jim C

2017-02-01

The absence of definitive data or explicit guidelines regarding the use of digital rectal examination for prostate cancer screening may lead to confusion for physicians and patients alike. We evaluated the prognostic value of abnormal digital rectal examination and prostate specific antigen following the widespread dissemination of prostate specific antigen testing in the U.S. Collectively, men comprising the screening arm of the PLCO cancer screening trial who underwent digital rectal examination screening (35,350) were followed for 314,033 person-years. Adjusted analyses with competing risks regression were performed to assess the association of suspicious (nodularity, induration, asymmetry) digital rectal examination and abnormal prostate specific antigen (4 ng/ml or greater) with the detection of clinically significant prostate cancer, prostate cancer specific mortality and overall mortality. Among all screening encounters with a suspicious digital rectal examination only 15.4% had a concurrently abnormal prostate specific antigen (McNemar's test p <0.001). During followup there were 1,612 clinically significant prostate cancers detected, 64 prostate cancer specific deaths and 4,600 deaths. On multivariable analysis suspicious digital rectal examination and abnormal prostate specific antigen were associated with a greater risk of clinically significant prostate cancer (HR 2.21, 95% CI 1.99-2.44 vs HR 5.48, 95% CI 5.05-5.96, p <0.001 and p <0.001) and prostate cancer specific mortality (HR 2.54, 95% CI 1.41-4.58 vs HR 5.23, 95% CI 3.08-8.88, p=0.002 and p <0.001), respectively. In a secondary analysis of a contemporary U.S. cohort, suspicious digital rectal examination and abnormal prostate specific antigen on routine screening were independently associated with clinically significant prostate cancer and prostate cancer specific mortality. However, additional research is needed to optimize screening protocols. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Relative value of race, family history and prostate specific antigen as indications for early initiation of prostate cancer screening.

PubMed

Vertosick, Emily A; Poon, Bing Ying; Vickers, Andrew J

2014-09-01

Many guidelines suggest earlier screening for prostate cancer in men at high risk, with risk defined in terms of race and family history. Recent evidence suggests that baseline prostate specific antigen is strongly predictive of the long-term risk of aggressive prostate cancer. We compared the usefulness of risk stratifying early screening by race, family history and prostate specific antigen at age 45 years. Using estimates from the literature we calculated the proportion of men targeted for early screening using family history, black race or prostate specific antigen as the criterion for high risk. We calculated the proportion of prostate cancer deaths that would occur in those men by age 75 years. Screening based on family history involved 10% of men, accounting for 14% of prostate cancer deaths. Using black race as a risk criterion involved 13% of men, accounting for 28% of deaths. In contrast, 44% of prostate cancer deaths occurred in the 10% of men with the highest prostate specific antigen at age 45 years. In no sensitivity analysis for race and family history did the ratio of risk group size to number of prostate cancer deaths in that risk group approach that of prostate specific antigen. Basing decisions for early screening on prostate specific antigen at age 45 years provided the best ratio between men screened and potential cancer deaths avoided. Given the lack of evidence that race or family history affects the relationship between prostate specific antigen and risk, prostate specific antigen based risk stratification would likely include any black men or men with a family history who are destined to experience aggressive disease. Differential screening based on risk should be informed by baseline prostate specific antigen. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate volume did not affect voiding function improvements in diode laser enucleation of the prostate.

PubMed

Yang, Stephen Shei-Dei; Hsieh, Cheng-Hsing; Chiang, I-Ni; Lin, Chia-Da; Chang, Shang-Jen

2013-03-01

We compared safety and surgical outcomes in patients with different prostate sizes treated with diode laser enucleation of the prostate. From 2008 to 2012 consecutive patients with benign prostatic obstruction undergoing diode laser prostate enucleation at our institution were enrolled for analysis. A single surgeon performed diode laser prostate enucleation with an end firing, continuous wave diode laser (980 nm). Based on preoperative prostate volume on transrectal ultrasound, patients were stratified into 2 groups, including group 1-65 with less than 60 ml and group 2-55 with 60 ml or greater. Baseline and perioperative characteristics, and postoperative surgical outcomes were compared between the 2 groups. A total of 120 men with a mean ± SD age of 70.2 ± 9.0 years were enrolled for analysis. Compared with group 1 patients, those in group 2 had larger mean total prostate volume (85.0 ± 24.6 vs 40.9 ± 10.8 ml), longer mean operative time (117.7 ± 48.2 vs 60.7 ± 25.0 minutes), higher mean retrieved prostate weight (37.3 ± 16.1 vs 12.5 ± 7.3 gm) and a higher mean tissue retrieval ratio (74.4% ± 22.2% vs 58.8% ± 23.2%, p <0.01). There was no significant difference in the postoperative hemoglobin decrease in the 2 groups (median 0.5 vs 0.9 mg/dl, p = 0.11). The rate of temporary postoperative urinary retention after Foley catheter removal was significantly lower in group 2 (15.4% vs 3.6%, p = 0.04). Postoperative improvements in the peak flow rate, post-void residual urine volume and International Prostate Symptom Score were comparable in the 2 groups. Although patients with a larger prostate required significantly longer operative time and laser energy, voiding function improvements and surgical complication rates of diode laser prostate enucleation were comparable in patients with a larger vs smaller prostate. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate cancer prediction using the random forest algorithm that takes into account transrectal ultrasound findings, age, and serum levels of prostate-specific antigen.

PubMed

Xiao, Li-Hong; Chen, Pei-Ran; Gou, Zhong-Ping; Li, Yong-Zhong; Li, Mei; Xiang, Liang-Cheng; Feng, Ping

2017-01-01

The aim of this study is to evaluate the ability of the random forest algorithm that combines data on transrectal ultrasound findings, age, and serum levels of prostate-specific antigen to predict prostate carcinoma. Clinico-demographic data were analyzed for 941 patients with prostate diseases treated at our hospital, including age, serum prostate-specific antigen levels, transrectal ultrasound findings, and pathology diagnosis based on ultrasound-guided needle biopsy of the prostate. These data were compared between patients with and without prostate cancer using the Chi-square test, and then entered into the random forest model to predict diagnosis. Patients with and without prostate cancer differed significantly in age and serum prostate-specific antigen levels (P < 0.001), as well as in all transrectal ultrasound characteristics (P < 0.05) except uneven echo (P = 0.609). The random forest model based on age, prostate-specific antigen and ultrasound predicted prostate cancer with an accuracy of 83.10%, sensitivity of 65.64%, and specificity of 93.83%. Positive predictive value was 86.72%, and negative predictive value was 81.64%. By integrating age, prostate-specific antigen levels and transrectal ultrasound findings, the random forest algorithm shows better diagnostic performance for prostate cancer than either diagnostic indicator on its own. This algorithm may help improve diagnosis of the disease by identifying patients at high risk for biopsy.

Prostate-Specific Antigen (PSA) Test: MedlinePlus Lab Test Information

MedlinePlus

... gov/labtests/prostatespecificantigenpsatest.html Prostate-Specific Antigen (PSA) Test To use the sharing features on this page, ... JavaScript. What is a prostate-specific antigen (PSA) test? A prostate-specific antigen (PSA) test measures the ...

Ex vivo evaluation of safety and efficacy of vaporization of the prostate using a 300 W high-power laser diode with the wavelength of 980 nm

NASA Astrophysics Data System (ADS)

Takada, Junya; Honda, Norihiro; Hazama, Hisanao; Awazu, Kunio

2014-03-01

Laser vaporization of the prostate is one of the promising technique for less-invasive treatment of benign prostatic hyperplasia. However, shorter operative duration and higher hemostatic ability are expected. The wavelength of 980 nm offers a high simultaneous absorption by water and hemoglobin, so that it combines the efficient vaporization with good hemostasis. Therefore, we have evaluated the safety and efficacy of vaporization of the prostate using a recently developed 300 W high-power laser diode with the wavelength of 980 nm. First, validity of bovine prostate tissue as the sample was confirmed by measuring the optical properties of bovine and human prostate tissue using a double integrating sphere optical system. Next, contact and non-contact ex vivo irradiations were performed for various irradiation powers and times, and vaporized and coagulated depths were measured. In the contact irradiation, the vaporized depth at the power of 300 W was significantly deeper than that at the power of 100 W, while the difference was relatively smaller for the coagulated depths at 300 and 100 W. In the non-contact irradiation, coagulation as thick as that in the contact irradiation was observed almost without vaporization. Therefore, it is suggested that the treatment in the contact irradiation using the high-power laser diode can vaporize the prostate more efficiently without increasing the risk of perforation. Hemostasis with the coagulation would be possible in both irradiation methods. To prevent the postoperative perforation, operators need to understand the relationship between the coagulated depth and the irradiation conditions.

Do Ultrasensitive Prostate Specific Antigen Measurements Have a Role in Predicting Long-Term Biochemical Recurrence-Free Survival in Men after Radical Prostatectomy?

PubMed

Sokoll, Lori J; Zhang, Zhen; Chan, Daniel W; Reese, Adam C; Bivalacqua, Trinity J; Partin, Alan W; Walsh, Patrick C

2016-02-01

In this study we evaluate an ultrasensitive prostate specific antigen assay in patients with prostate cancer after radical prostatectomy to predict long-term biochemical recurrence-free survival. A total of 754 men who underwent radical prostatectomy and had an undetectable prostate specific antigen after surgery (less than 0.1 ng/ml) were studied. Prostate specific antigen was measured in banked serum specimens with an ultrasensitive assay (Hybritech® PSA, Beckman Coulter Access® 2) using a cutoff of 0.01 ng/ml. Prostate specific antigen was also measured in 44 men after cystoprostatectomy who had no pathological evidence of prostate cancer with the Hybritech assay and with the Quanterix AccuPSA™ assay. Of the 754 men 17% (131) experienced biochemical recurrence (median 4.0 years). Those men without biochemical recurrence (83%, 623) had a minimum of 5 years of followup (median 11). Prostate specific antigen was less than 0.01 ng/ml in 93.4% of men with no biochemical recurrence, whereas 30.5% of men with biochemical recurrence had a prostate specific antigen of 0.01 ng/ml or greater. On multivariate analysis postoperative prostate specific antigen at a 0.01 ng/ml cutoff, pathological stage and Gleason score, and surgical margins were significant independent predictors of biochemical recurrence risk. Kaplan-Meier estimates for mean biochemical recurrence-free survival were 15.2 years (95% CI 14.9-15.6) for prostate specific antigen less than 0.01 ng/ml and 10.0 years (95% CI 8.4-11.5) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Biochemical recurrence-free rates 11 years after surgery were 86.1% (95% CI 83.2-89.0) for prostate specific antigen less than 0.01 ng/ml and 48.9% (95% CI 37.5-60.3) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Prostate specific antigen concentrations in 44 men after cystoprostatectomy were all less than 0.03 ng/ml, with 95.4% less than 0.01 ng/ml. In men with a serum prostate specific antigen less than 0.1 ng/ml after radical prostatectomy a tenfold lower cutoff (0.01 ng/ml) stratified biochemical recurrence-free survival and was a significant independent predictor of biochemical recurrence, as were pathological features. Prostate specific antigen concentrations in men without pathological evidence of prostate cancer suggest that a higher prostate specific antigen concentration (0.03 ng/ml) in the ultrasensitive range may be needed to define the detection threshold. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Pathological Outcome following Radical Prostatectomy in Men with Prostate Specific Antigen Greater than 10 ng/ml and Histologically Favorable Risk Prostate Cancer.

PubMed

Yu, Jiwoong; Kwon, Young Suk; Kim, Sinae; Han, Christopher Sejong; Farber, Nicholas; Kim, Jongmyung; Byun, Seok Soo; Kim, Wun-Jae; Jeon, Seong Soo; Kim, Isaac Yi

2016-05-01

Active surveillance is now the treatment of choice in men with low risk prostate cancer. Although there is no consensus on which patients are eligible for active surveillance, prostate specific antigen above 10 ng/ml is generally excluded. In an attempt to determine the validity of using a prostate specific antigen cutoff of 10 ng/ml to counsel men considering active surveillance we analyzed a multi-institution database to determine the pathological outcome in men with prostate specific antigen greater than 10 ng/ml but histologically favorable risk prostate cancer. We queried a prospectively maintained database of men with histologically favorable risk prostate cancer who underwent radical prostatectomy between 2003 and 2015. The cohort was categorized into 3 groups based on prostate specific antigen level, including low-less than 10 ng/ml, intermediate-10 or greater to less than 20 and high-20 or greater. Associations of prostate specific antigen group with adverse pathological and oncologic outcomes were analyzed. Of 2,125 patients 1,327 were categorized with histologically favorable risk disease. However on multivariate analyses the rates of up staging and upgrading were similar between the intermediate and low prostate specific antigen groups. In contrast compared to the intermediate prostate specific antigen group the high group had higher incidences of up staging (p = 0.02) and upgrading to 4 + 3 or greater disease (p = 0.046). Biochemical recurrence-free survival rates revealed no pairwise intergroup differences except between the low and high groups. Patients with preoperatively elevated prostate specific antigen between 10 and less than 20 ng/ml who otherwise had histologically favorable risk prostate cancer were not at higher risk for adverse pathological outcomes than men with prostate specific antigen less than 10 ng/ml. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate cancer

MedlinePlus

... of prostate cancer. But, it can increase your prostate-specific antigen (PSA) blood test result. Symptoms With early prostate ... 2009 Best Practice Statement. www.auanet.org/guidelines/prostate-specific-antigen-(2009-amended-2013) . Accessed October 9, 2017. Moyer ...

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…

MRI-Derived Cellularity Index as a Potential Noninvasive Imaging Biomarker of Prostate Cancer

DTIC Science & Technology

2014-10-01

previously diagnosed with prostate cancer via standard transrectal ultrasound guided prostate biopsy after prostate specific antigen (PSA) elevation or...around 70% and specificity of 55% (72). Functional MR techniques enhance detection, grading, and staging of prostate cancer through the use of dynamic...and specificity in the diagnosis of prostate cancer by increasing tumor conspicuity on DWI or quantitative ADC maps. How- ever, hemorrhage, inflammatory

Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer.

PubMed

Halpern, Joshua A; Oromendia, Clara; Shoag, Jonathan E; Mittal, Sameer; Cosiano, Michael F; Ballman, Karla V; Vickers, Andrew J; Hu, Jim C

2018-04-01

Guidelines from the NCCN ® (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person-years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. A total of 1,713 clinically significant prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95% CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examination. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Clinicopathological Overview of Granulomatous Prostatitis: An Appraisal

PubMed Central

Dravid, Nandkumar; Nikumbh, Dhiraj; Patil, Ashish; Nagappa, Karibasappa Gundabaktha

2016-01-01

Introduction Granulomatous prostatitis is a rare inflammatory condition of the prostate. Granulomatous prostatitis is important because, it mimics prostatic carcinoma clinically and hence the diagnosis can be made only by histopathological examination. Aim To study the histomorphological features and to know the prevalence of granulomatous prostatitis. Materials and Methods Histopathological records of 1,203 prostatic specimens received in the Department of the Pathology over a period of five years (June 2009 – June 2014). Seventeen cases of histopathologically, diagnosed granulomatous prostatitis were retrieved and reterospective data was collected from the patient’s records. Results Out of 17 cases of granulomatous prostatitis, we encountered 9 cases of non-specific granulomatous prostatitis, 5 cases of xanthogranulomatous prostatitis and 3 cases of specific tubercular prostatitis. The common age ranged from 51-75 years (mean 63 years) with mean PSA level of 15.8ng/ml. Six patients showed focal hypoechoic areas on TRUS and 11 cases revealed hard and fixed nodule on DRE. Conclusion Non-specific granulomatous prostatitis is the most common type of granulomatous prostatitis. There is no specific pattern of clinical, biochemical and ultrasound findings that allows the diagnosis of granulomatous prostatitis or differentiates it from prostatic carcinoma. Hence, histomorphological diagnosis is the gold standard in differentiating various prostatic lesions. PMID:27014642

Prostate Cancer Relevant Antigens and Enzymes for Targeted Drug Delivery

PubMed Central

Barve, Ashutosh; Jin, Wei; Cheng, Kun

2014-01-01

Chemotherapy is one of the most widely used approaches in combating advanced prostate cancer, but its therapeutic efficacy is usually insufficient due to lack of specificity and associated toxicity. Lack of targeted delivery to prostate cancer cells is also the primary obstacles in achieving feasible therapeutic effect of other promising agents including peptide, protein, and nucleic acid. Consequently, there remains a critical need for strategies to increase the selectivity of anti-prostate cancer agents. This review will focus on various prostate cancer-specific antigens and enzymes that could be exploited for prostate cancer targeted drug delivery. Among various targeting strategies, active targeting is the most advanced approach to specifically deliver drugs to their designated cancer cells. In this approach, drug carriers are modified with targeting ligands that can specifically bind to prostate cancer-specific antigens. Moreover, there are several specific enzymes in the tumor microenvironment of prostate cancer that can be exploited for stimulus-responsive drug delivery systems. These systems can specifically release the active drug in the tumor microenvironment of prostate cancer, leading to enhanced tumor penetration efficiency. PMID:24878184

Antigen specific T-cell responses against tumor antigens are controlled by regulatory T cells in patients with prostate cancer.

PubMed

Hadaschik, Boris; Su, Yun; Huter, Eva; Ge, Yingzi; Hohenfellner, Markus; Beckhove, Philipp

2012-04-01

Immunotherapy is a promising approach in an effort to control castration resistant prostate cancer. We characterized tumor antigen reactive T cells in patients with prostate cancer and analyzed the suppression of antitumor responses by regulatory T cells. Peripheral blood samples were collected from 57 patients with histologically confirmed prostate cancer, 8 patients with benign prostatic hyperplasia and 16 healthy donors. Peripheral blood mononuclear cells were isolated and antigen specific interferon-γ secretion of isolated T cells was analyzed by enzyme-linked immunospot assay. T cells were functionally characterized and T-cell responses before and after regulatory T-cell depletion were compared. As test tumor antigens, a panel of 11 long synthetic peptides derived from a total of 8 tumor antigens was used, including prostate specific antigen and prostatic acid phosphatase. In patients with prostate cancer we noted a 74.5% effector T-cell response rate compared with only 25% in patients with benign prostatic hyperplasia and 31% in healthy donors. In most patients 2 or 3 tumor antigens were recognized. Comparing various disease stages there was a clear increase in the immune response against prostate specific antigens from intermediate to high risk tumors and castration resistant disease. Regulatory T-cell depletion led to a significant boost in effector T-cell responses against prostate specific antigen and prostatic acid phosphatase. Tumor specific effector T cells were detected in most patients with prostate cancer, especially those with castration resistant prostate cancer. Since effector T-cell responses against prostate specific antigens strongly increased after regulatory T-cell depletion, our results indicate that immunotherapy efficacy could be enhanced by decreasing regulatory T cells. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Incidental Detection of Type B2 Thymoma on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT Imaging.

PubMed

Krishnaraju, Venkata Subramanian; Basher, Rajender Kumar; Singh, Harmandeep; Singh, Shrawan Kumar; Bal, Amanjit; Mittal, Bhagwant Rai

2018-05-01

Ga-labeled prostate-specific membrane antigen is a novel radiotracer for imaging of prostate cancer. We report a hormonally treated patient with prostate carcinoma, presenting with lower urinary tract symptoms and rising prostate-specific antigen levels, who underwent Ga-labeled prostate-specific membrane antigen PET/CT for suspected recurrence. No tracer avid lesion was noted in the prostate gland and locoregional area. However, intense tracer avid heterogeneously enhancing soft tissue lesion with cystic areas and coarse calcifications was seen in the anterior mediastinum. PET/CT-guided biopsy from the mediastenal lesion revealed type B2 thymoma.

Synchronous Detection of Male Breast Cancer and Prostatic Cancer in a Patient With Suspected Prostatic Carcinoma on 68Ga-PSMA PET/CT Imaging.

PubMed

Kumar, Rajender; Mittal, Bhagwant Rai; Bhattacharya, Anish; Singh, Harmandeep; Singh, Shrawan Kumar

2018-06-01

The male breast cancer is very less common as compared with the female breast cancer. We report a case of 64-year-old man who presented with the history of lower urinary tract symptoms. The digital rectal examination revealed hard and nodular prostate, and serum prostate-specific antigen level was 23.4 ng/mL. Ga-labeled prostate-specific membrane antigen PET/CT revealed prostate-specific membrane antigen-expressing lesions in the prostate, axillary tail of the right breast, and axillary lymph nodes. Histology from prostate revealed prostate carcinoma, whereas fine-needle aspiration from the breast revealed invasive ductal carcinoma of the breast.

Identification of threshold prostate specific antigen levels to optimize the detection of clinically significant prostate cancer by magnetic resonance imaging/ultrasound fusion guided biopsy.

PubMed

Shakir, Nabeel A; George, Arvin K; Siddiqui, M Minhaj; Rothwax, Jason T; Rais-Bahrami, Soroush; Stamatakis, Lambros; Su, Daniel; Okoro, Chinonyerem; Raskolnikov, Dima; Walton-Diaz, Annerleim; Simon, Richard; Turkbey, Baris; Choyke, Peter L; Merino, Maria J; Wood, Bradford J; Pinto, Peter A

2014-12-01

Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum. We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed. A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis. Prostate cancer upgrading with targeted biopsy increases with an increasing prostate specific antigen cutoff. Above a prostate specific antigen threshold of 5.2 ng/ml most upgrading to clinically significant disease was achieved by targeted biopsy. In our population this corresponded to potentially sparing biopsy in 36% of patients who underwent multiparametric magnetic resonance imaging. Below this value 12-core biopsy detected more clinically insignificant cancer. Thus, the diagnostic usefulness of targeted biopsy is optimized in patients with prostate specific antigen 5.2 ng/ml or greater. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Synthesis of hemoglobin Gun Hill: increased synthesis of the heme-free βGH globin chain and subunit exchange with a free α-chain pool

PubMed Central

Rieder, Ronald F.

1971-01-01

Hemoglobin Gun Hill is an unstable mutant hemoglobin associated with mild compensated hemolysis. This abnormal protein has a deletion of five amino acids in the β-chains. The deletion includes the heme-binding proximal histidine at position 92. The β-chains of hemoglobin Gun Hill lack heme groups. Approximately 32% of the circulating hemoglobin in heterozygous subjects consists of the mutant hemoglobin. When reticulocytes were incubated with radioactive amino acid the specific activity of hemoglobin Gun Hill was three to six times that of hemoglobin A. Total incorporation of radioactivity into hemoglobin Gun Hill was two to three times that into hemoglobin A. There were 20-50% more total counts in β-Gun Hill (βGH) than in βA. These results indicate that in reticulocytes there was greater synthesis of the abnormal β-chains than βA-chains. The ratio of the specific activities of the α-chains of hemoglobin Gun Hill to the α-chains of hemoglobin A was 20: 1. There was evidence of a free pool of α-chains in the reticulocytes containing hemoglobin Gun Hill. After 10 min of incubation approximately 40% of the total α-chain radioactivity was in the free pool. When protein synthesis was blocked by incubation of reticulocytes with puromycin, the specific activity of the α-chains of hemoglobin Gun Hill continued to increase due to direct exchange of α-subunits between the free pool and preformed hemoglobin Gun Hill. Studies of the assembly of βA and βGH revealed that the rates of translation of the two polypeptide chains were equal and uniform. No evidence was obtained for the existence of “slow points” in the process of globin chain assembly. The studies also suggest that lack of strong heme-globin binding does not hinder the synthesis of globin chains. PMID:5540175

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging

PubMed Central

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging. PMID:27004542

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging.

PubMed

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging.

Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy.

PubMed

Page, Stephanie T; Hirano, Lianne; Gilchriest, Janet; Dighe, Manjiri; Amory, John K; Marck, Brett T; Matsumoto, Alvin M

2011-07-01

Benign prostatic hyperplasia and hypogonadism are common disorders in aging men. There is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia. We examined whether combining dutasteride, which inhibits testosterone to dihydrotestosterone conversion, with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone. We conducted a double-blind, placebo controlled trial of 53 men 51 to 82 years old with symptomatic benign prostatic hyperplasia, prostate volume 30 cc or greater and serum total testosterone less than 280 ng/dl (less than 9.7 nmol/l). Subjects were randomized to daily transdermal 1% T gel plus oral placebo or dutasteride for 6 months. Testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl. The primary outcomes were prostate volume measured by magnetic resonance imaging, serum prostate specific antigen and androgen levels. A total of 46 subjects completed all procedures. Serum testosterone increased similarly into the mid-normal range in both groups. Serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group. In the testosterone plus dutasteride group prostate volume and prostate specific antigen (mean ± SEM) decreased 12% ± 2.5% and 35% ± 5%, respectively, compared to the testosterone only group in which prostate volume and prostate specific antigen increased 7.5% ± 3.3% and 19% ± 7% (p = 0.03 and p = 0.008), respectively, after 6 months of treatment. Prostate symptom scores improved in both groups. Combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only. Coadministration of a 5α-reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older, hypogonadal men with symptomatic benign prostatic hyperplasia. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A two-stage model in a Bayesian framework to estimate a survival endpoint in the presence of confounding by indication.

PubMed

Bellera, Carine; Proust-Lima, Cécile; Joseph, Lawrence; Richaud, Pierre; Taylor, Jeremy; Sandler, Howard; Hanley, James; Mathoulin-Pélissier, Simone

2018-04-01

Background Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure. Objective Our aim was to highlight the flexibility of a two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework. For this purpose, we monitored the prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. We focused on the assessment of the prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure. Methods We used a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. We modeled prostate-specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability was expressed as a function of prostate-specific antigens concentration. Covariates in the survival model included hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process. Results We showed positive associations between an increased prostate-specific antigens nadir, an earlier changepoint and a steeper post-nadir slope with an increased risk of failure. Importantly, we highlighted a significant benefit of hormone therapy, an effect that was not observed when the prostate-specific antigens trajectory was not accounted for in the survival model. Conclusion Our modeling strategy was particularly flexible and accounted for multiple complex features of longitudinal and survival data, including the presence of a random changepoint and a time-dependent covariate.

Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

DOEpatents

Jensen, Ronald H.; Vanderlaan, Martin; Bigbee, William L.; Stanker, Larry H.; Branscomb, Elbert W.; Grabske, Robert J.

1988-01-01

The present invention provides monoclonal antibodies specific to and distinguish between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype.

Molecular Characterization of Indolent Prostate Cancer

DTIC Science & Technology

2016-12-01

prostate - specific antigen (PSA) test, and treated aggressively following diagnosis, leading to the contemporary problem of prostate cancer over-diagnosis... specific purpose of comparing low- risk and high-risk prostate cancer. Figure 3 shows the mapping rates for exon, intron, and inter-genic sequences. The...FFPE specimens, for the specific comparison of low-risk and high-risk prostate cancer. 5. Identified sufficient number of biopsy cases and sections

Hemoglobin Cleavage Site-Specificity of the Plasmodium falciparum Cysteine Proteases Falcipain-2 and Falcipain-3

PubMed Central

Subramanian, Shoba; Hardt, Markus; Choe, Youngchool; Niles, Richard K.; Johansen, Eric B.; Legac, Jennifer; Gut, Jiri; Kerr, Iain D.; Craik, Charles S.; Rosenthal, Philip J.

2009-01-01

The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches. First, using random P1 – P4 amino acid substrate libraries, falcipain-2 and falcipain-3 demonstrated strong preference for cleavage sites with Leu at the P2 position. Second, with overlapping peptides spanning α and β globin and proteolysis-dependent 18O labeling, hydrolysis was seen at many cleavage sites. Third, with intact hemoglobin, numerous cleavage products were identified. Our results suggest that hemoglobin hydrolysis by malaria parasites is not a highly ordered process, but rather proceeds with rapid cleavage by falcipains at multiple sites. However, falcipain-2 and falcipain-3 show strong specificity for P2 Leu in small peptide substrates, in agreement with the specificity in optimized small molecule inhibitors that was identified previously. These results are consistent with a principal role of falcipain-2 and falcipain-3 in the hydrolysis of hemoglobin by P. falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents. PMID:19357776

Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer.

PubMed

Hatano, Koji; Nishimura, Kazuo; Nakai, Yasutomo; Yoshida, Takahiro; Sato, Mototaka; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Uemura, Motohide; Oka, Daizo; Nakayama, Masashi; Takayama, Hitoshi; Shimizu, Kiyonori; Meguro, Norio; Tanigawa, Tsuyoshi; Yamaguchi, Seiji; Tsujimura, Akira; Nonomura, Norio

2013-08-01

A low-dose chemotherapy consisting of docetaxel, estramustine and dexamethasone was investigated for its beneficial effect and feasibility in Japanese patients with metastatic castration-resistant prostate cancer (CRPC). Seventy-two Japanese patients with metastatic CRPC were enrolled to receive docetaxel (25 mg/m(2) on days 2 and 9), estramustine phosphate (280 mg orally twice daily from day 1 to day 3 and from day 8 to day 10) and dexamethasone (0.5 mg orally twice daily) every 21 days. The median age of the patients was 72 years and 64 patients (89 %) had ≥grade 1 anemia at entry. The median total number of courses administered was 8.5 (range 1-93). Forty-two patients (58 %) had a prostate-specific antigen (PSA) decline of ≥50 %. The median progression-free survival and overall survival were 6 and 23 months, respectively. Fifteen patients (21 %) improved and 53 patients (74 %) were stable in their performance status. Of the 40 patients with bone pain, 25 patients (63 %) showed pain reduction. Among 71 patients assessable for their hemoglobin levels, 21 patients (30 %) achieved an increase of at least 1.0 g/dl. Of the 5 patients who terminated treatment because of ≥grade 3 toxicity, 4 patients had pneumonitis and one patient had anemia. Only one patient developed ≥grade 3 neutropenia. The low-dose combination of docetaxel, estramustine and dexamethasone is active and tolerable with beneficial effects on serum PSA levels, performance status, anemia and bone pain in Japanese patients with CRPC. This regimen is a reasonable option for elderly patients with bone disease at risk of hematologic toxicity.

Radium-223 IN metastatic hormone-sensitive high-grade prostate cancer: initial experience.

PubMed

Osvaldo, García-Pérez Francisco; Salvador, Medina-Ornelas Sevastián; Zael, Santana-Ríos; Nora, Sobrevilla-Moreno

2017-01-01

Our study evaluates the feasibility of compassionate exemption of Radium-223 ( 223 Ra) treatment in metastatic hormone-sensitive high-grade prostate cancer (mHSHGPC) patients with concomitant androgen deprivation-therapy (ADT). Seven patients with mHSHGPC, were treated with six cycles of 223 Ra plus ADT. All patients had undergone to 18 F-NaF-PET/CT. A qualitative analyses of the 18 F-NaF-PET/CT was performed in conjunction with Alkaline Phosphatase (ALP), Lactate-dehydrogenase (LDH) and Prostatic-Specific Antigen (PSA) values. The mean of SUVmax values were used as a quantitative measure of tumoral burden. Changes in PSA, ALP, LDH from baseline were evaluated, and were defined as increase or decrease of at least 30%. Clinical response was achieved if there was pain reduction using visual analogic scale. Four patients showed a significant reduction in mean SUVmax after 3 cycles of 223 Ra, and one after 6 cycles. Patients who showed reductions in mean SUVmax after Ra-223 also showed reductions in PSA, ALP and LDH. Four weeks after the last cycle of 223 Ra all patients had decreased total PSA, ALP and LDH values ≥ 30% also significant improvement on pain. No progress disease was documented after 14 ± 4 weeks. We found slight to moderate decreases in neutrophils and hemoglobin in two patients. We concluded that 223 Ra plus ADT can be useful in mHSHGPC; the semi-quantitative 18 F-NaF-PET/CT as a method effective to monitor the treatment response. Due to concomitant administration of ADT, 18 F-NaF-PET/CT cannot differentiate whether the findings were due to androgen blockade or the 223 Ra; nevertheless, data supporting the efficacy of 223 Ra is the significant improvement on pain.

Incidental Metastatic Melanoma Identified on 68Ga-Prostate-Specific Membrane Antigen PET/CT for Metastatic Prostate Cancer.

PubMed

Snow, Hayden A; Hofman, Michael S; Mitchell, Catherine A; Gyorki, David E; Smith, Myles J F

2018-07-01

A 78-year-old man with a history of surgically treated prostate cancer and melanoma underwent Ga-prostate-specific membrane antigen (PSMA) PET/CT for biochemical recurrence of his prostate cancer. This revealed locoregionally recurrent prostate cancer and a separate PSMA-avid nodule in his left arm. Subsequent F-FDG PET/CT and excision confirmed this to be an in-transit melanoma metastasis. Prostate-specific membrane antigen PET/CT has become a widely used and valuable tool in the assessment of prostate cancer, particularly biochemically recurrent. Uptake of PSMA has been described in a multitude of different benign and malignant conditions, but it has only rarely been documented in melanoma.

Prostate Specific Membrane Antigen Positron Emission Tomography May Improve the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging in Localized Prostate Cancer.

PubMed

Rhee, H; Thomas, P; Shepherd, B; Gustafson, S; Vela, I; Russell, P J; Nelson, C; Chung, E; Wood, G; Malone, G; Wood, S; Heathcote, P

2016-10-01

Positron emission tomography using ligands targeting prostate specific membrane antigen has recently been introduced. Positron emission tomography imaging with (68)Ga-PSMA-HBED-CC has been shown to detect metastatic prostate cancer lesions at a high rate. In this study we compare multiparametric magnetic resonance imaging and prostate specific membrane antigen positron emission tomography of the prostate with whole mount ex vivo prostate histopathology to determine the true sensitivity and specificity of these imaging modalities for detecting and locating tumor foci within the prostate. In a prospective clinical trial setting 20 patients with localized prostate cancer and a planned radical prostatectomy were recruited. All patients underwent multiparametric magnetic resonance imaging and positron emission tomography before surgery, and whole mount histopathology slides were directly compared to the images. European Society of Urogenital Radiology guidelines for reporting magnetic resonance imaging were used as a template for regional units of analysis. The uropathologist and radiologists were blinded to individual components of the study, and the final correlation was performed by visual and deformable registration analysis. A total of 50 clinically significant lesions were identified from the whole mount histopathological analysis. Based on regional analysis the sensitivity, specificity, positive predictive value and negative predictive value for multiparametric magnetic resonance imaging were 44%, 94%, 81% and 76%, respectively. With prostate specific membrane antigen positron emission tomography the sensitivity, specificity, positive predictive value and negative predictive value were 49%, 95%, 85% and 88%, respectively. Prostate specific membrane antigen positron emission tomography yielded a higher specificity and positive predictive value. A significant proportion of cancers are potentially missed and underestimated by both imaging modalities. Prostate specific membrane antigen positron emission tomography may be used in addition to multiparametric magnetic resonance imaging to help improve local staging in those patients undergoing retropubic radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Reassessment of the risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer treated using radical prostatectomy.

PubMed

Narita, Shintaro; Mitsuzuka, Koji; Tsuchiya, Norihiko; Koie, Takuya; Kawamura, Sadafumi; Ohyama, Chikara; Tochigi, Tatsuo; Yamaguchi, Takuhiro; Arai, Yoichi; Habuchi, Tomonori

2015-11-01

To assess the risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer patients treated using radical prostatectomy. We retrospectively reviewed the medical records of 1268 men with prostate cancer treated using radical prostatectomy without neoadjuvant therapy. The association between various risk factors and biochemical recurrence was then statistically evaluated. The Kaplan-Meier method, log-rank tests and Cox proportional hazards models were used for statistical analysis. In the intermediate-risk group, 96 patients (14.5%) experienced biochemical recurrence during a median follow up of 41 months. In the intermediate-risk group, preoperative prostate-specific antigen level, prostate volume and prostate-specific antigen density were significant preoperative risk factors for biochemical recurrence, whereas other factors including age, primary Gleason 4, clinical stage >T2 and percentage of positive biopsies were not. In multivariate analysis, higher preoperative prostate-specific antigen level and density, and a smaller prostate volume were independent risk factors for biochemical recurrence in the intermediate-risk group. Biochemical recurrence-free survival of patients in the intermediate-risk group with a higher prostate-specific antigen level and density (≥15 ng/mL, ≥0.6 ng/mL/cm(3), respectively), and lower prostate volume (≤10 mL) was comparable with that of high-risk group individuals (P = 0.632, 0.494 and 0.961, respectively). Preoperative prostate-specific antigen, prostate volume and prostate-specific antigen density are significant risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer patients treated using radical prostatectomy. Using these variables, a subset of the intermediate-risk patients can be identified as having equivalent outcomes to high-risk patients. © 2015 The Japanese Urological Association.

Technology diffusion and diagnostic testing for prostate cancer.

PubMed

Schroeck, Florian R; Kaufman, Samuel R; Jacobs, Bruce L; Skolarus, Ted A; Miller, David C; Weizer, Alon Z; Montgomery, Jeffrey S; Wei, John T; Shahinian, Vahakn B; Hollenbeck, Brent K

2013-11-01

While the dissemination of robotic prostatectomy and intensity modulated radiotherapy may fuel the increased use of prostatectomy and radiotherapy, these new technologies may also have spillover effects related to diagnostic testing for prostate cancer. Therefore, we examined the association of regional technology penetration with the receipt of prostate specific antigen testing and prostate biopsy. In this retrospective cohort study we included 117,857 men 66 years old or older from the 5% sample of Medicare beneficiaries living in Surveillance, Epidemiology and End Results (SEER) areas from 2003 to 2007. Regional technology penetration was measured as the number of providers performing robotic prostatectomy or intensity modulated radiotherapy per population in a health care market, ie hospital referral region. We assessed the association of technology penetration with the prostate specific antigen testing rate and prostate biopsy using generalized estimating equations. High technology penetration was associated with an increased rate of prostate specific antigen testing (442 vs 425/1,000 person-years, p<0.01) and a similar rate of prostate biopsy (10.1 vs 9.9/1,000 person-years, p=0.69). The impact of technology penetration on prostate specific antigen testing and prostate biopsy was much less than the effect of age, race and comorbidity, eg the prostate specific antigen testing rate per 1,000 person-years was 485 vs 373 for men with only 1 vs 3+ comorbid conditions (p<0.01). Increased technology penetration is associated with a slightly higher rate of prostate specific antigen testing and no change in the prostate biopsy rate. Collectively, our findings temper concerns that adopting new technology accelerates diagnostic testing for prostate cancer. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

DOEpatents

Jensen, R.H.; Vanderlaan, M.; Bigbee, W.L.; Stanker, L.H.; Branscomb, E.W.; Grabske, R.J.

1984-11-29

The present invention provides monoclonal antibodies specific to and distinguishing between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype. 4 figs.

Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer

PubMed Central

O'Hurley, Gillian; Busch, Christer; Fagerberg, Linn; Hallström, Björn M.; Stadler, Charlotte; Tolf, Anna; Lundberg, Emma; Schwenk, Jochen M.; Jirström, Karin; Bjartell, Anders; Gallagher, William M.; Uhlén, Mathias; Pontén, Fredrik

2015-01-01

To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL. PMID:26237329

Contribution of Caudal Müllerian Duct Mesenchyme to Prostate Development

PubMed Central

Brechka, Hannah; McAuley, Erin M.; Lamperis, Sophia M.; Paner, Gladell P.

2016-01-01

A fundamental understanding of prostate development and tissue homeostasis has the high potential to reveal mechanisms for prostate disease initiation and identify novel therapeutic approaches for disease prevention and treatment. Our current understanding of prostate lineage specification stems from the use of developmental model systems that rely upon the embryonic preprostatic urogenital sinus mesenchyme to induce the formation of mature prostate epithelial cells. It is unclear, however, how the urogenital sinus epithelium can derive both adult urethral glands and prostate epithelia. Furthermore, the vast disparity in disease initiation between these two glands highlights key developmental factors that predispose prostate epithelia to hyperplasia and cancer. In this study we demonstrate that the caudal Müllerian duct mesenchyme (CMDM) drives prostate epithelial differentiation and is a key determinant in cell lineage specification between urethral glands and prostate epithelia. Utilizing both human embryonic stem cells and mouse embryonic tissues, we document that the CMDM is capable of inducing the specification of androgen receptor, prostate-specific antigen, NKX3.1, and Hoxb13-positive prostate epithelial cells. These results help to explain key developmental differences between prostate and urethral gland differentiation, and implicate factors secreted by the caudal Müllerian duct as novel targets for prostate disease prevention and treatment. PMID:27595922

Comparison of transrectal photoacoustic, Doppler, and magnetic resonance imaging for prostate cancer detection

NASA Astrophysics Data System (ADS)

Ishihara, Miya; Horiguchi, Akio; Shinmoto, Hiroshi; Tsuda, Hitoshi; Irisawa, Kaku; Wada, Takatsugu; Asano, Tomohiko

2016-03-01

Transrectal ultrasonography (TRUS) is the most popular imaging modality for diagnosing and treating prostate cancer. TRUS-guided prostate biopsy is mandatory for the histological diagnosis of patients with elevated serum prostatespecific antigen (PSA), but its diagnostic accuracy is not satisfactory due to TRUS's low resolution. As a result, a considerable number of patients are required to undergo an unnecessary repeated biopsy. Photoacoustic imaging (PAI) can be used to provide microvascular network imaging using hemoglobin as an intrinsic, optical absorption molecule. We developed an original TRUS-type PAI probe consisting of a micro-convex array transducer with an optical illumination system to provide superimposed PAI and ultrasound images. TRUS-type PAI has the advantage of having much higher resolution and greater contrast than does Doppler TRUS. The purpose of this study was to demonstrate the clinical feasibility of the transrectal PAI system. We performed a clinical trial to compare the image of the cancerous area obtained by transrectal PAI with that obtained by TRUS Doppler during prostate biopsy. The obtained prostate biopsy cores were stained with anti-CD34 antibodies to provide a microvascular distribution map. We also confirmed its consistency with PAI and pre-biopsy MRI findings. Our study demonstrated that transrectal identification of tumor angiogenesis under superimposed photoacoustic and ultrasound images was easier than that under TRUS alone. We recognized a consistent relationship between PAI and MRI findings in most cases. However, there were no correspondences in some cases.

Prostate-specific membrane antigen-targeted liposomes specifically deliver the Zn(2+) chelator TPEN inducing oxidative stress in prostate cancer cells.

PubMed

Stuart, Christopher H; Singh, Ravi; Smith, Thomas L; D'Agostino, Ralph; Caudell, David; Balaji, K C; Gmeiner, William H

2016-05-01

To evaluate the potential use of zinc chelation for prostate cancer therapy using a new liposomal formulation of the zinc chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN). TPEN was encapsulated in nontargeted liposomes or liposomes displaying an aptamer to target prostate cancer cells overexpression prostate-specific membrane antigen. The prostate cancer selectivity and therapeutic efficacy of liposomal (targeted and nontargeted) and free TPEN were evaluated in vitro and in tumor-bearing mice. TPEN chelates zinc and results in reactive oxygen species imbalance leading to cell death. Delivery of TPEN using aptamer-targeted liposomes results in specific delivery to targeted cells. In vivo experiments show that TPEN-loaded, aptamer-targeted liposomes reduce tumor growth in a human prostate cancer xenograft model.

Diet and dietary supplement intervention trials for the prevention of prostate cancer recurrence: a review of the randomized controlled trial evidence.

PubMed

Van Patten, Cheri L; de Boer, Johan G; Tomlinson Guns, Emma S

2008-12-01

We review the effect of diet and dietary supplement interventions on prostate cancer progression, recurrence and survival. A literature search was conducted in MEDLINE, EMBASE and CINAHL to identify diet and dietary supplement intervention studies in men with prostate cancer using prostate specific antigen or prostate specific antigen doubling time as a surrogate serum biomarker of prostate cancer recurrence and/or survival. Of the 32 studies identified 9 (28%) were randomized controlled trials and the focus of this review. In these studies men had confirmed prostate cancer and elevated or increasing prostate specific antigen. Only 1 trial included men with metastatic disease. When body mass index was reported, men were overweight or obese. A significant decrease in prostate specific antigen was observed in some studies using a low fat vegan diet, soy beverage or lycopene supplement. While not often reported as an end point, a significant increase in prostate specific antigen doubling time was observed in a study on lycopene supplementation. In only 1 randomized controlled trial in men undergoing orchiectomy was a survival end point of fewer deaths with lycopene supplementation reported. A limited number of randomized controlled trials were identified in which diet and dietary supplement interventions appeared to slow disease progression in men with prostate cancer, although results vary. Studies were limited by reliance on the surrogate biomarker prostate specific antigen, sample size and study duration. Well designed trials are warranted to expand knowledge, replicate findings and further assess the impact of diet and dietary supplement interventions on recurrence and treatment associated morbidities.

Different optical spectral characteristics in a necrotic transmissible venereal tumor and a cystic lesion in the same canine prostate observed by triple-band trans-rectal optical tomography under trans-rectal ultrasound guidance

NASA Astrophysics Data System (ADS)

Jiang, Zhen; Holyoak, G. Reed; Ritchey, Jerry W.; Bartels, Kenneth E.; Rock, Kendra; Ownby, Charlotte L.; Slobodov, Gennady; Bunting, Charles F.; Piao, Daqing

2011-03-01

Different optical spectral characteristics were observed in a necrotic transmissible venereal tumor (TVT) and a cystic lesion in the same canine prostate by triple-wavelength trans-rectal optical tomography under trans-rectal ultrasound (TRUS) guidance. The NIR imager acquiring at 705nm, 785nm and 808nm was used to quantify both the total hemoglobin concentration (HbT) and oxygen saturation (StO2) in the prostate. The TVT tumor in the canine prostate as a model of prostate cancer was induced in a 7-year old, 27 kg dog. A 2 mL suspension of 2.5x106 cells/mL of homogenized TVT cells recovered from an in vivo subcutaneously propagated TVT tumor in an NOD/SCID mouse were injected in the cranial aspect of the right lobe of the canine prostate. The left lobe of the prostate had a cystic lesion present before TVT inoculation. After the TVT homogenate injection, the prostate was monitored weekly over a 9-week period, using trans-rectal NIR and TRUS in grey-scale and Doppler. A TVT mass within the right lobe developed a necrotic center during the later stages of this study, as the mass presented with substantially increased [HbT] in the periphery, with an area of reduced StO2 less than the area of the mass itself shown on ultrasonography. Conversely, the cystic lesion presented with slightly increased [HbT] in the periphery of the lesion shown on ultrasound with oxygen-reduction inside and in the periphery of the lesion. There was no detectable change of blood flow on Doppler US in the periphery of the cystic lesion. The slightly increased [HbT] in the periphery of the cystic lesion was correlated with intra-lesional hemorrhage upon histopathologic examination.

A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

DTIC Science & Technology

2012-09-01

micrometastases that may be targeted with radioimmunotherapy. Prostate specific membrane antigen (PSMA) is the single, most well-established, highly restricted...Radiolabeled anti- prostate specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu-J591) for nonmetastatic castration-resistant prostate cancer...rationale for systemic salvage targeted anti- prostate specific membrane antigen radioimmunotherapy. Adv Urol 2012, Article ID 921674, doi:10.1155

Prostate-Specific G-Protein Coupled Receptor, an Emerging Biomarker Regulating Inflammation and Prostate Cancer Invasion.

PubMed

Rodriguez, M; Siwko, S; Liu, M

2016-01-01

Prostate cancer is highly prevalent among men in developed countries, but a significant proportion of detected cancers remain indolent, never progressing into aggressive carcinomas. This highlights the need to develop refined biomarkers that can distinguish between indolent and potentially dangerous cases. The prostate-specific G-protein coupled receptor (PSGR, or OR51E2) is an olfactory receptor family member with highly specific expression in human prostate epithelium that is highly overexpressed in PIN and prostate cancer. PSGR has been functionally implicated in prostate cancer cell invasiveness, suggesting a potential role in the transition to metastatic PCa. Recently, transgenic mice overexpressing PSGR in the prostate were reported to develop an acute inflammatory response followed by emergence of low grade PIN, whereas mice with compound PSGR overexpression and loss of PTEN exhibited accelerated formation of invasive prostate adenocarcinoma. This article will review recent PSGR findings with a focus on its role as a potential prostate cancer biomarker and regulator of prostate cancer invasion and inflammation.

21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's Solution...

Prostate-specific antigen and acute myocardial infarction: a possible new intriguing scenario.

PubMed

Patanè, Salvatore; Marte, Filippo

2009-05-29

Prostate-specific antigen (PSA) has been identified as a member of the human kallikrein family of serine proteases and it is an established marker for detection of prostate cancer. Apparently spurious result has been reported in a work about mean serum PSA concentration during acute myocardial infarction with mean serum PSA concentration significantly lower on day 2 than either day 1 or day 3 and it has been reported that these preliminary results could reflect several factors, such as antiinfarctual treatment, reduced physical activity or an acute-phase response. Elevation of prostate-specific antigen has also been reported during acute myocardial infarction in three patients and in another one also after transurethral resection of the prostate (TURP) and without histological diagnosis of prostate cancer. In our report we present three cases of diminution of serum PSA concentration during acute myocardial infarction. Our report extends the evaluation of PSA during acute myocardial infarction. It seems that when elevation of prostate-specific antigen occurs during acute myocardial infarction, coronary lesions are frequent and often more severe than when diminution of prostate-specific antigen occurs during acute myocardial infarction. It opens a possible new intriguing scenario of the role of the prostate-specific antigen in acute myocardial infarction.

Prostate Cancer Screening: Should You Get a PSA Test?

MedlinePlus

... Mayo Clinic Staff Cancer screening tests — including the prostate-specific antigen (PSA) test to look for signs of prostate ... of harm to the person undergoing the testing. Prostate-specific antigen (PSA) is a protein produced by both cancerous ( ...

A case report of prostate cancer metastasis to the stomach resembling undifferentiated-type early gastric cancer.

PubMed

Inagaki, Chiaki; Suzuki, Takuto; Kitagawa, Yoshiyasu; Hara, Taro; Yamaguchi, Taketo

2017-08-07

Occurrence of metastatic cancer to the stomach is rare, particularly in patients with prostate cancer. Gastric metastasis generally presents as a solitary and submucosal lesion with a central depression. We describe a case of gastric metastasis arising from prostate cancer, which is almost indistinguishable from the undifferentiated-type gastric cancer. A definitive diagnosis was not made until endoscopic resection. On performing both conventional and magnifying endoscopies, the lesion appeared to be slightly depressed and discolored area and it could not be distinguished from undifferentiated early gastric cancer. Biopsy from the lesion was negative for immunohistochemical staining of prostate-specific antigen, a sensitive and specific marker for prostate cancer. Thus, false initial diagnosis of an early primary gastric cancer was made and endoscopic submucosal dissection was performed. Pathological findings from the resected specimen aroused suspicion of a metastatic lesion. Consequently, immunostaining was performed. The lesion was positive for prostate-specific acid phosphatase and negative for prostate-specific antigen, cytokeratin 7, and cytokeratin 20. Accordingly, the final diagnosis was a metastatic gastric lesion originating from prostate cancer. In this patient, the definitive diagnosis as a metastatic lesion was difficult due to its unusual endoscopic appearance and the negative stain for prostate-specific antigen. We postulate that both of these are consequences of hormonal therapy against prostate cancer.

Echo-Planar Imaging Based J-Resolved Spectroscopic Imaging for Improved Metabolite Detection in Prostate Cancer

DTIC Science & Technology

2013-10-01

Scope: A major outcome is expected to be on improved detection ( specificity ) in differentiating malignant from benign prostate cancer using a novel...Digital Rectal Examination, prostate specific antigen , Four Dimensional (4D) Echo-Planar J-Resolved Spectroscopic Imaging (EP-JRESI); Citrate, Choline... prostate biopsy ranged from 3 to 8, while prostate - specific antigen varied from 2.8 to 20.6 ng/mL (mean of 6.84 ng/mL). A Siemens 3T MRI Scanner with

Prostate-Specific Natural Health Products (Dietary Supplements) Radiosensitize Normal Prostate Cells

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

Hasan, Yasmin; Schoenherr, Diane; Martinez, Alvaro A.

Purpose: Prostate-specific health products (dietary supplements) are taken by cancer patients to alleviate the symptoms linked with poor prostate health. However, the effect of these agents on evidence-based radiotherapy practice is poorly understood. The present study aimed to determine whether dietary supplements radiosensitized normal prostate or prostate cancer cell lines. Methods and Materials: Three well-known prostate-specific dietary supplements were purchased from commercial sources available to patients (Trinovin, Provelex, and Prostate Rx). The cells used in the study included normal prostate lines (RWPE-1 and PWR-1E), prostate tumor lines (PC3, DU145, and LNCaP), and a normal nonprostate line (HaCaT). Supplement toxicity wasmore » assessed using cell proliferation assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and cellular radiosensitivity using conventional clonogenic assays (0.5-4Gy). Cell cycle kinetics were assessed using the bromodeoxyuridine/propidium iodide pulse-labeling technique, apoptosis by scoring caspase-3 activation, and DNA repair by assessing gammaH2AX. Results: The cell growth and radiosensitivity of the malignant PC3, DU145, and LNcaP cells were not affected by any of the dietary prostate supplements (Provelex [2mug/mL], Trinovin [10mug/mL], and Prostate Rx [50 mug/mL]). However, both Trinovin (10mug/mL) and Prostate Rx (6mug/mL) inhibited the growth rate of the normal prostate cell lines. Prostate Rx increased cellular radiosensitivity of RWPE-1 cells through the inhibition of DNA repair. Conclusion: The use of prostate-specific dietary supplements should be discouraged during radiotherapy owing to the preferential radiosensitization of normal prostate cells.« less

Semiconductor nanocrystal-aptamer bioconjugate probes for specific prostate carcinoma cell targeting

NASA Astrophysics Data System (ADS)

Shieh, Felice; Lavery, Laura; Chu, Chitai T.; Richards-Kortum, Rebecca; Ellington, Andrew D.; Korgel, Brian A.

2005-04-01

Cancer of the prostate affects approximately 1 in 11 men. Current early screening for prostate cancer utilizes digital rectal examinations to detect anomalies in the prostate gland and blood test screenings for upregulated levels of prostate specific antigen (PSA). Many of these tests are invasive and can often be inconclusive as PSA levels may be heightened due to benign factors. Prostate specific membrane antigen (PSMA), a well-characterized integral membrane protein, is expressed in virtually all prostate cancers and often correlates with cancer aggressiveness. Therefore, it may be used as an indicator of cancer growth and metastases. PSMA-specific antibodies have been identified and conjugated to fluorescent markers for cancer cell targeting; however, both the antibodies and markers possess significant limitations in their pharmaceutical and diagnostic value. Here we report the use of semiconductor nanocrystals bioconjugated to PSMA-specific aptamer recognition molecules for prostate carcinoma cell targeting. The nanocrystal/aptamer bioconjugates are small biocompatible probes with the potential for color-tunability for multicolor imaging. Ongoing in vitro and in vivo research seeks to introduce these nanoparticle bioconjugates into medical diagnostics.

Autoantibody signatures as biomarkers to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate specific antigen.

PubMed

O'Rourke, Dennis J; DiJohnson, Daniel A; Caiazzo, Robert J; Nelson, James C; Ure, David; O'Leary, Michael P; Richie, Jerome P; Liu, Brian C-S

2012-03-22

Serum prostate specific antigen (PSA) concentrations lack the specificity to differentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We identified 5 autoantibody signatures to specific cancer targets which might be able to differentiate prostate cancer from BPH in patients with increased serum PSA. To identify autoantibody signatures as biomarkers, a native antigen reverse capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayed onto nanoparticle slides to capture native antigens from prostate cancer cells. Prostate cancer patient serum samples (n=41) and BPH patient samples (collected starting at the time of initial diagnosis) with a mean follow-up of 6.56 y without the diagnosis of cancer (n=39) were obtained. One hundred micrograms of IgGs were purified and labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and the intensity was quantified. Receiver operating characteristic curves were produced and the area under the curve (AUC) was determined. Using our microarray platform, we identified autoantibody signatures capable of distinguishing between prostate cancer and BPH. The top 5 autoantibody signatures were TARDBP, TLN1, PARK7, LEDGF/PSIP1, and CALD1. Combining these signatures resulted in an AUC of 0.95 (sensitivity of 95% at 80% specificity) compared to AUC of 0.5 for serum concentration PSA (sensitivity of 12.2% at 80% specificity). Our preliminary results showed that we were able to identify specific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in the reduction of unnecessary biopsies in patients with increased serum PSA. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of Epoetin Alfa Titration Practices, Implemented After Changes to Product Labeling, on Hemoglobin Levels, Transfusion Use, and Hospitalization Rates.

PubMed

Molony, Julia T; Monda, Keri L; Li, Suying; Beaubrun, Anne C; Gilbertson, David T; Bradbury, Brian D; Collins, Allan J

2016-08-01

Little is known about epoetin alfa (EPO) dosing at dialysis centers after implementation of the US Medicare prospective payment system and revision of the EPO label in 2011. Retrospective cohort study. Approximately 412,000 adult hemodialysis patients with Medicare Parts A and B as primary payer in 2009 to 2012 to describe EPO dosing and hemoglobin patterns; of these, about 70,000 patients clustered in about 1,300 dialysis facilities to evaluate facility-level EPO titration practices and patient-level outcomes in 2012. Facility EPO titration practices when hemoglobin levels were <10 and >11g/dL (grouped treatment variable) determined from monthly EPO dosing and hemoglobin level patterns. Patient mean hemoglobin levels, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates using a facility-based analysis. Monthly EPO dose and hemoglobin level, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates. Monthly EPO doses declined across all hemoglobin levels, with the greatest decline in patients with hemoglobin levels < 10g/dL (July-October 2011). In 2012, nine distinct facility titration practices were identified. Across groups, mean hemoglobin levels differed slightly (10.5-10.8g/dL) but within-patient hemoglobin standard deviations were similar (∼0.68g/dL). Patients at facilities implementing greater dose reductions and smaller dose escalations had lower hemoglobin levels and higher transfusion rates. In contrast, patients at facilities that implemented greater dose escalations (and large or small dose reductions) had higher hemoglobin levels and lower transfusion rates. There were no clinically meaningful differences in all-cause or cause-specific hospitalization events across groups. Possibly incomplete claims data; excluded small facilities and those without consistent titration patterns; hemoglobin levels reported monthly; inferred facility practice from observed dosing. Following prospective payment system implementation and labeling revisions, EPO doses declined significantly. Under the new label, facility EPO titration practices were associated with mean hemoglobin levels (but not standard deviations) and transfusion use, but not hospitalization rates. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Cellular prostatic acid phosphatase, a PTEN-functional homologue in prostate epithelia, functions as a prostate-specific tumor suppressor

PubMed Central

Muniyan, Sakthivel; Ingersoll, Matthew A.; Batra, Surinder K.; Lin, Ming-Fong

2014-01-01

The inactivation of tumor suppressor genes (TSGs) plays a vital role in the progression of human cancers. Nevertheless, those ubiquitous TSGs have been shown with limited roles in various stages of diverse carcinogenesis. Investigation on identifying unique TSG, especially for early stage of carcinogenesis, is imperative. As such, the search for organ-specific TSGs has emerged as a major strategy in cancer research. Prostate cancer (PCa) has the highest incidence in solid tumors in US males. Cellular prostatic acid phosphatase (cPAcP) is a prostate-specific differentiation antigen. Despite intensive studies over the past several decades on PAcP as a PCa biomarker, the role of cPAcP as a PCa-specific tumor suppressor has only recently been emerged and validated. The mechanism underlying the pivotal role of cPAcP as a prostate-specific TSG is, in part, due to its function as a protein tyrosine phosphatase (PTP) as well as a phosphoinositide phosphatase (PIP), an apparent functional homologue to Phosphatase and tensin homolog (PTEN) in PCa cells. This review is focused on discussing the function of this authentic prostate-specific tumor suppressor and the mechanism behind the loss of cPAcP expression leading to prostate carcinogenesis. We review other phosphatases’ roles as TSGs which regulate oncogenic PI3K signaling in PCa and discuss the functional similarity between cPAcP and PTEN in prostate carcinogenesis. PMID:24747769

Plasma cell-free DNA and its DNA integrity as biomarker to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate-specific antigen.

PubMed

Feng, Jiang; Gang, Feng; Li, Xiao; Jin, Tang; Houbao, Huang; Yu, Cao; Guorong, Li

2013-08-01

To investigate whether plasma cell-free DNA (cfDNA) or its integrity could differentiate prostate cancer from benign prostate hyperplasia (BPH) in patients with serum prostate-specific antigen (PSA) ≥ 4 ng/ml. Ninety-six patients with prostate cancer and 112 patients with BPH were enrolled. cfDNA levels in plasma before prostate biopsy were quantified by real-time PCR amplification of ALU gene (product size of 115 bp), and quantitative ratio of ALU (247 bp) to ALU (115 bp) reflected the integrity of cfDNA. In patients with serum PSA ≥ 4 ng/ml, there were significant differences in plasma cfDNA or its integrity between the patients with prostate cancer (19.74 ± 4.43, 0.34 ± 0.05) and patients with BPH (7.36 ± 1.58, 0.19 ± 0.03; P < 0.001, P < 0.001). Prostate cancer could be differentiated with a sensitivity of 73.2 % and a specificity of 72.7 % by cfDNA (AUC = 0.864). The integrity of cfDNA had a sensitivity of 81.7 % and a specificity of 78.8 % for the distinguishing prostate cancer from BPH (AUC = 0.910). cfDNA and its integrity could be applied to differentiate prostate cancer from BPH in patients with serum PSA ≥ 4 ng/ml.

Heterobivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2014-11-01

Prostate-Specific Membrane Antigen ( PSMA ) and Hepsin PRINCIPAL INVESTIGATOR: Youngjoo Byun, Ph. D. CONTRACTING ORGANIZATION: Korea...Simultaneous Targeting Prostate-Specific Membrane Antigen ( PSMA ) and Hepsin 5b. GRANT NUMBER W81XWH-10-1-0189 5c. PROGRAM ELEMENT NUMBER 6...heterobivalent conjugates of PSMA /hepsin-binding ligands labeled with optical dyes or radionuclides. The sensitivity and accuracy of prostate cancer

High serum dihydrotestosterone examined by ultrasensitive LC-MS/MS as a predictor of benign prostatic hyperplasia or Gleason score 6 cancer in men with prostate-specific antigen levels of 3-10 ng/mL.

PubMed

Miyoshi, Y; Uemura, H; Suzuki, K; Shibata, Y; Honma, S; Harada, M; Kubota, Y

2017-03-01

There has been no consensus on the role of serum androgen concentrations in prostate cancer detection in men with prostate-specific antigen levels of 3-10 ng/mL. In this study, testosterone and dihydrotestosterone concentrations in blood were examined by a newly developed method using ultrasensitive liquid chromatography with two serially linked mass spectrometers (LC-MS/MS). We investigated the correlation between serum androgen levels and Gleason scores at biopsy. We analyzed data of 157 men with a total prostate-specific antigen range of 3-10 ng/mL who underwent initial systematic prostate needle biopsy for suspected prostate cancer between April 2000 and July 2003. Peripheral blood testosterone and dihydrotestosterone concentrations were determined by LC-MS/MS. Blood levels of testosterone and dihydrotestosterone were compared with pathological findings by multivariate analyses. Median values of prostate-specific antigen and prostate volume measured by ultrasound were 5.7 ng/mL and 31.4 cm 3 , respectively. Benign prostatic hyperplasia was diagnosed in 97 patients (61.8%), and prostate cancer was diagnosed in 60 (38.2%) patients, including 31 (19.7%) patients with a Gleason score of 6 and 29 (18.5%) patients with a Gleason score of 7-10. Median values of testosterone and dihydrotestosterone in blood were 3798.7 and 371.7 pg/mL, respectively. There was a strong correlation between serum testosterone and dihydrotestosterone. In multivariate analysis, age, prostate volume, and serum dihydrotestosterone were significant predictors of benign prostatic hyperplasia or prostate cancer with a Gleason score of 6. The area under the receiver operating characteristics curve for age, prostate volume, and serum dihydrotestosterone were 0.67, 0.67, and 0.67, respectively . We confirmed that high dihydrotestosterone blood levels can predict benign prostatic hyperplasia or prostate cancer with a Gleason score of 6 in men with prostate-specific antigen levels of 3-10 ng/mL. © 2016 American Society of Andrology and European Academy of Andrology.

[Real-time elastography in the diagnosis of prostate cancer: personal experience].

PubMed

Romagnoli, Andrea; Autieri, Gaspare; Centrella, Danilo; Gastaldi, Christian; Pedaci, Giuseppe; Rivolta, Lorenzo; Pozzi, Emilio; Anghileri, Alessio; Cerabino, Maurizio; Bianchi, Carlo Maria; Roggia, Alberto

2010-01-01

Prostate cancer is the most common cancer in men. In the future, a significant further increase in the incidence of prostate cancer is expected. The indication to perform a prostate biopsy is digital rectal examination suspicious for prostate cancer, total prostate specific antigen (PSA) value, free PSA/total PSA ratio, PSA density and PSA velocity, and an evidence of hypoechoic area at transrectal ultrasound scan. Unfortunately the specificity and sensibility are still poor. The aim of this retrospective study is to evaluate the specificity and sensibility of real time elastography versus ultrasound transrectal B-mode scan. We retrospectively evaluated 108 pts. having undergone TRUS-guided transrectal prostate biopsy (10 samples). The indication for biopsy is: digital rectal examination, total prostate specific antigen (PSA) value, PSA ratio, PSA density and PSA velocity suspicious for prostate cancer, and/or an evidence of hypoechoic area at transrectal ultrasound scan, and/or hard area at real-time elastography. The mean age of patients is 66.8 years, mean PSA 6.5 ng/mL, and mean ratio 16.5%. We compared the histopathological findings of needle prostate biopsies with the results of transrectal ultrasound and transrectal real-time elastography. 32/108 (29.6%) pts. were positive for prostate cancer (mean Gleason score 7.08), mean PSA 14 ng/mL and mean ratio 9.5%. Transrectal ultrasound scan shows a sensibility of 69% and specificity of 68%. Transrectal ultrasound scan shows a VPP of 51.4%. Transrectal ultrasound scan shows a VPN of 80.9%. Real-time elastography shows a sensibility of 56% and specificity of 85.7%. Real-time elastography shows a VPP of 60.1%. Real-time elastography shows a VPN of 83%. Elastography has a significantly higher specificity for the detection of prostate cancer than the conventionally used examinations including DRE and TRUS. It is a useful real-time diagnostic method because it is not invasive, and simultaneous evaluation is possible while performing TRUS.

Herniated Thoracic Spleen Mimicking Lung Metastasis on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT in a Patient With Prostate Cancer.

PubMed

Malik, Dharmender; Basher, Rajender K; Sood, Apurva; Devana, Sudheer Kumar; Bhattacharya, Anish; Mittal, Bhagwant Rai

2017-06-01

We report a case of clinically asymptomatic patient of prostate cancer who was previously subjected to radical prostatectomy presenting with a rising serum prostate-specific antigen level of 6.6 ng/mL. Whole-body PET/CT with Ga-labeled prostate-specific membrane antigen ligand was performed to assess for disease recurrence, which revealed an intense tracer uptake in a soft tissue mass in left hemithorax mimicking lung metastasis; which later turned out to be splenic tissue.

An overview of prostate diseases and their characteristics specific to Asian men.

PubMed

Xia, Shu-Jie; Cui, Di; Jiang, Qi

2012-05-01

In this paper, we reviewed the features of common prostate diseases, such as benign prostatic hyperplasia (BPH), prostate cancer (PCa) and chronic prostatitis (CP) that are specific to Asian men. Compared to the Westerners, Asians exhibit particular characteristics of prostate diseases. Through summarizing the epidemiology, symptomatology, diagnostics and therapeutics of these diseases, we find that Asians have a lower incidence of PCa than whites, but the incidences of BPH and CP are similar. Asian men with CP often suffer from fewer disease sites, but have a higher frequency of pain during urination rather than after sexual climax. Prostate-specific antigen (PSA) is a widely used marker for the diagnosis of PCa in both Asian and Western countries. Although the PSA level may be lower in Asians, the threshold used is based on whites. After reviewing the treatments available for these diseases, we did not find a fundamental difference between Asians and whites. Furthermore, the selection for the most appropriate treatment based on the individual needs of patients remains a challenge to urologists in Asia. After considering the traits of prostate diseases that are specific to Asian men, we hope to pave the way for the development of specific diagnostic and therapeutic strategies targeted specifically to Asian men.

Potential surrogate endpoints for prostate cancer survival: analysis of a phase III randomized trial.

PubMed

Ray, Michael E; Bae, Kyounghwa; Hussain, Maha H A; Hanks, Gerald E; Shipley, William U; Sandler, Howard M

2009-02-18

The identification of surrogate endpoints for prostate cancer-specific survival may shorten the length of clinical trials for prostate cancer. We evaluated distant metastasis and general clinical treatment failure as potential surrogates for prostate cancer-specific survival by use of data from the Radiation Therapy and Oncology Group 92-02 randomized trial. Patients (n = 1554 randomly assigned and 1521 evaluable for this analysis) with locally advanced prostate cancer had been treated with 4 months of neoadjuvant and concurrent androgen deprivation therapy with external beam radiation therapy and then randomly assigned to no additional therapy (control arm) or 24 additional months of androgen deprivation therapy (experimental arm). Data from landmark analyses at 3 and 5 years for general clinical treatment failure (defined as documented local disease progression, regional or distant metastasis, initiation of androgen deprivation therapy, or a prostate-specific antigen level of 25 ng/mL or higher after radiation therapy) and/or distant metastasis were tested as surrogate endpoints for prostate cancer-specific survival at 10 years by use of Prentice's four criteria. All statistical tests were two-sided. At 3 years, 1364 patients were alive and contributed data for analysis. Both distant metastasis and general clinical treatment failure at 3 years were consistent with all four of Prentice's criteria for being surrogate endpoints for prostate cancer-specific survival at 10 years. At 5 years, 1178 patients were alive and contributed data for analysis. Although prostate cancer-specific survival was not statistically significantly different between treatment arms at 5 years (P = .08), both endpoints were consistent with Prentice's remaining criteria. Distant metastasis and general clinical treatment failure at 3 years may be candidate surrogate endpoints for prostate cancer-specific survival at 10 years. These endpoints, however, must be validated in other datasets.

A Prospective Randomized Trial of Two Different Prostate Biopsy Schemes

ClinicalTrials.gov

2016-07-03

Prostate Cancer; Local Anesthesia; Prostate-Specific Antigen/Blood; Biopsy/Methods; Image-guided Biopsy/Methods; Prostatic Neoplasms/Diagnosis; Prostate/Pathology; Prospective Studies; Humans; Male; Ultrasonography, Interventional/Methods

A large, benign prostatic cyst presented with an extremely high serum prostate-specific antigen level.

PubMed

Chen, Han-Kuang; Pemberton, Richard

2016-01-08

We report a case of a patient who presented with an extremely high serum prostate specific antigen (PSA) level and underwent radical prostatectomy for presumed prostate cancer. Surprisingly, the whole mount prostatectomy specimen showed only small volume, organ-confined prostate adenocarcinoma and a large, benign intraprostatic cyst, which was thought to be responsible for the PSA elevation. 2016 BMJ Publishing Group Ltd.

[Age peculiarities in prostate cancer detection based on the prostate-specific antigen and its alterations control].

PubMed

Ponkratov, S V; Kheyfets, V Kh; Kagan, O F

2017-01-01

Data on epidemiology of a prostate cancer are presented in article, high prevalence and body height of a case rate cause relevance of researches on this oncopathology. It is shown that the number augmentation for the first time of the taped cases is bound including to the program of a screening of inspection of men by determination of level of prostates-specific antigen (PSA). Modern diagnostic methods of identification of modifications of PSA, possessing larger sensitivity and specificity concerning a prostate cancer are lit. The attention to change of level of PSA depending on age is focused that needs to be considered at diagnostics of malignant neoplasms of a prostate.

A novel minimally invasive dual-modality fiber optic probe for prostate cancer detection

NASA Astrophysics Data System (ADS)

Sharma, Vikrant

Prostate cancer is the most common form of cancer in males, and is the second leading cause of cancer related deaths in United States. In prostate cancer diagnostics and therapy, there is a critical need for a minimally invasive tool for in vivo evaluation of prostate tissue. Such a tool finds its niche in improving TRUS (trans-rectal ultrasound) guided biopsy procedure, surgical margin assessment during radical prostatectomy, and active surveillance of patients with a certain risk levels. This work is focused on development of a fiber-based dual-modality optical device (dMOD), to differentiate prostate cancer from benign tissue, in vivo. dMOD utilizes two independent optical techniques, LRS (light reflectance spectroscopy) and AFLS (auto-fluorescence lifetime spectroscopy). LRS quantifies scattering coefficient of the tissue, as well as concentrations of major tissue chromophores like hemoglobin derivatives, β-carotene and melanin. AFLS was designed to target lifetime signatures of multiple endogenous fluorophores like flavins, porphyrins and lipo-pigments. Each of these methods was independently developed, and the two modalities were integrated using a thin (1-mm outer diameter) fiber-optic probe. Resulting dMOD probe was implemented and evaluated on animal models of prostate cancer, as well as on human prostate tissue. Application of dMOD to human breast cancer (invasive ductal carcinoma) identification was also evaluated. The results obtained reveal that both LRS and AFLS are excellent techniques to discriminate prostate cancer tissue from surrounding benign tissue in animal models. Each technique independently is capable of providing near absolute (100%) accuracy for cancer detection, indicating that either of them could be used independently without the need of implementing them together. Also, in case of human breast cancer, LRS and AFLS provided comparable accuracies to dMOD, LRS accuracy (96%) being the highest for the studied population. However, the dual-modality integration proved to be ideal for human prostate cancer detection, as dMOD provided much better accuracy i.e., 82.7% for cancer detection in intra-capsular prostatic tissues (ICT), and 92.4% for cancer detection in extra-capsular prostatic tissues (ECT), when compared with either LRS (74.7% ICT, 86.6% ECT) or AFLS(67.1% ICT, 82.1% ECT) alone. A classification algorithm was also developed to identify different grades of prostate cancers based on Gleason scores (GS). When stratified by grade, each high grade prostate cancer (GS 7, 8 and 9) was successfully identified using dMOD with excellent accuracy in ICT (88%, 90%, 85%), as well as ECT (91%, 92%, 94%).

Clinical Outcomes of Transurethral Enucleation with Bipolar for Benign Prostatic Hypertrophy.

PubMed

Kawamura, Yoshiaki; Tokunaga, Masatoshi; Hoshino, Hideaki; Matsushita, Kazuo; Terachi, Toshiro

2015-12-20

This study compared outcomes of transurethral enucleation with bipolar (TUEB) with transurethral resection in saline (TURis). Thirty patients who underwent TURis were compared with 30 who underwent TUEB. Perioperative treatment outcomes, preoperative and 1-month postoperative International Prostrate Symptom Scores (IPSS), quality of life (QOL) index, maximum flow rate, average urinary flow, post- void residual urinary volume, and complications were compared. There were no significant differences in IPSS, measurements of urinary flow, or duration of catheterization. However, the improvement of QOL index after surgery was significantly greater in the TUEB group than the TURis group. The TUEB group had significantly longer surgical time, but tended to have greater enucleated tissue weight than the TURis group. There was no significant difference in enucleated tissue weight per unit time between the groups. The TUEB group also tended to have less hemoglobin decrease at postoperative day 1; this tendency was more prominent in patients with an estimated prostate volume of ≥ 50 ml. No significant differences in postoperative complications were observed. This study confirmed that the previously reported safety and efficacy of TUEB are comparable to those of TURis. TUEB appears especially safe for those with a large benign hypertrophic prostate.

Photoacoustic physio-chemical analysis for prostate cancer diagnosis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Xu, Guan; Cheng, Qian; Huang, Shengsong; Qin, Ming; Hopkins, Thomas; Lee, Chang H.; Kopelman, Raoul; Chao, Wan-yu; Keller, Evan T.; Wu, Denglong; Wang, Xueding

2017-03-01

Photoacoustic physio-chemical analysis (PAPCA) is a recently developed technology capable of simultaneously quantifying the content of molecular components and the corresponding microarchitectures in biological tissue. We have successfully quantified the diagnostic information in livers with PAPCA. In this study, we implemented PAPCA to the diagnosis of prostate cancers. 4 human prostates were scanned ex vivo. The PA signals from normal and cancerous regions in the prostates were acquired by an interstitial needle PA probe. A total of 14 interstitial measurements, including 6 within the normal regions and 8 in the cancerous regions, were acquired. The observed changes in molecular components, including lipid, collagen and hemoglobin were consistent with the findings by other research groups. The changes were quantified by PA spectral analysis (PASA) at wavelengths where strong optical absorption of the relevant molecular components was found. Statistically significant differences among the PASA parameters were observed (p=0.025 at significance of 0.05). A support vector machine model for differentiating the normal and cancerous tissue was established. With the limited number of samples, an 85% diagnostic accuracy was found. The diagnostic information in the PCPCA can be further enriched by targeted optical contrast agents visualizing the microarchitecture in PCa tissues. F3 PAA-PEG nanoparticles was employed to stain the PCa cells in a transgenic mouse model, in which the microarchitectures of normal and cancerous prostate tissues are comparable to that in human. Statistically significant differences were observed between the contrast-enhanced normal and cancerous regions (p=0.038 at a significance of 0.05).

Laser transurethral resection of the prostate: Safety study of a novel system of photoselective vaporization with high power diode laser in prostates larger than 80mL.

PubMed

Andrés, G; Arance, I; Gimbernat, H; Redondo, C; García-Tello, A; Angulo, J C

2015-01-01

To present the feasibility of photoselective vaporization of the prostate (PVP) with of a new diode laser-resection system. Surgical treatment of benign prostatic hyperplasia (BPH) is constantly evolving. Laser techniques are increasingly used in prostates of large size. A prospective study was performed to evaluate operative data and patient outcomes with PVP using high-power diode laser (HPD) and a novel quartz-head fiber with shovel shape in patients with prostate>80mL. Demographic data, operative time, hemoglobin loss, operative results (IPSS, quality of life (QoL), Qmax, post void residue (PVR), IIEF-5 and micturition diary) and complications following Clavien-Dindo classification are described. Thirty-one patients were included in the study. Sixteen (51.6%) were on active antiplatelet treatment and 12 (38.7%) had received anticoagulants before surgery. All cases were followed at least 6mo. No intraoperative or postoperative major complications occurred. Three patients (9.7%) had minor complications according to Clavien-Dindo classification. Twenty-seven (87.1%) were discharged on postoperative day one without catheter. There were significant improvements in IPSS, QoL, Qmax and PVR, both at 3 and 6mo (P<.0001), but sexual function according to IIEF-5 showed no differences. Urgency (any grade) increased at 3mo (48.4%; P=.002) and considerably decreased at 6mo (9.7%; P<.0001). This pilot experience with shovel shape fiber and HPD is encouraging. It shows that laser-resection is a safe procedure, achieving excellent results in terms of IPSS, QoL and Qmax in large prostates even in high-risk patients. Longer follow-up, comparative and randomized controlled studies are needed to widespread these results. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Prostate-specific antigen-based prostate cancer screening: Past and future.

PubMed

Alberts, Arnout R; Schoots, Ivo G; Roobol, Monique J

2015-06-01

Prostate-specific antigen-based prostate cancer screening remains a controversial topic. Up to now, there is worldwide consensus on the statement that the harms of population-based screening, mainly as a result of overdiagnosis (the detection of clinically insignificant tumors that would have never caused any symptoms), outweigh the benefits. However, worldwide opportunistic screening takes place on a wide scale. The European Randomized Study of Screening for Prostate Cancer showed a reduction in prostate cancer mortality through prostate-specific antigen based-screening. These population-based data need to be individualized in order to avoid screening in those who cannot benefit and start screening in those who will. For now, lacking a more optimal screening approach, screening should only be started after the process of shared decision-making. The focus of future research is the reduction of unnecessary testing and overdiagnosis by further research to better biomarkers and the value of the multiparametric magnetic resonance imaging, potentially combined in already existing prostate-specific antigen-based multivariate risk prediction models. © 2015 The Japanese Urological Association.

T CELLS LOCALIZED TO THE ANDROGEN-DEPRIVED PROSTATE ARE TH1 AND TH17 BIASED

PubMed Central

Morse, Matthew D.; McNeel, Douglas G.

2013-01-01

BACKGROUND T cells infiltrate the prostates of prostate cancer patients undergoing neoadjuvant androgen deprivation. These prostate-infiltrating T cells have an oligoclonal phenotype, suggesting the development of an antigen-specific T-cell response. We hypothesized that androgen deprivation might elicit a prostate tissue-specific T-cell response that could potentially be combined with other immune-active therapies, and consequently sought to investigate the nature and timing of this T-cell response following castration. METHODS We investigated the phenotype and cytokine expression of T cells at various time points in the prostates of Lewis rats following surgical castration, and used adoptive transfer of prostate-infiltrating lymphocytes to determine whether the infiltration by T cells was mediated by effects of castration on the prostate or lymphocytes. RESULTS Prostate T-cell infiltration shortly after castration was TH1 biased up to approximately 30 days, followed by a predominance of TH17-type cells, which persisted until at least 90 days post castration. Prostate-infiltrating lymphocytes from sham-treated or castrate rats localized to the prostates of castrate animals. CONCLUSIONS These observations suggest castration elicits a time-dependent prostate-specific T-cell infiltration, and this infiltration is likely mediated by effects of castration on prostate tissue rather than T cells. These findings have implications for the timing of immunotherapies combined with androgen deprivation as treatments for prostate cancer. PMID:22213030

Cancer Today

MedlinePlus

... your doctor if you are considering having a prostate-specific antigen (PSA) test or digital rectal examination (DRE). Skin ... regular colonoscopy for cancer of the colon, serum prostatic-specific antigen (PSA) for prostate cancer, mammography for breast cancer, ...

Prostate-specific antigen kallikrein: from prostate cancer to cardiovascular system.

PubMed

Patanè, Salvatore; Marte, Filippo

2009-05-01

Prostate-specific antigen (PSA), considered only an established marker for the detection of prostate cancer, has been identified as a member (hK3) of the human kallikrein family of serine proteases and now, it is known that PSA is not specific to prostate, semen, and gender. Increased PSA serum levels have been reported also in cardiovascular patients and both elevated as well as diminished PSA have been reported during acute myocardial infarction (AMI). Preliminary observations have concluded that when elevation of prostate-specific antigen occurs during AMI, it seems to relate to a higher occurrence of major adverse cardiac events and that coronary lesions are frequent and often more severe than when a diminution of PSA occurs. Large studies need to be done to confirm these preliminary results but the journey of PSA could be longer than expected.

Expression of single-chain Fv gene specific for gamma-seminoprotein by RTS and its biological activity identification.

PubMed

Han, Yuedong; Haun, Yi; Deng, Jinlan; Gao, Feng; Pan, Bifeng; Cui, Daxiang

2006-01-01

Fabricating a single-chain variable fragment specific for human seminoprotein is very important in antibody-directed enzyme prodrug therapy and NMR imaging for prostate cancer. Here a single-chain Fv specific for gamma-seminoprotein was expressed by RTS. Its activity and the efficiency of entry into prostate cancer cells are investigated by immunoprecipitation and Western blotting and immunofluorescent staining, as well as entry of conjugated magnetic beads into cells. Results showed that ScFv peptides specific for gamma-seminoprotein were successfully prepared, which can bind with the prostate cells specifically and can bring magnetic beads into prostate cancer cells within 15 min, the amount of magnetic beads inside prostate cancer cells increased as the culture time prolonged. ScFv-conjugated magnetic beads did not enter into control cells. In conclusion, the ScFv peptide against human gamma-seminoprotein with biological activity was successfully fabricated, which can take magnetic beads to prostate cancer cells specifically and not to the control cells. This ScFv peptide against human gamma-seminoprotein should be useful in improving the detection and therapy of prostate cancer at early stages and NMR imaging.

Body mass index influences prostate cancer risk at biopsy in Japanese men.

PubMed

Masuda, Hitoshi; Kagawa, Makoto; Kawakami, Satoru; Numao, Noboru; Matsuoka, Yoh; Yokoyama, Minato; Yamamoto, Shinya; Yonese, Junji; Fukui, Iwao; Kihara, Kazunori

2013-07-01

To determine the relationship between body mass index and prostate cancer risk at biopsy in Japanese men, and to compared the risk with that of Caucasian men. We retrospectively evaluated 3966 men with prostate-specific antigen levels from 2.5 to 19.9 ng/mL who underwent an initial extended prostate biopsy. Using logistic regression, odds ratios of each body mass index category for risk of prostate cancer and high-grade disease (Gleason score ≥4 + 3) were estimated after controlling for age, prostate-specific antigen, %free prostate-specific antigen, prostate volume, digital rectal examination findings, family history of prostate cancer and the number of biopsy cores. Patients were divided into six categories according to their body mass index (kg/m(2) ) as follows: <21.0, 21.0-22.9, 23.0-24.9, 25.0-26.9, 27.0-29.9 and ≥30.0. A significant positive association was observed between body mass index and prostate cancer risk at biopsy, with an increased risk observed in men whose body mass index was ≥27.0 compared with the reference group. A significantly increased risk starting at body mass index ≥25.0 was found in high-grade disease. In contrast to our results, there has been no reported increase in the risk of prostate cancer at biopsy in Caucasians within the overweight range (body mass index of 25.0-29.9 based on World Health Organization classification). Japanese men within the overweight body mass index range who have an elevated prostate-specific antigen level also have a significant risk of harboring prostate cancer, especially high-grade disease. Overweight Japanese might be at greater prostate cancer risk at biopsy than overweight Caucasians. © 2012 The Japanese Urological Association.

Effects of 8-Year Treatment of Long-Acting Testosterone Undecanoate on Metabolic Parameters, Urinary Symptoms, Bone Mineral Density, and Sexual Function in Men With Late-Onset Hypogonadism.

PubMed

Permpongkosol, Sompol; Khupulsup, Kalayanee; Leelaphiwat, Supatra; Pavavattananusorn, Sarawan; Thongpradit, Supranee; Petchthong, Thanom

2016-08-01

The long-term effects of long-acting testosterone undecanoate (TU) and androgen receptor CAG repeat lengths in Thai men with late-onset hypogonadism (LOH) have not been reported. To analyze the 8-year follow-up effects of intramuscular TU therapy on metabolic parameters, urinary symptoms, bone mineral density, and sexual function and investigate CAG repeat lengths in men with LOH. We reviewed the medical records of 428 men with LOH who had been treated with TU and 5 patients were diagnosed with prostate cancer during TU therapy. There were 120 patients (mean age = 65.6 ± 8.9 years) who had 5 to 8 years of continuous TU supplementation and sufficiently completed records for analysis. Genomic DNA was extracted from peripheral blood and the CAG repeat region was amplified by polymerase chain reaction. Fragment analysis, sequencing, electropherography, and chromatography were performed. The main outcome measure was dynamic parameter changes during testosterone supplementation. TU did not improve all obesity parameters. A statistically significant decrease was found in waist circumference, percentage of body fat, glycated hemoglobin, cholesterol, low-density lipoprotein, and International Prostate Symptom Score (P < .05). TU did not produce differences in body mass index, high-density lipoprotein, triglyceride, or the Aging Male Symptoms score from baseline. However, a statistically significant increase was found in the level of testosterone, prostate-specific antigen, hematocrit, International Index of Erectile Function score, and vertebral and femoral bone mineral density (P < .05). No major adverse cardiovascular events or prostate cancer occurred during this study. The CAG repeat length was 14 to 28 and the median CAG length was 22. There was no association between CAG repeat length and any of the anthropometric measurements. Long-term TU treatment in men with LOH for up to 8 years appears to be safe, tolerable, and effective in correcting obesity parameters. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Hemoglobins, programmed cell death and somatic embryogenesis.

PubMed

Hill, Robert D; Huang, Shuanglong; Stasolla, Claudio

2013-10-01

Programmed cell death (PCD) is a universal process in all multicellular organisms. It is a critical component in a diverse number of processes ranging from growth and differentiation to response to stress. Somatic embryogenesis is one such process where PCD is significantly involved. Nitric oxide is increasingly being recognized as playing a significant role in regulating PCD in both mammalian and plant systems. Plant hemoglobins scavenge NO, and evidence is accumulating that events that modify NO levels in plants also affect hemoglobin expression. Here, we review the process of PCD, describing the involvement of NO and plant hemoglobins in the process. NO is an effector of cell death in both plants and vertebrates, triggering the cascade of events leading to targeted cell death that is a part of an organism's response to stress or to tissue differentiation and development. Expression of specific hemoglobins can alter this response in plants by scavenging the NO, thus, interrupting the death process. Somatic embryogenesis is used as a model system to demonstrate how cell-specific expression of different classes of hemoglobins can alter the embryogenic process, affecting hormone synthesis, cell metabolite levels and genes associated with PCD and embryogenic competence. We propose that plant hemoglobins influence somatic embryogenesis and PCD through cell-specific expression of a distinct plant hemoglobin. It is based on the premise that both embryogenic competence and PCD are strongly influenced by cellular NO levels. Increases in cellular NO levels result in elevated Zn(2+) and reactive-oxygen species associated with PCD, but they also result in decreased expression of MYC2, a transcription factor that is a negative effector of indoleacetic acid synthesis, a hormone that positively influences embryogenic competence. Cell-specific hemoglobin expression reduces NO levels as a result of NO scavenging, resulting in cell survival. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Prostatic specific antigen. From its early days until becoming a prostate cancer biomarker.

PubMed

Dellavedova, T

2016-01-01

Prostate-specific antigen (PSA) has been since the mid 80's the most commonly used biomarker for measuring current and future risk of prostate cancer, for its early detection and to measure response to treatments and detecting recurrence in all stages of the disease. PSA's early development came along with progress in the field of immunology, which allowed detection and study of antigens from different tissues and fluids when injecting them into rabbits to promote immune response. Rubin Flocks in 1960 was the first to investigate and discover prostate-specific antigens in benign and malignant tissue. Some years later, Hara, a Japanese forensic investigator, found 'gamma seminoprotein', that he used to detect human semen in rape cases. However, his work published in Japanese did not reach the Englishspeaking scientific community. In 1970 Ablin discovered both in prostatic fluid and tissue what he called "prostate-specific antigen", but he didn't characterize or describe it. Investigators Li and Beling, and Sensabaugh, approached the current PSA, but they were limited by available technology at that time. Dr T Ming Chu led a research team on prostate cancer in New York, USA and published their results in 1979. He finally received the patent for the discovery of "human purified prostate antigen" in 1984. Due to this work, the Food and Drug Administration (FDA), in USA, approved the use of PSA for monitoring recurrence after treatment. It was later known that PSA was not prostate-specific since it was produced in other tissues and fluids, but it was recognized that it was human species-specific. Works by Papsidero and Stamey showed new indications and utilities for PSA, but it was Catalona who first used it as a marker for prostate cancer in 1991. Thanks to these advances FDA authorized in 1994 the clinical use of PSA for early detection of prostate cancer.

Gastric Metastasis of Prostate Cancer as an Unusual Presentation Using 68Ga-Prostate-Specific Membrane Antigen PET/CT.

PubMed

Solis Lara, Hugo Enrique; Villarreal Del Bosque, Natalia; Sada Treviño, Miguel Antonio; Yamamoto Ramos, Masao; Argueta Ruiz, Rocío Del Carmen

2018-05-01

A 79-year-old man with prostate cancer underwent Ga prostate-specific membrane antigen (Ga-PSMA) dual-time-point PET/CT scan to evaluate tumor activity due to early satiety, unquantified weight loss, and elevation of prostate-specific antigen (PSA), demonstrating thickening of the gastric wall with intense tracer uptake. The immunohistochemistry of gastric biopsy showed CDX2 and CK20: negative; CK7, focal positive; PSA, positive, which confirmed metastatic disease. Metastatic disease was also found in bones, right lung, and retroperitoneal and pelvic lymphadenopathies.

[New Radiopharmaceuticals Based on Prostate-Specific Inhibitors of Membrane Antigen for Diagnostics and Therapy of Metastatic Prostate Cancer].

PubMed

Vlasova, O P; German, K E; Krilov, V V; Petriev, V M; Epstein, N B

2015-01-01

About 10.7% cases of prostate cancer were registered in Russia in 2011 (40,000 patients). More than half of cancer cases were revealed in advanced (III-IV) stages when metastases inevitably developed quickly. Clinical problem of early diagnostics and treatment of metastatic prostate cancer is still not solved. Anatomical imaging techniques have low sensitivity and specificity for the detection of this disease. Metabolic visualization methods which use prostate specific antigen (PSA) as a marker are also ineffective. This article describes prostate-specific membrane antigens (PSMA) that are proposed as a marker for diagnostics and therapy of prostate cancer. The most promising PSMA-based radiopharmaceutical agent for diagnostics has been developed and clinically tested in the European countries. These pharmaceuticals are based on small peptide molecules modified with urea, and have the highest affinity to PSMA. Favorable phannacokinetics, rapid accumulation in the tumor and rapid excretion from the body are beneficial features of these pharmaceuticals.

Epithelial Plasticity in Castration-Resistant Prostate Cancer: Biology of the Lethal Phenotype

DTIC Science & Technology

2012-07-01

mCRPC, with metastatic progres- sion by prostate - specific antigen (PSA; 2 consecutive rises over nadir separated by more than 1 week) or radiologic...Abbreviations: CRPC, castration-resistant prostate cancer; PSA, prostate specific antigen . Armstrong et al. Mol Cancer Res; 9(8) August 2011 Molecular... antigen , which we found did correlate with PSA outcomes and high risk disease among men with localized prostate cancer who were undergoing radical

Novel In Vivo Model for Combinatorial Fluorescence Labeling in Mouse Prostate

PubMed Central

Fang, Xiaolan; Gyabaah, Kenneth; Nickkholgh, Bita; Cline, J. Mark; Balaji, K.C.

2015-01-01

BACKGROUND The epithelial layer of prostate glands contains several types of cells, including luminal and basal cells. Yet there is paucity of animal models to study the cellular origin of normal or neoplastic development in the prostate to facilitate the treatment of heterogenous prostate diseases by targeting individual cell lineages. METHODS We developed a mouse model that expresses different types of fluorescent proteins (XFPs) specifically in prostatic cells. Using an in vivo stochastic fluorescent protein combinatorial strategy, XFP signals were expressed specifically in prostate of Protein Kinase D1 (PKD1) knock-out, K-RasG12D knock-in, and Phosphatase and tensin homolog (PTEN) and PKD1 double knock-out mice under the control of PB-Cre promoter. RESULTS In vivo XFP signals were observed in prostate of PKD1 knock-out, K-RasG12D knock-in, and PTEN PKD1 double knock-out mice, which developed normal, hyperplastic, and neoplastic prostate, respectively. The patchy expression pattern of XFPs in neoplasia tissue indicated the clonal origin of cancer cells in the prostate. CONCLUSIONS The transgenic mouse models demonstrate combinatorial fluorescent protein expression in normal and cancerous prostatic tissues. This novel prostate-specific fluorescent labeled mouse model, which we named Prorainbow, could be useful in studying benign and malignant pathology of prostate. PMID:25753731

Novel In Vivo model for combinatorial fluorescence labeling in mouse prostate.

PubMed

Fang, Xiaolan; Gyabaah, Kenneth; Nickkholgh, Bita; Cline, J Mark; Balaji, K C

2015-06-15

The epithelial layer of prostate glands contains several types of cells, including luminal and basal cells. Yet there is paucity of animal models to study the cellular origin of normal or neoplastic development in the prostate to facilitate the treatment of heterogenous prostate diseases by targeting individual cell lineages. We developed a mouse model that expresses different types of fluorescent proteins (XFPs) specifically in prostatic cells. Using an in vivo stochastic fluorescent protein combinatorial strategy, XFP signals were expressed specifically in prostate of Protein Kinase D1 (PKD1) knock-out, K-Ras(G) (12) (D) knock-in, and Phosphatase and tensin homolog (PTEN) and PKD1 double knock-out mice under the control of PB-Cre promoter. In vivo XFP signals were observed in prostate of PKD1 knock-out, K-Ras(G) (12) (D) knock-in, and PTEN PKD1 double knock-out mice, which developed normal, hyperplastic, and neoplastic prostate, respectively. The patchy expression pattern of XFPs in neoplasia tissue indicated the clonal origin of cancer cells in the prostate. The transgenic mouse models demonstrate combinatorial fluorescent protein expression in normal and cancerous prostatic tissues. This novel prostate-specific fluorescent labeled mouse model, which we named Prorainbow, could be useful in studying benign and malignant pathology of prostate. © 2015 Wiley Periodicals, Inc.

Heterobivalent Imaging Agents for Simultaneous Targeting Prostate-Specific Membrane Antigen (PSMA) and Hepsin

DTIC Science & Technology

2011-04-01

specific membrane antigen (PSMA), showed promise in the clinic for identifying candidates for salvage radiotherapy. (4, 5) Because of the important...removed benzyl group to afford the Lys- Urea-Glu 14 in 85% yield. Compound 14 was conjugated with the suberic acid bis-(N- hydroxysuccinimide ( DSS ) in...directed against human and mouse prostate-specific membrane antigen. Prostate 2004; 61: 1-11. 4. Chang SS, Heston WD. The clinical role of prostate

68Ga-Labeled Anti-Prostate-Specific Membrane Antigen Peptide as Marker for Androgen Deprivation Therapy Response in Prostate Cancer.

PubMed

Schlenkhoff, Carl Diedrich; Gaertner, Florian; Essler, Markus; Hauser, Stefan; Ahmadzadehfar, Hojjat

2016-05-01

Prostate cancer was diagnosed in a 71-year-old man with an elevated prostate-specific antigen. The CT of the abdomen showed multiple para-aortal lymph nodes, and thus, a Ga anti-prostate-specific membrane antigen (PSMA-11) PET/CT was initiated, which showed, aside from the prostate cancer and multiple iliacal and para-aortal lymph node metastases, an increased tracer uptake in a lymph node left cervical. According to this advanced disease, a palliative therapy with GnRH agonist was initiated. A second PSMA-11 PET/CT was performed 4 months later, which showed a very good response; thus, additional radiation of the pelvis and the draining lymphatic system was performed.

Combining population and patient-specific characteristics for prostate segmentation on 3D CT images

NASA Astrophysics Data System (ADS)

Ma, Ling; Guo, Rongrong; Tian, Zhiqiang; Venkataraman, Rajesh; Sarkar, Saradwata; Liu, Xiabi; Tade, Funmilayo; Schuster, David M.; Fei, Baowei

2016-03-01

Prostate segmentation on CT images is a challenging task. In this paper, we explore the population and patient-specific characteristics for the segmentation of the prostate on CT images. Because population learning does not consider the inter-patient variations and because patient-specific learning may not perform well for different patients, we are combining the population and patient-specific information to improve segmentation performance. Specifically, we train a population model based on the population data and train a patient-specific model based on the manual segmentation on three slice of the new patient. We compute the similarity between the two models to explore the influence of applicable population knowledge on the specific patient. By combining the patient-specific knowledge with the influence, we can capture the population and patient-specific characteristics to calculate the probability of a pixel belonging to the prostate. Finally, we smooth the prostate surface according to the prostate-density value of the pixels in the distance transform image. We conducted the leave-one-out validation experiments on a set of CT volumes from 15 patients. Manual segmentation results from a radiologist serve as the gold standard for the evaluation. Experimental results show that our method achieved an average DSC of 85.1% as compared to the manual segmentation gold standard. This method outperformed the population learning method and the patient-specific learning approach alone. The CT segmentation method can have various applications in prostate cancer diagnosis and therapy.

Should I Get Screened for Prostate Cancer?

MedlinePlus

... about being screened for prostate cancer with a prostate specific antigen (PSA) test. Before making a decision, men should ... Task Force Prostate Cancer Screening Final Recommendation Understanding Prostate Changes: A Health ... Cancer Institute) What Is Screening? ...

Emerging Roles of Human Prostatic Acid Phosphatase

PubMed Central

Kong, Hoon Young; Byun, Jonghoe

2013-01-01

Prostate cancer is one of the most prevalent non-skin related cancers. It is the second leading cause of cancer deaths among males in most Western countries. If prostate cancer is diagnosed in its early stages, there is a higher probability that it will be completely cured. Prostatic acid phosphatase (PAP) is a non-specific phosphomonoesterase synthesized in prostate epithelial cells and its level proportionally increases with prostate cancer progression. PAP was the biochemical diagnostic mainstay for prostate cancer until the introduction of prostate-specific antigen (PSA) which improved the detection of early-stage prostate cancer and largely displaced PAP. Recently, however, there is a renewed interest in PAP because of its usefulness in prognosticating intermediate to high-risk prostate cancers and its success in the immunotherapy of prostate cancer. Although PAP is believed to be a key regulator of prostate cell growth, its exact role in normal prostate as well as detailed molecular mechanism of PAP regulation is still unclear. Here, many different aspects of PAP in prostate cancer are revisited and its emerging roles in other environment are discussed. PMID:24009853

Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

PubMed

Parwani, Anil V; Marlow, Cameron; Demarzo, Angelo M; Mikolajczyk, Stephen D; Rittenhouse, Harry G; Veltri, Robert W; Chan, Theresa Y

2006-10-01

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

Detection of prostate cancer-specific transcripts in extracellular vesicles isolated from post-DRE urine

PubMed Central

Pellegrini, Kathryn L.; Patil, Dattatraya; Douglas, Kristen J.S.; Lee, Grace; Wehrmeyer, Kathryn; Torlak, Mersiha; Clark, Jeremy; Cooper, Colin S.; Moreno, Carlos S.; Sanda, Martin G.

2018-01-01

Background The measurement of gene expression in post-digital rectal examination (DRE) urine specimens provides a non-invasive method to determine a patient’s risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer-associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate-, kidney-, and bladder-specific transcripts and known prostate cancer biomarkers in urine EVs. Methods Cell pellets and EVs were recovered from post-DRE urine specimens, with the total RNA yield and quality determined by Bioanalyzer. The levels of prostate, kidney, and bladder-associated transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing. Results RNA was more consistently recovered from the urine EV specimens, with over 80% of the patients demonstrating higher RNA yields in the EV fraction as compared to urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post-DRE urine EVs indicated that prostate-specific transcripts were more abundant than kidney- or bladder-specific transcripts. Additionally, patients with prostate cancer had significantly higher levels of the prostate cancer-associated genes PCA3 and ERG. Conclusions Post-DRE urine EVs are a viable source of prostate-derived RNAs for biomarker discovery and prostate cancer status can be distinguished from analysis of these specimens. Continued analysis of urine EVs offers the potential discovery of novel biomarkers for pre-biopsy prostate cancer detection. PMID:28419548

Detection of prostate cancer-specific transcripts in extracellular vesicles isolated from post-DRE urine.

PubMed

Pellegrini, Kathryn L; Patil, Dattatraya; Douglas, Kristen J S; Lee, Grace; Wehrmeyer, Kathryn; Torlak, Mersiha; Clark, Jeremy; Cooper, Colin S; Moreno, Carlos S; Sanda, Martin G

2017-06-01

The measurement of gene expression in post-digital rectal examination (DRE) urine specimens provides a non-invasive method to determine a patient's risk of prostate cancer. Many currently available assays use whole urine or cell pellets for the analysis of prostate cancer-associated genes, although the use of extracellular vesicles (EVs) has also recently been of interest. We investigated the expression of prostate-, kidney-, and bladder-specific transcripts and known prostate cancer biomarkers in urine EVs. Cell pellets and EVs were recovered from post-DRE urine specimens, with the total RNA yield and quality determined by Bioanalyzer. The levels of prostate, kidney, and bladder-associated transcripts in EVs were assessed by TaqMan qPCR and targeted sequencing. RNA was more consistently recovered from the urine EV specimens, with over 80% of the patients demonstrating higher RNA yields in the EV fraction as compared to urine cell pellets. The median EV RNA yield of 36.4 ng was significantly higher than the median urine cell pellet RNA yield of 4.8 ng. Analysis of the post-DRE urine EVs indicated that prostate-specific transcripts were more abundant than kidney- or bladder-specific transcripts. Additionally, patients with prostate cancer had significantly higher levels of the prostate cancer-associated genes PCA3 and ERG. Post-DRE urine EVs are a viable source of prostate-derived RNAs for biomarker discovery and prostate cancer status can be distinguished from analysis of these specimens. Continued analysis of urine EVs offers the potential discovery of novel biomarkers for pre-biopsy prostate cancer detection. © 2017 Wiley Periodicals, Inc.

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China.

PubMed

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-02

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients.

Comparison of clinical and survival characteristics between prostate cancer patients of PSA-based screening and clinical diagnosis in China

PubMed Central

Xu, Libo; Wang, Jinguo; Guo, Baofeng; Zhang, Haixia; Wang, Kaichen; Wang, Ding; Dai, Chang; Zhang, Ling; Zhao, Xuejian

2018-01-01

Prostate-specific antigen (PSA)-based mass screening remains the most controversial topic in prostate cancer. PSA-based mass screening has not been widely used in China yet. The aim of our study was to evaluate the effect of the PSA-based screening in China. The cohort consisted of 1,012 prostate cancer patients. Data were retrospectively collected and clinical characteristics of the cohorts were investigated. Survival was analyzed for prostatic carcinoma of both PSA screened and clinically diagnosed patients according to clinical characteristics and the National Comprehensive Cancer Network (NCCN) risk classification. Cox Proportional Hazards Model analysis was done for risk predictor identification. The median age was 71 years old. Five-year overall and prostate-cancer-specific survival in prostatic adenocarcinoma patients were 77.52% and 79.65%; 10-year survivals were 62.57% and 68.60%, respectively. Survival was significantly poorer in patients with metastases and non-curative management. T staging and Gleason score by NCCN classification effectively stratified prostatic adenocarcinoma patients into different risk groups. T staging was a significant predictor of survival by COX Proportional Hazard Model. PSA screened patients had a significantly higher percentage diagnosed in early stage. PSA screened prostatic adenocarcinoma patients had a better prognosis in both overall and prostate cancer-specific survivals. This Chinese cohort had a lower overall and prostate cancer survival rate than it is reported in western countries. The incidence of early-stage prostate cancer found in PSA-based mass screening was high and there were significant differences in both overall and prostate cancer-specific survival between the PSA-screened and clinically diagnosed patients. PMID:29416625

Locus-specific gene repositioning in prostate cancer

PubMed Central

Leshner, Marc; Devine, Michelle; Roloff, Gregory W.; True, Lawrence D.; Misteli, Tom; Meaburn, Karen J.

2016-01-01

Genes occupy preferred spatial positions within interphase cell nuclei. However, positioning patterns are not an innate feature of a locus, and genes can alter their localization in response to physiological and pathological changes. Here we screen the radial positioning patterns of 40 genes in normal, hyperplasic, and malignant human prostate tissues. We find that the overall spatial organization of the genome in prostate tissue is largely conserved among individuals. We identify three genes whose nuclear positions are robustly altered in neoplastic prostate tissues. FLI1 and MMP9 position differently in prostate cancer than in normal tissue and prostate hyperplasia, whereas MMP2 is repositioned in both prostate cancer and hyperplasia. Our data point to locus-specific reorganization of the genome during prostate disease. PMID:26564800

The roles of prostate-specific antigen (PSA) density, prostate volume, and their zone-adjusted derivatives in predicting prostate cancer in patients with PSA less than 20.0 ng/mL.

PubMed

Shen, P; Zhao, J; Sun, G; Chen, N; Zhang, X; Gui, H; Yang, Y; Liu, J; Shu, K; Wang, Z; Zeng, H

2017-05-01

The aim of this study was to develop nomograms for predicting prostate cancer and its zonal location using prostate-specific antigen density, prostate volume, and their zone-adjusted derivatives. A total of 928 consecutive patients with prostate-specific antigen (PSA) less than 20.0 ng/mL, who underwent transrectal ultrasound-guided transperineal 12-core prostate biopsy at West China Hospital between 2011 and 2014, were retrospectively enrolled. The patients were randomly split into training cohort (70%, n = 650) and validation cohort (30%, n = 278). Predicting models and the associated nomograms were built using the training cohort, while the validations of the models were conducted using the validation cohort. Univariate and multivariate logistic regression was performed. Then, new nomograms were generated based on multivariate regression coefficients. The discrimination power and calibration of these nomograms were validated using the area under the ROC curve (AUC) and the calibration curve. The potential clinical effects of these models were also tested using decision curve analysis. In total, 285 (30.7%) patients were diagnosed with prostate cancer. Among them, 131 (14.1%) and 269 (29.0%) had transition zone prostate cancer and peripheral zone prostate cancer. Each of zone-adjusted derivatives-based nomogram had an AUC more than 0.75. All nomograms had higher calibration and much better net benefit than the scenarios in predicting patients with or without different zones prostate cancer. Prostate-specific antigen density, prostate volume, and their zone-adjusted derivatives have important roles in detecting prostate cancer and its zonal location for patients with PSA 2.5-20.0 ng/mL. To the best of our knowledge, this is the first nomogram using these parameters to predict outcomes of 12-core prostate biopsy. These instruments can help clinicians to increase the accuracy of prostate cancer screening and to avoid unnecessary prostate biopsy. © 2017 American Society of Andrology and European Academy of Andrology.

Identification of hemoglobin variants by top-down mass spectrometry using selected diagnostic product ions.

PubMed

Coelho Graça, Didia; Hartmer, Ralf; Jabs, Wolfgang; Beris, Photis; Clerici, Lorella; Stoermer, Carsten; Samii, Kaveh; Hochstrasser, Denis; Tsybin, Yury O; Scherl, Alexander; Lescuyer, Pierre

2015-04-01

Hemoglobin disorder diagnosis is a complex procedure combining several analytical steps. Due to the lack of specificity of the currently used protein analysis methods, the identification of uncommon hemoglobin variants (proteoforms) can become a hard task to accomplish. The aim of this work was to develop a mass spectrometry-based approach to quickly identify mutated protein sequences within globin chain variants. To reach this goal, a top-down electron transfer dissociation mass spectrometry method was developed for hemoglobin β chain analysis. A diagnostic product ion list was established with a color code strategy allowing to quickly and specifically localize a mutation in the hemoglobin β chain sequence. The method was applied to the analysis of rare hemoglobin β chain variants and an (A)γ-β fusion protein. The results showed that the developed data analysis process allows fast and reliable interpretation of top-down electron transfer dissociation mass spectra by nonexpert users in the clinical area.

Increasing Early Detection of Prostate Cancer in African American Men Through a Culturally Targeted Print Intervention

DTIC Science & Technology

2006-03-01

of a protein called prostate-specific antigen (PSA). Normally, PSA is found in the blood at very low levels. Elevated PSA readings can be a sign of...cancer. ♦ Prostate Specific Antigen test (also called PSA test) - This simple blood test measures the level of a protein called prostate- specific...meat ♦ Lycopene, a compound in cooked tomato products and watermelon . 9 A number of Black men say they have problems with their

Health Screening: What Tests You Need and When

MedlinePlus

... cancer screening if you are considering having a prostate-specific antigen (PSA) test or digital rectal examination (DRE). Sexually ... regular colonoscopy for cancer of the colon, serum prostatic-specific antigen (PSA) for prostate cancer, mammography for breast cancer, ...

The Infectious Pathogenesis of Prostate Cancer

DTIC Science & Technology

2010-03-01

of cancers, including prostate. Infections are important agents in the genesis of inflammation. For prostate cancer, several lines of evidence point...to a role of infections as important agents , although no specific infection has consistently been identified. In this project, we are examining two...specific infectious agents with respect to prostate cancer: T vaginalis, the most common non-viral sexually transmitted infection, and the recently

Age-related reference intervals for free and total prostate-specific antigen in a Singaporean population.

PubMed

Saw, S; Aw, T C

2000-11-01

Cancer of the prostate is the sixth most frequently found cancer in Singapore. Prostate-specific antigen (PSA) is the most clinically useful tumour marker available today for the diagnosis and management of prostate cancer. To enhance the value of PSA as a screening test we developed age-specific intervals for our ethnic population. The measurement of free PSA was included in the study to calculate the free:total ratio which enhances the differential diagnosis of prostate cancer from benign prostatic hyperplasia or prostatitis. The total PSA upper limits of 10-year intervals, beginning at 30-years-old, were 1.4, 1.7, 2.3, 4.0, 6.3 and 6.6 microg/l. Free PSA cut-off limits were 0.4, 0.5, 0.5, 1.0, 1.5 and 1.6 microg/l. The free:total ratio of PSA was not age dependent. Abbott AxSym standardised their calibration material for both free and total PSA assays with the Stanford 90:10 reference material. This laboratory has implemented these age-specific reference intervals and are currently following up their pick-up rate in the detection of prostate cancer.

An inducible model of abacterial prostatitis induces antigen specific inflammatory and proliferative changes in the murine prostate

PubMed Central

Haverkamp, Jessica M.; Charbonneau, Bridget; Meyerholz, David K.; Cohen, Michael B.; Snyder, Paul W.; Svensson, Robert U.; Henry, Michael D.; Wang, Hsing- Hui

2011-01-01

Background Prostatitis is a poorly understood disease and increasing evidence suggests inflammation is involved in other prostatic diseases, including prostate cancer. Methods The ability of pre-activated CD8 T cells to induce prostatitis was examined by adoptive transfer into POET-3 mice or POET-3/Luc/Pten−/+ mice. Characterization of the inflammatory response was determined by examining leukocyte infiltration by histological analysis, flow cytometry and by evaluating cytokine and chemokine levels in prostate tissue. The impact of inflammation on the prostate was evaluated by monitoring epithelial cell proliferation over time. Results Initiation of inflammation by ovalbumin specific CD8+ T cells (OT-I cells) resulted in development of acute prostatitis in the anterior, dorsolateral and anterior prostate of POET-3 and POET-3/Luc/Pten−/+ mice. Acute prostatitis was characterized by recruitment of adoptively transferred OT-I cells and importantly, autologous CD4+ and CD8+ T cells, myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg). In concert with leukocyte infiltration elevated levels of pro-inflammatory cytokines and chemokines were observed. Inflammation also resulted in marked epithelial cell proliferation that was sustained up to 80 days post adoptive-transfer of OT-I cells. Conclusions The POET-3 model represents a novel mouse model to study both acute and chronic prostate inflammation in an antigen-specific system. Further, the POET-3 mouse model can be crossed with other genetic models of disease such as the C57/Luc/Pten−/− model of prostate cancer, allowing the impact of prostatitis on other prostatic diseases to be evaluated. PMID:21656824

Modeling prostate cancer in mice: something old, something new, something premalignant, something metastatic.

PubMed

Irshad, Shazia; Abate-Shen, Cory

2013-06-01

More than 15 years ago, the first generation of genetically engineered mouse (GEM) models of prostate cancer was introduced. These transgenic models utilized prostate-specific promoters to express SV40 oncogenes specifically in prostate epithelium. Since the description of these initial models, there have been a plethora of GEM models of prostate cancer representing various perturbations of oncogenes or tumor suppressors, either alone or in combination. This review describes these GEM models, focusing on their relevance for human prostate cancer and highlighting their strengths and limitations, as well as opportunities for the future.

Bone Marrow-derived Mesenchymal Stem Cells (MSCs) as a Selective Delivery Vehicle for a PSA-Activated Protoxin for Advanced Prostate Cancer

DTIC Science & Technology

2014-04-01

other groups are seeking to develop MSCs as vectors to deliver prostate - specific antigen (PSA)-activated prodrugs (Denmeade et al. 2003) and protoxins...Denmeade SR, Jakobsen CM, Janssen S, Khan SR, Garrett ES, Lilja H, Christensen SB & Isaacs JT 2003 Prostate - specific antigen -activated thapsigargin...cells derived from benign prostatic hyperplasia specimens possess stem cell like property. Prostate 67 1265–1276. (doi:10.1002/ pros .20599) Lin G, Yang R

Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

PubMed

Hatano, Koji; Nonomura, Norio; Nishimura, Kazuo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Tsujimura, Akira; Okuyama, Akihiko

2011-02-01

To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

Prostate-Specific Membrane Antigen-Negative Metastases-A Potential Pitfall in Prostate-Specific Membrane Antigen PET.

PubMed

Noto, Benjamin; Auf der Springe, Katharina; Huss, Sebastian; Allkemper, Thomas; Stegger, Lars

2018-06-01

Ga-PSMA-11 PET/CT was performed in a 74-year-old man because of biochemical recurrence of prostate cancer following radiation therapy of the prostate gland 24 months earlier. Besides focal nuclide accumulation in the prostate gland suggestive of local recurrence, PET scan revealed no further pathologic uptake. However, CT showed multiple pulmonic nodules suggestive of metastases. Thoracotomy and pathologic examination revealed the nodules to be prostate cancer metastasis. Furthermore, immunohistochemical staining with PSMA antibodies demonstrated a virtual lack of PSMA expression. This case demonstrates the possibility of PSMA-negative metastases of prostate cancer an important pitfall that should be known to physicians interpreting PSMA PET.

Evaluation of a novel label-free photonic-crystal biosensor imaging system for the detection of prostate cancer cells

NASA Astrophysics Data System (ADS)

DeLuna, Frank; Ding, XiaoFie; Sun, Lu-Zhe; Ye, Jing Yong

2017-02-01

Biomarker screening for prostate-specific antigen (PSA) is the current clinical standard for detection of prostate cancer. However this method has shown many limitations, mainly in its specificity, which can lead to a high false positive rate. Thus, there is a growing need in developing a more specific detection system for prostate cancer. Using a Photonic- Crystal-based biosensor in a Total-Internal-Reflection (PC-TIR) configuration, we demonstrate the use of refractive index (RI) to accomplish label-free detection of prostate cancer cells against non-cancerous prostate epithelial cells. The PC-TIR biosensor possesses an open microcavity, which in contrast to traditional closed microcavities, allows for easier access of analyte molecules or cells to interact with its sensing surface. In this study, an imaging system was designed using the PC-TIR biosensor to quantify cell RI as the contrast parameter for prostate cancer detection. Non-cancerous BPH-1 prostate epithelial cells and prostate cancer PC-3 cells were placed on a single biosensor and measured concurrently. Recorded image data was then analyzed through a home-built MatLab program. Results demonstrate that RI is a suitable variable for differentiation between prostate cancer cells and non-cancerous prostate epithelial cells. Our study shows clinical potential in utilizing RI test for the detection of prostate cancer.

Prospective evaluation of magnetic resonance imaging guided in-bore prostate biopsy versus systematic transrectal ultrasound guided prostate biopsy in biopsy naïve men with elevated prostate specific antigen.

PubMed

Quentin, Michael; Blondin, Dirk; Arsov, Christian; Schimmöller, Lars; Hiester, Andreas; Godehardt, Erhard; Albers, Peter; Antoch, Gerald; Rabenalt, Robert

2014-11-01

Magnetic resonance imaging guided biopsy is increasingly performed to diagnose prostate cancer. However, there is a lack of well controlled, prospective trials to support this treatment method. We prospectively compared magnetic resonance imaging guided in-bore biopsy with standard systematic transrectal ultrasound guided biopsy in biopsy naïve men with increased prostate specific antigen. We performed a prospective study in 132 biopsy naïve men with increased prostate specific antigen (greater than 4 ng/ml). After 3 Tesla functional multiparametric magnetic resonance imaging patients were referred for magnetic resonance imaging guided in-bore biopsy of prostate lesions (maximum 3) followed by standard systematic transrectal ultrasound guided biopsy (12 cores). We analyzed the detection rates of prostate cancer and significant prostate cancer (greater than 5 mm total cancer length or any Gleason pattern greater than 3). A total of 128 patients with a mean ± SD age of 66.1 ± 8.1 years met all study requirements. Median prostate specific antigen was 6.7 ng/ml (IQR 5.1-9.0). Transrectal ultrasound and magnetic resonance imaging guided biopsies provided the same 53.1% detection rate, including 79.4% and 85.3%, respectively, for significant prostate cancer. Magnetic resonance imaging and transrectal ultrasound guided biopsies missed 7.8% and 9.4% of clinically significant prostate cancers, respectively. Magnetic resonance imaging biopsy required significantly fewer cores and revealed a higher percent of cancer involvement per biopsy core (each p <0.01). Combining the 2 methods provided a 60.9% detection rate with an 82.1% rate for significant prostate cancer. Magnetic resonance imaging guided in-bore and systematic transrectal ultrasound guided biopsies achieved equally high detection rates in biopsy naïve patients with increased prostate specific antigen. Magnetic resonance imaging guided in-bore biopsies required significantly fewer cores and revealed a significantly higher percent of cancer involvement per biopsy core. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Online updating of context-aware landmark detectors for prostate localization in daily treatment CT images

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

Dai, Xiubin; Gao, Yaozong; Shen, Dinggang, E-mail: dgshen@med.unc.edu

2015-05-15

Purpose: In image guided radiation therapy, it is crucial to fast and accurately localize the prostate in the daily treatment images. To this end, the authors propose an online update scheme for landmark-guided prostate segmentation, which can fully exploit valuable patient-specific information contained in the previous treatment images and can achieve improved performance in landmark detection and prostate segmentation. Methods: To localize the prostate in the daily treatment images, the authors first automatically detect six anatomical landmarks on the prostate boundary by adopting a context-aware landmark detection method. Specifically, in this method, a two-layer regression forest is trained as amore » detector for each target landmark. Once all the newly detected landmarks from new treatment images are reviewed or adjusted (if necessary) by clinicians, they are further included into the training pool as new patient-specific information to update all the two-layer regression forests for the next treatment day. As more and more treatment images of the current patient are acquired, the two-layer regression forests can be continually updated by incorporating the patient-specific information into the training procedure. After all target landmarks are detected, a multiatlas random sample consensus (multiatlas RANSAC) method is used to segment the entire prostate by fusing multiple previously segmented prostates of the current patient after they are aligned to the current treatment image. Subsequently, the segmented prostate of the current treatment image is again reviewed (or even adjusted if needed) by clinicians before including it as a new shape example into the prostate shape dataset for helping localize the entire prostate in the next treatment image. Results: The experimental results on 330 images of 24 patients show the effectiveness of the authors’ proposed online update scheme in improving the accuracies of both landmark detection and prostate segmentation. Besides, compared to the other state-of-the-art prostate segmentation methods, the authors’ method achieves the best performance. Conclusions: By appropriate use of valuable patient-specific information contained in the previous treatment images, the authors’ proposed online update scheme can obtain satisfactory results for both landmark detection and prostate segmentation.« less

Dendritic Cells Program Non-Immunogenic Prostate-Specific T Cell Responses Beginning at Early Stages of Prostate Tumorigenesis

PubMed Central

Mihalyo, Marianne A.; Hagymasi, Adam T.; Slaiby, Aaron M.; Nevius, Erin E.; Adler, Adam J.

2010-01-01

BACKGROUND Prostate cancer promotes the development of T cell tolerance towards prostatic antigens, potentially limiting the efficacy of prostate cancer vaccines targeting these antigens. Here, we sought to determine the stage of disease progression when T cell tolerance develops, as well as the role of steady state dendritic cells (DC) and CD4+CD25+ T regulatory cells (Tregs) in programming tolerance. METHODS The response of naïve HA-specific CD4+ T cells were analyzed following adoptive transfer into Pro-HA × TRAMP transgenic mice harboring variably-staged HA-expressing prostate tumors on two genetic backgrounds that display different patterns and kinetics of tumorigenesis. The role of DC and Tregs in programming HA-specific CD4 cell responses were assessed via depletion. RESULTS HA-specific CD4 cells underwent non-immunogenic responses at all stages of tumorigenesis in both genetic backgrounds. These responses were completely dependent on DC, but not appreciably influenced by Tregs. CONCLUSIONS These results suggest that tolerogenicity is an early and general property of prostate tumors. PMID:17221844

A single microfocus (5% or less) of Gleason 6 prostate cancer at biopsy--can we predict adverse pathological outcomes?

PubMed

Thong, Alan E; Shikanov, Sergey; Katz, Mark H; Gofrit, Ofer N; Eggener, Scott; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C

2008-12-01

Patients with Gleason score 6 microfocal prostate cancer, defined as 5% or less in 1 biopsy core, are often considered to have favorable disease. Few studies have addressed clinical parameters that predict pathological upgrading or up staging at radical prostatectomy. From a prospective database of 1,271 consecutive robot assisted laparoscopic prostatectomies performed from 2003 to 2008 patients with Gleason score 6 microfocal prostate cancer were identified. Adverse pathological outcome was defined as any upgrading and/or up staging on prostatectomy pathological findings. Multivariate logistic regression was used to evaluate the ability of patient age, clinical stage, the total number of biopsy cores, preoperative prostate specific antigen, prostate volume and pathological prostate specific antigen density to predict adverse pathological outcomes. A total of 192 patients with a median age of 59 years (range 42 to 73) were identified with Gleason score 6 prostate cancer involving 5% or less of 1 biopsy core, including 177 (92%) with clinical T1c disease. Mean +/- SD preoperative prostate specific antigen was 6.0 +/- 3.9 ng/ml (range 0.8 to 35). Overall 42 patients (22%) had adverse pathological outcomes, including upgrading in 35 (18%) and up staging in 16 (8%). Multivariate logistic regression revealed that age more than 65 years and pathological prostate specific antigen density greater than 0.20 ng/ml/gm were predictive of an increased risk of adverse pathological results (p = 0.0081 and 0.0169, respectively). While a microfocus of Gleason score 6 prostate cancer on biopsy is commonly considered low risk disease, there was a greater than 1/5 risk of pathological upgrading and/or up staging. Patients with Gleason score 6 microfocal prostate cancer should be counseled that they may harbor more aggressive disease, especially when pretreatment clinical risk factors are present, such as advanced age or high clinical prostate specific antigen density.

Prostate Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

Prostate cancer screening with the prostate-specific antigen (PSA) test or digital rectal exams has not been shown to reduce prostate cancer deaths. Get detailed information about prostate cancer screening, including potential benefits and harms, in this summary for clinicians.

Evidence of prostate cancer "reverse stage migration" toward more advanced disease at diagnosis: Data from the Pennsylvania Cancer Registry.

PubMed

Reese, Adam C; Wessel, Sean R; Fisher, Susan G; Mydlo, Jack H

2016-08-01

The widespread adoption of prostate-specific antigen-based prostate cancer screening caused a stage migration toward earlier stage disease at diagnosis. We investigated whether this stage migration has persisted in a contemporary analysis of a population-based statewide cancer registry. We analyzed the Pennsylvania Cancer Registry, a statewide registry of all newly diagnosed cancers. Data were collected on prostate cancers diagnosed between 1992 and 2012. We determined age-adjusted prostate cancer incidence and mortality rates, as well as the distribution of tumor stage (localized, regional, or metastatic) at diagnosis, and assessed for changes in these variables over time using joinpoint analysis. Between 1992 and 2012, 210,831 new cases of prostate cancer were diagnosed in Pennsylvania, and 33,948 men died of disease. Age-adjusted prostate cancer incidence rates, and specifically the incidence of localized disease, have decreased dramatically since 2007 to 2008. Due to the decreased diagnosis of localized disease, regional and metastatic tumors have made up a greater percentage of all prostate cancer diagnoses in recent years, despite a relatively stable incidence of these advanced stage tumors. Over the past 2 decades, age-adjusted prostate cancer incidence rates in Pennsylvania have decreased, primarily because of the decreased detection of early-stage disease. There has been a corresponding shift toward more advanced disease at diagnosis. These findings may be explained by the decreased use of prostate-specific antigen-based screening, among other factors. The 2012 United States Preventative Services Task Force recommendations against prostate cancer screening may exacerbate this concerning trend, potentially resulting in an increase in prostate cancer-specific mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

The KTP-(greenlight-) laser--principles and experiences.

PubMed

Bachmann, Alexander; Ruszat, Robin

2007-01-01

The most recent advance in laser technology for transurethral prostatectomy is represented by the KTP laser. A potassium-titanyl-phosphate-(KTP-) crystal doubles the frequency of pulsed Neodymium: Yttrium-Aluminum-Garnet (Nd:YAG) laser energy to a 532 nm wavelength, which is in the green electromagnetic spectrum (Greenlight-laser) and is selectively absorbed by hemoglobin and not at all by water. Reducing the wavelength leads to a completely different interaction between laser beam and prostatic tissue. In contrast to the early clinical experiences with the Nd:YAG lasers in which vaporization was observed as a side-effect during the procedure, the new KTP laser offers an immediate and efficient vaporization, leading to real tissue ablation. Because of the instant and nearly complete absorption in blood, the depth in vascularized tissue such as prostate is only 0.8 mm. The superficial coagulation prevents the large tissue necrosis that is seen with the Nd:YAG laser, leading to long lasting irritative symptoms due to sloughing of necrotic tissue. Initial experiences, made with a 60W KTP system, demonstrated that the procedure was as effective as conventional transurethral resection of the prostate (TURP) with a lower intraoperative complication rate. In order to speed up vaporization of the prostate laser power has been increased to 80W. The 80W KTP laser combines the tissue debulking properties of TURP and the favourable safety profile of laser surgery. With the new 120W High Performance System, introduced in 2006, vaporization will become more powerful and faster. Initial reports are awaited.

Thulium laser enucleation (ThuLEP) versus transurethral resection of the prostate in saline (TURis): A randomized prospective trial to compare intra and early postoperative outcomes.

PubMed

Bozzini, G; Seveso, M; Melegari, S; de Francesco, O; Buffi, N M; Guazzoni, G; Provenzano, M; Mandressi, A; Taverna, G

2017-06-01

To compare clinical intra and early postoperative outcomes between thulium laser transurethral enucleation of the prostate (ThuLEP) and transurethral bipolar resection of the prostate (TURis) for treating benign prostatic hyperplasia (BPH) in a prospective randomized trial. The study randomized 208 consecutive patients with BPH to ThuLEP (n=102) or TURis (n=106). For all patients were evaluated preoperatively with regards to blood loss, catheterization time, irrigation volume, hospital stay and operative time. At 3 months after surgery they were also evaluated by International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and postvoid residual urine volume (PVR). The patients in each study arm each showed no significant difference in preoperative parameters. Compared with TURIS, ThuLEP had same operative time (53.69±31.44 vs 61.66±18.70minutes, P=.123) but resulted in less hemoglobin decrease (0.45 vs 2.83g/dL, P=.005). ThuLEP also needed less catheterization time (1.3 vs 4.8 days, P=.011), irrigation volume (29.4 vs 69.2 L, P=.002), and hospital stay (1.7 vs 5.2 days, P=.016). During the 3 months of follow-up, the procedures did not demonstrate a significant difference in Qmax, IPSS, PVR, and QOLS. ThuLEP and TURis both relieve lower urinary tract symptoms equally, with high efficacy and safety. ThuLEP was statistically superior to TURis in blood loss, catheterization time, irrigation volume, and hospital stay. However, procedures did not differ significantly in Qmax, IPSS, PVR, and QOLS through 3 months of follow-up. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

In vivo cryoablation of prostate tissue with temperature monitoring by optoacoustic imaging

NASA Astrophysics Data System (ADS)

Petrova, Elena V.; Motamedi, Massoud; Oraevsky, Alexander A.; Ermilov, Sergey A.

2016-03-01

Cryoablation of prostate cancer is an FDA approved clinical procedure, which involves repetitive rapid cooling of a lesion to lethal temperatures of -40°C and below. The major drawback of the technique is the insufficient control over the fast thermal processes that may result in severe complications (impotence, incontinence, perforation of the rectal wall) and morbidity. The developed optoacoustic imaging technique provides non-invasive real-time temperature mapping of tissue adjacent to prostate and enables more efficient control over the procedure, which is necessary to reduce side effects and accelerate the physician's learning curve. In these studies we successfully demonstrated real-time transrectal optoacoustic imaging during prostate cryoablation in live canine model focused on optoacoustic thermography of the rectal wall within the depth of 1cm. Our method utilized previously discovered universal thermal dependence of the normalized optoacoustic response of blood. Nanosecond-pulse radiation of Ti-Sapphire laser tuned to the isosbestic point of hemoglobin (802+/-3 nm) was delivered via fiberoptic illuminators assembled on both sides of the linear array of the 128-channel transrectal ultrasound probe. Temperature readouts at discrete locations inside and nearby prostate were also performed using standard transperineal needle sensors. The effect of homeostasis on optoacoustic imaging in live tissue was examined during cooling and shown to be significant only within the range of +/-1.5°C in respect to the body temperature. Accuracy of in vivo optoacoustic temperature measurements was determined as +/-2°C for the range of temperature from +35 to -15°C, which is more than sufficient for tracking the essential isotherms in the course of clinical procedures.

Biomarkers in the Management and Treatment of Men with Metastatic Castration-Resistant Prostate Cancer

PubMed Central

Armstrong, Andrew J.; Eisenberger, Mario A.; Halabi, Susan; Oudard, Stephane; Nanus, David M.; Petrylak, Daniel P.; Sartor, A. Oliver; Scher, Howard I.

2012-01-01

Context We have recently witnessed a rapid increase in the number of effective systemic agents for men with metastatic castration-resistant prostate cancer (CRPC), including novel hormonal therapies (abiraterone acetate and MDV3100), immunotherapies (sipu-leucel-T), chemotherapies (cabazitaxel), and bone microenvironment targeting agents (denosumab, radium 223). Given the increasing complexity of treatment decisions for this disease, major research and clinical priorities are (1) finding biomarkers that enable an understanding of the natural history and complex biology of this heterogeneous malignancy, (2) defining predictive biomarkers that identify men most likely to benefit from a given therapy, and (3) identifying biomarkers of early response or progression to optimize outcomes. Objective In this review, we discuss existing and potential biomarkers in CRPC and how they may currently inform prognosis, aid in treatment selection (predictive value), and relate to survival outcomes (surrogacy). Evidence acquisition PubMed-based literature searches and abstracts through September 2011 provided the basis for this literature review as well as expert opinion. Evidence synthesis We address blood and urine-based biomarkers such as prostate-specific antigen, lactate dehydrogenase, total and bone alkaline phosphatase and other bone turnover markers, hemoglobin, and circulating tumor cells in the context of prognosis, prediction, and patient selection for therapy. Given the inherent problems associated with defining progression-free survival in CRPC, the importance of biomarker development and the needed steps are highlighted. We place the discussion of bio-markers within the context of the design/intent of a trial and mechanism of action of a given systemic therapy. We discuss novel biomarker development and the pathway for surrogate or predictive biomarkers to become credentialed as useful tests that inform therapeutic decisions. Conclusions A greater understanding of biomarkers in CRPC permits a more personalized approach to care that maximizes benefit and minimizes harm and can inform clinical trials tailored to men most likely to derive benefit. PMID:22099611

Circulating Tumor Cell Counts Are Prognostic of Overall Survival in SWOG S0421: A Phase III Trial of Docetaxel With or Without Atrasentan for Metastatic Castration-Resistant Prostate Cancer

PubMed Central

Goldkorn, Amir; Ely, Benjamin; Quinn, David I.; Tangen, Catherine M.; Fink, Louis M.; Xu, Tong; Twardowski, Przemyslaw; Van Veldhuizen, Peter J.; Agarwal, Neeraj; Carducci, Michael A.; Monk, J. Paul; Datar, Ram H.; Garzotto, Mark; Mack, Philip C.; Lara, Primo; Higano, Celestia S.; Hussain, Maha; Thompson, Ian Murchie; Cote, Richard J.; Vogelzang, Nicholas J.

2014-01-01

Purpose Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan. Patients and Methods CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees. Results Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus ≥ five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for ≥ five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55). Conclusion These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting. PMID:24616308

Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer.

PubMed

Goldkorn, Amir; Ely, Benjamin; Quinn, David I; Tangen, Catherine M; Fink, Louis M; Xu, Tong; Twardowski, Przemyslaw; Van Veldhuizen, Peter J; Agarwal, Neeraj; Carducci, Michael A; Monk, J Paul; Datar, Ram H; Garzotto, Mark; Mack, Philip C; Lara, Primo; Higano, Celestia S; Hussain, Maha; Thompson, Ian Murchie; Cote, Richard J; Vogelzang, Nicholas J

2014-04-10

Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan. CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees. Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus ≥ five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for ≥ five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55). These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting.

Updated Prognostic Model for Predicting Overall Survival in First-Line Chemotherapy for Patients With Metastatic Castration-Resistant Prostate Cancer

PubMed Central

Halabi, Susan; Lin, Chen-Yen; Kelly, W. Kevin; Fizazi, Karim S.; Moul, Judd W.; Kaplan, Ellen B.; Morris, Michael J.; Small, Eric J.

2014-01-01

Purpose Prognostic models for overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC) are dated and do not reflect significant advances in treatment options available for these patients. This work developed and validated an updated prognostic model to predict OS in patients receiving first-line chemotherapy. Methods Data from a phase III trial of 1,050 patients with mCRPC were used (Cancer and Leukemia Group B CALGB-90401 [Alliance]). The data were randomly split into training and testing sets. A separate phase III trial served as an independent validation set. Adaptive least absolute shrinkage and selection operator selected eight factors prognostic for OS. A predictive score was computed from the regression coefficients and used to classify patients into low- and high-risk groups. The model was assessed for its predictive accuracy using the time-dependent area under the curve (tAUC). Results The model included Eastern Cooperative Oncology Group performance status, disease site, lactate dehydrogenase, opioid analgesic use, albumin, hemoglobin, prostate-specific antigen, and alkaline phosphatase. Median OS values in the high- and low-risk groups, respectively, in the testing set were 17 and 30 months (hazard ratio [HR], 2.2; P < .001); in the validation set they were 14 and 26 months (HR, 2.9; P < .001). The tAUCs were 0.73 (95% CI, 0.70 to 0.73) and 0.76 (95% CI, 0.72 to 0.76) in the testing and validation sets, respectively. Conclusion An updated prognostic model for OS in patients with mCRPC receiving first-line chemotherapy was developed and validated on an external set. This model can be used to predict OS, as well as to better select patients to participate in trials on the basis of their prognosis. PMID:24449231

MD-miniRNA could be a more accurate biomarker for prostate cancer screening compared with serum prostate-specific antigen level.

PubMed

Xue, Dong; Zhou, Cui-Xing; Shi, Yun-Bo; Lu, Hao; He, Xiao-Zhou

2015-05-01

Prostate cancer and prostatic hyperplasia detection remains a great challenge, lacking of effective non-invasive and specific diagnostic biomarkers. In the current study, we aimed to identify the relative expression of plasma MD-miniRNA and its diagnostic performance in differentiating prostate cancer and prostatic hyperplasia patients from healthy controls, compared with serum prostate-specific antigen (PSA) level. All of the clinical participants (63 prostate cancer patients, 32 prostatic hyperplasia patients, and 50 healthy controls) were obtained from the Third Affiliated Hospital of Suzhou University in China between January 2013 and April 2014. Clinical characteristics were well matched. Plasma samples were extracted to test the relative expression of MD-miniRNA using the method of qRT-PCR. SPSS 22.0 statistical software package was used to analyze the data and GraphPad Prism 6.0 was used to generate the graphs. Relativity expression of plasma MD-miniRNA was significantly upregulated in prostate cancer, compared with prostatic hyperplasia patients and healthy controls. Serum PSA level revealed similar differences among these groups. MD-miniRNA presented a relatively high diagnostic accuracy with AUC of 0.86 (95 % CI 0.80-0.93) in differentiating prostate cancer patients from healthy controls. Simultaneously, MD-miniRNA was able to discriminate prostate cancer patients from prostatic hyperplasia controls with AUC of 0.79 (95 % CI 0.70-0.88). In addition, MD-miniRNA displayed a better diagnostic performance than PSA level. However, the panel of these two biomarkers revealed the best diagnostic performance, compared with either single biomarker. Results of this study showed that plasma MD-miniRNA could serve as a promising and noninvasive biomarker for diagnosing prostate cancer. Further large-scale studies are needed to confirm its clinical diagnosis accuracy.

Quantitative Proteomic Profiling of Prostate Cancer Reveals a Role for miR-128 in Prostate Cancer*

PubMed Central

Khan, Amjad P.; Poisson, Laila M.; Bhat, Vadiraja B.; Fermin, Damian; Zhao, Rong; Kalyana-Sundaram, Shanker; Michailidis, George; Nesvizhskii, Alexey I.; Omenn, Gilbert S.; Chinnaiyan, Arul M.; Sreekumar, Arun

2010-01-01

Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of biomarkers of cancer invasion and disease aggressiveness. Although alterations in gene expression have been extensively quantified during neoplastic progression, complementary analyses of proteomic changes have been limited. Here we interrogate the proteomic alterations in a cohort of 15 prostate-derived tissues that included five each from adjacent benign prostate, clinically localized prostate cancer, and metastatic disease from distant sites. The experimental strategy couples isobaric tags for relative and absolute quantitation with multidimensional liquid phase peptide fractionation followed by tandem mass spectrometry. Over 1000 proteins were quantified across the specimens and delineated into clinically localized and metastatic prostate cancer-specific signatures. Included in these class-specific profiles were both proteins that were known to be dysregulated during prostate cancer progression and new ones defined by this study. Enrichment analysis of the prostate cancer-specific proteomic signature, to gain insight into the functional consequences of these alterations, revealed involvement of miR-128-a/b regulation during prostate cancer progression. This finding was validated using real time PCR analysis for microRNA transcript levels in an independent set of 15 clinical specimens. miR-128 levels were elevated in benign prostate epithelial cell lines compared with invasive prostate cancer cells. Knockdown of miR-128 induced invasion in benign prostate epithelial cells, whereas its overexpression attenuated invasion in prostate cancer cells. Taken together, our profiles of the proteomic alterations of prostate cancer progression revealed miR-128 as a potentially important negative regulator of prostate cancer cell invasion. PMID:19955085

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

A novel shape similarity based elastography system for prostate cancer assessment

NASA Astrophysics Data System (ADS)

Wang, Haisu; Mousavi, Seyed Reza; Samani, Abbas

2012-03-01

Prostate cancer is the second common cancer among men worldwide and remains the second leading cancer-related cause of death in mature men. The disease can be cured if it is detected at early stage. This implies that prostate cancer detection at early stage is very critical for desirable treatment outcome. Conventional techniques of prostate cancer screening and detection, such as Digital Rectal Examination (DRE), Prostate-Specific Antigen (PSA) and Trans Rectal Ultra-Sonography (TRUS), are known to have low sensitivity and specificity. Elastography is an imaging technique that uses tissue stiffness as contrast mechanism. As the association between the degree of prostate tissue stiffness alteration and its pathology is well established, elastography can potentially detect prostate cancer with a high degree of sensitivity and specificity. In this paper, we present a novel elastography technique which, unlike other elastography techniques, does not require displacement data acquisition system. This technique requires the prostate's pre-compression and postcompression transrectal ultrasound images. The conceptual foundation of reconstructing the prostate's normal and pathological tissues elastic moduli is to determine these moduli such that the similarity between calculated and observed shape features of the post compression prostate image is maximized. Results indicate that this technique is highly accurate and robust.

A combined learning algorithm for prostate segmentation on 3D CT images.

PubMed

Ma, Ling; Guo, Rongrong; Zhang, Guoyi; Schuster, David M; Fei, Baowei

2017-11-01

Segmentation of the prostate on CT images has many applications in the diagnosis and treatment of prostate cancer. Because of the low soft-tissue contrast on CT images, prostate segmentation is a challenging task. A learning-based segmentation method is proposed for the prostate on three-dimensional (3D) CT images. We combine population-based and patient-based learning methods for segmenting the prostate on CT images. Population data can provide useful information to guide the segmentation processing. Because of inter-patient variations, patient-specific information is particularly useful to improve the segmentation accuracy for an individual patient. In this study, we combine a population learning method and a patient-specific learning method to improve the robustness of prostate segmentation on CT images. We train a population model based on the data from a group of prostate patients. We also train a patient-specific model based on the data of the individual patient and incorporate the information as marked by the user interaction into the segmentation processing. We calculate the similarity between the two models to obtain applicable population and patient-specific knowledge to compute the likelihood of a pixel belonging to the prostate tissue. A new adaptive threshold method is developed to convert the likelihood image into a binary image of the prostate, and thus complete the segmentation of the gland on CT images. The proposed learning-based segmentation algorithm was validated using 3D CT volumes of 92 patients. All of the CT image volumes were manually segmented independently three times by two, clinically experienced radiologists and the manual segmentation results served as the gold standard for evaluation. The experimental results show that the segmentation method achieved a Dice similarity coefficient of 87.18 ± 2.99%, compared to the manual segmentation. By combining the population learning and patient-specific learning methods, the proposed method is effective for segmenting the prostate on 3D CT images. The prostate CT segmentation method can be used in various applications including volume measurement and treatment planning of the prostate. © 2017 American Association of Physicists in Medicine.

42 CFR 493.15 - Laboratories performing waived tests.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Hemoglobin; (iv) Ketone; (v) Leukocytes; (vi) Nitrite; (vii) pH; (viii) Protein; (ix) Specific gravity; and... rate—non-automated; (6) Hemoglobin—copper sulfate—non-automated; (7) Blood glucose by glucose monitoring devices cleared by the FDA specifically for home use; (8) Spun microhematocrit; and (9) Hemoglobin...

42 CFR 493.15 - Laboratories performing waived tests.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Hemoglobin; (iv) Ketone; (v) Leukocytes; (vi) Nitrite; (vii) pH; (viii) Protein; (ix) Specific gravity; and... rate—non-automated; (6) Hemoglobin—copper sulfate—non-automated; (7) Blood glucose by glucose monitoring devices cleared by the FDA specifically for home use; (8) Spun microhematocrit; and (9) Hemoglobin...

Care Planning for Prostate Cancer Patients on Active Surveillance

DTIC Science & Technology

2016-10-01

intervention (PCPEP) for prostate cancer patients on active surveillance ( Study Specific Aim 1). As part of the adoption process, we will: (Aim 1a...evaluate the acceptability and feasibility of the program with prostate cancer patients on active surveillance in a small pilot study ( Study Specific...to a poster depicting the study finding on “Treatment 4 Decision-making and Adherence to Active Surveillance in Prostate Cancer Patients” presented

Radiation Effects on the Immune Response to Prostate Cancer

DTIC Science & Technology

2008-02-01

as an alternative treatment since the discovery of prostate tumor-associated antigens (TAA) and of corresponding tumor-specific T cells in prostate...class I and co-stimulatory molecules, which could promote T cell filtration into tumors and T cell activation. On the other hand, we recently showed...immunotherapy (IT) has gained in popularity by finding some patients have specific T cell response to prostate tumor-associated antigens such as

Convergent evolution of hemoglobin switching in jawed and jawless vertebrates.

PubMed

Rohlfing, Kim; Stuhlmann, Friederike; Docker, Margaret F; Burmester, Thorsten

2016-02-01

During development, humans and other jawed vertebrates (Gnathostomata) express distinct hemoglobin genes, resulting in different hemoglobin tetramers. Embryonic and fetal hemoglobin have higher oxygen affinities than the adult hemoglobin, sustaining the oxygen demand of the developing organism. Little is known about the expression of hemoglobins during development of jawless vertebrates (Agnatha). We identified three hemoglobin switches in the life cycle of the sea lamprey. Three hemoglobin genes are specifically expressed in the embryo, four genes in the filter feeding larva (ammocoete), and nine genes correspond to the adult hemoglobin chains. During the development from the parasitic to the reproductive adult, the composition of hemoglobin changes again, with a massive increase of chain aHb1. A single hemoglobin chain is expressed constitutively in all stages. We further showed the differential expression of other globin genes: Myoglobin 1 is most highly expressed in the reproductive adult, myoglobin 2 expression peaks in the larva. Globin X1 is restricted to the embryo; globin X2 was only found in the reproductive adult. Cytoglobin is expressed at low levels throughout the life cycle. Because the hemoglobins of jawed and jawless vertebrates evolved independently from a common globin ancestor, hemoglobin switching must also have evolved convergently in these taxa. Notably, the ontogeny of sea lamprey hemoglobins essentially recapitulates their phylogeny, with the embryonic hemoglobins emerging first, followed by the evolution of larval and adult hemoglobins.

The influence of PSA-RNA yield on the analysis of expressed prostatic secretions (EPS) for prostate cancer diagnosis.

PubMed

Whelan, Christopher; Crocitto, Laura; Kawachi, Mark; Chan, Kevin; Smith, David; Wilson, Timothy; Smith, Steven

2013-02-01

In patients with prostate cancer, luminal prostate-specific antigen (PSA) enters the circulation because the basement membrane and glandular epithelium are damaged. Given that excess mobilization of prostate cells during prostatic massage can influence normalization in diagnostic testing, we studied PSA mRNA levels in expressed prostatic secretions (EPS) from patients undergoing biopsy for prostate cancer to determine if prostate cells are preferentially mobilized from patients with prostate cancer during prostatic massage. Quantitative Reverse-Transcription PCR (qRT-PCR) was used to measure the RNA levels of GAPDH, PSA, TMPRSS2:ERG and PCA3 in EPS specimens obtained from patients undergoing biopsy for prostate cancer. The level of PSA mRNA is significantly elevated in EPS specimens obtained from patients with a subsequent diagnosis of prostate cancer. This correlation influenced diagnostic testing results from EPS in two ways. First, when used as an exclusion parameter it appears to improve the diagnostic performance of TMPRSS2:ERG in EPS. Second, when used as a normalization parameter it appears to decrease the performance of these same tests. When comparing the results of mRNA based prostate cancer diagnostics in EPS it will be essential to consider PSA mRNA as a prostate specific gene and not a housekeeping gene.

Screening and Characterization of a Novel RNA Aptamer That Specifically Binds to Human Prostatic Acid Phosphatase and Human Prostate Cancer Cells

PubMed Central

Kong, Hoon Young; Byun, Jonghoe

2015-01-01

Prostatic acid phosphatase (PAP) expression increases proportionally with prostate cancer progression, making it useful in prognosticating intermediate to high-risk prostate cancers. A novel ligand that can specifically bind to PAP would be very helpful for guiding prostate cancer therapy. RNA aptamers bind to target molecules with high specificity and have key advantages such as low immunogenicity and easy synthesis. Here, human PAP-specific aptamers were screened from a 2′-fluoropyrimidine (FY)-modified RNA library by SELEX. The candidate aptamer families were identified within six rounds followed by analysis of their sequences and PAP-specific binding. A gel shift assay was used to identify PAP binding aptamers and the 6N aptamer specifically bound to PAP with a Kd value of 118 nM. RT-PCR and fluorescence labeling analyses revealed that the 6N aptamer bound to PAP-positive mammalian cells, such as PC-3 and LNCaP. IMR-90 negative control cells did not bind the 6N aptamer. Systematic minimization analyses revealed that 50 nucleotide sequences and their two hairpin structures in the 6N 2′-FY RNA aptamer were equally important for PAP binding. Renewed interest in PAP combined with the versatility of RNA aptamers, including conjugation of anti-cancer drugs and nano-imaging probes, could open up a new route for early theragnosis of prostate cancer. PMID:25591398

Prostate-specific membrane antigen-directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells.

PubMed

Lee, Seung S; Roche, Philip Jr; Giannopoulos, Paresa N; Mitmaker, Elliot J; Tamilia, Michael; Paliouras, Miltiadis; Trifiro, Mark A

2017-03-01

Almost all biological therapeutic interventions cannot overcome neoplastic heterogeneity. Physical ablation therapy is immune to tumor heterogeneity, but nearby tissue damage is the limiting factor in delivering lethal doses. Multi-walled carbon nanotubes offer a number of unique properties: chemical stability, photonic properties including efficient light absorption, thermal conductivity, and extensive surface area availability for covalent chemical ligation. When combined together with a targeting moiety such as an antibody or small molecule, one can deliver highly localized temperature increases and cause extensive cellular damage. We have functionalized multi-walled carbon nanotubes by conjugating an antibody against prostate-specific membrane antigen. In our in vitro studies using prostate-specific membrane antigen-positive LNCaP prostate cancer cells, we have effectively demonstrated cell ablation of >80% with a single 30-s exposure to a 2.7-W, 532-nm laser for the first time without bulk heating. We also confirmed the specificity and selectivity of prostate-specific membrane antigen targeting by assessing prostate-specific membrane antigen-null PC3 cell lines under the same conditions (<10% cell ablation). This suggests that we can achieve an extreme nearfield cell ablation effect, thus restricting potential tissue damage when transferred to in vivo clinical applications. Developing this new platform will introduce novel approaches toward current therapeutic modalities and will usher in a new age of effective cancer treatment squarely addressing tumoral heterogeneity.

Prostate brachytherapy - discharge

MedlinePlus

... chap 84. Read More Prostate brachytherapy Prostate cancer Prostate-specific antigen (PSA) blood test Radical prostatectomy Review Date 2/21/2017 Updated by: Jennifer Sobol, DO, Urologist with the Michigan ... Cancer Browse the Encyclopedia A.D.A.M., ...

[Correlation of IL-8 and IL-6 in prostatic fluid with serum prostate-specific antigen level in patients with benign prostatic hyperplasia complicated by prostatitis].

PubMed

Ren, Xingfei; Wu, Chunlei; Yu, Qinnan; Zhu, Feng; Liu, Pei; Zhang, Huiqing

2016-01-01

To investigate the correlation of the levels of interleukin-8 (IL-8) and IL-6 in the prostatic fluid with serum levels of serum prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH) complicated by prostatitis. A series of 211 patients undergoing surgery of BPH were divided into BPH group (n=75) and BPH with prostatitis group (n=136) according to the white blood cell count in the prostatic fluid. The clinical and laboratory findings were compared between the two groups, and stepwise regression analysis was used to assess the association of IL-8 and IL-6 with serum PSA level. No significant differences were found in age, BMI, blood pressure, blood glucose, blood lipids, IPSS score, PSA-Ratio, or prostate volume between the two groups (P<0.05). The patients with prostatitis had significantly increased serum PSA and prostate fluid IL-8 and IL-6 levels compared with those without prostatitis (P<0.001). Multiple linear regression analysis showed that IL-8 and IL-6 levels and white blood cell count in the prostatic fluid were all positively correlated with serum PSA level. Prostatitis is an important risk factor for elevated serum PSA level in patients with BPH, and both IL-8 and IL-6 levels in the prostatic fluid are correlated with serum PSA level.

Measurement of serum isoform [-2]proPSA derivatives shows superior accuracy to magnetic resonance imaging in the diagnosis of prostate cancer in patients with a total prostate-specific antigen level of 2-10 ng/ml.

PubMed

Furuya, Kazuhiro; Kawahara, Takashi; Narahara, Masaki; Tokita, Takashi; Fukui, Sachi; Imano, Masashi; Mitome, Taku; Ito, Yusuke; Izumi, Koji; Osaka, Kimito; Yokomizo, Yumiko; Hayashi, Narihiko; Hasumi, Hisashi; Nawata, Shintaro; Kawano, Tsuyoshi; Yao, Masahiro; Uemura, Hiroji

2017-08-01

More accurate diagnostic procedures for prostate cancer are needed to avoid unnecessary biopsy due to the low specificity of prostate-specific antigen (PSA). Recent studies showed that the percentage of serum isoform [-2]proPSA (p2PSA) to free PSA (%p2PSA), the Prostate Health Index (PHI) and magnetic resonance imaging (MRI) were more accurate than PSA. The aim of this study was to test the accuracy of %p2PSA, PHI and MRI in discriminating patients with and without prostate cancer. The subjects were 50 consecutive men with a PSA level of 2.0-10.0 ng/ml, who underwent prostate biopsy from October 2012 to July 2014. These patients underwent multiparametric MRI before biopsy, and their serum samples were measured for PSA, free PSA and p2PSA. The sensitivity, specificity and accuracy of PHI, %p2PSA and MRI were compared with PSA in the diagnosis of biopsy-confirmed prostate cancer. In a univariate analysis, %p2PSA [area under the curve (AUC): 0.811] and PHI (AUC 0.795) were more accurate than MRI (AUC: 0.583) and PSA (AUC: 0.554) for prostate cancer detection. At 60% sensitivity, the specificity of PHI (76.5%) was higher than that of MRI (52.9%). For significant cancer detection, %p2PSA (AUC: 0.745), PHI (AUC: 0.791) and MRI (AUC: 0.739) were marginally more accurate than PSA (AUC: 0.696). At 85% sensitivity, the specificity of MRI (62.1%) was higher than that of PHI (34.5%). PHI and %p2PSA can be used for screening the general population and MRI can be used for detection of significant cancer in patients suspected, from screening tests, of having prostate cancer.

Tumor-specific RNA interference targeting Pokemon suppresses tumor growth and induces apoptosis in prostate cancer.

PubMed

Li, Yining; Xu, Shuxiong; Wang, Xiangwei; Shi, Hua; Sun, Zhaolin; Yang, Zhao

2013-02-01

To explore the exact mechanism of Pokemon in prostate cancer. Pokemon is a member of the POK family of transcriptional repressors. Its main function is suppression of the p14ARF (alternate reading frame) tumor suppressor gene. Although Pokemon expression has been found to be increased in various types of lymphoma, the exact mechanism of the gene in prostate cancer is not clear. In the present study, prostate cancer cells were transfected with the specific short hairpin ribonucleic acid (RNA) expression vector targeting Pokemon. The expression of Pokemon messenger RNA and its protein was detected by semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting, respectively. The cell growth and cell apoptosis were also examined using the methyl thiazolyl tetrazolium assay and flow cytometry. The results demonstrated that specific RNA interference (RNAi) could decrease the expression levels of Pokemon gene messenger RNA and protein in prostate cancer cells. In addition, that specific RNAi significantly inhibited the cell proliferation and increased the apoptotic rate. In vivo experiments showed that specific RNAi inhibited the tumorigenicity of prostate cancer cells and significantly suppressed tumor growth. Therefore, an RNAi-targeted Pokemon gene strategy could be a potential approach to prostate cancer therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

Men presenting with prostate-specific antigen (PSA) values of over 100 ng/mL.

PubMed

Ang, Mann; Rajcic, Branimir; Foreman, Darren; Moretti, Kim; O'Callaghan, Michael E

2016-04-01

To investigate overall survival and prostate cancer-specific mortality in men with prostate cancer presenting with a PSA level <100 ng/mL at the time of diagnosis. Five-thousand seven hundred and sixteen patients with prostate cancer and a recorded diagnostic PSA level extracted from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Men included were diagnosed between January 1998 and August 2013. Patients were divided into groups according to diagnostic PSA level: <20, 20-≤100, 100-≤200 ng/mL, 200-≤500 ng/mL, and >500 ng/mL. Outcomes measured include overall survival and prostate cancer-specific mortality. Clinical stage, Gleason score and the presence of bony metastasis was evaluated to determine if they were prognostic factors in patients with PSA over 100 at diagnosis. Cox proportional hazards and competing risks regression were used to model overall survival and prostate cancer-specific mortality outcomes respectively. Of this cohort, 241 patients (4.2%) had a diagnostic PSA level >100 ng/mL. Patients with PSA >100 ng/mL have a significant reduction in five (29.1% vs 62.5% vs 87%) and ten-year (18.2% vs 36.7% vs 70.7%) overall survival when compared to men with diagnostic PSA 20-100 and <20 ng/mL respectively. In this group, prostate cancer-specific mortality was associated with Gleason score and metastases, but not PSA level at diagnosis. Overall survival was associated with PSA level, Gleason score and age. There was a linear increase in risk (overall survival) as PSA increased until 200 and no association thereafter. Models of overall survival and prostate cancer-specific mortality incorporating a risk stratification developed by Izumi et al. predicted overall survival but not prostate cancer-specific mortality. The use of this stratification did not improve model accuracy. Only a small number of men (4.2%) with prostate cancer present with PSA >100 ng/mL at diagnosis. Overall survival at five and ten years was significantly poorer in patients with PSA >100 ng/mL. In this cohort of men presenting with PSA >100 at diagnosis, PSA level was not associated with prostate cancer-specific mortality. Gleason score and metastases are significant prognostic factors in this group of men. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Comparison of Perioperative Outcomes Between Holmium Laser Enucleation of the Prostate and Robot-Assisted Simple Prostatectomy.

PubMed

Zhang, Mimi W; El Tayeb, Marawan M; Borofsky, Michael S; Dauw, Casey A; Wagner, Kristofer R; Lowry, Patrick S; Bird, Erin T; Hudson, Tillman C; Lingeman, James E

2017-09-01

To compare perioperative outcomes for patients undergoing holmium laser enucleation of the prostate (HoLEP) and robotic-assisted simple prostatectomy (RSP) for benign prostatic hypertrophy (BPH). Patient demographics and perioperative outcomes were compared between 600 patients undergoing HoLEP and 32 patients undergoing RSP at two separate academic institutions between 2008 and 2015. Patients undergoing HoLEP and RSP had comparable ages (71 vs 71, p = 0.96) and baseline American Urological Association Symptom Scores (20 vs 24, p = 0.21). There was no difference in mean specimen weight (96 g vs 110 g, p = 0.15). Mean operative time was reduced in the HoLEP cohort (103 minutes vs 274 minutes, p < 0.001). Patients undergoing HoLEP had lesser decreases in hemoglobin, decreased transfusions rates, shorter hospital stays, and decreased mean duration of catheterization. There was no difference in the rate of complications Clavien grade 3 or greater (p = 0.33). HoLEP and RSP are both efficacious treatments for large gland BPH. In expert hands, HoLEP appears to have a favorable perioperative profile. Further studies are necessary to compare long-term efficacy, cost, and learning curve influences, especially as minimally invasive approaches become more widespread.

A Pooled Analysis of 15 Prospective Cohort Studies on the Association between Fruit, Vegetable, and Mature Bean Consumption and Risk of Prostate Cancer.

PubMed

Petimar, Joshua; Wilson, Kathryn M; Wu, Kana; Wang, Molin; Albanes, Demetrius; van den Brandt, Piet A; Cook, Michael B; Giles, Graham G; Giovannucci, Edward L; Goodman, Gary E; Goodman, Phyllis J; Håkansson, Niclas; Helzlsouer, Kathy; Key, Timothy J; Kolonel, Laurence N; Liao, Linda M; Männistö, Satu; McCullough, Marjorie L; Milne, Roger L; Neuhouser, Marian L; Park, Yikyung; Platz, Elizabeth A; Riboli, Elio; Sawada, Norie; Schenk, Jeannette M; Tsugane, Shoichiro; Verhage, Bas; Wang, Ying; Wilkens, Lynne R; Wolk, Alicja; Ziegler, Regina G; Smith-Warner, Stephanie A

2017-08-01

Background: Relationships between fruit, vegetable, and mature bean consumption and prostate cancer risk are unclear. Methods: We examined associations between fruit and vegetable groups, specific fruits and vegetables, and mature bean consumption and prostate cancer risk overall, by stage and grade, and for prostate cancer mortality in a pooled analysis of 15 prospective cohorts, including 52,680 total cases and 3,205 prostate cancer-related deaths among 842,149 men. Diet was measured by a food frequency questionnaire or similar instrument at baseline. We calculated study-specific relative risks using Cox proportional hazards regression, and then pooled these estimates using a random effects model. Results: We did not observe any statistically significant associations for advanced prostate cancer or prostate cancer mortality with any food group (including total fruits and vegetables, total fruits, total vegetables, fruit and vegetable juice, cruciferous vegetables, and tomato products), nor specific fruit and vegetables. In addition, we observed few statistically significant results for other prostate cancer outcomes. Pooled multivariable relative risks comparing the highest versus lowest quantiles across all fruit and vegetable exposures and prostate cancer outcomes ranged from 0.89 to 1.09. There was no evidence of effect modification for any association by age or body mass index. Conclusions: Results from this large, international, pooled analysis do not support a strong role of collective groupings of fruits, vegetables, or mature beans in prostate cancer. Impact: Further investigation of other dietary exposures, especially indicators of bioavailable nutrient intake or specific phytochemicals, should be considered for prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 26(8); 1276-87. ©2017 AACR . ©2017 American Association for Cancer Research.

Clinical outcomes of prostate cancer patients in Yokosuka City, Japan: A comparative study between cases detected by prostate-specific antigen-based screening in Yokosuka and those detected by other means.

PubMed

Sakai, Naoki; Taguri, Masataka; Kobayashi, Kazuki; Noguchi, Sumio; Ikeda, Shigeru; Koh, Hideshige; Satomi, Yoshiaki; Furuhata, Akihiko

2015-08-01

To investigate whether prostate-specific antigen-based screening reduced the prostate cancer mortality rate in Yokosuka, Japan. We carried out a cohort study, in which we compared clinical outcomes between patients detected by prostate-specific antigen-based screening (S group n = 524) versus those detected by other means (NS group n = 1044). Clinical and pathological factors were evaluated using Cox regression analyses and the Kaplan-Meier method. A total of 1.5% (8/524) of patients in the S group and 6.7% (70/1044) of those in the NS group died from prostate cancer during follow up. A total of 8.0% (42/524) of patients in the S group and 11.4% (119/1044) in the NS group died from other causes. The 10-year cancer specific survival rates of the S and NS groups were 97% and 86%, respectively (P < 0.001). The median age was significantly lower in the S group than the NS group: 71 and 73 years, respectively (P < 0.001). The rate of Gleason score 8-10 was significantly lower in the S group than the NS group: 9.7% and 16.7%, respectively (P < 0.001). The rate of patients with metastasis or prostate-specific antigen 100 ng/mL or more was significantly lower in the S group than the NS group: 7.8% and 23.0%, respectively (P < 0.001). On multivariate analysis, Gleason score 8-10 compared with Gleason score 6 was independently associated with cancer-specific survival (hazard ratio 4.808, 95% confidence interval 1.044-22.14, P = 0.044). Prostate-specific antigen-based population screening in Yokosuka City might help to reduce the prostate cancer mortality rate. © 2015 The Japanese Urological Association.

Rare expression of high-molecular-weight cytokeratin in adenocarcinoma of the prostate gland: a study of 100 cases of metastatic and locally advanced prostate cancer.

PubMed

Yang, X J; Lecksell, K; Gaudin, P; Epstein, J I

1999-02-01

Immunohistochemistry with antibodies for high-molecular-weight cytokeratin labels basal cells and is used as an ancillary study in diagnosing prostate carcinoma, which reportedly lacks expression of high-molecular-weight cytokeratin. A recent report questioned the specificity of this marker, describing immunopositivity for high-molecular-weight cytokeratin in a small series of metastatic prostate cancer. We have also noted rare cases of prostate lesions on biopsy with typical histological features of adenocarcinoma showing immunopositivity for high-molecular-weight cytokeratin, either in tumor cells or in patchy cells with the morphology of basal cells. In some of these cases, it was difficult to distinguish cancer from out-pouching of high-grade prostatic intraepithelial neoplasia. To investigate whether prostate cancer cells express high-molecular-weight cytokeratin, we studied 100 cases of metastatic prostate carcinoma and 10 cases of prostate cancer invading the seminal vesicles from surgical specimens. Metastatic sites included regional lymph nodes (n = 67), bone (n = 19), and miscellaneous (n = 14). Cases with any positivity for high-molecular-weight cytokeratin antibody (34betaE12) were verified as being of prostatic origin with immunohistochemistry for prostate-specific antigen and prostate-specific acid phosphatase. Only four cases were detected positive for high-molecular-weight cytokeratin. In two cases (one metastasis, one seminal vesicle invasion) there was weakly diffuse positivity above background level. Two metastases in lymph nodes showed scattered strong staining of clusters of tumor cells, which represented <0.2% of tumor cells in the metastatic deposits. These positive cells did not have the morphology of basal cells. We conclude that prostate cancer, even high grade, only rarely expresses high-molecular-weight cytokeratin. This marker remains a very useful adjunct in the diagnosis of prostate cancer.

Identification of structural and secretory lectin-binding glycoproteins of normal and cancerous human prostate.

PubMed

Lad, P M; Cooper, J F; Learn, D B; Olson, C V

1984-12-07

We have utilized the technique of lectin-loading of SDS gels with iodinated concanavalin A and wheat germ agglutinin to identify glycoproteins in prostatic and seminal fluids as well as in prostate tissue fractions. The following subunits which bound both lectins were detected: (a) 50, 43 and 38 kDa subunits common to prostatic and seminal fluids, and an additional 55 kDa subunit which predominates only in prostatic fluid; (b) 78, 55, 50 and 43 kDa subunits in prostatic tissue cytosol and (c) 195, 170, 135, 116 and 95 kDa subunits present in the particulate fractions of prostatic tissue. Immunoblotting using specific rabbit antibodies revealed the 50 kDa band to be prostatic acid phosphatase and the 38 kDa band to be prostate-specific antigen. Interestingly, antibodies directed toward prostatic acid phosphatase were found to cross-react with the 43 kDa band. Fractionation on sucrose gradients showed that several of these particulate glycoproteins were associated with a vesicle fraction enriched in adenylate cyclase activity, implying that they are plasma membrane glycoproteins. Comparison of soluble and particulate fractions of normal and cancerous tissue homogenates was made by densitometric scanning of autoradiograms of lectin-loaded gels. Similar relative intensities of lectin-binding were obtained for corresponding proteins in normal and cancerous tissue fractions. Also, immunoblotting showed no differences in prostatic acid phosphatase or prostate-specific antigen between normal and cancerous soluble homogenate fractions. Our results suggest that major lectin-binding proteins are conserved in the transition from normal to cancerous tissue. These results may be useful in developing a multiple-marker profile of metastatic prostate cancer and for the design of imaging agents, such as monoclonal antibodies, to prominent soluble and particulate prostate glycoproteins.

PSMA-Specific Theranostic Nanoplex for Combination of TRAIL Gene and 5-FC Prodrug Therapy of Prostate Cancer

PubMed Central

Chen, Zhihang; Penet, Marie-France; Krishnamachary, Balaji; Banerjee, Sangeeta R.; Pomper, Martin G.; Bhujwalla, Zaver M.

2015-01-01

Metastatic prostate cancer causes significant morbidity and mortality and there is a critical unmet need for effective treatments. We have developed a theranostic nanoplex platform for combined imaging and therapy of prostate cancer. Our prostate-specific membrane antigen (PSMA) targeted nanoplex is designed to deliver plasmid DNA encoding tumor necrosis factor related apoptosis-inducing ligand (TRAIL), together with bacterial cytosine deaminase (bCD) as a prodrug enzyme. Nanoplex specificity was tested using two variants of human PC3 prostate cancer cells in culture and in tumor xenografts, one with high PSMA expression and the other with negligible expression levels. The expression of EGFP-TRAIL was demonstrated by fluorescence optical imaging and real-time PCR. Noninvasive 19F MR spectroscopy detected the conversion of the nontoxic prodrug 5-fluorocytosine (5-FC) to cytotoxic 5-fluorouracil (5-FU) by bCD. The combination strategy of TRAIL gene and 5-FC/bCD therapy showed significant inhibition of the growth of prostate cancer cells and tumors. These data demonstrate that the PSMA-specific theranostic nanoplex can deliver gene therapy and prodrug enzyme therapy concurrently for precision medicine in metastatic prostate cancer. PMID:26706476

Biomarkers in localized prostate cancer

PubMed Central

Ferro, Matteo; Buonerba, Carlo; Terracciano, Daniela; Lucarelli, Giuseppe; Cosimato, Vincenzo; Bottero, Danilo; Deliu, Victor M; Ditonno, Pasquale; Perdonà, Sisto; Autorino, Riccardo; Coman, Ioman; De Placido, Sabino; Di Lorenzo, Giuseppe; De Cobelli, Ottavio

2016-01-01

Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer. PMID:26768791

Prostate Cancer: Serum and Tissue Markers

PubMed Central

Miller, Gary J; Brawer, Michael K; Sakr, Wael A; Thrasher, J Brantley; Townsend, Ronald

2001-01-01

The detection of prostate cancer, its clinical staging, and the prediction of its prognosis remain topics of paramount importance in clinical management. The digital rectal exam, although once the “gold standard,” has been largely supplanted by a variety of techniques including serum and tissue-based assays. This article reviews recent progress in the development of prostate-specific antigen assays with greater specificity; molecular markers for prostate cancer (DNA ploidy, nuclear morphometry, markers of proliferation, and cell adhesion molecules); the link between vitamin D deficiency and the clinical emergence of prostate cancer; the possible correlation of serum insulin-like growth factor levels with the risk for developing prostate cancer; and the latest advances in radiologic staging. PMID:16985995

Emerging Vaccine Therapy Approaches for Prostate Cancer

PubMed Central

Sonpavde, Guru; Slawin, Kevin M; Spencer, David M; Levitt, Jonathan M

2010-01-01

Prostate cancer vaccines attempt to induce clinically relevant, cancer-specific systemic immune responses in patients with prostate cancer and represent a new class of targeted, nontoxic therapies. With a growing array of vaccine technologies in preclinical or clinical development, autologous antigen-presenting cell vaccines loaded with the antigen, prostate acid phosphatase, and poxvirus vaccines targeting prostate-specific antigen have recently demonstrated a significant survival benefit in randomized trials of patients with metastatic castration-resistant prostate cancer, whereas others have failed to demonstrate any benefit. The combination of vaccines with chemotherapy, radiotherapy, and other biologic agents is also being evaluated. Efforts to optimize vaccine approaches and select ideal patient populations need to continue to build on these early successes. PMID:20428291

Prostate-specific Antigen (PSA) Density and Free to Total PSA Ratio in Diagnosing Prostate Cancer with Prostate-Specific Antigen Levels of 4.0 ng/ml or Less.

PubMed

Liu, Xin; Tang, Jie; Fei, Xiang; Li, Qiu-Yang

2015-11-01

We aimed to value the usefulness of free to total prostate-specific antigen and Prostate-specific antigen (PSA) density for prostate cancer in the patients with PSA levels of 4.0 ng/ml or less. A total of 343 subjects with PSA levels of 4.0 ng/ml or less were biopsied. All patients were divided into four groups according to the PSA levels: 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml. The reliability of cancer detection in relation to the f/t PSA ratio and PSAD were estimated. Overall, 65 people were diagnosed with prostate cancer. The detection rate was 16.28%、17.17%, 21.82%, 25.00% in subjects with PSA levels of 0 to 1.0 ng/ml, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml, and 3.1 to 4.0 ng/ml, respectively. The f/t PSA ratio was significantly lower in patients with prostate cancer and PSA levels of 2.1 to 4.0 ng/ml (P<0.05). The PSAD had no statistical significance between the two groups. Routine prostate biopsy should be undertaken if the f/t PSA ratio less than 15% with /without abnormal DRE/TRUS findings.

Progress Against Prostate Cancer | NIH MedlinePlus the Magazine

MedlinePlus

... those diagnosed being 45 or older. What Is PSA? Prostate specific antigen, or PSA, is a substance produced by the prostate and released into the blood. PSA levels are often high in men with prostate ...

Prostate Cancer Screening: MedlinePlus Health Topic

MedlinePlus

... unusual. Another test is the prostate-specific antigen (PSA) blood test. Your PSA level may be high if you have prostate ... Research) Prostate Cancer Screening: Should You Get a PSA Test? (Mayo Foundation for Medical Education and Research) ...

Photoacoustic imaging with an acoustic lens detects prostate cancer cells labeled with PSMA-targeting near-infrared dye-conjugates

NASA Astrophysics Data System (ADS)

Dogra, Vikram; Chinni, Bhargava; Singh, Shalini; Schmitthenner, Hans; Rao, Navalgund; Krolewski, John J.; Nastiuk, Kent L.

2016-06-01

There is an urgent need for sensitive and specific tools to accurately image early stage, organ-confined human prostate cancers to facilitate active surveillance and reduce unnecessary treatment. Recently, we developed an acoustic lens that enhances the sensitivity of photoacoustic imaging. Here, we report the use of this device in conjunction with two molecular imaging agents that specifically target the prostate-specific membrane antigen (PSMA) expressed on the tumor cell surface of most prostate cancers. We demonstrate successful imaging of phantoms containing cancer cells labeled with either of two different PSMA-targeting agents, the ribonucleic acid aptamer A10-3.2 and a urea-based peptidomimetic inhibitor, each linked to the near-infrared dye IRDye800CW. By specifically targeting cells with these agents linked to a dye chosen for optimal signal, we are able to discriminate prostate cancer cells that express PSMA.

The fate of phenylhydroxylamine in human red cells.

PubMed

Kiese, M; Taeger, K

1976-01-01

Phenylhydroxylamine added to human red cells under aerobic conditions and in the presence of glucose was partly reduced to aniline. About half the hydroxylamine was recovered as amine after a 2-hr incubation. The aniline, after acetylation, was identified as acetanilide by melting point, Rf-value in TCL as well as UV, IR, and NMR spectroscopy. The fate of the remaining phenylhydroxylamine was followed by use of 14C-labeled phenylhydroxylamine. About 30% of the total radioactivity was bound to hemoglobin or other proteins and about 20% was found in highly polar low-molecular substances which were insoluble in organic solvents. The elucidation of the sites at which phenylhydroxylamine was bound to hemoglobin was complicated by the lability of the bonds. When purified human hemoglobin had reacted with radioactive phenylhydroxylamine, large proportions of the radioactivity bound to hemoglobin were removed by treatment with acid or with PMB for separation of alpha- and beta-chains. The radioactive compound liberated from hemoglobin by acid was found to be aniline. After reaction with phenylhydroxylamine the number of SH groups titrable with PMB was found to be diminished. Pretreatment of hemoglobin with N-ethylmaleimide or PMB decreased the amount of phenylhydroxylamine bound to hemoglobin but did not fully prevent the reaction. Tryptic digestion of hemoglobin after reaction with radioactive phenylhydroxylamine yielded tryptic peptides with lower specific activity than that of hemoglobin. Chymotryptic digestion of the tryptic core yielded a core with specific activity much higher than that of hemoglobin. Fingerprinting of the tryptic or chymotryptic hydrolyzates showed the presence of peptides with high and other ones with low or no radioactivity and of radioactive compounds which did not react with ninhydrin. In the covalent binding of phenylhydroxylamine to globin the SH group beta93 plays an important role, but other yet unknown sites are also reactive.

Radioligand therapy of metastatic castration-resistant prostate cancer: current approaches.

PubMed

Awang, Zool Hilmi; Essler, Markus; Ahmadzadehfar, Hojjat

2018-05-23

Prostate Cancer is the forth most common type of cancer. Prostate-specific membrane antigen (PSMA) is anchored in the cell membrane of prostate epithelial cells. PSMA is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer. Therefore it is an appropriate target for diagnostic and therapy of prostate cancer and its metastases. This article discusses several articles on radionuclide treatments in prostate cancer and the results on PSMA therapy with either beta or alpha emitters as a salvage therapy.

[Development of a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse tanscription polymerase chain reaction (qRT-PCR)].

PubMed

Pavlov, K A; Shkoporov, A N; Khokhlova, E V; Korchagina, A A; Sidorenkov, A V; Grigor'ev, M É; Pushkar', D Iu; Chekhonin, V P

2013-01-01

The wide introduction of prostatic specific antigen (PSA) determination into clinical practice has resulted in a larger number of prostate biopsies, while the lower age threshold for PSA has led to a larger number of unnecessary prostate biopsies. Hence, there is a need for new biomarkers that can detect prostate cancer. PCA3 is a noncoding messenger ribonucleic acid (mRNA) that is expressed exclusively in prostate cells. The aim of the study has been to develop a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of the study, a laboratory diagnostic test system prototype has been designed, an application methodology has been developed and specificity and sensitivity data of the method has been assessed. The diagnostic system has demonstrated its ability to detect significantly elevated levels of PCA 3/KLK 3 in samples from prostate cancer (PCa) patients compared with those from healthy men. The findings have shown relatively high diagnostic sensitivity, specificity and negative-predictive values for an early non-invasive screening of prostate cancer

Serum antibodies to huntingtin interacting protein-1: a new blood test for prostate cancer.

PubMed

Bradley, Sarah V; Oravecz-Wilson, Katherine I; Bougeard, Gaelle; Mizukami, Ikuko; Li, Lina; Munaco, Anthony J; Sreekumar, Arun; Corradetti, Michael N; Chinnaiyan, Arul M; Sanda, Martin G; Ross, Theodora S

2005-05-15

Huntingtin-interacting protein 1 (HIP1) is frequently overexpressed in prostate cancer. HIP1 is a clathrin-binding protein involved in growth factor receptor trafficking that transforms fibroblasts by prolonging the half-life of growth factor receptors. In addition to human cancers, HIP1 is also overexpressed in prostate tumors from the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model. Here we provide evidence that HIP1 plays an important role in mouse tumor development, as tumor formation in the TRAMP mice was impaired in the Hip1null/null background. In addition, we report that autoantibodies to HIP1 developed in the sera of TRAMP mice with prostate cancer as well as in the sera from human prostate cancer patients. This led to the development of an anti-HIP1 serum test in humans that had a similar sensitivity and specificity to the anti-alpha-methylacyl CoA racemase (AMACR) and prostate-specific antigen tests for prostate cancer and when combined with the anti-AMACR test yielded a specificity of 97%. These data suggest that HIP1 plays a functional role in tumorigenesis and that a positive HIP1 autoantibody test may be an important serum marker of prostate cancer.

Measurement of refractive index of hemoglobin in the visible/NIR spectral range

NASA Astrophysics Data System (ADS)

Lazareva, Ekaterina N.; Tuchin, Valery V.

2018-03-01

This study is focused on the measurements of the refractive index of hemoglobin solutions in the visible/near-infrared (NIR) spectral range at room temperature for characteristic laser wavelengths: 480, 486, 546, 589, 644, 656, 680, 930, 1100, 1300, and 1550 nm. Measurements were performed using the multiwavelength Abbe refractometer. Aqua hemoglobin solutions of different concentrations obtained from human whole blood were investigated. The specific increment of refractive index on hemoglobin concentration and the Sellmeier coefficients were calculated.

The Diagnostic Performance of Multiparametric Magnetic Resonance Imaging to Detect Significant Prostate Cancer.

PubMed

Thompson, J E; van Leeuwen, P J; Moses, D; Shnier, R; Brenner, P; Delprado, W; Pulbrook, M; Böhm, M; Haynes, A M; Hayen, A; Stricker, P D

2016-05-01

We assess the accuracy of multiparametric magnetic resonance imaging for significant prostate cancer detection before diagnostic biopsy in men with an abnormal prostate specific antigen/digital rectal examination. A total of 388 men underwent multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted and dynamic contrast enhanced imaging before biopsy. Two radiologists used PI-RADS to allocate a score of 1 to 5 for suspicion of significant prostate cancer (Gleason 7 with more than 5% grade 4). PI-RADS 3 to 5 was considered positive. Transperineal template guided mapping biopsy of 18 regions (median 30 cores) was performed with additional manually directed cores from magnetic resonance imaging positive regions. The anatomical location, size and grade of individual cancer areas in the biopsy regions (18) as the primary outcome and in prostatectomy specimens (117) as the secondary outcome were correlated to the magnetic resonance imaging positive regions. Of the 388 men who were enrolled in the study 344 were analyzed. Multiparametric magnetic resonance imaging was positive in 77.0% of patients, 62.5% had prostate cancer and 41.6% had significant prostate cancer. The detection of significant prostate cancer by multiparametric magnetic resonance imaging had a sensitivity of 96%, specificity of 36%, negative predictive value of 92% and positive predictive value of 52%. Adding PI-RADS to the multivariate model, including prostate specific antigen, digital rectal examination, prostate volume and age, improved the AUC from 0.776 to 0.879 (p <0.001). Anatomical concordance analysis showed a low mismatch between the magnetic resonance imaging positive regions and biopsy positive regions (4 [2.9%]), and the significant prostate cancer area in the radical prostatectomy specimen (3 [3.3%]). In men with an abnormal prostate specific antigen/digital rectal examination, multiparametric magnetic resonance imaging detected significant prostate cancer with an excellent negative predictive value and moderate positive predictive value. The use of multiparametric magnetic resonance imaging to diagnose significant prostate cancer may result in a substantial number of unnecessary biopsies while missing a minimum of significant prostate cancers. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

TU-F-BRF-02: MR-US Prostate Registration Using Patient-Specific Tissue Elasticity Property Prior for MR-Targeted, TRUS-Guided HDR Brachytherapy

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

Yang, X; Rossi, P; Ogunleye, T

2014-06-15

Purpose: High-dose-rate (HDR) brachytherapy has become a popular treatment modality for prostate cancer. Conventional transrectal ultrasound (TRUS)-guided prostate HDR brachytherapy could benefit significantly from MR-targeted, TRUS-guided procedure where the tumor locations, acquired from the multiparametric MRI, are incorporated into the treatment planning. In order to enable this integration, we have developed a MR-TRUS registration with a patient-specific biomechanical elasticity prior. Methods: The proposed method used a biomechanical elasticity prior to guide the prostate volumetric B-spline deformation in the MRI and TRUS registration. The patient-specific biomechanical elasticity prior was generated using ultrasound elastography, where two 3D TRUS prostate images were acquiredmore » under different probe-induced pressures during the HDR procedure, which takes 2-4 minutes. These two 3D TRUS images were used to calculate the local displacement (elasticity map) of two prostate volumes. The B-spline transformation was calculated by minimizing the Euclidean distance between the normalized attribute vectors of the prostate surface landmarks on the MR and TRUS. This technique was evaluated through two studies: a prostate-phantom study and a pilot study with 5 patients undergoing prostate HDR treatment. The accuracy of our approach was assessed through the locations of several landmarks in the post-registration and TRUS images; our registration results were compared with the surface-based method. Results: For the phantom study, the mean landmark displacement of the proposed method was 1.29±0.11 mm. For the 5 patients, the mean landmark displacement of the surface-based method was 3.25±0.51 mm; our method, 1.71±0.25 mm. Therefore, our proposed method of prostate registration outperformed the surfaced-based registration significantly. Conclusion: We have developed a novel MR-TRUS prostate registration approach based on patient-specific biomechanical elasticity prior. Successful integration of multi-parametric MR and TRUS prostate images provides a prostate-cancer map for treatment planning, enables accurate dose planning and delivery, and potentially enhances prostate HDR treatment outcome.« less

Validation of the German prostate-specific module.

PubMed

Bestmann, Beate; Rohde, Volker; Siebmann, Jens-Ulrich; Galalae, Razvan; Weidner, Wolfgang; Küchler, Thomas

2006-02-01

Theoretically, all patients newly diagnosed with prostate cancer are faced with a choice of treatment options: radical prostatectomy or radio therapy. Although these different treatments may have no differences in terms of survival, they may have very different consequences on the subsequent quality of life (QoL). Prerequisite to analyze QoL is a reliable and valid instrument to assess these differences not only in terms of general QoL (EORTC QLQ-C30) but prostate specific symptoms with a prostate specific module as well. Therefore, the aim of this study was a psychometric evaluation (validation) of the prostate-specific module (PSM). Five historical cohort studies were put together for an empirical meta-analysis. The main objective was to analyze the module's psychometric properties. The total sample consisted of 1,185 patients, of whom 950 completed the QoL questionnaires (EORTC QLQ-C30 and a prostate specific module developed by Kuechler et al.). First step of analysis was a principal component analysis that revealed the following scales: urinary problems, incontinence, erectile dysfunction, sexual problems, problems with partner, pain, heat, nutrition, and psychic strain. The module showed good reliability and concurrent validity and very good construct validity, since the module is able to discriminate between different treatment regimes, tumor stages and age. The German PSM is a reliable, valid and applicable tool for QoL in patients with prostate cancer.

Configurations of a two-tiered amplified gene expression system in adenoviral vectors designed to improve the specificity of in vivo prostate cancer imaging

PubMed Central

Sato, M; Figueiredo, ML; Burton, JB; Johnson, M; Chen, M; Powell, R; Gambhir, SS; Carey, M; Wu, L

2009-01-01

Effective treatment for recurrent, disseminated prostate cancer is notably limited. We have developed adenoviral vectors with a prostate-specific two-step transcriptional amplification (TSTA) system that would express therapeutic genes at a robust level to target metastatic disease. The TSTA system employs the prostate-specific antigen (PSA) promoter/enhancer to drive a potent synthetic activator, which in turn activates the expression of the therapeutic gene. In this study, we explored different configurations of this bipartite system and discovered that physical separation of the two TSTA components into E1 and E3 regions of adenovirus was able to enhance androgen regulation and cell-discriminatory expression. The TSTA vectors that express imaging reporter genes were assessed by noninvasive imaging technologies in animal models. The improved selectivity of the E1E3 configured vector was reflected in silenced ectopic expression in the lung. Significantly, the enhanced specificity of the E1E3 vector enabled the detection of lung metastasis of prostate cancer. An E1E3 TSTA vector that expresses the herpes simplex virus thymidine kinase gene can effectively direct positron emission tomography (PET) imaging of the tumor. The prostate-targeted gene delivery vectors with robust and cell-specific expression capability will advance the development of safe and effective imaging guided therapy for recurrent metastatic stages of prostate cancer. PMID:18305574

A Glu-urea-Lys Ligand-conjugated Lipid Nanoparticle/siRNA System Inhibits Androgen Receptor Expression In Vivo

PubMed Central

Lee, Justin B; Zhang, Kaixin; Tam, Yuen Yi C; Quick, Joslyn; Tam, Ying K; Lin, Paulo JC; Chen, Sam; Liu, Yan; Nair, Jayaprakash K; Zlatev, Ivan; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Rennie, Paul S; Cullis, Pieter R

2016-01-01

The androgen receptor plays a critical role in the progression of prostate cancer. Here, we describe targeting the prostate-specific membrane antigen using a lipid nanoparticle formulation containing small interfering RNA designed to silence expression of the messenger RNA encoding the androgen receptor. Specifically, a Glu-urea-Lys PSMA-targeting ligand was incorporated into the lipid nanoparticle system formulated with a long alkyl chain polyethylene glycol-lipid to enhance accumulation at tumor sites and facilitate intracellular uptake into tumor cells following systemic administration. Through these features, and by using a structurally refined cationic lipid and an optimized small interfering RNA payload, a lipid nanoparticle system with improved potency and significant therapeutic potential against prostate cancer and potentially other solid tumors was developed. Decreases in serum prostate-specific antigen, tumor cellular proliferation, and androgen receptor levels were observed in a mouse xenograft model following intravenous injection. These results support the potential clinical utility of a prostate-specific membrane antigen–targeted lipid nanoparticle system to silence the androgen receptor in advanced prostate cancer. PMID:28131285

The effect of increasing doses of saw palmetto fruit extract on serum prostate specific antigen: analysis of the CAMUS randomized trial.

PubMed

Andriole, Gerald L; McCullum-Hill, Christie; Sandhu, Gurdarshan S; Crawford, E David; Barry, Michael J; Cantor, Alan

2013-02-01

Saw palmetto extracts are used to treat lower urinary tract symptoms in men despite level I evidence that saw palmetto is ineffective in reducing these lower urinary tract symptoms. We determined whether higher doses of saw palmetto as studied in the CAMUS (Complementary and Alternative Medicine for Urologic Symptoms) trial affect serum prostate specific antigen levels. The CAMUS trial was a randomized, placebo controlled, double-blind, multicenter, North American trial conducted between June 5, 2008 and October 10, 2012, in which 369 men older than 45 years with an AUA symptom score of 8 to 24 were randomly assigned to placebo or dose escalation of saw palmetto, which consisted of 320 mg for the first 24 weeks, 640 mg for the next 24 weeks and 960 mg for the last 24 weeks of this 72-week trial. Serum prostate specific antigen levels were obtained at baseline and at weeks 24, 48 and 72, and were compared between treatment groups using the pooled t test and Fisher's exact test. Serum prostate specific antigen was similar at baseline for the placebo (mean ± SD 1.93 ± 1.59 ng/ml) and saw palmetto groups (2.20 ± 1.95, p = 0.16). Changes in prostate specific antigen during the study were similar, with a mean change in the placebo group of 0.16 ± 1.08 ng/ml and 0.23 ± 0.83 ng/ml in the saw palmetto group (p = 0.50). In addition, no differential effect on serum prostate specific antigen was observed between treatment arms when the groups were stratified by baseline prostate specific antigen. Saw palmetto extract does not affect serum prostate specific antigen more than placebo, even at relatively high doses. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

New Bacterial Infection in the Prostate after Transrectal Prostate Biopsy.

PubMed

Seo, Yumi; Lee, Gilho

2018-04-23

The prostate is prone to infections. Hypothetically, bacteria can be inoculated into the prostate during a transrectal prostate biopsy (TRPB) and progress into chronic bacterial prostatitis. Therefore, we examined new bacterial infections in biopsied prostates after TRPB and whether they affect clinical characteristics in the biopsied patients. Of men whose prostate cultures have been taken prior to TRPB, 105 men with bacteria-free benign prostate pathology underwent an additional repeated prostate culture within a year after TRPB. Twenty out of 105 men (19.05%) acquired new bacteria in their naïve prostates after TRPB. Except for one single case of Escherichia coli infection, 19 men had acquired gram-positive bacteria species. Between the culture-positive and negative groups, there were no significant differences in age, serum prostate-specific antigen (PSA) level, white blood cell (WBC) counts in expressed prostatic secretion (EPS), prostate volume, symptom severities in Korean version of the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) questionnaire, and patient-specific risk factors for biopsy associated infectious complications. Additionally, the TRPB procedure increased the WBC counts in post-biopsy EPS ( P = 0.031, McNemar test), but did not increase the serum PSA level and symptoms of NIH-CPSI in 20 men who acquired new bacteria after TRPB. The TRPB procedure was significantly associated with acquiring new bacterial infections in the biopsied prostate, but these localized bacteria did not affect patients' serum PSA level and symptoms after biopsy.

Prostate-specific Membrane Antigen PET: Clinical Utility in Prostate Cancer, Normal Patterns, Pearls, and Pitfalls.

PubMed

Hofman, Michael S; Hicks, Rodney J; Maurer, Tobias; Eiber, Matthias

2018-01-01

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in prostate cancer. Radiolabeled small molecules that bind with high affinity to its active extracellular center have emerged as a potential new diagnostic standard of reference for prostate cancer, resulting in images with extraordinary tumor-to-background contrast. Currently, gallium 68 ( 68 Ga)-PSMA-11 (or HBED-PSMA) is the most widely used radiotracer for PSMA positron emission tomography (PET)/computed tomography (CT) or PSMA PET/magnetic resonance (MR) imaging. Evolving evidence demonstrates superior sensitivity and specificity of PSMA PET compared to conventional imaging, with frequent identification of subcentimeter prostate cancer lesions. PSMA PET is effective for imaging disease in the prostate, lymph nodes, soft tissue, and bone in a "one-stop-shop" examination. There is emerging evidence for its clinical value in staging of high-risk primary prostate cancer and localization of disease in biochemical recurrence. The high sensitivity provided by PSMA PET, with frequent identification of small-volume disease, is redefining patterns of disease spread compared with those seen at conventional imaging. In metastatic castration-resistant prostate cancer, PSMA PET is frequently used for theranostic selection (eg, lutetium 177-PSMA radionuclide therapy), but its potential use for therapy monitoring is still under debate. However, evidence on its proper use to improve patient-related outcomes, particularly in the setting of early biochemical recurrence and targeted treatment of oligometastatic disease, is still missing. Despite the term prostate specific, PSMA functions as a folate hydrolase and is expressed in a range of normal tissues and in other benign and malignant processes. Knowledge of its physiologic distribution and other causes of uptake is essential to minimize false-positive imaging findings. © RSNA, 2018.

A single-chain fragment against prostate specific membrane antigen as a tool to build theranostic reagents for prostate cancer.

PubMed

Frigerio, B; Fracasso, G; Luison, E; Cingarlini, S; Mortarino, M; Coliva, A; Seregni, E; Bombardieri, E; Zuccolotto, G; Rosato, A; Colombatti, M; Canevari, S; Figini, M

2013-06-01

Prostate carcinoma is the most common non-cutaneous cancer in developed countries and represents the second leading cause of death. Early stage androgen dependent prostate carcinoma responds well to conventional therapies, but relatively few treatment options exist for patients with hormone-refractory prostate cancer. One of the most suitable targets for antibody-mediated approaches is prostate specific membrane antigen (PSMA) which is a well known tumour associated antigen. PSMA is a type II integral cell-surface membrane protein that is not secreted, and its expression density and enzymatic activity are increased progressively in prostate cancer compared to normal prostate epithelium, thereby making PSMA an ideal target for monoclonal antibody imaging and therapy. To obtain a small protein that can better penetrate tissue, we have engineered a single-chain variable fragment (scFv) starting from the variable heavy and light domains of the murine anti-PSMA monoclonal antibody D2B. scFvD2B was analysed in vitro for activity, stability, internalisation ability and in vivo for targeting specificity. Maintenance of function and immunoreactivity as well as extremely high radiolabelling efficiency and radiochemical purity were demonstrated by in vitro assays and under different experimental conditions. Despite its monovalent binding, scFvD2B retained a good strength of binding and was able to internalise around 40% of bound antigen. In vivo we showed its ability to specifically target only PSMA expressing prostate cancer xenografts. Due to these advantageous properties, scFvD2B has the potential to become a good theranostic reagent for early detection and therapy of prostate cancers. Published by Elsevier Ltd.

Concurrent Hepsin overexpression and adenomatous polyposis coli deletion causes invasive prostate carcinoma in mice.

PubMed

Valkenburg, Kenneth C; Hostetter, Galen; Williams, Bart O

2015-10-01

A clinical need to better categorize patients with prostate cancer exists. The Wnt/β-catenin signaling pathway plays important roles in human prostate cancer progression. Deletion of the endogenous Wnt antagonist adenomatous polyposis coli (Apc) in mice causes high grade prostate intraepithelial neoplasia, widely thought to be the precursor to prostate cancer. However, no metastasis occurrs in this model. New mouse models are needed to determine molecular causes of tumorigenesis, progression, and metastasis. To determine whether the overexpression of the prostate oncogene Hepsin could cause prostate cancer progression, we crossed a prostate-specific Hepsin overexpression model to a prostate-specific Apc-deletion model and classified the observed phenotype. When Apc was deleted and Hepsin overexpressed concurrently, mice displayed invasive carcinoma, with loss of membrane characteristics and increase of fibrosis. These tumors had both luminal and basaloid characteristics. Though no metastasis was observed, there was evidence of adenomas and lung necrosis, inflammation, and chronic hemorrhage. This work indicates that the Wnt/β-catenin pathway and the Hepsin pathway act in concert to promote prostate cancer progression. Both of these pathways are up-regulated in human prostate cancer and could represent chemotherapeutic targets. © 2015 Wiley Periodicals, Inc.

Pomegranate and Its Components as Alternative Treatment for Prostate Cancer

PubMed Central

Wang, Lei; Martins-Green, Manuela

2014-01-01

Prostate cancer is the second leading cause of cancer deaths in men in the United States. There is a major need for less toxic but yet effective therapies to treat prostate cancer. Pomegranate fruit from the tree Punica granatum has been used for centuries for medicinal purposes and is described as “nature’s power fruit”. Recent research has shown that pomegranate juice (PJ) and/or pomegranate extracts (PE) significantly inhibit the growth of prostate cancer cells in culture. In preclinical murine models, PJ and/or PE inhibit growth and angiogenesis of prostate tumors. More recently, we have shown that three components of PJ, luteolin, ellagic acid and punicic acid together, have similar inhibitory effects on prostate cancer growth, angiogenesis and metastasis. Results from clinical trials are also promising. PJ and/or PE significantly prolonged the prostate specific antigen (PSA) doubling time in patients with prostate cancer. In this review we discuss data on the effects of PJ and PE on prostate cancer. We also discuss the effects of specific components of the pomegranate fruit and how they have been used to study the mechanisms involved in prostate cancer progression and their potential to be used in deterring prostate cancer metastasis. PMID:25158234

Novel Prostate Cancer Pathway Modeling using Boolean Implication

DTIC Science & Technology

2012-09-01

cause of cancer deaths in men. Diagnosis and pathogenesis of this disease is poorly understood. Prostate specific antigen (PSA) test is still the... specific database, I combined 14 different datasets (global prostate cancer database, total n=891) that are in Affymetrix U133A (n=456), U133A 2.0...immunohistochemistry and flow cytometry are limited by the availability of antigen - specific monoclonal antibodies and by the small number of parallel

Determining the sensitivity of transrectal ultrasonography on a consecutive series of prostate cancers in a clinical and screening setting.

PubMed

Ciatto, Stefano; Bonardi, Rita; Lombardi, Claudio; Zappa, Marco; Gervasi, Ginetta

2002-01-01

To evaluate the sensitivity at transrectal ultrasonography (TRUS) for prostate cancer. A consecutive series of 170 prostate cancers identified by matching local cancer registry and TRUS archives at the Centro per lo Studio e la Prevenzione Oncologica of Florence. TRUS sensitivity was determined as the ratio of TRUS positive to total prostate cancers occurring at different intervals from TRUS date. Univariate and multivariate analyses of sensitivity determinants were performed. Sensitivity at 6 months, 1, 2 and 3 years after the test was 94.1% (95% CI, 90-98), 89.8% (95% CI, 85-95), 80.4% (95% CI, 74-87) and 74.1% (95% CI, 68-81%), respectively. A higher sensitivity (statistically significant) of TRUS was observed only if digital rectal examination was suspicious, whereas no association to sensitivity was observed for age, prostate-specific antigen or prostate-specific antigen density. The study provided a reliable estimate of TRUS sensitivity, particularly reliable being checked against a cancer registry: observed sensitivity was high, at least of the same magnitude of other cancer screening tests. TRUS, which is known to allow for considerable diagnostic anticipation and is more specific than prostate-specific antigen, might still be considered for its contribution to a screening approach.

Deep Learning Role in Early Diagnosis of Prostate Cancer

PubMed Central

Reda, Islam; Khalil, Ashraf; Elmogy, Mohammed; Abou El-Fetouh, Ahmed; Shalaby, Ahmed; Abou El-Ghar, Mohamed; Elmaghraby, Adel; Ghazal, Mohammed; El-Baz, Ayman

2018-01-01

The objective of this work is to develop a computer-aided diagnostic system for early diagnosis of prostate cancer. The presented system integrates both clinical biomarkers (prostate-specific antigen) and extracted features from diffusion-weighted magnetic resonance imaging collected at multiple b values. The presented system performs 3 major processing steps. First, prostate delineation using a hybrid approach that combines a level-set model with nonnegative matrix factorization. Second, estimation and normalization of diffusion parameters, which are the apparent diffusion coefficients of the delineated prostate volumes at different b values followed by refinement of those apparent diffusion coefficients using a generalized Gaussian Markov random field model. Then, construction of the cumulative distribution functions of the processed apparent diffusion coefficients at multiple b values. In parallel, a K-nearest neighbor classifier is employed to transform the prostate-specific antigen results into diagnostic probabilities. Finally, those prostate-specific antigen–based probabilities are integrated with the initial diagnostic probabilities obtained using stacked nonnegativity constraint sparse autoencoders that employ apparent diffusion coefficient–cumulative distribution functions for better diagnostic accuracy. Experiments conducted on 18 diffusion-weighted magnetic resonance imaging data sets achieved 94.4% diagnosis accuracy (sensitivity = 88.9% and specificity = 100%), which indicate the promising results of the presented computer-aided diagnostic system. PMID:29804518

Prostate biopsy

MedlinePlus

... shows that you have a higher than normal prostate specific antigen (PSA) level Your provider discovers a lump or abnormality in your prostate during a digital rectal exam Normal Results Normal ...

Label-free in vitro prostate cancer cell detection via photonic-crystal biosensor

NASA Astrophysics Data System (ADS)

DeLuna, Frank; Ding, XiaoFei; Sagredo, Ismael; Bustamante, Gilbert; Sun, Lu-Zhe; Ye, Jing Yong

2018-02-01

Prostate-specific antigen (PSA) biomarker assays are the current clinical method for mass screening of prostate cancer. However, high false-positive rates are often reported due to PSA's low specificity, leading to an urgent need for the development of a more specific detection system independent of PSA levels. In our previous research, we demonstrated the feasibility of using cellular refractive indices (RI) as a unique contrast parameter to accomplish label-free detection of prostate cancer cells via variance testing, but were unable to determine if a specific cell was cancerous or noncancerous. In this paper, we report the use of our Photonic-Crystal biosensor in a Total-Internal-Reflection (PC-TIR) configuration to construct a label-free imaging system, which allows for the detection of individual prostate cancer cells utilizing cellular RI as the only contrast parameter. Noncancerous prostate (BPH-1) cells and prostate cancer (PC-3) cells were mixed at varied ratios and measured concurrently. Additionally, we isolated and induced PC-3 cells to undergo epithelial-mesenchymal transition (EMT) by exposing these cells to soluble factors such as TGF-β1. The biophysical characteristics of the cellular RI were quantified extensively in comparison to non-induced PC-3 cells as well as BPH-1 cells. EMT is a crucial mechanism for the invasion and metastasis of epithelial tumors characterized by the loss of cell-cell adhesion and increased cell mobility. Our study shows promising clinical potential in utilizing the PC-TIR biosensor imaging system to not only detect prostate cancer cells, but also evaluate prostate cancer progression.

Transcriptional regulation of fetal to adult hemoglobin switching: new therapeutic opportunities

PubMed Central

Wilber, Andrew; Nienhuis, Arthur W.

2011-01-01

In humans, embryonic, fetal, and adult hemoglobins are sequentially expressed in developing erythroblasts during ontogeny. For the past 40 years, this process has been the subject of intensive study because of its value to enlighten the biology of developmental gene regulation and because fetal hemoglobin can significantly ameliorate the clinical manifestations of both sickle cell disease and β-thalassemia. Understanding the normal process of loss of fetal globin expression and activation of adult globin expression could potentially lead to new therapeutic approaches for these hemoglobin disorders. Herein, we briefly review the history of the study of hemoglobin switching and then focus on recent discoveries in the field that now make new therapeutic approaches seem feasible in the future. Erythroid-specific knockdown of fetal gene repressors or enforced expression of fetal gene activators may provide clinically applicable approaches for genetic treatment of hemoglobin disorders that would benefit from increased fetal hemoglobin levels. PMID:21321359

Modeling hemoglobin at optical frequency using the unconditionally stable fundamental ADI-FDTD method.

PubMed

Heh, Ding Yu; Tan, Eng Leong

2011-04-12

This paper presents the modeling of hemoglobin at optical frequency (250 nm - 1000 nm) using the unconditionally stable fundamental alternating-direction-implicit finite-difference time-domain (FADI-FDTD) method. An accurate model based on complex conjugate pole-residue pairs is proposed to model the complex permittivity of hemoglobin at optical frequency. Two hemoglobin concentrations at 15 g/dL and 33 g/dL are considered. The model is then incorporated into the FADI-FDTD method for solving electromagnetic problems involving interaction of light with hemoglobin. The computation of transmission and reflection coefficients of a half space hemoglobin medium using the FADI-FDTD validates the accuracy of our model and method. The specific absorption rate (SAR) distribution of human capillary at optical frequency is also shown. While maintaining accuracy, the unconditionally stable FADI-FDTD method exhibits high efficiency in modeling hemoglobin.

Modeling hemoglobin at optical frequency using the unconditionally stable fundamental ADI-FDTD method

PubMed Central

Heh, Ding Yu; Tan, Eng Leong

2011-01-01

This paper presents the modeling of hemoglobin at optical frequency (250 nm – 1000 nm) using the unconditionally stable fundamental alternating-direction-implicit finite-difference time-domain (FADI-FDTD) method. An accurate model based on complex conjugate pole-residue pairs is proposed to model the complex permittivity of hemoglobin at optical frequency. Two hemoglobin concentrations at 15 g/dL and 33 g/dL are considered. The model is then incorporated into the FADI-FDTD method for solving electromagnetic problems involving interaction of light with hemoglobin. The computation of transmission and reflection coefficients of a half space hemoglobin medium using the FADI-FDTD validates the accuracy of our model and method. The specific absorption rate (SAR) distribution of human capillary at optical frequency is also shown. While maintaining accuracy, the unconditionally stable FADI-FDTD method exhibits high efficiency in modeling hemoglobin. PMID:21559129

68Ga-PSMA Expression in Pseudoangiomatous Stromal Hyperplasia of the Breast.

PubMed

Malik, Dharmender; Basher, Rajender K; Mittal, Bhagwant Rai; Jain, Tarun Kumar; Bal, Amanjit; Singh, Shrawan Kumar

2017-01-01

Ga-labeled prostate-specific membrane antigen ligand PET-CT has emerged as a promising technique to evaluate the extent of disease in patients with prostate carcinoma. We are reporting a 63-year-old man with prostatic carcinoma subjected to Ga-prostate-specific membrane antigen ligand PET-CT for initial staging. In addition to the radiotracer uptake in known primary site (prostate), focal increased radiotracer uptake was also noticed in the left breast. Subsequent biopsy of the breast lesion revealed PASH (pseudoangiomatous stromal hyperplasia), which is a benign mesenchymal proliferative lesion that may present clinically as palpable mass requiring further evaluation to rule out malignancy.

Prostate Cancer Disparities in an Incarcerated Community

DTIC Science & Technology

2012-09-01

smoking habits , dietary intake, physical activity levels, anthropometrics, sun exposure, frequency of general health care utilization and prostate...such as impactful conversations and exposures, others are tangible and noteworthy and listed below. (1) Dr. Borysova accepted an invitation to...SOW has been retained. Specific Aims Specific Aim 1: Compare the lifestyle factors thought to be associated with prostate cancer including

Polyphenols and Prostate Cancer Chemoprevention

DTIC Science & Technology

2004-03-01

The polyphenols, catechin, (-)- epigallocatechin -3- gallate ( EGCG ), genistein and resveratrol, are associated with reduced incidences of prostate and...protective effect without adverse effects with possible elevated exposure. The specific aims are 1) to investigate the potential of genistein, EGCG and...genistein, EGCG and resveratrol to regulate sex steroid- and specific growth factor-receptor and ligand expression as mechanism of prostate cancer

Truncated hemoglobins in actinorhizal nodules of Datisca glomerata.

PubMed

Pawlowski, K; Jacobsen, K R; Alloisio, N; Ford Denison, R; Klein, M; Tjepkema, J D; Winzer, T; Sirrenberg, A; Guan, C; Berry, A M

2007-11-01

Three types of hemoglobins exist in higher plants, symbiotic, non-symbiotic, and truncated hemoglobins. Symbiotic (class II) hemoglobins play a role in oxygen supply to intracellular nitrogen-fixing symbionts in legume root nodules, and in one case ( Parasponia Sp.), a non-symbiotic (class I) hemoglobin has been recruited for this function. Here we report the induction of a host gene, dgtrHB1, encoding a truncated hemoglobin in Frankia-induced nodules of the actinorhizal plant Datisca glomerata. Induction takes place specifically in cells infected by the microsymbiont, prior to the onset of bacterial nitrogen fixation. A bacterial gene (Frankia trHBO) encoding a truncated hemoglobin with O (2)-binding kinetics suitable for the facilitation of O (2) diffusion ( ) is also expressed in symbiosis. Nodule oximetry confirms the presence of a molecule that binds oxygen reversibly in D. glomerata nodules, but indicates a low overall hemoglobin concentration suggesting a local function. Frankia trHbO is likely to be responsible for this activity. The function of the D. glomerata truncated hemoglobin is unknown; a possible role in nitric oxide detoxification is suggested.

Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation

PubMed Central

Chua, Chee Wai; Epsi, Nusrat J; Leung, Eva Y; Xuan, Shouhong; Lei, Ming; Li, Bo I; Bergren, Sarah K; Hibshoosh, Hanina; Mitrofanova, Antonina

2018-01-01

Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important in cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated. We have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing cells), a luminal stem/progenitor cell that functions in prostate regeneration. Using genetically--engineered mouse models and novel prostate epithelial cell lines, we find that progenitor properties of CARNs are largely unaffected by AR deletion, apart from decreased proliferation in vivo. Furthermore, AR loss suppresses tumor formation after deletion of the Pten tumor suppressor in CARNs; however, combined Pten deletion and activation of oncogenic Kras in AR-deleted CARNs result in tumors with focal neuroendocrine differentiation. Our findings show that AR modulates specific progenitor properties of CARNs, including their ability to serve as a cell of origin for prostate cancer. PMID:29334357

Prostate-Specific Antigen (PSA) Bounce After Dose-Escalated External Beam Radiation Therapy Is an Independent Predictor of PSA Recurrence, Metastasis, and Survival in Prostate Adenocarcinoma Patients.

PubMed

Romesser, Paul B; Pei, Xin; Shi, Weiji; Zhang, Zhigang; Kollmeier, Marisa; McBride, Sean M; Zelefsky, Michael J

2018-01-01

To evaluate the difference in prostate-specific antigen (PSA) recurrence-free, distant metastasis-free, overall, and cancer-specific survival between PSA bounce (PSA-B) and non-bounce patients treated with dose-escalated external beam radiation therapy (DE-EBRT). During 1990-2010, 1898 prostate adenocarcinoma patients were treated with DE-EBRT to ≥75 Gy with ≥5 years follow-up. Patients receiving neoadjuvant/concurrent androgen-deprivation therapy (n=1035) or with fewer than 4 PSA values obtained 6 months or more after post-EBRT completion (n=87) were excluded. The evaluable 776 patients were treated (median, 81.0 Gy). Prostate-specific antigen bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below. Prostate-specific antigen relapse was defined as post-radiation therapy PSA nadir + 2 ng/mL. Median follow-up was 9.2 years (interquartile range, 6.9-11.3 years). One hundred twenty-three patients (15.9%) experienced PSA-B after DE-EBRT at a median of 24.6 months (interquartile range, 16.1-38.5 months). On multivariate analysis, younger age (P=.001), lower Gleason score (P=.0003), and higher radiation therapy dose (P=.0002) independently predicted PSA-B. Prostate-specific antigen bounce was independently associated with decreased risk for PSA relapse (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.33-0.85; P=.008), distant metastatic disease (HR 0.34; 95% CI 0.12-0.94; P=.04), and all-cause mortality (HR 0.53; 95% CI 0.29-0.96; P=.04) on multivariate Cox analysis. Because all 50 prostate cancer-specific deaths in patients without PSA-B were in the non-bounce cohort, competing-risks analysis was not applicable. A nonparametric competing-risks test demonstrated that patients with PSA-B had superior cancer-specific survival compared with patients without PSA-B (P=.004). Patients treated with dose-escalated radiation therapy for prostate adenocarcinoma who experience posttreatment PSA-B have improved PSA recurrence-free survival, distant metastasis-free survival, overall survival, and cancer-specific survival outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR).

PubMed

Sarkar, F H; Sakr, W A; Li, Y W; Sreepathi, P; Crissman, J D

1993-01-01

Human papillomavirus (HPV) infections are strongly linked to the pathogenesis of uterine cervical neoplasms, and have been implicated in other cancers of the female genital tract. In contrast, the association of HPV with the cancers of the male urogenital tract is less evident, except in anal and penile cancers. However, recent studies reporting the prevalence of HPV infections in human prostate cancers (60-100% HPV 16 positive vs. no infection of HPV) have raised controversies regarding the prevalence of HPV in benign and neoplastic human prostate. We investigated the prevalence of HPV infections in prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinomas in 23 surgically resected prostates. Polymerase chain reaction (PCR) was used to amplify HPV 6b/11, 16, and 18 specific DNA sequences, using type specific HPV primers selected from the transforming gene E6-E7. The areas of PIN and cancer in 6 microns H&E stained tissue sections were identified, and respective areas of PIN and cancer were isolated from the adjacent serial sections and used for DNA amplification and HPV detection (Fig. 1). Our results demonstrated the presence of HPV 16 in three carcinomas (13%), using type specific primers in PCR amplified samples. We were not able to demonstrate the presence of other HPV types (HPV 6b/11 or HPV 18) in any of the samples using specific primers. Two of these prostates showed relatively strong positive signals by dot blot analysis, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. One more sample showed weak positivity, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. Subsequently, we have confirmed these results by Southern hybridization of the samples transferred to nylon membrane after agarose gel electrophoresis and detected by HPV 16 type specific oligonucleotide probe, using chemiluminescent assay. We, therefore, conclude that HPV infections of the prostate in general are not as common as has been previously claimed by other investigators.

IL-17 is not essential for inflammation and chronic pelvic pain development in an experimental model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Motrich, Ruben D; Breser, María L; Sánchez, Leonardo R; Godoy, Gloria J; Prinz, Immo; Rivero, Virginia E

2016-03-01

Pain and inflammation in the absence of infection are hallmarks in chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) patients. The etiology of CP/CPPS is unclear, and autoimmunity has been proposed as a cause. Experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. Herein, we studied prostate inflammation induction and chronic pelvic pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization in C57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainly composed of CD4 T cells and macrophages. Moreover, chronic pelvic pain was evidenced by increased allodynia responses. In immunized IL-17-KO mice, the presence of a prominent PAg-specific Th1 immune response caused similar prostate inflammation and chronic pelvic pain. Furthermore, markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronic pelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2 immune responses, characterized by high IL-4 secretion and neither infiltration nor damage in the prostate. As observed in wild-type control animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvic pain is a consequence of prostate inflammation. After PAg immunization, a Th1-associated immune response develops and induces prostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines, respectively, diminishes or enhances EAP susceptibility. In addition, IL-17 showed not to be essential for pathology induction and chronic pelvic pain development.

An Analytical Study of Prostate-Specific Antigen Dynamics.

PubMed

Esteban, Ernesto P; Deliz, Giovanni; Rivera-Rodriguez, Jaileen; Laureano, Stephanie M

2016-01-01

The purpose of this research is to carry out a quantitative study of prostate-specific antigen dynamics for patients with prostatic diseases, such as benign prostatic hyperplasia (BPH) and localized prostate cancer (LPC). The proposed PSA mathematical model was implemented using clinical data of 218 Japanese patients with histological proven BPH and 147 Japanese patients with LPC (stages T2a and T2b). For prostatic diseases (BPH and LPC) a nonlinear equation was obtained and solved in a close form to predict PSA progression with patients' age. The general solution describes PSA dynamics for patients with both diseases LPC and BPH. Particular solutions allow studying PSA dynamics for patients with BPH or LPC. Analytical solutions have been obtained and solved in a close form to develop nomograms for a better understanding of PSA dynamics in patients with BPH and LPC. This study may be useful to improve the diagnostic and prognosis of prostatic diseases.

Prostate-specific antigen density values among patients with symptomatic prostatic enlargement in Nigeria.

PubMed

Udeh, Emeka I; Nnabugwu, Ikenna I; Ozoemena, Francis O; Ugwumba, Fred O; Aderibigbe, Adesina S O; Ohayi, Samuel R; Echetabu, Kevin N

2016-06-29

This study aims to estimate the prostate-specific antigen density (PSAD) cutoff level for detecting prostate cancer (CAP) in Nigerian men with "grey zone PSA" (4-10 ng/ml) and normal digital rectal examination findings. We addressed this research question: Is the international PSAD cutoff of 0.15 ideal for detecting CAP in our symptomatic patients with "grey zone PSA?" To estimate the prostate-specific antigen density (PSAD) cutoff level for detecting CAP in Nigerian men with "grey zone PSA" (4-10 ng/ml) and normal digital rectal examination findings. Prospective. A tertiary medical center in Enugu, Nigeria. Two hundred and fifty-four men with either benign prostatic hyperplasia (BPH) or CAP were recruited. Patients with PSA above 4 ng/ml or abnormal digital rectal examination or hypoechoic lesion in the prostate were biopsied. PSAD and histology report of BPH or CAP. Ninety-seven patients had CAP while 157 had benign prostatic hyperplasia (BPH). Seventy-two patients had their serum PSA value within the range of 4.0 and 10 ng/ml. PSAD cutoff level to detect CAP was 0.04 (sensitivity 95.88 %; specificity 28.7 %). The PSAD cutoff level generated for Nigerian men in this study is 0.04 which is relatively different from international consensus. This PSAD cutoff level has a positive correlation with histology and could detect patients with CAP who have "grey zone PSA."

Measurement of refractive index of hemoglobin in the visible/NIR spectral range.

PubMed

Lazareva, Ekaterina N; Tuchin, Valery V

2018-03-01

This study is focused on the measurements of the refractive index of hemoglobin solutions in the visible/near-infrared (NIR) spectral range at room temperature for characteristic laser wavelengths: 480, 486, 546, 589, 644, 656, 680, 930, 1100, 1300, and 1550 nm. Measurements were performed using the multiwavelength Abbe refractometer. Aqua hemoglobin solutions of different concentrations obtained from human whole blood were investigated. The specific increment of refractive index on hemoglobin concentration and the Sellmeier coefficients were calculated. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Incidental detection of prostate-specific antigen-negative metastatic prostate cancer initially presented with solitary pulmonary nodule on fluorodeoxyglucose positron emission tomography/computed tomography

PubMed Central

Erdogan, Ezgi Basak; Buyukpinarbasili, Nur; Ziyade, Sedat; Akman, Tolga; Turk, Haci Mehmet; Aydin, Mehmet

2015-01-01

A 71-year-old male patient with solitary pulmonary nodule underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showing slightly increased FDG uptake in this nodule. In addition, PET/CT detected hypermetabolic sclerotic bone lesions in the right second rib and 7th thoracic vertebrae, which were interpreted as possible metastases, and mildly increased FDG uptake in the prostate gland highly suspicious of malignancy. The patient's prostate-specific antigen (PSA) level was within normal range (3.8 ng/dL). The histopathological examination of the lung nodule and right second rib lesion proved metastases from prostate cancer, then the prostate biopsy-confirmed prostate adenocarcinoma. The unique feature of this case is to emphasize the importance of performing PET/CT for solitary pulmonary nodule in detecting PSA-negative metastatic prostate cancer. This case indicated that it should be kept in mind that, even if the PSA is negative, a lung metastasis of prostate cancer may be an underlying cause in patients evaluated for solitary pulmonary nodule by FDG PET/CT. PMID:26170575

Identification of prostate cancer biomarkers in urinary exosomes

PubMed Central

Øverbye, Anders; Skotland, Tore; Koehler, Christian J.; Thiede, Bernd; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

2015-01-01

Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer. PMID:26196085

Identification of prostate cancer biomarkers in urinary exosomes.

PubMed

Øverbye, Anders; Skotland, Tore; Koehler, Christian J; Thiede, Bernd; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

2015-10-06

Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer.

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

PubMed

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

2014-12-01

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

Targeting the prostate for destruction through a vascular address

PubMed Central

Arap, Wadih; Haedicke, Wolfgang; Bernasconi, Michele; Kain, Renate; Rajotte, Daniel; Krajewski, Stanislaw; Ellerby, H. Michael; Bredesen, Dale E.; Pasqualini, Renata; Ruoslahti, Erkki

2002-01-01

Organ specific drug targeting was explored in mice as a possible alternative to surgery to treat prostate diseases. Peptides that specifically recognize the vasculature in the prostate were identified from phage-displayed peptide libraries by selecting for phage capable of homing into the prostate after an i.v. injection. One of the phage selected in this manner homed to the prostate 10–15 times more than to other organs. Unselected phage did not show this preference. The phage bound also to vasculature in the human prostate. The peptide displayed by the prostate-homing phage, SMSIARL (single letter code), was synthesized and shown to inhibit the homing of the phage when co-injected into mice with the phage. Systemic treatment of mice with a chimeric peptide consisting of the SMSIARL homing peptide, linked to a proapoptotic peptide that disrupts mitochondrial membranes, caused tissue destruction in the prostate, but not in other organs. The chimeric peptide delayed the development of the cancers in prostate cancer-prone transgenic mice (TRAMP mice). These results suggest that it may be possible to develop an alternative to surgical prostate resection and that such a treatment may also reduce future cancer risk. PMID:11830668

Favorable outcome of intraoperative radiotherapy to the primary site in patients with metastatic prostate cancer.

PubMed

Kanda, Toshihiro; Fukuda, Syohei; Fukui, Naotaka; Ohkubo, Yu; Kazumoto, Tomoko; Saito, Yoshihiro; Ishikawa, Ayataka; Kurosumi, Masafumi; Kageyama, Yukio; Fujii, Yasuhisa; Kihara, Kazunori

2016-08-01

The aim of this study was to determine whether local radiotherapy to the prostate by intraoperative radiotherapy (IORT) increases the overall and cancer-specific survival rates of patients with metastatic prostate cancer. Between 1993 and 2000, 102 patients with prostate cancer were treated with a combination of (a) IORT of the prostate (25 or 30 Gy per fraction); (b) external beam radiotherapy of the prostate (30 Gy in 10 fractions), starting approximately 1 week post-operatively; and (c) endocrine treatment. Of these, 16 patients had stage D1 disease (D1 IORT group), 32 had stage D2 disease without visceral metastasis (D2 IORT group), and 38 had stage D2 disease without visceral metastasis and did not receive local therapy (D2 control group). Overall and cancer-specific survival rates were compared. The 5- and 10-year cancer-specific survival rates were 75.9 and 52.7 %, respectively, in the (D1 + D2) IORT group and 45.8 and 33.5 %, respectively, in the D2 control group, with cancer-specific survival being significantly longer in the D2 IORT than in the D2 control group (P = 0.030). Univariate and multivariate reduced-rank regression analyses showed that extent of skeletal disease Grade 4 and non-regional lymph node metastasis were significantly prognostic of poorer cancer-specific survival (P < 0.001 each). Local radiotherapy to the prostate by IORT in patients with metastatic prostate cancer may contribute to better survival, especially in patients without extent of skeletal disease Grade 4 or non-regional lymph node metastasis.

Formulation of the bivalent prostate cancer vaccine with surgifoam elicits antigen-specific effector T cells in PSA-transgenic mice.

PubMed

Karan, Dev

2017-10-13

We previously developed and characterized an adenoviral-based prostate cancer vaccine for simultaneous targeting of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA). We also demonstrated that immunization of mice with the bivalent vaccine (Ad 5 -PSA+PSCA) inhibited the growth of established prostate tumors. However, there are multiple challenges hindering the success of immunological therapies in the clinic. One of the prime concerns has been to overcome the immunological tolerance and maintenance of long-term effector T cells. In this study, we further characterized the use of the bivalent vaccine (Ad 5 -PSA+PSCA) in a transgenic mouse model expressing human PSA in the mouse prostate. We demonstrated the expression of PSA analyzed at the mRNA level (by RT-PCR) and protein level (by immunohistochemistry) in the prostate lobes harvested from the PSA-transgenic (PSA-Tg) mice. We established that the administration of the bivalent vaccine in surgifoam to the PSA-Tg mice induces strong PSA-specific effector CD8 + T cells as measured by IFN-γ secretion and in vitro cytotoxic T-cell assay. Furthermore, the use of surgifoam with Ad 5 -PSA+PSCA vaccine allows multiple boosting vaccinations with a significant increase in antigen-specific CD8 + T cells. These observations suggest that the formulation of the bivalent prostate cancer vaccine (Ad 5 -PSA+PSCA) with surgifoam bypasses the neutralizing antibody response, thus allowing multiple boosting. This formulation is also helpful for inducing an antigen-specific immune response in the presence of self-antigen, and maintains long-term effector CD8 + T cells. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Molecular Innovations Toward Theranostics of Aggressive Prostate Cancer

DTIC Science & Technology

2014-09-01

to develop dendrimer -based theranostic agent with prostate cancer specificity and positron emission tomography imaging capability that can prevent...laboratories to develop a new molecular medicine. The goal of this project is to construct dendrimer nanoconjuate containing a prostate specific...cell permeation peptide, peptide therapeutic(s) and bifunctional chelator for PET imaging. Dr. Simanek’s laboratory will make dendrimers that bear

Molecular Innovations Toward Theranostics of Aggressive Prostate Cancer

DTIC Science & Technology

2013-09-01

objective is to develop dendrimer -based theranostic agent with prostate cancer specificity and positron emission tomography imaging capability that...The goal of this project is to construct dendrimer nanoconjuate containing a prostate specific cell permeation peptide, peptide therapeutic(s) and...bifunctional chelator for PET imaging. Dr. Simanek’s laboratory will make dendrimers that bear functional handles for conjugation with imaging

The biosynthesis of human hemoglobin A1c. Slow glycosylation of hemoglobin in vivo.

PubMed Central

Bunn, H F; Haney, D N; Kamin, S; Gabbay, K H; Gallop, P M

1976-01-01

Hemoglobin A1c, the most abundant minor hemoglobin component in human erythrocytes, is formed by the condensation of glucose with the N-terminal amino groups of the beta-chains of Hb A. The biosynthesis of this glycosylated hemoglobin was studied in vitro by incubating suspensions of reticulocytes and bone marrow cells with [3H]leucine or 59Fe-bound transferrin. In all experiments, the specific activity of Hb A1c was significantly lower than that of Hb A, suggesting that the formation of Hb A1c is a posttranslational modification. The formation of Hb A1c in vivo was determined in two individuals who were given an infusion of 59Fe-labeled transferrin. As expected, the specific activity of Hb A rose promptly to a maximum during the 1st week and remained nearly constant thereafter. In contrast, the specific activity of Hb A1c and also of Hbs A1a and A1b rose slowly, reaching that of Hb A by about day 60. These results indicate that Hb A1c is slowly formed during the 120-day life-span of the erythrocyte, probably by a nonenzymatic process. Patients with shortened erythrocyte life-span due to hemolysis had markedly decreased levels of Hb A1c. PMID:932199

Usage of GreenLight HPS 180-W laser vaporisation for treatment of benign prostatic hyperplasia.

PubMed

Jovanović, M; Džamić, Z; Aćimović, M; Kajmaković, B; Pejčić, T

2014-01-01

Laser therapy has gained increasing acceptance as a relatively less invasive treatment for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). From the early procedure of interstitial laser coagulation through to the use of holmium laser enucleation of the prostate, there has been an expanding body of evidence on the efficacy of such procedures. One of the newer lasers is the Green Light HPS 180 W laser. Studies with this GreenLight laser (GLL) (American Medical Systems, Inc, Minnetonka, MN, USA) showing results as good as those of transurethral resection of the prostate (TURP). In this paper, the efficacy of the new GLL 180-W versus the gold standard TURP in patients with LUTS due to BPH was tested in a prospective clinical trial. To compare results of Green light laser (GLL) evaporisation of the prostatae and transurethral resection of the prostate (TURP) for treatment of BPH. MATERIJALS AND METHODS: A total of 62 patients with BPH were randomly assigned to two equal groups: TURP or GLL. Both groups were compared regarding all relevant preoperative, operative, and postoperative parameters. Functional results in terms of improvement of International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and postvoid residual (PVR) urine were assessed at 1, 3, 6 and 12 mo. A total of 62 patients completed 12 mo of follow-up in the TURP and GLL groups, respectively. Baseline characteristics were comparable. Mean operative time was significantly shorter for TURP. Compared to preoperative values, there was significant reduction in hemoglobin levels at the end of TURP only. A significant difference in favor of GLL was achieved regarding the duration of catheterization and hospital stay. In the GLL, no major intraoperative complications were recorded and none of the patients required blood transfusion. Among TURP patients, 6 required transfusion, 1 developed TUR syndrome, and capsule perforation was observed in 5 patients. There was dramatic improvement in Qmax, IPSS, and GLL compared with preoperative values and the degree of improvement was comparable in both groups at all time points of follow-up. Four TURP patients and one GLL patients developed bladder neck contracture treated by bladder neck incision; none in either group experienced urethral stricture or urinary incontinence. Compared to transurethral resection of the prostate, GreenLight HPS 180-W laser photoselective vaporization of the prostate is safe and effective in the treatment of patients suffering from lower urinary tract symptoms due to benign prostatic hyperplasia.

National Trends in Prostate Biopsy and Radical Prostatectomy Volumes Following the US Preventive Services Task Force Guidelines Against Prostate-Specific Antigen Screening.

PubMed

Halpern, Joshua A; Shoag, Jonathan E; Artis, Amanda S; Ballman, Karla V; Sedrakyan, Art; Hershman, Dawn L; Wright, Jason D; Shih, Ya Chen Tina; Hu, Jim C

2017-02-01

Studies demonstrate that use of prostate-specific antigen screening decreased significantly following the US Preventive Services Task Force (USPSTF) recommendation against prostate-specific antigen screening in 2012. To determine downstream effects on practice patterns in prostate cancer diagnosis and treatment following the 2012 USPSTF recommendation. Procedural volumes of certifying and recertifying urologists from 2009 through 2016 were evaluated for variation in prostate biopsy and radical prostatectomy (RP) volume. Trends were confirmed using the New York Statewide Planning and Research Cooperative System and Nationwide Inpatient Sample. The study included a representative sample of urologists across practice settings and nationally representative sample of all RP discharges. We obtained operative case logs from the American Board of Urology and identified urologists performing at least 1 prostate biopsy (n = 5173) or RP (n = 3748), respectively. The 2012 USPSTF recommendation against routine population-wide prostate-specific antigen screening. Change in median biopsy and RP volume per urologist and national procedural volume. Following the USPSTF recommendation, median biopsy volume per urologist decreased from 29 to 21 (interquartile range [IQR}, 12-34; P < .001). After adjusting for physician and practice characteristics, biopsy volume decreased by 28.7% following 2012 (parameter estimate, -0.25; SE, 0.03; P < .001). Similarly, following the USPSTF recommendation, median RP volume per urologist decreased from 7 (IQR, 3-15) to 6 (IQR, 2-12) (P < .001), and in adjusted analyses, RP volume decreased 16.2% (parameter estimate, -0.15; SE, 0.05; P = .003). Following the 2012 USPSTF recommendation, prostate biopsy and RP volumes decreased significantly. A panoramic vantage point is needed to evaluate the long-term consequences of the 2012 USPSTF recommendation.

[Animal models of autoimmune prostatitis and their evaluation criteria].

PubMed

Shen, Jia-ming; Lu, Jin-chun; Yao, Bing

2016-03-01

Chronic prostatitis is a highly prevalent disease of unclear etiology. Researches show that autoimmune reaction is one cause of the problem. An effective animal model may help a lot to understand the pathogenesis and find proper diagnostic and therapeutic strategies of the disease. Currently used autoimmune prostatitis-related animal models include those of age-dependent spontaneous prostatitis, autoimmune regulator-dependent spontaneous prostatitis, self antigen-induced prostatitis, and steroid-induced prostatitis. Whether an animal model of autoimmune prostatitis is successfully established can be evaluated mainly from the five aspects: histology, morphology, specific antigens, inflammatory factors, and pain intensity.

EDB Fibronectin Specific Peptide for Prostate Cancer Targeting.

PubMed

Han, Zheng; Zhou, Zhuxian; Shi, Xiaoyue; Wang, Junpeng; Wu, Xiaohui; Sun, Da; Chen, Yinghua; Zhu, Hui; Magi-Galluzzi, Cristina; Lu, Zheng-Rong

2015-05-20

Extradomain-B fibronectin (EDB-FN), one of the oncofetal fibronectin (onfFN) isoforms, is a high-molecular-weight glycoprotein that mediates cell adhesion and migration. The expression of EDB-FN is associated with a number of cancer-related biological processes such as tumorigenesis, angiogenesis, and epithelial-to-mesenchymal transition (EMT). Here, we report the development of a small peptide specific to EDB-FN for targeting prostate cancer. A cyclic nonapeptide, CTVRTSADC (ZD2), was identified using peptide phage display. A ZD2-Cy5 conjugate was synthesized to accomplish molecular imaging of prostate cancer in vitro and in vivo. ZD2-Cy5 demonstrated effective binding to up-regulated EDB-FN secreted by TGF-β-induced PC3 cancer cells following EMT. Following intravenous injections, the targeted fluorescent probe specifically bound to and delineated PC3-GFP prostate tumors in nude mice bearing the tumor xenografts. ZD2-Cy5 also showed stronger binding to human prostate tumor specimens with a higher Gleason score (GS9) compared to those with a lower score (GS 7), with no binding in benign prostatic hyperplasia (BPH). Thus, the ZD2 peptide is a promising strategy for molecular imaging and targeted therapy of prostate cancer.

Vertebral Hemangioma Mimicking Bone Metastasis in 68Ga-PSMA Ligand PET/CT.

PubMed

Artigas, Carlos; Otte, François-Xavier; Lemort, Marc; van Velthoven, Roland; Flamen, Patrick

2017-05-01

Ga-PSMA PET/CT was performed in a 68-year-old man to evaluate recurrent prostate cancer due to elevated serum prostate-specific antigen level. Images showed a focal uptake in the prostatic gland, suggesting local relapse, and an intense uptake in the 12th thoracic vertebra, with no morphological abnormalities in CT slices. In order to confirm extraprostatic disease and before radiotherapy planning, a full-spine MRI was performed, resulting with the morphological pattern of a vertebral hemangioma. Hystological analysis confirmed the local relapse in the prostate. No radiotherapy treatment was given to the vertebra, and after 1 year of follow-up without systemic treatment, prostate-specific antigen is still undetectable.

DNA methylation as a dynamic regulator of development and disease processes: spotlight on the prostate.

PubMed

Keil, Kimberly P; Vezina, Chad M

2015-01-01

Prostate development, benign hyperplasia and cancer involve androgen and growth factor signaling as well as stromal-epithelial interactions. We review how DNA methylation influences these and related processes in other organ systems such as how proliferation is restricted to specific cell populations during defined temporal windows, how androgens elicit their actions and how cells establish, maintain and remodel DNA methylation in a time and cell specific fashion. We also discuss mechanisms by which hormones and endocrine disrupting chemicals reprogram DNA methylation in the prostate and elsewhere and examine evidence for a reawakening of developmental epigenetic pathways as drivers of prostate cancer and benign prostate hyperplasia.

DNA methylation as a dynamic regulator of development and disease processes: spotlight on the prostate

PubMed Central

Keil, Kimberly P; Vezina, Chad M

2015-01-01

Prostate development, benign hyperplasia and cancer involve androgen and growth factor signaling as well as stromal–epithelial interactions. We review how DNA methylation influences these and related processes in other organ systems such as how proliferation is restricted to specific cell populations during defined temporal windows, how androgens elicit their actions and how cells establish, maintain and remodel DNA methylation in a time and cell specific fashion. We also discuss mechanisms by which hormones and endocrine disrupting chemicals reprogram DNA methylation in the prostate and elsewhere and examine evidence for a reawakening of developmental epigenetic pathways as drivers of prostate cancer and benign prostate hyperplasia. PMID:26077429

Internet-Based Education for Prostate Cancer Screening

DTIC Science & Technology

2006-12-01

an accrual site, significantly enlarge the sample size, and add a specific aim over the course of a five year study. However, the NCI funding did...problems can a man have? Benign Prostatic Hyperplasia (BPH) BPH is enlargement of the prostate. BPH is not... enlarged prostate. • This approach

Prostate Cancer: Symptoms, Diagnosis and Treatment | NIH MedlinePlus the Magazine

MedlinePlus

... The prostate is checked for growths or enlargement. Prostate-specific antigen (PSA) test —A simple blood test to measure the amount of PSA, which is a marker for tumors. Biopsy —Tissue samples are extracted from the prostate with a long needle by a specialist. They ...

Feasibility of minimally invasive radical prostatectomy in prostate cancer patients with high prostate-specific antigen: feasibility and 1-year outcomes.

PubMed

Do, Minh; Ragavan, Narasimhan; Dietel, Anja; Liatsikos, Evangelos; Anderson, Chris; McNeill, Alan; Stolzenburg, Jens-Uwe

2012-10-01

Urologists are cautious to offer minimally invasive radical prostatectomy in prostate cancer patients with high prostate-specific antigen (and therefore anticipated to have locally advanced or metastatic disease) because of concerns regarding lack of complete cure after minimally invasive radical prostatectomy and of worsening of continence if adjuvant radiotherapy is used. A retrospective review of our institutional database was carried out to identify patients with PSA ≥20 ng/mL who underwent minimally invasive radical prostatectomy between January 2002 and October 2010. Intraoperative, pathological, functional and short-term oncological outcomes were assessed. Overall, 233 patients met study criteria and were included in the analysis. The median prostate-specific antigen and prostate size were 28.5 ng/mL and 47 mL, respectively. Intraoperative complications were the following: rectal injury (0.86%) and blood transfusion (1.7%). Early postoperative complications included prolonged (>6 days) catheterization (9.4%), hematoma (4.7%), deep venous thrombosis (0.86%) and lymphocele (5.1%). Late postoperative complications included cerebrovascular accident (0.4%) and anastomotic stricture (0.8%). Pathology revealed poorly differentiated cancer in 48.9%, pT3/pT4 disease in 55.8%, positive margins in 28.3% and lymph node disease in 20.2% of the cases. Adverse pathological findings were more frequent in patients with prostate-specific antigen >40 ng/mL and (or) in those with locally advanced disease (pT3/pT4). In 62.2% of the cases, adjuvant radiotherapy was used. At 1-year follow up, 80% of patients did not show evidence of biochemical recurrence and 98.8% of them had good recovery of continence. Minimally invasive radical prostatectomy might represent a reasonable option in prostate cancer patients with high prostate-specific antigen as a part of a multimodality treatment approach. © 2012 The Japanese Urological Association.

Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.

PubMed

Abugharib, Ahmed; Jackson, William C; Tumati, Vasu; Dess, Robert T; Lee, Jae Y; Zhao, Shuang G; Soliman, Moaaz; Zumsteg, Zachary S; Mehra, Rohit; Feng, Felix Y; Morgan, Todd M; Desai, Neil; Spratt, Daniel E

2017-03-01

Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy. We performed a multi-institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made to determine the optimal definition of early salvage radiotherapy, including 1) the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to 21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen deprivation therapy, and biochemical relapse-free, distant metastases-free and prostate cancer specific survival. Median followup was 9.8 years. Time from radical prostatectomy to salvage radiotherapy did not correlate with 10-year biochemical relapse-free survival rates (R 2 = 0.18). Increasing pre-salvage radiotherapy prostate specific antigen strongly correlated with biochemical relapse-free survival (R 2 = 0.91). Increasing detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than 0.5 ng/ml) predicted worse 10-year biochemical relapse-free survival (62%, 44% and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%), distant metastases-free survival (86%, 79% and 66%, each p <0.001) and prostate cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On multivariable analysis early salvage radiotherapy (prostate specific antigen greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in biochemical failure, use of salvage androgen deprivation therapy and distant metastases compared to very early salvage radiotherapy (prostate specific antigen 0.01 to 0.2 ng/ml). The duration from radical prostatectomy to salvage radiotherapy is not independently prognostic for outcomes after salvage radiotherapy and it should not be used to define early salvage radiotherapy. Grouping all patients with pre-salvage radiotherapy prostate specific antigen 0.5 ng/ml or less may be inadequate to define early salvage radiotherapy and it has a relevant impact on ongoing and future clinical trials. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prostate-Specific Membrane Antigen Expression in Adrenocortical Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET/CT.

PubMed

Arora, Saurabh; Damle, Nishikant Avinash; Aggarwal, Sameer; Passah, Averilicia; Behera, Abhishek; Arora, Geetanjali; Bal, Chandrasekhar; Tripathi, Madhavi

2018-06-01

We present here a case of metastatic adrenocortical carcinoma with bilateral lung nodules. The patient had been treated with mitotane therapy initially and then was later referred for chemotherapy. There was progression of disease noted on the F-FDG PET/CT. Ga prostate-specific membrane antigen (PSMA) PET/CT was planned to explore the possibility of future treatment with Lu-DKFZ-PSMA-617. It revealed peripheral increased uptake of Ga-HBED-CC-PSMA equal to liver uptake.

Integrating Molecular Imaging Approaches to Monitor Prostate Targeted Suicide and Anti-angiogenic Gene Therapy

DTIC Science & Technology

2005-02-01

tissue-specific expression of prostate-specific antigen. Cancer Res. 57: 495–499. 11. Schuur, E. R ., Henderson, G . A., Kmetec, L. A., Miller, J. D...Lamparski, H. G ., and Henderson, D. R . (1996). Prostate-specific antigen expression is regulated by an up- stream enhancer. J. Biol. Chem. 271: 7043...5: 223–232. 29. Blasberg, R . G ., and Tjuvajev, J. G . (1999). Herpes simplex virus thymidine kinase as a marker/reporter gene for PET imaging of gene

Serum ferritin in combination with prostate-specific antigen improves predictive accuracy for prostate cancer.

PubMed

Wang, Xijuan; An, Peng; Zeng, Jiling; Liu, Xiaoyan; Wang, Bo; Fang, Xuexian; Wang, Fudi; Ren, Guoping; Min, Junxia

2017-03-14

Ferritin is highly expressed in many cancer types. Although a few studies have reported an association between high serum ferritin levels and an increased risk of prostate cancer, the results are inconsistent. Therefore, we performed a large case-control study consisting of 2002 prostate cancer patients and 951 control patients with benign prostatic hyperplasia (BPH). We found that high ferritin levels were positively associated with increased serum prostate-specific antigen (PSA) levels and prostate cancer risk; each 100 ng/ml increase in serum ferritin increased the odds ratio (OR) by 1.20 (95% CI: 1.13-1.36). In the prostate cancer group, increased serum ferritin levels were significantly correlated with higher Gleason scores (p < 0.001). Notably, serum PSA values had even higher predictive accuracy among prostate cancer patients with serum ferritin levels > 400 ng/ml (Gleason score + total PSA correlation: r = 0.38; Gleason score + free PSA correlation: r = 0.49). Moreover, using immunohistochemistry, we found that prostate tissue ferritin levels were significantly higher (p < 0.001) in prostate cancer patients (n = 129) compared to BPH controls (n = 31). Prostate tissue ferritin levels were also highly correlated with serum ferritin when patients were classified by cancer severity (r = 0.81). Importantly, we found no correlation between serum ferritin levels and the inflammation marker C-reactive protein (CRP) in prostate cancer patients. In conclusion, serum ferritin is significantly associated with prostate cancer and may serve as a non-invasive biomarker to complement the PSA test in the diagnosis and prognostic evaluation of prostate cancer.

Prostate cancer-specific mortality and the extent of therapy in healthy elderly men with high-risk prostate cancer.

PubMed

Hoffman, Karen E; Chen, Ming-Hui; Moran, Brian J; Braccioforte, Michelle H; Dosoretz, Daniel; Salenius, Sharon; Katin, Michael J; Ross, Rudi; D'Amico, Anthony V

2010-06-01

The risk of prostate cancer-specific mortality (PCSM) in healthy elderly men may depend on extent of treatment. The authors of this report compared the use of brachytherapy alone with combined brachytherapy, external-beam radiation to the prostate and seminal vesicles, and androgen-suppression therapy (CMT) in this population. The study cohort comprised 764 men aged > or = 65 years with high-risk prostate cancer (T3 or T4N0M0, prostate-specific antigen >20 ng/mL, and/or Gleason score 8-10) who received either brachytherapy alone (n = 206) or CMT (n = 558) at the Chicago Prostate Cancer Center or at a 21st Century Oncology facility. Men either had no history of myocardial infarction (MI) or had a history of MI treated with a stent or surgical intervention. Fine and Gray regression analysis was used to identify the factors associated with PCSM. The median patient age was 73 years (interquartile range, 70-77 years). After a median follow-up of 4.9 years, 25 men died of prostate cancer. After adjusting for age and prostate cancer prognostic factors, the risk of PCSM was significantly less (adjusted hazard ratio, 0.29; 95% confidence interval, 0.12-0.68; P = .004) for men who received CMT than for men who received brachytherapy alone. Other factors that were associated significantly with an increased risk of PCSM included a Gleason score of 8 to 10 (P = .017). Elderly men who had high-risk prostate cancer without cardiovascular disease or with surgically corrected cardiovascular disease had a lower risk of PCSM when they received CMT than when they received brachytherapy alone. These results support aggressive locoregional treatment in healthy elderly men with high-risk prostate cancer. (c) 2010 American Cancer Society.

The Utility of PET/CT in the Planning of External Radiation Therapy for Prostate Cancer.

PubMed

Calais, Jeremie; Cao, Minsong; Nickols, Nicholas G

2018-04-01

Radiotherapy and radical prostatectomy are the definitive treatment options for patients with localized prostate cancer. A rising level of prostate-specific antigen after radical prostatectomy indicates prostate cancer recurrence, and these patients may still be cured with salvage radiotherapy. To maximize chance for cure, the irradiated volumes should completely encompass the extent of disease. Therefore, accurate estimation of the location of disease is critical for radiotherapy planning in both the definitive and the salvage settings. Current first-line imaging for prostate cancer has limited sensitivity for detection of disease both at initial staging and at biochemical recurrence. Integration of PET into routine evaluation of prostate cancer patients may improve both staging accuracy and radiotherapy planning. 18 F-FDG PET/CT is now routinely used in radiation planning for several cancer types. However, 18 F-FDG PET/CT has low sensitivity for prostate cancer. Additional PET probes evaluated in prostate cancer include 18 F-sodium fluoride, 11 C-acetate, 11 C- or 18 F-choline, 18 F-fluciclovine, and 68 Ga- or 18 F-labeled ligands that bind prostate-specific membrane antigen (PSMA). PSMA ligands appear to be the most sensitive and specific but have not yet received Food and Drug Administration New Drug Application approval for use in the United States. Retrospective and prospective investigations suggest a potential major impact of PET/CT on prostate radiation treatment planning. Prospective trials randomizing patients to routine radiotherapy planning versus PET/CT-aided planning may show meaningful clinical outcomes. Prospective clinical trials evaluating the addition of 18 F-fluciclovine PET/CT for planning of salvage radiotherapy with clinical endpoints are under way. Prospective trials evaluating the clinical impact of PSMA PET/CT on prostate radiation planning are indicated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

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

PubMed

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

2016-01-12

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

In Vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent

DTIC Science & Technology

2015-09-01

detection of early stage prostate cancer, development of near infrared dyes - labeled RNA aptamer that recognizes the prostate specific cell surface protein...the application of PAI for the detection of early stage prostate cancer, development of a NIR dye - labeled RNA aptamer that recognizes the prostate...proposed to enhance the application of PAI for the detection of early stage PrCa: 1. Use of a NIR dye labeled RNA aptamer that recognizes the prostate

Digoxin and prostate cancer survival in the Finnish Randomized Study of Screening for Prostate Cancer.

PubMed

Kaapu, Kalle J; Murtola, Teemu J; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo Lj; Auvinen, Anssi

2016-11-22

Protective effects have been suggested for digoxin against prostate cancer risk. However, few studies have evaluated the possible effects on prostate cancer-specific survival. We studied the association between use of digoxin or beta-blocker sotalol and prostate cancer-specific survival as compared with users of other antiarrhythmic drugs in a retrospective cohort study. Our study population consisted of 6537 prostate cancer cases from the Finnish Randomized Study of Screening for Prostate Cancer diagnosed during 1996-2009 (485 digoxin users). The median exposure for digoxin was 480 DDDs (interquartile range 100-1400 DDDs). During a median follow-up of 7.5 years after diagnosis, 617 men (48 digoxin users) died of prostate cancer. We collected information on antiarrhythmic drug purchases from the national prescription database. Both prediagnostic and postdiagnostic drug usages were analysed using the Cox regression method. No association was found for prostate cancer death with digoxin usage before (HR 1.00, 95% CI 0.56-1.80) or after (HR 0.81, 95% CI 0.43-1.51) prostate cancer diagnosis. The results were also comparable for sotalol and antiarrhythmic drugs in general. Among men not receiving hormonal therapy, prediagnostic digoxin usage was associated with prolonged prostate cancer survival (HR 0.20, 95% CI 0.05-0.86). No general protective effects against prostate cancer were observed for digoxin or sotalol usage.

Effects of homeopathic preparations on human prostate cancer growth in cellular and animal models.

PubMed

MacLaughlin, Brian W; Gutsmuths, Babett; Pretner, Ewald; Jonas, Wayne B; Ives, John; Kulawardane, Don Victor; Amri, Hakima

2006-12-01

The use of dietary supplements for various ailments enjoys unprecedented popularity. As part of this trend, Sabal serrulata (saw palmetto) constitutes the complementary treatment of choice with regard to prostate health. In homeopathy, Sabal serrulata is commonly prescribed for prostate problems ranging from benign prostatic hyperplasia to prostate cancer. The authors' work assessed the antiproliferative effects of homeopathic preparations of Sabal serrulata, Thuja occidentalis, and Conium maculatum, in vivo, on nude mouse xenografts, and in vitro, on PC-3 and DU-145 human prostate cancer as well as MDA-MB-231 human breast cancer cell lines. Treatment with Sabal serrulata in vitro resulted in a 33% decrease of PC-3 cell proliferation at 72 hours and a 23% reduction of DU-145 cell proliferation at 24 hours (P<.01). The difference in reduction is likely due to the specific doubling time of each cell line. No effect was observed on MDA-MB-231 human breast cancer cells. Thuja occidentalis and Conium maculatum did not have any effect on human prostate cancer cell proliferation. In vivo, prostate tumor xenograft size was significantly reduced in Sabal serrulata-treated mice compared to untreated controls (P=.012). No effect was observed on breast tumor growth. Our study clearly demonstrates a biologic response to homeopathic treatment as manifested by cell proliferation and tumor growth. This biologic effect was (i)significantly stronger to Sabal serrulata than to controls and (ii)specific to human prostate cancer. Sabal serrulata should thus be further investigated as a specific homeopathic remedy for prostate pathology.

Serum total prostate-specific antigen values in men with symptomatic prostate enlargement in Nigeria: role in clinical decision-making.

PubMed

Nnabugwu, Ikenna I; Ugwumba, Fred O; Enivwenae, Oghenekaro A; Udeh, Emeka I; Otene, Chris O; Nnabugwu, Chinwe A

2015-01-01

Prostatic enlargement is a common cause of bladder outlet obstruction in men in Nigeria. Malignant enlargements must be differentiated from benign enlargements for adequate treatment of each patient. High serum total prostate-specific antigen (tPSA) levels suggest malignancy, but some of the biopsies done due to a serum tPSA value >4 ng/mL would be negative for malignancy because of the low specificity of tPSA for prostate cancer. This study aims to compare the histologic findings of all prostate specimens obtained from core needle biopsy, open simple prostatectomy, and transurethral resection of the prostate with the respective serum tPSA values in an attempt to decipher the role of serum tPSA in the management of these patients. The case notes of patients attended to from April 2009 to March 2012 were analyzed. Essentially, the age of the patient, findings on digital rectal examination, abdominopelvic ultrasonography report on the prostate, serum tPSA, and histology reports from biopsy or prostatectomy specimens as indicated were extracted for analysis. The relationship between age, findings on digital rectal examination, serum tPSA, abdominopelvic ultrasonography report, and histology are compared. A statistically significant relationship existed between a malignant histology and age 65 years and older, suspicious findings on digital rectal examination, suspicious ultrasonography findings, and serum tPSA >10 ng/mL, but not tPSA >4 ng/mL. In Nigerian patients with symptomatic prostate enlargement, serum tPSA should be seen as a continuum with increasing risk of prostate malignancy.

What do prostate cancer patients die of?

PubMed

Riihimäki, Matias; Thomsen, Hauke; Brandt, Andreas; Sundquist, Jan; Hemminki, Kari

2011-01-01

A recent rise in the incidence of prostate cancer and a more favorable outcome have increased the proportions of other causes of death in affected men. Extending the survival of prostate cancer patients thus requires knowledge of all causes of death. Data on the population, cancers, and causes of death were gathered from the nationwide Swedish Family-Cancer Database. A Cox regression model, comparing prostate cancer patients with all other men, was applied. Hazard ratios (HR) were calculated both for the underlying cause and for dying with a specific cause listed among multiple causes of death. Among 686,500 observed deaths, 62,500 were prostate cancer patients. For underlying causes other than prostate cancer, the highest cause-specific HRs were found for external causes (HR, 1.24; 95% confidence interval [CI], 1.16-1.31), diseases of the pulmonary circulation (HR, 1.22; 95% CI, 1.09-1.37), and heart failure (HR, 1.18; 95% CI, 1.11-1.24). For specific multiple causes, the highest HRs were found for anemia (HR, 2.28; 95% CI, 2.14-2.42), diseases of the pulmonary circulation (HR, 1.61; 95% CI, 1.55-1.68), and urinary system disease (HR, 1.90; 95% CI, 1.84-1.96). Prostate cancer patients have a higher risk for dying from various causes other than prostate cancer, including external causes and heart failure. Mechanisms have been proposed linking these elevated risks to both cancer and treatment. More attention should be paid to comorbidities in men with prostate cancer. The present study fulfills a gap in the knowledge of death causes in prostate cancer patients.

Pim-1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

DTIC Science & Technology

2005-10-01

Reiter RE, Lilly MB: Gene expression profiling in R- flurbiprofen -treated prostate cancer: Identification of prostate stem cell antigen as a... flurbiprofen -regulated gene. (submitted, 2006). 51. Holder SL, Zemskova M, Bremner R, Neidigh J, Lilly MB: Identification of specific, cell-permeable...profiling in R- flurbiprofen - treated prostate cancer: Identification of prostate stem cell antigen as a flurbiprofen - regulated gene. (poster

Combination therapy for biochemically recurrent prostate cancer tested in new trial | Center for Cancer Research

Cancer.gov

Prostate-specific antigen (PSA) is an enzyme released by the prostate gland and is found in abnormally high concentrations in the blood of men with prostate cancer. “Biochemical recurrence” is when PSA levels continue to rise after initial treatment for prostate cancer, such as surgery or radiation. Marijo Bilusic, M.D., of the Genitourinary Malignancies Branch is leading the

Evaluation of the Efficiency of the Reticulocyte Hemoglobin Content on Diagnosis for Iron Deficiency Anemia in Chinese Adults.

PubMed

Cai, Jie; Wu, Meng; Ren, Jie; Du, Yali; Long, Zhangbiao; Li, Guoxun; Han, Bing; Yang, Lichen

2017-05-02

Our aim was to evaluate the cut-off value and efficiency of using reticulocyte hemoglobin content as a marker to diagnose iron deficiency anemia in Chinese adults. 140 adults who needed bone marrow aspiration for diagnosis at the hematology department of the Peking Union Medical College Hospital were enrolled according to the inclusive and exclusive criteria. Venous blood samples were collected to detect complete blood count, including hemoglobin, reticulocyte hemoglobin content, hematocrit, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, free erythrocyte protoporphyrin; iron indexes of serum ferritin, serum transferrin receptor, and unsaturated iron-binding capacity; and inflammation markers of C-reactive protein and α-acid glycoprotein. Bone marrow samples were obtained for the bone marrow iron staining, which was used as the standard for the evaluation of iron status in this study. Subjects were divided into three groups according to hemoglobin levels and bone marrow iron staining results: the IDA (iron deficiency anemia) group, the NIDA (non-iron deficiency anemia) group, and the control group. The differences of the above-mentioned indexes were compared among the three groups and the effect of inflammation was also considered. The cut-off value of reticulocyte hemoglobin content was determined by receiver operation curves. The IDA group ( n = 56) had significantly lower reticulocyte hemoglobin content, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, and serum ferritin; and higher free erythrocyte protoporphyrin, unsaturated iron-binding capacity, and serum transferrin receptor ( p < 0.05) compared with the NIDA group ( n = 38) and control group ( n = 46). Hematocrit, serum ferritin, and unsaturated iron-binding capacity were significantly affected by inflammation while reticulocyte hemoglobin content and other parameters were not. The cut-off value of reticulocyte hemoglobin content for diagnosing iron deficiency anemia was 27.2 pg, with a sensitivity of 87.5% and a specificity of 92.9%. The cut-off values for mean cellular volume, serum ferritin, and serum transferrin receptor were 76.6, 12.9, and 4.89 mg/L, respectively. Reticulocyte hemoglobin content had the largest area under the curve of 0.929, while those for mean cellular volume, serum ferritin, serum transferrin receptor were 0.922, 0.887, and 0.900, respectively. Reticulocyte hemoglobin content has a high sensitivity and specificity in the diagnosis of iron deficiency anemia, and its comprehensive diagnostic efficacy is better than other traditional indicators-such as serum ferritin and serum transferrin receptor.

Recognition of prostate-specific antigenic peptide determinants by human CD4 and CD8 T cells.

PubMed

Corman, J M; Sercarz, E E; Nanda, N K

1998-11-01

It is now becoming accepted that one is not tolerant to all the determinants of self proteins: the T cell repertoire directed to some sequences in self proteins is intact and can be activated. When a self protein is exclusively expressed by tumour cells, the T cell repertoire directed to the particular self antigen can potentially be activated to attack the tumour: this would amount to induction of a beneficial autoimmune response. Prostate cancer offers a unique opportunity for activation of a tumour-specific immune response owing to the exclusive synthesis of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) by prostatic tissue and prostate tumour cells. In this study we examine the CD4 and CD8 T cell repertoires specific for peptides of PSA and PSM in normal human male individuals, using short-term, peptide antigen-driven CD4 and CD8 T cell lines. We show that short-term, CD4 T cell lines derived from six HLA-DR4 individuals showed strong proliferative responses to six of 10 tested peptides of PSA, selected as to contain a DR4 binding motif. Short-term, CD8 T cell lines from three HLA-A1 individuals showed specific cytolytic activity for autologous targets loaded with five of five tested peptides of PSA and PSM, selected to possess an HLA-A1 binding motif. One of the peptides chosen is termed a 'dual-motif' peptide, as it encodes determinants for both CD4 and CD8 T cells. These results, indicating the existence of CD4 and CD8 T cells against determinants of the self proteins, PSA and PSM, in healthy male individuals reveal the potential of the T cell repertoire from the typical prostate cancer patient to eradicate prostate tumours upon being appropriately activated.

Prostate cancer: a patient's perspective.

PubMed

Howe, R J

1994-11-01

During the last few years a tremendous amount of media attention has been focused on prostate cancer. This increased visibility has been the direct result of the prostate specific antigen test, which has led to a doubling of the number of new cases detected in just 4 years. With this visibility has come controversy about which treatment is the most effective or whether this disease should be treated aggressively at all. The formation and rapid expansion of the prostate cancer support group movement are reviewed, and the positive and negative impacts of media coverage on present and future patients are assessed. My personal case is reviewed briefly to make a specific point about the hazards of watchful waiting. Other issues, such as mass screening, Prostate Cancer Awareness Week and expenditures for prostate cancer research, are examined in some detail.

Utility Estimates of Disease-Specific Health States in Prostate Cancer from Three Different Perspectives.

PubMed

Gries, Katharine S; Regier, Dean A; Ramsey, Scott D; Patrick, Donald L

2017-06-01

To develop a statistical model generating utility estimates for prostate cancer specific health states, using preference weights derived from the perspectives of prostate cancer patients, men at risk for prostate cancer, and society. Utility estimate values were calculated using standard gamble (SG) methodology. Study participants valued 18 prostate-specific health states with the five attributes: sexual function, urinary function, bowel function, pain, and emotional well-being. Appropriateness of model (linear regression, mixed effects, or generalized estimating equation) to generate prostate cancer utility estimates was determined by paired t-tests to compare observed and predicted values. Mixed-corrected standard SG utility estimates to account for loss aversion were calculated based on prospect theory. 132 study participants assigned values to the health states (n = 40 men at risk for prostate cancer; n = 43 men with prostate cancer; n = 49 general population). In total, 792 valuations were elicited (six health states for each 132 participants). The most appropriate model for the classification system was a mixed effects model; correlations between the mean observed and predicted utility estimates were greater than 0.80 for each perspective. Developing a health-state classification system with preference weights for three different perspectives demonstrates the relative importance of main effects between populations. The predicted values for men with prostate cancer support the hypothesis that patients experiencing the disease state assign higher utility estimates to health states and there is a difference in valuations made by patients and the general population.

A new model consists of intravesical prostatic protrusion, prostate volume and serum prostatic-specific antigen in the evaluation of prostate cancer.

PubMed

Xu, Ding; Yu, Yongjiang; Zhu, Yunkai; Huang, Tao; Chen, Yaqing; Qi, Jun

2014-04-01

The Prostate-specific antigen (PSA) level is largely used to diagnose prostate cancer (PCa) in last decades. However, its specificity is low in patients with a PSA level ranging from 4.0 to 10.0 ng/ml. This study aims to define the correlation between intravesical prostatic protrusion (IPP) and PSA and to establish a new model to predict PCa. A total of 339 patients order than 45 years examined between October 2010 and June 2012 were enrolled. Eligible patients were recommended for transrectal ultrasonography (TRUS)-guided prostate biopsies after measuring total prostate volume (TPV), tranzisional zone volume (TZV) and IPP. The levels of total PSA (tPSA), free PSA (fPSA) were analyzed by using Hybritech calibrated Access tPSA and fPSA assays. A new mathematical model, named IPP removed PCa predicting score (IRPPS), consists of tPSA, TZV and IPP was established. The predictive accuracy of IRPPS, PSA density (PSAD), %PSA and tPSA were compared using receiver-operator characteristic (ROC) analysis. Eighty-six patients had PSA levels of 4.0-10.0 ng/ml. Twenty of them were diagnosed as PCa. Using ROC curves, the areas under the curve for IRPPS, PSAD and %PSA and tPSA were 0.786, 0.768 and 0.664 and 0.585, respectively. We suggested IPP grade had a significant relationship with serum tPSA levels. The predictive accuracy of IRPPS was higher than the other 3 indictors.

Gene signatures distinguish stage-specific prostate cancer stem cells isolated from transgenic adenocarcinoma of the mouse prostate lesions and predict the malignancy of human tumors.

PubMed

Mazzoleni, Stefania; Jachetti, Elena; Morosini, Sara; Grioni, Matteo; Piras, Ignazio Stefano; Pala, Mauro; Bulfone, Alessandro; Freschi, Massimo; Bellone, Matteo; Galli, Rossella

2013-09-01

The relevant social and economic impact of prostate adenocarcinoma, one of the leading causes of death in men, urges critical improvements in knowledge of the pathogenesis and cure of this disease. These can also be achieved by implementing in vitro and in vivo preclinical models by taking advantage of prostate cancer stem cells (PCSCs). The best-characterized mouse model of prostate cancer is the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice develop a progressive lesion called prostatic intraepithelial neoplasia that evolves into adenocarcinoma (AD) between 24 and 30 weeks of age. ADs often metastasize to lymph nodes, lung, bones, and kidneys. Eventually, approximately 5% of the mice develop an androgen-independent neuroendocrine adenocarcinoma. Here we report the establishment of long-term self-renewing PCSC lines from the different stages of TRAMP progression by application of the neurosphere assay. Stage-specific prostate cell lines were endowed with the critical features expected from malignant bona fide cancer stem cells, namely, self-renewal, multipotency, and tumorigenicity. Notably, transcriptome analysis of stage-specific PCSCs resulted in the generation of well-defined, meaningful gene signatures, which identify distinct stages of human tumor progression. As such, TRAMP-derived PCSCs represent a novel and valuable preclinical model for elucidating the pathogenetic mechanisms leading to prostate adenocarcinoma and for the identification of molecular mediators to be pursued as therapeutic targets.

Configuration and validation of a novel prostate disease nomogram predicting prostate biopsy outcome: A prospective study correlating clinical indicators among Filipino adult males with elevated PSA level.

PubMed

Chua, Michael E; Tanseco, Patrick P; Mendoza, Jonathan S; Castillo, Josefino C; Morales, Marcelino L; Luna, Saturnino L

2015-04-01

To configure and validate a novel prostate disease nomogram providing prostate biopsy outcome probabilities from a prospective study correlating clinical indicators and diagnostic parameters among Filipino adult male with elevated serum total prostate specific antigen (PSA) level. All men with an elevated serum total PSA underwent initial prostate biopsy at our institution from January 2011 to August 2014 were included. Clinical indicators, diagnostic parameters, which include PSA level and PSA-derivatives, were collected as predictive factors for biopsy outcome. Multiple logistic-regression analysis involving a backward elimination selection procedure was used to select independent predictors. A nomogram was developed to calculate the probability of the biopsy outcomes. External validation of the nomogram was performed using separate data set from another center for determination of sensitivity and specificity. A receiver-operating characteristic (ROC) curve was used to assess the accuracy in predicting differential biopsy outcome. Total of 552 patients was included. One hundred and ninety-one (34.6%) patients had benign prostatic hyperplasia, and 165 (29.9%) had chronic prostatitis. The remaining 196 (35.5%) patients had prostate adenocarcinoma. The significant independent variables used to predict biopsy outcome were age, family history of prostate cancer, prior antibiotic intake, PSA level, PSA-density, PSA-velocity, echogenic findings on ultrasound, and DRE status. The areas under the receiver-operating characteristic curve for prostate cancer using PSA alone and the nomogram were 0.688 and 0.804, respectively. The nomogram configured based on routinely available clinical parameters, provides high predictive accuracy with good performance characteristics in predicting the prostate biopsy outcome such as presence of prostate cancer, high Gleason prostate cancer, benign prostatic hyperplasia, and chronic prostatitis.

The Infectious Pathogenesis Of Prostate Cancer

DTIC Science & Technology

2011-04-01

agents in the genesis of inflammation. For prostate cancer, several lines of evidence point to a role of infections as important agents , although no...specific infection has consistently been identified. In this project, we are examining two specific infectious agents with respect to prostate cancer: T...Infectious agents are likely targets involved in the initiation and exacerbation of chronic inflammation, and infections can lead to increased risk of

Development of a PET Prostate-Specific Membrane Antigen Imaging Agent: Preclinical Translation for Future Clinical Application

DTIC Science & Technology

2016-10-01

small-molecule peptidomimetic imaging agents labeled with positron emitting fluorine- 18 . These data will enable the filing of an exploratory IND...outcome. 15. SUBJECT TERMS Prostate Cancer, Prostate Specific Membrane Antigen (PSMA), Fluorine- 18 , Molecular Imaging, Radiotracer, Automated...Synthesis, Phosphoramidate, Inhibitor, Peptide Mimic, Peptidomimetic 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18 . NUMBER OF PAGES 19a

Allele related mutation specific-polymerase chain reaction for rapid diagnosis of Hb New York (beta 113 (G15) Val-->Glu, beta(CD113 GTG-->GAG)).

PubMed

Viprakasit, Vip; Tachavanich, Kalaya; Suwantol, Lerlugsn; Pung-Amritt, Parichat; Chinchang, Worawut; Tanphaichitr, Voravarn S

2002-08-01

Hemoglobin New York (beta 113 (G15) Val-->Glu), a beta-globin variant, was first reported in a Chinese family living in New York. Subsequently, this abnormal hemoglobin was reported in many Chinese descendants from several groups and it was also known as Hb Kaohsiung. The subtle change in alpha1beta1 contact region apart from the heme group connecting area by Val-->Glu substitution has minor changes in both the electrophoretic mobility and stability making this hemoglobin variant difficult to distinguish from Hb A using routine hemoglobin analysis. The authors described a case of heterozygosity of Hb New York diagnosed by a molecular technique and revealed a mutation in beta(CD113 GTG-->GAG). A novel Allele Related Mutation Specific-Polymerase Chain Reaction (ARMS-PCR) for rapid diagnosis of this mutation has been proposed.

Quality of Prostate Cancer Treatment Information on Cancer Center Websites.

PubMed

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

2016-04-20

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. 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. 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 (R(2) = 0.42, p < 0.001). 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.

Finasteride Treatment Alters Tissue Specific Androgen Receptor Expression in Prostate Tissues

PubMed Central

Bauman, Tyler M.; Sehgal, Priyanka D.; Johnson, Karen A.; Pier, Thomas; Bruskewitz, Reginald C.; Ricke, William A.; Huang, Wei

2014-01-01

BACKGROUND Normal and pathologic growth of the prostate is dependent on the synthesis of dihydrotestosterone (DHT) from testosterone by 5α-reductase. Finasteride is a selective inhibitor of 5α-reductase 2, one isozyme of 5α-reductase found in abundance in the human prostate. The objective of this study was to investigate the effects of finasteride on androgen receptor expression and tissue morphology in human benign prostatic hyperplasia specimens. METHODS Patients undergoing transurethral resection of the prostate and either treated or not treated with finasteride between 2004 and 2010 at the University of Wisconsin-Hospital were retrospectively identified using an institutional database. Prostate specimens from each patient were triple-stained for androgen receptor, prostate-specific antigen, and basal marker cytokeratin 5. Morphometric analysis was performed using the multispectral imaging, and results were compared between groups of finasteride treated and non-treated patients. RESULTS Epithelial androgen receptor but not stromal androgen receptor expression was significantly lower in patients treated with finasteride than in non-treated patients. Androgen receptor-regulated prostate-specific antigen was not significantly decreased in finasteride-treated patients. Significant luminal epithelial atrophy and basal cell hyperplasia were prevalent in finasteride treated patients. Epithelial androgen receptor expression was highly correlated to the level of luminal epithelial atrophy. CONCLUSIONS In this study, finasteride decreased the expression of epithelial androgen receptor in a tissue specific manner. The correlation between epithelial androgen receptor and the extent of luminal epithelial atrophy suggests that epithelial androgen receptor may be directly regulating the atrophic effects observed with finasteride treatment. PMID:24789081

Residual Prostate Cancer in Patients Treated With Endocrine Therapy With or Without Radical Radiotherapy: A Side Study of the SPCG-7 Randomized Trial

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

Solberg, Arne, E-mail: arne.solberg@stolav.n; Haugen, Olav A.; Department of Pathology and Medical Genetics, St. Olav's Hospital, Trondheim University Hospital, Trondheim

2011-05-01

Purpose: The Scandinavian Prostate Cancer Group-7 randomized trial demonstrated a survival benefit of combined endocrine therapy and external-beam radiotherapy over endocrine therapy alone in patients with high-risk prostate cancer. In a subset of the study population, the incidence and clinical implications of residual prostate cancer in posttreatment prostate biopsy specimens was evaluated. Methods and Materials: Biopsy specimens were obtained from 120 of 875 men in the Scandinavian Prostate Cancer Group-7 study. Results: Biopsies were performed at median of 45 months follow-up. In 63 patients receiving endocrine treatment only and 57 patients receiving combined treatment, residual cancer was found in 66%more » (n = 41) and 22% (n = 12), respectively (p < 0.0001). The vast majority of residual tumors were poorly differentiated (Gleason score {>=}8). Endocrine therapy alone was predictive of residual prostate cancer: odds ratio 7.49 (3.18-17.7), p < 0.0001. In patients with positive vs. negative biopsy the incidences of clinical events were as follows: biochemical recurrence 74% vs. 27% (p < 0.0001), local progression 26% vs. 4.7% (p = 0.002), distant recurrence 17% vs. 9.4% (p = 0.27), clinical recurrence 36% vs. 13% (p = 0.006), cancer-specific death 19% vs. 9.7% (p = 0.025). In multivariable analysis, biochemical recurrence was significantly associated with residual cancer: hazard ratio 2.69 (1.45-4.99), p = 0.002, and endocrine therapy alone hazard ratio 3.45 (1.80-6.62), p < 0.0001. Conclusions: Radiotherapy combined with hormones improved local tumor control in comparison with endocrine therapy alone. Residual prostate cancer was significantly associated with serum prostate-specific antigen recurrence, local tumor progression, clinical recurrence, and cancer-specific death in univariable analysis. Residual cancer was predictive of prostate-specific antigen recurrence in multivariable analysis.« less

Efficacy Against Human Prostate Cancer by Prostate-specific Membrane Antigen-specific, Transforming Growth Factor-β Insensitive Genetically Targeted CD8+ T-cells Derived from Patients with Metastatic Castrate-resistant Disease.

PubMed

Zhang, Qiang; Helfand, Brian T; Carneiro, Benedito A; Qin, Weijun; Yang, Ximing J; Lee, Chung; Zhang, Weipeng; Giles, Francis J; Cristofanilli, Massimo; Kuzel, Timothy M

2018-05-01

Current immunotherapy has limited efficacy on metastatic castrate-resistant prostate cancer (mCRPC). We therefore sought to improve the antitumor ability of mCRPC patient-derived CD8 + T-cells by the endowment of specificity to prostate-specific membrane antigen (PSMA) and insensitivity to immunosuppressant molecule transforming growth factor-β (TGF-ß) under the control of herpes simplex virus-1 thymidine kinase. CD8 + T-cells were collected by leukapheresis and cultured in a Food and Drug Administration-approved Cell Processing Work Station. We developed a chimeric antigen receptor retroviral construct using an anti-PSMA chimeric immunoglobulin-T-cell receptor(ζ) gene (PZ1) and dominant negative TGF-ß type II receptor (TßRIIDN), that could induce CD8 + T-cells to be PSMA reactive and insensitive to TGF-ß. Cr 51 release assay was performed on PC-3 and PC-3-PSMA. The further antitumor functions of PSMA-specific, TGF-ß insensitive CD8 + T-cells was evaluated using an immunodeficient RAG-1 -/- mouse model. We found PSMA-specific, TGF-ß insensitive CD8 + T-cells from mCRPC were expanded with strong expression of PZ1 and thymidine kinase genes, and their growth was not suppressed by TGF-ß. The survival of these cells decreased sharply after treatment with ganciclovir. Treatment of PSMA-specific TGF-ß, insensitive CD8 + T-cells was associated with 61.58% specific lysis on PC-3-PSMA, and significantly suppressed PC3-PSMA tumor compared with the PC3 tumor. A large amount of tumor apoptosis and CD8 + T-cell infiltration were found only in the PC3-PSMA tumor. This study verified that PSMA-specific, TGF-ß insensitive CD8 + T-cells derived from mCRPC patients could be successfully expanded and used to overcome the immunosuppressive effects of the tumor microenvironment to control PSMA-expressing PC in vitro and in vivo. This may provide a promising approach for men with mCRPC who fail androgen deprivation therapy. We investigated the role of a novel chimeric antigen receptor T-immunotherapy based on autologous metastatic castrate-resistant prostate cancer patient-derived prostate-specific membrane antigen (PSMA)-specific, transforming growth factor-ß insensitive CD8 + T-cells on PSMA-positive prostate cancer. We found that this chimeric antigen receptor T-cells could kill PSMA-positive prostate cancer specifically. The results suggest that this novel immunotherapy treatment is a potential new approach for men with metastatic castrate-resistant prostate cancer. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Relationship of hemoglobin A1c to mortality in nonsmoking insurance applicants.

PubMed

Stout, Robert L; Fulks, Michael; Dolan, Vera F; Magee, Mark E; Suarez, Luis

2007-01-01

Determine the relationship between hemoglobin A1c value and 5-year, all-cause mortality in nonsmoking life insurance applicants. By use of the Social Security Master Death Index, mortality was examined in 286,443 non-smoking insurance applicants aged 40 and up for whom blood samples for hemoglobin A1c were submitted to the Clinical Reference Laboratory. Results were stratified by hemoglobin A1c value, gender and age bands 40 to 59, 60 to 69 and 70 and up. Increased mortality is apparent at hemoglobin A1c values of 6% and above, is linear, and on a percentage basis decreases with age. Hemoglobin A1c values less than 5% also are associated with increased mortality. Absolute mortality rates for females with elevated hemoglobin A1c are generally lower than rates for males, although mortality relative to the gender-specific reference group with hemoglobin A1c of 5% to 5.9% is generally the same for both. The importance of even small elevations of hemoglobin A1c above 5.9% is apparent. For screening, it is the degree of blood sugar elevation as measured by hemoglobin A1c rather than any diagnostic label that is critical in risk assessment.

18F-DCFBC Prostate-Specific Membrane Antigen-Targeted PET/CT Imaging in Localized Prostate Cancer: Correlation With Multiparametric MRI and Histopathology.

PubMed

Turkbey, Baris; Mena, Esther; Lindenberg, Liza; Adler, Stephen; Bednarova, Sandra; Berman, Rose; Ton, Anita T; McKinney, Yolanda; Eclarinal, Philip; Hill, Craig; Afari, George; Bhattacharyya, Sibaprasad; Mease, Ronnie C; Merino, Maria J; Jacobs, Paula M; Wood, Bradford J; Pinto, Peter A; Pomper, Martin G; Choyke, Peter L

2017-10-01

To assess the ability of (N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-F-fluorobenzyl-L-cysteine) (F-DCFBC), a prostate-specific membrane antigen-targeted PET agent, to detect localized prostate cancer lesions in correlation with multiparametric MRI (mpMRI) and histopathology. This Health Insurance Portability and Accountability Act of 1996-compliant, prospective, institutional review board-approved study included 13 evaluable patients with localized prostate cancer (median age, 62.8 years [range, 51-74 years]; median prostate-specific antigen, 37.5 ng/dL [range, 3.26-216 ng/dL]). Patients underwent mpMRI and F-DCFBC PET/CT within a 3 months' window. Lesions seen on mpMRI were biopsied under transrectal ultrasound/MRI fusion-guided biopsy, or a radical prostatectomy was performed. F-DCFBC PET/CT and mpMRI were evaluated blinded and separately for tumor detection on a lesion basis. For PET image analysis, MRI and F-DCFBC PET images were fused by using software registration; imaging findings were correlated with histology, and uptake of F-DCFBC in tumors was compared with uptake in benign prostatic hyperplasia nodules and normal peripheral zone tissue using the 80% threshold SUVmax. A total of 25 tumor foci (mean size, 1.8 cm; median size, 1.5 cm; range, 0.6-4.7 cm) were histopathologically identified in 13 patients. Sensitivity rates of F-DCFBC PET/CT and mpMRI were 36% and 96%, respectively, for all tumors. For index lesions, the largest tumor with highest Gleason score, sensitivity rates of F-DCFBC PET/CT and mpMRI were 61.5% and 92%, respectively. The average SUVmax for primary prostate cancer was higher (5.8 ± 4.4) than that of benign prostatic hyperplasia nodules (2.1 ± 0.3) or that of normal prostate tissue (2.1 ± 0.4) at 1 hour postinjection (P = 0.0033). The majority of index prostate cancers are detected with F-DCFBC PET/CT, and this may be a prognostic indicator based on uptake and staging. However, for detecting prostate cancer with high sensitivity, it is important to combine prostate-specific membrane antigen PET/CT with mpMRI.

Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Treatment of Prostate Cancer

DTIC Science & Technology

2009-07-01

prostate lysate (0.1 to 10 ug/ml) hemocyanin (0.1 to 1 ug/ml) MDCK (1 ug/ml) or canine vaccine (Parvo, rabies, and distemper at a 1:500 dilution of...We determined that a prostate cell lysate prepared from canine prostate tissue was immunogenic when injected in female dogs. In addition to the...known prostate antigen, canine prostate specific esterase (CPSE), we identified by molecular weight several other proteins against which the dog made IgG

Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells.

PubMed

Olson, Brian M; Gamat, Melissa; Seliski, Joseph; Sawicki, Thomas; Jeffery, Justin; Ellis, Leigh; Drake, Charles G; Weichert, Jamey; McNeel, Douglas G

2017-12-01

Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR . ©2017 American Association for Cancer Research.

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

Prostate Cancer in Deceased Liver Donors.

PubMed

Skalski, M; Gierej, B; Ziarkiewicz-Wróblewska, B; Hołówko, W; Krawczyk, M

2016-06-01

Prostate cancer is the second most common malignant tumor (13%) among male subjects in Poland. The aim of this study was to assess the prevalence of prostate cancer in a group of deceased liver donors. A total of 784 liver procurement attempts from deceased donors were performed in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, from January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver transplant. A retrospective analysis was performed based on these data. Among male donors (n = 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of the prostate performed before making the decision regarding liver graft utilization. In the group of 30 donors who underwent prostate examination, 3 (10%) were diagnosed as having prostate cancer of a moderate invasive stage. In 2 other cases, fresh frozen section suggested prostate cancer; however, this fact was not confirmed in routine section. liver transplantation was not performed in these cases of suspicion of prostate cancer (5 of 30 [17%]) in the frozen biopsy specimens. The difference between groups of donors with prostate cancer and benign pathology of the prostate gland according to prostate-specific antigen serum concentration (P = .578) or age (P = .730) was not statistically significant. Increased prostate-specific antigen serum concentrations without a diagnosis of prostate cancer in histopathologic examinations should not be an independent contraindication for performing organ transplantation. Nevertheless, for recipient safety, even when prostate cancer is only suspected in the frozen biopsy sample, the procured organ should not be used for transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Combining immunotherapies for the treatment of prostate cancer.

PubMed

Redman, Jason M; Gulley, James L; Madan, Ravi A

2017-12-01

Sipuleucel-T, a therapeutic dendritic-cell vaccine, was Food and Drug Administration-approved for prostate cancer in 2010. No new immunotherapies for prostate cancer have been approved since. However, novel agents and combination approaches offer great promise for improving outcomes for prostate cancer patients. Here we review the latest developments in immunotherapy for prostate cancer. Sipuleucel-T has demonstrated a survival advantage of 4.1 months in metastatic castration-resistant prostate cancer. PSA-TRICOM (PROSTVAC), a prostate-specific antigen-targeted vaccine platform, showed evidence of clinical and immunologic efficacy in early-phase clinical trials, and results from a phase III trial in advanced disease are pending. While immune checkpoint inhibitors appear to have modest activity as monotherapy, preclinical and clinical data suggest that they may synergize with vaccines, poly [ADP-ribose] polymerase inhibitors, and other agents. Several clinical studies that combine these therapies are underway. Combining prostate cancer vaccines with immune checkpoint inhibitors has great potential for improving clinical outcomes in prostate cancer. Such combination approaches may create and then recruit tumor-specific T cells to tumor while also increasing their effector function. Other emerging agents may also enhance immune-mediated tumor destruction. Copyright © 2017. Published by Elsevier Inc.

Prostate-specific antigen (PSA) as a possible biomarker in non-prostatic cancer: A review.

PubMed

Pérez-Ibave, Diana Cristina; Burciaga-Flores, Carlos Horacio; Elizondo-Riojas, Miguel-Ángel

2018-06-01

Prostate-specific antigen (PSA) is a serine protease produced by epithelial prostatic cells and its main function is to liquefy seminal coagulum. Currently, PSA is a biomarker for the diagnosis and screening of prostate cancer and it was the first cancer biomarker approved by the FDA. The quantity and serum isoforms of male PSA, allows distinguishing between carcinoma and benign inflammatory disease of the prostate. Initially, it was thought that PSA was produced only by the prostate, and thus, a protein that was expressed exclusively in men. However, several authors report that PSA is a protein that is expressed by multiple non-prostatic tissues not only in men but also in women. Some authors also report that in women, the expression of this protein is highly related to breast and colon cancer and therefore can act as a possible biomarker for early detection, diagnosis and prognosis of these cancers in women. In this review, we will focus on the characteristics of the PSA at a molecular level, its current clinical implications, the expression of this protein in non-prostatic tissues, and its relationship with cancer, especially in women. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adoptive cell therapy of prostate cancer using female mice-derived T cells that react with prostate antigens

PubMed Central

Yi, Huanfa; Yu, Xiaofei; Guo, Chunqing; Manjili, Masoud H.; Repasky, Elizabeth A.; Wang, Xiang-Yang

2011-01-01

In this study, we report a novel treatment strategy that could potentially be used to improve efficacy of adoptive cell therapy for patients with prostate cancer. We show that female C57BL/6 mice are able to effectively reject two syngeneic prostate tumors (TRAMP-C2 and RM1) in a T cell-dependent manner. The protective antitumor immunity appears to primarily involve T cell responses reactive against general prostate tumor/tissue antigens, rather than simply to male-specific H-Y antigen. For the first time we show that adoptive transfer of lymphocytes from TRAMP-C2-primed or naive female mice effectively control prostate tumor growth in male mice, when combined with host pre-conditioning (i.e., non-myeloablative lymphodepletion) and IL-2 administration. No pathological autoimmune response was observed in the treated tumor-bearing male mice. Our studies provide new insights regarding the immune-mediated recognition of male-specific tissue, such as the prostate, and may offer new immunotherapy treatment strategies for advanced prostate cancer. PMID:21088965

Fungal prostatitis: an update.

PubMed

Mayayo, Emilio; Fernández-Silva, Fabiola

2014-06-01

Prostate pathology is a daily occurrence in urological and general medical consultations. Besides hyperplasia and neoplastic pathology, other processes, such as infectious ones, are also documented. Their etiology is diverse and varied. Within the infectious prostatic processes, fungi can also be a specific cause of prostatitis. Fungal prostatitis often appears in patients with impaired immunity and can also be rarely found in healthy patients. It can result from a disseminated infection, but it can also be localized. Fungal prostatitis is a nonspecific and harmless process. Diagnosis is commonly made by fine needle aspiration cytology or by biopsy. A number of fungi can be involved. Although there are not many reported cases, they are becoming more frequent, in particular in patients with some degree of immunodeficiency or those who live in areas where specific fungi are endemic or in visitors of those areas. We present a comprehensive review of the various forms of fungal prostatitis, and we describe the morphological characteristics of the fungi more frequently reported as causes of fungal prostatitis. We also report our own experience, aiming to alert physicians, urologists and pathologists of these particular infections.

Male Oncology Research and Education program for men at high risk for prostate cancer.

PubMed

Lorentz, J; Liu, S K; Vesprini, D

2018-04-01

Three groups of men are at high risk of developing prostate cancer: men with a strong family history of prostate cancer, men of West African or Caribbean ancestry, and men with a germline pathogenic variant in a prostate cancer-associated gene. Despite the fact that those men constitute a significant portion of the male population in North America, few recommendations for prostate cancer screening specific to them have been developed. For men at general population risk for prostate cancer, screening based on prostate-specific antigen (psa) has remained controversial despite the abundance of literature on the topic. As a result, recommendations made by major screening authorities are inconsistent (ranging from no psa screening to baseline psa screening at age 45), allowing physicians to pick and choose how to screen their patients. The Male Oncology Research and Education (more) program is an observational research program that serves as an academic platform for multiple research foci. For its participants, serum and dna are biobanked, medical information is collected, and contact for relevant research-related opportunities is maintained. This research program is paired with a specialized clinic called the more clinic, where men at high risk are regularly screened for prostate cancer in a standard approach that includes physical examination and serum psa measurement. In this article, we describe the goals, participant accrual to date, and projects specific to this unique program.

Pittsburgh Tuskegee Prostate Training Program

DTIC Science & Technology

2014-05-01

11 . SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT X Approved for public release; distribution...Prostate Specific Membrane Antigen ( Psma ) and Folate Levels on Gene Expression and Proliferation in Prostatic Cancer Cells Denise O’Keefe Table...

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.

Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

DTIC Science & Technology

2016-10-01

mediator of prostate cancer tumor growth. Specifically, phagocytic macrophages and efferocytosis were found to be upregulated in the blood of...patients with metastatic prostate cancer. Moreover, inhibiting phagocytic macrophages with the chemotherapeutic trabectedin reduced efferocytosis and

Gene cooption and convergent evolution of oxygen transport hemoglobins in jawed and jawless vertebrates

PubMed Central

Hoffmann, Federico G.; Opazo, Juan C.; Storz, Jay F.

2010-01-01

Natural selection often promotes evolutionary innovation by coopting preexisting genes for new functions, and this process may be greatly facilitated by gene duplication. Here we report an example of cooptive convergence where paralogous members of the globin gene superfamily independently evolved a specialized O2 transport function in the two deepest branches of the vertebrate family tree. Specifically, phylogenetic evidence demonstrates that erythroid-specific O2 transport hemoglobins evolved independently from different ancestral precursor proteins in jawed vertebrates (gnathostomes) and jawless fish (cyclostomes, represented by lamprey and hagfish). A comprehensive phylogenetic analysis of the vertebrate globin gene superfamily revealed that the erythroid hemoglobins of cyclostomes are orthologous to the cytoglobin protein of gnathostome vertebrates, a hexacoordinate globin that has no O2 transport function and that is predominantly expressed in fibroblasts and related cell types. The phylogeny reconstruction also revealed that vertebrate-specific globins are grouped into four main clades: (i) cyclostome hemoglobin + cytoglobin, (ii) myoglobin + globin E, (iii) globin Y, and (iv) the α- and β-chain hemoglobins of gnathostomes. In the hemoglobins of gnathostomes and cyclostomes, multisubunit quaternary structures provide the basis for cooperative O2 binding and allosteric regulation by coupling the effects of ligand binding at individual subunits with interactions between subunits. However, differences in numerous structural details belie their independent origins. This example of convergent evolution of protein function provides an impressive demonstration of the ability of natural selection to cobble together complex design solutions by tinkering with different variations of the same basic protein scaffold. PMID:20660759

The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogues in prostate cancer.

PubMed

Navarro-Pelayo Láinez, M M; Rodríguez-Fernández, A; Gómez-Río, M; Vázquez-Alonso, F; Cózar-Olmo, J M; Llamas-Elvira, J M

2014-11-01

prostate cancer is the most frequent solid malignant tumor in Western Countries. Positron emission tomography/x-ray computed tomography imaging with radiolabeled choline analogues is a useful tool for restaging prostate cancer in patients with rising prostate-specific antigen after radical treatment (in whom conventional imaging techniques have important limitations) as well as in the initial assessment of a selected group of prostate cancer patients. For this reason a literature review is necessary in order to evaluate the usefulness of this imaging test for the diagnosis and treatment of prostate cancer. a MEDLINE (PubMed way) literature search was performed using the search parameters: «Prostate cancer» and «Choline-PET/CT». Other search terms were «Biochemical failure» and/or «Staging» and/or «PSA kinetics». English and Spanish papers were selected; original articles, reviews, systematic reviews and clinical guidelines were included. according to available data, radiolabeled choline analogues plays an important role in the management of prostate cancer, especially in biochemical relapse because technique accuracy is properly correlated with prostate-specific antigen values and kinetics. Although is an emerging diagnostic technique useful in treatment planning of prostate cancer, final recommendations have not been submitted. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Prostate-specific antigen increase during dutasteride to indicate the need for prostate biopsy: influence of prostatic inflammation.

PubMed

Sciarra, Alessandro; Maggi, Martina; Fasulo, Andrea; Salciccia, Stefano; Gentile, Vincenzo; Cattarino, Susanna; Gentilucci, Alessandro

2017-08-01

The aim of this study was to analyze the significance of an increase in total prostate-specific antigen (PSA) serum levels despite dutasteride treatment as a predictor of prostate cancer (PC) at biopsy. We focused our attention on the rate of the first PSA increase and on the influence of prostatic inflammation. From 2011 to 2016, 365 men with a previous negative prostate biopsy and persistent elevated PSA levels received dutasteride treatment. The population was followed for a range of 12-48 months. One hundred twelve cases with a confirmed PSA increase >0.5 ng/ml over the nadir value during the follow-up were included in Group A and underwent a new prostate biopsy. In Group A, the PSA increase was associated with PC at the re-biopsy in 66% of cases. The percentage of PSA reduction after 6 months of treatment was not a significant indicator of the risk for PC. The distribution of inflammatory infiltrates significantly (p<00.01) varied from positive to negative prostate biopsies. The relative risk for PC at biopsy significantly increased according to PSA level during dutasteride. Treatment with dutasteride can help to analyze PSA kinetic. A persistent prostatic inflammation is a factor able to reduce the performance of PSA kinetic during dutasteride treatment.

[Prevalence of hemoglobinopathies in pregnant women in the Lanzarote health sanitary area].

PubMed

Calvo-Villas, J M; Zapata Ramos, M F; Cuesta Tovar, J; de la Iglesia Iñigo, S; Ropero Gradilla, P; Carreter de Granda, E; Sicilia Guillén, F

2006-05-01

The aim of this study is to analyze the global prevalence of carriers of heterozygous hemoglobinopathies among pregnant women settled in Lanzarote. A epidemiologic cross-sectional observational investigation was undertaken to study the prevalence of hemoglobinopathies in 2,436 pregnant women in Lanzarote. The techniques of primary screening were hemoglobin electrophoresis on cellulose acetate at alkaline pH for the detection of hemoglobin variants, and the quantification of HbA2 and HbF for the diagnosis of b thalassemia trait. The study to confirm the diagnosis of structural hemoglobinopathies was based on hemoglobin electrophoresis on citrate agar at acid pH, isolectric focusing and high-performance liquid chromatography (HPLC). The molecular characterization of b thalassemia trait (HbA2 >3.5%) was carried out by techniques using a real time PCR procedure with specific fluorescently labelled hybridization probes and allele-specific amplification (PCR-ARMS). The global prevalence of hemoglobinopathies was 11.90 corresponding to 9.44 for structural hemoglobinopathies and 2.46 for heterozygous b thalassemias. A variant hemoglobin was detected on 23 women and the distribution was as follows: thirteen carriers of hemoglobin S, seven HbC trait, two HbD trait and one "unstable" hemoglobin. 82.6% of the variant hemoglobins found were from migrant population from Africa and America. The high prevalence of carriers of structural hemoglobinopathies in Lanzarote justifies the initiation of programs for screening for hemoglobinopathies to prevent the emergence of severe states causing disease.

Current Approaches, Challenges and Future Directions for Monitoring Treatment Response in Prostate Cancer

PubMed Central

Wallace, T.J.; Torre, T.; Grob, M.; Yu, J.; Avital, I.; Brücher, BLDM; Stojadinovic, A.; Man, Y.G.

2014-01-01

Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm in men in the United States and the second leading cause of cancer mortality. One in 7 men will be diagnosed with prostate cancer during their lifetime. As a result, monitoring treatment response is of vital importance. The cornerstone of current approaches in monitoring treatment response remains the prostate-specific antigen (PSA). However, with the limitations of PSA come challenges in our ability to monitor treatment success. Defining PSA response is different depending on the individual treatment rendered potentially making it difficult for those not trained in urologic oncology to understand. Furthermore, standard treatment response criteria do not apply to prostate cancer further complicating the issue of treatment response. Historically, prostate cancer has been difficult to image and no single modality has been consistently relied upon to measure treatment response. However, with newer imaging modalities and advances in our understanding and utilization of specific biomarkers, the future for monitoring treatment response in prostate cancer looks bright. PMID:24396494

The hemoglobin system of the serpent eel Ophisurus serpens: structural and functional characterization.

PubMed

Manconi, Barbara; Pellegrini, Mariagiuseppina; Messana, Irene; Sanna, Maria Teresa; Castagnola, Massimo; Iavarone, Federica; Coluccia, Elisabetta; Giardina, Bruno; Olianas, Alessandra

2013-10-01

The hemoglobin system of the serpent eel Ophisurus serpens was structurally and functionally characterized with the aim of comparing it to the hemoglobin system of other fish species, as oxygen loading under the severe habitat conditions experienced by O. serpens could have necessitated specific adaptation mechanisms during evolution. The hemoglobin system of O. serpens includes one cathodic and four anodic components. The molecular mass of the α and β chains of the cathodic component as well as the 2 α and 4 β of the anodic components were determined. Analysis of the intact α and β chains from cathodic hemoglobin and their proteolytic digestion products by high-resolution MS and MS/MS experiments resulted in 92 and 95 % sequence coverage of the α and β globins, respectively. The oxygen binding properties of both hemoglobin components were analyzed with respect to their interactions with their physiological effectors. Stripped cathodic hemoglobin displayed the highest oxygen affinity among Anguilliformes with no significant effect of pH on O2-affinity. In the presence of both chloride and organic phosphates, O2-affinity was strongly reduced, and cooperativity was enhanced; moreover, cathodic hemoglobin contains two indistinguishable GTP-binding sites. Stripped anodic hemoglobins exhibited both low O2-affinity and low cooperativity and a larger Bohr effect than cathodic hemoglobin. The cathodic hemoglobin of O. serpens and the corresponding component of Conger conger share the greatest structural and functional similarity among hemoglobin systems of Anguilliformes studied to date, consistent with their phylogenetic relationship.

Bladder urothelial carcinoma extending to rectal mucosa and presenting with rectal bleeding

PubMed Central

Aneese, Andrew M; Manuballa, Vinayata; Amin, Mitual; Cappell, Mitchell S

2017-01-01

An 87-year-old-man with prostate-cancer-stage-T1c-Gleason-6 treated with radiotherapy in 1996, recurrent prostate cancer treated with leuprolide hormonal therapy in 2009, and bladder-urothelial-carcinoma in situ treated with Bacillus-Calmette-Guerin and adriamycin in 2010, presented in 2015 with painless, bright red blood per rectum coating stools daily for 5 mo. Rectal examination revealed bright red blood per rectum; and a hard, fixed, 2.5 cm × 2.5 cm mass at the normal prostate location. The hemoglobin was 7.6 g/dL (iron saturation = 8.4%, indicating iron-deficiency-anemia). Abdominopelvic-CT-angiography revealed focal wall thickening at the bladder neck; a mass containing an air cavity replacing the normal prostate; and adjacent rectal invasion. Colonoscopy demonstrated an ulcerated, oozing, multinodular, friable, 2.5 cm × 2.5 cm mass in anterior rectal wall, at the usual prostate location. Histologic and immunohistochemical analysis of colonoscopic biopsies of the mass revealed poorly-differentiated-carcinoma of urothelial origin. At visceral angiography, the right-superior-rectal-artery was embolized to achieve hemostasis. The patient subsequently developed multiple new metastases and expired 13 mo post-embolization. Comprehensive literature review revealed 16 previously reported cases of rectal involvement from bladder urothelial carcinoma, including 11 cases from direct extension and 5 cases from metastases. Patient age averaged 63.7 ± 9.6 years (all patients male). Rectal involvement was diagnosed on average 13.5 ± 11.8 mo after initial diagnosis of bladder urothelial carcinoma. Symptoms included constipation/gastrointestinal obstruction-6, weight loss-5, diarrhea-3, anorexia-3, pencil thin stools-3, tenesmus-2, anorectal pain-2, and other-5. Rectal examination in 9 patients revealed annular rectal constriction-6, and rectal mass-3. The current patient had the novel presentation of daily bright red blood per rectum coating the stools simulating hemorrhoidal bleeding; the novel mechanism of direct bladder urothelial carcinoma extension into rectal mucosa via the prostate; and the novel aforementioned colonoscopic findings underlying the clinical presentation. PMID:28690772

Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men.

PubMed

Sjoberg, Daniel D; Vickers, Andrew J; Assel, Melissa; Dahlin, Anders; Poon, Bing Ying; Ulmert, David; Lilja, Hans

2018-06-01

Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of <7.5%, translating into 1.7% risk of prostate cancer death at 15 yr-a similar estimate to that of a man with a PSA of 1.6ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Nine-year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer.

PubMed

Dall'Era, Marc A; Lo, Mary J; Chen, Jaclyn; Cress, Rosemary; Hamilton, Ann S

2018-05-01

To the authors' knowledge, the survival benefit of local therapy in the setting of advanced prostate cancer remains unknown. The authors investigated whether prostate-directed treatment with either surgery or radiotherapy versus conservative treatment in the setting of locally advanced or metastatic disease was associated with improved survival within a cohort of men from the Centers for Disease Control and Prevention's (CDC) Breast and Prostate Cancer Data Quality and Patterns of Care Study (CDC POC-BP). Men diagnosed with locally advanced (cT3-T4 or N+ and M0) or metastatic prostate cancer were identified. The authors compared survival by treatment type, categorized as conservative (androgen deprivation therapy only) versus aggressive (radical prostatectomy or any type of radiotherapy). Nine-year overall survival and prostate cancer-specific survival were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to determine factors independently associated with 9-year prostate cancer-specific survival. For men with advanced, nonmetastatic prostate cancer, conservative treatment alone was associated with a 4 times higher likelihood of prostate cancer mortality compared with men treated with surgery (hazard ratio, 4.18; 95% confidence interval, 1.44-12.14). In contrast, no difference was found between conservative versus aggressive treatment after adjusting for covariates for men with metastatic disease. The 9-year prostate cancer-specific survival rate was 27% for those receiving aggressive treatment versus 24% for men undergoing conservative treatment. The authors did not observe a survival advantage with local therapy in addition to standard androgen deprivation therapy for men with metastatic prostate cancer. However, the results of the current study did affirm advantages in the setting of locally advanced disease. Aggressive local therapy in the setting of metastatic disease needs to be studied carefully before clinical adoption. Cancer 2018;124:1921-8. © 2018 American Cancer Society. © 2018 American Cancer Society.

Prospective validation of %p2PSA and the Prostate Health Index, in prostate cancer detection in initial prostate biopsies of Asian men, with total PSA 4-10 ng ml-1.

PubMed

Tan, Lincoln Gl; Tan, Yung Khan; Tai, Bee Choo; Tan, Karen Ml; Gauhar, Vineet; Tiong, Ho Yee; Hawkins, Robert Cw; Thamboo, Thomas P; Hong, Felicia Sk; Chiong, Edmund

2017-01-01

Despite its widespread use for prostate cancer screening, low specificity makes PSA a suboptimal biomarker, especially in the diagnostic "gray zone" of 4-10 ng ml-1 . False-positives lead to unnecessary biopsies with attendant morbidities. This is the first prospective validation study of %p2PSA and the Prostate Health Index (PHI) in Asian men presenting with a total PSA between 4.0 and 10 ng ml-1 . We studied 157 Asian men between 50 and 75 years old, with normal per rectal prostate examinations, undergoing their first prostate biopsy, using a standardized biopsy protocol, for PSA levels of 4-10 ng ml-1 . Thirty (19.1%) were found to have prostate cancer on biopsy. Statistically significant differences between patients with and without prostate cancer were found for total PSA, p2PSA, %p2PSA, and PHI. The areas under the curve of the receiver operating characteristic curve for total PSA, %fPSA, %p2PSA, and PHI were 0.479, 0.420, 0.695, and 0.794, respectively. PHI predicts prostatic biopsies results best. At a sensitivity of 90%, the specificity (95% CI) of PHI was 58.3%, more than triple the specificity of total PSA at 17.3%, potentially avoiding 77 (49%) unnecessary biopsies. Similar to studies in mainly Caucasian populations, we have prospectively shown that %p2PSA and PHI greatly outperform total and free to total PSA ratio, in the detection of prostate cancer at first biopsy. Higher PHI levels also correspond to increasing the risk of detecting GS ≥7 cancers. We have validated the use of PHI to aid decision-making regarding prostate biopsies in Asian men with serum PSA between 4 and 10 ng ml-1 .

Prostate cancer diagnosis in a resource-poor setting: the changing role of digital rectal examination.

PubMed

Ahmed, Muhammed

2011-07-01

We undertook this study in order to determine the current role of digital rectal examination (DRE) in the diagnosis of prostate cancer in a resource-poor setting. The diagnosis of prostate cancer has been revolutionized by the introduction of prostate-specific antigen (PSA), transrectal ultrasound (TRUS) for biopsy guidance and more efficient biopsy equipment, but they are not readily available in most developing countries. This is a prospective study of 131 patients with suspected prostate cancer based on clinical presentation, DRE and elevated PSA. The presence or absence of cancer was confirmed by biopsy and histologic examination. Patients with screen- or incidentally-detected prostate cancer were excluded. The most common symptom was the development of lower urinary tract symptoms (LUTS). All patients had abnormal DRE and indurated prostate was the most frequent finding (50%). The mean PSA was 33.9 ng/mL: of the 131 patients, 80 (61.1%) had a malignant histology following biopsy, 47 (35.9%) were benign and four (3.0%) were prostate intraepithelial neoplasia (PIN). The low specificity of DRE in the diagnosis of prostate cancer requires that it should be combined with other diagnostic modalities such as PSA and TRUS-guided prostate biopsy. Thus government and health-care providers in resource-poor countries must strive to make these facilities available in order to improve prostate cancer diagnosis.

Sleep disruption, chronotype, shift work, and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins.

PubMed

Dickerman, Barbra A; Markt, Sarah C; Koskenvuo, Markku; Hublin, Christer; Pukkala, Eero; Mucci, Lorelei A; Kaprio, Jaakko

2016-11-01

Sleep disruption and shift work have been associated with cancer risk, but epidemiologic evidence for prostate cancer remains limited. We aimed to prospectively investigate the association between midlife sleep- and circadian-related parameters and later prostate cancer risk and mortality in a population-based cohort of Finnish twins. Data were drawn from the Older Finnish Twin Cohort and included 11,370 twins followed from 1981 to 2012. Over the study period, 602 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between midlife sleep duration, sleep quality, chronotype, and shift work with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were employed to account for potential familial confounding. Compared to "definite morning" types, "somewhat evening" types had a significantly increased risk of prostate cancer (HR 1.3; 95 % CI 1.1, 1.6). Chronotype significantly modified the relationship between shift work and prostate cancer risk (p-interaction <0.001). We found no significant association between sleep duration, sleep quality, or shift work and prostate cancer risk in the overall analyses and no significant association between any sleep- or circadian-related parameter and risk in co-twin analyses. Neither sleep- nor circadian-related parameters were significantly associated with prostate cancer-specific mortality. The association between sleep disruption, chronotype, and shift work with prostate cancer risk and mortality has never before been studied in a prospective study of male twins. Our findings suggest that chronotype may be associated with prostate cancer risk and modify the association between shift work and prostate cancer risk. Future studies of circadian disruption and prostate cancer should account for this individual-level characteristic.

A Quantitative Model for the Dynamics of Serum Prostate-Specific Antigen as a Marker for Cancerous Growth

PubMed Central

Swanson, Kristin R.; True, Lawrence D.; Lin, Daniel W.; Buhler, Kent R.; Vessella, Robert; Murray, James D.

2001-01-01

Prostate-specific antigen (PSA) is an enzyme produced by both normal and cancerous prostate epithelial cells. Although PSA is the most widely used serum marker to detect and follow patients with prostatic adenocarcinoma, there are certain anomalies in the values of serum levels of PSA that are not understood. We developed a mathematical model for the dynamics of serum levels of PSA as a function of the tumor volume. Our model results show good agreement with experimental observations and provide an explanation for the existence of significant prostatic tumor mass despite a low-serum PSA. This result can be very useful in enhancing the use of serum PSA levels as a marker for cancer growth. PMID:11395397

Imaging Prostate Cancer With Prostate-Specific Membrane Antigen PET/CT and PET/MRI: Current and Future Applications.

PubMed

Hope, Thomas A; Afshar-Oromieh, Ali; Eiber, Matthias; Emmett, Louise; Fendler, Wolfgang P; Lawhn-Heath, Courtney; Rowe, Steven P

2018-06-27

The purpose of this article is to describe the large number of radiotracers being evaluated for prostate-specific membrane antigen (PSMA) PET, which is becoming a central tool in the staging of prostate cancer. PSMA PET is a highly promising modality for the staging of prostate cancer because of its higher detection rate compared with that of conventional imaging. Both PET/CT and PET/MRI offer benefits with PSMA radiotracers, and PSMA PET findings frequently lead to changes in management. It is imperative that subsequent treatment changes be evaluated to show improved outcomes. PSMA PET also has potential applications, including patient selection for PSMA-based radioligand therapy and evaluation of treatment response.

PSES-a Novel Prostate Specific Chimeric Enhancer for Prostate Cancer Gene Therapy

DTIC Science & Technology

2007-02-01

CMV-Luc R e la ti v e L u c if e ra s e a c ti v it y Figure 1 . D. 5.7 x 109 virus particles of Ad-CMV-luciferase () or Ad- PSES-luciferase...6. Rodriguez R , Schuur ER, Lim HY, Henderson GA, Simons JW, Henderson DR. Prostate attenuated repli- cation competent adenovirus (ARCA) CN706: a...12. Lee SJ, Kim HS, Yu R , et al. Novel prostate-specific promoter derived from PSA and PSMA enhancers. Mol Ther 2002;6:415–21. 13. Graham FL. Growth of

Prostate Specific or Enriched Genes as Composite Biomarkers for Prostate Cancer

DTIC Science & Technology

2008-02-01

isotope dilution by comparing to the 13C- or 15N-labeled reference peptides. The MRM method is best practiced utilizing a triple quadrupole mass...specific, androgen- regulated gene. Here, we evaluate its utility as a prostate cancer tissue marker for diagnosis and prognostic evaluation. Experimental...prevalence of adverse prognostic factors such as capsular penetration, seminal vesicle invasion, and positive surgical margins is rather high compared with

Management of Men with Prostate-specific Antigen Failure After Prostate Radiotherapy: The Case Against Early Androgen Deprivation.

PubMed

Brand, Douglas; Parker, Chris

2018-04-01

In men with prostate-specific antigen failure after radical radiotherapy, androgen deprivation therapy should be delayed until the site of recurrence is known to allow consideration of curative treatment options, to delay androgen deprivation therapy-related morbidity, and to enable earlier access to abiraterone and docetaxel. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Antagonizing effects of membrane-acting androgens on the eicosanoid receptor OXER1 in prostate cancer

PubMed Central

Kalyvianaki, Konstantina; Gebhart, Veronika; Peroulis, Nikolaos; Panagiotopoulou, Christina; Kiagiadaki, Fotini; Pediaditakis, Iosif; Aivaliotis, Michalis; Moustou, Eleni; Tzardi, Maria; Notas, George; Castanas, Elias; Kampa, Marilena

2017-01-01

Accumulating evidence during the last decades revealed that androgen can exert membrane initiated actions that involve signaling via specific kinases and the modulation of significant cellular processes, important for prostate cancer cell growth and metastasis. Results of the present work clearly show that androgens can specifically act at the membrane level via the GPCR oxoeicosanoid receptor 1 (OXER1) in prostate cancer cells. In fact, OXER1 expression parallels that of membrane androgen binding in prostate cancer cell lines and tumor specimens, while in silico docking simulation of OXER1 showed that testosterone could bind to OXER1 within the same grove as 5-OxoETE, the natural ligand of OXER1. Interestingly, testosterone antagonizes the effects of 5-oxoETE on specific signaling pathways and rapid effects such as actin cytoskeleton reorganization that ultimately can modulate cell migration and metastasis. These findings verify that membrane-acting androgens exert specific effects through an antagonistic interaction with OXER1. Additionally, this interaction between androgen and OXER1, which is an arachidonic acid metabolite receptor expressed in prostate cancer, provides a novel link between steroid and lipid actions and renders OXER1 as new player in the disease. These findings should be taken into account in the design of novel therapeutic approaches in prostate cancer. PMID:28290516

Simultaneous targeting of prostate stem cell antigen and prostate-specific membrane antigen improves the killing of prostate cancer cells using a novel modular T cell-retargeting system.

PubMed

Arndt, Claudia; Feldmann, Anja; Koristka, Stefanie; Cartellieri, Marc; Dimmel, Maria; Ehninger, Armin; Ehninger, Gerhard; Bachmann, Michael

2014-09-01

Recently, we described a novel modular platform technology in which T cell-recruitment and tumor-targeting domains of conventional bispecific antibodies are split to independent components, a universal effector module (EM) and replaceable monospecific/monovalent target modules (TMs) that form highly efficient T cell-retargeting complexes. Theoretically, our unique strategy should allow us to simultaneously retarget T cells to different tumor antigens by combining the EM with two or more different monovalent/monospecific TMs or even with bivalent/bispecific TMs, thereby overcoming limitations of a monospecific treatment such as the selection of target-negative tumor escape variants. In order to advance our recently introduced prostate stem cell antigen (PSCA)-specific modular system for a dual-targeting of prostate cancer cells, two additional TMs were constructed: a monovalent/monospecific TM directed against the prostate-specific membrane antigen (PSMA) and a bivalent/bispecific TM (bsTM) with specificity for PSMA and PSCA. The functionality of the novel dual-targeting strategies was analyzed by performing T cell activation and chromium release assays. Similar to the PSCA-specific modular system, the novel PSMA-specific modular system mediates an efficient target-dependent and -specific tumor cell lysis at low E:T ratios and picomolar Ab concentrations. Moreover, by combination of the EM with either the bispecific TM directed to PSMA and PSCA or both monospecifc TMs directed to either PSCA or PSMA, dual-specific targeting complexes were formed which allowed us to kill potential escape variants expressing only one or the other target antigen. Overall, the novel modular system represents a promising tool for multiple tumor targeting. © 2014 Wiley Periodicals, Inc.

Detection of prostate-specific antigen with biomolecule-gated AlGaN/GaN high electron mobility transistors

NASA Astrophysics Data System (ADS)

Li, Jia-dong; Cheng, Jun-jie; Miao, Bin; Wei, Xiao-wei; Xie, Jie; Zhang, Jin-cheng; Zhang, Zhi-qiang; Wu, Dong-min

2014-07-01

In order to improve the sensitivity of AlGaN/GaN high electron mobility transistor (HEMT) biosensors, a simple biomolecule-gated AlGaN/GaN HEMT structure was designed and successfully fabricated for prostate specific antigen (PSA) detection. UV/ozone was used to oxidize the GaN surface and then a 3-aminopropyl trimethoxysilane (APTES) self-assembled monolayer was bound to the sensing region. This monolayer serves as a binding layer for attachment of the prostate specific antibody (anti-PSA). The biomolecule-gated AlGaN/GaN HEMT sensor shows a rapid and sensitive response when the target prostate-specific antigen in buffer solution was added to the antibody-immobilized sensing area. The current change showed a logarithm relationship against the PSA concentration from 0.1 pg/ml to 0.993 ng/ml. The sensitivity of 0.215% is determined for 0.1 pg/ml PSA solution. The above experimental result of the biomolecule-gated AlGaN/GaN HEMT biosensor suggested that this biosensor might be a useful tool for prostate cancer screening.

Age-Specific Prostate Specific Antigen Cutoffs for Guiding Biopsy Decision in Chinese Population

PubMed Central

Xu, Jianfeng; Jiang, Haowen; Ding, Qiang

2013-01-01

Background Age-specific prostate specific antigen (PSA) cutoffs for prostate biopsy have been widely used in the USA and European countries. However, the application of age-specific PSA remains poorly understood in China. Methods Between 2003 and 2012, 1,848 men over the age of 40, underwent prostate biopsy for prostate cancer (PCa) at Huashan Hospital, Shanghai, China. Clinical information and blood samples were collected prior to biopsy for each patient. Men were divided into three age groups (≤60, 61 to 80, and >80) for analyses. Digital rectal examination (DRE), transrectal ultrasound (prostate volume and nodule), total PSA (tPSA), and free PSA (fPSA) were also included in the analyses. Logistic regression was used to build the multi-variate model. Results Serum tPSA levels were age-dependent (P = 0.008), while %fPSA (P = 0.051) and PSAD (P = 0.284) were age-independent. At a specificity of 80%, the sensitivities for predicting PCa were 83%, 71% and 68% with tPSA cutoff values of 19.0 ng/mL (age≤60),21.0 ng/mL (age 61–80), and 23.0 ng/mL (age≥81). Also, sensitivities at the same tPSA levels were able to reach relatively high levels (70%–88%) for predicting high-grade PCa. Area (AUC) under the receive operating curves (ROCs) of tPSA, %fPSA, PSAD and multi-variate model were different in age groups. When predicting PCa, the AUC of tPSA, %fPSA, PSAD and multi-variate model were 0.90, 0.57, 0.93 and 0.87 respectively in men ≤60 yr; 0.82, 0.70, 0.88 and 0.86 respectively in men 61–80 yr; 0.79, 0.78, 0.87 and 0.88 respectively in men>80 yr. When predicting Gleason Score ≥7 or 8 PCa, there were no significant differences between AUCs of each variable. Conclusion Age-specific PSA cutoff values for prostate biopsy should be considered in the Chinese population. Indications for prostate biopsies (tPSA, %fPSA and PSAD) should be considered based on age in the Chinese population. PMID:23825670

Genome-wide DNA methylation measurements in prostate tissues uncovers novel prostate cancer diagnostic biomarkers and transcription factor binding patterns.

PubMed

Kirby, Marie K; Ramaker, Ryne C; Roberts, Brian S; Lasseigne, Brittany N; Gunther, David S; Burwell, Todd C; Davis, Nicholas S; Gulzar, Zulfiqar G; Absher, Devin M; Cooper, Sara J; Brooks, James D; Myers, Richard M

2017-04-17

Current diagnostic tools for prostate cancer lack specificity and sensitivity for detecting very early lesions. DNA methylation is a stable genomic modification that is detectable in peripheral patient fluids such as urine and blood plasma that could serve as a non-invasive diagnostic biomarker for prostate cancer. We measured genome-wide DNA methylation patterns in 73 clinically annotated fresh-frozen prostate cancers and 63 benign-adjacent prostate tissues using the Illumina Infinium HumanMethylation450 BeadChip array. We overlaid the most significantly differentially methylated sites in the genome with transcription factor binding sites measured by the Encyclopedia of DNA Elements consortium. We used logistic regression and receiver operating characteristic curves to assess the performance of candidate diagnostic models. We identified methylation patterns that have a high predictive power for distinguishing malignant prostate tissue from benign-adjacent prostate tissue, and these methylation signatures were validated using data from The Cancer Genome Atlas Project. Furthermore, by overlaying ENCODE transcription factor binding data, we observed an enrichment of enhancer of zeste homolog 2 binding in gene regulatory regions with higher DNA methylation in malignant prostate tissues. DNA methylation patterns are greatly altered in prostate cancer tissue in comparison to benign-adjacent tissue. We have discovered patterns of DNA methylation marks that can distinguish prostate cancers with high specificity and sensitivity in multiple patient tissue cohorts, and we have identified transcription factors binding in these differentially methylated regions that may play important roles in prostate cancer development.

The Role of Positron Emission Tomography With (68)Gallium (Ga)-Labeled Prostate-specific Membrane Antigen (PSMA) in the Management of Patients With Organ-confined and Locally Advanced Prostate Cancer Prior to Radical Treatment and After Radical Prostatectomy.

PubMed

Rai, Bhavan Prasad; Baum, Richard Paul; Patel, Amit; Hughes, Robert; Alonzi, Roberto; Lane, Tim; Adshead, Jim; Vasdev, Nikhil

2016-09-01

The role of positron emission tomography (PET) with (68)Gallium (Ga)-labeled prostate-specific membrane antigen (PSMA) imaging for prostate cancer is gaining prominence. Current imaging strategies, despite having progressed significantly, have limitations, in particular their ability to diagnose metastatic lymph node involvement. Preliminary results of PET with (68)Ga-labeled PSMA have shown encouraging results, particularly in the recurrent prostate cancer setting. Furthermore, the ability of PET with (68)Ga-labeled PSMA of playing a dual diagnostic and therapeutic setting (theranostics) is currently being investigated as well. PET with (68)Ga-labeled PSMA certainly has a role to play in bridging some of the voids in contemporary prostate cancer imaging tools. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Health Changes in Low Income Men Transitioning from a State Funded Prostate Cancer Program to Comprehensive Insurance.

PubMed

Nabhani, Jamal A; Kuang, Ruby; Liu, Hui; Kwan, Lorna; Litwin, Mark S

2018-07-01

We evaluated the effect of transitioning from a prostate cancer specific treatment program to comprehensive insurance under the ACA (Patient Protection and Affordable Care Act) on the physical, mental and prostate cancer related health of poor, previously uninsured men. We assessed general and prostate cancer specific health related quality of life using the RAND SF-12v2™ (12-Item Short Form Survey, version 2) and the UCLA PCI (Prostate Cancer Index) at 3 time points in 24 men who transitioned to comprehensive insurance as the insured group relative to 39 who remained in the prostate cancer program as the control group. We used mixed effects models controlling for treatment and patient factors to measure health differences between the groups during the transition period. Demographics, prostate cancer treatment patterns, and mental, physical and general health were similar before transition in the control and insured groups. After transition men who gained insurance coverage reported significantly worse physical health than men who remained in the prostate cancer program (p = 0.0038). After adjustment in the mixed effects model physical health remained worse in men who gained insurance (p = 0.0036). Mental health and prostate cancer related quality of life did not differ with time between the groups. Compared to controls who remained in the state funded prostate cancer treatment program for poor, uninsured men, newly insured men reported worse physical health after transitioning to ACA coverage. Providers and policy makers may draw important lessons from understanding the mechanisms of this paradoxical worsening in physical health after gaining insurance. These results inform the development of disease specific models of care in the broader health insurance context. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Characterization of neuroendocrine differentiation in human benign prostate and prostatic adenocarcinoma.

PubMed

Aprikian, A G; Cordon-Cardo, C; Fair, W R; Reuter, V E

1993-06-15

This report describes an immunohistopathologic analysis characterizing the incidence, pattern of distribution, and hormonal content of neuroendocrine (NE) cells in human benign prostate and prostatic adenocarcinoma. Formaldehyde-fixed, paraffin-embedded material from 15 benign prostates, 31 primary prostatic adenocarcinomas, 16 metastatic lesions, 21 primary tumors treated with short-course diethylstilbestrol (DES), and 10 specimens from hormone-refractory patients were examined. NE cells were identified using silver histochemistry and a panel of immunohistochemical NE markers (chromogranin-A, serotonin, neuron-specific enolase), and specific peptide hormone antibodies. NE cells were identified in all benign prostates. NE cells were identified in 77% of primary untreated adenocarcinomas with no significant differences with respect to pathologic stage. NE cells were found isolated and dispersed in the tumor, composing the minority of malignant cells. Double-labeling and serial section immunohistochemistry demonstrated the coexpression of prostate-specific antigen (PSA) in NE cells. In addition to serotonin, some tumors expressed multiple hormone immunoreactivities. NE cells were identified in 56% of metastatic deposits, with a similar pattern of distribution. In DES-treated cases, NE cells were found consistently in the adjacent benign epithelium, whereas 52% of tumors contained NE cells. Hormone-refractory tumors contained NE cells in 60% of cases. This analysis demonstrates that a significant proportion of primary and metastatic prostatic adenocarcinomas contain a subpopulation of NE cells, the expression of which does not appear to be suppressed with androgen ablation and does not correlate with pathologic stage. Furthermore, NE cells coexpress PSA, suggesting a common precursor cell of origin. The elaboration of biogenic amines and neuropeptides suggests that NE cells dispersed in prostatic carcinoma may play a paracrine growth-regulatory role.

Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma.

PubMed

Chuang, Ai-Ying; DeMarzo, Angelo M; Veltri, Robert W; Sharma, Rajni B; Bieberich, Charles J; Epstein, Jonathan I

2007-08-01

The histologic distinction between high-grade prostate cancer and infiltrating high-grade urothelial cancer may be difficult, and has significant implications because each disease may be treated very differently (ie, hormone therapy for prostate cancer and chemotherapy for urothelial cancer). Immunohistochemistry of novel and established prostatic and urothelial markers using tissue microarrays (TMAs) were studied. Prostatic markers studied included: prostate-specific antigen (PSA), prostein (P501s), prostate-specific membrane antigen (PSMA), NKX3.1 (an androgen-related tumor suppressor gene), and proPSA (pPSA) (precursor form of PSA). "Urothelial markers" included high molecular weight cytokeratin (HMWCK), p63, thrombomodulin, and S100P (placental S100). TMAs contained 38 poorly differentiated prostate cancers [Gleason score 8 (n=2), Gleason score 9 (n=18), Gleason score 10 (n=18)] and 35 high-grade invasive urothelial carcinomas from radical prostatectomy and cystectomy specimens, respectively. Each case had 2 to 8 tissue spots (0.6-mm diameter). If all spots for a case showed negative staining, the case was called negative. The sensitivities for labeling prostate cancers were PSA (97.4%), P501S (100%), PSMA (92.1%), NKX3.1 (94.7%), and pPSA (94.7%). Because of PSA's high sensitivity on the TMA, we chose 41 additional poorly differentiated primary (N=36) and metastatic (N=5) prostate carcinomas which showed variable PSA staining at the time of diagnosis and performed immunohistochemistry on routine tissue sections. Compared to PSA, which on average showed 18.8% of cells with moderate to strong positivity, cases stained for P501S, PSMA, and NKX3.1 had on average 42.5%, 53.7%, 52.9% immunoreactivity, respectively. All prostatic markers showed excellent specificity. HMWCK, p63, thrombomodulin, and S100P showed lower sensitivities in labeling high-grade invasive urothelial cancer in the TMAs with 91.4%, 82.9%, 68.6%, and 71.4% staining, respectively. These urothelial markers were relatively specific with only a few prostate cancers showing scattered (

Long leukocyte telomere length in prostate cancer patients at diagnosis is associated with poor metastasis-free and cancer-specific survival.

PubMed

Svenson, Ulrika; Roos, Göran; Wikström, Pernilla

2017-02-01

Previous studies have suggested that leukocyte telomere length is associated with risk of developing prostate cancer. Investigations of leukocyte telomere length as a prognostic factor in prostate cancer are, however, lacking. In this study, leukocyte telomere length was investigated both as a risk marker, comparing control subjects and patient risk groups (based on serum levels of prostate-specific antigen, tumor differentiation, and tumor stage), and as a prognostic marker for metastasis-free and cancer-specific survival. Relative telomere length was measured by a well-established quantitative polymerase chain reaction method in 415 consecutively sampled individuals. Statistical evaluation included 162 control subjects without cancer development during follow-up and 110 untreated patients with newly diagnosed localized prostate cancer at the time of blood draw. Leukocyte telomere length did not differ significantly between control subjects and patients, or between patient risk groups. Interestingly, however, and in line with our previous results in breast and kidney cancer patients, relative telomere length at diagnosis was an independent prognostic factor. Patients with long leukocyte telomeres (⩾median) had a significantly worse prostate cancer-specific and metastasis-free survival compared to patients with short telomere length. In contrast, for patients who died of other causes than prostate cancer, long relative telomere length was not coupled to shorter survival time. To our knowledge, these results are novel and give further strength to our hypothesis that leukocyte telomere length might be used as a prognostic marker in malignancy.

Prostate cancer involving bilateral seminal vesicles along with bone and testicular metastases: a case report.

PubMed

Gao, Qingqiang; Chen, Jianhuai; Dai, Yutian

2018-03-09

In the past 20 years, the incidence of prostate cancer has risen rapidly. It has been ranked as the third most common malignant tumor of the male genitourinary system. Testicular metastasis is uncommon in prostate cancer. Most cases are incidentally found in the treatment of prostate cancer with orchiectomy. Therefore, we believed it was necessary to report the case of our patient with this disease. We present a case of a 69-year-old Han Chinese man with a high total prostate-specific antigen level. A transrectal ultrasound-guided prostate biopsy was performed. A pathology report showed prostate cancer tissue with a Gleason score of 4 + 4 = 8/10. Imaging findings suggested that the prostate cancer tissue involved bilateral seminal vesicles and multiple bones. Next, radioactive seed implantation was carried out, and endocrine therapy was continued after the operation. Then enlargement of the left scrotum was found along with a total prostate-specific antigen level of 19.21 ng/ml. Computed tomography of the middle abdomen and pelvic cavity revealed 2.0 × 1.3-cm lesions of the left testis. The patient underwent a left testicular high resection and right orchiectomy. The postoperative pathology report showed metastatic prostate cancer cells in the left testis. Testicular metastasis of prostate cancer is rare. Therefore, a testicular physical examination is necessary for patients without relapse to avoid a missed diagnosis. Testicular metastasis should be treated according to the principle of treatment for advanced prostate adenocarcinoma if testicular metastasis of prostate adenocarcinoma is detected.

Prognostic Importance of Small Prostate Size in Men Receiving Definitive Prostate Brachytherapy

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

Taira, Al V.; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org; Galbreath, Robert W.

Purpose: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. Methods and Materials: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size ({<=}20 cm{sup 3}) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. Results: Median prostate sizemore » for the entire cohort was 32.7 cm{sup 3}. For the 167 men with small prostates, median prostate size was 17.4 cm{sup 3}. There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. Conclusion: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.« less

Adoptive Immunotherapy Combined with Hematopoietic Cell Transplantation as a Therapeutic Approach to Treatment of Prostate Cancer

DTIC Science & Technology

2008-10-01

NOTES 14. ABSTRACT We determined that cell lysates prepared from canine prostate tissue was immunogenic when injected in female dogs. In addition...to the known prostate antigen, canine prostate specific esterase (CPSE), we identified by molecular weight several other proteins against which the...appeared to be superior to prostate lysate antigen-loaded canine autologous dendritic cells when both were injected subcutaneously near the popliteal lymph

A Community-Driven Intervention for Prostate Cancer Screening in African Americans

ERIC Educational Resources Information Center

Patel, Kushal; Ukoli, Flora; Liu, Jianguo; Beech, Derrick; Beard, Katina; Brown, Byron; Sanderson, Maureen; Kenerson, Donna; Cooper, Leslie; Canto, Marie; Blot, Bill; Hargreaves, Margaret

2013-01-01

The purpose of the study was to assess the impact of an educational intervention on prostate cancer screening behavior and knowledge. Participants were 104 African American men, 45 years and older, who had not been screened for prostate cancer with a prostate-specific antigen and/or digital rectal exam within the past year. All participants…

Immunohistochemical expression of ERG in the molecular epidemiology of fatal prostate cancer study.

PubMed

Weinmann, Sheila; Van Den Eeden, Stephen K; Haque, Reina; Chen, Chuhe; Richert-Boe, Kathryn; Schwartzman, Jacob; Gao, Lina; Berry, Deborah L; Kallakury, Bhaskar V S; Alumkal, Joshi J

2013-09-01

Gene fusions between the ERG transcription factor and the androgen-regulated gene TMPRSS2 occur in a subset of prostate cancers and contribute to transformation of prostatic epithelial cells. Prior reports have used fluorescence in situ hybridization (FISH) or quantitative PCR (QPCR) to determine the presence of TMPRSS2-ERG fusions or ERG expression, respectively. Recently, several groups have reported on immunohistochemistry (IHC) to measure ERG expression, which is much more readily performed in clinical practice. However, the prior studies examining ERG expression by IHC had small sample sizes or they failed to clarify the association of ERG protein expression with important clinico-pathological features or prostate cancer-specific mortality. To address these deficits, we evaluated ERG expression by IHC in 208 radical prostatectomy samples from the Kaiser Permanente Molecular Epidemiology of Fatal Prostate Cancer (MEFPC) study, a case-control study of prostate cancer-specific mortality. Nuclear ERG expression was seen in neoplastic prostate epithelia in 49 of the samples (23.7%). ERG expression in tumor cells was associated with higher tumor stage (OR = 2.0, 95% confidence interval 1.0-4.0, P value = 0.04). ERG immunoreactivity was positively associated with prostate cancer-specific mortality, although the confidence interval was wide (OR = 1.9, 95% confidence interval 0.88-4.0, P value = 0.10). Our results demonstrate that ERG protein expression is readily quantifiable with an existing commercial antibody. Evaluating ERG protein expression may improve our ability to identify the subset of more aggressive, invasive prostate cancers. © 2013 Wiley Periodicals, Inc.

P110β Inhibition Reduces Histone H3K4 Di-Methylation in Prostate Cancer.

PubMed

Pang, Jun; Yang, Yue-Wu; Huang, Yiling; Yang, Jun; Zhang, Hao; Chen, Ruibao; Dong, Liang; Huang, Yan; Wang, Dongying; Liu, Jihong; Li, Benyi

2017-02-01

Epigenetic alteration plays a major role in the development and progression of human cancers, including prostate cancer. Histones are the key factors in modulating gene accessibility to transcription factors and post-translational modification of the histone N-terminal tail including methylation is associated with either transcriptional activation (H3K4me2) or repression (H3K9me3). Furthermore, phosphoinositide 3-kinase (PI3 K) signaling and the androgen receptor (AR) are the key determinants in prostate cancer development and progression. We recently showed that prostate-targeted nano-micelles loaded with PI3 K/p110beta specific inhibitor TGX221 blocked prostate cancer growth in vitro and in vivo. Our objective of this study was to determine the role of PI3 K signaling in histone methylation in prostate cancer, with emphasis on histone H3K4 methylation. PI3 K non-specific inhibitor LY294002 and p110beta-specific inhibitor TGX221 were used to block PI3 K/p110beta signaling. The global levels of H3K4 and H3K9 methylation in prostate cancer cells and tissue specimens were evaluated by Western blot assay and immunohistochemical staining. A synthetic androgen R1881 was used to stimulate AR activity in prostate cancer cells. A castration-resistant prostate cancer (CRPC) specific human tissue microarray (TMA) was used to assess the global levels of H3K4me2 methylation by immunostaining approach. Our data revealed that H3K4me2 levels were significantly elevated after androgen stimulation. With RNA silencing and pharmacology approaches, we further defined that inhibition of PI3 K/p110beta activity through gene-specific knocking down and small chemical inhibitor TGX221 abolished androgen-stimulated H3K4me2 methylation. Consistently, prostate cancer-targeted delivery of TGX221 in vivo dramatically reduced the global levels of H3K4me2 as assessed by immunohistochemical staining on tissue section of mouse xenografts from CRPC cell lines 22RV1 and C4-2. Finally, immunostaining data revealed a strong H3K4me2 immunosignal in CRPC tissues compared to primary tumors and benign prostate tissues. Taken together, our results suggest that PI3 K/p110beta-dependent signaling is involved in androgen-stimulated H3K4me2 methylation in prostate cancer, which might be used as a novel biomarker for disease prognosis and targeted therapy. Prostate 77:299-308, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Measurement of affective and activity pain interference using the Brief Pain Inventory (BPI): Cancer and Leukemia Group B 70903.

PubMed

Atkinson, Thomas M; Halabi, Susan; Bennett, Antonia V; Rogak, Lauren; Sit, Laura; Li, Yuelin; Kaplan, Ellen; Basch, Ethan

2012-11-01

The Brief Pain Inventory (BPI) was designed to yield separate scores for pain intensity and interference. It has been proposed that the pain interference factor can be further broken down into unique factors of affective (e.g., mood) and activity (e.g., work) interference. The purpose of this analysis was to confirm this affective/activity interference dichotomy. A retrospective confirmatory factor analysis was completed for a sample of 184 individuals diagnosed with castrate-resistant prostate cancer (age 40-86, mean = 65.46, 77% White non-Hispanic) who had been administered the BPI as part of Cancer and Leukemia Group B trial 9480. A one-factor model was compared against two-factor and three-factor models that were developed based on the design of the instrument. Root mean squared error of approximation (0.075), comparative fit index (0.971), and change in chi-square, given the corresponding change in degrees of freedom (13.33, P < 0.05) values for the three-factor model (i.e., pain intensity, activity interference, and affective interference), were statistically superior in comparison with the one- and two-factor models. This three-factor structure was found to be invariant across age, mean prostate-specific antigen, and hemoglobin levels. These results confirm that the BPI can be used to quantify the degree to which pain separately interferes with affective and activity aspects of a patient's everyday life. These findings will provide clinical trialists, pharmaceutical sponsors, and regulators with confidence in the flexibility of the BPI as they consider the use of this instrument to assist with understanding the patient experience as it relates to treatment. Wiley Periodicals, Inc.

Prostate tumor-induced angiogenesis is blocked by exosomes derived from menstrual stem cells through the inhibition of reactive oxygen species

PubMed Central

Alcayaga-Miranda, Francisca; González, Paz L.; Lopez-Verrilli, Alejandra; Varas-Godoy, Manuel; Aguila-Díaz, Carolina; Contreras, Luis; Khoury, Maroun

2016-01-01

Mesenchymal stem cells (MSCs) secrete exosomes that are capable of modifying the tumor environment through different mechanisms including changes in the cancer-cell secretome. This activity depends on their cargo content that is largely defined by their cellular origin. Endometrial cells are fine regulators of the angiogenic process during the menstrual cycle that includes an angiostatic condition that is associated with the end of the cycle. Hence, we studied the angiogenic activity of menstrual stem cells (MenSCs)-secreted exosomes on prostate PC3 tumor cells. Our results showed that exosomes induce a reduction in VEGF secretion and NF-κB activity. Lower reactive oxygen species (ROS) production in exosomes-treated cells was detected by the DCF method, suggesting that the inhibition of the intracellular ROS impacts both NF-κB and VEGF pathways. We confirmed using tubule formation and plug transplantation assays that MenSCs-exosomes suppress the secretion of pro-angiogenic factors by the PC3 cells in a ROS-dependent manner. The inhibition of the tumor angiogenesis and, consequently, the tumor growth was also confirmed using a xenograft mouse model. Additionally, the anti-tumoral effect was associated with a reduction of tumor hemoglobin content, vascular density and inhibition of VEGF and HIF-1α expression. Importantly, we demonstrate that the exosomes anti-angiogenic effect is specific to the menstrual cell source, as bone marrow MSCs-derived exosomes showed an opposite effect on the VEGF and bFGF expression in tumor cells. Altogether, our results indicate that MenSCs-derived exosomes acts as blockers of the tumor-induced angiogenesis and therefore could be suitable for anti-cancer therapies. PMID:27286448

Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism: a multicenter, randomized controlled trial in Japan (EARTH Study)

PubMed Central

Konaka, Hiroyuki; Sugimoto, Kazuhiro; Orikasa, Hideki; Iwamoto, Teruaki; Takamura, Toshinari; Takeda, Yoshiyu; Shigehara, Kazuyoshi; Iijima, Masashi; Koh, Eitetsu; Namiki, Mikio

2016-01-01

Androgen replacement therapy (ART) efficacy on late-onset hypogonadism (LOH) has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores (IPSS), International Index of Erectile Function-5 (IIEF-5) scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients > 40 years with LOH were randomly assigned to either the ART (n = 169) or control groups (n = 165). Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey (SF-36) scale (P = 0.0318). ART was also associated with significant decreases in waist circumstance (P = 0.002) and serum triglyceride (TG) (P = 0.013) and with significant increases in whole-body and leg muscle mass volumes (P = 0.071 and 0.0108, respectively), serum hemoglobin (P < 0.001), IPSS voiding subscore (P = 0.0418), and the second question on IIEF-5 (P = 0.0049). There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area. PMID:25761833

Automated computer-aided detection of prostate cancer in MR images: from a whole-organ to a zone-based approach

NASA Astrophysics Data System (ADS)

Litjens, G. J. S.; Barentsz, J. O.; Karssemeijer, N.; Huisman, H. J.

2012-03-01

MRI has shown to have great potential in prostate cancer localization and grading, but interpreting those exams requires expertise that is not widely available. Therefore, CAD applications are being developed to aid radiologists in detecting prostate cancer. Existing CAD applications focus on the prostate as a whole. However, in clinical practice transition zone cancer and peripheral zone cancer are considered to have different appearances. In this paper we present zone-specific CAD, in addition to an atlas based segmentation technique which includes zonal segmentation. Our CAD system consists of a detection and a classification stage. Prior to the detection stage the prostate is segmented into two zones. After segmentation features are extracted. Subsequently a likelihood map is generated on which local maxima detection is performed. For each local maximum a region is segmented. In the classification stage additional shape features are calculated, after which the regions are classified. Validation was performed on 288 data sets with MR-guided biopsy results as ground truth. Freeresponse Receiver Operating Characteristic (FROC) analysis was used for statistical evaluation. The difference between whole-prostate and zone-specific CAD was assessed using the difference between the FROCs. Our results show that evaluating the two zones separately results in an increase in performance compared to whole-prostate CAD. The FROC curves at .1, 1 and 3 false positives have a sensitivity of 0.0, 0.55 and 0.72 for whole-prostate and 0.08, 0.57 and 0.80 for zone-specific CAD. The FROC curve of the zone-specific CAD also showed significantly better performance overall (p < 0.05).

Prostate-targeted biodegradable nanoparticles loaded with androgen receptor silencing constructs eradicate xenograft tumors in mice

PubMed Central

Yang, Jun; Xie, Sheng-Xue; Huang, Yiling; Ling, Min; Liu, Jihong; Ran, Yali; Wang, Yanlin; Thrasher, J Brantley; Berkland, Cory; Li, Benyi

2012-01-01

Background Prostate cancer is the major cause of cancer death in men and the androgen receptor (AR) has been shown to play a critical role in the progression of the disease. Our previous reports showed that knocking down the expression of the AR gene using a siRNA-based approach in prostate cancer cells led to apoptotic cell death and xenograft tumor eradication. In this study, we utilized a biodegradable nanoparticle to deliver the therapeutic AR shRNA construct specifically to prostate cancer cells. Materials & methods The biodegradable nanoparticles were fabricated using a poly(dl-lactic-co-glycolic acid) polymer and the AR shRNA constructs were loaded inside the particles. The surface of the nanoparticles were then conjugated with prostate-specific membrane antigen aptamer A10 for prostate cancer cell-specific targeting. Results A10-conjugation largely enhanced cellular uptake of nanoparticles in both cell culture- and xenograft-based models. The efficacy of AR shRNA encapsulated in nanoparticles on AR gene silencing was confirmed in PC-3/AR-derived xenografts in nude mice. The therapeutic property of A10-conjugated AR shRNA-loaded nanoparticles was evaluated in xenograft models with different prostate cancer cell lines: 22RV1, LAPC-4 and LNCaP. Upon two injections of the AR shRNA-loaded nanoparticles, rapid tumor regression was observed over 2 weeks. Consistent with previous reports, A10 aptamer conjugation significantly enhanced xenograft tumor regression compared with nonconjugated nanoparticles. Discussion These data demonstrated that tissue-specific delivery of AR shRNA using a biodegradable nanoparticle approach represents a novel therapy for life-threatening prostate cancers. PMID:22583574

Phase II Study of Dutasteride for Recurrent Prostate Cancer During Androgen Deprivation Therapy

PubMed Central

Shah, Satyan K.; Trump, Donald L.; Sartor, Oliver; Tan, Wei; Wilding, Gregory E.; Mohler, James L.

2010-01-01

Purpose We determined the response rate to and safety of a dual 5α-reductase inhibitor, dutasteride, in men with castration recurrent prostate cancer. Materials and Methods A total of 28 men with asymptomatic castration recurrent prostate cancer were treated with 3.5 mg dutasteride daily (luteinizing hormone-releasing hormone treatment continued), and evaluated monthly for response and toxicity. Eligibility included appropriate duration antiandrogen withdrawal, baseline prostate specific antigen 2.0 ng/ml or greater and a new lesion on bone scan, increase in measurable disease using Response Evaluation Criteria in Solid Tumors criteria, or 2 or more consecutive prostate specific antigen measurements increased over baseline. Outcomes were progression, stable disease, partial response (prostate specific antigen less than 50% of enrollment for 4 or more weeks) or complete response. Results There were 25 evaluable men with a mean age of 70 years (range 57 to 88), a mean prostate specific antigen of 61.9 ng/ml (range 5.0 to 488.9) and mean Gleason score 8 (range 6 to 10), 15 of whom had bone metastases. Eight men had 10 grade 3 or higher adverse events using National Cancer Institute Common Terminology Criteria, all of which were judged to be unrelated to treatment. Of the 25 men 14 had disease progression by 2 months, 9 had stable (2.5, 3, 3, 4, 4, 5, 5, 8.5, 9 months) disease, 2 had a partial response and none had a complete response. Overall median time to progression was 1.87 months (range 1 to 10, 95% CI 1.15–3.91). Conclusions Dutasteride rarely produces biochemical responses in men with castration recurrent prostate cancer. However, further study is warranted given its favorable safety profile. PMID:19091347

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

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

PubMed

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

2016-01-01

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

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

PubMed Central

Toivanen, Roxanne

2017-01-01

Prostate organogenesis is a complex process that is primarily mediated by the presence of androgens and subsequent mesenchyme-epithelial interactions. The investigation of prostate development is partly driven by its potential relevance to prostate cancer, in particular the apparent re-awakening of key developmental programs that occur during tumorigenesis. However, our current knowledge of the mechanisms that drive prostate organogenesis is far from complete. Here, we provide a comprehensive overview of prostate development, focusing on recent findings regarding sexual dimorphism, bud induction, branching morphogenesis and cellular differentiation. PMID:28400434

Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer.

PubMed

Brawer, M K; Cheli, C D; Neaman, I E; Goldblatt, J; Smith, C; Schwartz, M K; Bruzek, D J; Morris, D L; Sokoll, L J; Chan, D W; Yeung, K K; Partin, A W; Allard, W J

2000-05-01

Determining serum total prostate specific antigen (PSA) has proved to be a valuable diagnostic aid for detecting prostatic carcinoma, although the lack of specificity has limited its usefulness. Studies indicate that the use of percent free PSA would improve specificity while maintaining sensitivity. Since complexed PSA represents the major proportion of measurable PSA in serum, we determined whether it represents a single test alternative to the use of percent free PSA for the early detection of prostate cancer. Archival serum was obtained from 385 men with no evidence of malignancy on biopsy and 272 with biopsy confirmed prostate cancer. We determined the concentration and proportion of total, complexed and free PSA. Receiver operating characteristics analysis using total PSA results from all samples (range 0.32 to 117 ng./ml.) indicated that the areas under the curve for complexed PSA alone as well as the free-to-total and complexed-to-total PSA ratios were similar and significantly greater than those for total PSA alone. Within the range of 85% to 95% sensitivity receiver operating characteristics analysis revealed that the specificity of complexed PSA was higher than that of total PSA and equivalent to that of the free-to-total PSA ratio. We noted a similar improvement in specificity in the 4 to 10 ng./ml. total PSA range. Using published cutoff values for complexed, total and percent free PSA when total PSA was in the 4 to 10 ng./ml. range the sensitivity and specificity of complexed and percent free PSA were similar. Within the 4 to 10 ng./ml. total PSA range the population of patients with no evidence of malignancy and complexed PSA below the upper limit was different with respect to total PSA from that with no evidence of malignancy and free PSA greater than 25%. The measurement of complexed PSA represents an alternative to the use of percent free PSA, although the patient populations identified by the 2 tests are different.

Development of a Nanotechnology Platform for Prostate Cancer Gene Therapy

DTIC Science & Technology

2011-07-01

NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b . ABSTRACT U c. THIS PAGE U UU 19b. TELEPHONE NUMBER (include...condense pDNA into nano-size particles (nanocarriers), b ) a PC-3 specific targeting motif (TM) to target prostate cancer cells, c) an endosome...particles (nanocarriers), b ) a PC-3 specific targeting motif (TM) to target prostate cancer cells, c) an endosome disrupting motif (EDM) to disrupt

Highly specific expression of luciferase gene in lungs of naive nude mice directed by prostate-specific antigen promoter

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

Li Hongwei; Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA 22908; Li Jinzhong

PSA promoter has been demonstrated the utility for tissue-specific toxic gene therapy in prostate cancer models. Characterization of foreign gene overexpression in normal animals elicited by PSA promoter should help evaluate therapy safety. Here we constructed an adenovirus vector (AdPSA-Luc), containing firefly luciferase gene under the control of the 5837 bp long prostate-specific antigen promoter. A charge coupled device video camera was used to non-invasively image expression of firefly luciferase in nude mice on days 3, 7, 11 after injection of 2 x 10{sup 9} PFU of AdPSA-Luc virus via tail vein. The result showed highly specific expression of themore » luciferase gene in lungs of mice from day 7. The finding indicates the potential limitations of the suicide gene therapy of prostate cancer based on selectivity of PSA promoter. By contrary, it has encouraging implications for further development of vectors via PSA promoter to enable gene therapy for pulmonary diseases.« less

Allosteric properties of hemoglobin and the plasma membrane of the erythrocyte: new insights in gas transport and metabolic modulation.

PubMed

De Rosa, Maria Cristina; Carelli Alinovi, Cristiana; Galtieri, Antonio; Russo, Annamaria; Giardina, Bruno

2008-02-01

Within the red blood cell the hemoglobin molecule is subjected to modulation mechanisms, namely homo- and heterotropic interactions, which optimize its functional behavior to the specific physiological requirements. At the cellular level, these modulation mechanisms are utilized to perform a number of other functions that are not minor with respect to the basic function of oxygen transport. Here we report some key examples concerning: (i) the interaction of hemoglobin with band 3 and its influence on glucose metabolism; (ii) the role of the ligand-linked quaternary transition of hemoglobin in the control of "NO bioactivity" and of gas diffusion; (iii) the interaction of plasma membrane with the various oxidative derivatives of the hemoglobin molecule. (c) 2008 IUBMB.

Prostate-Specific Antigen and Prostate-Specific Antigen Velocity as Threshold Indicators in 11C-Acetate PET/CTAC Scanning for Prostate Cancer Recurrence

PubMed Central

Dusing, Reginald W.; Peng, Warner; Lai, Sue-Min; Grado, Gordon L.; Holzbeierlein, Jeffrey M.; Thrasher, J. Brantley; Hill, Jacqueline; Van Veldhuizen, Peter J.

2014-01-01

Purpose The aim of this study was to identify which patient characteristics are associated with the highest likelihood of positive findings on 11C-acetate PET/computed tomography attenuation correction (CTAC) (PET/CTAC) scan when imaging for recurrent prostate cancer. Methods From 2007 to 2011, 250 11C-acetate PET/CTAC scans were performed at a single institution on patients with prostate cancer recurrence after surgery, brachytherapy, or external beam radiation. Of these patients, 120 met our inclusion criteria. Logistic regression analysis was used to examine the relationship between predictability of positive findings and patients’ characteristics, such as prostate-specific antigen (PSA) level at the time of scan, PSA kinetics, Gleason score, staging, and type of treatment before scan. Results In total, 68.3% of the 120 11C-acetate PET/CTAC scans were positive. The percentage of positive scans and PSA at the time of scanning and PSA velocity (PSAV) had positive correlations. The putative sensitivity and specificity were 86.6% and 65.8%, respectively, when a PSA level greater than 1.24 ng/mL was used as the threshold for scanning. The putative sensitivity and specificity were 74% and 75%, respectively, when a PSAV level greater than 1.32 ng/mL/y was used as the threshold. No significant associations were found between scan positivity and age, PSA doubling time, Gleason score, staging, or type of treatment before scanning. Conclusions This retrospective study suggests that threshold models of PSA greater than 1.24 ng/mL or PSAV greater than 1.32 ng/mL per year are independent predictors of positive findings in 11C-acetate PET/CTAC imaging of recurrent prostate cancer. PMID:25036021

Prostate specific antigen bounce is related to overall survival in prostate brachytherapy.

PubMed

Hinnen, Karel A; Monninkhof, Evelyn M; Battermann, Jan J; van Roermund, Joep G H; Frank, Steven J; van Vulpen, Marco

2012-02-01

To investigate the association between prostate specific antigen (PSA) bounce and disease outcome after prostate brachytherapy. We analyzed 975 patients treated with (125)I implantation monotherapy between 1992 and 2006. All patients had tumor Stage ≤ 2c, Gleason score ≤ 7 prostate cancer, a minimum follow-up of 2 years with at least four PSA measurements, and no biochemical failure in the first 2 years. Median follow-up was 6 years. Bounce was defined as a PSA elevation of +0.2 ng/mL with subsequent decrease to previous nadir. We used the Phoenix +2 ng/mL definition for biochemical failure. Additional endpoints were disease-specific and overall survival. Multivariate Cox regression analysis was performed to adjust for potential confounding factors. Bounce occurred in 32% of patients, with a median time to bounce of 1.6 years. More than 90% of bounces took place in the first 3 years after treatment and had disappeared within 2 years of onset. Ten-year freedom from biochemical failure, disease-specific survival, and overall survival rates were, respectively, 90%, 99%, and 88% for the bounce group and 70%, 93%, and 82% for the no-bounce group. Only 1 patient (0.3%) died of prostate cancer in the bounce group, compared with 40 patients (6.1%) in the no-bounce group. Adjusted for confounding, a 70% biochemical failure risk reduction was observed for patients experiencing a bounce (hazard ratio 0.31; 95% confidence interval 0.20-0.48). A PSA bounce after prostate brachytherapy is strongly related to better outcome in terms of biochemical failure, disease-specific survival, and overall survival. Copyright © 2012 Elsevier Inc. All rights reserved.

Predicting the risk of patients with biopsy Gleason score 6 to harbor a higher grade cancer.

PubMed

Gofrit, Ofer N; Zorn, Kevin C; Taxy, Jerome B; Lin, Shang; Zagaja, Gregory P; Steinberg, Gary D; Shalhav, Arieh L

2007-11-01

Prostate cancer Gleason score 3 + 3 = 6 is currently the most common score assigned on prostatic biopsies. We analyzed the clinical variables that predict the likelihood of a patient with biopsy Gleason score 6 to harbor a higher grade tumor. The study population consisted of 448 patients with a mean age of 59.1 years who underwent radical prostatectomy between February 2003 to October 2006 for Gleason score 6 adenocarcinoma. The effect of preoperative variables on the probability of a Gleason score upgrade on final pathological evaluation was evaluated using logistic regression, and classification and regression tree analysis. Gleason score upgrade was found in 91 of 448 patients (20.3%). Logistic regression showed that only serum prostate specific antigen and the greatest percent of cancer in a core were significantly associated with a score upgrade (p = 0.0014 and 0.023, respectively). Classification and regression tree analysis showed that the risk of a Gleason score upgrade was 62% when serum prostate specific antigen was higher than 12 ng/ml and 18% when serum prostate specific antigen was 12 ng/ml or less. In patients with serum prostate specific antigen lower than 12 ng/ml the risk of a score upgrade could be dichotomized at a greatest percent of cancer in a core of 5%. The risk was 22.6% and 10.5% when the greatest percent of cancer in a core was higher than 5% and 5% or lower, respectively. The probability of patients with a prostate biopsy Gleason score of 6 to conceal a Gleason score of 7 or higher can be predicted using serum prostate specific antigen and the greatest percent of cancer in a core. With these parameters it is possible to predict upgrade rates as high as 62% and as low as 10.5%.

Estimate of population coverage with the prostate specific antigen (PSA) test to screen for prostate cancer in a metropolitan area of northern Italy.

PubMed

Russo, A; Autelitano, M; Bellini, A; Bisanti, L

2002-01-01

The use of the prostate specific antigen (PSA) test in the period 1999-2000 in a population of 311 822 men, aged 40 years or more, resident in Milan, Italy, was examined. Data were drawn from the outpatient database of the local health information system. A total of 139 350 PSA tests were used in 83 943 subjects. Overall, 26.9% of the male population aged 40 or older, with no history of prostate cancer, received a PSA test in the 2 year study period. For subjects older than 50 the rate rose to 34%. Results show a high coverage of the male population in northern Italy with screening using the PSA test for prostate cancer.

CD8+ T-cell responses rapidly select for antigen-negative tumor cells in the prostate.

PubMed

Bak, S Peter; Barnkob, Mike Stein; Wittrup, K Dane; Chen, Jianzhu

2013-12-01

Stimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respectively. However, the long-term effects of immune responses on selection and outgrowth of antigen-negative tumor cells in specific tumor types must be determined to understand and achieve long-term therapeutic effects. In this study, we have investigated the expression of a tumor-specific antigen in situ after treatment with tumor-specific CD8(+) T cells in an autochthonous mouse model of prostate cancer. After T-cell treatment, aggregates of dead antigen-positive tumor cells were concentrated in the lumen of the prostate gland and were eventually eliminated from the prostate tissue. Despite the elimination of antigen-positive tumor cells, prostate tumor continued to grow in T-cell-treated mice. Interestingly, the remaining tumor cells were antigen negative and downregulated MHC class I expression. These results show that CD8(+) T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells. These findings provide insights into the requirements for an effective cancer immunotherapy within the prostate that not only induces potent immune responses but also avoids selection and outgrowth of antigen-negative tumor cells. ©2013 AACR.

Stage-specific incidence rates and trends of prostate cancer by age, race, and ethnicity, United States, 2004-2014.

PubMed

Li, Jun; Siegel, David A; King, Jessica B

2018-05-01

Current literature shows different findings on the contemporary trends of distant-stage prostate cancer incidence, in part, due to low study population coverage and wide age groupings. This study aimed to examine the stage-specific incidence rates and trends of prostate cancer by age (5-year grouping), race, and ethnicity using nationwide cancer registry data. Data on prostate cancer cases came from the 2004-2014 United States Cancer Statistics data set. We calculated stage-specific incidence and 95% confidence intervals by age (5-year age grouping), race, and ethnicity. To measure the changes in rates over time, we calculated annual percentage change (APC). We identified 2,137,054 incident prostate cancers diagnosed during 2004-2014, with an age-adjusted incidence rate of 453.8 per 100,000. Distant-stage prostate cancer incidence significantly decreased during 2004-2010 (APC = -1.2) and increased during 2010-2014 (APC = 3.3). Significant increases in distant prostate cancer incidence also occurred in men aged older than or equal to 50 years except men aged 65-74 and older than or equal to 85 years, in men with white race (APC = 3.9), and non-Hispanic ethnicity (APC = 3.5). Using data representing over 99% of U.S. population, we found that incidence rates of distant-stage prostate cancer significantly increased during 2010-2014 among men in certain ages, in white, and with non-Hispanic ethnicity. Published by Elsevier Inc.

Promoter methylation of MCAM, ERα and ERβ in serum of early stage prostate cancer patients.

PubMed

Brait, Mariana; Banerjee, Mithu; Maldonado, Leonel; Ooki, Akira; Loyo, Myriam; Guida, Elisa; Izumchenko, Evgeny; Mangold, Leslie; Humphreys, Elizabeth; Rosenbaum, Eli; Partin, Alan; Sidransky, David; Hoque, Mohammad Obaidul

2017-02-28

Prostate cancer (PC) is the second most common cancer among men worldwide. Currently, the most common non-invasive approach for screening and risk assessment of PC is measuring the level of serum prostate-specific antigen (PSA). However, the sensitivity of PSA is 42.8 % and specificity is 41.1%. As a result, the serum PSA test leads to numerous unneeded biopsies. Therefore, a rigorous search for biomarkers for early detection of PC is ongoing. In this study, we aim to assess a panel of epigenetic markers in an intend to develop an early detection test for PC. The sensitivity and specificity of hypermethylation of MCAM was 66% and 73% respectively which is an improvement from the sensitivity and specificity of PSA. Considering a combination marker panel of MCAM, ERα and ERβ increased the sensitivity to 75% and the specificity became 70% for the minimally invasive early detection test of PC. Sixteen primary matched tumor and serum were analyzed by quantitative methylation specific PCR (QMSP) to determine analytical and clinical sensitivity of the genes tested (SSBP2, MCAM, ERα, ERβ, APC, CCND2, MGMT, GSTP1, p16 and RARβ2). Additionally, serum samples from eighty four cases of PC, thirty controls and seven cases diagnosed as high grade Prostatic Intraepithelial Neoplasia (HGPIN) were analyzed. Promoter methylation of MCAM, ERα and ERβ have a potential to be utilized as biomarker for the early detection of prostate PC as their sensitivity and specificity seem to be better than serum PSA in our cohort of samples. After robust validation in a larger prospective cohort, our findings may reduce the numbers of unwarranted prostate biopsies.

Cancer Specific Mortality in Men Diagnosed with Prostate Cancer before Age 50 Years: A Nationwide Population Based Study.

PubMed

Thorstenson, Andreas; Garmo, Hans; Adolfsson, Jan; Bratt, Ola

2017-01-01

We compared clinical characteristics and cancer specific mortality in men diagnosed with prostate cancer before vs after age 50 years. A total of 919 men 35 to 49 years old and 45,098 men 50 to 66 years old who were diagnosed with prostate cancer between 1998 and 2012 were identified in PCBaSe (Prostate Cancer data Base Sweden). Cancer specific mortality was compared among age groups (35 to 49, 50 to 59, 60 to 63 and 64 to 66 years) with and without adjusting for cancer characteristics, comorbidity and education in a multivariable Cox proportional hazards model. Clinical cancer characteristics indicated that most nonmetastatic cancer in men younger than 50 years was detected after prostate specific antigen testing. The proportion of nonmetastatic vs metastatic disease at diagnosis was similar in all age groups. A strong association between younger age and poor prognosis was apparent in men in whom metastatic disease was diagnosed before age 50 to 55 years. The crude and adjusted HRs of cancer specific mortality were 1.41 (95% CI 1.12-1.79) and 1.28 (95% CI 1.01-1.62) in men diagnosed before age 50 and at age 50 to 59 years, respectively. In men with nonmetastatic disease crude cancer specific mortality increased with older age but adjusted cancer specific mortality was similar in all age groups. Our findings suggest that an aggressive form of metastatic prostate cancer is particularly common in men younger than 50 to 55 years. Genetic studies and trials of intensified systemic treatment are warranted in this patient group. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Association of Hemoglobin Concentration With Total and Cause-Specific Mortality in a Cohort of Postmenopausal Women.

PubMed

Kabat, Geoffrey C; Kim, Mimi Y; Verma, Amit K; Manson, JoAnn E; Lessin, Lawrence S; Kamensky, Victor; Lin, Juan; Wassertheil-Smoller, Sylvia; Rohan, Thomas E

2016-05-15

Anemia and low and high levels of hemoglobin have been associated with increased mortality and morbidity. However, most studies have measured hemoglobin at only 1 time point, and few studies have considered possible reverse causation. We used data from the Women's Health Initiative, in which baseline hemoglobin was measured in 160,081 postmenopausal women and year 3 hemoglobin was measured in 75,658 participants, to examine the associations of hemoglobin concentration with total mortality, coronary heart disease mortality, and cancer mortality. Women were enrolled from 1993 to 1998 and followed for a median of 16 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline hemoglobin and the mean of baseline + year 3 hemoglobin. Both low and high deciles of baseline hemoglobin were positively associated with all 3 outcomes in the total cohort. In analyses restricted to women with 2 measurements, a low mean hemoglobin level was robustly and positively associated with all 3 outcomes, after exclusion of the early years of follow-up. High mean hemoglobin was also associated with increased risk of total mortality, whereas associations with heart disease mortality and cancer mortality were weaker and inconsistent. Our results provide evidence that low and high levels of hemoglobin are associated with increased risk of mortality in otherwise healthy women. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

68Ga-PSMA-11 PET/CT in Newly Diagnosed Carcinoma of the Prostate: Correlation of Intraprostatic PSMA Uptake with Several Clinical Parameters.

PubMed

Koerber, Stefan A; Utzinger, Maximilian T; Kratochwil, Clemens; Kesch, Claudia; Haefner, Matthias F; Katayama, Sonja; Mier, Walter; Iagaru, Andrei H; Herfarth, Klaus; Haberkorn, Uwe; Debus, Juergen; Giesel, Frederik L

2017-12-01

68 Ga-prostate-specific membrane antigen (PSMA) PET/CT is a promising diagnostic tool for patients with prostate cancer. Our study evaluates SUVs in benign prostate tissue and malignant, intraprostatic tumor lesions and correlates results with several clinical parameters. Methods: One hundred four men with newly diagnosed prostate carcinoma and no previous therapy were included in this study. SUV max was measured and correlated with biopsy findings and MRI. Afterward, data were compared with current prostate-specific antigen (PSA) values, Gleason score (GS), and d'Amico risk classification. Results: In this investigation a mean SUV max of 1.88 ± 0.44 in healthy prostate tissue compared with 10.77 ± 8.45 in malignant prostate lesions ( P < 0.001) was observed. Patients with higher PSA, higher GS, and higher d'Amico risk score had statistically significant higher PSMA uptake on PET/CT ( P < 0.001 each). Conclusion: PSMA PET/CT is well suited for detecting the intraprostatic malignant lesion in patients with newly diagnosed prostate cancer. Our findings indicate a significant correlation of PSMA uptake with PSA, GS, and risk classification according to the d'Amico scale. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Evidence that insulin-like growth factor I and growth hormone are required for prostate gland development.

PubMed

Ruan, W; Powell-Braxton, L; Kopchick, J J; Kleinberg, D L

1999-05-01

Insulin-like growth factor I (IGF-I) has been implicated as a factor that may predispose one to prostate cancer. However, no specific relationship between IGF-I and prostate development or cancer in vivo has been established. To determine whether IGF-I was important in prostate development, we examined prostate architecture in IGF-I(-/-) null mice and wild-type littermates. Glands from 44-day-old IGF-I-deficient animals were not only smaller than those from wild-type mice, but also had fewer terminal duct tips and branch points and deficits in tertiary and quaternary branching (P < 0.0001), indicating a specific impairment in gland structure. Administration of des(1-3)-IGF-I for 7 days partially reversed the deficit by increasing those parameters of prostate development (P < 0.006). That IGF-I production probably mediates an effect of GH in this process was indicated by the observations that GH antagonist transgenic mice also had significantly impaired prostate development (P < 0.0002) and that bovine GH had no independent effect on stimulating prostate development in IGF-I null animals. The data indicate that IGF-I deficiency is the proximate cause of impaired prostate development and give credence to the idea that, like testosterone, GH and IGF-I may be involved in prostate cancer growth as an extension of a normal process.

ANALYSIS OF TMEFF2 ALLOGRAFTS AND TRANSGENIC MOUSE MODELS REVEALS ROLES IN PROSTATE REGENERATION AND CANCER

PubMed Central

Corbin, JM.; Overcash, RF.; Wren, JD.; Coburn, A.; Tipton, GJ.; Ezzell, JA.; McNaughton, KK.; Fung, KM; Kosanke, SD.; Ruiz-Echevarria, MJ

2015-01-01

BACKGROUND Previous results from our lab indicate a tumor suppressor role for the transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) in prostate cancer (PCa). Here, we further characterize this role and uncover new functions for TMEFF2 in cancer and adult prostate regeneration. METHODS The role of TMEFF2 was examined in PCa cells using Matrigel™ cultures and allograft models of PCa cells. In addition, we developed a transgenic mouse model that expresses TMEFF2 from a prostate specific promoter. Anatomical, histological and metabolic characterizations of the transgenic mouse prostate were conducted. The effect of TMEFF2 in prostate regeneration was studied by analyzing branching morphogenesis in the TMEFF2-expressing mouse lobes and alterations in branching morphogenesis were correlated with the metabolomic profiles of the mouse lobes. The role of TMEFF2 in prostate tumorigenesis in whole animals was investigated by crossing the TMEFF2 transgenic mice with the TRAMP mouse model of PCa and analyzing the histopathological changes in the progeny. RESULTS Ectopic expression of TMEFF2 impairs growth of PCa cells in Matrigel or allograft models. Surprisingly, while TMEFF2 expression in the TRAMP mouse did not have a significant effect on the glandular prostate epithelial lesions, the double TRAMP/TMEFF2 transgenic mice displayed an increased incidence of neuroendocrine type tumors. In addition, TMEFF2 promoted increased branching specifically in the dorsal lobe of the prostate suggesting a potential role in developmental processes. These results correlated with data indicating an alteration in the metabolic profile of the dorsal lobe of the transgenic TMEFF2 mice. CONCLUSIONS Collectively, our results confirm the tumor suppressor role of TMEFF2 and suggest that ectopic expression of TMEFF2 in mouse prostate leads to additional lobe-specific effects in prostate regeneration and tumorigenesis. This points to a complex and multifunctional role for TMEFF2 during PCa progression. PMID:26417683

Analysis of TMEFF2 allografts and transgenic mouse models reveals roles in prostate regeneration and cancer.

PubMed

Corbin, Joshua M; Overcash, Ryan F; Wren, Jonathan D; Coburn, Anita; Tipton, Greg J; Ezzell, Jennifer A; McNaughton, Kirk K; Fung, Kar-Ming; Kosanke, Stanley D; Ruiz-Echevarria, Maria J

2016-01-01

Previous results from our lab indicate a tumor suppressor role for the transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) in prostate cancer (PCa). Here, we further characterize this role and uncover new functions for TMEFF2 in cancer and adult prostate regeneration. The role of TMEFF2 was examined in PCa cells using Matrigel(TM) cultures and allograft models of PCa cells. In addition, we developed a transgenic mouse model that expresses TMEFF2 from a prostate specific promoter. Anatomical, histological, and metabolic characterizations of the transgenic mouse prostate were conducted. The effect of TMEFF2 in prostate regeneration was studied by analyzing branching morphogenesis in the TMEFF2-expressing mouse lobes and alterations in branching morphogenesis were correlated with the metabolomic profiles of the mouse lobes. The role of TMEFF2 in prostate tumorigenesis in whole animals was investigated by crossing the TMEFF2 transgenic mice with the TRAMP mouse model of PCa and analyzing the histopathological changes in the progeny. Ectopic expression of TMEFF2 impairs growth of PCa cells in Matrigel or allograft models. Surprisingly, while TMEFF2 expression in the TRAMP mouse did not have a significant effect on the glandular prostate epithelial lesions, the double TRAMP/TMEFF2 transgenic mice displayed an increased incidence of neuroendocrine type tumors. In addition, TMEFF2 promoted increased branching specifically in the dorsal lobe of the prostate suggesting a potential role in developmental processes. These results correlated with data indicating an alteration in the metabolic profile of the dorsal lobe of the transgenic TMEFF2 mice. Collectively, our results confirm the tumor suppressor role of TMEFF2 and suggest that ectopic expression of TMEFF2 in mouse prostate leads to additional lobe-specific effects in prostate regeneration and tumorigenesis. This points to a complex and multifunctional role for TMEFF2 during PCa progression. © 2015 Wiley Periodicals, Inc.

Bacterial prostatitis.

PubMed

Gill, Bradley C; Shoskes, Daniel A

2016-02-01

The review provides the infectious disease community with a urologic perspective on bacterial prostatitis. Specifically, the article briefly reviews the categorization of prostatitis by type and provides a distillation of new findings published on bacterial prostatitis over the past year. It also highlights key points from the established literature. Cross-sectional prostate imaging is becoming more common and may lead to more incidental diagnoses of acute bacterial prostatitis. As drug resistance remains problematic in this condition, the reemergence of older antibiotics such as fosfomycin, has proven beneficial. With regard to chronic bacterial prostatitis, no clear clinical risk factors emerged in a large epidemiological study. However, bacterial biofilm formation has been associated with more severe cases. Surgery has a limited role in bacterial prostatitis and should be reserved for draining of a prostatic abscess or the removal of infected prostatic stones. Prostatitis remains a common and bothersome clinical condition. Antibiotic therapy remains the basis of treatment for both acute and chronic bacterial prostatitis. Further research into improving prostatitis treatment is indicated.

Progesterone receptor expression during prostate cancer progression suggests a role of this receptor in stromal cell differentiation.

PubMed

Yu, Yue; Yang, Ou; Fazli, Ladan; Rennie, Paul S; Gleave, Martin E; Dong, Xuesen

2015-07-01

The progesterone receptor, like the androgen receptor, belongs to the steroid receptor superfamily. Our previous studies have reported that the PR is expressed specifically in prostate stroma. PR inhibits proliferation of, and regulates cytokine secretion by stromal cells. However, PR protein expression in cancer-associated stroma during prostate cancer progression has not been profiled. Since the phenotypes of prostate stromal cells change dynamically as tumors progress, whether the PR plays a role in regulating stromal cell differentiation needs to be investigated. Immunohistochemistry assays measured PR protein levels on human prostate tissue microarrays containing 367 tissue cores from benign prostate, prostate tumors with different Gleason scores, tumors under various durations of castration therapy, and tumors at the castration-resistant stage. Immunoblotting assays determined whether PR regulated the expression of alpha smooth muscle actin (α-SMA), vimentin, and fibroblast specific protein (FSP) in human prostate stromal cells. PR protein levels decreased in cancer-associated stroma when compared with that in benign prostate stroma. This reduction in PR expression was not correlated with Gleason scores. PR protein levels were elevated by castration therapy, but reduced to pre-castration levels when tumors progressed to the castration-resistant stage. Enhanced PR expression in human prostate stromal cells increased α-SMA, but decreased vimentin and FSP protein levels ligand-independently. These results suggest that PR plays an active role in regulating stromal cell phenotypes during prostate cancer progression. © 2015 Wiley Periodicals, Inc.

Identification and Targeting of Tyrosine Kinase Activity in Prostate Cancer Initiation, Progression, and Metastasis

DTIC Science & Technology

2012-10-01

accomplishments. Aim 1: Identify the specific tyrosine kinases activated during initiation and progression of genetically altered prostate cancer... Genetics Departmental Retreat (October 2011). (see appendices) • Presented research findings at the AACR Advances in Prostate Cancer Research Conference... genetic backgrounds. However, preliminary data suggests that phosphopeptides from metastatic tumors do indeed segregate from primary prostate tumors and

GTI-2040 and Docetaxel in Treating Patients With Recurrent, Metastatic, or Unresectable Locally Advanced Non-Small Cell Lung Cancer, Prostate Cancer, or Other Solid Tumors

ClinicalTrials.gov

2013-01-23

Recurrent Non-small Cell Lung Cancer; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

DTIC Science & Technology

2015-10-01

prostate cancer bone metastasis through the phagocytosis of apoptotic tumor cells (efferocytosis). Specific Aims: 1. To identify the phagocytic ...2: To identify the phagocytic /efferocytic macrophage population in the tumor microenvironment of prostate bone metastases and determine its ability...preparation for Cancer Research. We obtained an array of prostate cancer tissue including bone metastasis (N=72) and stained the tissue for the phagocytic

225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer.

PubMed

Kratochwil, Clemens; Bruchertseifer, Frank; Giesel, Frederik L; Weis, Mirjam; Verburg, Frederik A; Mottaghy, Felix; Kopka, Klaus; Apostolidis, Christos; Haberkorn, Uwe; Morgenstern, Alfred

2016-12-01

Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to 225 Ac-PSMA-617 therapy. 68 Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of 225 Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with 68 Ga-PSMA-11 PET/CT. Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect. Targeted α-therapy with 225 Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Inhibition of 5α-Reductase in Rat Prostate Reveals Differential Regulation of Androgen-Response Gene Expression by Testosterone and Dihydrotestosterone

PubMed Central

Dadras, Soheil S.; Cai, Xiaoyan; Abasolo, Ibane; Wang, Zhou

2001-01-01

The growth and development of some of the male sex accessory organs such as the prostate requires the conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase. To provide insights into the role of testosterone versus DHT in the prostate, we studied the impact of finasteride, a potent and specific inhibitor of 5α-reductase, on the expression of prostatic androgen-response genes in testis-intact rats and in 7-day castrated rats. Finasteride inhibition of the conversion of testosterone to DHT was confirmed by measuring serum and intraprostatic androgens. As expected, finasteride treatment caused a reduction in the wet weight of the prostate in the testis-intact rats and inhibited the testosterone-stimulated prostatic regrowth in the 7-day castrated rats. Although finasteride treatment had little or no effect on the expression of the surveyed androgen-response genes in testis-intact rats, its administration enhanced the expression of many androgen-response genes during the testosterone-stimulated regrowth of the regressed prostate in castrated rats. These observations suggest that testosterone is more potent than DHT in stimulating the expression of many androgen-response genes in the regressed prostate. The expression of androgen-response genes is mainly prostate specific and thus is likely to be associated with androgen-dependent prostatic differentiation. Therefore, testosterone is more potent than DHT in inducing differentiation and weaker in stimulating proliferation during prostate regrowth. The fact that testosterone is a strong inducer of prostatic differentiation has potential clinical implications. PMID:11444528

Incidental Finding of Cryptococcus on Prostate Biopsy for Prostate Adenocarcinoma Following Cardiac Transplant: Case Report and Review of the Literature.

PubMed

Shah, Sujal I; Bui, Hai; Velasco, Nelson; Rungta, Shilpa

2017-11-06

BACKGROUND Cryptococcus is the third most common invasive fungal organism in immunocompromised patients, including transplant patients, and usually involves the central nervous system and lungs, with a median time to infection of 25 months. We report a case of Cryptococcus of the prostate gland, found as an incidental finding on prostate biopsy for prostate adenocarcinoma, four months following cardiac transplantation. CASE REPORT A 62-year-old male African-American who had a cardiac transplant four months previously, underwent a six-core prostate biopsy for a two-year history of increasing prostate-specific antigen (PSA) levels, and a recent history of non-specific urinary tract symptoms. A prostatic adenocarcinoma, Gleason grade 4+4=8, was diagnosed on histopathology, and 'foamy' cells were seen in the biopsies. Histochemical stains, including Grocott methenamine silver (GMS), and periodic acid-Schiff (PAS) showed abundant round and oval 5-7 µm diameter fungal elements; mucicarmine highlighted the fungal polysaccharide capsule, diagnostic for Cryptococcus. Cryptococcal antigen detection was made by the latex agglutination test and cultures. We reviewed the literature and found 70 published cases (from 1946-2008) of Cryptococcus of the prostate gland, with only one previous case presenting five years following cardiac transplantation. CONCLUSIONS Fungal infections of the prostate are rare, and occur mainly in immunocompromised patients. We present a unique case of prostatic Cryptococcus found incidentally at four months following cardiac transplantation. This case report highlights the need to consider atypical fungal infection as a differential diagnosis for prostatitis in immunosuppressed patients, including transplant patients.

Enhanced detection sensitivity of prostate-specific antigen via PSA-conjugated gold nanoparticles based on localized surface plasmon resonance: GNP-coated anti-PSA/LSPR as a novel approach for the identification of prostate anomalies.

PubMed

Jazayeri, M H; Amani, H; Pourfatollah, A A; Avan, A; Ferns, G A; Pazoki-Toroudi, H

2016-10-01

Prostate-specific antigen (PSA) is used to screen for prostate disease, although it has several limitations in its application as an organ-specific or cancer-specific marker. Furthermore, a highly specific/sensitive and/or label-free identification of PSA still remains a challenge in the diagnosis of prostate anomalies. We aimed to develop a gold nanoparticle (GNP)-conjugated anti-PSA antibody-based localized surface plasmon resonance (LSPR) as a novel approach to detect prostatic disease. A total of 25 nm colloidal gold particles were prepared followed by conjugation with anti-PSA pAb (GNPs-PSA pAb). LSPR was used to monitor the absorption changes of the aggregation of the particles. The size, shape and stability of the GNP-anti-PSA were evaluated by dynamic light scattering transmission electron microscopy (TEM) and zetasizer. The GNPs-conjugated PSA-pAb was successfully synthesized and subsequently characterized using ultraviolet absorption spectroscopy and TEM to determine the size distribution, crystallinity and stability of the particles (for example, stability of GNP: 443 mV). To increase the stability of the particles, we pegylated GNPs using an N-(3-dimethylaminopropyl)-N*-ethylcarbodiimide hydrochloride (EDC)/N-hydroxylsuccinimide (NHS) linker (for example, stability of GNP after pegylation: 272 mV). We found a significant increase in the absorbance and intensity of the particles with extinction peak at 545/2 nm, which was shifted by ~1 nm after conjugation. To illustrate the potential of the GNPs-PSA pAb to bind specifically to PSA, LSPR was used. We found that the extinction peak shifted 3 nm for a solution of 100 nM unlabeled antigen. In summary, we have established a novel approach for improving the efficacy/sensitivity of PSA in the assessment of prostate disease, supporting further investigation on the diagnostic value of GNP-conjugated anti-PSA/LSPR for the detection of prostate cancer.

68Ga-PSMA PET/CT for the detection of bone metastasis in recurrent prostate cancer and a PSA level <2 ng/ml: Two case reports and a literature review

PubMed Central

Petersen, Lars J.; Nielsen, Julie B.; Dettmann, Katja; Fisker, Rune V.; Haberkorn, Uwe; Stenholt, Louise; Zacho, Helle D.

2017-01-01

Localization of prostate cancer recurrence, particularly in the bones, is a major challenge with standard of care imaging in patients with biochemical recurrence following curatively intended treatment. Gallium-68-labeled prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on 68Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (<2 ng/ml) and PSA doubling time >6 months. The bone metastases were verified by supplementary imaging with 18F-sodium fluoride PET/CT and magnetic resonance imaging as well as biochemical responses to androgen deprivation therapy. Therefore, 68Ga-PSMA PET/CT is promising for the restaging of patients with prostate cancer with biochemical recurrence, including patients with low PSA levels and low PSA kinetics. PMID:28685078

Bombesin functionalized 64Cu-copper sulfide nanoparticles for targeted imaging of orthotopic prostate cancer.

PubMed

Cai, Huawei; Xie, Fang; Mulgaonkar, Aditi; Chen, Lihong; Sun, Xiankai; Hsieh, Jer-Tsong; Peng, Fangyu; Tian, Rong; Li, Lin; Wu, Changqiang; Ai, Hua

2018-05-22

To synthesize and evaluate the imaging potential of Bom-PEG-[ 64 Cu]CuS nanoparticles (NPs) in orothotopic prostate tumor. [ 64 Cu]CuS NPs were synthesized in aqueous solution by 64 CuCl 2 and Na 2 S reaction. Then PEG linker with or without bombesin peptide were conjugated to the surface of [ 64 Cu]CuS NPs to produce Bom-PEG-[ 64 Cu]CuS and PEG-[ 64 Cu]CuS NPs. These two kinds of NPs were used for testing specific uptake in prostate cancer cells in vitro and imaging of orthotopic prostate tumor in vivo. Bom-PEG-[ 64 Cu]CuS and PEG-[ 64 Cu]CuS NPs were successfully synthesized with core diameter of approximately 5 nm. Radioactive cellular uptake revealed that Bom-PEG-[ 64 Cu]CuS was able to specifically bind to prostate cancer cells, and the microPET-CT imaging indicated clear visualization of orthotopic prostate tumors. Radiolabeled Bom-PEG-[ 64 Cu]CuS NPs have potential as an ideal agent for orthotopic prostate tumor imaging by microPET-CT.

Characterization of Desmoglein Expression in the Normal Prostatic Gland. Desmoglein 2 Is an Independent Prognostic Factor for Aggressive Prostate Cancer

PubMed Central

Barber, Alison G.; Castillo-Martin, Mireia; Bonal, Dennis M.; Rybicki, Benjamin A.; Christiano, Angela M.; Cordon-Cardo, Carlos

2014-01-01

Purpose The expression of desmogleins (DSGs), which are known to be crucial for establishing and maintaining the cell-cell adhesion required for tissue integrity, has been well characterized in the epidermis and hair follicle; however, their expression in other epithelial tissues such as prostate is poorly understood. Although downregulation of classical cadherins, such as E-cadherin, has been described in prostate cancer tissue samples, the expression of desmogleins has only been previously reported in prostate cancer cell lines. In this study we characterized desmoglein expression in normal prostate tissues, and further investigated whether Desmoglein 2 (DSG2) expression specifically can serve as a potential clinical prognostic factor for patients diagnosed with primary prostate cancer. Experimental Design We utilized immunofluorescence to examine DSG2 expression in normal prostate (n = 50) and in a clinically well-characterized cohort of prostate cancer patients (n = 414). Correlation of DSG2 expression with clinico-pathological characteristics and biochemical recurrence was analyzed to assess its clinical significance. Results These studies revealed that DSG2 and DSG4 were specifically expressed in prostatic luminal cells, whereas basal cells lack their expression. In contrast, DSG1 and DSG3 were not expressed in normal prostate epithelium. Further analyses of DSG2 expression in prostate cancer revealed that reduced levels of this biomarker were a significant independent marker of poor clinical outcome. Conclusion Here we report for the first time that a low DSG2 expression phenotype is a useful prognostic biomarker of tumor aggressiveness and may serve as an aid in identifying patients with clinically significant prostate cancer. PMID:24896103

Optical coherence elastography (OCE) as a method for identifying benign and malignant prostate biopsies

NASA Astrophysics Data System (ADS)

Li, Chunhui; Guan, Guangying; Ling, Yuting; Lang, Stephen; Wang, Ruikang K.; Huang, Zhihong; Nabi, Ghulam

2015-03-01

Objectives. Prostate cancer is the most frequently diagnosed malignancy in men. Digital rectal examination (DRE) - a known clinical tool based on alteration in the mechanical properties of tissues due to cancer has traditionally been used for screening prostate cancer. Essentially, DRE estimates relative stiffness of cancerous and normal prostate tissue. Optical coherence elastography (OCE) are new optical imaging techniques capable of providing cross-sectional imaging of tissue microstructure as well as elastogram in vivo and in real time. In this preliminary study, OCE was used in the setting of the human prostate biopsies ex vivo, and the images acquired were compared with those obtained using standard histopathologic methods. Methods. 120 prostate biopsies were obtained by TRUS guided needle biopsy procedures from 9 patients with clinically suspected cancer of the prostate. The biopsies were approximately 0.8mm in diameter and 12mm in length, and prepared in Formalin solution. Quantitative assessment of biopsy samples using OCE was obtained in kilopascals (kPa) before histopathologic evaluation. The results obtained from OCE and standard histopathologic evaluation were compared provided the cross-validation. Sensitivity, specificity, and positive and negative predictive values were calculated for OCE (histopathology was a reference standard). Results. OCE could provide quantitative elasticity properties of prostate biopsies within benign prostate tissue, prostatic intraepithelial neoplasia, atypical hyperplasia and malignant prostate cancer. Data analysed showed that the sensitivity and specificity of OCE for PCa detection were 1 and 0.91, respectively. PCa had significantly higher stiffness values compared to benign tissues, with a trend of increasing in stiffness with increasing of malignancy. Conclusions. Using OCE, microscopic resolution elastogram is promising in diagnosis of human prostatic diseases. Further studies using this technique to improve the detection and staging of malignant cancer of the prostate are ongoing.

The Stockholm-3 (STHLM3) Model can Improve Prostate Cancer Diagnostics in Men Aged 50-69 yr Compared with Current Prostate Cancer Testing.

PubMed

Eklund, Martin; Nordström, Tobias; Aly, Markus; Adolfsson, Jan; Wiklund, Peter; Brandberg, Yvonne; Thompson, James; Wiklund, Fredrik; Lindberg, Johan; Presti, Joseph C; StLezin, Mark; Clements, Mark; Egevad, Lars; Grönberg, Henrik

2016-11-23

Prostate cancer screening is associated with low specificity, unnecessary biopsies, and overdiagnosis. We have previously shown that the Stockholm-3 model (S3M) can reduce biopsies compared with using prostate-specific antigen (PSA) ≥3ng/ml as an indication for biopsy. Urologists in today's current prostate cancer testing (CPT) have access to numerous variables in addition to PSA (eg, age, ethnicity, family history, free PSA, PSA velocity, digital rectal examination, and prostate volume) to support biopsy decisions. We estimated the number of prostate cancers diagnosed and prostate biopsies performed if S3M replaced CPT in Stockholm, Sweden, by comparing biopsy results in 56 282 men who underwent PSA testing according to CPT in Stockholm in 2011 with the 47 688 men enrolled in the STHLM3 validation cohort 2012-2015. With the same sensitivity as CPT to diagnose Gleason score ≥7 prostate cancer, S3M was estimated to reduce the number of men biopsied by 53% (95% confidence interval [CI]: 41-65%), avoid 76% (95% CI: 67-81%) of negative biopsies, and reduce Gleason score 6 cancers by 23% (95% CI: 6-40%). S3M has the potential to improve prostate cancer diagnostics by better selecting men with high risk of GS ≥7 prostate cancer. We modeled the effect the Stockholm-3 model would have on prostate cancer diagnostics if it replaced current clinical practice. We found that Stockholm-3 model may substantially reduce the number of biopsies, while maintaining the same sensitivity to diagnose clinically significant prostate cancer. Copyright © 2016. Published by Elsevier B.V.

Racial and Ethnic Variation in Time to Prostate Biopsy After an Elevated Screening Level of Serum Prostate-specific Antigen.

PubMed

Reading, Stephanie R; Porter, Kimberly R; Hsu, Jin-Wen Y; Wallner, Lauren P; Loo, Ronald K; Jacobsen, Steven J

2016-10-01

To examine the racial and ethnic variation in time to prostate biopsy after an elevated screening level of serum prostate-specific antigen (PSA). Male members of the Kaiser Permanente of Southern California health plan, 45 years of age or older, with no history of prostate cancer or a prostate biopsy, and at least 1 elevated screening level of serum PSA between January 1, 1998 and December 31, 2007 were retrospectively identified (n = 59,506). All participants were passively followed via electronic health records until their time of prostate biopsy, death, membership disenrollment, or study conclusion (December 31, 2014), whichever was the initial event. Proportional hazard regression analyses were used to estimate the association between time from an elevated screening level of serum PSA to prostate biopsy, adjusting for age, benign prostatic hyperplasia, prostatitis, type 2 diabetes mellitus, hypertension, and Charlson Comorbidity Index score. Median time until biopsy was 0.6 years (214 days), with approximately 41% of participants receiving a prostate biopsy within the study period. Results from the fully adjusted analysis indicated that the non-Hispanic Asian or Pacific Islanders (hazard ratio: 1.10, 95% confidence interval: [1.04, 1.15]) and the non-Hispanic blacks (hazard ratio: 1.04, 95% confidence interval: [1.00, 1.08]) had a slightly shorter time to prostate biopsy after an elevated screening level of serum PSA compared to the non-Hispanic whites. These data suggest that, within an integrated healthcare organization, minimal differences exist between racial and ethnic subgroups in their time to prostate biopsy after an elevated screening level of serum PSA. Copyright © 2016. Published by Elsevier Inc.

Healthy Family 2009: Practicing Healthy Adult Living

MedlinePlus

... doctor the pros and cons of having a prostate-specific antigen (PSA) test or digital rectal examination (DRE) to ... colonoscopies for cancer of the colon, serum prostatin-specific antigen (PSA) tests for prostate cancer, and mammograms for breast cancer. Work out ...

Investigating the Functional Role of Prostate-Specific Membrane Antigen and its Enzymatic Activity in Prostate Cancer Metastasis

DTIC Science & Technology

2007-02-01

saponin (Calbiochem, San Diego, CA) in PBS. Results, Significance, Obstacles and Alternative Approaches: We have generated several different fluorescent...1 integrin antibody P4C10 (Life technologies ). We will conjugate the fluorescent probes to these functional blocking antibodies for live cell...characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. Int. J. Cancer. 62:552-558. 1995. 9. Wright GL Jr

Targeting prostate cancer: Prostate-specific membrane antigen based diagnosis and therapy.

PubMed

Wüstemann, Till; Haberkorn, Uwe; Babich, John; Mier, Walter

2018-05-17

The high incidence rates of prostate cancer (PCa) raise demand for improved therapeutic strategies. Prostate tumors specifically express the prostate-specific membrane antigen (PSMA), a membrane-bound protease. As PSMA is highly overexpressed on malignant prostate tumor cells and as its expression rate correlates with the aggressiveness of the disease, this tumor-associated biomarker provides the possibility to develop new strategies for diagnostics and therapy of PCa. Major advances have been made in PSMA targeting, ranging from immunotherapeutic approaches to therapeutic small molecules. This review elaborates the diversity of PSMA targeting agents while focusing on the radioactively labeled tracers for diagnosis and endoradiotherapy. A variety of radionuclides have been shown to either enable precise diagnosis or efficiently treat the tumor with minimal effects to nontargeted organs. Most small molecules with affinity for PSMA are based on either a phosphonate or a urea-based binding motif. Based on these pharmacophores, major effort has been made to identify modifications to achieve ideal pharmacokinetics while retaining the specific targeting of the PSMA binding pocket. Several tracers have now shown excellent clinical usability in particular for molecular imaging and therapy as proven by the efficiency of theranostic approaches in current studies. The archetypal expression profile of PSMA may be exploited for the treatment with alpha emitters to break radioresistance and thus to bring the power of systemic therapy to higher levels. © 2018 Wiley Periodicals, Inc.

Long-Term Trial Results Show No Mortality Benefit from Annual Prostate Cancer Screening

Cancer.gov

Thirteen year follow-up data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial show higher incidence but similar mortality among men screened annually with the prostate-specific antigen (PSA) test and digital rectal examination

Interplay of tumor vascular oxygenation and pO2 in tumors using NIRS and needle electrode

NASA Astrophysics Data System (ADS)

Kim, Jae Gwan; Song, Yulin; Zhao, Dawen; Constantinescu, Anca; Mason, Ralph P.; Liu, Hanli

2001-06-01

The effective measurement of dynamic changes of blood and tissue oxygenation of tumors could be valuable for optimizing tumor treatment plans. For this study, a near- infrared spectroscopy system and pO2 needle electrode were used to measure simultaneously changes in total hemoglobin concentration ([Hb]total), oxygenated hemoglobin concentration ([HbO2[) and local oxygen tension (pO2) in the vascular bed of prostate tumors implanted in rats in response to respiratory challenge. The inhaled gas was alternated between air and carbogen (95% oxygen, 5% CO2). Significant changes in tumor vascular oxygenation were observed with an apparent threshold for variation in [HbO2]/[HbO2]max. For comparison, a phantom study was undertaken with 1% intralipid solution and blood. The slope of [HbO2]/[HbO2[max vs. pO2 in the phantom was ten times larger than in the tumor indicating that tumor cells are relatively resistant to oxygenation. This study demonstrates that the NIR technology can provide an efficient, real-time, non-invasive approach to monitoring tumor physiology and is compatible with additional techniques.

Assessing quality of life in patients with prostate cancer: a systematic and standardized comparison of available instruments.

PubMed

Schmidt, Stefanie; Garin, Olatz; Pardo, Yolanda; Valderas, José M; Alonso, Jordi; Rebollo, Pablo; Rajmil, Luis; Garcia-Forero, Carlos; Ferrer, Montse

2014-10-01

The objective was to obtain a standardized evaluation of available prostate cancer-specific quality of life instruments used in patients with early-stage disease. We carried out systematic literature reviews in the PubMed database to identify manuscripts which contained information regarding either the development process or metric properties of prostate cancer-specific quality of life instruments. Each instrument was evaluated by two experts, independently, using the Evaluating Measures of Patient-Reported Outcomes (EMPRO) tool. An overall and seven attribute-specific EMPRO scores were calculated (range 0-100, worst to best): measurement model, reliability, validity, responsiveness, interpretability, burden and alternative forms. Eight instruments and 57 manuscripts (2-15 per instrument) were identified. The Expanded Prostate Cancer Index Composite (EPIC) was the best rated (overall EMPRO score 83.1 points). Good results were also obtained by University of California Los Angeles-Prostate Cancer Index (UCLA-PCI), Patient-Oriented Prostate Utility Scale (PORPUS) and Prostate Cancer Quality of Life Instrument (PC-QoL) with 77.3, 70.5 and 64.8 points, respectively. These four instruments passed with distinction the validity and responsiveness evaluation. Insufficient reliability results were observed for UCLA-PCI and PORPUS. Current evidence supports the choice of EPIC, PORPUS or PC-QoL. Attribute-specific EMPRO results facilitate selecting the adequate instrument for every purpose. For longitudinal studies or clinical trials, where responsiveness is the priority, EPIC or PC-QoL should be considered. We recommend the PORPUS for economic evaluations because it allows cost-utility analysis, and EPIC short versions to minimize administration burden.

Significance of serum total prostate specific antigen and digital rectal examination in the diagnosis of prostate cancer.

PubMed

Abdrabo, Abdelkarim A; Fadlalla, Adil I; Fadl-Elmula, Imad M

2011-11-01

To assess the significance of serum total prostate specific antigen (tPSA) and digital rectal examination (DRE) in the diagnosis of prostate cancer (PC). One hundred and eighteen patients with serum tPSA ranging between 2.5 and 10 ng/ml with lower urinary tract symptoms presented at the Urology Clinic of Soba University Hospital, Khartoum, Sudan from August 2008 and January 2010 were included in the study. Serum tPSA was measured using enzyme immunoassay method, and accordingly, the patients were classified into 2 groups: patients that had tPSA between 2.5-4.0 ng/ml; and patients that had tPSA between 4.1-10 ng/ml. The DRE was performed on all patients by a qualified urologist, and were recorded as a group with suspicion of PC, and a group with no suspicion of PC. All patients underwent transrectal sextant prostate biopsy. The DRE alone showed 63.8% sensitivity and 68% specificity with 46.9% positive predictive value (PPV) for the diagnosis of PC. The tPSA test revealed 91.6% sensitivity and 24% specificity with PPV of 34%. However, when combining DRE and tPSA, the sensitivity reached 100% and the specificity increased to 92% with PPV of 49%. Combining DRE and tPSA test increases the sensitivity, specificity, and PPV of PC detection.

Proteasome-associated deubiquitinase ubiquitin-specific protease 14 regulates prostate cancer proliferation by deubiquitinating and stabilizing androgen receptor.

PubMed

Liao, Yuning; Liu, Ningning; Hua, Xianliang; Cai, Jianyu; Xia, Xiaohong; Wang, Xuejun; Huang, Hongbiao; Liu, Jinbao

2017-02-02

Androgen receptor (AR) is frequently over-expressed and plays a critical role in the growth and progression of human prostate cancer. The therapy attempting to target AR signalling was established in decades ago but the treatment of prostate cancer is far from being satisfactory. The assignable cause is that our understanding of the mechanism of AR regulation and re-activation remains incomplete. Increasing evidence suggests that deubiquitinases are involved in the regulation of cancer development and progression but the specific underlying mechanism often is not elucidated. In the current study, we have identified ubiquitin-specific protease 14 (USP14) as a novel regulator of AR, inhibiting the degradation of AR via deubiquitinating this oncoprotein in the androgen-responsive prostate cancer cells. We found that (i) USP14 could bind to AR, and additionally, both genetic and pharmacological inhibition of USP14 accelerated the ubiquitination and degradation of AR; (ii) downregulation or inhibition of USP14 suppressed cell proliferation and colony formation of LNcap cells and, conversely, overexpression of USP14 promoted the proliferation; and (iii) reduction or inhibition of USP14 induced G0/G1 phase arrest in LNcap prostate cancer cells. Hence, we conclude that USP14 promotes prostate cancer progression likely through stabilization of AR, suggesting that USP14 could be a promising therapeutic target for prostate cancer.

Should modest elevations in prostate-specific antigen, International Prostate Symptom Score, or their rates of increase over time be used as surrogate measures of incident benign prostatic hyperplasia?

PubMed

Schenk, Jeannette M; Hunter-Merrill, Rachel; Zheng, Yingye; Etzioni, Ruth; Gulati, Roman; Tangen, Catherine; Thompson, Ian M; Kristal, Alan R

2013-09-01

Although surrogate measures of benign prostatic hyperplasia (BPH) are often used in epidemiologic studies, their performance characteristics are unknown. Using data from the Prostate Cancer Prevention Trial (n = 5,986), we evaluated prostate-specific antigen (PSA), International Prostate Symptom Score (IPSS), and their rates of change as predictors of incident BPH. BPH (n = 842 cases) was defined as medical or surgical treatment or at least 2 IPSS of 15 or higher. Proportional hazards models were used to measure the associations of baseline PSA, IPSS, and their velocities over 2 years with BPH risk, and time-dependent receiver-operating characteristic curves were used to measure their discriminatory performance. Unit increases in PSA, IPSS, and IPSS velocity were associated with 34%, 35%, and 29% (all P < 0.001) increases in BPH risk, respectively. The areas under the receiver-operating characteristic curves were significantly greater than 0.5 for PSA (0.58, 95% confidence interval (CI): 0.56, 0.60), IPSS (0.77, 95% CI: 0.75, 0.78), and IPSS velocity (0.63, 95% CI: 0.61, 0.65); however there were no cut points at which sensitivity and specificity were both above 75%. We concluded that moderate elevations in PSA, IPSS, or their rates of change should not be used as surrogate measures of incident BPH.

Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection.

PubMed

Sutcliffe, Siobhan; Nevin, Remington L; Pakpahan, Ratna; Elliott, Debra J; Langston, Marvin E; De Marzo, Angelo M; Gaydos, Charlotte A; Isaacs, William B; Nelson, William G; Sokoll, Lori J; Walsh, Patrick C; Zenilman, Jonathan M; Cersovsky, Steven B; Platz, Elizabeth A

2016-05-01

Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (≥ 20 ng/mL: 19.7% versus 8.8%, p = 0.027; ≥ 40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men. © 2015 UICC.

Clinical Utility of Five Genetic Variants for Predicting Prostate Cancer Risk and Mortality

PubMed Central

Salinas, Claudia A.; Koopmeiners, Joseph S.; Kwon, Erika M.; FitzGerald, Liesel; Lin, Daniel W.; Ostrander, Elaine A.; Feng, Ziding; Stanford, Janet L.

2009-01-01

Background A recent report suggests that the combination of five single-nucleotide polymorphisms (SNPs) at 8q24, 17q12, 17q24.3 and a family history of the disease may predict risk of prostate cancer. The present study tests the performance of these factors in prediction models for prostate cancer risk and prostate cancer-specific mortality. Methods SNPs were genotyped in population-based samples from Caucasians in King County, Washington. Incident cases (n=1308), aged 35–74, were compared to age-matched controls (n=1266) using logistic regression to estimate odds ratios (OR) associated with genotypes and family history. Cox proportional hazards models estimated hazard ratios for prostate cancer-specific mortality according to genotypes. Results The combination of SNP genotypes and family history was significantly associated with prostate cancer risk (ptrend=1.5 × 10−20). Men with ≥ five risk factors had an OR of 4.9 (95% CI 1.6 to 18.5) compared to men with none. However, this combination of factors did not improve the ROC curve after accounting for known risk predictors (i.e., age, serum PSA, family history). Neither the individual nor combined risk factors was associated with prostate cancer-specific mortality. Conclusion Genotypes for five SNPs plus family history are associated with a significant elevation in risk for prostate cancer and may explain up to 45% of prostate cancer in our population. However, they do not improve prediction models for assessing who is at risk of getting or dying from the disease, once known risk or prognostic factors are taken into account. Thus, this SNP panel may have limited clinical utility. PMID:19058137

A national survey of medical students' beliefs and knowledge in screening for prostate cancer.

PubMed

Marcella, Stephen; Delnevo, Cristine D; Coughlin, Steven S

2007-01-01

Today's medical students are being educated at a time when there are no evidence-based guidelines for prostate cancer screening. To examine medical students' knowledge and beliefs concerning prostate cancer screening and specific determinants for their beliefs. One thousand six hundred and forty four students were sampled at 20 medical schools using a web-based, cross-sectional survey. Basic knowledge and beliefs about prostate cancer testing, epidemiology, and therapy were ascertained. Four of 8 knowledge items were answered incorrectly by 50% or more of students. Seven of 8 students believe that early diagnosis from screening can improve survival from prostate cancer. Second- and third-year students were more likely than fourth-year students to believe that the digital rectal exam (DRE) and the prostate-specific antigen test were accurate, adjusted odds ratio (AOR) 1.8; 95% confidence interval (CI), 1.2 to 2.7 and 1.7; 1.3 to 2.2 for second and third years, respectively, for the DRE. Black and Hispanic students were no more likely than white students to agree that early screening diagnosis improves survival, but blacks were more likely to agree with screening black or Hispanic men (AOR 7.8; 95% CI, 5.3 to 11.4 and 3.2; 2.2 to 4.7, respectively). More knowledgeable students were less likely to believe in the benefit of early detection and the accuracy of the prostate-specific antigen (AOR 0.3; 95%CI, 0.2 to 0.5). Medical students generally are very optimistic about the benefits of screening for prostate cancer. Increased knowledge about prostate cancer is associated with a more conservative view of screening. Other predictors are independent of this knowledge.

Cell Penetrating Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate Cancer

DTIC Science & Technology

2016-12-01

biochemical and biologic assay systems. The final specific aim was tol examine the ability of the bispecific antibody to perturb the growth of prostate ...designated by other documentation. TITLE: Cell-Penetrating Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate ...Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate Cancer Michael Lilly, MD Richard Weisbart, MD Medical

Identification and Characterization of Prostate Cancer Associated Protein Biomarkers Using High-Throughput Mass Spectrometry

DTIC Science & Technology

2006-09-01

Specific examples using serum samples from prostate cancer and hepatocellular carcinoma subjects are provided, along with suggested experimental...from prostate cancer and hepatocellular carcinoma subjects are provided, along with suggested experimental strategies for integration of lectin based...application of different lectins to enrich for serum glycoforms found in sera from prostate cancer and hepatocellular carcinoma subjects. For the

Prostate Cancer Risk and DNA Methylation Signatures in Aging Rats following Developmental BPA Exposure: A Dose-Response Analysis.

PubMed

Prins, Gail S; Ye, Shu-Hua; Birch, Lynn; Zhang, Xiang; Cheong, Ana; Lin, Han; Calderon-Gierszal, Esther; Groen, Jacob; Hu, Wen-Yang; Ho, Shuk-Mei; van Breemen, Richard B

2017-07-11

Previous studies have uncovered heightened prostatic susceptibility to hormone-induced neoplasia from early-life exposure to low-dose bisphenol A (BPA). However, significant data gaps remain that are essential to address for biological relevance and necessary risk assessment. A complete BPA dose-response analysis of prostate lesions across multiple prostatic lobes was conducted that included internal BPA dosimetry, progression to adenocarcinoma with aging and mechanistic connections to epigenetically reprogramed genes. Male neonatal Sprague-Dawley rats were briefly exposed to 0.1 to 5,000 μg BPA/kg BW on postnatal days (PND) 1, 3, and 5. Individual prostate lobes plus periurethral prostatic ducts were evaluated at 7 mo or 1 y of age without or with adult testosterone plus estradiol (T+E) to promote carcinogenesis. DNA methylation of five genes was quantified by bisulfite genomic sequencing in d-200 dorsal prostates across BPA doses. Serum free-BPA and BPA-glucuronide were quantitated in sera of individual PND 3 pups collected 1 hr postexposure utilizing ultra-high-pressure tandem mass spectrometry (UHPLC-MS-MS). The lowest BPA dose initiated maximal hormonal carcinogenesis in lateral prostates despite undetectable free BPA 1 hr postexposure. Further, prostatic intraepithelial neoplasia (PIN) progressed to carcinoma in rats given neonatal low-dose BPA with adult T+E but not in rats given adult T+E alone. The dorsal and ventral lobes and periurethral prostatic ducts exhibited a nonmonotonic dose response with peak PIN, proliferation and apoptotic values at 10–100 μg/kg BW. This was paralleled by nonmonotonic and dose-specific DNA hypomethylation of genes that confer carcinogenic risk, with greatest hypomethylation at the lowest BPA doses. Developmental BPA exposures heighten prostate cancer susceptibility in a complex dose- and lobe-specific manner. Importantly, elevated carcinogenic risk is found at doses that yield undetectable serum free BPA. Dose-specific epigenetic modifications of selected genes provide a mechanistic framework that may connect early-life BPA to later-life predisposition to prostate carcinogenesis. https://doi.org/10.1289/EHP1050.

Prostate Cancer Risk and DNA Methylation Signatures in Aging Rats following Developmental BPA Exposure: A Dose–Response Analysis

PubMed Central

Ye, Shu-Hua; Birch, Lynn; Zhang, Xiang; Cheong, Ana; Lin, Han; Calderon-Gierszal, Esther; Groen, Jacob; Hu, Wen-Yang; Ho, Shuk-Mei; van Breemen, Richard B.

2017-01-01

Background: Previous studies have uncovered heightened prostatic susceptibility to hormone-induced neoplasia from early-life exposure to low-dose bisphenol A (BPA). However, significant data gaps remain that are essential to address for biological relevance and necessary risk assessment. Objectives: A complete BPA dose–response analysis of prostate lesions across multiple prostatic lobes was conducted that included internal BPA dosimetry, progression to adenocarcinoma with aging and mechanistic connections to epigenetically reprogramed genes. Methods: Male neonatal Sprague-Dawley rats were briefly exposed to 0.1 to 5,000μg BPA/kg BW on postnatal days (PND) 1, 3, and 5. Individual prostate lobes plus periurethral prostatic ducts were evaluated at 7 mo or 1 y of age without or with adult testosterone plus estradiol (T+E) to promote carcinogenesis. DNA methylation of five genes was quantified by bisulfite genomic sequencing in d-200 dorsal prostates across BPA doses. Serum free-BPA and BPA-glucuronide were quantitated in sera of individual PND 3 pups collected 1 hr postexposure utilizing ultra-high-pressure tandem mass spectrometry (UHPLC-MS-MS). Results: The lowest BPA dose initiated maximal hormonal carcinogenesis in lateral prostates despite undetectable free BPA 1 hr postexposure. Further, prostatic intraepithelial neoplasia (PIN) progressed to carcinoma in rats given neonatal low-dose BPA with adult T+E but not in rats given adult T+E alone. The dorsal and ventral lobes and periurethral prostatic ducts exhibited a nonmonotonic dose response with peak PIN, proliferation and apoptotic values at 10–100μg/kg BW. This was paralleled by nonmonotonic and dose-specific DNA hypomethylation of genes that confer carcinogenic risk, with greatest hypomethylation at the lowest BPA doses. Conclusions: Developmental BPA exposures heighten prostate cancer susceptibility in a complex dose- and lobe-specific manner. Importantly, elevated carcinogenic risk is found at doses that yield undetectable serum free BPA. Dose-specific epigenetic modifications of selected genes provide a mechanistic framework that may connect early-life BPA to later-life predisposition to prostate carcinogenesis. https://doi.org/10.1289/EHP1050 PMID:28728135

Body mass index and mortality in men with prostate cancer.

PubMed

Cantarutti, Anna; Bonn, Stephanie E; Adami, Hans-Olov; Grönberg, Henrik; Bellocco, Rino; Bälter, Katarina

2015-08-01

Body Mass index (BMI) has been shown to affect risk and mortality of several cancers. Prostate cancer and obesity are major public health concerns for middle-aged and older men. Previous studies of pre-diagnostic BMI have found an increased risk of prostate cancer mortality in obese patients. To study the associations between BMI at time of prostate cancer diagnosis and prostate cancer specific and overall mortality. BMI was analyzed both as a continuous variable and categorized into four groups based on the observed distribution in the cohort (BMI < 22.5, 22.5 < 25, 25 < 27.5 and ≥27.5 kg/m2). The association between BMI and mortality was assessed using stratified Cox proportional hazards models and by fitting regression splines for dose response analysis in 3,161 men diagnosed with prostate cancer. After 11 years of follow up via linkage to the population-based cause of death registry, we identified 1,161 (37%) deaths off which 690 (59%) were due to prostate cancer. High BMI (BMI ≥ 27.5 kg/m2) was associated with a statistically significant increased risk of prostate cancer specific mortality (HR:1.44, 95% CI: 1.09-1.90) and overall mortality (HR:1.33, 95% CI: 1.09-1.63) compared to the reference group (BMI 22.5 < 25 kg/m2). Additionally, men with a low BMI (<22.5 kg/m2 ), had a statistically significant increased risk of prostate cancer specific mortality (HR:1.33, 95% CI: 1.02-1.74) and overall mortality (HR:1.36, 95% CI: 1.11-1.67) compared to the reference. However, this effect disappeared when men who died within the first two years of follow-up were excluded from the analyses while the increased risk of prostate cancer specific mortality and overall mortality remained statistically significant for men with a BMI ≥ 27.5 kg/m2 (HR:1.44, 95% CI: 1.09-1.90 and HR: 1.33, 95% CI: 1.09-1.63, respectively). This study showed that a high BMI at time of prostate cancer diagnosis was associated with increased overall mortality. © 2015 Wiley Periodicals, Inc.

Medium term outcome of bipolar plasma vaporization in prostate cancer patients--a palliative modality of preserving spontaneous voiding.

PubMed

Geavlete, B; Moldoveanu, C; Niţă, Gh; Stănescu, F; Jecu, M; Geavlete, P

2012-12-15

This retrospective analysis evaluated the efficiency, safety, and medium term postoperative results of bipolar plasma vaporization (BPV) in prostate cancer (PCa) cases associating complete urinary retention. A series of 40 patients diagnosed with locally advanced or metastatic PCa and complete urinary retention requiring a Foley catheter indwelling underwent BPV aiming to restore spontaneous voiding. A total of 35 patients completed the one year evaluation protocol consisting of International Prostate Symptom Score (IPSS), quality of life score (QoL), maximum flow rate (Q(max)) and post-voiding residual urinary volume (PVR), measured at 1, 3, 6 and 12 months after surgery. BPV was successfully performed in all cases with satisfactory efficiency, as confirmed by the mean operation time (42.8 minutes) and hemoglobin drop (0.7 g/dl). A fast and safe postoperative recovery period was described in this series (hematuria rate--7.5%; mean catheterization period--36 hours; mean hospital stay--2.5 days; early-irritative symptoms' rate--15%). At 1, 3, 6 and 12 months, satisfactory values were determined in terms of IPSS, Qmax, QoL and PVR. These parameters emphasized a stable evolution throughout the entire follow-up, as 88.6% of the patients maintained spontaneous voiding. The present trial confirmed the plasma-button vaporization as a promising therapeutic approach in PCa cases associating complete urinary retention. The technique displayed good efficacy, low perioperative morbidity, short convalescence, and satisfactory urodynamics and symptom score parameters during the one-year follow-up period.

Role of Hsp90 in Androgen-Refractory Prostate Cancer

DTIC Science & Technology

2010-03-01

designed siRNA sequence using Intergrated DNA Technologies RNAi online software tool (IDT, Coralville, IA). The sequence of siRNA specific for...proliferation and production of prostate-specific antigen in androgen-sensitive pros- tatic cancer cells, LNCaP, by dihydrotestosterone. Endocrinology 136

Performance of 68Ga-PSMA PET/CT for Prostate Cancer Management at Initial Staging and Time of Biochemical Recurrence.

PubMed

Bailey, Jason; Piert, Morand

2017-09-09

Recently introduced Gallium-68 labeled PSMA-ligands such as HBED-CC ( 68 Ga-PSMA) have shown promise for unmet diagnostic needs in prostate cancer. 68 Ga-PSMA has demonstrated improved detection rates and specificity for prostate cancer compared to standard imaging approaches. In the setting of primary disease, 68 Ga-PSMA appears to preferentially identify treatment-relevant intermediate and high-risk prostate cancer. There is also a growing evidence that 68 Ga-PSMA positron emission tomography (PET) outperforms alternative conventional imaging methods including choline-based radiotracers for the localization of disease sites at biochemical recurrence, particularly at lower prostate-specific antigen (PSA) levels (< 1 ng/mL). However, the majority of published work lacks rigorous verification of imaging results. 68 Ga-PSMA offers significant promise for both, primary disease and biochemically recurrent prostate cancer. The evidence base to support 68 Ga-PSMA is however still underdeveloped, and more rigorous studies substantiating efficacy are needed.

Wide variation of prostate-specific antigen doubling time of untreated, clinically localized, low-to-intermediate grade, prostate carcinoma.

PubMed

Choo, Richard; Klotz, Laurence; Deboer, Gerrit; Danjoux, Cyril; Morton, Gerard C

2004-08-01

To assess the prostate specific antigen (PSA) doubling time of untreated, clinically localized, low-to-intermediate grade prostate carcinoma. A prospective single-arm cohort study has been in progress since November 1995 to assess the feasibility of a watchful-observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The PSA doubling time was estimated from a linear regression of ln(PSA) against time, assuming a simple exponential growth model. As of March 2003, 231 patients had at least 6 months of follow-up (median 45) and at least three PSA measurements (median 8, range 3-21). The distribution of the doubling time was: < 2 years, 26 patients; 2-5 years, 65; 5-10 years, 42; 10-20 years, 26; 20-50 years, 16; >50 years, 56. The median doubling time was 7.0 years; 42% of men had a doubling time of >10 years. The doubling time of untreated clinically localized, low-to-intermediate grade prostate cancer varies widely.

[11C]choline-PET-guided helical tomotherapy and estramustine in a patient with pelvic-recurrent prostate cancer: local control and toxicity profile after 24 months.

PubMed

Alongi, Filippo; Schipani, Stefano; Samanes Gajate, Ana Maria; Rosso, Alberto; Cozzarini, Cesare; Fiorino, Claudio; Alongi, Pierpaolo; Picchio, Maria; Gianolli, Luigi; Messa, Cristina; Di Muzio, Nadia

2010-01-01

[11C]choline positron emission tomograhy can be useful to detect metastatic disease and to localize isolated lymph node relapse after primary treatment in case of prostate-specific antigen failure. In case of lymph node failure in prostate cancer patients, surgery or radiotherapy can be proposed with a curative intent. Some reports have suggested that radiotherapy could have a role in local control of oligometastatic lymph node disease. This is the first reported case of [11C]choline positron emission tomography-guided helical tomotherapy concomitant with estramustine for the treatment of pelvic-recurrent prostate cancer. At 24 months after the end of helical tomotherapy, prostate-specific antigen was undetectable and no late toxicities were recorded. A disease-free survival of 24 months, in the absence of any type of systemic therapy, is uncommon in metastatic prostate cancer. The therapeutic approach of the case report is discussed and a literature review on the issue is presented.

Prostate cancer diagnostics: Clinical challenges and the ongoing need for disruptive and effective diagnostic tools.

PubMed

Sharma, Shikha; Zapatero-Rodríguez, Julia; O'Kennedy, Richard

The increased incidence and the significant health burden associated with carcinoma of the prostate have led to substantial changes in its diagnosis over the past century. Despite technological advancements, the management of prostate cancer has become progressively more complex and controversial for both early and late-stage disease. The limitations and potential harms associated with the use of prostate-specific antigen (PSA) as a diagnostic marker have stimulated significant investigation of numerous novel biomarkers that demonstrate varying capacities to detect prostate cancer and can decrease unnecessary biopsies. However, only a few of these markers have been approved for specific clinical settings while the others have not been adequately validated for use. This review systematically and critically assesses ongoing issues and emerging challenges in the current state of prostate cancer diagnostic tools and the need for disruptive next generation tools based on analysis of combinations of these biomarkers to enhance predictive accuracy which will benefit clinical diagnostics and patient welfare. Copyright © 2016. Published by Elsevier Inc.

The performance characteristics of prostate-specific antigen and prostate-specific antigen density in Chinese men.

PubMed

Teoh, Jeremy Yc; Yuen, Steffi Kk; Tsu, James Hl; Wong, Charles Kw; Ho, Brian Sh; Ng, Ada Tl; Ma, Wai-Kit; Ho, Kwan-Lun; Yiu, Ming-Kwong

2017-01-01

We investigated the performance characteristics of prostate-specific antigen (PSA) and PSA density (PSAD) in Chinese men. All Chinese men who underwent transrectal ultrasound-guided prostate biopsy (TRUS-PB) from year 2000 to 2013 were included. The receiver operating characteristic (ROC) curves for both PSA and PSAD were analyzed. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) at different cut-off levels were calculated. A total of 2606 Chinese men were included. For the ROC, the area under curve was 0.770 for PSA (P < 0.001) and 0.823 for PSAD (P < 0.001). PSA of 4.5 ng ml-1 had sensitivity of 94.4%, specificity of 14.1%, PPV of 29.5%, and NPV of 86.9%; PSAD of 0.12 ng ml-1 cc-1 had sensitivity of 94.5%, specificity of 26.6%, PPV of 32.8%, and NPV of 92.7%. On multivariate logistic regression analyses, PSA cut-off at 4.5 ng ml-1 (OR 1.61, 95% CI 1.05-2.45, P= 0.029) and PSAD cut-off at 0.12 ng ml-1 cc-1 (OR 6.22, 95% CI 4.20-9.22, P< 0.001) were significant predictors for prostate cancer detection on TRUS-PB. In conclusion, the performances of PSA and PSAD at different cut-off levels in Chinese men were very different from those in Caucasians. PSA of 4.5 ng ml-1 and PSAD of 0.12 ng ml-1 cc-1 had near 95% sensitivity and were significant predictors of prostate cancer detection in Chinese men.

Synchronous prostate and rectal adenocarcinomas irradiation utilising volumetric modulated arc therapy.

PubMed

Ng, Sweet Ping; Tran, Thu; Moloney, Philip; Sale, Charlotte; Mathlum, Maitham; Ong, Grace; Lynch, Rod

2015-12-01

Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high-dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was delivered to the prostate only, using VMAT. Treatment-related toxicities and follow-up prostate-specific antigen and carcinoembryonic antigen were collected for data analysis. At 12 months, the patient achieved complete response for both rectal and prostate cancers without significant treatment-related toxicities.

NKX3.1 Genotype and IGF-1 Interact in Prostate Cancer Risk

DTIC Science & Technology

2009-05-01

Steadman DJ, Giuffrida D, Gelmann EP. DNA-binding sequence of the human prostate-specific homeodomain protein NKX3.1. Nucleic Acids Res 2000;28...Gelmann EP. DNA-binding sequence of the human prostate-specific homeodomain protein NKX3.1. Nucleic Acids Res 2000;28:2389–95. 20. Wu X, Senechal K...3212836 /UG=Hs.21765 fatty acid desaturase 3 204733_at 5.74 gb:NM_002774.1 /DEF=Homo sapiens kallikrein 6 (neurosin, zyme) (KLK6), mRNA. /FEA=mRNA /GEN

Advancing the Capabilities of an Authentic Ex Vivo Model of Primary Human Prostate Cancer

DTIC Science & Technology

2014-10-01

maintained the PTEN expression of the native tissues after 5 days in culture. Prostate-specific membrane antigen ( PSMA ) was detected in benign and malignant...room temperature 1 h room temperature 30 min room temperature Abcam, Cambridge, MA, USA p63 SMA CD68 PSMA Mouse monoclonal Mouse monoclonal Mouse...Prostate-specific membrane antigen ( PSMA ) was detected in benign and malignant glands as expected in both native tissue and in TSCs after 5 days.47

Prostate-specific membrane antigen-based imaging in prostate cancer: impact on clinical decision making process.

PubMed

Demirkol, Mehmet Onur; Acar, Ömer; Uçar, Burcu; Ramazanoğlu, Sultan Rana; Sağlıcan, Yeşim; Esen, Tarık

2015-05-01

There is an ongoing need for an accurate imaging modality which can be used for staging purposes, metastatic evaluation, predicting biologic aggresiveness and investigating recurrent disease in prostate cancer. Prostate specific membrane antigen, given its favorable molecular characteristics, holds a promise as an ideal target for prostate cancer-specific nuclear imaging. In this study, we evaluated our initial results of PSMA based PET/CT imaging in prostate cancer. A total of 22 patients with a median age and serum PSA level of 68 years and 4.15 ng/ml, respectively underwent Ga-68 PSMA PET/CT in our hospital between Februrary and August 2014. Their charts were retrospectively reviewed in order to document the clinical characteristics, the indications for and the results of PSMA based imaging and the impact of Ga-68 PSMA PET/CT findings on disease management. The most common indications were rising PSA after local ± adjuvant treatment followed by staging and metastatic evaluation before definitive or salvage treatment. All except 2 patients had prostatic ± extraprostatic PSMA positive lesions. For those who had a positive result; treatment strategies were tailored accordingly. Above the PSA level of 2 ng/ml, none of the PSMA based nuclear imaging studies revealed negative results. PSMA based nuclear imaging has significantly impacted our way of handling patients with prostate cancer. Its preliminary performance in different clinical scenarios and ability to detect lesions even in low PSA values seems fairly promising and deserves to be supplemented with further clinical studies. © 2015 Wiley Periodicals, Inc.

IR Spectra of Different O2-Content Hemoglobin from Computational Study: Promising Detector of Hemoglobin Variant in Medical Diagnosis.

PubMed

Zhou, Su-Qin; Chen, Tu-Nan; Ji, Guang-Fu; Wang, En-Ren

2017-06-01

IR spectra of heme and different O 2 -content hemoglobin were studied by the quantum computation method at the molecule level. IR spectra of heme and different O 2 -content hemoglobin were quantificationally characterized from 0 to 100 THz. The IR spectra of oxy-heme and de-oxy-heme are obviously different at the frequency regions of 9.08-9.48, 38.38-39.78, 50.46-50.82, and 89.04-91.00 THz. At 24.72 THz, there exists the absorption peak for oxy-heme, whereas there is not the absorption peak for de-oxy-heme. Whether the heme contains Fe-O-O bond or not has the great influence on its IR spectra and vibration intensities of functional groups in the mid-infrared area. The IR adsorption peak shape changes hardly for different O 2 -content hemoglobin. However, there exist three frequency regions corresponding to the large change of IR adsorption intensities for containing-O 2 hemoglobin in comparison with de-oxy-hemoglobin, which are 11.08-15.93, 44.70-50.22, and 88.00-96.68 THz regions, respectively. The most differential values with IR intensity of different O 2 -content hemoglobin all exceed 1.0 × 10 4  L mol -1  cm -1 . With the increase of oxygen content, the absorption peak appears in the high-frequency region for the containing-O 2 hemoglobin in comparison with de-oxy-hemoglobin. The more the O 2 -content is, the greater the absorption peak is at the high-frequency region. The IR spectra of different O 2 -content hemoglobin are so obviously different in the mid-infrared region that it is very easy to distinguish the hemoglobin variant by means of IR spectra detector. IR spectra of hemoglobin from quantum computation can provide scientific basis and specific identification of hemoglobin variant resulting from different O 2 contents in medical diagnosis.

New technologies in benign prostatic hyperplasia management.

PubMed

Roberts, William W

2016-05-01

Surgical debulking of the adenoma/transition zone has been the fundamental principle which underpins transurethral resection of the prostate - still acknowledged to be the gold-standard therapy for benign prostatic hyperplasia (BPH). However, there has been a recent resurgence in development of new BPH technologies driven by enhanced understanding of prostate pathophysiology, development of new ablative technologies, and the need for less morbid alternatives as the mean age and complexity of the treatment population continues to increase. The objective of this review is to highlight new BPH technologies and review their available clinical data with specific emphasis on unique features of the technology, procedural effectiveness and safety, and potential impact on current treatment paradigms. New technologies have emerged that alter the shape of the prostate to decrease urinary obstruction and enhance delivery of a lethal thermal dose by steam injection into the transition zone of the prostate. Energy can be delivered to the prostate via a beam of high-pressure saline or focused acoustic energy to mechanically disintegrate prostate tissue. Methods of cell death are being targeted with selectivity by the arterial supply with embolization and specific to prostate cells via injectable biological therapies. A number of new technologies are at various stages of development and improve on the transurethral resection of the prostate paradigm by moving closer to the ideal BPH therapy which is definitive, can be performed in minutes, in the office setting, with only local anesthesia and oral sedation.

Elevated insulin and reduced insulin like growth factor binding protein-3/prostate specific antigen ratio with increase in prostate size in Benign Prostatic Hyperplasia.

PubMed

Sreenivasulu, Karli; Nandeesha, Hanumanthappa; Dorairajan, Lalgudi Narayanan; Rajappa, Medha; Vinayagam, Vickneshwaran

2017-06-01

Insulin and insulin like growth factor-1 (IGF-1) have growth promoting effects, while insulin like growth factor binding protein-3 (IGFBP-3) has growth inhibitory effects. The present study was designed to assess the concentrations of insulin, IGF-1, IGFBP-3 and their association with prostate size in patients with BPH. Ninety 90 BPH cases and 90 controls were enrolled in the study. Insulin, IGF-1, IGFBP-3, PSA, testosterone and estradiol were estimated in both the groups. Insulin, IGF-1 and estradiol were increased and IGFBP-3/PSA was decreased in BPH cases when compared with controls. Insulin (r=0.64, p=0.001) and IGF-1 (r=0.22, p=0.03) were positively correlated and IGFBP-3/PSA (r=-0.316, p=0.002) were negatively correlated with prostate size in BPH. Multivariate analysis showed that insulin (p=0.001) and IGFBP-3/PSA (p=0.004) predicts the prostate size in patients with BPH. Insulin was increased and IGFBP-3/PSA was reduced in BPH patients with increased prostate size. At a cutoff concentration of 527.52, IGFBP-3/PSA ratio was found to differentiate benign growth of prostate from normal prostate with 96% sensitivity and 96% specificity. Insulin is elevated and IGFBP-3/PSA is reduced with increase prostate size in BPH cases. Copyright © 2017 Elsevier B.V. All rights reserved.

Clopidogrel use and cancer-specific mortality: a population-based cohort study of colorectal, breast and prostate cancer patients.

PubMed

Hicks, Blánaid M; Murray, Liam J; Hughes, Carmel; Cardwell, Chris R

2015-08-01

Concerns were raised about the safety of antiplatelet thienopyridine derivatives after a randomized control trial reported increased risks of cancer and cancer deaths in prasugrel users. We investigate whether clopidogrel, a widely used thienopyridine derivative, was associated with increased risk of cancer-specific or all-cause mortality in cancer patients. Colorectal, breast and prostate cancer patients, newly diagnosed from 1998 to 2009, were identified from the National Cancer Data Repository. Cohorts were linked to the UK Clinical Practice Research Datalink, providing prescription records, and to the Office of National Statistics mortality data (up to 2012). Unadjusted and adjusted hazard ratios (HRs) for cancer-specific and all-cause mortality in post-diagnostic clopidogrel users were calculated using time-dependent Cox regression models. The analysis included 10 359 colorectal, 17 889 breast and 13 155 prostate cancer patients. There was no evidence of an increase in cancer-specific mortality in clopidogrel users with colorectal (HR = 0.98 95% confidence interval (CI) 0.77, 1.24) or prostate cancer (HR = 1.03 95%CI 0.82, 1.28). There was limited evidence of an increase in breast cancer patients (HR = 1.22 95%CI 0.90, 1.65); however, this was attenuated when removing prescriptions in the year prior to death. This novel study of large population-based cohorts of colorectal, breast and prostate cancer patients found no evidence of an increased risk of cancer-specific mortality among colorectal, breast and prostate cancer patients using clopidogrel. Copyright © 2015 John Wiley & Sons, Ltd.

Biases in Recommendations for and Acceptance of Prostate Biopsy Significantly Affect Assessment of Prostate Cancer Risk Factors: Results From Two Large Randomized Clinical Trials

PubMed Central

Goodman, Phyllis J.; Till, Cathee; Schenk, Jeannette M.; Lucia, M. Scott; Thompson, Ian M.

2016-01-01

Purpose To identify factors related to who undergoes a prostate biopsy in a screened population and to estimate the impact of biopsy verification on risk factor–prostate cancer associations. Patients and Methods Men who were screened regularly from the placebo arms of two large prostate cancer prevention trials (Prostate Cancer Prevention Trial [PCPT] and Selenium and Vitamin E Cancer Prevention Trial [SELECT]) were examined to define incident prostate cancer cohorts. Because PCPT had an end-of-study biopsy, prostate cancer cases were categorized by a preceding prostate-specific antigen/digital rectal examination prompt (yes/no) and noncases by biopsy-proven negative status (yes v no). We estimated the association of risk factors (age, ethnicity, family history, body mass index, medication use) with prostate cancer and quantified differences in risk associations across cohorts. Results Men 60 to 69 years of age, those with benign prostatic hyperplasia, and those with a family history of prostate cancer were more likely, and those with a higher body mass index (≥ 25), diabetes, or a smoking history were less likely, to undergo biopsy, adjusting for age and longitudinal prostate-specific antigen and digital rectal examination. Medication use, education, and marital status also influenced who underwent biopsy. Some risk factor estimates for prostate cancer varied substantially across cohorts. Black (v other ethnicities) had odds ratios (ORs) that varied from 1.20 for SELECT (community screening standards, epidemiologic-like cohort) to 1.83 for PCPT (end-of-study biopsy supplemented with imputed end points). Statin use in SELECT provided an OR of 0.65 and statin use in in PCPT provided an OR of 0.99, a relative difference of 34%. Conclusion Among screened men enrolled in prostate cancer prevention trials, differences in risk factor estimates for prostate cancer likely underestimate the magnitude of bias found in other cohorts with varying screening and biopsy recommendations and acceptance. Risk factors for prostate cancer derived from epidemiologic studies not only may be erroneous but may lead to misdirected research efforts. PMID:27998216

Risk assessment models to evaluate the necessity of prostate biopsies in North Chinese patients with 4-50 ng/mL PSA.

PubMed

Zhao, Jing; Liu, Shuai; Gao, Dexuan; Ding, Sentai; Niu, Zhihong; Zhang, Hui; Huang, Zhilong; Qiu, Juhui; Li, Qing; Li, Ning; Xie, Fang; Cui, Jilei; Lu, Jiaju

2017-02-07

Prostate-specific antigen (PSA) is widely used for prostate cancer screening, but low specificity results in high false positive rates of prostate biopsies. To develop new risk assessment models to overcome the diagnostic limitation of PSA and reduce unnecessary prostate biopsies in North Chinese patients with 4-50 ng/mL PSA. A total of 702 patients in seven hospitals with 4-10 and 10-50 ng/mL PSA, respectively, who had undergone transrectal ultrasound-guided prostate biopsies, were assessed. Analysis-modeling stage for several clinical indexes related to prostate cancer and renal function was carried out. Multiple logistic regression analyses were used to develop new risk assessment models of prostate cancer for both PSA level ranges 4-10 and 10-50 ng/mL. External validation stage of the new models was performed to assess the necessity of biopsy. The new models for both PSA ranges performed significantly better than PSA for detecting prostate cancers. Both models showed higher areas under the curves (0.937 and 0.873, respectively) compared with PSA alone (0.624 and 0.595), at pre-determined cut-off values of 0.1067 and 0.6183, respectively. Patients above the cut-off values were recommended for immediate biopsy, while the others were actively observed. External validation of the models showed significantly increased detection rates for prostate cancer (4-10 ng/mL group, 39.29% vs 17.79%, p=0.006; 10-50 ng/mL group, 71.83% vs 50.0%, p=0.015). We developed risk assessment models for North Chinese patients with 4-50 ng/mL PSA to reduce unnecessary prostate biopsies and increase the detection rate of prostate cancer.

Unemployment and prostate cancer mortality in the OECD, 1990–2009

PubMed Central

Maruthappu, Mahiben; Watkins, Johnathan; Taylor, Abigail; Williams, Callum; Ali, Raghib; Zeltner, Thomas; Atun, Rifat

2015-01-01

The global economic downturn has been associated with increased unemployment in many countries. Insights into the impact of unemployment on specific health conditions remain limited. We determined the association between unemployment and prostate cancer mortality in members of the Organisation for Economic Co-operation and Development (OECD). We used multivariate regression analysis to assess the association between changes in unemployment and prostate cancer mortality in OECD member states between 1990 and 2009. Country-specific differences in healthcare infrastructure, population structure, and population size were controlled for and lag analyses conducted. Several robustness checks were also performed. Time trend analyses were used to predict the number of excess deaths from prostate cancer following the 2008 global recession. Between 1990 and 2009, a 1% rise in unemployment was associated with an increase in prostate cancer mortality. Lag analysis showed a continued increase in mortality years after unemployment rises. The association between unemployment and prostate cancer mortality remained significant in robustness checks with 46 controls. Eight of the 21 OECD countries for which a time trend analysis was conducted, exhibited an estimated excess of prostate cancer deaths in at least one of 2008, 2009, or 2010, based on 2000–2007 trends. Rises in unemployment are associated with significant increases in prostate cancer mortality. Initiatives that bolster employment may help to minimise prostate cancer mortality during times of economic hardship. PMID:26045715

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

Comparison of intravesical prostatic protrusion, prostate volume and serum prostatic-specific antigen in the evaluation of bladder outlet obstruction.

PubMed

Lim, Kok Bin; Ho, Henry; Foo, Keong Tatt; Wong, Michael Yuet Chen; Fook-Chong, Stephanie

2006-12-01

The aims of this study were to define the relationship between intravesical prostatic protrusion (IPP), prostate-specific antigen (PSA) and prostate volume (PV) and to determine which one of them is the best predictor of bladder outlet obstruction (BOO) due to benign prostatic enlargement. A prospective study of 114 male patients older than 50 years examined between November 2001 and 2002 was performed. They were evaluated with digital rectal examination, International Prostate Symptoms Score, PSA, uroflowmetry, postvoid residual urine measurement, IPP and PV using transabdominal ultrasound scan. Statistical analysis included scatter plot with Spearman's correlation coefficients and nominal logistic regression Prostate volume, IPP and PSA showed parallel correlation. Although all three indices had good correlation with BOO index, IPP was the best. The Spearman rho correlation coefficients were 0.314, 0.408 and 0.507 for PV, PSA and IPP, respectively. Using receiver-operator characteristic curves, the areas under the curve for PV, PSA and IPP were 0.637, 0.703 and 0.772, respectively. The positive predictive values of PV, PSA and IPP were 65%, 68% and 72%, respectively. Using a nominal regression model, IPP remained the most significant independent index to determine BOO. All three non-invasive indices correlate with one another. The study showed that IPP is a better predictor for BOO than PSA or PV.

Unemployment and prostate cancer mortality in the OECD, 1990-2009.

PubMed

Maruthappu, Mahiben; Watkins, Johnathan; Taylor, Abigail; Williams, Callum; Ali, Raghib; Zeltner, Thomas; Atun, Rifat

2015-01-01

The global economic downturn has been associated with increased unemployment in many countries. Insights into the impact of unemployment on specific health conditions remain limited. We determined the association between unemployment and prostate cancer mortality in members of the Organisation for Economic Co-operation and Development (OECD). We used multivariate regression analysis to assess the association between changes in unemployment and prostate cancer mortality in OECD member states between 1990 and 2009. Country-specific differences in healthcare infrastructure, population structure, and population size were controlled for and lag analyses conducted. Several robustness checks were also performed. Time trend analyses were used to predict the number of excess deaths from prostate cancer following the 2008 global recession. Between 1990 and 2009, a 1% rise in unemployment was associated with an increase in prostate cancer mortality. Lag analysis showed a continued increase in mortality years after unemployment rises. The association between unemployment and prostate cancer mortality remained significant in robustness checks with 46 controls. Eight of the 21 OECD countries for which a time trend analysis was conducted, exhibited an estimated excess of prostate cancer deaths in at least one of 2008, 2009, or 2010, based on 2000-2007 trends. Rises in unemployment are associated with significant increases in prostate cancer mortality. Initiatives that bolster employment may help to minimise prostate cancer mortality during times of economic hardship.

CCR study: evidence for benefit of TARP vaccine for men with early stage prostate cancer | Center for Cancer Research

Cancer.gov

Results from a pilot clinical trial found that TARP, or T-cell receptor gamma chain alternate reading frame protein, vaccination slowed prostate-specific antigen (PSA) rise in the majority of patients with early stage prostate cancer.

Comparison of 68Ga-PSMA PET/CT and multiparametric MRI for staging of high-risk prostate cancer68Ga-PSMA PET and MRI in prostate cancer.

PubMed

Tulsyan, Shruti; Das, Chandan J; Tripathi, Madhavi; Seth, Amlesh; Kumar, Rajeev; Bal, Chandrasekhar

2017-12-01

We carried out this study to compare Glu-NH-CO-NH-Lys-(Ahx) [Ga(HBED-CC)] [Ga prostate-specific membrane antigen-11 (PSMA-11)] PET with multiparametric MRI (mpMRI) for the staging of high-risk prostate cancer. This was a prospective study in which 36 patients with high-risk prostate cancer were included. The criteria for inclusion were biopsy-proven prostate cancer with a serum prostate specific antigen of at least 20 and/or Gleason's score of at least 8. Each patient then underwent both gallium-68 (Ga)-PSMA PET/computed tomography (CT) and mpMRI including diffusion-weighted whole-body imaging with background body signal suppression within an interval of 1 week and both modalities were compared for staging of primary disease, lymph node, and distant metastasis. The median age of the 36 patients included was 65 years (range: 44-80 years) and the median prostate specific antigen was 94.3 ng/ml (range: 20-19005  ng/ml). Concordance for localization of primary on Ga-PSMA PET/CT and MRI was observed in 19/36 (52.7%) patients. Concurrence for T staging on Ga-PSMA and MRI was observed in 58.3% of patients. Ga-PSMA PET/CT detected higher numbers of patients with regional (29) and nonregional (15) lymph nodes in comparison with MRI (20 and 5, respectively). Concurrence for regional and nonregional lymph node staging was observed in 72.2% of patients. Additional sites of metastatic disease reported on Ga-PSMA PET/CT were to the skeleton in one patient, the lung in two patients, and the liver in one patient. This study suggests that Ga-PSMA PET/CT is useful for lymph node and metastases staging in high-risk prostate cancers, whereas its utility for staging of disease in the prostate is limited.

Validity of Prostate Health Index and Percentage of [-2] Pro-Prostate-Specific Antigen as Novel Biomarkers in the Diagnosis of Prostate Cancer: Omani Tertiary Hospitals Experience

PubMed Central

Al Saidi, Safana S.; Al Riyami, Nafila B.; Al Marhoon, Mohammed S.; Al Saraf, Mohammed S.; Al Busaidi, Salim S.; Bayoumi, Riad; Mula-Abed, Waad-Allah S.

2017-01-01

Objectives Prostate cancer is the leading cancer in older men. The Ministry of Health Oman Cancer Incidence Registry 2013 lists cancer of the prostate as the first most common cancer in males. Therefore, early detection is important and prostate-specific antigen (PSA) is widely used as an established laboratory test. However, despite its wide use, its value in screening, particularly in asymptomatic males, is controversial when considering the risks and benefits of early detection. Methods This prospective, observational study included 136 males (67.0±8.9 years; range 45–90) who were scheduled for a prostate biopsy in two different tertiary care teaching hospitals in Oman: the Royal Hospital and Sultan Qaboos University Hospital. Blood specimens from these patients were collected at the same setting before obtaining a prostatic biopsy. Three PSA markers (total PSA (tPSA), free PSA (fPSA), and [-2]proPSA (p2PSA)) were measured and the Prostate Health Index (phi) calculated. The histopathological report of the prostatic biopsy for each patient was obtained from the histopathology laboratory of the concerned hospital along with clinical and laboratory data through the hospital information system. Results Phi has the highest validity markers compared with other prostate markers, with a sensitivity of 82.1%, specificity of 80.6%, and area under the curve (AUC) value of 0.81 at a cutoff of 41.9. The other prostatic markers showed sensitivities and specificities of 78.6% and 25.9% for tPSA; 35.7% and 92.6% for %fPSA; and 64.3% and 82.4% for %p2PSA, respectively. The AUCs at the best cutoff values were 0.67 at 10.1 µg/L for tPSA; 0.70 at 11.6% for %fPSA; and 0.55 at 1.4% for %p2PSA. An association between phi values and aggressiveness of prostate malignancy was noted. Of the 28 patients with prostate cancer, 22 patients had tPSA > 4 µg/L. However, no patient had phi in the low-risk category, and five, six, and 17 patients had phi in the moderate-, high-, and very high-risk categories, respectively. Conclusions Phi outperforms tPSA and fPSA when used alone or in combination, and appears to be more accurate than both markers in excluding prostate cancer before biopsy. Use of this biomarker helps clinicians to avoid unnecessary biopsies, particularly in patients with gray-zone tPSA level. Phi is the strongest marker that correlates proportionally with Gleason Score; therefore, it is also useful in predicting the aggressiveness of the disease. This is the first reported experience for the use of p2PSA and phi in Oman, the Middle East, and North Africa. PMID:28804579

Centrosome-Based Mechanisms, Prognostics and Therapeutics in Prostate Cancer

DTIC Science & Technology

2006-12-01

progression of prostate carcinomas. The specific aims of the original proposal were designed to test several features of this model . 1. Are centrosome...features of this model . 1. Are centrosome defects present in early prostate cancer and can they predict aggressive disease? 2. Do pericentrin’s...cells, supports this model . The ability to block the cell cycle in prostate cells by depletion of any of 14 centrosome proteins identifies several

High-sensitivity detection of PSA by time-resolved fluorometry with Europium chelate

NASA Astrophysics Data System (ADS)

Nahm, Kie B.; Jeong, Jin H.; Kim, Byoung C.; Kim, Jae H.; Kim, Young M.; Jeong, Dong S.; Oh, Sang W.; Choi, Eui Y.; Ko, Dong S.

2006-01-01

Prostate-specific antigen (PSA) is an androgen-dependent glycoprotein protease (M.W. 33 kDa) and a member of kallikrein super-family of serine protease, and has chymotrypsin-like enzymatic activity. It is synthesized by the prostate epithelial cells and found in the prostate gland and seminal plasma as a major protein. It is widely used as a clinical marker for diagnosis, screening, monitoring and prognosis of prostate cancer. In normal male adults, the concentration of PSA in the blood is below 4 ng/ml and this value increases in patients with the prostate cancer or the benign prostatic hyperplasia (BPH) due to its leakage into the circulatory system. As such, systematic monitoring of the PSA level in the blood can provide critical information about the progress of the prostatic disease. We have fabricated a bread-board time resolved fluorescence system that could detect a concentration of Prostate Specific Antigen t-PSA) at clinically meaningful level in plasma as well as in whole blood sample. We chose Europium chelates as the fluorescence markers to attach to the PSA for its long decay lifetime and relative photostability. We have simplified the electronic circuits considerably by employing a MCS. With this setup, we have successfully proved that PSA concentration of 4pg/mL can be detected with acceptable reliability.

Prostate Stem Cell Antigen DNA Vaccination Breaks Tolerance to Self-antigen and Inhibits Prostate Cancer Growth

PubMed Central

Ahmad, Sarfraz; Casey, Garrett; Sweeney, Paul; Tangney, Mark; O'Sullivan, Gerald C

2009-01-01

Prostate stem cell antigen (PSCA) is a cell surface antigen expressed in normal human prostate and over expressed in prostate cancer. Elevated levels of PSCA protein in prostate cancer correlate with increased tumor stage/grade, with androgen independence and have higher expression in bone metastases. In this study, the PSCA gene was isolated from the transgenic adenocarcinoma mouse prostate cell line (TRAMPC1), and a vaccine plasmid construct was generated. This plasmid PSCA (pmPSCA) was delivered by intramuscular electroporation (EP) and induced effective antitumor immune responses against subcutaneous TRAMPC1 tumors in male C57 BL/6 mice. The pmPSCA vaccination inhibited tumor growth, resulting in cure or prolongation in survival. Similarly, the vaccine inhibited metastases in PSCA expressing B16 F10 tumors. There was activation of Th-1 type immunity against PSCA, indicating the breaking of tolerance to a self-antigen. This immunity was tumor specific and was transferable by adoptive transfer of splenocytes. The mice remained healthy and there was no evidence of collateral autoimmune responses in normal tissues. EP-assisted delivery of the pmPSCA evoked strong specific responses and could, in neoadjuvant or adjuvant settings, provide a safe and effective immune control of prostate cancer, given that there is significant homology between human and mouse PSCA. PMID:19337234

Mutational load of the mitochondrial genome predicts pathological features and biochemical recurrence in prostate cancer.

PubMed

Kalsbeek, Anton M F; Chan, Eva F K; Grogan, Judith; Petersen, Desiree C; Jaratlerdsiri, Weerachai; Gupta, Ruta; Lyons, Ruth J; Haynes, Anne-Maree; Horvath, Lisa G; Kench, James G; Stricker, Phillip D; Hayes, Vanessa M

2016-10-05

Prostate cancer management is complicated by extreme disease heterogeneity, which is further limited by availability of prognostic biomarkers. Recognition of prostate cancer as a genetic disease has prompted a focus on the nuclear genome for biomarker discovery, with little attention given to the mitochondrial genome. While it is evident that mitochondrial DNA (mtDNA) mutations are acquired during prostate tumorigenesis, no study has evaluated the prognostic value of mtDNA variation. Here we used next-generation sequencing to interrogate the mitochondrial genomes from prostate tissue biopsies and matched blood of 115 men having undergone a radical prostatectomy for which there was a mean of 107 months clinical follow-up. We identified 74 unique prostate cancer specific somatic mtDNA variants in 50 patients, providing significant expansion to the growing catalog of prostate cancer mtDNA mutations. While no single variant or variant cluster showed recurrence across multiple patients, we observe a significant positive correlation between the total burden of acquired mtDNA variation and elevated Gleason Score at diagnosis and biochemical relapse. We add to accumulating evidence that total acquired genomic burden, rather than specific mtDNA mutations, has diagnostic value. This is the first study to demonstrate the prognostic potential of mtDNA mutational burden in prostate cancer.

Individual and mutual predictors of marital satisfaction among prostate cancer patients and their spouses.

PubMed

Chien, Ching-Hui; Chuang, Cheng-Keng; Liu, Kuan-Lin; Huang, Xuan-Yi; Pang, See-Tong; Wu, Chun-Te; Chang, Ying-Hsu; Liu, Hsueh-Erh

2017-12-01

To determine the individual and mutual predictors of the marital satisfaction of couples in which the husband experienced prostate cancer. Marital satisfaction of patients with prostate cancer has been insufficiently studied in Asian countries as compared with Western countries. This study used a prospective and repeated-measures design. Seventy Taiwanese couples in which the husband had prostate cancer completed measures at 6 and 12 months post-treatment. Assessments of physical symptoms, marital satisfaction, coping behaviour and psychological distress were made. Multiple linear regression was used to analyse the data. The marital satisfaction of patients with prostate cancer and that of their spouses were significantly correlated. At 6 months, spouses' marital satisfaction, patients' appraisal of prostate cancer as a threat and patients' serum prostate-specific antigen levels were found to be the predictors of patients' marital satisfaction. Furthermore, patients' marital satisfaction and their spouses' psychological distress were predictors of spouses' marital satisfaction. At 12 months, spouses' marital satisfaction and patients' appraisal of prostate cancer as harm were predictors of patients' marital satisfaction. Finally, spouses' marital satisfaction (at 6 months) and appraisal of prostate cancer as a threat were predictors of spouses' marital satisfaction. At 6 months post-treatment, patients' and spouses' marital satisfaction will influence each other. However, at 12 months, patients' marital satisfaction exerts an insignificant effect on spouses' marital satisfaction. Moreover, patients' serum prostate-specific antigen level or the negative appraisal of prostate cancer affects their marital satisfaction. Spouses' marital satisfaction is affected by psychological distress and their negative appraisal of prostate cancer. The results can be used to develop interventions for prostate cancer couples. Such an intervention can be used to modify couples' appraisal of prostate cancer by changing incorrect thinking or to ease the psychological distress to improve marital satisfaction. © 2017 John Wiley & Sons Ltd.

Development of glycan specific lectin based immunoassay for detection of prostate specific antigen.

PubMed

Bhanushali, Paresh B; Badgujar, Shamkant B; Tripathi, Mukesh M; Gupta, Sanjeev; Murthy, Vedang; Krishnasastry, Musti V; Puri, Chander P

2016-05-01

We describe an analytical approach for the detection and verification of glycosylation patterns of prostate specific antigen (PSA), a key biomarker currently used for understanding the onset and prognosis of prostate cancer. PSA has been purified from the human seminal plasma and total PSA from prostate cancer sera. PSA is a monomeric glycoprotein with an apparent molecular mass 28040.467 Da, which exhibits a characteristic protease activity against casein and gelatin. Its optimal protease activity is centered on neutral pH. Peptide mass fingerprint analysis of the purified PSA has yielded peptides that partially match with known database sequences (Uniprot ID P07288). Tryptic digestion profile of isolated PSA, infer the exclusive nature of PSA and may be additive molecule in the dictionary of seminal proteins. Surface plasmon resonance and lectin immunoassay revealed direct interaction between a newly developed anti-PSA monoclonal antibody (C4E6) and PSA. A lectin based immunoassay is reported here which was achieved with the C4E6 anti-PSA antibody and biotinylated plant lectins. This investigation provides an alternative method to isolate and quantify PSA with altered glycosylation which might be seen in the prostate cancer and developing a lectin based immunoassay to detect PSA in serum of prostate cancer patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Prostate-specific acid phosphatase versus acid phosphatase in monitoring patients with prostate cancer.

PubMed

Killian, C S; Vargas, F P; Slack, N H; Murphy, G P; Chu, T M

1982-01-01

Serial levels of PAP and AcP activity were compared for their relative values in monitoring 57 early and 33 advanced prostate cancer patients. Several findings regarding the patients' disease status and the enzyme levels have been observed that may be beneficial to therapeutic management of these patients. They are: [1] an elevated PAP activity in disease recurrence and disease progression generally precedes an elevated AcP activity, and thus represents a more sensitive index for patients with early and advanced disease; [2] serial mean levels of PAP activity greater than the mean + 3 SD are more predictive for disease recurrence and progression than are those of AcP activity in both groups of patients; [3] PAP activity is a more sensitive monitor for changes in objective treatment response than is AcP activity; and [4] PAP is more specific than AcP for prostate, thus offering a more reliable marker to identify metastasis of unknown origin, or to confirm metastasis derived from a primary prostate tumor that may have been suggested by other non-prostate-specific marker[s]. In addition, data suggest a favorable prognosis for patients receiving therapy as inferred by a serial mean of PAP activity that is less than mean + 3 SD.

Advances in prostate-specific membrane antigen PET of prostate cancer.

PubMed

Bouchelouche, Kirsten; Choyke, Peter L

2018-05-01

In recent years, a large number of reports have been published on prostate-specific membrane antigen (PSMA)/PET in prostate cancer (PCa). This review highlights advances in PSMA PET in PCa during the past year. PSMA PET/computed tomography (CT) is useful in detection of biochemical recurrence, especially at low prostate-specific antigen (PSA) values. The detection rate of PSMA PET is influenced by PSA level. For primary PCa, PSMA PET/CT shows promise for tumour localization in the prostate, especially in combination with multiparametric MRI (mpMRI). For primary staging, PSMA PET/CT can be used in intermediate and high-risk PCa. Intraoperative PSMA radioligand guidance seems promising for detection of malignant lymph nodes. While the use of PSMA PET/MRI in primary localized disease is limited to high and intermediate-risk patients and localized staging, in the recurrence setting, PET/MRI can be particularly helpful when the lesions are subtle. PSMA PET/CT is superior to choline PET/CT and other conventional imaging modalities. Molecular imaging with PSMA PET continues to pave the way for personalized medicine in PCa.However, large prospective clinical studies are still needed to fully evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa.

Geraniol suppresses prostate cancer growth through down-regulation of E2F8.

PubMed

Lee, Sanghoon; Park, Yu Rang; Kim, Su-Hwa; Park, Eun-Jung; Kang, Min Ji; So, Insuk; Chun, Jung Nyeo; Jeon, Ju-Hong

2016-10-01

Geraniol, an acyclic dietary monoterpene, has been found to suppress cancer survival and growth. However, the molecular mechanism underlying the antitumor action of geraniol has not been investigated at the genome-wide level. In this study, we analyzed the microarray data obtained from geraniol-treated prostate cancer cells. Geraniol potently altered a gene expression profile and primarily down-regulated cell cycle-related gene signatures, compared to linalool, another structurally similar monoterpene that induces no apparent phenotypic changes. Master regulator analysis using the prostate cancer-specific regulatory interactome identified that the transcription factor E2F8 as a specific target molecule regulates geraniol-specific cell cycle signatures. Subsequent experiments confirmed that geraniol down-regulated E2F8 expression and the knockdown of E2F8 was sufficient to suppress cell growth by inducing G 2 /M arrest. Epidemiological analysis showed that E2F8 is up-regulated in metastatic prostate cancer and associated with poor prognosis. These results indicate that E2F8 is a crucial transcription regulator controlling cell cycle and survival in prostate cancer cells. Therefore, our study provides insight into the role of E2F8 in prostate cancer biology and therapeutics. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Cell type specific gene expression analysis of prostate needle biopsies resolves tumor tissue heterogeneity

PubMed Central

Krönig, Malte; Walter, Max; Drendel, Vanessa; Werner, Martin; Jilg, Cordula A.; Richter, Andreas S.; Backofen, Rolf; McGarry, David; Follo, Marie; Schultze-Seemann, Wolfgang; Schüle, Roland

2015-01-01

A lack of cell surface markers for the specific identification, isolation and subsequent analysis of living prostate tumor cells hampers progress in the field. Specific characterization of tumor cells and their microenvironment in a multi-parameter molecular assay could significantly improve prognostic accuracy for the heterogeneous prostate tumor tissue. Novel functionalized gold-nano particles allow fluorescence-based detection of absolute mRNA expression levels in living cells by fluorescent activated flow cytometry (FACS). We use of this technique to separate prostate tumor and benign cells in human prostate needle biopsies based on the expression levels of the tumor marker alpha-methylacyl-CoA racemase (AMACR). We combined RNA and protein detection of living cells by FACS to gate for epithelial cell adhesion molecule (EPCAM) positive tumor and benign cells, EPCAM/CD45 double negative mesenchymal cells and CD45 positive infiltrating lymphocytes. EPCAM positive epithelial cells were further sub-gated into AMACR high and low expressing cells. Two hundred cells from each population and several biopsies from the same patient were analyzed using a multiplexed gene expression profile to generate a cell type resolved profile of the specimen. This technique provides the basis for the clinical evaluation of cell type resolved gene expression profiles as pre-therapeutic prognostic markers for prostate cancer. PMID:25514598

No Detrimental Effect of a Positive Family History on Long-Term Outcomes Following Radical Prostatectomy.

PubMed

Brath, Johannes M S; Grill, Sonja; Ankerst, Donna P; Thompson, Ian M; Gschwend, Juergen E; Herkommer, Kathleen

2016-02-01

Overall 1 in 5 patients with prostate cancer has a positive family history. In this report we evaluated the association between family history and long-term outcomes following radical prostatectomy. Patients treated with radical prostatectomy were identified from a German registry, and separated into positive first-degree family history vs negative family history (strictly negative, requiring at least 1 male first-degree relative older than 60 years and no prostate cancer in the family). Kaplan-Meier curves and Cox proportional hazards models were used for association analyses with biochemical recurrence-free and prostate cancer specific survival. Median followup for 7,690 men included in the study was 8.4 years. Of the 754 younger patients less than 55 years old 50.9% (384) had a family history compared to 40.4% of the older patients (2,803; p <0.001). The 10-year biochemical recurrence-free (62.5%) and prostate cancer specific survival (96.1%) rates did not differ between patients with vs without a family history, nor between the younger vs older patient groups (all p >0.05). Prostate specific antigen, pathological stage, node stage and Gleason score were the only significant predictors for biochemical recurrence-free survival, while pathological stage, node stage (all p <0.005) and Gleason score (Gleason 7 vs 6 or less-HR 1.711, 95% CI 1.056-2.774, p = 0.03; Gleason 8 or greater vs 6 or less-HR 4.516, 95% CI 2.776-7.347, p <0.0001) were the only predictors for prostate cancer specific survival. A family history of prostate cancer has no bearing on long-term outcomes after radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Biorepository for Prostate Cancer Prevention Trial (PCPT) | Division of Cancer Prevention

Cancer.gov

The PCPT biorepository and extended data was used to further explore the initial suggestion that some men taking finasteride were at risk of developing high-grade prostate cancers, and to look at the value of prostate-specific antigen (PSA) for early detection. Researchers showed that: |

USE OF AGRICULTURAL PESTICIDES AND PROSTATE CANCER RISK IN THE AGRICULTURAL HEALTH STUDY COHORT

EPA Science Inventory

The role of specific agricultural chemicals in relation to prostate cancer risk has not been firmly established due to the lack of precise exposure data. We examined the relationship between 45 common agricultural pesticides and prostate cancer incidence in a prospective cohor...

Psychosocial and Cultural Barriers to Prostate Cancer Screening: Racial Comparisons

DTIC Science & Technology

2009-03-01

37 REPORTABLE OUTCOMES ............................................................................................... 38 KEY RESEARCH...difference in outcome for prostate cancer, then a fatalistic attitude can develop and discourage screening behavior. Belief in one’s ability to...cancer screening among African American men and reduce racial disparities in prostate cancer outcomes . Specifically, the proposed project examines

Targeting prostate cancer cells with hybrid elastin-like polypeptide/liposome nanoparticles

PubMed Central

Zhang, Wei; Song, Yunmei; Eldi, Preethi; Guo, Xiuli; Hayball, John D; Garg, Sanjay; Albrecht, Hugo

2018-01-01

Prostate cancer cells frequently overexpress the gastrin-releasing peptide receptor, and various strategies have been applied in preclinical settings to target this receptor for the specific delivery of anticancer compounds. Recently, elastin-like polypeptide (ELP)-based self-assembling micelles with tethered GRP on the surface have been suggested to actively target prostate cancer cells. Poorly soluble chemotherapeutics such as docetaxel (DTX) can be loaded into the hydrophobic cores of ELP micelles, but only limited drug retention times have been achieved. Herein, we report the generation of hybrid ELP/liposome nanoparticles which self-assembled rapidly in response to temperature change, encapsulated DTX at high concentrations with slow release, displayed the GRP ligand on the surface, and specifically bound to GRP receptor expressing PC-3 cells as demonstrated by flow cytometry. This novel type of drug nanocarrier was successfully used to reduce cell viability of prostate cancer cells in vitro through the specific delivery of DTX. PMID:29391790

Treatment- and Disease-Related Complications of Prostate Cancer

PubMed Central

Simoneau, Anne R

2006-01-01

One of the highlights of the 16th International Prostate Cancer Update was a session on treatment- and disease-related complications of prostate disease. It began with presentation of a challenging case of rising prostate-specific antigen levels after radical prostatectomy, followed by an overview of the use of zoledronic acid in prostate cancer, a review of side effects of complementary medicines, an overview of complications of cryotherapy, an assessment of complications of brachytherapy and external beam radiation therapy, and a comparison of laparoscopy versus open prostatectomy. PMID:17021643

Implementation of a 5-Minute Magnetic Resonance Imaging Screening Protocol for Prostate Cancer in Men With Elevated Prostate-Specific Antigen Before Biopsy.

PubMed

Weiss, Jakob; Martirosian, Petros; Notohamiprodjo, Mike; Kaufmann, Sascha; Othman, Ahmed E; Grosse, Ulrich; Nikolaou, Konstantin; Gatidis, Sergios

2018-03-01

The aims of this study were to establish a 5-minute magnetic resonance (MR) screening protocol for prostate cancer in men before biopsy and to evaluate effects on Prostate Imaging Reporting and Data System (PI-RADS) V2 scoring in comparison to a conventional, fully diagnostic multiparametric MR imaging (mpMRI) approach. Fifty-two patients with elevated prostate-specific antigen levels and without prior biopsy were prospectively included in this institutional review board-approved study. In all patients, an mpMRI protocol according to the PI-RADS recommendations was acquired on a 3 T MRI system. In addition, an accelerated diffusion-weighted imaging sequence was acquired using simultaneous multislice technique (DW-EPISMS). Two readers independently evaluated the images for the presence/absence of prostate cancer according to the PI-RADS criteria and for additional findings. In a first reading session, only the screening protocol consisting of axial T2-weighted and DW-EPISMS images was made available. In a subsequent reading session, the mpMRI protocol was assessed blinded to the results of the first reading, serving as reference standard. Both readers successfully established a final diagnosis according to the PI-RADS criteria in the screening and mpMRI protocol. Mean lesion size was 1.2 cm in the screening and 1.4 cm in the mpMRI protocol (P = 0.4) with 35% (18/52) of PI-RADS IV/V lesions. Diagnostic performance of the screening protocol was excellent with a sensitivity and specificity of 100% for both readers with no significant differences in comparison to the mpMRI standard (P = 1.0). In 3 patients, suspicious lymph nodes were reported as additional finding, which were equally detectable in the screening and mpMRI protocol. A 5-minute MR screening protocol for prostate cancer in men with elevated prostate-specific antigen levels before biopsy is applicable for clinical routine with similar diagnostic performance as the full diagnostic mpMRI approach.

Optimization and comprehensive characterization of a faithful tissue culture model of the benign and malignant human prostate.

PubMed

Maund, Sophia Lisette; Nolley, Rosalie; Peehl, Donna Mae

2014-02-01

Few preclinical models accurately depict normal human prostate tissue or primary prostate cancer (PCa). In vitro systems typically lack complex cellular interactions among structured prostatic epithelia and a stromal microenvironment, and genetic and molecular fidelity are concerns in both in vitro and in vivo models. 'Tissue slice cultures' (TSCs) provide realistic preclinical models of diverse tissues and organs, but have not been fully developed or widely utilized for prostate studies. Problems encountered include degeneration of differentiated secretory cells, basal cell hyperplasia, and poor survival of PCa. Here, we optimized, characterized, and applied a TSC model of primary human PCa and benign prostate tissue that overcomes many deficiencies of current in vitro models. Tissue cores from fresh prostatectomy specimens were precision-cut at 300 μm and incubated in a rotary culture apparatus. The ability of varied culture conditions to faithfully maintain benign and cancer cell and tissue structure and function over time was evaluated by immunohistological and biochemical assays. After optimization of the culture system, molecular and cellular responses to androgen ablation and to piperlongumine (PL), purported to specifically reduce androgen signaling in PCa, were investigated. Optimized culture conditions successfully maintained the structural and functional fidelity of both benign and PCa TSCs for 5 days. TSCs exhibited androgen dependence, appropriately undergoing ductal degeneration, reduced proliferation, and decreased prostate-specific antigen expression upon androgen ablation. Further, TSCs revealed cancer-specific reduction of androgen receptor and increased apoptosis upon treatment with PL, validating data from cell lines. We demonstrate a TSC model that authentically recapitulates the structural, cellular, and genetic characteristics of the benign and malignant human prostate, androgen dependence of the native tissue, and cancer-specific response to a potentially new therapeutic for PCa. The work described herein provides a basis for advancing the experimental utility of the TSC model.

The Utility of [18F]DASA-23 for Molecular Imaging of Prostate Cancer with Positron Emission Tomography.

PubMed

Beinat, Corinne; Haywood, Tom; Chen, Yun-Sheng; Patel, Chirag B; Alam, Israt S; Murty, Surya; Gambhir, Sanjiv Sam

2018-05-07

There is a strong, unmet need for superior positron emission tomography (PET) imaging agents that are able to measure biochemical processes specific to prostate cancer. Pyruvate kinase M2 (PKM2) catalyzes the concluding step in glycolysis and is a key regulator of tumor growth and metabolism. Elevation of PKM2 expression was detected in Gleason 8-10 tumors compared to Gleason 6-7 carcinomas, indicating that PKM2 may potentially be a marker of aggressive prostate cancer. We have recently reported the development of a PKM2-specific radiopharmaceutical [ 18 F]DASA-23 and herein describe its evaluation in cell culture and preclinical models of prostate cancer. The cellular uptake of [ 18 F]DASA-23 was evaluated in a panel of prostate cancer cell lines and compared to that of [ 18 F]FDG. The specificity of [ 18 F]DASA-23 to measure PKM2 levels in cell culture was additionally confirmed through the use of PKM2-specific siRNA. PET imaging studies were then completed utilizing subcutaneous prostate cancer xenografts using either PC3 or DU145 cells in mice. [ 18 F]DASA-23 uptake values over 60-min incubation period in PC3, LnCAP, and DU145 respectively were 23.4 ± 4.5, 18.0 ± 2.1, and 53.1 ± 4.6 % tracer/mg protein. Transient reduction in PKM2 protein expression with siRNA resulted in a 50.1 % reduction in radiotracer uptake in DU145 cells. Small animal PET imaging revealed 0.86 ± 0.13 and 1.6 ± 0.2 % ID/g at 30 min post injection of radioactivity in DU145 and PC3 subcutaneous tumor bearing mice respectively. Herein, we evaluated a F-18-labeled PKM2-specific radiotracer, [ 18 F]DASA-23, for the molecular imaging of prostate cancer with PET. [ 18 F]DASA-23 revealed rapid and extensive uptake levels in cellular uptake studies of prostate cancer cells; however, there was only modest tumor uptake when evaluated in mouse subcutaneous tumor models.

The prevalence and overlap of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome in men: results of the RAND Interstitial Cystitis Epidemiology male study.

PubMed

Suskind, Anne M; Berry, Sandra H; Ewing, Brett A; Elliott, Marc N; Suttorp, Marika J; Clemens, J Quentin

2013-01-01

As part of the RICE (RAND Interstitial Cystitis Epidemiology) study, we developed validated case definitions to identify interstitial cystitis/bladder pain syndrome in women and chronic prostatitis/chronic pelvic pain syndrome in men. Using population based screening methods, we applied these case definitions to determine the prevalence of these conditions in men. A total of 6,072 households were contacted by telephone to screen for men who had symptoms of interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome. An initial 296 men screened positive, of whom 149 met the inclusionary criteria and completed the telephone interview. For interstitial cystitis/bladder pain syndrome 2 case definitions were applied (1 with high sensitivity and 1 with high specificity), while for chronic prostatitis/chronic pelvic pain syndrome a single case definition (with high sensitivity and specificity) was used. These case definitions were used to classify subjects into groups based on diagnosis. The interstitial cystitis/bladder pain syndrome weighted prevalence estimates for the high sensitivity and high specificity definitions were 4.2% (3.1-5.3) and 1.9% (1.1-2.7), respectively. The chronic prostatitis/chronic pelvic pain syndrome weighted prevalence estimate was 1.8% (0.9-2.7). These values equate to 1,986,972 (95% CI 966,042-2,996,924) men with chronic prostatitis/chronic pelvic pain syndrome and 2,107,727 (95% CI 1,240,485-2,974,969) men with the high specificity definition of interstitial cystitis/bladder pain syndrome in the United States. The overlap between men who met the high specificity interstitial cystitis/bladder pain syndrome case definition or the chronic prostatitis/chronic pelvic pain syndrome case definition was 17%. Symptoms of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome are widespread among men in the United States. The prevalence of interstitial cystitis/bladder pain syndrome symptoms in men approaches that in women, suggesting that this condition may be underdiagnosed in the male population. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2018-06-22

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

Prostate health index and prostate cancer gene 3 score but not percent-free Prostate Specific Antigen have a predictive role in differentiating histological prostatitis from PCa and other nonneoplastic lesions (BPH and HG-PIN) at repeat biopsy.

PubMed

De Luca, Stefano; Passera, Roberto; Fiori, Cristian; Bollito, Enrico; Cappia, Susanna; Mario Scarpa, Roberto; Sottile, Antonino; Franco Randone, Donato; Porpiglia, Francesco

2015-10-01

To determine if prostate health index (PHI), prostate cancer antigen gene 3 (PCA3) score, and percentage of free prostate-specific antigen (%fPSA) may be used to differentiate asymptomatic acute and chronic prostatitis from prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostate intraepithelial neoplasia (HG-PIN) in patients with elevated PSA levels and negative findings on digital rectal examination at repeat biopsy (re-Bx). In this prospective study, 252 patients were enrolled, undergoing PHI, PCA3 score, and %fPSA assessments before re-Bx. We used 3 multivariate logistic regression models to test the PHI, PCA3 score, and %fPSA as risk factors for prostatitis vs. PCa, vs. BPH, and vs. HG-PIN. All the analyses were performed for the whole patient cohort and for the "gray zone" of PSA (4-10ng/ml) cohort (171 individuals). Of the 252 patients, 43 (17.1%) had diagnosis of PCa. The median PHI was significantly different between men with a negative biopsy and those with a positive biopsy (34.9 vs. 48.1, P<0.001), as for the PCA3 score (24 vs. 54, P<0.001) and %fPSA (11.8% vs. 15.8%, P = 0.012). The net benefit of using PCA3 and PHI to differentiate prostatitis and PCa was moderate, although it extended to a good range of threshold probabilities (40%-100%), whereas that from using %fPSA was negligible: this pattern was reported for the whole population as for the "gray zone" PSA cohort. In front of a good diagnostic performance of all the 3 biomarkers in distinguishing negative biopsy vs. positive biopsy, the clinical benefit of using the PCA3 score and PHI to estimate prostatitis vs. PCa was comparable. PHI was the only determinant for prostatitis vs. BPH, whereas no biomarkers could differentiate prostate inflammation from HG-PIN. Copyright © 2015 Elsevier Inc. All rights reserved.

The role of prostate-specific antigen in light of new scientific evidence.

PubMed

Hernández, C; Morote, J; Miñana, B; Cózar, J M

2013-06-01

Review the scientific evidence acquired in recent years on Prostate-Specific Antigen (PSA). Analysis of the available evidence on the current role of PSA, according to a panel of experts who recorded their experience on the subject. Currently, PSA cannot be considered solely an indicator of the presence or absence of prostate cancer. Rather, the determination of PSA assists the urologist in indicating the most appropriate treatment for a patient with benign prostatic hypertrophic (BPH), as well as in suspecting a prostatic tumour when the PSA reading increases >0,3 ng/ml, in patients treated with 5-alpha-reductase inhibitor, over the reading achieved at six months of having initiated this treatment. Moreover, PSA is a key factor in the follow-up of patients with prostate adenocarcinoma who undergo surgery, radiation therapy or minimally invasive techniques. PSA helps to define biochemical recurrence, suggest the existence of a local or distal recurrence and propose or rule out adjuvant therapies. New data on the current role of PSA in the management of patients treated for BPH and/or prostate cancer should be taken into account. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2016-05-01

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

Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids.

PubMed

Karandish, Fataneh; Haldar, Manas K; You, Seungyong; Brooks, Amanda E; Brooks, Benjamin D; Guo, Bin; Choi, Yongki; Mallik, Sanku

2016-11-30

Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly ( p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems.

Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids

PubMed Central

2016-01-01

Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly (p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems. PMID:27917408

Targeting PSMA by radioligands in non-prostate disease-current status and future perspectives.

PubMed

Backhaus, Philipp; Noto, Benjamin; Avramovic, Nemanja; Grubert, Lena Sophie; Huss, Sebastian; Bögemann, Martin; Stegger, Lars; Weckesser, Matthias; Schäfers, Michael; Rahbar, Kambiz

2018-05-01

Prostate-specific membrane antigen (PSMA) is the up-and-coming target for molecular imaging of prostate cancer. Despite its name, non-prostate-related PSMA expression in physiologic tissue as well as in benign and malignant disease has been reported in various publications. Unlike in prostate cancer, PSMA expression is only rarely observed in non-prostate tumor cells. Instead, expression occurs in endothelial cells of tumor-associated neovasculature, although no endothelial expression is observed under physiologic conditions. The resulting potential for tumor staging in non-prostate malignant tumors has been demonstrated in first patient studies. This review summarizes the first clinical studies and deduces future perspectives in staging, molecular characterization, and PSMA-targeted radionuclide therapy based on histopathologic examinations of PSMA expression. The non-exclusivity of PSMA in prostate cancer opens a window to utilize the spectrum of available radioactive PSMA ligands for imaging and molecular characterization and maybe even therapy of non-prostate disease.

Ratio of prostate specific antigen to the outer gland volume of prostrate as a predictor for prostate cancer.

PubMed

Zhang, Hai-Min; Yan, Yang; Wang, Fang; Gu, Wen-Yu; Hu, Guang-Hui; Zheng, Jun-Hua

2014-01-01

As a definite diagnosis of prostate cancer, puncture biopsy of the prostate is invasive method. The aim of this study was to evaluate the value of OPSAD (the ratio of PSA to the outer gland volume of prostate) as a non-invasive screening and diagnosis method for prostate cancer in a select population. The diagnosis data of 490 subjects undergoing ultrasound-guided biopsy of the prostate were retrospectively analyzed. This included 133 patients with prostate cancer, and 357 patients with benign prostate hyperplasia (BPH). The OPSAD was significantly greater in patients with prostate cancer (1.87 ± 1.26 ng/ml(2)) than those with BPH (0.44 ± 0.21 ng/ml(2)) (P < 0.05). Receiver operating characteristic (ROC) curve analysis revealed that the performance of OPSAD as a diagnostic tool is superior to PSA and PSAD for the diagnosis of prostate cancer. In the different groups divided according to the Gleason score of prostate cancer, OPSAD is elevated with the rise of the Gleason score. OPSAD may be used as a new indicator for the diagnosis and prognosis of prostate cancer, and it can reduce the use of unnecessary puncture biopsy of the prostate.

Relationship of chronic histologic prostatic inflammation in biopsy specimens with serum isoform [-2]proPSA (p2PSA), %p2PSA, and prostate health index in men with a total prostate-specific antigen of 4-10 ng/ml and normal digital rectal examination.

PubMed

Lazzeri, Massimo; Abrate, Alberto; Lughezzani, Giovanni; Gadda, Giulio Maria; Freschi, Massimo; Mistretta, Francesco; Lista, Giuliana; Fossati, Nicola; Larcher, Alessandro; Kinzikeeva, Ella; Buffi, Nicolòmaria; Dell'Acqua, Vincenzo; Bini, Vittorio; Montorsi, Francesco; Guazzoni, Giorgio

2014-03-01

To investigate the relationship between serum [-2]proPSA (p2PSA) and derivatives with chronic histologic prostatic inflammation (CHPI) in men undergoing prostate biopsy for suspected prostate cancer (PCa). This nested case-control study resulted from an observational prospective trial for the definition of sensibility, specificity, and accuracy of p2PSA, %p2PSA, and Beckman Coulter Prostate Health Index (PHI), in men undergoing prostate biopsy, with a total prostate-specific antigen (PSA) of 4-10 ng/mL and normal digital rectal examination. CHPI was the outcome of interest and defined as the presence of moderate to large infiltration of lymphomononuclear cells with interstitial and/or glandular disruption in absence of PCa. p2PSA, %p2PSA, and PHI were considered the index tests and compared with the established biomarker reference standard tests: tPSA, fPSA, %fPSA. Of 267 patients subjected to prostate biopsy, 73 (27.3%) patients were diagnosed with CHPI. Comparing CHPI with PCa patients, %p2PSA and PHI were found to be significantly lower, whereas fPSA and %fPSA were significantly higher. %p2PSA and PHI were the most accurate predictors of CHPI at biopsy, significantly outperforming tPSA, fPSA, and %fPSA. On the contrary, no significant differences were found in PSA, p2PSA, and derivatives between CHPI and benign prostatic hyperplasia (BPH) patients. Our findings showed that p2PSA, %p2PSA, and PHI values might discriminate PCa from CHPI or BPH, but not CHPI from BPH, in men with a total PSA 4-10 ng/mL and normal digital rectal examination. p2PSA isoform and its derivatives could be useful in clinical decision making to avoid unnecessary biopsies in patients with CHPI and elevated tPSA value. Copyright © 2014 Elsevier Inc. All rights reserved.

The use of a gas chromatography-sensor system combined with advanced statistical methods, towards the diagnosis of urological malignancies

PubMed Central

Aggio, Raphael B. M.; de Lacy Costello, Ben; White, Paul; Khalid, Tanzeela; Ratcliffe, Norman M.; Persad, Raj; Probert, Chris S. J.

2016-01-01

Prostate cancer is one of the most common cancers. Serum prostate-specific antigen (PSA) is used to aid the selection of men undergoing biopsies. Its use remains controversial. We propose a GC-sensor algorithm system for classifying urine samples from patients with urological symptoms. This pilot study includes 155 men presenting to urology clinics, 58 were diagnosed with prostate cancer, 24 with bladder cancer and 73 with haematuria and or poor stream, without cancer. Principal component analysis (PCA) was applied to assess the discrimination achieved, while linear discriminant analysis (LDA) and support vector machine (SVM) were used as statistical models for sample classification. Leave-one-out cross-validation (LOOCV), repeated 10-fold cross-validation (10FoldCV), repeated double cross-validation (DoubleCV) and Monte Carlo permutations were applied to assess performance. Significant separation was found between prostate cancer and control samples, bladder cancer and controls and between bladder and prostate cancer samples. For prostate cancer diagnosis, the GC/SVM system classified samples with 95% sensitivity and 96% specificity after LOOCV. For bladder cancer diagnosis, the SVM reported 96% sensitivity and 100% specificity after LOOCV, while the DoubleCV reported 87% sensitivity and 99% specificity, with SVM showing 78% and 98% sensitivity between prostate and bladder cancer samples. Evaluation of the results of the Monte Carlo permutation of class labels obtained chance-like accuracy values around 50% suggesting the observed results for bladder cancer and prostate cancer detection are not due to over fitting. The results of the pilot study presented here indicate that the GC system is able to successfully identify patterns that allow classification of urine samples from patients with urological cancers. An accurate diagnosis based on urine samples would reduce the number of negative prostate biopsies performed, and the frequency of surveillance cystoscopy for bladder cancer patients. Larger cohort studies are planned to investigate the potential of this system. Future work may lead to non-invasive breath analyses for diagnosing urological conditions. PMID:26865331

High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma: Preliminary prostate-specific antigen response, disease-free survival, and toxicity assessment.

PubMed

Fuller, Donald B; Wurzer, James; Shirazi, Reza; Bridge, Stephen S; Law, Jonathan; Mardirossian, George

2015-01-01

Patients with locally recurrent adenocarcinoma of the prostate following radiation therapy (RT) present a challenging problem. We prospectively evaluated the use of "high-dose-rate-like" prostate stereotactic body RT (SBRT) salvage for this circumstance, evaluating prostate-specific antigen response, disease-free survival, and toxicity. Between February 2009 and March 2014, 29 patients with biopsy-proven recurrent locally prostate cancer >2 years post-RT were treated. Median prior RT dose was 73.8 Gy and median interval to SBRT salvage was 88 months. Median recurrence Gleason score was 7 (79% was ≥7). Pre-existing RT toxicity >grade 1 was a reason for exclusion. Magnetic resonance imaging-defined prostate volume including any suspected extraprostatic extension, comprising the planning target volume. A total of 34 Gy/5 fractions was given, delivering a heterogeneous, high-dose-rate-like dose-escalation pattern. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0, criteria. Twenty-nine treated patients had a median 24-month follow-up (range, 3-60 months). A median pre-SBRT salvage baseline prostate-specific antigen level of 3.1 ng/mL decreased to 0.65 ng/mL and 0.16 ng/mL at 1 and 2 years, respectively. Actuarial 2-year biochemical disease-free survival measured 82%, with no local failures. Toxicity >grade 1 was limited to the genitourinary domain, with 18% grade 2 or higher and 7% grade 3 or higher. No gastrointestinal toxicity >grade 1 occurred. Two-year disease-free survival is encouraging, and the prostate-specific antigen response kinetic appears comparable with that seen in de novo patients treated with SBRT, albeit still a preliminary finding. Grade ≥2 genitourinary toxicity was occasionally seen with no obvious predictive factor. Noting that our only brachytherapy case was 1 of the 2 cases with ≥grade 3 genitourinary toxicity, caution is recommended treating these patients. SBRT salvage of post-RT local recurrence appears clinically feasible, with longer term evaluation required to assess ultimate efficacy and late toxicity rates. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Bohr effect of hemoglobins: Accounting for differences in magnitude.

PubMed

Okonjo, Kehinde O

2015-09-07

The basis of the difference in the Bohr effect of various hemoglobins has remained enigmatic for decades. Fourteen amino acid residues, identical in pairs and located at specific 'Bohr group positions' in human hemoglobin, are implicated in the Bohr effect. All 14 are present in mouse, 11 in dog, eight in pigeon and 13 in guinea pig hemoglobin. The Bohr data for human and mouse hemoglobin are identical: the 14 Bohr groups appear at identical positions in both molecules. The dog data are different from the human because three Bohr group positions are occupied by non-ionizable groups in dog hemoglobin; the pigeon data are vastly different from the human because six Bohr group positions are occupied by non-ionizable groups in pigeon hemoglobin. The guinea pig data are quite complex. Quantitative analyses showed that only the pigeon data could be fitted with the Wyman equation for the Bohr effect. We demonstrate that, apart from guinea pig hemoglobin, the difference between the Bohr effect of each of the other hemoglobins and of pigeon hemoglobin can be accounted for quantitatively on the basis of the occupation of some of their Bohr group positions by non-ionizable groups in pigeon hemoglobin. We attribute the anomalous guinea pig result to a new salt-bridge formed in its R2 quaternary structure between the terminal NH3(+) group of one β-chain and the COO(-) terminal group of the partner β-chain in the same molecule. The pKas of this NH3(+) group are 6.33 in the R2 and 4.59 in the T state. Copyright © 2015 Elsevier Ltd. All rights reserved.

Overcoming Drug Resistant Prostate Cancer with APE1/Ref 1 Blockade

DTIC Science & Technology

2016-10-01

prostate cancer specimens. Genetic knockdown of APE1/Ref-1 disrupts prostate cancer cell growth and survival in cell culture. In addition...inhibition of the redox function selectively of Ref-1 results in cell growth inhibition, with this therapy preferentially inhibiting prostate cancer cell... growth above that in non-cancerous cells. Specific blockade of Ref-1 redox activity in tumors is a novel concept in tumor therapy. If we are successful

Irreversible Electroporation for Prostate Cancer as Salvage Treatment Following Prior Radiation and Cryotherapy.

PubMed

Murray, Katie S; Akin, Oguz; Coleman, Jonathan A

2017-01-01

Salvage treatment options after localized primary treatment failure of prostate cancer are limited and associated with risk for serious complications. We report on the management details of a 57-year-old African American man treated with partial-gland ablation using irreversible electroporation following local recurrence after brachytherapy and prior salvage cryoablation. Therapeutic and functional outcomes were assessed by conventional means, including serum prostate-specific antigen values and prostate biopsy results.

Development of a Novel, Non-Invasive Diagnostic Test for Prostate Cancer

DTIC Science & Technology

2006-01-01

Chang JJ, Bhargava V , Shinohara K. The optimal systematic prostate biopsy scheme should include 8 rather than 6 biopsies: results of a prospective...sextant and laterally directed biopsies for the detection of prostate cancer. J Urol, 2001, 165:1554-9. 19. Djavan B, Ravery V , Zlotta A, Dobronski P...Smith-Jones PM, Navarro V , Goldsmith SJ, Bander NH. Radioimmunotherapy of prostate cancer in human xenografts using monoclonal antibodies specific to

Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology

DTIC Science & Technology

2017-10-01

development and patterning, and to become more knowledgeable in molecular genetics and the pathology of human prostatic diseases. Specific Aims: 1...AWARD NUMBER: W81XWH-15-1-0661 TITLE: Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and...COVERED 30 Sept 2016 – 29 Sept 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Comprehensive Molecular Profiling of African-American Prostate Cancer to

Prostate Expression Databases: Gene Expression Resources for Comparative Studies of Prostate Carcinogenesis

DTIC Science & Technology

2008-01-01

lesions of low -grade prostatic intraepithelial neoplasia (PIN). Over time, osteopontin expressing dysplastic cells seemed to increase in number in high...neoplasia (PIN) lesions, not seen at 2.5 months, were mostly low grade at 12 months and then turning to an abundant combination of low -grade PIN...Prostate specific antigen (PSA) allows the diagnosis of low grade, localized PCa, that allows the physician to offer the patient several efficacious

Tumorigenic Potential of Transit Amplifying Prostate Cells

DTIC Science & Technology

2012-06-01

by ChIP-Seq showed that in both the human prostate cell line LNCaP and in mouse prostate, NKX3.1 bound DNA fragments are significantly enriched in...progression. Cancer Cell. 2010;17(5):443–454. 29. Steadman DJ, Giuffrida D, Gelmann EP. DNA - binding sequence of the human prostate-specific...bind nucleosomal DNA and destabilize nucleosomes thereby allowing other transcription factors to access their sites (7),(8). BODY Aim 1: To

Magnetic Resonance-Based Electrical Property Tomography (MR-EPT) for Prostate Cancer Grade Imaging

DTIC Science & Technology

2016-07-01

Award Number: W81XWH-13-1-0127 TITLE: Magnetic Resonance-Based Electrical Property Tomography (MR- EPT) for Prostate Cancer Grade Imaging...SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0127 Magnetic Resonance-Based Electrical Property Tomography (MR- EPT) for Prostate Cancer Grade Imaging...developing Magnetic Resonance – Electrical Property Tomography (MR-EPT) specifically for prostate imaging. MR-EPT is an imaging modality that may enable

Interactions between Dietary Factors and Inflammation in Prostate Carcinogenesis

DTIC Science & Technology

2006-12-01

prostatic inflammation/cell damage as measured by serum prostate specific antigen concentration. J Urol. 2006 May;175(5):1937-42. Sutcliffe S...diets rich in red meat and animal fat, and low in vegetables and fruits, are consumed in Western cultures. Although not unequivocal, there is...epidemiologic evidence of a link between prostate cancer incidence and mortality and consumption of red meat and animal fats (6–9). The biological mechanism by

Identification of Prostate Cancer-Specific Circular RNAs

DTIC Science & Technology

2015-10-01

AND SUBTITLE Identification of Prostate Cancer-Specific Circular RNAs ” 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0384 5c. PROGRAM ELEMENT...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The major goal of this application is to determine whether newly identified circular RNAs can

Primary structure of the hemoglobins from Sphenodon (Sphenodon punctatus, Tuatara, Rynchocephalia). Evidence for the expression of alpha D-gene.

PubMed

Abbasi, A; Wells, R M; Brittain, T; Braunitzer, G

1988-08-01

Sphenodon is the sole representative of the "beakhead" reptiles which were widely distributed during the Triassic period before the spectacular rise of dinosaurs. Sphenodon punctatus is the only survivor ("living fossil") of this period. The morphological features of Sphenodon are remarkably conservative and differ little from reptiles living 200 million years ago. In the present paper the determination of the primary structure of the tetrameric hemoglobins is described: three components are identified: hemoglobin A' (alpha A2 beta II2), hemoglobin A (alpha A2 beta I2) and hemoglobin D (alpha D2 beta II2). The components were characterized electrophoretically, the four different peptide chains were characterized by Triton electrophoresis as well as by high-performance liquid chromatography. The hemoglobins and--under dissociating conditions--also the chains, were isolated on columns of cellulose ion exchangers. Sequence determination was carried out after cleavage of the individual chains with trypsin and after a specific chemical cleavage of the Asp-Pro bond. For sequence determination the film technique and gas-phase method were employed. The data are compared with the sequence of the human hemoglobin, and interpretations of the amino-acid sequences are given. Particularly notable is the evidence of hemoglobin D: this hemoglobin (alpha D2 beta II2) is found only in birds, and in two cases in turtles. However, this component is not found in other reptiles. The results make possible an interpretation of the relatively high oxygen affinity and explain the lack of cooperativity (myoglobin properties) of these tetrameric hemoglobins.

A retrospective study: correlation of histologic inflammation in biopsy specimens of Chinese men undergoing surgery for benign prostatic hyperplasia with serum prostate-specific antigen.

PubMed

Song, Lingmin; Zhu, Yuchun; Han, Ping; Chen, Ni; Lin, Dao; Lai, Jianyu; Wei, Qiang

2011-03-01

To reveal the correlation between benign prostatic hyperplasia (BPH) histologic inflammation and serum prostate-specific antigen (sPSA) concentrations, and the possible mechanism. Patients underwent surgery at the Urology Department of West China Hospital of Sichuan University were retrospectively studied. Preoperative sPSA and transrectal ultrasonography were measured. According to the histopathological classification system for chronic prostatic inflammation proposed by the Chronic Prostatitis Collaborative Research Network (CPCRN) and the International Prostatitis Collaborative Network (IPCN), we classified the histologic sections of prostatic biopsy into glandular, periglandular, and stromal inflammation by the anatomical location of inflammatory infiltration. The glandular inflammation was graded according to the inflammatory aggressiveness. The periglandular and stromal inflammation were graded according to the inflammatory density. The correlation between histologic inflammation and sPSA was studied by a multiple regression model in conjunction with age and total prostatic volume. A total of 454 patients with exclusively BPH were analyzed. The periglandular inflammatory infiltration was the most common pattern (95.6%). Single regression analysis revealed that total prostatic volume, the aggressiveness of glandular inflammation, and the intensity of periglandular and stromal inflammation were correlated with sPSA. However, the multiple regression analysis revealed that only the total prostatic volume and the aggressiveness of glandular inflammation were correlated significantly with sPSA (R = .389, 0.289; P = .000). The aggressiveness of glandular inflammatory infiltration in BPH is a significant contributor to elevated sPSA levels. The theory of leakage may be the most reasonable mechanism to reveal the correlation morphologically. We should take inflammation into consideration when interpreting the abnormal elevating of sPSA levels. Copyright © 2011 Elsevier Inc. All rights reserved.

The Prostate Health Index in predicting initial prostate biopsy outcomes in Asian men with prostate-specific antigen levels of 4-10 ng/mL.

PubMed

Ng, C F; Chiu, Peter K F; Lam, N Y; Lam, H C; Lee, Kim W M; Hou, Simon S M

2014-04-01

To investigate the role of the Prostate Health Index (phi) in prostate cancer (PCa) detection in patients with a prostate-specific antigen (PSA) level of 4-10 ng/mL receiving their first prostatic biopsy in an Asian population. This was a retrospective study of archived serum samples from patients enlisted in our tissue bank. Patients over 50 years old, with PSA level of 4-10 ng/mL, a negative digital rectal examination, and received their first prostatic biopsy between April 2008 and April 2013, were recruited. The serum sample collected before biopsy was retrieved for the measurement of various PSA derivatives and the phi value was calculated for each patient. The performance of these parameters in predicting the prostatic biopsy results was assessed. Two hundred and thirty consecutive patients, with 21 (9.13 %) diagnosed with PCa, were recruited for this study. Statistically significant differences between PCa patients and non-PCa patients were found for total PSA, PSA density, [-2]proPSA (p2PSA), free-to-total PSA ratio (%fPSA), p2PSA-to-free PSA ratio (%p2PSA), and phi. The areas under the curve of the receiver operating characteristic curve for total PSA, PSA density, %fPSA, %p2PSA, and phi were 0.547, 0.634, 0.654, 0.768, and 0.781, respectively. The phi was the best predictor of the prostatic biopsies results. At a sensitivity of 90 %, the use of the phi could have avoided unnecessary biopsies in 104 (45.2 %) patients. Use of the phi could improve the accuracy of PCa detection in patients with an elevated PSA level and thus avoid unnecessary prostatic biopsies.

Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy.

PubMed

Janbaziroudsari, Hamid; Mirzaei, Arezoo; Maleki, Nasrollah

2016-09-01

To investigate the relationship of serum prostate-specific antigen (PSA) levels with outcomes of prostate needle biopsy in men 50 or more years old. We measured serum PSA levels in 1472 healthy men 50 or more years old. Men who had serum PSA values 4.0ng/mL or higher underwent digital rectal examination. If there were either an elevated PSA level (≥4ng/mL) or abnormal digital rectal examination, a transrectal ultrasound-guided prostate biopsy was performed. The mean serum total PSA level was 13.73±11.44ng/mL, and the mean serum free PSA level was 4.99±0.97ng/mL. Of the 260 men who had serum total PSA levels of≥4ng/mL, 139 underwent biopsy. Of these 139 men, 45 (32.4%) had prostate cancer. Benign prostatic hyperplasia with or without prostatitis was diagnosed in 94 patients (67.6%). There was no significant correlation between age and histologic results of prostate needle biopsy (P-value=0.469). The serum free PSA showed no significant correlation with histologic results of prostate needle biopsy, whereas the serum total PSA level had a significant correlation in patients with adenocarcinoma compared with other diagnosis. The overall frequency of detection of prostate adenocarcinoma was 32.4%. This study revealed that no level of PSA was associated with a 100% positive predictive value and negative biopsy can occur virtually at any PSA level. There is a need to create awareness among the general population and health professionals for an early diagnosis of this common form of cancer. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

The Relationship of Baseline Prostate Specific Antigen and Risk of Future Prostate Cancer and Its Variance by Race.

PubMed

Verges, Daniel P; Dani, Hasan; Sterling, William A; Weedon, Jeremy; Atallah, William; Mehta, Komal; Schreiber, David; Weiss, Jeffrey P; Karanikolas, Nicholas T

2017-01-01

Several studies suggest that a baseline prostate specific antigen (PSA) measured in young men predicts future risk of prostate cancer. Considering recent recommendations against PSA screening, high-risk populations (e.g. black men, men with a high baseline PSA) may be particularly vulnerable in the coming years. Thus, we investigated the relationship between baseline PSA and future prostate cancer in a black majority-minority urban population. A retrospective analysis was performed of the prostate biopsy database (n = 994) at the Brooklyn Veterans Affairs Hospital. These men were referred to urology clinic for elevated PSA and biopsied between 2007 and 2014. Multivariate logistic regression was used to predict positive prostate biopsy from log-transformed baseline PSA, race (black, white, or other), and several other variables. The majority of men identified as black (50.2%). Median age at time of baseline PSA and biopsy was 58.6 and 64.8, respectively. Median baseline PSA was similar among black men and white men (2.70 vs 2.91 for black men vs white men, p = 0.232). Even so, black men were more likely than white men to be diagnosed with prostate cancer (OR 1.62, p < 0.0001). Black men less than age 70 were at particularly greater risk than their white counterparts. Baseline PSA was not a statistically significant predictor of future prostate cancer (p = 0.101). Black men were more likely to be diagnosed with prostate cancer than were white men, despite comparable baseline PSA. In our pre-screened population at the urology clinic, a retrospective examination of baseline PSA did not predict future prostate cancer. Copyright © 2016 National Medical Association. Published by Elsevier Inc. All rights reserved.

Effects of pumpkin seed oil and saw palmetto oil in Korean men with symptomatic benign prostatic hyperplasia.

PubMed

Hong, Heeok; Kim, Chun-Soo; Maeng, Sungho

2009-01-01

This study was to investigate the role of complementary and alternative medicine in the prevention and treatment of benign prostatic hyperplasia. For this purpose, a randomized, double-blind, placebo-controlled trial was performed over 12 months on 47 benign prostatic hyperplasia patients with average age of 53.3 years and international prostate symptom score over 8. Subjects received either sweet potato starch (group A, placebo, 320 mg/day), pumpkin seed oil (group B, 320 mg/day), saw palmetto oil (group C, 320 mg/day) or pumpkin seed oil plus saw palmetto oil (group D, each 320 mg/day). International prostate symptom score, quality of life, serum prostate specific antigen, prostate volume and maximal urinary flow rate were measured. In groups B, C and D, the international prostate symptom score were reduced by 3 months. Quality of life score was improved after 6 months in group D, while those of groups B and C were improved after 3 months, compared to the baseline value. Serum prostate specific antigen was reduced only in group D after 3 months, but no difference was observed in prostate volume in all treatment groups. Maximal urinary flow rate were gradually improved in groups B and C, with statistical significance after 6 months in group B and after 12 months in group C. None of the parameters were significantly improved by combined treatment with pumpkin seed oil and saw palmetto oil. From these results, it is suggested that administrations of pumpkin seed oil and saw palmetto oil are clinically safe and may be effective as complementary and alternative medicine treatments for benign prostatic hyperplasia.

Effects of pumpkin seed oil and saw palmetto oil in Korean men with symptomatic benign prostatic hyperplasia

PubMed Central

Hong, Heeok; Kim, Chun-Soo

2009-01-01

This study was to investigate the role of complementary and alternative medicine in the prevention and treatment of benign prostatic hyperplasia. For this purpose, a randomized, double-blind, placebo-controlled trial was performed over 12 months on 47 benign prostatic hyperplasia patients with average age of 53.3 years and international prostate symptom score over 8. Subjects received either sweet potato starch (group A, placebo, 320 mg/day), pumpkin seed oil (group B, 320 mg/day), saw palmetto oil (group C, 320 mg/day) or pumpkin seed oil plus saw palmetto oil (group D, each 320 mg/day). International prostate symptom score, quality of life, serum prostate specific antigen, prostate volume and maximal urinary flow rate were measured. In groups B, C and D, the international prostate symptom score were reduced by 3 months. Quality of life score was improved after 6 months in group D, while those of groups B and C were improved after 3 months, compared to the baseline value. Serum prostate specific antigen was reduced only in group D after 3 months, but no difference was observed in prostate volume in all treatment groups. Maximal urinary flow rate were gradually improved in groups B and C, with statistical significance after 6 months in group B and after 12 months in group C. None of the parameters were significantly improved by combined treatment with pumpkin seed oil and saw palmetto oil. From these results, it is suggested that administrations of pumpkin seed oil and saw palmetto oil are clinically safe and may be effective as complementary and alternative medicine treatments for benign prostatic hyperplasia. PMID:20098586

Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

PubMed

Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

2017-11-01

Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

Extraction of prostatic lumina and automated recognition for prostatic calculus image using PCA-SVM.

PubMed

Wang, Zhuocai; Xu, Xiangmin; Ding, Xiaojun; Xiao, Hui; Huang, Yusheng; Liu, Jian; Xing, Xiaofen; Wang, Hua; Liao, D Joshua

2011-01-01

Identification of prostatic calculi is an important basis for determining the tissue origin. Computation-assistant diagnosis of prostatic calculi may have promising potential but is currently still less studied. We studied the extraction of prostatic lumina and automated recognition for calculus images. Extraction of lumina from prostate histology images was based on local entropy and Otsu threshold recognition using PCA-SVM and based on the texture features of prostatic calculus. The SVM classifier showed an average time 0.1432 second, an average training accuracy of 100%, an average test accuracy of 93.12%, a sensitivity of 87.74%, and a specificity of 94.82%. We concluded that the algorithm, based on texture features and PCA-SVM, can recognize the concentric structure and visualized features easily. Therefore, this method is effective for the automated recognition of prostatic calculi.

Long-term response to combination therapy with estramustine and somatostatin analogue in a patient with androgen ablation-refractory prostate cancer.

PubMed

Cerulli, Costantino; Sciarra, Alessandro; Salvatori, Gianfilippo; Di Silverio, Franco

2004-12-01

We report on a patient with androgen ablation-refractory prostate adenocarcinoma who had an objective response for longer than 24 months using a combination of estramustine and lanreotide. At baseline from our combination therapy, his prostate-specific antigen level was 21.30 ng/mL and serum chromogranin A level was 816 ng/mL. The patient discontinued complete androgen deprivation therapy and underwent combination therapy with oral estramustine 420 mg/day plus lanreotide acetate 73.9 mg intramuscularly every 4 weeks. After 33 months of follow-up, the patient was alive without clinical disease progression, and his prostate-specific antigen and chromogranin A level was 0.10 and 12 ng/mL, respectively.

Theranostics of prostate cancer: from molecular imaging to precision molecular radiotherapy targeting the prostate specific membrane antigen.

PubMed

Kulkarni, Harshad R; Singh, Aviral; Langbein, Thomas; Schuchardt, Christiane; Mueller, Dirk; Zhang, Jingjing; Lehmann, Coline; Baum, Richard P

2018-06-01

Alterations at the molecular level are a hallmark of cancer. Prostate cancer is associated with the overexpression of prostate-specific membrane antigen (PSMA) in a majority of cases, predominantly in advanced tumors, increasing with the grade or Gleason's score. PSMA can be selectively targeted using radiolabeled PSMA ligands. These small molecules binding the PSMA can be radiolabeled with γ-emitters like 99m Tc and 111 In or positron emitters like 68 Ga and 18 F for diagnosis as well as with their theranostic pairs such as 177 Lu (β-emitter) or 225 Ac (α-emitter) for therapy. This review summarizes the theranostic role of PSMA ligands for molecular imaging and targeted molecular radiotherapy, moving towards precision oncology.

INITIAL SYMPTOMATIC PITUITARY METASTASIS IN A PATIENT WITH PROSTATE FOAMY GLAND CARCINOMA: TAILORING SAFE AND EFFECTIVE THERAPY.

PubMed

Prpić, Marin; Fröbe, Ana; Zadravec, Dijana; Pažanin, Leo; Jakšić, Blanka; Bolanča, Ante; Kusić, Zvonko

2015-06-01

Metastases to pituitary gland are unusual and mostly asymptomatic, presenting with local symptoms in one of ten patients, and only 3%-5% of them are of prostate origin. Here we report and evaluate the effectiveness and safety of multimodal treatment in a patient with pituitary metastasis of a prostate foamy gland carcinoma. A 78-year-old male patient presented with blurred vision and headache without a previous history of malignancy. Magnetic resonance imaging scans revealed a large sellar mass, with infiltration of the surrounding structures. Maximal transsphenoidal reduction of pituitary metastasis was performed, with a histologic finding of metastatic prostate foamy gland adenocarcinoma. Evaluation of the prostate specific antigen revealed a very high level (1461 ng/mL) and foamy gland carcinoma was found on prostate needle biopsy. The patient received 3D conformal external beam radiotherapy with 6 MV photons to the sellar and parasellar region with a tumor dose of 44 Gy, followed by androgen deprivation therapy. Follow up magnetic resonance imaging done after radiotherapy showed shrinkage of the tumor process, with rapid prostate specific antigen decline to 0.3 ng/mL. The visual function was fully established and headache resolved. On the last follow up 14 months after the diagnosis, the patient was alive and free from clinical signs of disease. Tailored treatment, including limited radiotherapy in a higher palliative dose, in a patient with foamy gland symptomatic pituitary metastatic disease resulted in good local and systemic control of the disease. In older male patients with clinical and/or radiologic characteristics suggestive of metastatic pituitary disease, the prostate specific antigen test should be included as part of the work-up.

Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer.

PubMed

Brägelmann, Johannes; Klümper, Niklas; Offermann, Anne; von Mässenhausen, Anne; Böhm, Diana; Deng, Mario; Queisser, Angela; Sanders, Christine; Syring, Isabella; Merseburger, Axel S; Vogel, Wenzel; Sievers, Elisabeth; Vlasic, Ignacija; Carlsson, Jessica; Andrén, Ove; Brossart, Peter; Duensing, Stefan; Svensson, Maria A; Shaikhibrahim, Zaki; Kirfel, Jutta; Perner, Sven

2017-04-01

Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches. Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities ( n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer ( n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq. Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancer was marked by high expression of CDK19 In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8 were present in metastases. In vitro , inhibition of CDK19 and CDK8 by knockdown or treatment with a selective CDK8/CDK19 inhibitor significantly decreased migration and invasion. Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer. Clin Cancer Res; 23(7); 1829-40. ©2016 AACR . ©2016 American Association for Cancer Research.

Urinary prostate-specific antigen: predictor of benign prostatic hyperplasia progression?

PubMed

Pejcic, Tomislav P; Tulic, Cane Dz; Lalic, Natasa V; Glisic, Biljana D; Ignjatovic, Svetlana D; Markovic, Biljana B; Hadzi-Djokic, Jovan B

2013-04-01

Urinary prostate-specific antigen (uPSA) can be used as additional parameter of benign prostatic hyperplasia (BPH) progression. From January 2001 to December 2011, uPSA was determined in 265 patients with benign prostate. Based on total prostate volume (TPV), the patients with benign prostate were divided in two groups: TPV < 31 mL and TPV ≥ 31 mL. Additional three groups were formed upon MTOPS study criteria: non- progressive BPH group (TPV < 31 mL, PSA < 1.6 ng/mL, age < 62 yrs), intermediate group (one, or two parameters {TPV, PSA, age} increased) and progressive BPH group (TPV ≥ 31 ml, PSA ≥ 1.6 ng/mL, age ≥ 62 yrs). Average uPSA values in the groups TPV < 31 mL and TPV ≥ 31 mL were 119.3 ± 124.5 and 255.5 ± 204.9 ng/mL, respectively and they were significantly different (p < 0.0001). Average uPSA values in the non- progressive BPH group, intermediate group and progressive BPH group were 86.8 ± 82.4 ng/mL, 166.6 ± 164.9 ng/mL and 274.9 ± 208.3 ng/mL, respectively and they were significantly different (p < 0.0001). The level of uPSA correlated significantly with TPV (r = 0.32, p < 0.0001). The cut off uPSA level of 150 ng/mL discriminates the patients with non-progressive BPH and progressive BPH with specificity of 0.83 and sensitivity of 0.67. The level of uPSA reflects prostatic hormonal activity and correlates with TPV, PSA and age. UPSA level ≥ 150 ng/mL can be used as additional predictive parameter of BPH progression.

Randomized Clinical Trial of Brewed Green and Black Tea in Men with Prostate Cancer Prior to Prostatectomy

PubMed Central

Henning, Susanne M.; Wang, Piwen; Said, Jonathan W.; Huang, Min; Grogan, Tristan; Elashoff, David; Carpenter, Catherine L.; Heber, David; Aronson, William J.

2014-01-01

Background Preclinical and epidemiologic studies suggest chemopreventive effects of green tea (GT) and black tea (BT) in prostate cancer. In the current study we determined the effect of GT and BT consumption on biomarkers related to prostate cancer development and progression. Methods In this exploratory, open label, phase II trial 113 men diagnosed with prostate cancer were randomized to consume six cups daily of brewed GT, BT or water (control) prior to radical prostatectomy (RP). The primary endpoint was prostate tumor markers of cancer development and progression determined by tissue immunostaining of proliferation (Ki67), apoptosis (Bcl-2, Bax, Tunel), inflammation [nuclear and cytoplasmic nuclear factor kappa B (NFκB)] and oxidation [8-hydroxydeoxy- guanosine (8OHdG)]. Secondary endpoints of urinary oxidation, tea polyphenol uptake in prostate tissue, and serum prostate specific antigen (PSA) were evaluated by high performance liquid chromatography and ELISA analysis. Results Ninety three patients completed the intervention. There was no significant difference in markers of proliferation, apoptosis and oxidation in RP tissue comparing GT and BT to water control. Nuclear staining of NFkB was significantly decreased in RP tissue of men consuming GT (p=0.013) but not BT (p=0.931) compared to water control. Tea polyphenols were detected in prostate tissue from 32 of 34 men consuming GT but not in the other groups. Evidence of a systemic antioxidant effect was observed (reduced urinary 8OHdG) only with GT consumption (p=0.03). GT, but not BT or water, also led to a small but statistically significant decrease in serum prostate-specific antigen (PSA) levels (p=0.04). Conclusion Given the GT-induced changes in NFkB and systemic oxidation, and uptake of GT polyphenols in prostate tissue, future longer-term studies are warranted to further examine the role of GT for prostate cancer prevention and treatment, and possibly for other prostate conditions such as prostatitis. PMID:25545744

Hypoexpression and epigenetic regulation of candidate tumor suppressor gene CADM-2 in human prostate cancer.

PubMed

Chang, Guimin; Xu, Shuping; Dhir, Rajiv; Chandran, Uma; O'Keefe, Denise S; Greenberg, Norman M; Gingrich, Jeffrey R

2010-11-15

Cell adhesion molecules (CADM) comprise a newly identified protein family whose functions include cell polarity maintenance and tumor suppression. CADM-1, CADM-3, and CADM-4 have been shown to act as tumor suppressor genes in multiple cancers including prostate cancer. However, CADM-2 expression has not been determined in prostate cancer. The CADM-2 gene was cloned and characterized and its expression in human prostatic cell lines and cancer specimens was analyzed by reverse transcription-PCR and an immunohistochemical tissue array, respectively. The effects of adenovirus-mediated CADM-2 expression on prostate cancer cells were also investigated. CADM-2 promoter methylation was evaluated by bisulfite sequencing and methylation-specific PCR. We report the initial characterization of CADM-2 isoforms: CADM-2a and CADM-2b, each with separate promoters, in human chromosome 3p12.1. Prostate cancer cell lines, LNCaP and DU145, expressed negligible CADM-2a relative to primary prostate tissue and cell lines, RWPE-1 and PPC-1, whereas expression of CADM-2b was maintained. Using immunohistochemistry, tissue array results from clinical specimens showed statistically significant decreased expression in prostate carcinoma compared with normal donor prostate, benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and normal tissue adjacent to tumor (P < 0.001). Adenovirus-mediated CADM-2a expression suppressed DU145 cell proliferation in vitro and colony formation in soft agar. The decrease in CADM-2a mRNA in cancer cell lines correlated with promoter region hypermethylation as determined by bisulfite sequencing and methylation-specific PCR. Accordingly, treatment of cells with the demethylating agent 5-aza-2'-deoxycytidine alone or in combination with the histone deacetylase inhibitor trichostatin A resulted in the reactivation of CADM-2a expression. CADM-2a protein expression is significantly reduced in prostate cancer. Its expression is regulated in part by promoter methylation and implicates CADM-2 as a previously unrecognized tumor suppressor gene in a proportion of human prostate cancers. ©2010 AACR.

Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study

PubMed Central

Brunner, Clair; Davies, Neil M.; Martin, Richard M.; Eeles, Rosalind; Easton, Doug; Kote‐Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A.; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C.; Neal, David; Donovan, Jenny; Hamdy, Freddie C.; 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.; Pandha, Hardev

2016-01-01

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol‐metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study‐specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol‐metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer‐specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta‐analysed using fixed‐effect and random‐effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed‐effect meta‐analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low‐grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression. PMID:27643404

Evaluation of [-2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis.

PubMed

Filella, Xavier; Giménez, Nuria

2013-04-01

The usefulness of %[-2] proPSA and Prostate Health Index (phi) in the detection of prostate cancer are currently unknown. It has been suggested that these tests can distinguish prostate cancer from benign prostatic diseases better than PSA or %fPSA. We performed a systematic review and meta-analysis of the available scientific evidence to evaluate the clinical usefulness of %[-2] proPSA and phi. Relevant published papers were identified by searching computerized bibliographic systems. Data on sensitivity and specificity were extracted from 12 studies: 10 studies about %[-2] proPSA (3928 patients in total, including 1762 with confirmed prostate cancer) and eight studies about phi (2919 patients in total, including 1515 with confirmed prostate cancer). The sensitivity for the detection of prostate cancer was 90% for %[-2] proPSA and phi, while the pooled specificity was 32.5% (95% CI 30.6-34.5) and 31.6% (95% CI 29.2-34.0) for %[-2] proPSA and phi, respectively. The measurement of %[-2] proPSA improves the accuracy of prostate cancer detection in comparison with PSA or %fPSA, particularly in the group of patients with PSA between 2 μg/L and 10 μg/L. Similar results were obtained measuring phi. Using these tests, it is possible to reduce the number of unnecessary biopsies, maintaining a high cancer detection rate. Published results also showed that %[-2] proPSA and phi are related to the aggressiveness of the tumor.

Prostate-specific antigen screening in a high-risk population: lessons from the community and how they relate to large-scale population-based studies.

PubMed

Shelton, Jeremy B; Barocas, Daniel A; Conway, Frances; Hart, Kathleen; Nelson, Kinloch; Richstone, Lee; Gonzalez, Ricardo R; Raman, Jay D; Scherr, Douglas S

2005-05-01

To estimate the incidence of prostate cancer among African-American men and Caribbean immigrants to the United States, to assess the applicability of large-scale prostate screening trials to a community screening program, and to recruit unscreened men. African-American and Caribbean-American men were targeted with a community-based prostate cancer screening program in Jamaica, New York. Serum prostate-specific antigen determination and digital rectal examination were used to determine abnormal findings. The incidence of an abnormal screening examination was used to project the incidence of prostate cancer, which was compared with that in other reported trials. The projected incidence of prostate cancer among African-Americans and Caribbean-Americans older than 50 years was 8% and 7%, respectively, similar to that reported in other trials of African-American men. The projected incidence of prostate cancer in Caribbean-American men aged 40 to 49 years was 1%, the same as the high rate reported among Caribbean men. As in other trials, a family history of prostate cancer and age were strong predictors of abnormal findings. Of the recruited men older than 50 years, 58% had never been screened compared with 42% nationally. Large population-based screening trials have identified ethnic groups at high risk of prostate cancer. This trial detected high rates of abnormal screening findings by targeting ethnicity. The incidence of an abnormal examination was high in Caribbean-American men younger than 50 years old. Finally, this trial successfully recruited underscreened men.

Association of Reported Prostate Cancer Risk Alleles With PSA Levels Among Men Without a Diagnosis of Prostate Cancer

PubMed Central

Wiklund, Fredrik; Zheng, S. Lilly; Sun, Jielin; Adami, Hans-Olov; Lilja, Hans; Hsu, Fang-Chi; Stattin, Pär; Adolfsson, Jan; Cramer, Scott D.; Duggan, David; Carpten, John D.; Chang, Bao-Li; Isaacs, William B.; Grönberg, Henrik; Xu, Jianfeng

2012-01-01

BACKGROUND Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels. METHODS We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer. RESULTS Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P≤0.05) were found for six SNPs. These six SNPs had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend=3.4×10−14. In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients. CONCLUSIONS Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening. PMID:19116992

Maturation of the developing human fetal prostate in a rodent xenograft model

PubMed Central

Saffarini, Camelia M.; McDonnell, Elizabeth V.; Amin, Ali; Spade, Daniel J.; Huse, Susan M.; Kostadinov, Stefan; Hall, Susan J.; Boekelheide, Kim

2015-01-01

Background Prostate cancer is the most commonly diagnosed non-skin cancer in men. The etiology of prostate cancer is unknown, although both animal and epidemiologic data suggest that early life exposures to various toxicants, may impact DNA methylation status during development, playing an important role. Methods We have developed a xenograft model to characterize the growth and differentiation of human fetal prostate implants (gestational age 12-24 weeks) that can provide new data on the potential role of early life stressors on prostate cancer. The expression of key immunohistochemical markers responsible for prostate maturation was evaluated, including p63, cytokeratin 18, α-smooth muscle actin, vimentin, caldesmon, Ki-67, prostate specific antigen, estrogen receptor-α, and androgen receptor. Xenografts were separated into epithelial and stromal compartments using laser capture microdissection (LCM), and the DNA methylation status was assessed in >480,000 CpG sites throughout the genome. Results Xenografts demonstrated growth and maturation throughout the 200 days of post-implantation evaluation. DNA methylation profiles of laser capture micro-dissected tissue demonstrated tissue-specific markers clustered by their location in either the epithelium or stroma of human prostate tissue. Differential methylated promoter region CpG-associated gene analysis revealed significantly more stromal than epithelial DNA methylation in the 30 and 90-day xenografts. Functional classification analysis identified CpG-related gene clusters in methylated epithelial and stromal human xenografts. Conclusion This study of human fetal prostate tissue establishes a xenograft model that demonstrates dynamic growth and maturation, allowing for future mechanistic studies of the developmental origins of later life proliferative prostate disease. PMID:24038131

Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement.

PubMed

Grossman, David C; Curry, Susan J; Owens, Douglas K; Bibbins-Domingo, Kirsten; Caughey, Aaron B; Davidson, Karina W; Doubeni, Chyke A; Ebell, Mark; Epling, John W; Kemper, Alex R; Krist, Alex H; Kubik, Martha; Landefeld, C Seth; Mangione, Carol M; Silverstein, Michael; Simon, Melissa A; Siu, Albert L; Tseng, Chien-Wen

2018-05-08

In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 13%, and the lifetime risk of dying of prostate cancer is 2.5%. The median age of death from prostate cancer is 80 years. Many men with prostate cancer never experience symptoms and, without screening, would never know they have the disease. African American men and men with a family history of prostate cancer have an increased risk of prostate cancer compared with other men. To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on prostate-specific antigen (PSA)-based screening for prostate cancer. The USPSTF reviewed the evidence on the benefits and harms of PSA-based screening for prostate cancer and subsequent treatment of screen-detected prostate cancer. The USPSTF also commissioned a review of existing decision analysis models and the overdiagnosis rate of PSA-based screening. The reviews also examined the benefits and harms of PSA-based screening in patient subpopulations at higher risk of prostate cancer, including older men, African American men, and men with a family history of prostate cancer. Adequate evidence from randomized clinical trials shows that PSA-based screening programs in men aged 55 to 69 years may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 men screened. Screening programs may also prevent approximately 3 cases of metastatic prostate cancer per 1000 men screened. Potential harms of screening include frequent false-positive results and psychological harms. Harms of prostate cancer treatment include erectile dysfunction, urinary incontinence, and bowel symptoms. About 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence, and 2 in 3 men will experience long-term erectile dysfunction. Adequate evidence shows that the harms of screening in men older than 70 years are at least moderate and greater than in younger men because of increased risk of false-positive results, diagnostic harms from biopsies, and harms from treatment. The USPSTF concludes with moderate certainty that the net benefit of PSA-based screening for prostate cancer in men aged 55 to 69 years is small for some men. How each man weighs specific benefits and harms will determine whether the overall net benefit is small. The USPSTF concludes with moderate certainty that the potential benefits of PSA-based screening for prostate cancer in men 70 years and older do not outweigh the expected harms. For men aged 55 to 69 years, the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one and should include discussion of the potential benefits and harms of screening with their clinician. Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men. However, many men will experience potential harms of screening, including false-positive results that require additional testing and possible prostate biopsy; overdiagnosis and overtreatment; and treatment complications, such as incontinence and erectile dysfunction. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the balance of benefits and harms on the basis of family history, race/ethnicity, comorbid medical conditions, patient values about the benefits and harms of screening and treatment-specific outcomes, and other health needs. Clinicians should not screen men who do not express a preference for screening. (C recommendation) The USPSTF recommends against PSA-based screening for prostate cancer in men 70 years and older. (D recommendation).

Prostate-Specific Membrane Antigen Expression in Distal Radius Fracture.

PubMed

Hoberück, Sebastian; Michler, Enrico; Kaiser, Daniel; Röhnert, Anne; Zöphel, Klaus; Kotzerke, Jörg

2018-06-12

A 79-year old man with prostate cancer under active surveillance for 5 years was referred for a PSMA-PET/MRI for re-evaluation because of a rising prostate-specific antigen value. PET/MRI revealed a ribbonlike tracer accumulation in a healing fracture of the distal radius. This case illustrates that PSMA expression may occur in healing bone fractures in the distal radius. It can be assumed that benign causes of tracer accumulations in the upper extremities are missed in PET/CT due to elevated position of the arms during image acquisition.

Multifunctional iron platinum stealth immunomicelles: targeted detection of human prostate cancer cells using both fluorescence and magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Taylor, Robert M.; Huber, Dale L.; Monson, Todd C.; Ali, Abdul-Mehdi S.; Bisoffi, Marco; Sillerud, Laurel O.

2011-10-01

Superparamagnetic iron oxide nanoparticles (SPIONs) are the most common type of contrast agents used in contrast agent-enhanced magnetic resonance imaging (MRI). Still, there is a great deal of room for improvement, and nanoparticles with increased MRI relaxivities are needed to increase the contrast enhancement in MRI applied to various medical conditions including cancer. We report the synthesis of superparamagnetic iron platinum nanoparticles (SIPPs) and subsequent encapsulation using PEGylated phospholipids to create stealth immunomicelles (DSPE-SIPPs) that can be specifically targeted to human prostate cancer cell lines and detected using both MRI and fluorescence imaging. SIPP cores and DSPE-SIPPs were 8.5 ± 1.6 nm and 42.9 ± 8.2 nm in diameter, respectively, and the SIPPs had a magnetic moment of 120 A m2/kg iron. J591, a monoclonal antibody against prostate specific membrane antigen (PSMA), was conjugated to the DSPE-SIPPs (J591-DSPE-SIPPs), and specific targeting of J591-DSPE-SIPPs to PSMA-expressing human prostate cancer cell lines was demonstrated using fluorescence confocal microscopy. The transverse relaxivity of the DSPE-SIPPs, measured at 4.7 Tesla, was 300.6 ± 8.5 s-1 mM-1, which is 13-fold better than commercially available SPIONs (23.8 ± 6.9 s-1 mM-1) and 3-fold better than reported relaxivities for Feridex® and Resovist®. Our data suggest that J591-DSPE-SIPPs specifically target human prostate cancer cells in vitro, are superior contrast agents in T 2-weighted MRI, and can be detected using fluorescence imaging. To our knowledge, this is the first report on the synthesis of multifunctional SIPP micelles and using SIPPs for the specific detection of prostate cancer.

WAXS studies of the structural diversity of hemoglobin in solution.

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

Makowski, L.; Bardhan, J.; Gore, D.

2011-01-01

Specific ligation states of hemoglobin are, when crystallized, capable of taking on multiple quaternary structures. The relationship between these structures, captured in crystal lattices, and hemoglobin structure in solution remains uncertain. Wide-angle X-ray solution scattering (WAXS) is a sensitive probe of protein structure in solution that can distinguish among similar structures and has the potential to contribute to these issues. We used WAXS to assess the relationships among the structures of human and bovine hemoglobins in different liganded forms in solution. WAXS data readily distinguished among the various forms of hemoglobins. WAXS patterns confirm some of the relationships among hemoglobinmore » structures that have been defined through crystallography and NMR and extend others. For instance, methemoglobin A in solution is, as expected, nearly indistinguishable from HbCO A. Interestingly, for bovine hemoglobin, the differences between deoxy-Hb, methemoglobin and HbCO are smaller than the corresponding differences in human hemoglobin. WAXS data were also used to assess the spatial extent of structural fluctuations of various hemoglobins in solution. Dynamics has been implicated in allosteric control of hemoglobin, and increased dynamics has been associated with lowered oxygen affinity. Consistent with that notion, WAXS patterns indicate that deoxy-Hb A exhibits substantially larger structural fluctuations than HbCO A. Comparisons between the observed WAXS patterns and those predicted on the basis of atomic coordinate sets suggest that the structures of Hb in different liganded forms exhibit clear differences from known crystal structure.« less

The role of blood neutrophil count and the neutrophil-to-lymphocyte ratio as a predictive factor for prostate biopsy results.

PubMed

Kamali, Koosha; Ashrafi, Mojtaba; Shadpour, Pejman; Ameli, Mojtaba; Khayyamfar, Amirmahdi; Abolhasani, Maryam; Azizpoor, Amin

2018-04-01

It is apparent that prostate cancer has harmful effects on the erythrocytes, leucocytes, and platelets. In addition, it has been suggested that the toxic granules in neutrophils lead to inflammation in the cancerous tissues besides the activation of monocytes, so in this study we aimed to evaluate the blood neutrophil count besides the neutrophil-to-lymphocyte ratio as a predictive factor for prostate biopsy results and their relationship with prostate cancer grade in patients undergoing biopsy of the prostate. For all men with irritative lower urinary tract symptoms visiting Hasheminezhad Hospital from January to July 2015, in case of having a suspicious digital rectal examination or aged above 40 years, prostate-specific antigen was requested and in case of abnormal results, they underwent prostate biopsy. In order to examine the study hypothesis, the blood neutrophil count and the neutrophil-to-lymphocyte ratio were measured and compared with the abnormal prostate-specific antigen results and suspicious digital rectal examination. Among the 500 referred samples for biopsy, 352 (70.4%) had a negative biopsy result, while it was positive in the other 148 (29.6). The mean neutrophil count showed no statistical difference regarding the biopsy results (p = 0.381). When measuring the neutrophil-to-lymphocyte ratio again with biopsy results, no statistically significant difference was obtained based on the biopsy results (p = 0.112). Neutrophil count and neutrophil-to-lymphocyte ratio cannot be predictive factors for positive prostate cancer biopsy.

Fluorescence of prostate-specific antigen as measured with a portable 1D scanner

NASA Astrophysics Data System (ADS)

Kim, Byeong C.; Jeong, Jin H.; Jeong, Dong S.; Kim, Young M.; Oh, Sang W.; Choi, Eui Y.; Kim, Jae H.; Nahm, Kie B.

2005-01-01

Prostate-specific antigen (PSA) is an androgen-dependent glycoprotein protease (M.W. 33 kDa) and a member of kallikrein super-family of serine protease, and has chymotrypsin-like enzymatic activity. It is synthesized by the prostate epithelial cells and found in the prostate gland and seminal plasma as a major protein. It is widely used as a clinical marker for diagnosis, screening, monitoring and prognosis of prostate cancer. In normal male adults, the concentration of PSA in the blood is below 4 ng/ml and this value increases in patients with the prostate cancer or the benign prostatic hyperplasia (BPH) due to its leakage into the circulatory system. As such, systematic monitoring of the PSA level in the blood can provide critical information about the progress of the prostatic disease. We have developed a compact integral system that can quantitatively measure the concentration of total PSA in human blood. This system utilizes the fluorescence emitted from the dye molecules attached to PSA molecules after appropriate immunoassay-based processing. Developed for the purpose of providing an affordable means of fast point-of-care testing of the prostate cancer, this system proved to be able to detect the presence of the PSA at the level of 0.18 ng/ml in less than 12 minutes, with the actual measurement taking less than 2 minutes. The design concept for this system is presented together with the result for a few representative samples.

Slow Disease Progression in a C57BL/6 Pten-Deficient Mouse Model of Prostate Cancer

PubMed Central

Svensson, Robert U.; Haverkamp, Jessica M.; Thedens, Daniel R.; Cohen, Michael B.; Ratliff, Timothy L.; Henry, Michael D.

2011-01-01

Prostate-specific deletion of Pten in mice has been reported to recapitulate histological progression of human prostate cancer. To improve on this model, we introduced the conditional ROSA26 luciferase reporter allele to monitor prostate cancer progression via bioluminescence imaging and extensively backcrossed mice onto the albino C57BL/6 genetic background to address variability in tumor kinetics and to enhance imaging sensitivity. Bioluminescence signal increased rapidly in Ptenp−/− mice from 3 to 11 weeks, but was much slower from 11 to 52 weeks. Changes in bioluminescence signal were correlated with epithelial proliferation. Magnetic resonance imaging revealed progressive increases in prostate volume, which were attributed to excessive fluid retention in the anterior prostate and to expansion of the stroma. Development of invasive prostate cancer in 52-week-old Ptenp−/− mice was rare, indicating that disease progression was slowed relative to that in previous reports. Tumors in these mice exhibited a spontaneous inflammatory phenotype and were rapidly infiltrated by myeloid-derived suppressor cells. Although Ptenp−/− tumors responded to androgen withdrawal, they failed to exhibit relapsed growth for up to 1 year. Taken together, these data identify a mild prostate cancer phenotype in C57BL/6 prostate-specific Pten-deficient mice, reflecting effects of the C57BL/6 genetic background on cancer progression. This model provides a platform for noninvasive assessment of how genetic and environmental risk factors may affect disease progression. PMID:21703427

Androgenic Regulation of White Adipose Tissue-Prostate Cancer Interactions

DTIC Science & Technology

2012-05-01

ijo.2011.953. Epub 2011 Feb 23. 6. Sharma PK, Singh R, Novakovic KR, Eaton JW, Grizzle WE, Singh S. CCR9 mediates PI3K/AKT-dependent antiapoptotic...Cooper, C.R., Novakovic , K.R., Grizzle, W.E., Lillard Jr., J.W., 2009. Serum CXCL13 positively correlates with prostatic disease, prostate-specific

The Interactions between Insulin and Androgens in Progression to Castrate-Resistant Prostate Cancer

PubMed Central

Gunter, Jennifer H.; Lubik, Amy A.; McKenzie, Ian; Pollak, Michael; Nelson, Colleen C.

2012-01-01

An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer. PMID:22548055

Multiplexed targeted mass spectrometry assays for prostate cancer-associated urinary proteins

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

Shi, Tujin; Quek, Sue-Ing; Gao, Yuqian

Biomarkers for effective early diagnosis and prognosis of prostate cancer are still lacking. Multiplexed assays for cancer-associated proteins could be useful for identifying biomarkers for cancer detection and stratification. Herein, we report the development of sensitive targeted mass spectrometry assays for simultaneous quantification of 10 prostate cancer-associated proteins in urine. The diagnostic utility of these markers was evaluated with an initial cohort of 20 clinical urine samples. Individual marker concentration was normalized against the measured urinary prostate-specific antigen level as a reference of prostate-specific secretion. The areas under the receiver-operating characteristic curves for the 10 proteins ranged from 0.75 formore » CXCL14 to 0.87 for CEACAM5. Furthermore, MMP9 level was found to be significantly higher in patients with high Gleason scores, suggesting a potential of MMP9 as a marker for risk level assessment. Taken together, our work illustrated the feasibility of accurate multiplexed measurements of low-abundance cancer-associated proteins in urine and provided a viable path forward for preclinical verification of candidate biomarkers for prostate cancer.« less

Glycosylation potential of human prostate cancer cell lines

PubMed Central

Gao, Yin; Chachadi, Vishwanath B.; Cheng, Pi-Wan

2014-01-01

Altered glycosylation is a universal feature of cancer cells and altered glycans can help cancer cells escape immune surveillance, facilitate tumor invasion, and increase malignancy. The goal of this study was to identify specific glycoenzymes, which could distinguish prostate cancer cells from normal prostatic cells. We investigated enzymatic activities and gene expression levels of key glycosyl- and sulfotransferases responsible for the assembly of O- and N-glycans in several prostatic cells. These cells included immortalized RWPE-1 cells derived from normal prostatic tissues, and prostate cancer cells derived from metastasis in bone (PC-3), brain (DU145), lymph node (LNCaP), and vertebra (VCaP). We found that all cells were capable of synthesizing complex N-glycans and O-glycans with the core 1 structure, and each cell line had characteristic bio-synthetic pathways to modify these structures. The in vitro measured activities corresponded well to the mRNA levels of glycosyltransferases and sulfotransferases. Lectin and antibody binding to whole cells supported these results, which form the basis for the development of tumor cell-specific targeting strategies. PMID:22843320

Body mass index as a classifier to predict biochemical recurrence after radical prostatectomy in patients with lower prostate-specific antigen levels

PubMed Central

Goto, Keisuke; Nagamatsu, Hirotaka; Teishima, Jun; Kohada, Yuki; Fujii, Shinsuke; Kurimura, Yoshimasa; Mita, Koji; Shigeta, Masanobu; Maruyama, Satoshi; Inoue, Yoji; Nakahara, Mitsuru; Matsubara, Akio

2017-01-01

Prostate cancer, one of the most common malignant tumors among men, is closely associated with obesity and, thus far, several studies have suggested the association between obesity and aggressive pathological characteristics in the United States. However, the effect of obesity on prostate cancer mortality is controversial, and it remains unclear whether obesity contributes to the aggressiveness of prostate cancer in Asian patients. The aim of the present study was to investigate the association between body mass index (BMI) and the clinicopathological characteristics of prostate cancer in 2,003 Japanese patients who underwent radical prostatectomy. There was a significant association between higher BMI and higher Gleason score (GS). The multivariate analysis also revealed that BMI was an independent indicator for GS ≥8 at surgery. Moreover, among patients with lower prostate-specific antigen levels, biochemical recurrence-free survival was significantly worse in those with higher BMI. These results suggest that BMI may be a classifier for predicting adverse pathological findings and biochemical recurrence after radical prostatectomy in Japanese patients. PMID:28515927

Age-Specific Cutoff Value for the Application of Percent Free Prostate-Specific Antigen (PSA) in Chinese Men with Serum PSA Levels of 4.0-10.0 ng/ml.

PubMed

Chen, Rui; Huang, Yiran; Cai, Xiaobing; Xie, Liping; He, Dalin; Zhou, Liqun; Xu, Chuanliang; Gao, Xu; Ren, Shancheng; Wang, Fubo; Ma, Lulin; Wei, Qiang; Yin, Changjun; Tian, Ye; Sun, Zhongquan; Fu, Qiang; Ding, Qiang; Zheng, Junhua; Ye, Zhangqun; Ye, Dingwei; Xu, Danfeng; Hou, Jianquan; Xu, Kexin; Yuan, Jianlin; Gao, Xin; Liu, Chunxiao; Pan, Tiejun; Sun, Yinghao

2015-01-01

The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies. Consecutive patients with a prostate-specific antigen (PSA) level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis. The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60-69, 70-79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0-10.0 ng/ml to detect 90% of all PCa. The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population.

Age-Specific Cutoff Value for the Application of Percent Free Prostate-Specific Antigen (PSA) in Chinese Men with Serum PSA Levels of 4.0–10.0 ng/ml

PubMed Central

Xie, Liping; He, Dalin; Zhou, Liqun; Xu, Chuanliang; Gao, Xu; Ren, Shancheng; Wang, Fubo; Ma, Lulin; Wei, Qiang; Yin, Changjun; Tian, Ye; Sun, Zhongquan; Fu, Qiang; Ding, Qiang; Zheng, Junhua; Ye, Zhangqun; Ye, Dingwei; Xu, Danfeng; Hou, Jianquan; Xu, Kexin; Yuan, Jianlin; Gao, Xin; Liu, Chunxiao; Pan, Tiejun; Sun, Yinghao

2015-01-01

Objective The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies. Methods Consecutive patients with a prostate-specific antigen (PSA) level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis. Results The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60–69, 70–79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0–10.0 ng/ml to detect 90% of all PCa. Conclusions The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population. PMID:26091007

Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis).

PubMed

Lokant, M T; Naz, R K

2015-04-01

Prostate-specific antigen (PSA), produced by the prostate, liquefies post-ejaculate semen. PSA is detected in semen and blood. Increased circulating PSA levels indicate prostate abnormality [prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis (PTIS)], with variance among individuals. As the prostate has been proposed as an immune organ, we hypothesise that variation in PSA levels among men may be due to presence of auto-antibodies against PSA. Sera from healthy men (n = 28) and men having prostatitis (n = 25), BPH (n = 30) or PC (n = 29) were tested for PSA antibody presence using enzyme-linked immunosorbent assay (ELISA) values converted to standard deviation (SD) units, and Western blotting. Taking ≥2 SD units as cut-off for positive immunoreactivity, 0% of normal men, 0% with prostatitis, 33% with BPH and 3.45% with PC demonstrated PSA antibodies. One-way analysis of variance (anova) performed on the mean absorbance values and SD units of each group showed BPH as significantly different (P < 0.01) compared with PC and prostatitis. All others were nonsignificant (P < 0.05). Men (33%) with BPH had PSA antibodies by ELISA and Western blot. These discoveries may find clinical application in differential diagnosis among prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis. © 2014 Blackwell Verlag GmbH.

Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

PubMed

Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

2017-09-01

Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors

PubMed Central

Hubert, Rene S.; Vivanco, Igor; Chen, Emily; Rastegar, Shiva; Leong, Kahan; Mitchell, Steve C.; Madraswala, Rashida; Zhou, Yanhong; Kuo, James; Raitano, Arthur B.; Jakobovits, Aya; Saffran, Douglas C.; Afar, Daniel E. H.

1999-01-01

In search of novel genes expressed in metastatic prostate cancer, we subtracted cDNA isolated from benign prostatic hypertrophic tissue from cDNA isolated from a prostate cancer xenograft model that mimics advanced disease. One novel gene that is highly expressed in advanced prostate cancer encodes a 339-amino acid protein with six potential membrane-spanning regions flanked by hydrophilic amino- and carboxyl-terminal domains. This structure suggests a potential function as a channel or transporter protein. This gene, named STEAP for six-transmembrane epithelial antigen of the prostate, is expressed predominantly in human prostate tissue and is up-regulated in multiple cancer cell lines, including prostate, bladder, colon, ovarian, and Ewing sarcoma. Immunohistochemical analysis of clinical specimens demonstrates significant STEAP expression at the cell–cell junctions of the secretory epithelium of prostate and prostate cancer cells. Little to no staining was detected at the plasma membranes of normal, nonprostate human tissues, except for bladder tissue, which expressed low levels of STEAP at the cell membrane. Protein analysis located STEAP at the cell surface of prostate-cancer cell lines. Our results support STEAP as a cell-surface tumor-antigen target for prostate cancer therapy and diagnostic imaging. PMID:10588738

The relationship between histological prostatitis and lower urinary tract symptoms and sexual function.

PubMed

Kumsar, Sukru; Kose, Osman; Aydemir, Huseyin; Halis, Fikret; Gokce, Ahmet; Adsan, Oztug; Akkaya, Zeynep Kahyaoglu

2016-01-01

This prospective analysis assessed the effect of histological prostatitis on lower urinary tract functions and sexual function. The patients were separated into two groups as histologically observed prostatitis (Group A) and no prostatitis (Group B) according to the biopsy outcomes. International prostate symptom score, international index of erectile function-5 scores, maximal and average flow rate, and residual urine volumes were compared statistically between groups. There was no significant difference (P>0.05) in baseline age (t=0.64), body mass index value (t=0.51), prostate volume (t=0.87), prostate-specific antigen levels (t=0.43), maximal (t=0.84) and average flow rate (t=0.59), and post-void residual urine volume (t=0.71). Mean international prostate symptom score in patients with prostatitis was numerically but not significantly higher than that in those without prostatitis (t=0.794, P=0.066). Mean international index of erectile function-5 score in the prostatitis group was significantly lower than that in those without prostatitis (t=1.854, P=0.013). Histological prostatitis notably affected sexual function of patients and may serve as a major risk factor for sexual dysfunction while having little effect on lower urinary tract symptoms.

Androgen-induced programs for prostate epithelial growth and invasion arise in embryogenesis and are reactivated in cancer

PubMed Central

Schaeffer, EM; Marchionni, L; Huang, Z; Simons, B; Blackman, A; Yu, W; Parmigiani, G; Berman, DM

2008-01-01

Cancer cells differentiate along specific lineages that largely determine their clinical and biologic behavior. Distinct cancer phenotypes from different cells and organs likely result from unique gene expression repertoires established in the embryo and maintained after malignant transformation. We used comprehensive gene expression analysis to examine this concept in the prostate, an organ with a tractable developmental program and a high propensity for cancer. We focused on gene expression in the murine prostate rudiment at three time points during the first 48 h of exposure to androgen, which initiates proliferation and invasion of prostate epithelial buds into surrounding urogenital sinus mesenchyme. Here, we show that androgen exposure regulates genes previously implicated in prostate carcinogenesis comprising pathways for the phosphatase and tensin homolog (PTEN), fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK), and Wnt signaling along with cellular programs regulating such ‘hallmarks’ of cancer as angiogenesis, apoptosis, migration and proliferation. We found statistically significant evidence for novel androgeninduced gene regulation events that establish and/or maintain prostate cell fate. These include modulation of gene expression through microRNAs, expression of specific transcription factors, and regulation of their predicted targets. By querying public gene expression databases from other tissues, we found that rather than generally characterizing androgen exposure or epithelial budding, the early prostate development program more closely resembles the program for human prostate cancer. Most importantly, early androgen-regulated genes and functional themes associated with prostate development were highly enriched in contrasts between increasingly lethal forms of prostate cancer, confirming a ‘reactivation’ of embryonic pathways for proliferation and invasion in prostate cancer progression. Among the genes with the most significant links to the development and cancer, we highlight coordinate induction of the transcription factor Sox9 and suppression of the proapoptotic phospholipid-binding protein Annexin A1 that link early prostate development to early prostate carcinogenesis. These results credential early prostate development as a reliable and valid model system for the investigation of genes and pathways that drive prostate cancer. PMID:18794802

[Prostate histopathology of NIH category IV prostatitis detected by sextant prostate needle biopsy from the patients with high prostatic specific antigen].

PubMed

Shimomura, Tatsuya; Kiyota, Hiroshi; Takahashi, Hiroyuki; Madarame, Jun; Kimura, Takahiro; Onodera, Shouichi

2003-08-01

Asymptomatic prostatitis is classified as category IV in NIH classification of prostatitis syndrome (1999). No report concerning this category has been present. We investigated this category histopathologically and clinically, in order to clarify the histopathological distribution and its correlation to the clinical features, in this study. Among 785 patients who were suspected prostate cancer because of their high prostatic specific antigen (PSA) values and to have a sextant prostate needle biopsy was performed between January, 1996 and December, 2000, 88 patients (11.2%) were diagnosed as NIH category IV prostatitis (asymptomatic prostatitis). We observed all pathological specimens stained with Hematoxylin-Eosine, and classified them into subtypes according to the classification criteria for prostatitis defined by True et al. (1999). We also investigated the relationship between histopathological distribution and clinical features such as PSA values, PSA density, the incidence of pyuria or bacteriuria. In the histopathological study, grade distributions were 12.5% (11/88) in mild, 71.6% (63/88) in moderate, and 15.9% (14/88) in severe. Location distributions were 2.3% (2/88) in glandular, 68.2% (60/88) in periglandular, and 29.5% (26/88) in stromal. No relationship between these subtypes and clinical features was recognized statistically. However, 7 patients (7.95%) were diagnosed as prostate cancers, later. Pyuria was found in 29.1% (23/79). Bacteriuria was present in 14.3% (11/77). Isolated bacteria were 4 strains of Enterococcus faccalis, 2 strains of each of Pseudomonas aeruginosa and Staphylococcus aureus, and one strain of each of Escherichia coli, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Staphylococcus haemolyticus, and Staphylococcus epidermidis. Gram positive rod, and Candida sp. No relationship between these subtypes and bacterial species was recognized. These results indicated that the incidence of NIII category IV prostatits was not low without correlation to any clinical features. However, we should pay attention to the presence of prostate cancer, because a small number of the patients were diagnosed as prostate cancer, later.

Diagnostic and prognostic significance of prostate specific antigen and serum interleukin 18 and 10 in patients with locally advanced prostate cancer: a prospective study.

PubMed

Dwivedi, Shailendra; Goel, Apul; Natu, Shanker M; Mandhani, Anil; Khattri, Sanjay; Pant, Kamlesh K

2011-01-01

Prostate cancer is one of the most common cancers afflicting men today. Prostate biopsy, an invasive procedure is generally used for diagnoses but attempts are being made to find accurate and precise non-invasive biomarkers. Diagnostic accuracy of prostate specific antigen (PSA) has been well documented. Serum interleukin-18 (IL-18) and interleukin-10 (IL-10) have shown their diagnostic ability in other cancers but not investigated well in prostate cancer. This study, thus determines the diagnostic and prognostic significance of PSA, IL-18 and IL-10 prospectively in patients with carcinoma prostate. A total of 149 patients, aged 40-84 yrs were investigated during April 2007 to July 2010 and recruited for this study after Institutional ethical approval. Of the total of 149 patients, 71 had biopsy proven prostate cancers (TNM stage: T2=17, T3=26 and T4=28) and 78 clinical benign prostate hyperplasia (BPH). Peripheral blood samples of all patients and 71 age matched control subjects were obtained at baseline and estimation of PSA, IL-18 and IL-10 was done by enzyme linked immunosorbent assay (ELISA). Carcinoma prostate patients were followed for three years. Data were analyzed with ANOVA, ROC curve analysis and survival analysis. The baseline levels of PSA, IL-18 and IL-10 in all groups of carcinoma prostate were found to be significantly (p<0.01) higher than both Control and BPH. The levels of IL-18 and IL-10 also found to be elevated significantly in stage T3 (p<0.05) and T4 (p<0.01) as compared to stage T2. The levels especially of IL-18 is found to be well associated with progression of the disease of various groups (r=0.84, p<0.01). In contrast, IL-10 showed significant direct association with progression of carcinoma (r=0.84, p<0.01) while inverse relation with survival duration (r=-0.48, p<0.01) and survival rate (χ2=8.98, p=0.0027; Hazard ratio=0.37, 95% CI=0.18-0.69). Study concluded that serum IL-18 has potential to be a better diagnostic marker with higher specificity and sensitivity and IL-10 may be valuable as a prognostic marker than PSA in carcinoma prostate.

Preliminary Crystallographic Study of Hemoglobin from Buffalo (Bubalus bubalis): A Low Oxygen Affinity Species.

PubMed

Balasubramanian, Moovarkumudalvan; Moorthy, Ponnuraj Sathya; Neelagandan, Kamariah; Ponnuswamy, Mondikalipudur Nanjappa Gounder

2009-01-01

Hemoglobin is a tetrameric, iron-containing metalloprotein, which plays a vital role in the transportation of oxygen from lungs to tissues and carbon dioxide back to lungs. Though good amount of work has already been done on hemoglobins, the scarcity of data on three dimensional structures pertaining to low oxygen affinity hemoglobins from mammalian species, motivated our group to work on this problem specifically. Herein, we report the preliminary crystallographic analysis of buffalo hemoglobin, which belongs to low oxygen affinity species. The buffalo blood was collected, purified by anion exchange chromatography and crystallized with PEG 3350 using 50mM phosphate buffer at pH 6.7 as a precipitant by hanging drop vapor diffusion method. Data collection was carried out using mar345dtb image plate detector system. Buffalo hemoglobin crystallizes in orthorhombic space group P2(1)2(1)2(1) with one whole biological molecule (alpha2beta2) in the asymmetric unit with cell dimensions a=63.064A, b=74.677A, c=110.224A.

Giant multilocular cystadenoma of the prostate: a rare cause of huge cystic pelvic mass.

PubMed

Olgun, Deniz Cebi; Onal, Bulent; Mihmanli, Ismail; Kantarci, Fatih; Durak, Haydar; Demir, Hale; Cetinel, Bulent

2012-03-01

Giant multilocular prostatic cystadenoma is a rare benign tumor that evolves from the prostate gland. Obstructive voiding symptoms occur in all reported cases. These lesions do not invade adjacent structures. Preoperative radiologic evaluation can define the benign nature of the lesion. Here we report a case of large cystic lesions identified by magnetic resonance imaging and sonographic findings that caused an extensive mass effect in the pelvis. When retrovesical, huge cystic lesions fill the pelvis completely in young men, with high levels of serum prostate-specific antigen, giant multilocular prostatic cystadenoma should be considered as a differential diagnosis. To our knowledge, this is the youngest case of prostatic cystadenoma reported in the literature.

[Prostate cancer detection by assessing stiffness of different tissues using shear wave ultrasound elastog- raphy].

PubMed

Glybochko, P V; Alyaev, Yu G; Amosov, A V; Krupinov, G E; Ganzha, T M; Vorobev, A V; Lumpov, I S; Semendyaev, R I

2016-08-01

Early detection of prostate cancer (PCa) remains a challenging issue. There are studies underway aimed to develop and implement new methods for prostate cancer screening by tumor imaging and obtaining tissue samples from suspicious areas for morphological examination. One of these new methods is shear wave ultrasound elastography (SWUE). The current literature is lacking sufficient coverage of informativeness and specificity of SWUE in the prostate cancer detection, there is no clear criteria for assessing tissue stiffness at different values of PSA and tumor grade, and in prostate hyperplasia and prostatitis. To evaluate the informativeness and specificity of SWUE compared with other diagnostic methods. SWUE has been used in the Clinic of Urology of Sechenov First MSMU since October 2015. During this period, 302 patients were examined using SWUE. SWUE was performed with Aixplorer ultrasound system (Super Sonic Imagine), which provides a single-stage SWUE imaging with both B-mode and real-time mode. The first group (prospective study) included 134 men aged 47 to 81 years with suspected prostate cancer scheduled to either initial or repeat prostate biopsy. PSA levels ranged from 4 to 24 ng/ml. The second group (retrospective study) comprised 120 men with confirmed prostate cancer and PSA levels between 4 and 90 ng/ml. The third group (the control group), comprised 48 healthy men whose PSA level did not exceed 3 ng/ml. All patients of the groups 1 and 2 underwent a standard comprehensive examination. Patients in group 1 were subsequently subjected to transrectal prostate biopsy guided by localization of areas with abnormal tissue stiffness. PCa was detected in 100 of 134 patients. 217 patients of groups 1 and 2 underwent radical prostatectomy. In 28 of them, the match between the cancer location and differentiation in the removed prostate and SWUE findings before surgery was examined. Contrast-enhanced magnetic resonance imaging of pelvic organs was performed in 63 patients of groups 1 and 2. Threshold values of stiffness (Emean) were determined, which normally range from 0 to 23 kPa, from 23.4 to 50 kPa in prostatic hyperplasia and 50.5 kPa and greater in prostate cancer. A total of 220 patients in groups 1 and 2 were found to have prostate cancer. The findings showed increased stiffness of prostate tissue depending on tumor differentiation, Gleason score, and hence, cancer risk. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) were calculated for SWUE, biopsy based on 6 peripheral points used during SWUE, and for histologic findings from prostate cross sections. When compared to needle biopsy, Se, Sp, PPV, NPV for SWUE were 90.8, 94.6, 56.6 and 97.9%, respectively. The study findings suggest a high diagnostic performance of SWUE in detecting prostate cancer.

Serum pro-gastrin-releasing peptide (31-98) in benign prostatic hyperplasia and prostatic carcinoma.

PubMed

Nagakawa, Osamu; Furuya, Yuzo; Fujiuchi, Yasuyoshi; Fuse, Hideki

2002-09-01

To clarify whether serum levels of pro-gastrin-releasing peptide (ProGRP) (31-98) could be a useful marker in patients with prostatic carcinoma. GRP is produced and secreted by prostatic neuroendocrine cells. Serum levels of ProGRP(31-98) were measured by enzyme-linked immunosorbent assay in 20 patients with benign prostatic hyperplasia and 107 patients with prostatic carcinoma. The mean serum levels of ProGRP(31-98) in patients with distant metastasis and hormone-resistant prostate cancer were significantly elevated compared with those in patients with organ-confined disease. Significantly elevated levels of ProGRP(31-98) were detected in 9 patients with prostatic carcinoma before any treatment. During hormone-resistant prostate cancer progression, ProGRP(31-98) levels were elevated in 9 patients (23%). Of the 9 patients with Stage D3 and elevated serum ProGRP, 4 had a normal serum prostate-specific antigen level. ProGRP may be a potential tumor marker for prostate cancer. Additional studies in large groups of patients are needed to define the clinical value of ProGRP.

Discoveries and application of prostate-specific antigen, and some proposals to optimize prostate cancer screening.

PubMed

Tokudome, Shinkan; Ando, Ryosuke; Koda, Yoshiro

2016-01-01

The discoveries and application of prostate-specific antigen (PSA) have been much appreciated because PSA-based screening has saved millions of lives of prostate cancer (PCa) patients. Historically speaking, Flocks et al first identified antigenic properties in prostate tissue in 1960. Then, Barnes et al detected immunologic characteristics in prostatic fluid in 1963. Hara et al characterized γ-semino-protein in semen in 1966, and it has been proven to be identical to PSA. Subsequently, Ablin et al independently reported the presence of precipitation antigens in the prostate in 1970. Wang et al purified the PSA in 1979, and Kuriyama et al first applied an enzyme-linked immunosorbent assay for PSA in 1980. However, the positive predictive value with a cutoff figure of 4.0 ng/mL appeared substantially low (∼30%). There are overdiagnoses and overtreatments for latent/low-risk PCa. Controversies exist in the PCa mortality-reducing effects of PSA screening between the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. For optimizing PCa screening, PSA-related items may require the following: 1) adjustment of the cutoff values according to age, as well as setting limits to age and screening intervals; 2) improving test performance using doubling time, density, and ratio of free: total PSA; and 3) fostering active surveillance for low-risk PCa with monitoring by PSA value. Other items needing consideration may include the following: 1) examinations of cell proliferation and cell cycle markers in biopsy specimens; 2) independent quantification of Gleason grading; 3) developing ethnicity-specific staging nomograms based on tumor stage, PSA value, and Gleason score; 4) delineation of the natural history; 5) revisiting the significance of the androgen/testosterone hypothesis; and 6) devoting special attention to individuals with a certain genetic predisposition. Finally, considering the uncertainty that exists in medicine, risk communication on PSA-based screening is indeed due.

MRI Fusion-Targeted Transrectal Prostate Biopsy and the Role of Prostate-Specific Antigen Density and Prostate Health Index for the Detection of Clinically Significant Prostate Cancer in Southeast Asian Men.

PubMed

Tan, Teck Wei; Png, Keng Siang; Lee, Chau Hung; Yuwono, Arianto; Yeow, Yuyi; Chong, Kian Tai; Lee, Yee Mun; Tan, Cher Heng; Tan, Yung Khan

2017-11-01

To test the hypothesis that targeted biopsy has a higher detection rate for clinically significant prostate cancer (csPCa) than systematic biopsy. We defined csPCa as any Gleason sum ≥7 cancer. In patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, to determine if factors, such as prostate-specific antigen density (PSAD) and prostate health index (PHI), can predict csPCa and help select patients for biopsy. We report the first series of targeted biopsies in Southeast Asian men, with comparison against systematic biopsy. Consecutive patients were registered into a prospective institutional review board-approved database in our institution. We reviewed patients who underwent biopsy from May 2016 to June 2017. Inclusion criteria for our study were patients with at least one PI-RADS ≥3, and who underwent both targeted and systematic biopsies in the same sitting. There were 115 patients in the study, of whom 74 (64.3%) had a previous negative systematic biopsy. Targeted biopsies detected significantly less Gleason 6 cancers than systematic biopsies (p < 0.01), and demonstrated significantly higher sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for the detection of csPCa. For patients with PI-RADS 3 lesions, PHI and PSAD were found to be the best predictors for csPCa. PSAD <0.10 ng/mL/mL had an NPV of 93% and sensitivity of 92%, while allowing 20% of patients to avoid biopsy. PHI cutoff of <27 would allow 34% of patients to avoid biopsy, with both sensitivity and NPV of 100%. Targeted prostate biopsies were found to be significantly superior to systematic biopsies for the detection of csPCa, while detecting less Gleason 6 cancer. Usage of PSAD and PHI cutoff levels in patients with PI-RADS 3 lesions may enable a number of patients to avoid unnecessary biopsy.

Patient-reported outcome (PRO) questionnaires for men who have radical surgery for prostate cancer: a conceptual review of existing instruments.

PubMed

Protopapa, Evangelia; van der Meulen, Jan; Moore, Caroline M; Smith, Sarah C

2017-10-01

To critically review conceptual frameworks for available patient-reported outcome (PRO) questionnaires in men having radical prostatectomy (RP), psychometrically evaluate each questionnaire, and identify whether each is appropriate for use at the level of the individual patient. We searched PubMed, the Reports and Publications database of the University of Oxford Patient-Reported Outcomes Measurement Group and the website of the International Consortium for Health Outcomes Measurement (ICHOM) for psychometric reviews of prostate cancer-specific PRO questionnaires. From these we identified relevant questionnaires and critically appraised the conceptual content, guided by the Wilson and Cleary framework and psychometric properties, using well established criteria. The searches found four reviews and one recommendation paper. We identified seven prostate cancer-specific PROs: the Expanded Prostate Cancer Index Composite-26 (EPIC-26), Expanded Prostate Cancer Index Composite-50 (EPIC-50), University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), Functional Assessment of Cancer Therapy - Prostate Cancer Subscale (FACT-P PCS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - prostate specific 25-item (EORTC QLQ-PR25), Prostate Cancer - Quality of Life (PC-QoL), and Symptom Tracking and Reporting (STAR). Six out of seven measures purported to measure health-related quality of life (HRQL), but items focused strongly on urinary and sexual symptoms/functioning. The remaining questionnaire (STAR) claimed to assess functional recovery after RP. The psychometric evidence for these questionnaires was incomplete and variable in quality; none had evidence that they were appropriate for use with individual patients. Several questionnaires provide the basis of measures of urinary and/or sexual symptoms/functioning. Further work should explore other aspects of HRQL that are important for men having RP. Further psychometric work is also needed to determine whether they can be used at the individual level. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Specific PET Imaging Probes for Early Detection of Prostate Cancer Metastases

DTIC Science & Technology

2010-05-01

penetrating cell membranes. In one of our studies using such a peptide to deliver a therapeutic moiety to various prostate cancer cell lines, we...to exploit this group of peptides for the early detection of prostate tumor metastases. Promisingly, in our preliminary studies , th e peptide lab...cancer. Based on one of our studies using a polyarginine (NH2GR11) to deliver a therapeutic moiety to various prostate cancer cell lines, we hypothesize

Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology

DTIC Science & Technology

2016-10-01

prostate cancer through sequencing xenografts and tissue samples. Qualify novel drivers of AR- prostate cancer through in vitro models. Develop novel...ability of RNASEH2A to modulate radio-sensitivity in prostate cancer cell lines and xenograft models. 3: Investigate RNASEH2A as a marker of radio...lung cancer clinical management. List of the Specific Aims: Aim 1: To establish patient-derived xenografts (PDX) models of pre-neoplastic lesions

The predictive value of 2-year posttreatment biopsy after prostate cancer radiotherapy for eventual biochemical outcome

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

Vance, Waseet; Tucker, Susan L.; Crevoisier, Renaud de

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 wasmore » 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.« less

Strain-specific induction of experimental autoimmune prostatitis (EAP) in mice.

PubMed

Jackson, Christopher M; Flies, Dallas B; Mosse, Claudio A; Parwani, Anil; Hipkiss, Edward L; Drake, Charles G

2013-05-01

Prostatitis, a clinical syndrome characterized by pelvic pain and inflammation, is common in adult males. Although several induced and spontaneous murine models of prostatitis have been explored, the role of genetic background on induction has not been well-defined. Using a standard methodology for the induction of experimental autoimmune prostatitis (EAP), we investigated both acute and chronic inflammation on several murine genetic backgrounds. In our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was not augmented by immunization with rat prostate extract (RPE). In contrast, the standard laboratory strain Balb/c developed chronic inflammation in response to RPE immunization. Development of EAP in other strains was variable. These data suggest that Balb/c mice injected with RPE may provide a useful model for chronic prostatic inflammation. Copyright © 2012 Wiley Periodicals, Inc.

Strain-Specific Induction of Experimental Autoimmune Prostatitis (EAP) in Mice

PubMed Central

Jackson, Christopher M.; Flies, Dallas B.; Mosse, Claudio A.; Parwani, Anil; Hipkiss, Edward L.; Drake, Charles G.

2013-01-01

BACKGROUND Prostatitis, a clinical syndrome characterized by pelvic pain and inflammation, is common in adult males. Although several induced and spontaneous murine models of prostatitis have been explored, the role of genetic background on induction has not been well-defined. METHODS Using a standard methodology for the induction of experimental autoimmune prostatitis (EAP), we investigated both acute and chronic inflammation on several murine genetic backgrounds. RESULTS In our colony, nonobese diabetic (NOD) mice evinced spontaneous prostatitis that was not augmented by immunization with rat prostate extract (RPE). In contrast, the standard laboratory strain Balb/c developed chronic inflammation in response to RPE immunization. Development of EAP in other strains was variable. CONCLUSIONS These data suggest that Balb/c mice injected with RPE may provide a useful model for chronic prostatic inflammation. PMID:23129407

Mass Spectrometric Analysis of Glyoxal and Methylglyoxal-Induced Modifications in Human Hemoglobin from Poorly Controlled Type 2 Diabetes Mellitus Patients.

PubMed

Chen, Hauh-Jyun Candy; Chen, Yu-Chin; Hsiao, Chiung-Fong; Chen, Pin-Fan

2015-12-21

Glyoxal and methylglyoxal are oxoaldehydes derived from the degradation of glucose-protein conjugates and from lipid peroxidation, and they are also present in the environment. This study investigated the site-specific reaction of glyoxal and methylglyoxal with the amino acid residues on human hemoglobin using a shot-gun proteomic approach with nanoflow liquid chromatography/nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS). In human hemoglobin incubated with glyoxal, modification on 8 different sites, including lysine residues at α-Lys-11, α-Lys-16, α-Lys-56, β-Lys-17, β-Lys-66, β-Lys-144, and arginine residues at α-Arg-92 and β-Arg-30, was observed using a data-dependent scan. In methylglyoxal-treated hemoglobin, there were specific residues, namely, α-Arg-92, β-Lys-66, β-Arg-30, and β-Lys-144, forming carboxyethylation as well as the dehydrated product hydroimidazolone at α-Arg-92 and β-Arg-30. These lysine and arginine modifications were confirmed by accurate mass measurement and the MS(2) and MS(3) spectra. The most intensive signal of each modified peptide was used as the precursor ion to perform the product ion scan. The relative extent of modifications was semiquantified simultaneously relative to the native reference peptide by nanoLC-NSI/MS/MS under the selected reaction monitoring (SRM) mode. The extent of these modifications increased dose-dependently with increasing concentrations of glyoxal or methylglyoxal. Six out of the eight modifications induced by glyoxal and three out of the six modifications induced by methylglyoxal were detected in hemoglobin freshly isolated from human blood samples. The relative extent of modification of these post-translational modifications was quantified in poorly controlled type 2 diabetes mellitus patients (n = 20) and in nondiabetic control subjects (n = 21). The results show that the carboxymethylated peptides at α-Lys-16, α-Arg-92, β-Lys-17, β-Lys-66, and the peptide at α-Arg-92 with methylglyoxal-derived hydroimidazolone are significantly higher in diabetic patients than in normal individuals (p value <0.05). This report identified and quantified glyoxal- and methylglyoxal-modified hemoglobin peptides in humans and revealed the association of the extent of modifications at specific sites with T2DM. Only one drop (10 μL) of fresh blood is needed for this assay, and only an equivalent of 1 μg of hemoglobin was analyzed by the nanoLC-NSI/MS/MS-SRM system. These results suggest the potential use of these specific post-translational modifications in hemoglobin as feasible biomarker candidates to assess protein damage induced by glyoxal and methylglyoxal.

Does [-2]Pro-Prostate Specific Antigen Meet the Criteria to Justify Its Inclusion in the Clinical Decision-Making Process?

PubMed

Sanchis-Bonet, Angeles; Barrionuevo-González, Marta; Bajo-Chueca, Ana; Morales-Palacios, Nelson; Sanchez-Chapado, Manuel

2018-01-01

To assess whether [-2]pro-prostate-specific antigen (p2PSA) meets the criteria to justify its inclusion in a predictive model of prostate cancer (PCa) diagnosis and in the clinical decision-making process. A total 172 men with total prostate-specific antigen of 2-10 ng/mL underwent measurement of free PSA and p2PSA before prostate biopsy in an observational and prospective study. From these measurements, the Prostate Health Index (PHI) was calculated. Clinical and analytical predictive models were created incorporating PHI. Of 172 men, 72 (42%) were diagnosed with PCa, 33 (46%) of whom were found to be with high-grade disease. PHI score was the most predictive of biopsy outcomes in terms of discriminative ability (area under the curve = 0.79), with an added gain in predictive accuracy of 17%. All the models that incorporated PHI worked better in terms of calibration close to 45° on the slope. In the decision curve analysis, at a threshold probability of 40% we could prevent 82 biopsies, missing only 16 tumors and 5 high-grade tumors. PHI score is a more discriminant biomarker, has superior calibration and superior net benefit, and provides a higher rate of avoided biopsies; thus, it can be useful for aiding in making a more informed decision for each patient. © 2018 S. Karger AG, Basel.