YK-4-279 inhibits ERG and ETV1 mediated prostate cancer cell invasion.

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Said Rahim

2011-04-01

Full Text Available Genomic rearrangements involving the ETS family of transcription factors occur in 40-70% of prostate cancer cases. ERG and ETV1 are the most common ETS members observed in these genetic alterations. The high prevalence of these rearrangements and their biological significance represents a novel therapeutic target for the treatment of prostate cancer.We recently reported the development of YK-4-279, a small molecule inhibitor of EWS-FLI1 oncoprotein in Ewing's Sarcoma. Since ERG and ETV1 belong to the same class of ETS factors as FLI1, we tested the ability of YK-4-279 to inhibit biological functions of ERG and ETV1 proteins in prostate cancer. YK-4-279 inhibited ERG and ETV1 mediated transcriptional activity in a luciferase assay. YK-4-279 also decreased ERG and ETV1 downstream target mRNA and protein expression in ETV1-fusion positive LNCaP and ERG fusion positive VCaP cells. YK-4-279 reduced the motility of LNCaP cells in a scratch assay and the invasive phenotype of both LNCaP and VCaP cells in a HUVEC invasion assay. Fusion-negative PC3 cells were unresponsive to YK-4-279. SiRNA mediated ERG knockdown in VCaP cells resulted in a loss of drug responsiveness. Concurrently, transient ERG expression in PC-3 cells resulted in increased invasive potential, which was reduced by YK-4-279.These data demonstrate that YK-4-279 inhibits ERG and ETV1 biological activity in fusion-positive prostate cancer cells leading to decreased motility and invasion. Therefore, YK-4-279 may have an impact on metastasis in prostate cancer and it may be further evaluated for its clinical applications in prostate cancer in addition to Ewing's sarcoma.

The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate cancer is limited to ERG-fusion positive tumors lacking PTEN deletion

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Burdelski, Christoph; Menan, Devi; Tsourlakis, Maria Christina; Kluth, Martina; Hube-Magg, Claudia; Melling, Nathaniel; Minner, Sarah; Koop, Christina; Graefen, Markus; Heinzer, Hans; Wittmer, Corinna; Sauter, Guido; Simon, Ronald; Schlomm, Thorsten; Steurer, Stefan; Krech, Till

2015-01-01

Posttranscriptional protein modification by SUMOylation plays an important role in tumor development and progression. In the current study we analyzed prevalence and prognostic impact of the de-SUMOylation enzyme SENP1 in prostate cancer. SENP1 expression was analyzed by immunohistochemistry on a tissue microarray containing more than 12,400 prostate cancer specimens. Results were compared to tumor phenotype, ERG status, genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence. SENP1 immunostaining was detectable in 34.5 % of 9,516 interpretable cancers and considered strong in 7.3 %, moderate in 14.9 % and weak in 12.3 % of cases. Strong SENP1 expression was linked to advanced pT stage (p < 0.0001), high Gleason grade (p < 0.0001), positive lymph node status (p = 0.0019), high pre-operative PSA levels (p = 0.0037), and PSA recurrence (p < 0.0001). SENP1 expression was strongly associated with positive ERG fusion status as determined by both in situ hybridization (FISH) and immunohistochemistry as well as with PTEN deletions. Detectable SENP1 immunostaining was found in 41 % of ERG positive and in 47 % of PTEN deleted cancers but in only 30 % of ERG negative and 30 % of PTEN non-deleted cancers (p < 0.0001 each). Deletions of 3p, 5q, and 6q were unrelated to SENP1 expression. Subset analyses revealed that the prognostic impact of SENP1 expression was solely driven by the subgroup of ERG positive, PTEN undeleted cancers. In this subgroup, the prognostic role of SENP1 expression was independent of the preoperative PSA level, tumor stage, Gleason grade, and the status of the resection margin. SENP1 expression has strong prognostic impact in a molecularly defined subset of cancers. This is per se not surprising as the biologic impact of each individual molecular event is likely to be dependent on its cellular environment. However, such findings challenge the concept of finding clinically relevant molecular signatures that are equally applicable to all

Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer

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2015-10-01

MD Anderson. Fusion analysis of the first 19 cases demonstrates 10 cases are ETS fusion positive, while 9 cases are ETS fusion negative. Notably...Foundation Grants Officer: Jane Zuber, Director, Contracts & Grants, Texas A&M Univ. System 400 Harvey Mitchell Pkwy South, Suite 300 College Station, TX...prostate cancer PDXs for expression of targets of interest to company. 18 ARAUJO, John None BROOM, Bradley ACTIVE Bioinformatics Gift ( Weinstein

Overall Survival Benefit From Postoperative Radiation Therapy for Organ-Confined, Margin-Positive Prostate Cancer

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Dillman, Robert O.; Hafer, Russell; Cox, Craig; McClure, Stephanie E.

2011-01-01

Purpose: Radical prostatectomy for invasive prostate cancer is associated with positive margin rates in 10% to 50% of resected specimens. Postoperative radiation therapy may benefit patients who have organ-confined prostate cancer with positive margins. Methods and Materials: We performed a retrospective analysis to examine whether adjunctive radiation therapy enhanced long-term survival for prostate cancer patients who underwent prostatectomy for localized prostate cancer but with positive margins. We used the Hoag Cancer Center database to identify patients diagnosed with invasive prostate cancer. Relative and overall survival rates were calculated. Results: Among 1,474 patients diagnosed with localized invasive prostate cancer during the years 1990 to 2006 and undergoing prostatectomy, 113 (7.7%) were identified who had positive margins and did not have local extension of disease, positive lymph nodes, or distant metastases. A total of 17 patients received adjunctive radiation therapy (Group A), whereas 96 did not (Group B; 3 received hormonal therapy). Both groups had a median age of 64 years and median follow-up of 7.5 years. In Group A, no patients have died as of last follow-up, but in Group B, 18 have died. Estimated 10-year and 15-year overall survival rates were both 100% for Group A compared with 85% and 57% respectively for Group B (p 2 = 0.050, log rank). Relative 10- and 15 year survival rates were both 100% for Group A compared with 100% and 79% respectively for Group B. Conclusions: This retrospective analysis suggests that prostate cancer patients with localized disease but positive margins do derive a survival benefit from adjuvant radiation therapy.

X-ray-assisted positioning of patients treated by conformal arc radiotherapy for prostate cancer: Comparison of setup accuracy using implanted markers versus bony structures

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Soete, Guy; Cock, Mieke de; Verellen, Dirk; Michielsen, Dirk; Keuppens, Frans; Storme, Guy

2007-01-01

Purpose: The aim of this study was to compare setup accuracy of NovalisBody stereoscopic X-ray positioning using implanted markers in the prostate vs. bony structures in patients treated with dynamic conformal arc radiotherapy for prostate cancer. Methods and Materials: Random and systematic setup errors (RE and SE) of the isocenter with regard to the center of gravity of three fiducial markers were measured by means of orthogonal verification films in 120 treatment sessions in 12 patients. Positioning was performed using NovalisBody semiautomated marker fusion. The results were compared with a control group of 261 measurements in 15 patients who were positioned with NovalisBody automated bone fusion. In addition, interfraction and intrafraction prostate motion was registered in the patients with implanted markers. Results: Marker-based X-ray positioning resulted in a reduction of RE as well as SE in the anteroposterior, craniocaudal, and left-right directions compared with those in the control group. The interfraction prostate displacements with regard to the bony pelvis that could be avoided by marker positioning ranged between 1.6 and 2.8 mm for RE and between 1.3 and 4.3 mm for SE. Intrafraction random and systematic prostate movements ranged between 1.4 and 2.4 mm and between 0.8 and 1.3 mm, respectively. Conclusion: The problem of interfraction prostate motion can be solved by using implanted markers. In addition, the NovalisBody X-ray system performs more accurately with markers compared with bone fusion. Intrafraction organ motion has become the limiting factor for margin reduction around the clinical target volume

Magnetic Resonance and Ultrasound Image Fusion Supported Transperineal Prostate Biopsy Using the Ginsburg Protocol: Technique, Learning Points, and Biopsy Results.

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Hansen, Nienke; Patruno, Giulio; Wadhwa, Karan; Gaziev, Gabriele; Miano, Roberto; Barrett, Tristan; Gnanapragasam, Vincent; Doble, Andrew; Warren, Anne; Bratt, Ola; Kastner, Christof

2016-08-01

Prostate biopsy supported by transperineal image fusion has recently been developed as a new method to the improve accuracy of prostate cancer detection. To describe the Ginsburg protocol for transperineal prostate biopsy supported by multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound (TRUS) image fusion, provide learning points for its application, and report biopsy results. The article is supplemented by a Surgery in Motion video. This single-centre retrospective outcome study included 534 patients from March 2012 to October 2015. A total of 107 had no previous prostate biopsy, 295 had benign TRUS-guided biopsies, and 159 were on active surveillance for low-risk cancer. A Likert scale reported mpMRI for suspicion of cancer from 1 (no suspicion) to 5 (cancer highly likely). Transperineal biopsies were obtained under general anaesthesia using BiopSee fusion software (Medcom, Darmstadt, Germany). All patients had systematic biopsies, two cores from each of 12 anatomic sectors. Likert 3-5 lesions were targeted with a further two cores per lesion. Any cancer and Gleason score 7-10 cancer on biopsy were noted. Descriptive statistics and positive predictive values (PPVs) and negative predictive values (NPVs) were calculated. The detection rate of Gleason score 7-10 cancer was similar across clinical groups. Likert scale 3-5 MRI lesions were reported in 378 (71%) of the patients. Cancer was detected in 249 (66%) and Gleason score 7-10 cancer was noted in 157 (42%) of these patients. PPV for detecting 7-10 cancer was 0.15 for Likert score 3, 0.43 for score 4, and 0.63 for score 5. NPV of Likert 1-2 findings was 0.87 for Gleason score 7-10 and 0.97 for Gleason score ≥4+3=7 cancer. Limitations include lack of data on complications. Transperineal prostate biopsy supported by MRI/TRUS image fusion using the Ginsburg protocol yielded high detection rates of Gleason score 7-10 cancer. Because the NPV for excluding Gleason score 7-10 cancer was very

Cancer-related identity and positive affect in survivors of prostate cancer.

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Bellizzi, Keith M; Blank, Thomas O

2007-03-01

Despite a shift in the cancer culture and language used to describe individuals diagnosed with this disease, the extent to which individuals with cancer adopt a particular cancer-related identity and the impact of these identities in relation to their well-being is virtually unknown. Using a cross-sectional study design and a metropolitan tumor registry, a mail questionnaire to examine post-treatment quality of life was sent to prostate cancer (PCa) survivors. The sample consisted of 490 PCa survivors, ranging in age from 49-88 (M = 69.7; SD = 7.8), one to eight years after diagnosis. The outcome measure used in these analyses was the PANAS to assess positive and negative affect. The most frequently reported cancer-related identity was "someone who has had PCa" (57%). The least reported self view was "victim" (1%). Twenty-six percent of men self-identified as "survivors" while 6% thought of themselves as "cancer conquerors." Only 9% self-identified as a "patient." Multivariate analyses, adjusted for potential confounders, show respondents who identified themselves as "survivors" or "cancer conquerors" reported significantly higher scores on positive affect than men who self-identified as "patients" (p < .001). Although the majority of respondents identified themselves as "someone who has had cancer," identifying as a "survivor" or "someone who has conquered cancer" appears to have adaptive value for positive mood. Those who perceive themselves as survivors of prostate cancer may derive some benefit in well-being associated with this self assessment.

Characterization of KRAS Rearrangements in Metastatic Prostate Cancer

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Wang, Xiao-Song; Shankar, Sunita; Dhanasekaran, Saravana M.; Ateeq, Bushra; Sasaki, Atsuo T.; Jing, Xiaojun; Robinson, Daniel; Cao, Qi; Prensner, John R.; Yocum, Anastasia K.; Wang, Rui; Fries, Daniel F.; Han, Bo; Asangani, Irfan A.; Cao, Xuhong; Li, Yong; Omenn, Gilbert S.; Pflueger, Dorothee; Gopalan, Anuradha; Reuter, Victor E.; Kahoud, Emily Rose; Cantley, Lewis C.; Rubin, Mark A.; Palanisamy, Nallasivam; Varambally, Sooryanarayana; Chinnaiyan, Arul M.

2011-01-01

Using an integrative genomics approach called Amplification Breakpoint Ranking and Assembly (ABRA) analysis, we nominated KRAS as a gene fusion with the ubiquitin-conjugating enzyme UBE2L3 in the DU145 cell line, originally derived from prostate cancer metastasis to the brain. Interestingly, analysis of tissues revealed that 2 of 62 metastatic prostate cancers harbored aberrations at the KRAS locus. In DU145 cells, UBE2L3-KRAS produces a fusion protein, specific knock-down of which, attenuates cell invasion and xenograft growth. Ectopic expression of the UBE2L3-KRAS fusion protein exhibits transforming activity in NIH 3T3 fibroblasts and RWPE prostate epithelial cells in vitro and in vivo. In NIH 3T3 cells, UBE2L3-KRAS attenuates MEK/ERK signaling, commonly engaged by oncogenic mutant KRAS, and instead signals via AKT and p38 MAPK pathways. This is the first report of a gene fusion involving Ras family suggesting that this aberration may drive metastatic progression in a rare subset of prostate cancers. PMID:22140652

Image Guidance Based on Prostate Position for Prostate Cancer Proton Therapy

International Nuclear Information System (INIS)

Vargas, Carlos; Wagner, Marcus; Indelicato, Daniel; Fryer, Amber; Horne, David; Chellini, Angela; McKenzie, Craig; Lawlor, Paula; Mahajan, Chaitali; Li Zuofeng; Lin Liyong; Keole, Sameer

2008-01-01

Purpose: To determine the target coverage for proton therapy with and without image guidance and daily prebeam reorientation. Methods and Materials: A total of 207 prostate positions were analyzed for 9 prostate cancer patients treated using our low-risk prostate proton therapy protocol (University of Florida Proton Therapy Institute 001). The planning target volume was defined as the prostate plus a 5-mm axial and 8-mm superoinferior extension. The prostate was repositioned using 5- and 10-mm shifts (anteriorly, inferiorly, posteriorly, and superiorly) and for Points A-D using a combination of 10-mm multidimensional movements (anteriorly or inferiorly; posteriorly or superiorly; and left or right). The beams were then realigned using the new prostate position. The prescription dose was 78 Gray equivalent (GE) to 95% of the planning target volume. Results: For small movements in the anterior, inferior, and posterior directions within the planning target volume (≤5 mm), treatment realignment demonstrated small, but significant, improvements in the clinical target volume (CTV) coverage to the prescribed dose (78 GE). The anterior and posterior shifts also significantly increased the minimal CTV dose (Δ +1.59 GE). For prostate 10-mm movements in the inferior, posterior, and superior directions, the beam realignment produced larger and significant improvements for both the CTV V 78 (Δ +6.4%) and the CTV minimal dose (Δ +8.22 GE). For the compounded 10-mm multidimensional shifts, realignment significantly improved the CTV V 78 (Δ +11.8%) and CTV minimal dose (Δ +23.6 GE). After realignment, the CTV minimal dose was >76.6 GE (>98%) for all points (A-D). Conclusion: Proton beam realignment after target shift will enhance CTV coverage for different prostate positions

Optimal preprocessing of serum and urine metabolomic data fusion for staging prostate cancer through design of experiment

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Zheng, Hong; Cai, Aimin; Zhou, Qi; Xu, Pengtao; Zhao, Liangcai; Li, Chen; Dong, Baijun; Gao, Hongchang

2017-01-01

Accurate classification of cancer stages will achieve precision treatment for cancer. Metabolomics presents biological phenotypes at the metabolite level and holds a great potential for cancer classification. Since metabolomic data can be obtained from different samples or analytical techniques, data fusion has been applied to improve classification accuracy. Data preprocessing is an essential step during metabolomic data analysis. Therefore, we developed an innovative optimization method to select a proper data preprocessing strategy for metabolomic data fusion using a design of experiment approach for improving the classification of prostate cancer (PCa) stages. In this study, urine and serum samples were collected from participants at five phases of PCa and analyzed using a 1 H NMR-based metabolomic approach. Partial least squares-discriminant analysis (PLS-DA) was used as a classification model and its performance was assessed by goodness of fit (R 2 ) and predictive ability (Q 2 ). Results show that data preprocessing significantly affect classification performance and depends on data properties. Using the fused metabolomic data from urine and serum, PLS-DA model with the optimal data preprocessing (R 2  = 0.729, Q 2  = 0.504, P < 0.0001) can effectively improve model performance and achieve a better classification result for PCa stages as compared with that without data preprocessing (R 2  = 0.139, Q 2  = 0.006, P = 0.450). Therefore, we propose that metabolomic data fusion integrated with an optimal data preprocessing strategy can significantly improve the classification of cancer stages for precision treatment. - Highlights: • NMR metabolomic analysis of body fluids can be used for staging prostate cancer. • Data preprocessing is an essential step for metabolomic analysis. • Data fusion improves information recovery for cancer classification. • Design of experiment achieves optimal preprocessing of metabolomic data fusion.

IL-6 Overexpression in ERG-Positive Prostate Cancer Is Mediated by Prostaglandin Receptor EP2.

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Merz, Constanze; von Mässenhausen, Anne; Queisser, Angela; Vogel, Wenzel; Andrén, Ove; Kirfel, Jutta; Duensing, Stefan; Perner, Sven; Nowak, Michael

2016-04-01

Prostate cancer is the most diagnosed cancer in men and multiple risk factors and genetic alterations have been described. The TMPRSS2-ERG fusion event and the overexpression of the transcription factor ERG are present in approximately 50% of all prostate cancer patients, however, the clinical outcome is still controversial. Prostate tumors produce various soluble factors, including the pleiotropic cytokine IL-6, regulating cellular processes such as proliferation and metastatic segregation. Here, we used prostatectomy samples in a tissue microarray format and analyzed the co-expression and the clinicopathologic data of ERG and IL-6 using immunohistochemical double staining and correlated the read-out with clinicopathologic data. Expression of ERG and IL-6 correlated strongly in prostate tissue samples. Forced expression of ERG in prostate tumor cell lines resulted in significantly increased secretion of IL-6, whereas the down-regulation of ERG decreased IL-6 secretion. By dissecting the underlying mechanism in prostate tumor cell lines we show the ERG-mediated up-regulation of the prostanoid receptors EP2 and EP3. The prostanoid receptor EP2 was overexpressed in human prostate cancer tissue. Furthermore, the proliferation rate and IL-6 secretion in DU145 cells was reduced after treatment with EP2-receptor antagonist. Collectively, our study shows that the expression of ERG in prostate cancer is linked to the expression of IL-6 mediated by the prostanoid receptor EP2. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies.

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Hansel, D E; DeMarzo, A M; Platz, E A; Jadallah, S; Hicks, J; Epstein, J I; Partin, A W; Netto, G J

2007-05-01

Early prostate cancer antigen is a nuclear matrix protein that was recently shown to be expressed in prostate adenocarcinoma and adjacent benign tissue. Previous studies have demonstrated early prostate cancer antigen expression in benign prostate tissue up to 5 years before a diagnosis of prostate carcinoma, suggesting that early prostate cancer antigen could be used as a potential predictive marker. We evaluated early prostate cancer antigen expression by immunohistochemistry using a polyclonal antibody (Onconome Inc., Seattle, Washington) on benign biopsies from 98 patients. Biopsies were obtained from 4 groups that included 39 patients with first time negative biopsy (group 1), 24 patients with persistently negative biopsies (group 2), 8 patients with initially negative biopsies who were subsequently diagnosed with prostate carcinoma (group 3) and negative biopsies obtained from 27 cases where other concurrent biopsies contained prostate carcinoma (group 4). Early prostate cancer antigen staining was assessed by 2 of the authors who were blind to the group of the examined sections. Staining intensity (range 0 to 3) and extent (range 1 to 3) scores were assigned. The presence of intensity 3 staining in any of the blocks of a biopsy specimen was considered as positive for early prostate cancer antigen for the primary outcome in the statistical analysis. In addition, as secondary outcomes we evaluated the data using the proportion of blocks with intensity 3 early prostate cancer antigen staining, the mean of the product of staining intensity and staining extent of all blocks within a biopsy, and the mean of the product of intensity 3 staining and extent. Primary outcome analysis revealed the proportion of early prostate cancer antigen positivity to be highest in group 3 (6 of 8, 75%) and lowest in group 2 (7 of 24, 29%, p=0.04 for differences among groups). A relatively higher than expected proportion of early prostate cancer antigen positivity was present in

A small molecule inhibitor of ETV1, YK-4-279, prevents prostate cancer growth and metastasis in a mouse xenograft model.

Directory of Open Access Journals (Sweden)

Said Rahim

Full Text Available The erythroblastosis virus E26 transforming sequences (ETS family of transcription factors consists of a highly conserved group of genes that play important roles in cellular proliferation, differentiation, migration and invasion. Chromosomal translocations fusing ETS factors to promoters of androgen responsive genes have been found in prostate cancers, including the most clinically aggressive forms. ERG and ETV1 are the most commonly translocated ETS proteins. Over-expression of these proteins in prostate cancer cells results in a more invasive phenotype. Inhibition of ETS activity by small molecule inhibitors may provide a novel method for the treatment of prostate cancer.We recently demonstrated that the small molecule YK-4-279 inhibits biological activity of ETV1 in fusion-positive prostate cancer cells leading to decreased motility and invasion in-vitro. Here, we present data from an in-vivo mouse xenograft model. SCID-beige mice were subcutaneously implanted with fusion-positive LNCaP-luc-M6 and fusion-negative PC-3M-luc-C6 tumors. Animals were treated with YK-4-279, and its effects on primary tumor growth and lung metastasis were evaluated. YK-4-279 treatment resulted in decreased growth of the primary tumor only in LNCaP-luc-M6 cohort. When primary tumors were grown to comparable sizes, YK-4-279 inhibited tumor metastasis to the lungs. Expression of ETV1 target genes MMP7, FKBP10 and GLYATL2 were reduced in YK-4-279 treated animals. ETS fusion-negative PC-3M-luc-C6 xenografts were unresponsive to the compound. Furthermore, YK-4-279 is a chiral molecule that exists as a racemic mixture of R and S enantiomers. We established that (S-YK-4-279 is the active enantiomer in prostate cancer cells.Our results demonstrate that YK-4-279 is a potent inhibitor of ETV1 and inhibits both the primary tumor growth and metastasis of fusion positive prostate cancer xenografts. Therefore, YK-4-279 or similar compounds may be evaluated as a potential

Improving Positioning in High-Dose Radiotherapy for Prostate Cancer: Safety and Visibility of Frequently Used Gold Fiducial Markers

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Fonteyne, Valerie, E-mail: valerie.fonteyne@uzgent.be [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Ost, Piet [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Villeirs, Geert [Department of Radiology, Ghent University Hospital, Ghent (Belgium); Oosterlinck, Willem [Department of Urology, Ghent University Hospital, Ghent (Belgium); Impens, Aline; De Gersem, Werner; De Wagter, Carlos; De Meerleer, Gert [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)

2012-05-01

Purpose: The use of gold fiducial markers (GFMs) for prostate positioning in high-dose radiotherapy is gaining interest. The purpose of this study was to compare five GFMs regarding feasibility of ultrasound-based implantation in the prostate and intraprostatic lesion (IPL); toxicity; visibility on transabdominal ultrasound (TU) and cone-beam CT (CBCT); reliability of automatic, soft tissue, and GFM-based CBCT patient positioning by comparing manual and automatic fusion CBCT. Methods and Materials: Twenty-five patients were included. Pain and toxicity were scored after implantation and high-dose radiotherapy. Fisher exact test was used to evaluate the correlation of patients' characteristics and prostatitis. Positioning was evaluated on TU and kilovoltage CBCT images. CBCT fusion was performed automatically (Elekta XVI technology, release 3.5.1 b27, based on grey values) and manually on soft tissue and GFMs. Pearson correlation statistics and Bland-Altman evaluation were used. Five GFMs were compared. Results: Twenty percent of the patients developed prostatitis despite antibiotic prophylaxis. Cigarette smoking was significantly correlated with prostatitis. The visualization of all GFMs on TU was disappointing. Consequently we cannot recommend the use of these GFMs for TU-based prostate positioning. For all GFMs, there was only fair to poor linear correlation between automatic and manual CBCT images, indicating that even when GFMs are used, an operator evaluation is imperative. However, when GFMs were analyzed individually, a moderate to very strong correlation between automatic and manual positioning was found for larger GFMs in all directions. Conclusion: The incidence of prostatitis in our series was high. Further research is imperative to define the ideal preparation protocol preimplantation and to select patients. Automatic fusion is more reliable with larger GFMs at the cost of more scatter. The stability of all GFMs was proven.

Risk score predicts high-grade prostate cancer in DNA-methylation positive, histopathologically negative biopsies.

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Van Neste, Leander; Partin, Alan W; Stewart, Grant D; Epstein, Jonathan I; Harrison, David J; Van Criekinge, Wim

2016-09-01

Prostate cancer (PCa) diagnosis is challenging because efforts for effective, timely treatment of men with significant cancer typically result in over-diagnosis and repeat biopsies. The presence or absence of epigenetic aberrations, more specifically DNA-methylation of GSTP1, RASSF1, and APC in histopathologically negative prostate core biopsies has resulted in an increased negative predictive value (NPV) of ∼90% and thus could lead to a reduction of unnecessary repeat biopsies. Here, it is investigated whether, in methylation-positive men, DNA-methylation intensities could help to identify those men harboring high-grade (Gleason score ≥7) PCa, resulting in an improved positive predictive value. Two cohorts, consisting of men with histopathologically negative index biopsies, followed by a positive or negative repeat biopsy, were combined. EpiScore, a methylation intensity algorithm was developed in methylation-positive men, using area under the curve of the receiver operating characteristic as metric for performance. Next, a risk score was developed combining EpiScore with traditional clinical risk factors to further improve the identification of high-grade (Gleason Score ≥7) cancer. Compared to other risk factors, detection of DNA-methylation in histopathologically negative biopsies was the most significant and important predictor of high-grade cancer, resulting in a NPV of 96%. In methylation-positive men, EpiScore was significantly higher for those with high-grade cancer detected upon repeat biopsy, compared to those with either no or low-grade cancer. The risk score resulted in further improvement of patient risk stratification and was a significantly better predictor compared to currently used metrics as PSA and the prostate cancer prevention trial (PCPT) risk calculator (RC). A decision curve analysis indicated strong clinical utility for the risk score as decision-making tool for repeat biopsy. Low DNA-methylation levels in PCa-negative biopsies led

MR imaging of the prostate

International Nuclear Information System (INIS)

Asbach, P.; Haas, M.; Hamm, B.

2015-01-01

Prostate cancer is the most common form of cancer in men in Germany; however, there is a distinct difference between incidence and mortality. The detection of prostate cancer is based on clinical and laboratory testing using serum prostate-specific antigen (PSA) levels and transrectal ultrasound with randomized biopsy. Multiparametric MR imaging of the prostate can provide valuable diagnostic information for detection of prostate cancer, especially after negative results of a biopsy prior to repeat biopsy. In addition the use of MR ultrasound fusion-guided biopsy has gained in diagnostic importance and has increased the prostate cancer detection rate. The prostate imaging reporting and data system (PI-RADS) classification has standardized the reporting of prostate MRI which has positively influenced the acceptance by urologists. (orig.) [de

Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer: Potential opportunities for synergistic targeted therapeutics.

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Udager, Aaron M; DeMarzo, Angelo M; Shi, Yang; Hicks, Jessica L; Cao, Xuhong; Siddiqui, Javed; Jiang, Hui; Chinnaiyan, Arul M; Mehra, Rohit

2016-06-01

Recurrent ERG gene fusions, the most common genetic alterations in prostate cancer, drive overexpression of the nuclear transcription factor ERG, and are early clonal events in prostate cancer progression. The nuclear transcription factor MYC is also frequently overexpressed in prostate cancer and may play a role in tumor initiation and/or progression. The relationship between nuclear ERG and MYC protein overexpression in prostate cancer, as well as the clinicopathologic characteristics and prognosis of ERG-positive/MYC high tumors, is not well understood. Immunohistochemistry (IHC) for ERG and MYC was performed on formalin-fixed, paraffin-embedded tissue from prostate cancer tissue microarrays (TMAs), and nuclear staining was scored semi-quantitatively (IHC product score range = 0-300). Correlation between nuclear ERG and MYC protein expression and association with clinicopathologic parameters and biochemical recurrence after radical prostatectomy was assessed. 29.1% of all tumor nodules showed concurrent nuclear ERG and MYC protein overexpression (i.e., ERG-positive/MYC high), including 35.0% of secondary nodules. Overall, there was weak positive correlation between ERG and MYC expression across all tumor nodules (rpb  = 0.149, P = 0.045), although this correlation was strongest in secondary nodules (rpb  = 0.520, P = 0.019). In radical prostatectomy specimens, ERG-positive/MYC high tumors were positively associated with the presence of extraprostatic extension (EPE), relative to all other ERG/MYC expression subgroups, however, there was no significant association between concurrent nuclear ERG and MYC protein overexpression and time to biochemical recurrence. Concurrent nuclear ERG and MYC protein overexpression is common in prostate cancer and defines a subset of locally advanced tumors. Recent data indicates that BET bromodomain proteins regulate ERG gene fusion and MYC gene expression in prostate cancer, suggesting possible synergistic

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

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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

Chemical biology drug sensitivity screen identifies sunitinib as synergistic agent with disulfiram in prostate cancer cells.

Directory of Open Access Journals (Sweden)

Kirsi Ketola

Full Text Available Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects.In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression.Taken together, our results propose novel combinatorial approaches to inhibit prostate cancer cell growth. Disulfiram

Loss of the NKX3.1 tumorsuppressor promotes the TMPRSS2-ERG fusion gene expression in prostate cancer

International Nuclear Information System (INIS)

Thangapazham, Rajesh; Saenz, Francisco; Katta, Shilpa; Mohamed, Ahmed A; Tan, Shyh-Han; Petrovics, Gyorgy; Srivastava, Shiv; Dobi, Albert

2014-01-01

In normal prostate epithelium the TMPRSS2 gene encoding a type II serine protease is directly regulated by male hormones through the androgen receptor. In prostate cancer ERG protooncogene frequently gains hormonal control by seizing gene regulatory elements of TMPRSS2 through genomic fusion events. Although, the androgenic activation of TMPRSS2 gene has been established, little is known about other elements that may interact with TMPRSS2 promoter sequences to modulate ERG expression in TMPRSS2-ERG gene fusion context. Comparative genomic analyses of the TMPRSS2 promoter upstream sequences and pathway analyses were performed by the Genomatix Software. NKX3.1 and ERG genes expressions were evaluated by immunoblot or by quantitative Real-Time PCR (qRT-PCR) assays in response to siRNA knockdown or heterologous expression. QRT-PCR assay was used for monitoring the gene expression levels of NKX3.1-regulated genes. Transcriptional regulatory function of NKX3.1 was assessed by luciferase assay. Recruitment of NKX3.1 to its cognate elements was monitored by Chromatin Immunoprecipitation assay. Comparative analysis of the TMPRSS2 promoter upstream sequences among different species revealed the conservation of binding sites for the androgen inducible NKX3.1 tumor suppressor. Defects of NKX3.1, such as, allelic loss, haploinsufficiency, attenuated expression or decreased protein stability represent established pathways in prostate tumorigenesis. We found that NKX3.1 directly binds to TMPRSS2 upstream sequences and negatively regulates the expression of the ERG protooncogene through the TMPRSS2-ERG gene fusion. These observations imply that the frequently noted loss-of-function of NKX3.1 cooperates with the activation of TMPRSS2-ERG fusions in prostate tumorigenesis

Reciprocal positive regulation between TRPV6 and NUMB in PTEN-deficient prostate cancer cells

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Kim, Sung-Young; Hong, Chansik; Wie, Jinhong [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Kim, Euiyong [Department of Physiology, College of Medicine, Inje University, Busan 614-735 (Korea, Republic of); Kim, Byung Joo [Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 626-870 (Korea, Republic of); Ha, Kotdaji [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Cho, Nam-Hyuk; Kim, In-Gyu [Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Jeon, Ju-Hong [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); So, Insuk, E-mail: insuk@snu.ac.kr [Department of Physiology, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

2014-04-25

Highlights: • TRPV6 interacts with tumor suppressor proteins. • Numb has a selective effect on TRPV6, depending on the prostate cancer cell line. • PTEN is a novel regulator of TRPV6–Numb complex. - Abstract: Calcium acts as a second messenger and plays a crucial role in signaling pathways involved in cell proliferation. Recently, calcium channels related to calcium influx into the cytosol of epithelial cells have attracted attention as a cancer therapy target. Of these calcium channels, TRPV6 is overexpressed in prostate cancer and is considered an important molecule in the process of metastasis. However, its exact role and mechanism is unclear. NUMB, well-known tumor suppressor gene, is a novel interacting partner of TRPV6. We show that NUMB and TRPV6 have a reciprocal positive regulatory relationship in PC-3 cells. We repeated this experiment in two other prostate cancer cell lines, DU145 and LNCaP. Interestingly, there were no significant changes in TRPV6 expression following NUMB knockdown in DU145. We revealed that the presence or absence of PTEN was the cause of NUMB–TRPV6 function. Loss of PTEN caused a positive correlation of TRPV6–NUMB expression. Collectively, we determined that PTEN is a novel interacting partner of TRPV6 and NUMB. These results demonstrated a novel relationship of NUMB–TRPV6 in prostate cancer cells, and show that PTEN is a novel regulator of this complex.

Concurrent deletion of 16q23 and PTEN is an independent prognostic feature in prostate cancer.

Science.gov (United States)

Kluth, Martina; Runte, Frederic; Barow, Philipp; Omari, Jazan; Abdelaziz, Zaid M; Paustian, Lisa; Steurer, Stefan; Christina Tsourlakis, Maria; Fisch, Margit; Graefen, Markus; Tennstedt, Pierre; Huland, Hartwig; Michl, Uwe; Minner, Sarah; Sauter, Guido; Simon, Ronald; Adam, Meike; Schlomm, Thorsten

2015-11-15

The deletion of 16q23-q24 belongs to the most frequent chromosomal changes in prostate cancer, but the clinical consequences of this alteration have not been studied in detail. We performed fluorescence in situ hybridization analysis using a 16q23 probe in more than 7,400 prostate cancers with clinical follow-up data assembled in a tissue microarray format. Chromosome 16q deletion was found in 21% of cancers, and was linked to advanced tumor stage, high Gleason grade, accelerated cell proliferation, the presence of lymph node metastases (p Deletion was more frequent in ERG fusion-positive (27%) as compared to ERG fusion-negative cancers (16%, p deletions including phosphatase and tensin homolog (PTEN) (p deletion of 16q was linked to early biochemical recurrence independently from the ERG status (p deletion of 16q alone. Multivariate modeling revealed that the prognostic value of 16q/PTEN deletion patterns was independent from the established prognostic factors. In summary, the results of our study demonstrate that the deletion of 16q and PTEN cooperatively drives prostate cancer progression, and suggests that deletion analysis of 16q and PTEN could be of important clinical value particularly for preoperative risk assessment of the clinically most challenging group of low- and intermediated grade prostate cancers. © 2015 UICC.

Deep sequencing reveals distinct patterns of DNA methylation in prostate cancer.

Science.gov (United States)

Kim, Jung H; Dhanasekaran, Saravana M; Prensner, John R; Cao, Xuhong; Robinson, Daniel; Kalyana-Sundaram, Shanker; Huang, Christina; Shankar, Sunita; Jing, Xiaojun; Iyer, Matthew; Hu, Ming; Sam, Lee; Grasso, Catherine; Maher, Christopher A; Palanisamy, Nallasivam; Mehra, Rohit; Kominsky, Hal D; Siddiqui, Javed; Yu, Jindan; Qin, Zhaohui S; Chinnaiyan, Arul M

2011-07-01

Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in select prostate tissues and cell lines using MethylPlex-next-generation sequencing (M-NGS). Hidden Markov model-based next-generation sequence analysis identified ∼68,000 methylated regions per sample. While global CpG island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation significantly increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively (P-value prostate tissues, 2481 differentially methylated regions (DMRs) are cancer-specific, including numerous novel DMRs. A novel cancer-specific DMR in the WFDC2 promoter showed frequent methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization, and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion-positive and -negative cancers, and we confirmed this observation using pyrosequencing on a tissue panel. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression.

T2*-weighted image/T2-weighted image fusion in postimplant dosimetry of prostate brachytherapy

International Nuclear Information System (INIS)

Katayama, Norihisa; Takemoto, Mitsuhiro; Yoshio, Kotaro

2011-01-01

Computed tomography (CT)/magnetic resonance imaging (MRI) fusion is considered to be the best method for postimplant dosimetry of permanent prostate brachytherapy; however, it is inconvenient and costly. In T2 * -weighted image (T2 * -WI), seeds can be easily detected without the use of an intravenous contrast material. We present a novel method for postimplant dosimetry using T2 * -WI/T2-weighted image (T2-WI) fusion. We compared the outcomes of T2 * -WI/T2-WI fusion-based and CT/T2-WI fusion-based postimplant dosimetry. Between April 2008 and July 2009, 50 consecutive prostate cancer patients underwent brachytherapy. All the patients were treated with 144 Gy of brachytherapy alone. Dose-volume histogram (DVH) parameters (prostate D90, prostate V100, prostate V150, urethral D10, and rectal D2cc) were prospectively compared between T2 * -WI/T2-WI fusion-based and CT/T2-WI fusion-based dosimetry. All the DVH parameters estimated by T2 * -WI/T2-WI fusion-based dosimetry strongly correlated to those estimated by CT/T2-WI fusion-based dosimetry (0.77≤ R ≤0.91). No significant difference was observed in these parameters between the two methods, except for prostate V150 (p=0.04). These results show that T2 * -WI/T2-WI fusion-based dosimetry is comparable or superior to MRI-based dosimetry as previously reported, because no intravenous contrast material is required. For some patients, rather large differences were observed in the value between the 2 methods. We thought these large differences were a result of seed miscounts in T2 * -WI and shifts in fusion. Improving the image quality of T2 * -WI and the image acquisition speed of T2 * -WI and T2-WI may decrease seed miscounts and fusion shifts. Therefore, in the future, T2 * -WI/T2-WI fusion may be more useful for postimplant dosimetry of prostate brachytherapy. (author)

Prostate stromal cell telomere shortening is associated with risk of prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial.

Science.gov (United States)

Heaphy, Christopher M; Gaonkar, Gaurav; Peskoe, Sarah B; Joshu, Corinne E; De Marzo, Angelo M; Lucia, M Scott; Goodman, Phyllis J; Lippman, Scott M; Thompson, Ian M; Platz, Elizabeth A; Meeker, Alan K

2015-08-01

Telomeres are repetitive nucleoproteins that help maintain chromosomal stability by inhibiting exonucleolytic degradation, prohibiting inappropriate homologous recombination, and preventing chromosomal fusions by suppressing double-strand break signals. We recently observed that men treated for clinically localized prostate cancer with shorter telomeres in their cancer-associated stromal cells, in combination with greater variation in cancer cell telomere lengths, were significantly more likely to progress to distant metastases, and die from their disease. Here, we hypothesized that shorter stromal cell telomere length would be associated with prostate cancer risk at time of biopsy. Telomere-specific fluorescence in situ hybridization (FISH) analysis was performed in normal-appearing stromal, basal epithelial, and luminal epithelial cells in biopsies from men randomized to the placebo arm of the Prostate Cancer Prevention Trial. Prostate cancer cases (N = 32) were either detected on a biopsy performed for cause or at the end of the study per trial protocol, and controls (N = 50), defined as negative for cancer on an end-of-study biopsy performed per trial protocol (e.g., irrespective of indication), were sampled. Logistic regression was used to estimate the association between mean telomere length of the particular cell populations, cell-to-cell telomere length variability, and risk of prostate cancer. Men with short stromal cell telomere lengths (below median) had 2.66 (95% CI 1.04-3.06; P = 0.04) times the odds of prostate cancer compared with men who had longer lengths (at or above median). Conversely, we did not observe statistically significant associations for short telomere lengths in normal-appearing basal (OR = 2.15, 95% CI 0.86-5.39; P= 0 .10) or luminal (OR = 1.15, 95% CI 0.47-2.80; P = 0.77) cells. These findings suggest that telomere shortening in normal stromal cells is associated with prostate cancer risk. It is essential

Can gene fusions serve for fingerprints of radiogenic cancers?

International Nuclear Information System (INIS)

Nakamura, Nori

2016-01-01

It has been recognized that malignancies in blood cells often bear specific chromosome translocations or gene fusions. In recent years, the presence of fusion genes became to be known also among solid cancers as driver mutations. However, representative solid cancers bearing specific gene fusions are limited to cancers of thyroid, prostate, and sarcomas among which only thyroid cancer risk is known to be related to radiation exposures. On the other hand, it is extremely rare to find recurrent reciprocal translocations among common cancers such as in the lung, stomach, breast, and colon, which form a major component of radiation risks. It is therefore unlikely that radiation increases the risk of cancer by inducing specific translocations (gene fusions) but more likely through induction of mutations (including deletions). Although gene fusions could play a role in radiation carcinogenesis, it does not seem good enough to serve for a radiation fingerprint. (author)

Incremental diagnostic value of targeted biopsy using mpMRI-TRUS fusion versus 14-fragments prostatic biopsy. A prospective controlled study

International Nuclear Information System (INIS)

Mariotti, Guilherme C.; Falsarella, Priscila M.; Garcia, Rodrigo G.; Queiroz, Marcos R.G.; Lemos, Gustavo C.; Baroni, Ronaldo H.

2018-01-01

To compare the incremental diagnostic value of targeted biopsy using real-time multiparametric magnetic resonance imaging and transrectal ultrasound (mpMRI-TRUS) fusion to conventional 14-cores biopsy. Uni-institutional, institutional review board (IRB) approved prospective blinded study comparing TRUS-guided random and targeted biopsy using mpMRI-TRUS fusion, in 100 consecutive men. We included men with clinical-laboratorial suspicious for prostate cancer and Likert score ≥ 3 mp-MRI. Patients previously diagnosed with prostate cancer were excluded. All patients were submitted to 14-cores TRUS-guided biopsy (mpMRI data operator-blinded), followed by targeted biopsy using mpMRI-TRUS fusion. There was an overall increase in cancer detection rate, from 56% with random technique to 62% combining targeted biopsy using mpMRI-TRUS fusion; incremental diagnosis was even more relevant for clinically significant lesions (Gleason ≥ 7), diagnosing 10% more clinically significant lesions with fusion biopsy technique. Diagnosis upgrade occurred in 5 patients that would have negative results in random biopsies and had clinically significant tumours with the combined technique, and in 5 patients who had the diagnosis of significant tumours after fusion biopsy and clinically insignificant tumours in random biopsies(p=0.0010). Targeted biopsy using mpMRI-TRUS fusion has incremental diagnostic value in comparison to conventional random biopsy, better detecting clinically significant prostate cancers. (orig.)

Incremental diagnostic value of targeted biopsy using mpMRI-TRUS fusion versus 14-fragments prostatic biopsy. A prospective controlled study

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Mariotti, Guilherme C.; Falsarella, Priscila M.; Garcia, Rodrigo G.; Queiroz, Marcos R.G. [Hospital Israelita Albert Einstein, Department of Interventional Radiology, Sao Paulo (Brazil); Lemos, Gustavo C. [Hospital Israelita Albert Einstein, Department of Urology, Sao Paulo (Brazil); Baroni, Ronaldo H. [Hospital Israelita Albert Einstein, Department of Radiology, Sao Paulo (Brazil)

2018-01-15

To compare the incremental diagnostic value of targeted biopsy using real-time multiparametric magnetic resonance imaging and transrectal ultrasound (mpMRI-TRUS) fusion to conventional 14-cores biopsy. Uni-institutional, institutional review board (IRB) approved prospective blinded study comparing TRUS-guided random and targeted biopsy using mpMRI-TRUS fusion, in 100 consecutive men. We included men with clinical-laboratorial suspicious for prostate cancer and Likert score ≥ 3 mp-MRI. Patients previously diagnosed with prostate cancer were excluded. All patients were submitted to 14-cores TRUS-guided biopsy (mpMRI data operator-blinded), followed by targeted biopsy using mpMRI-TRUS fusion. There was an overall increase in cancer detection rate, from 56% with random technique to 62% combining targeted biopsy using mpMRI-TRUS fusion; incremental diagnosis was even more relevant for clinically significant lesions (Gleason ≥ 7), diagnosing 10% more clinically significant lesions with fusion biopsy technique. Diagnosis upgrade occurred in 5 patients that would have negative results in random biopsies and had clinically significant tumours with the combined technique, and in 5 patients who had the diagnosis of significant tumours after fusion biopsy and clinically insignificant tumours in random biopsies(p=0.0010). Targeted biopsy using mpMRI-TRUS fusion has incremental diagnostic value in comparison to conventional random biopsy, better detecting clinically significant prostate cancers. (orig.)

TMPRSS2-ERG gene fusion status in minute (minimal) prostatic adenocarcinoma.

Science.gov (United States)

Albadine, Roula; Latour, Mathieu; Toubaji, Antoun; Haffner, Michael; Isaacs, William B; A Platz, Elizabeth; Meeker, Alan K; Demarzo, Angelo M; Epstein, Jonathan I; Netto, George J

2009-11-01

Minute prostatic adenocarcinomas are considered to be of insufficient virulence. Given recent suggestions of TMPRSS2-ERG gene fusion association with aggressive prostatic adenocarcinoma, we evaluated the incidence of TMPRSS2-ERG fusion in minute prostatic adenocarcinomas. A total of 45 consecutive prostatectomies with minute adenocarcinoma were used for tissue microarray construction. A total of 63 consecutive non-minimal, Gleason Score 6 tumors, from a separate PSA Era prostatectomy tissue microarray, were used for comparison. FISH was carried out using ERG break-apart probes. Tumors were assessed for fusion by deletion (Edel) or split (Esplit), duplicated fusions and low-level copy number gain in normal ERG gene locus. Minute adenocarcinomas: Fusion was evaluable in 32/45 tumors (71%). Fifteen out of 32 (47%) tumors were positive for fusion. Six (19%) were of the Edel class and 7 (22%) were classified as combined Edel+Esplit. Non-minute adenocarcinomas (pT2): Fusion was identified in 20/30 tumors (67%). Four (13%) were of Edel class and 5 (17%) were combined Edel+Esplit. Duplicated fusions were encountered in 5 (16%) tumors. Non-minute adenocarcinomas (pT3): Fusion was identified in 19/33 (58%). Fusion was due to a deletion in 6 (18%) tumors. Seven tumors (21%) were classified as combined Edel+Esplit. One tumor showed Esplit alone. Duplicated fusions were encountered in 3 (9%) cases. The incidence of duplicated fusions was higher in non-minute adenocarcinomas (13 vs 0%; P=0.03). A trend for higher incidence of low-level copy number gain in normal ERG gene locus without fusion was noted in non-minute adenocarcinomas (10 vs 0%; P=0.07). We found a TMPRSS2-ERG fusion rate of 47% in minute adenocarcinomas. The latter is not significantly different from that of grade matched non-minute adenocarcinomas. The incidence of duplicated fusion was higher in non-minute adenocarcinomas. Our finding of comparable rate of TMPRSS2-ERG fusion in minute adenocarcinomas may argue

Matched Cohort Analysis of Outcomes of Definitive Radiotherapy for Prostate Cancer in Human Immunodeficiency Virus-Positive Patients

International Nuclear Information System (INIS)

Kahn, Shannon; Jani, Ashesh; Edelman, Scott; Rossi, Peter; Godette, Karen; Landry, Jerome; Anderson, Cynthia

2012-01-01

Purpose: To compare the biochemical outcome and toxicity scores of men with human immunodeficiency virus (HIV) and prostate cancer with a matched control population with negative or unknown HIV status when treated with external-beam radiotherapy (EBRT). Methods and Materials: A single-institution database of men with prostate cancer treated with EBRT from 1999 to 2009 was reviewed. Thirteen men with HIV were identified and matched to 2 control patients according to age, race, T stage, prostate-specific antigen level, Gleason score, RT dose, intensity-modulated RT vs. three-dimensional conformal RT, and whole-pelvis vs. prostate-only RT, for a total of 39 cases. The median follow-up time was 39 months (range, 3–110 months). Results: The 4-year biochemical failure (BF)-free survival rate was 87% in the HIV-positive group vs. 89% in the controls (p = 0.94). Pre- and post-RT viral loads were found to be predictive of BF (p = 0.04 and p = 0.04, respectively). No men with HIV died, whereas 2 in the control group died of causes unrelated to prostate cancer. Acute and chronic genitourinary and gastrointestinal toxicity were less in the HIV-positive patients than in controls (p 3 . Conclusions: Our findings suggest that men with HIV treated with EBRT have a similar risk of BF; however, high viral loads may contribute to an increased risk. This analysis supports that HIV-positive men with prostate cancer can be treated with definitive EBRT with similar disease control and toxicity outcomes as in the general population.

Comparison of MRI-based and CT/MRI fusion-based postimplant dosimetric analysis of prostate brachytherapy

International Nuclear Information System (INIS)

Tanaka, Osamu; Hayashi, Shinya; Matsuo, Masayuki; Sakurai, Kota; Nakano, Masahiro; Maeda, Sunaho; Kajita, Kimihiro R.T.; Deguchi, Takashi; Hoshi, Hiroaki

2006-01-01

Purpose: The aim of this study was to compare the outcomes between magnetic resonance imaging (MRI)-based and computed tomography (CT)/MRI fusion-based postimplant dosimetry methods in permanent prostate brachytherapy. Methods and Materials: Between October 2004 and March 2006, a total of 52 consecutive patients with prostate cancer were treated by brachytherapy, and postimplant dosimetry was performed using CT/MRI fusion. The accuracy and reproducibility were prospectively compared between MRI-based dosimetry and CT/MRI fusion-based dosimetry based on the dose-volume histogram (DVH) related parameters as recommended by the American Brachytherapy Society. Results: The prostate volume was 15.97 ± 6.17 cc (mean ± SD) in MRI-based dosimetry, and 15.97 ± 6.02 cc in CT/MRI fusion-based dosimetry without statistical difference. The prostate V100 was 94.5% and 93.0% in MRI-based and CT/MRI fusion-based dosimetry, respectively, and the difference was statistically significant (p = 0.002). The prostate D90 was 119.4% and 114.4% in MRI-based and CT/MRI fusion-based dosimetry, respectively, and the difference was statistically significant (p = 0.004). Conclusion: Our current results suggested that, as with fusion images, MR images allowed accurate contouring of the organs, but they tended to overestimate the analysis of postimplant dosimetry in comparison to CT/MRI fusion images. Although this MRI-based dosimetric discrepancy was negligible, MRI-based dosimetry was acceptable and reproducible in comparison to CT-based dosimetry, because the difference between MRI-based and CT/MRI fusion-based results was smaller than that between CT-based and CT/MRI fusion-based results as previously reported

Toxicity and outcome of pelvic IMRT for node-positive prostate cancer

International Nuclear Information System (INIS)

Mueller, A.C.; Luetjens, J.; Eckert, F.; Bamberg, M.; Alber, M.; Schilling, D.; Belka, C.; Gaswindt, U.

2012-01-01

Background and purpose: This study reports on the treatment techniques, toxicity, and outcome of pelvic intensity-modulated radiotherapy (IMRT) for lymph node-positive prostate cancer (LNPPC, T1-4, c/pN1 cM0). Patients and methods: Pelvic IMRT to 45-50.4 Gy was applied in 39 cases either after previous surgery of involved lymph nodes (n = 18) or with a radiation boost to suspicious nodes (n = 21) with doses of 60-70 Gy, usually combined with androgen deprivation (n = 37). The prostate and seminal vesicles received 70-74 Gy. In cases of previous prostatectomy, prostatic fossa and remnants of seminal vesicles were given 66-70 Gy. Treatment-related acute and late toxicity was graded according to the RTOG criteria. Results: Acute radiation-related toxicity higher than grade 2 occurred in 2 patients (with the need for urinary catheter/subileus related to adhesions after surgery). Late toxicity was mild (grade 1-2) after a median follow-up of 70 months. Over 50% of the patients reported no late morbidity (grade 0). PSA control and cancer-specific survival reached 67% and 97% at over 5 years. Conclusion: Pelvic IMRT after the removal of affected nodes or with a radiation boost to clinically positive nodes led to an acceptable late toxicity (no grade 3/4 events), thus justifying further evaluation of this approach in a larger cohort. (orig.)

Where Do Transrectal Ultrasound- and Magnetic Resonance Imaging-guided Biopsies Miss Significant Prostate Cancer?

DEFF Research Database (Denmark)

Boesen, Lars; Nørgaard, Nis; Løgager, Vibeke

2017-01-01

-guided biopsy (reTRUSbx) and targeted mpMRIbx (image fusion) of any suspicious lesion. Biopsy results were compared and the locations of missed sPCa lesions were registered. Cancer significance was defined as (1) any core with a Gleason score of >6, (2) cancer core involvement of ≥50% and for re......TRUSbx on patient level, and (3) the presence of ≥3 positive cores. RESULTS: Of the 289 patients, prostate cancer was detected in 128 (44%) with 88 (30%) having sPCa. Overall, 165 separate prostate cancer lesions were detected with 100 being sPCa. Of these, mpMRIbx and reTRUSbx detected 90% (90/100) and 68% (68...... TRUSbx and mpMRIbx missed sPCa lesions in specific segments of the prostate. Missed sPCa lesions at repeat biopsy were primarily located anteriorly for TRUSbx and posterolateral midprostatic for mpMRIbx. Localization of these segments may improve biopsy techniques in men undergoing repeat biopsies....

Prostate cancer

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

1987-01-01

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

Prostate cancer

International Nuclear Information System (INIS)

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

1987-01-01

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

Fused-data transrectal EIT for prostate cancer imaging.

Science.gov (United States)

Murphy, Ethan K; Wu, Xiaotian; Halter, Ryan J

2018-05-25

Prostate cancer is a significant problem affecting 1 in 7 men. Unfortunately, the diagnostic gold-standard of ultrasound-guided biopsy misses 10%-30% of all cancers. The objective of this study was to develop an electrical impedance tomography (EIT) approach that has the potential to image the entire prostate using multiple impedance measurements recorded between electrodes integrated onto an end-fired transrectal ultrasound (TRUS) device and a biopsy probe (BP). Simulations and sensitivity analyses were used to investigate the best combination of electrodes, and measured tank experiments were used to evaluate a fused-data transrectal EIT (fd-TREIT) and BP approach. Simulations and sensitivity analysis revealed that (1) TREIT measurements are not sufficiently sensitive to image the whole prostate, (2) the combination of TREIT  +  BP measurements increases the sensitive region of TREIT-only measurements by 12×, and (3) the fusion of multiple TREIT  +  BP measurements collected during a routine or customized 12-core biopsy procedure can cover up to 76.1% or 94.1% of a nominal 50 cm 3 prostate, respectively. Three measured tank experiments of the fd-TREIT  +  BP approach successfully and accurately recovered the positions of 2-3 metal or plastic inclusions. The measured tank experiments represent important steps in the development of an algorithm that can combine EIT from multiple locations and from multiple probes-data that could be collected during a routine TRUS-guided 12-core biopsy. Overall, this result is a step towards a clinically deployable impedance imaging approach to scanning the entire prostate, which could significantly help to improve prostate cancer diagnosis.

Advanced research on separating prostate cancer stem cells

International Nuclear Information System (INIS)

Hao Yumei; He Xin; Song Naling

2013-01-01

Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

Cancer Patient T Cells Genetically Targeted to Prostate-Specific Membrane Antigen Specifically Lyse Prostate Cancer Cells and Release Cytokines in Response to Prostate-Specific Membrane Antigen

Directory of Open Access Journals (Sweden)

Michael C. Gong

1999-06-01

Full Text Available The expression of immunoglobulin-based artificial receptors in normal T lymphocytes provides a means to target lymphocytes to cell surface antigens independently of major histocompatibility complex restriction. Such artificial receptors have been previously shown to confer antigen-specific tumoricidal properties in murine T cells. We constructed a novel ζ chain fusion receptor specific for prostate-specific membrane antigen (PSMA termed Pz-1. PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and the neovascular endothelium of multiple carcinomas. We show that primary T cells harvested from five of five patients with different stages of prostate cancer and transduced with the Pz-1 receptor readily lyse prostate cancer cells. Having established a culture system using fibroblasts that express PSMA, we next show that T cells expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA. Furthermore, we show that the cytokine release is greatly augmented by B7.1-mediated costimulation. Thus, our findings support the feasibility of adoptive cell therapy by using genetically engineered T cells in prostate cancer patients and suggest that both CD4+ and CD8+ T lymphocyte functions can be synergistically targeted against tumor cells.

Initial clinical assessment of CT-MRI image fusion software in localization of the prostate for 3D conformal radiation therapy

International Nuclear Information System (INIS)

Kagawa, Kazufumi; Lee, W. Robert; Schultheiss, Timothy E.; Hunt, Margie A.; Shaer, Andrew H.; Hanks, Gerald E.

1997-01-01

Purpose: To assess the utility of image fusion software and compare MRI prostate localization with CT localization in patients undergoing 3D conformal radiation therapy of prostate cancer. Materials and Methods: After a phantom study was performed to ensure the accuracy of image fusion procedure, 22 prostate cancer patients had CT and MRI studies before the start of radiotherapy. Immobilization casts used during radiation treatment were also used for both imaging studies. After the clinical target volume (CTV) (prostate or prostate + seminal vesicles) was defined on CT, slices from the MRI study were reconstructed to precisely match the CT slices by identifying three common bony landmarks on each study. The CTV was separately defined on the matched MRI slices. Data related to the size and location of the prostate were compared between CT and MRI. The spatial relationship between the tip of urethrogram cone on CT and prostate apex seen on MRI was also estimated. Results: The phantom study showed the registration discrepancies between CT and MRI smaller than 1.0 mm in any pair in comparison. The patient study showed a mean image registration error of 0.9 (± 0.6) mm. The average prostate volume was 63.0 (± 25.8) cm 3 and 50.9 (± 22.9) cm 3 determined by CT and MRI, respectively. The difference in prostate location with the two studies usually differed at the base and at the apex of the prostate. On the transverse MRI, the prostate apex was situated 7.1 (± 4.5) mm dorsal and 15.1 (± 4.0) mm cephalad to the tip of urethrogram cone. Conclusions: CT-MRI image fusion study made it possible to compare the two modalities directly. MRI localization of the prostate is more accurate than CT, and indicates the distance from cone to apex is 15 mm. CT-MRI image fusion technique provides valuable supplements to CT technology for more precise targeting of the prostate cancer

Matched Cohort Analysis of Outcomes of Definitive Radiotherapy for Prostate Cancer in Human Immunodeficiency Virus-Positive Patients

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Kahn, Shannon, E-mail: shannonkahn@yahoo.com [Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA (United States); Jani, Ashesh; Edelman, Scott; Rossi, Peter; Godette, Karen; Landry, Jerome; Anderson, Cynthia [Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA (United States); Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA (United States)

2012-05-01

Purpose: To compare the biochemical outcome and toxicity scores of men with human immunodeficiency virus (HIV) and prostate cancer with a matched control population with negative or unknown HIV status when treated with external-beam radiotherapy (EBRT). Methods and Materials: A single-institution database of men with prostate cancer treated with EBRT from 1999 to 2009 was reviewed. Thirteen men with HIV were identified and matched to 2 control patients according to age, race, T stage, prostate-specific antigen level, Gleason score, RT dose, intensity-modulated RT vs. three-dimensional conformal RT, and whole-pelvis vs. prostate-only RT, for a total of 39 cases. The median follow-up time was 39 months (range, 3-110 months). Results: The 4-year biochemical failure (BF)-free survival rate was 87% in the HIV-positive group vs. 89% in the controls (p = 0.94). Pre- and post-RT viral loads were found to be predictive of BF (p = 0.04 and p = 0.04, respectively). No men with HIV died, whereas 2 in the control group died of causes unrelated to prostate cancer. Acute and chronic genitourinary and gastrointestinal toxicity were less in the HIV-positive patients than in controls (p < 0.001, p < 0.001, p = 0.003, and p < 0.001, respectively). The HIV-positive men experienced an average decline in CD4 count of 193 cells/mm{sup 3}. Conclusions: Our findings suggest that men with HIV treated with EBRT have a similar risk of BF; however, high viral loads may contribute to an increased risk. This analysis supports that HIV-positive men with prostate cancer can be treated with definitive EBRT with similar disease control and toxicity outcomes as in the general population.

Comparison of telomerase activity in prostate cancer, prostatic intraepithelial neoplasia and benign prostatic hyperplasia

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Soleiman Mahjoub

2006-11-01

Full Text Available BACKGROUND: Telomerase is a reverse transcriptase enzyme that synthesizes telomeric DNA on chromosome ends. The enzyme is important for the immortalization of cancer cells because it maintains the telomeres. METHODS: Telomerase activity (TA was measured by fluorescence-based telomeric repeat amplification protocol (FTRAP assay in prostate carcinoma and benign prostatic hyperplasia (BPH. RESULTS: TA was present in 91.4% of 70 prostate cancers, 68.8% of 16 prostatic intraepithelial neoplasia (PIN, 43.3% of 30 BPH*, 21.4% of 14 atrophy and 20% of 15 normal samples adjacent to tumor. There was not any significant correlation between TA, histopathological tumor stage or gleason score. In contrast to high TA in the BPH* tissue from the cancer-bearing gland, only 6.3% of 32 BPH specimens from patients only diagnosed with BPH were telomerase activity-positive. CONCLUSIONS: These results indicate that TA is present in most prostate cancers. The high rate of TA in tissue adjacent to tumor may be attributed either to early molecular alteration of cancer that was histologically unapparent, or to the presence of occult cancer cells. Our findings suggest that the re-expression of telomerase activity could be one step in the transformation of BPH to PIN. KEY WORDS: Telomerase activity, prostate cancer, prostatic intraepithelial neoplasia, benign prostatic hyperplasia.

Racial differences in prostate cancer risk in young HIV-positive and HIV-negative men: a prospective cohort study.

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Dutta, Anupriya; Uno, Hajime; Holman, Alex; Lorenz, David R; Gabuzda, Dana

2017-07-01

African American men have the highest incidence of prostate cancer among ethnic groups, and racial disparity is highest in younger men. Prostate cancer prevalence is rising in HIV-infected men due to improved survival on antiretroviral therapies, yet little is known about racial differences in prostate cancer risk by HIV-infection status and age. This is a prospective cohort study of prostate cancer risk in 2,800 HIV-infected and -uninfected men who have sex with men (MSM) aged 40-70 years (22% African American) who were enrolled in the multicenter AIDS cohort study from 1996 to 2010. Poisson regression models were used to examine associations between race and HIV-infection status and prostate cancer risk among men aged 40-70, 40-55, and 56-70 years. Among men aged 40-70 years, incidence rates (IR) per 100,000 person-years were 169 among all men and 276 among African American HIV-infected men. Prostate cancer risk was similar by HIV-infection status (IRR 1.0, 95% CI 0.55-1.82), but nearly threefold higher in African Americans compared to non-African Americans in adjusted models (IRRs 2.66 and 3.22, 95% CIs 1.36-5.18 and 1.27-8.16 for all or HIV-infected men, respectively). Racial disparity in prostate cancer risk was greatest in African American men aged 40-55 years (adjusted IRR 3.31, 95% CI 1.19-9.22). Prostate cancer risk showed associations with family history of prostate cancer (p = 0.001), but not heavy smoking, androgen supplement use, or HIV-related factors. Among MSM, African American HIV-positive and HIV-negative men aged 40-55 years have threefold increased risk of young-onset prostate cancer compared to non-African American men, highlighting the need to make informed decisions about screening in this population.

The Role of SPINK1 in ETS Rearrangement Negative Prostate Cancers

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Tomlins, Scott A.; Rhodes, Daniel R.; Yu, Jianjun; Varambally, Sooryanarayana; Mehra, Rohit; Perner, Sven; Demichelis, Francesca; Helgeson, Beth E.; Laxman, Bharathi; Morris, David S.; Cao, Qi; Cao, Xuhong; Andrén, Ove; Fall, Katja; Johnson, Laura; Wei, John T.; Shah, Rajal B.; Al-Ahmadie, Hikmat; Eastham, James A.; Eggener, Scott E.; Fine, Samson W.; Hotakainen, Kristina; Stenman, Ulf-Håkan; Tsodikov, Alex; Gerald, William L.; Lilja, Hans; Reuter, Victor E.; Kantoff, Phillip W.; Scardino, Peter T.; Rubin, Mark A.; Bjartell, Anders S.; Chinnaiyan, Arul M.

2009-01-01

Summary ETS gene fusions have been characterized in a majority of prostate cancers, however the key molecular alterations in ETS negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier-expression exclusively in a subset of ETS rearrangement negative cancers (~10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier-expression can be detected non-invasively in urine and observed that SPINK1 outlier-expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier-expression model, and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement negative prostate cancers. PMID:18538735

Transcriptome sequencing in prostate cancer identifies inter-tumor heterogeneity

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Janet Mendonca

2015-06-01

Full Text Available Given the dearth of gene mutations in prostate cancer, [1] ,[2] it is likely that genomic rearrangements play a significant role in the evolution of prostate cancer. However, in the search for recurrent genomic alterations, "private alterations" have received less attention. Such alterations may provide insights into the evolution, behavior, and clinical outcome of an individual tumor. In a recent report in "Genome Biology" Wyatt et al. [3] defines unique alterations in a cohort of high-risk prostate cancer patient with a lethal phenotype. Utilizing a transcriptome sequencing approach they observe high inter-tumor heterogeneity; however, the genes altered distill into three distinct cancer-relevant pathways. Their analysis reveals the presence of several non-ETS fusions, which may contribute to the phenotype of individual tumors, and have significance for disease progression.

Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression.

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Bonkhoff, Helmut

2018-01-01

The androgen receptor (AR) is the classical target for prostate cancer prevention and treatment, but more recently estrogens and their receptors have also been implicated in prostate cancer development and tumor progression. Recent experimental and clinical data were reviewed to elucidate pathogenetic mechanisms how estrogens and their receptors may affect prostate carcinogenesis and tumor progression. The estrogen receptor beta (ERβ) is the most prevalent ER in the human prostate, while the estrogen receptor alpha (ERα) is restricted to basal cells of the prostatic epithelium and stromal cells. In high grade prostatic intraepithelial neoplasia (HGPIN), the ERα is up-regulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models. The partial loss of the ERβ in HGPIN indicates that the ERβ acts as a tumor suppressor. The tumor promoting function of the TMPRSS2-ERG fusion, a major driver of prostate carcinogenesis, is triggered by the ERα and repressed by the ERβ. The ERβ is generally retained in hormone naïve and metastatic prostate cancer, but is partially lost in castration resistant disease. The progressive emergence of the ERα and ERα-regulated genes (eg, progesterone receptor (PR), PS2, TMPRSS2-ERG fusion, and NEAT1) during prostate cancer progression and hormone refractory disease suggests that these tumors can bypass the AR by using estrogens and progestins for their growth. In addition, nongenomic estrogen signaling pathways mediated by orphan receptors (eg, GPR30 and ERRα) has also been implicated in prostate cancer progression. Increasing evidences demonstrate that local estrogen signaling mechanisms are required for prostate carcinogenesis and tumor progression. Despite the recent progress in this research topic, the translation of the current information into potential therapeutic applications remains highly challenging and clearly warrants further investigation. © 2017 Wiley Periodicals, Inc.

Prostate cancer detection: Fusion of cytological and textural features.

Science.gov (United States)

Nguyen, Kien; Jain, Anil K; Sabata, Bikash

2011-01-01

A computer-assisted system for histological prostate cancer diagnosis can assist pathologists in two stages: (i) to locate cancer regions in a large digitized tissue biopsy, and (ii) to assign Gleason grades to the regions detected in stage 1. Most previous studies on this topic have primarily addressed the second stage by classifying the preselected tissue regions. In this paper, we address the first stage by presenting a cancer detection approach for the whole slide tissue image. We propose a novel method to extract a cytological feature, namely the presence of cancer nuclei (nuclei with prominent nucleoli) in the tissue, and apply this feature to detect the cancer regions. Additionally, conventional image texture features which have been widely used in the literature are also considered. The performance comparison among the proposed cytological textural feature combination method, the texture-based method and the cytological feature-based method demonstrates the robustness of the extracted cytological feature. At a false positive rate of 6%, the proposed method is able to achieve a sensitivity of 78% on a dataset including six training images (each of which has approximately 4,000×7,000 pixels) and 1 1 whole-slide test images (each of which has approximately 5,000×23,000 pixels). All images are at 20X magnification.

Multiparametric magnetic resonance imaging in the detection of prostate cancer

International Nuclear Information System (INIS)

Durmus, T.; Baur, A.; Hamm, B.

2014-01-01

Prostate cancer is the most common malignancy in men, but only about 10 % of patients die from that cancer. Recent studies suggest that not all patients benefit from a radical therapeutic approach. When prostate cancer is suspected, magnetic resonance imaging (MRI) can make an important contribution to cancer localization within the prostate. Many studies show that T2-weighted morphologic imaging should be supplemented by multiparametric MRI techniques including diffusion-weighted imaging, contrast-enhanced sequences, and MR spectroscopy. This approach detects aggressive prostate cancer with high sensitivity and specificity. The findings of multiparametric MRI additionally contribute information to the assessment of cancer aggressiveness. The use of these multiparametric MRI techniques will gain an increasing role in the clinical management of prostate cancer patients. They can help in establishing a definitive diagnosis with a minimum of invasiveness and may also contribute to optimal individualized treatment. This review article presents the different techniques of multiparametric MRI and discusses their contribution to the detection of prostate cancer. Moreover, this review outlines an objective approach to image interpretation and structured reporting of MRI findings using the PI-RADS criteria. The review concludes with an outline of approaches to prostate biopsy on the basis of MRI (transrectal ultrasound, direct MRI guidance of tissue sampling, and MRI-ultrasound fusion biopsy) and emerging future uses of MRI in the planning of focal treatment options and in the active surveillance of patients diagnosed with prostate cancer. (orig.)

Pubertal development and prostate cancer risk

DEFF Research Database (Denmark)

Bonilla, Carolina; Lewis, Sarah J; Martin, Richard M

2016-01-01

, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade. CONCLUSIONS: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease.......BACKGROUND: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain...... to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI...

Prostatic MR imaging. Accuracy in differentiating cancer from other prostatic disorders

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Ikonen, S.; Kivisaari, L.; Tervahartiala, P. [Helsinki Univ. Central Hospital (Finland). Dept of Radiology; Vehmas, T. [Finnish Inst. of Occupational Health, Helsinki (Finland); Taari, K.; Rannikko, S. [Helsinki Univ. Central Hospital (Finland). Dept of Urology

2001-03-01

Purpose: We assessed the accuracy of MR imaging in differentiating between cancer and other prostatic disorders, and evaluated the diagnostic criteria for various prostatic diseases. Material and Methods: A total of 74 endorectal coil MR studies were performed on 72 patients. Twenty patients had prostatic cancer, 20 benign prostatic hyperplasia (BPH), 4 acute bacterial prostatitis, 5 chronic bacterial prostatitis (2 also belonging to the previous category), 19 chronic non-bacterial prostatitis/chronic pelvic pain syndrome, and 6 were symptomless voluntary controls. All studies were interpreted by two experienced radiologists in random order. Radiologists were blinded to all clinical data including the age of the patients. Based on MR findings, both radiologists filled in a form covering diagnostic criteria and diagnosis. Results: Accuracy in diagnosing prostate cancer was 74%. Sensitivity was 50% and specificity 83%, and positive and negative predictive values were 53 and 82%, respectively. Bacterial prostatitis showed some features similar to carcinoma. Abundant BPH rendered cancer detection more difficult. No diagnostic criterion was clearly better than the others. Interobserver agreement on the MR diagnosis ranged from moderate to good. Conclusion: Without knowledge of accurate clinical data, MR seems to be too insensitive in detecting prostate cancer to be used as a primary diagnostic tool.

Lesion volume predicts prostate cancer risk and aggressiveness: validation of its value alone and matched with prostate imaging reporting and data system score.

Science.gov (United States)

Martorana, Eugenio; Pirola, Giacomo Maria; Scialpi, Michele; Micali, Salvatore; Iseppi, Andrea; Bonetti, Luca Reggiani; Kaleci, Shaniko; Torricelli, Pietro; Bianchi, Giampaolo

2017-07-01

To demonstrate the association between magnetic resonance imaging (MRI) estimated lesion volume (LV), prostate cancer detection and tumour clinical significance, evaluating this variable alone and matched with Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score. We retrospectively analysed 157 consecutive patients, with at least one prior negative systematic prostatic biopsy, who underwent transperineal prostate MRI/ultrasonography fusion-targeted biopsy between January 2014 and February 2016. Suspicious lesions were delineated using a 'region of interest' and the system calculated prostate volume and LV. Patients were divided in groups considering LV (≤0.5, 0.5-1, ≥1 mL) and PI-RADS score (1-5). We considered clinically significant prostate cancer as all cancers with a Gleason score of ≥3 + 4 as suggested by PI-RADS v2. A direct comparison between MRI estimated LV (MRI LV) and histological tumour volume (HTV) was done in 23 patients who underwent radical prostatectomy during the study period. Differences between MRI LV and HTV were assessed using the paired sample t-test. MRI LV and HTV concordance was verified using a Bland-Altman plot. The chi-squared test and logistic and ordinal regression models were used to evaluate difference in frequencies. The MRI LV and PI-RADS score were associated both with prostate cancer detection (both P prostate cancer detection (P Prostate cancer detection was 1.4-times higher for LVs of 0.5-1 mL and 1.8-times higher for LVs of ≥1 mL; significant prostate cancer detection was 2.6-times for LVs of 0.5-1 mL and 4-times for LVs of ≥1 mL. There was a positive correlation between MRI LV and HTV (r = 0.9876, P prostate cancer detection and with tumour clinical significance. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Childhood height, adult height, and the risk of prostate cancer

DEFF Research Database (Denmark)

Bjerregaard, Lise Geisler; Aarestrup, Julie; Gamborg, Michael

2016-01-01

PURPOSE: We previously showed that childhood height is positively associated with prostate cancer risk. It is, however, unknown whether childhood height exerts its effects independently of or through adult height. We investigated whether and to what extent childhood height has a direct effect...... on the risk of prostate cancer apart from adult height. METHODS: We included 5,871 men with height measured at ages 7 and 13 years in the Copenhagen School Health Records Register who also had adult (50-65 years) height measured in the Danish Diet, Cancer and Health study. Prostate cancer status was obtained...... through linkage to the Danish Cancer Registry. Direct and total effects of childhood height on prostate cancer risk were estimated from Cox regressions. RESULTS: From 1996 to 2012, 429 prostate cancers occurred. Child and adult heights were positively and significantly associated with prostate cancer risk...

VEGFR-1 Overexpression Identifies a Small Subgroup of Aggressive Prostate Cancers in Patients Treated by Prostatectomy

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Maria Christina Tsourlakis

2015-04-01

Full Text Available The VEGFR-1 is suggested to promote tumor progression. In the current study we analyzed prevalence and prognostic impact of the VEGFR-1 by immunohistochemistry on a tissue microarray containing more than 3000 prostate cancer specimens. Results were compared to tumor phenotype, ETS-related gene (ERG status, and biochemical recurrence. Membranous VEGFR-1 expression was detectable in 32.6% of 2669 interpretable cancers and considered strong in 1.7%, moderate in 6.7% and weak in 24.2% of cases. Strong VEGFR-1 expression was associated with TMPRSS2:ERG fusion status as determined by fluorescence in situ hybridization (FISH and immunohistochemistry (p < 0.0001 each. Elevated VEGFR-1 expression was linked to high Gleason grade and advanced pT stage in TMPRSS2:ERG negative cancers (p = 0.0008 and p = 0.001, while these associations were absent in TMPRSS2:ERG positive cancers. VEGFR-1 expression was also linked to phosphatase and tensin homolog (PTEN deletions. A comparison with prostate specific antigen (PSA recurrence revealed that the 1.7% of prostate cancers with the highest VEGFR-1 levels had a strikingly unfavorable prognosis. This could be seen in all cancers, in the subsets of TMPRSS2:ERG positive or negative, PTEN deleted or undeleted carcinomas (p < 0.0001 each. High level VEGFR-1 expression is infrequent in prostate cancer, but identifies a subgroup of aggressive cancers, which may be candidates for anti-VEGFR-1 targeted therapy.

The value of endorectal MR imaging to predict positive biopsies in clinically intermediate-risk prostate cancer patients

International Nuclear Information System (INIS)

Vilanova, J.C.; Barcelo, J.; Comet, J.; Capdevila, A.; Dolz, J.L.; Huguet, M.; Aldoma, J.; Delgado, E.; Barcelo, C.

2001-01-01

The aim of this study was to assess the effectiveness of endorectal MR imaging in predicting the positive biopsy results in patients with clinically intermediate risk for prostate cancer. We performed a prospective endorectal MR imaging study with 81 patients at intermediate risk to detect prostate cancer between January 1997 and December 1998. Intermediate risk was defined as: prostatic specific antigen (PSA) levels between 4 and 10 ng/ml or PSA levels in the range of 10-20 ng/ml but negative digital rectal examination (DRE) or PSA levels progressively higher (0.75 ng/ml year -1 ). A transrectal sextant biopsy was performed after the endorectal MR exam, and also of the area of suspicion detected by MR imaging. The accuracies were measured, both singly for MR imaging and combined for PSA level and DRE, by calculating the area index of the receiver operating characteristics (ROC) curve. Cancer was detected in 23 patients (28 %). Overall sensitivity and specificity of endorectal MRI was 70 and 76 %, respectively. Accuracy was 71 % estimated from the area under the ROC curve for the total patient group and 84 % for the group of patients with PSA level between 10-20 ng/ml. Positive biopsy rate (PBR) was 63 % for the group with PSA 10-20 ng/ml and a positive MR imaging, and 15 % with a negative MR exam. The PBR was 43 % for the group with PSA 4-10 ng/ml and a positive MR study, and 13 % with a negative MR imaging examination. We would have avoided 63 % of negative biopsies, while missing 30 % of cancers for the total group of patients. Endorectal MR imaging was not a sufficient predictor of positive biopsies for patients clinically at intermediate risk for prostate cancer. Although we should not avoid performing systematic biopsies in patients with endorectal MR imaging negative results, as it will miss a significant number of cancers, selected patients with a PSA levels between 10-20 ng/ml or clinical-biopsy disagreement might benefit from endorectal MR imaging. (orig.)

The value of endorectal MR imaging to predict positive biopsies in clinically intermediate-risk prostate cancer patients

Energy Technology Data Exchange (ETDEWEB)

Vilanova, J.C.; Barcelo, J. [Ressonancia Girona, Clinica Girona, Girona (Spain); Comet, J. [Dept. of Urology, Univ. Hospital of Girona (Spain); Capdevila, A.; Dolz, J.L.; Huguet, M.; Aldoma, J.; Delgado, E. [Centre Diagnostic Pedralbes, Cetir Grup Medic, Barcelona (Spain); Barcelo, C. [Dept. of Computer Science and Applied Mathematics, University of Girona (Spain)

2001-02-01

The aim of this study was to assess the effectiveness of endorectal MR imaging in predicting the positive biopsy results in patients with clinically intermediate risk for prostate cancer. We performed a prospective endorectal MR imaging study with 81 patients at intermediate risk to detect prostate cancer between January 1997 and December 1998. Intermediate risk was defined as: prostatic specific antigen (PSA) levels between 4 and 10 ng/ml or PSA levels in the range of 10-20 ng/ml but negative digital rectal examination (DRE) or PSA levels progressively higher (0.75 ng/ml year{sup -1}). A transrectal sextant biopsy was performed after the endorectal MR exam, and also of the area of suspicion detected by MR imaging. The accuracies were measured, both singly for MR imaging and combined for PSA level and DRE, by calculating the area index of the receiver operating characteristics (ROC) curve. Cancer was detected in 23 patients (28 %). Overall sensitivity and specificity of endorectal MRI was 70 and 76 %, respectively. Accuracy was 71 % estimated from the area under the ROC curve for the total patient group and 84 % for the group of patients with PSA level between 10-20 ng/ml. Positive biopsy rate (PBR) was 63 % for the group with PSA 10-20 ng/ml and a positive MR imaging, and 15 % with a negative MR exam. The PBR was 43 % for the group with PSA 4-10 ng/ml and a positive MR study, and 13 % with a negative MR imaging examination. We would have avoided 63 % of negative biopsies, while missing 30 % of cancers for the total group of patients. Endorectal MR imaging was not a sufficient predictor of positive biopsies for patients clinically at intermediate risk for prostate cancer. Although we should not avoid performing systematic biopsies in patients with endorectal MR imaging negative results, as it will miss a significant number of cancers, selected patients with a PSA levels between 10-20 ng/ml or clinical-biopsy disagreement might benefit from endorectal MR imaging

Stages of Prostate Cancer

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... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate Cancer Treatment (PDQ®)–Patient Version General Information About Prostate Cancer Go to Health Professional Version Key Points Prostate ...

Prostate Cancer FAQs

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... Fundraise for PCF: Many vs Cancer Contact Us Prostate Cancer FAQs Top 10 Things You Should Know About ... prostate cancer detected? What are the symptoms of prostate cancer? If the cancer is caught at its earliest ...

Prostate cancer detection: Fusion of cytological and textural features

Directory of Open Access Journals (Sweden)

Kien Nguyen

2011-01-01

Full Text Available A computer-assisted system for histological prostate cancer diagnosis can assist pathologists in two stages: (i to locate cancer regions in a large digitized tissue biopsy, and (ii to assign Gleason grades to the regions detected in stage 1. Most previous studies on this topic have primarily addressed the second stage by classifying the preselected tissue regions. In this paper, we address the first stage by presenting a cancer detection approach for the whole slide tissue image. We propose a novel method to extract a cytological feature, namely the presence of cancer nuclei (nuclei with prominent nucleoli in the tissue, and apply this feature to detect the cancer regions. Additionally, conventional image texture features which have been widely used in the literature are also considered. The performance comparison among the proposed cytological textural feature combination method, the texture-based method and the cytological feature-based method demonstrates the robustness of the extracted cytological feature. At a false positive rate of 6%, the proposed method is able to achieve a sensitivity of 78% on a dataset including six training images (each of which has approximately 4,000x7,000 pixels and 1 1 whole-slide test images (each of which has approximately 5,000x23,000 pixels. All images are at 20X magnification.

Prostate immobilization can be achieved with patient positioning

International Nuclear Information System (INIS)

Huang, David T.; Silverman, Larry N.; Tercilla, Oscar F.; Lutz, Stephen T.

1995-01-01

Purpose/Objective: With advances in 3D conformal therapy, daily variation in the position of the prostate poses increasing problems for radiation oncologists. In this study we attempt to define the optimal treatment position for patients with prostate cancer by measuring the range of movement of the prostate. Materials and Methods: Ten patients with biopsy proven adenocarcinoma of the prostate underwent prone and supine CT scans with IV and oral contrast. Foley catheters (FC) were placed in the urinary bladder, and renograffin was used to make the balloon radiopaque. AP/PA and lateral radiographs were taken for patients in the supine and prone position with either empty bladder (EB) or partially filled bladder (PFB, containing 60 cc of contrast medium). Measurements were taken from the Foley catheter (represents prostatic urethra), to the anterior rectal wall and pubic symphysis (PS). The rectal gas pattern was analyzed to evaluate the rectum-sparing effect. The false table top was not used. Results: For radiographs taken in the supine position, the FC was located 1.4 ± 0.5 cm from the PS in the case of PFB versus EB. In the prone position the variation was significantly less, with an increase in FC to PS distance of only 0.5 ± 0.3 cm for a PFB versus EB. The rectal gas pattern was also noted to vary, with a more expanded and rounded shape in the prone position. Conclusion: Most institutions treat patients with prostate cancer in the supine position. The previous rationale for treatment in the prone position has been small bowel sparing. Here, however, we show that prone treatment also minimizes the motion of the prostate. With less posterior margin required, 3D conformal treatment could be delivered with an additional 30-50% rectal sparing

Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis).

Science.gov (United States)

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 prostatitis. All others were nonsignificant (P prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis. © 2014 Blackwell Verlag GmbH.

Prostate Cancer

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... breast cancer (BRCA1 or BRCA2) or a very strong family history of breast cancer, your risk of prostate cancer may be higher. Obesity. Obese men diagnosed with prostate cancer may be more likely ...

Prostate Cancer Symptoms

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... Fundraise for PCF: Many vs Cancer Contact Us Prostate Cancer Symptoms and Signs Prostate Cancer Basics Risk Factors ... earlier. So what are the warning signs of prostate cancer? Unfortunately, there usually aren’t any early warning ...

Prostate cancer - treatment

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... page: //medlineplus.gov/ency/patientinstructions/000403.htm Prostate cancer - treatment To use the sharing features on this page, ... drugs is recommended. References National Cancer Institute. Prostate cancer treatment (PDQ): Stages of prostate cancer. Updated July 31, ...

Spacer stability and prostate position variability during radiotherapy for prostate cancer applying a hydrogel to protect the rectal wall

International Nuclear Information System (INIS)

Pinkawa, Michael; Piroth, Marc D.; Holy, Richard; Escobar-Corral, Nuria; Caffaro, Mariana; Djukic, Victoria; Klotz, Jens; Eble, Michael J.

2013-01-01

Background and purpose: The aim was to evaluate the spacer dimensions and prostate position variability during the course of radiotherapy for prostate cancer. Materials and methods: CT scans were performed in a group of 15 patients (G1) after the 10 ml injection of a hydrogel spacer (SpaceOAR™) and 30 patients without a spacer (G2) before the beginning of treatment (CT1) and in the last treatment week, 10–12 weeks following spacer implantation (CT2). Spacer dimensions and displacements were determined and prostate displacements compared. Results: Mean volume of the hydrogel increased slightly (17%; p 2 cm 3 . The average displacement of the hydrogel center of mass was 0.6 mm (87% ⩽ 2.2 mm), −0.6 mm (100% ⩽ 2.2 mm) and 1.4 mm (87% ⩽ 4.3 mm) in the x-, y- and z-axes (not significant). The average distance between prostate and anterior rectal wall before/at the end of radiotherapy was 1.6 cm/1.5 cm, 1.2 cm/1.3 cm and 1.0 cm/1.1 cm at the level of the base, middle and apex (G1). Prostate position variations were similar comparing G1 and G2, but significant systematic posterior displacements were only found in G2. Conclusions: A stable distance between the prostate and anterior rectal wall results during the radiotherapy course after injection of the spacer before treatment planning. Larger posterior prostate displacements could be reduced

Functional roles for Rad9 in prostate cancer

International Nuclear Information System (INIS)

Lieberman, H.B.; Broustas, C.G.

2012-01-01

The goal of this work is to understand the mechanistic relationship between high levels of Rad9 protein and prostate cancer. The study is based on several findings suggesting a role for Rad9 in this disease. Rad9 has all the hallmark features of an oncogene or tumor suppressor. It regulates genomic stability, multiple cell cycle checkpoints, apoptosis and DNA repair. In addition, it can transactivate downstream target genes via direct interaction with promoter DNA sequences. We found Rad9 protein levels were very high in prostate cancer cell lines. Furthermore, we examined 52 primary normal prostate and 339 prostate cancer specimens for Rad9 protein by immunohistochemical staining. Statistical significance for Rad9 positive staining versus cancer, and stain intensity versus Stage were tested. We get a p-value of <0.001 when comparing percentage positive by cancer Stage, or stain intensity by cancer Stage. Based on these data, we sought to define the nature of the relationship between Rad9 and prostate cancer. We demonstrate that Rad9 acts as an oncogene in prostate cancer by playing a critical role in tumor formation in a mouse xenograph model. We also show that Rad9 is important for cellular phenotypes essential for metastasis, including tumor cell migration, invasion and resistance to programmed cell death after detachment from extracellular matrix. Therefore, Rad9 is critical for several aspects of prostate tumor progression, and could serve as a novel target for anti-cancer therapy

Genomic rearrangements of PTEN in prostate cancer

Directory of Open Access Journals (Sweden)

Sopheap ePhin

2013-09-01

Full Text Available The phosphatase and tensin homolog gene on chromosome 10q23.3 (PTEN is a negative regulator of the PIK3/Akt survival pathway and is the most frequently deleted tumor suppressor gene in prostate cancer. Monoallelic loss of PTEN is present in up to 60% of localized prostate cancers and complete loss of PTEN in prostate cancer is linked to metastasis and androgen independent progression. Studies on the genomic status of PTEN in prostate cancer initially used a two-color fluorescence in-situ hybridization (FISH assay for PTEN copy number detection in formalin fixed paraffin embedded tissue preparations. More recently, a four-color FISH assay containing two additional control probes flanking the PTEN locus with a lower false-positive rate was reported. Combined with the detection of other critical genomic biomarkers for prostate cancer such as ERG, AR, and MYC, the evaluation of PTEN genomic status has proven to be invaluable for patient stratification and management. Although less frequent than allelic deletions, point mutations in the gene and epigenetic silencing are also known to contribute to loss of PTEN function, and ultimately to prostate cancer initiation. Overall, it is clear that PTEN is a powerful biomarker for prostate cancer. Used as a companion diagnostic for emerging therapeutic drugs, FISH analysis of PTEN is promisingly moving human prostate cancer closer to more effective cancer management and therapies.

Vietnam military service history and prostate cancer

Directory of Open Access Journals (Sweden)

Fritschi Lin

2006-03-01

Full Text Available Abstract Background Three decades after US and Australian forces withdrew from Vietnam, there has been much public interest in the health consequences of service in Vietnam. One controversial question is whether the risk of prostate cancer amongst Vietnam veterans is increased. This paper examines relationships between military history, family history and risk of prostate cancer in a population-based case control study. Methods Cases were selected from the Cancer Registry of Western Australia as incident cases of histologically-confirmed prostate cancer, and controls were age-matched and selected from the Western Australian electoral roll. Study participants were asked to report any military service history and details about that service. Results Between January 2001 and September 2002, 606 cases and 471 controls aged between 40–75 years were recruited. An increased prostate cancer risk was observed in men reporting they were deployed in Vietnam although this was not statistically significant (OR = 2.12; 95% CI 0.88–5.06. An increased risk was also observed in men reporting prostate cancer in fathers (OR = 1.90; 95% CI 1.20–3.00 or brothers (OR = 2.05; 95% CI 1.20–3.50 diagnosed with prostate cancer. Conclusion These findings support a positive association between prostate cancer and military service history in the Vietnam war and a first degree relative family history of prostate cancer.

Expression and Function of ETS Genes in Prostate Cancer

NARCIS (Netherlands)

D. Gasi (Delila)

2013-01-01

markdownabstract__Abstract__ Prostate cancer is a heterogeneous disease that is very common in elderly men in developed countries. Understanding the molecular and biological processes that contribute to tumor development and progressive growth is a challenging task. The fusion of the genes ERG

Perceived causes of prostate cancer among prostate cancer survivors in the Netherlands

NARCIS (Netherlands)

Kok, D.E.G.; Cremers, R.G.H.M.; Aben, K.K.H.; Oort, van I.M.; Kampman, E.; Kiemeney, L.A.L.M.

2013-01-01

Introduction The aim of this study was to evaluate self-reported causes of prostate cancer among prostate cancer survivors in the Netherlands to obtain insight into the common beliefs and perceptions of risk factors for prostate cancer. Materials and methods A total of 956 prostate cancer survivors,

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.

Science.gov (United States)

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.

Childhood body mass index and the risk of prostate cancer in adult men

DEFF Research Database (Denmark)

Aarestrup, J; Gamborg, M; Cook, M B

2014-01-01

BACKGROUND: Prostate cancer aetiology is poorly understood. It may have origins early in life; previously we found a positive association with childhood height. The effects of early life body mass index (BMI; kg m(-2)) on prostate cancer remain equivocal. We investigated if childhood BMI...... to the Danish Cancer Registry. Cox proportional hazards regressions were performed. RESULTS: Overall, 3355 men were diagnosed with prostate cancer. Body mass index during childhood was positively associated with adult prostate cancer. The hazard ratio of prostate cancer was 1.06 (95% confidence interval (CI): 1...

A vaccine strategy with multiple prostatic acid phosphatase-fused cytokines for prostate cancer treatment.

Science.gov (United States)

Fujio, Kei; Watanabe, Masami; Ueki, Hideo; Li, Shun-Ai; Kinoshita, Rie; Ochiai, Kazuhiko; Futami, Junichiro; Watanabe, Toyohiko; Nasu, Yasutomo; Kumon, Hiromi

2015-04-01

Immunotherapy is one of the attractive treatment strategies for advanced prostate cancer. The US Food and Drug Administration (FDA) previously approved the therapeutic vaccine, sipuleucel-T, which is composed of autologous antigen-presenting cells cultured with a fusion protein [prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GMCSF)]. Although sipuleucel-T has been shown to prolong the median survival of patients for 4.1 months, more robust therapeutic effects may be expected by modifying the vaccination protocol. In the present study, we aimed to develop and validate a novel vaccination strategy using multiple PAP-fused cytokines for prostate cancer treatment. Using a super gene expression (SGE) system that we previously established to amplify the production of a recombinant protein, significant amounts of PAP-fused cytokines [human GMCSF, interleukin-2 (IL2), IL4, IL7 and mouse GMCSF and IL4] were obtained. We examined the activity of the fusion proteins in vitro to validate their cytokine functions. A significant upregulation of dendritic cell differentiation from monocytes was achieved by PAP-GMCSF when used with the other PAP-fused cytokines. The PAP-fused human IL2 significantly increased the proliferation of lymphocytes, as determined by flow cytometry. We also investigated the in vivo therapeutic effects of multiple PAP-fused cytokines in a mouse prostate cancer model bearing prostate-specific antigen (PSA)- and PAP-expressing tumors. The simultaneous intraperitoneal administration of PAP-GMCSF, -IL2, -IL4 and -IL7 significantly prevented tumor induction and inhibited the tumor growth in the PAP-expressing tumors, yet not in the PSA-expressing tumors. The in vivo therapeutic effects with the multiple PAP-fused cytokines were superior to the effects of PAP-GMCSF alone. We thus demonstrated the advantages of the combined use of multiple PAP-fused cytokines including PAP-GMCSF, and propose a promising prostatic

Ultrasound and PET-CT image fusion for prostate brachytherapy image guidance

International Nuclear Information System (INIS)

Hasford, F.

2015-01-01

Fusion of medical images between different cross-sectional modalities is widely used, mostly where functional images are fused with anatomical data. Ultrasound has for some time now been the standard imaging technique used for treatment planning of prostate cancer cases. While this approach is laudable and has yielded some positive results, latest developments have been the integration of images from ultrasound and other modalities such as PET-CT to compliment missing properties of ultrasound images. This study has sought to enhance diagnosis and treatment of prostate cancers by developing MATLAB algorithms to fuse ultrasound and PET-CT images. The fused ultrasound-PET-CT image has shown to contain improved quality of information than the individual input images. The fused image has the property of reduced uncertainty, increased reliability, robust system performance, and compact representation of information. The objective of co-registering the ultrasound and PET-CT images was achieved by conducting performance evaluation of the ultrasound and PET-CT imaging systems, developing image contrast enhancement algorithm, developing MATLAB image fusion algorithm, and assessing accuracy of the fusion algorithm. Performance evaluation of the ultrasound brachytherapy system produced satisfactory results in accordance with set tolerances as recommended by AAPM TG 128. Using an ultrasound brachytherapy quality assurance phantom, average axial distance measurement of 10.11 ± 0.11 mm was estimated. Average lateral distance measurements of 10.08 ± 0.07 mm, 20.01 ± 0.06 mm, 29.89 ± 0.03 mm and 39.84 ± 0.37 mm were estimated for the inter-target distances corresponding to 10 mm, 20 mm, 30 mm and 40 mm respectively. Volume accuracy assessment produced measurements of 3.97 cm 3 , 8.86 cm 3 and 20.11 cm 3 for known standard volumes of 4 cm 3 , 9 cm 3 and 20 cm 3 respectively. Depth of penetration assessment of the ultrasound system produced an estimate of 5.37 ± 0.02 cm

Molecular pathology of prostate cancer.

Science.gov (United States)

Cazares, L H; Drake, R R; Esquela-Kirscher, A; Lance, R S; Semmes, O J; Troyer, D A

2010-01-01

This chapter includes discussion of the molecular pathology of tissue, blood, urine, and expressed prostatic secretions. Because we are unable to reliably image the disease in vivo, a 12 core method that oversamples the peripheral zone is widely used. This generates large numbers of cores that need to be carefully processed and sampled. In spite of the large number of tissue cores, the amount of tumor available for study is often quite limited. This is a particular challenge for research, as new biomarker assays will need to preserve tissue architecture intact for histopathology. Methods of processing and reporting pathology are discussed. With the exception of ductal variants, recognized subtypes of prostate cancer are largely confined to research applications, and most prostate cancers are acinar. Biomarker discovery in urine and expressed prostatic secretions would be useful since these are readily obtained and are proximate fluids. The well-known challenges of biomarker discovery in blood and urine are referenced and discussed. Mediators of carcinogenesis can serve as biomarkers as exemplified by mutations in PTEN and TMPRSS2:ERG fusion. The use of proteomics in biomarker discovery with an emphasis on imaging mass spectroscopy of tissues is discussed. Small RNAs are of great interest, however, their usefulness as biomarkers in clinical decision making remains the subject of ongoing research. The chapter concludes with an overview of blood biomarkers such as circulating nucleic acids and tumor cells and bound/free isoforms of prostate specific antigen (PSA).

Synergistic interaction of benign prostatic hyperplasia and prostatitis on prostate cancer risk

Science.gov (United States)

Hung, S-C; Lai, S-W; Tsai, P-Y; Chen, P-C; Wu, H-C; Lin, W-H; Sung, F-C

2013-01-01

Background: The incidence of prostate cancer is much lower in Asian men than in Western men. This study investigated whether prostate cancer is associated with prostatitis, benign prostatic hyperplasia (BPH), and other medical conditions in the low-incidence population. Methods: From the claims data obtained from the universal National Health Insurance of Taiwan, we identified 1184 patients with prostate cancer diagnosed from 1997 to 2008. Controls comprised 4736 men randomly selected from a cancer-free population. Both groups were 50 years of age or above. Medical histories between the two groups were compared. Results: Multivariate logistic regression analysis showed that prostatitis and BPH had stronger association with prostate cancer than the other medical conditions tested. Compared with men without prostatitis and BPH, a higher odds ratio (OR) for prostate cancer was associated with BPH (26.2, 95% confidence interval (CI) 20.8–33.0) than with prostatitis (10.5, 95% CI=3.36–32.7). Men with both conditions had an OR of 49.2 (95% CI=34.7–69.9). Conclusion: Men with prostate cancer have strong association with prostatitis and/or BPH. Prostatitis interacts with BPH, resulting in higher estimated relative risk of prostate cancer in men suffering from both conditions. PMID:23612451

Value of Diffusion Tensor Imaging of Prostate Cancer: Comparison with Systemic Prostate Biopsy

Energy Technology Data Exchange (ETDEWEB)

Yoon, Seong Kuk; Kim, Dong Won; Ha, Dong Ho; Kwon, Hee Jin; Kang, Myong Jin; Choi, Sun Seob; Nam, Kyung Jin; Kim, Jung Il [Dong-A University, Medical Center, Busan (Korea, Republic of)

2011-02-15

This study was performed to evaluate the usefulness of diffusion tensor imaging (DTI) and to correlate systemic twelve biopsy in prostate cancer. Thirty-one patients with suspected prostate cancer underwent MR imaging. DTI was performed prior to a prostate biopsy. We prospectively calculated the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) value in each corresponding biopsy site. Twenty-three of 31 patients had histopathologically proven adenocarcinoma. Among the 276 biopsy cores of 23 patients with prostate cancer, 109 cores showed positive results (39%). The ADC and FA value of positive cores were 1.31 {+-} 0.34x10-3 mm2/s and 0.68 {+-} 0.07, and those of the negative cores were 1.74 {+-} 0.45x10-3 mm2/s and 0.54 {+-} 0.09, respectively. Eight patients without carcinoma showed an ADC value of 1.83 {+-} 0.26x10-3 mm2/s and an FA value of 0.47 {+-} 0.07. The ADC and FA value of positive cores were significantly lower and higher than those of negative cores and cancer-free patients, respectively (p < 0.05). The ADC and FA values using DTI may provide useful diagnostic information in the differentiation of cancerous tissues, although there is overlap in some cases

Clinical assessment of CT-MRI image fusion software in localization of the prostate for 3D conformal radiation therapy

International Nuclear Information System (INIS)

Kagawa, Kazufumi; Lee, W. Robert; Schultheiss, Timothy E.; Hunt, Margie A.; Shaer, Andrew H.; Hanks, Gerald E.

1996-01-01

Purpose: To assess the utility of image fusion software and compare MRI prostate localization with CT localization in patients undergoing 3D conformal radiation therapy of prostate cancer. Materials and Methods: After a phantom study was performed to ensure the accuracy of image fusion procedure, 22 prostate cancer patients had CT and MRI studies before the start of radiotherapy. Immobilization casts used during radiation treatment were also used for both imaging studies. After the clinical target volume (CTV) (prostate or prostate + seminal vesicles) was defined on CT, slices from MRI study were reconstructed to match precisely the corresponding CT slices by identifying three common bony landmarks on each study. The CTV was separately defined on the matched MRI slices. Data related to the size and location of the prostate were compared between CT and MRI. The spatial relationship between the tip of urethrogram cone on CT and prostate apex seen on MRI was also scrutinized. Results: The phantom study showed the registration discrepancies between CT and MRI smaller than 1.0 mm in any pair of comparison. The patient study showed mean image registration error of 0.9 (± 0.6) mm. The average prostate volume was 63.0 (± 25.8) cm 3 and 50.9 (± 22.9) cm 3 determined by CT and MRI respectively (Fig. 1). The difference in prostate location with the two studies most commonly differed at the base and at the apex of the prostate (Fig. 2). On transverse MRI, the prostate apex was situated 7.1 (± 4.5) mm dorsal and 15.1 (± 4.0) mm cephalad to the tip of urethrogram cone (Fig. 3). Conclusions: CT-MRI image fusion study made it possible to compare the two modalities directly. MRI localization of the prostate is more accurate than CT, and indicates the distance from cone to apex is 15 mm. In view of excellent treatment results obtained with current CT localization of the prostate, still it may not be wise to reduce target volume to that demonstrated on MRI

Does Small Prostate Predict High Grade Prostate Cancer?

International Nuclear Information System (INIS)

Caliskan, S.; Kaba, S.; Koca, O.; Ozturk, M. I.

2017-01-01

groups 1 and 2, respectively at final pathology (p=0.373). Conclusion: The present study demonstrated that smaller prostates are more likely to compose higher percentage of the high grade prostate cancer, local advanced disease, and the Gleason upgrading. The positive surgical margin rate is higher in patients with small prostates when it is compared with the other patients. (author)

Effect of Prostate Magnetic Resonance Imaging/Ultrasound Fusion-guided Biopsy on Radiation Treatment Recommendations

Energy Technology Data Exchange (ETDEWEB)

Reed, Aaron; Valle, Luca F.; Shankavaram, Uma; Krauze, Andra; Kaushal, Aradhana; Schott, Erica; Cooley-Zgela, Theresa [Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Wood, Bradford [Center for Interventional Oncology, National Institutes of Health, Bethesda, Maryland (United States); Pinto, Peter [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Choyke, Peter; Turkbey, Baris [Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Citrin, Deborah E., E-mail: citrind@mail.nih.gov [Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

2017-04-01

Purpose: Targeted magnetic resonance imaging (MRI)/ultrasound fusion prostate biopsy (MRI-Bx) has recently been compared with the standard of care extended sextant ultrasound-guided prostate biopsy (SOC-Bx), with the former associated with an increased rate of detection of clinically significant prostate cancer. The present study sought to determine the influence of MRI-Bx on radiation therapy and androgen deprivation therapy (ADT) recommendations. Methods and Materials: All patients who had received radiation treatment and had undergone SOC-Bx and MRI-Bx at our institution were included. Using the clinical T stage, pretreatment prostate-specific antigen, and Gleason score, patients were categorized into National Comprehensive Cancer Network risk groups and radiation treatment or ADT recommendations assigned. Intensification of the recommended treatment after multiparametric MRI, SOC-Bx, and MRI-Bx was evaluated. Results: From January 2008 to January 2016, 73 patients received radiation therapy at our institution after undergoing a simultaneous SOC-Bx and MRI-Bx (n=47 with previous SOC-Bx). Repeat SOC-Bx and MRI-Bx resulted in frequent upgrading compared with previous SOC-Bx (Gleason score 7, 6.7% vs 44.6%; P<.001; Gleason score 8-10, 2.1% vs 38%; P<.001). MRI-Bx increased the proportion of patients classified as very high risk from 24.7% to 41.1% (P=.027). Compared with SOC-Bx alone, including the MRI-Bx findings resulted in a greater percentage of pathologically positive cores (mean 37% vs 44%). Incorporation of multiparametric MRI and MRI-Bx results increased the recommended use and duration of ADT (duration increased in 28 of 73 patients and ADT was added for 8 of 73 patients). Conclusions: In patients referred for radiation treatment, MRI-Bx resulted in an increase in the percentage of positive cores, Gleason score, and risk grouping. The benefit of treatment intensification in accordance with the MRI-Bx findings is unknown.

Osteoblast-Prostate Cancer Cell Interaction in Prostate Cancer Bone Metastases

National Research Council Canada - National Science Library

Navone, Nora

2001-01-01

.... This suggests that prostate cancer cells interact with cells from the osteoblastic lineage. To understand the molecular bases of prostatic bone metastases, we established two prostate cancer cell lines, MDA PCa 2a and MDA PCa 2b (1...

Prostate Cancer Ambassadors

Science.gov (United States)

Vines, Anissa I.; Hunter, Jaimie C.; Carlisle, Veronica A.; Richmond, Alan N.

2016-01-01

African American men bear a higher burden of prostate cancer than Caucasian men, but knowledge about how to make an informed decision about prostate cancer screening is limited. A lay health advisor model was used to train “Prostate Cancer Ambassadors” on prostate cancer risk and symptoms, how to make an informed decision for prostate-specific antigen screening, and how to deliver the information to members of their community. Training consisted of two, 6-hour interactive sessions and was implemented in three predominantly African American communities over an 8-month period between 2013 and 2014. Following training, Ambassadors committed to contacting at least 10 people within 3 months using a toolkit composed of wallet-sized informational cards for distribution, a slide presentation, and a flip chart. Thirty-two Ambassadors were trained, with more than half being females (59%) and half reporting a family history of prostate cancer. Prostate cancer knowledge improved significantly among Ambassadors (p ≤ .0001). Self-efficacy improved significantly for performing outreach tasks (p < .0001), and among women in helping a loved one with making an informed decision (p = .005). There was also an improvement in collective efficacy in team members (p = .0003). Twenty-nine of the Ambassadors fulfilled their commitment to reach at least 10 people (average number of contacts per Ambassador was 11). In total, 355 individuals were reached with the prostate cancer information. The Ambassador training program proved successful in training Ambassadors to reach communities about prostate cancer and how to make an informed decision about screening. PMID:27099348

Analysis of histological findings obtained combining US/mp-MRI fusion-guided biopsies with systematic US biopsies: mp-MRI role in prostate cancer detection and false negative.

Science.gov (United States)

Faiella, Eliodoro; Santucci, Domiziana; Greco, Federico; Frauenfelder, Giulia; Giacobbe, Viola; Muto, Giovanni; Zobel, Bruno Beomonte; Grasso, Rosario Francesco

2018-02-01

To evaluate the diagnostic accuracy of mp-MRI correlating US/mp-MRI fusion-guided biopsy with systematic random US-guided biopsy in prostate cancer diagnosis. 137 suspected prostatic abnormalities were identified on mp-MRI (1.5T) in 96 patients and classified according to PI-RADS score v2. All target lesions underwent US/mp-MRI fusion biopsy and prostatic sampling was completed by US-guided systematic random 12-core biopsies. Histological analysis and Gleason score were established for all the samples, both target lesions defined by mp-MRI, and random biopsies. PI-RADS score was correlated with the histological results, divided in three groups (benign tissue, atypia and carcinoma) and with Gleason groups, divided in four categories considering the new Grading system of the ISUP 2014, using t test. Multivariate analysis was used to correlate PI-RADS and Gleason categories to PSA level and abnormalities axial diameter. When the random core biopsies showed carcinoma (mp-MRI false-negatives), PSA value and lesions Gleason median value were compared with those of carcinomas identified by mp-MRI (true-positives), using t test. There was statistically significant difference between PI-RADS score in carcinoma, atypia and benign lesions groups (4.41, 3.61 and 3.24, respectively) and between PI-RADS score in Gleason  7 group (4.14 and 4.79, respectively). mp-MRI performance was more accurate for lesions > 15 mm and in patients with PSA > 6 ng/ml. In systematic sampling, 130 (11.25%) mp-MRI false-negative were identified. There was no statistic difference in Gleason median value (7.0 vs 7.06) between this group and the mp-MRI true-positives, but a significant lower PSA median value was demonstrated (7.08 vs 7.53 ng/ml). mp-MRI remains the imaging modality of choice to identify PCa lesions. Integrating US-guided random sampling with US/mp-MRI fusion target lesions sampling, 3.49% of false-negative were identified.

Molecular assays for the detection of prostate tumor derived nucleic acids in peripheral blood

Directory of Open Access Journals (Sweden)

Kinnunen Martin

2010-07-01

Full Text Available Abstract Background Prostate cancer is the second leading cause of cancer mortality in American men. Although serum PSA testing is widely used for early detection, more specific prognostic tests are needed to guide treatment decisions. Recently, the enumeration of circulating prostate epithelial cells has been shown to correlate with disease recurrence and metastasis following definitive treatment. The purpose of our study was to investigate an immunomagnetic fractionation procedure to enrich circulating prostate tumor cells (CTCs from peripheral blood specimens, and to apply amplified molecular assays for the detection of prostate-specific markers (PSA, PCA3 and TMPRSS2:ERG gene fusion mRNAs. Results As few as five prostate cancer cells were detected per 5 mL of whole blood in model system experiments using anti-EpCAM magnetic particles alone or in combination with anti-PSMA magnetic particles. In our experiments, anti-EpCAM magnetic particles alone exhibited equivalent or better analytical performance with patient samples compared to a combination of anti-EpCAM + anti-PSMA magnetic particles. Up to 39% of men with advanced prostate cancer tested positive with one or more of the molecular assays tested, whereas control samples from men with benign prostate hyperplasia gave consistently negative results as expected. Interestingly, for the vast majority of men who tested positive for PSA mRNA following CTC enrichment, their matched plasma samples also tested positive, although CTC enrichment gave higher overall mRNA copy numbers. Conclusion CTCs were successfully enriched and detected in men with advanced prostate cancer using an immunomagnetic enrichment procedure coupled with amplified molecular assays for PSA, PCA3, and TMPRSS2:ERG gene fusion mRNAs. Our results indicate that men who test positive following CTC enrichment also exhibit higher detectable levels of non-cellular, circulating prostate-specific mRNAs.

Radiation therapy of newly diagnosed, advanced prostatic cancer and hormonally relapsed prostatic cancer

International Nuclear Information System (INIS)

Suzuki, Minoru; Fujiwara, Kazuhisa; Hayakawa, Katsumi; Hida, Shuichi

1994-01-01

Ten patients with newly diagnosed, advanced prostatic cancer were treated with radiotherapy and hormone therapy to improve tumor control and survival. Eight patients with hormonally relapsed prostatic cancer were treated with radiotherapy to improve their quality of life. Local control of the tumor was achieved in 9 of 10 patients with newly diagnosed, advanced prostatic cancer. Five of eight patients with hormonally relapsed prostatic cancer obtained improved quality of life. Combined radiotherapy and hormone therapy were effective in the treatment of newly diagnosed, advanced prostatic cancer, and radiotherapy was useful for improving the quality of life of patients with hormonally relapsed prostatic cancer. (author)

Prostate Cancer Screening : The effect on prostate cancer mortality and incidence

NARCIS (Netherlands)

P.J. van Leeuwen (Pim)

2012-01-01

textabstractAt first glance, deciding whether to get the PSA screening test for prostate cancer seems to be pretty straightforward and attractive. It’s a simple blood test that can pick up the prostate cancer long before your symptoms appear. After all, your prostate cancer is earlier treated

Prostate Cancer

Science.gov (United States)

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

Rare Presentation of Prostate Cancer Mimicking Malignant Lymphoma with Generalized Lymphadenopathy

Directory of Open Access Journals (Sweden)

Yu-Fen Tsai

2014-06-01

Full Text Available Prostate cancer typically metastasizes to bones and regional lymph nodes. Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. We report a case of prostate cancer in a 65-year-old male with initial presentation of generalized lymphadenopathy and no urinary symptoms. Lymph node biopsy revealed metastatic adenocarcinoma, and immunohistochemical staining was positive for prostate-specific antigen (PSA compatible with a prostatic origin. Directed biopsy confirmed that the tumor originated in the prostate. Therefore, the prostate should be considered a possible origin of metastatic adenocarcinoma in men, and presentations consistent with generalized lymphadenopathy cannot exclude a diagnosis of prostate cancer.

ETS-Associated Genomic Alterations including ETS2 Loss Markedly Affect Prostate Cancer Progression

Science.gov (United States)

2015-10-01

Approximately half of all prostate cancers contain a fusion between two genes, TMPRSS2 and ERG , and a further half of these contain a deletion of...the 14 genes lying between TMPRSS2 and ERG . I have now performed a screen involving inhibition of each of these 14 genes, and am currently...validating whether one or more of these genes does indeed affect cellular proliferation in vitro and in vivo. 15. SUBJECT TERMS prostate cancer, TMPRSS2- ERG

Prostate cancer epigenome.

Science.gov (United States)

Chinaranagari, Swathi; Sharma, Pankaj; Bowen, Nathan J; Chaudhary, Jaideep

2015-01-01

Prostate cancer is a major health burden within the ever-increasingly aging US population. The molecular mechanisms involved in prostate cancer are diverse and heterogeneous. In this context, epigenetic changes, both global and gene specific, are now an emerging alternate mechanism in disease initiation and progression. The three major risk factors in prostate cancer: age, geographic ancestry, and environment are all influenced by epigenetics and additional significant insight is required to gain an understanding of the underlying mechanisms. The androgen receptor and its downstream effector pathways, central to prostate cancer initiation and progression, are subject to a multitude of epigenetic alterations. In this review we focus on the global perspective of epigenetics and the use of recent next-generation sequencing platforms to interrogate epigenetic changes in the prostate cancer genome.

The value of prostate specific antigen and prostate specific antigen density in the diagnosis ad treatment of prostate cancer

International Nuclear Information System (INIS)

Hu Guoying; Yu Mingqi; Feng Xinli

2001-01-01

To study the clinical value of prostate specific antigen (PSA) and prostate specific antigen density (PSAD), the PSA levels of pre-and post-treatment were measured in 28 cases with prostate cancer (Pca) and 80 patients with being Prostate hyperplasia (BPH). PASD was measured in 18 cases Pca and 50 cases BPH of them. The results suggest that the sensitivity, specificity and accuracy of diagnosis for Pca were 85.7%, 80.0% and 81.4%, respectively. The false positive rate was 20%. PSAD is superior to PSA in distinguishing prostate cancer from benign prostate hyperplasia. The false positive rate was only 6%. But in the clinical application, the authors should combine PASD with other materials. The regular observation of post therapeutic PSA is of great value to the earlier discovery of local recurrence and metastasis as well as the judgement of curative effect and prognosis

Review article: Prostate cancer screening using prostate specific ...

African Journals Online (AJOL)

Background: Prostate cancer is the commonest cancer among men in Nigeria and early detection is key to cure and survival but its screening through prostate specific antigen (PSA) has remain controversial in literature. Screening with prostate specific antigen (PSA) has led to more men diagnosed with prostate cancer than ...

Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers.

Science.gov (United States)

Filella, Xavier; Foj, Laura

2016-10-26

Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis.

The diet as a cause of human prostate cancer.

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Nelson, William G; Demarzo, Angelo M; Yegnasubramanian, Srinivasan

2014-01-01

Asymptomatic prostate inflammation and prostate cancer have reached epidemic proportions among men in the developed world. Animal model studies implicate dietary carcinogens, such as the heterocyclic amines from over-cooked meats and sex steroid hormones, particularly estrogens, as candidate etiologies for prostate cancer. Each acts by causing epithelial cell damage, triggering an inflammatory response that can evolve into a chronic or recurrent condition. This milieu appears to spawn proliferative inflammatory atrophy (PIA) lesions, a type of focal atrophy that represents the earliest of prostate cancer precursor lesions. Rare PIA lesions contain cells which exhibit high c-Myc expression, shortened telomere segments, and epigenetic silencing of genes such as GSTP1, encoding the π-class glutathione S-transferase, all characteristic of prostatic intraepithelial neoplasia (PIN) and prostate cancer. Subsequent genetic changes, such as the gene translocations/deletions that generate fusion transcripts between androgen-regulated genes (such as TMPRSS2) and genes encoding ETS family transcription factors (such as ERG1), arise in PIN lesions and may promote invasiveness characteristic of prostatic adenocarcinoma cells. Lethal prostate cancers contain markedly corrupted genomes and epigenomes. Epigenetic silencing, which seems to arise in response to the inflamed microenvironment generated by dietary carcinogens and/or estrogens as part of an epigenetic "catastrophe" affecting hundreds of genes, persists to drive clonal evolution through metastatic dissemination. The cause of the initial epigenetic "catastrophe" has not been determined but likely involves defective chromatin structure maintenance by over-exuberant DNA methylation or histone modification. With dietary carcinogens and estrogens driving pro-carcinogenic inflammation in the developed world, it is tempting to speculate that dietary components associated with decreased prostate cancer risk, such as intake of

Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi-Institutional Validation Trial

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2016-10-01

aim 2: Evaluate a panel of four-kallikrein plasma-based markers to determine the presence of or progression to clinically relevant prostate cancer...and sent to Genomic Health, Inc. for processing. Task 3: Analysis of scientific Aim 2: Evaluate a panel of four-kallikrein plasma-based markers to...site: FHCRC) PCA3 and the TMPRSS2:ERG fusion are prostate cancer-specific biomarkers that hold promise for stratifying risk in the setting of AS

Activation of the hedgehog pathway in advanced prostate cancer

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McCormick Frank

2004-10-01

Full Text Available Abstract Background The hedgehog pathway plays a critical role in the development of prostate. However, the role of the hedgehog pathway in prostate cancer is not clear. Prostate cancer is the second most prevalent cause of cancer death in American men. Therefore, identification of novel therapeutic targets for prostate cancer has significant clinical implications. Results Here we report that activation of the hedgehog pathway occurs frequently in advanced human prostate cancer. We find that high levels of hedgehog target genes, PTCH1 and hedgehog-interacting protein (HIP, are detected in over 70% of prostate tumors with Gleason scores 8–10, but in only 22% of tumors with Gleason scores 3–6. Furthermore, four available metastatic tumors all have high expression of PTCH1 and HIP. To identify the mechanism of the hedgehog signaling activation, we examine expression of Su(Fu protein, a negative regulator of the hedgehog pathway. We find that Su(Fu protein is undetectable in 11 of 27 PTCH1 positive tumors, two of them contain somatic loss-of-function mutations of Su(Fu. Furthermore, expression of sonic hedgehog protein is detected in majority of PTCH1 positive tumors (24 out of 27. High levels of hedgehog target genes are also detected in four prostate cancer cell lines (TSU, DU145, LN-Cap and PC3. We demonstrate that inhibition of hedgehog signaling by smoothened antagonist, cyclopamine, suppresses hedgehog signaling, down-regulates cell invasiveness and induces apoptosis. In addition, cancer cells expressing Gli1 under the CMV promoter are resistant to cyclopamine-mediated apoptosis. All these data suggest a significant role of the hedgehog pathway for cellular functions of prostate cancer cells. Conclusion Our data indicate that activation of the hedgehog pathway, through loss of Su(Fu or overexpression of sonic hedgehog, may involve tumor progression and metastases of prostate cancer. Thus, targeted inhibition of hedgehog signaling may have

A DNA methylation microarray-based study identifies ERG as a gene commonly methylated in prostate cancer.

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Schwartzman, Jacob; Mongoue-Tchokote, Solange; Gibbs, Angela; Gao, Lina; Corless, Christopher L; Jin, Jennifer; Zarour, Luai; Higano, Celestia; True, Lawrence D; Vessella, Robert L; Wilmot, Beth; Bottomly, Daniel; McWeeney, Shannon K; Bova, G Steven; Partin, Alan W; Mori, Motomi; Alumkal, Joshi

2011-10-01

DNA methylation of promoter regions is a common event in prostate cancer, one of the most common cancers in men worldwide. Because prior reports demonstrating that DNA methylation is important in prostate cancer studied a limited number of genes, we systematically quantified the DNA methylation status of 1505 CpG dinucleotides for 807 genes in 78 paraffin-embedded prostate cancer samples and three normal prostate samples. The ERG gene, commonly repressed in prostate cells in the absence of an oncogenic fusion to the TMPRSS2 gene, was one of the most commonly methylated genes, occurring in 74% of prostate cancer specimens. In an independent group of patient samples, we confirmed that ERG DNA methylation was common, occurring in 57% of specimens, and cancer-specific. The ERG promoter is marked by repressive chromatin marks mediated by polycomb proteins in both normal prostate cells and prostate cancer cells, which may explain ERG's predisposition to DNA methylation and the fact that tumors with ERG DNA methylation were more methylated, in general. These results demonstrate that bead arrays offer a high-throughput method to discover novel genes with promoter DNA methylation such as ERG, whose measurement may improve our ability to more accurately detect prostate cancer.

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

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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.

High-Throughput Sequencing of Germline and Tumor From Men with Early-Onset Metastatic Prostate Cancer

Science.gov (United States)

2016-12-01

to previously-reported unselected populations suggesting that this may be used as a prognostic marker for aggressive disease in the future. Finally...although an ETV1 fusion was detected). Importantly, paired prostate cancer specimens—particularly those representing primary and distant metastases—are...two-sided Fisher’s exact test p=0.25) (8). These findings support TP53 alterations as a marker of aggressive prostate cancer, in addition to their

Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations.

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Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Björn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

2014-11-01

Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes. In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score. During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%. In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.

URG11 Regulates Prostate Cancer Cell Proliferation, Migration, and Invasion

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Bin Pan

2018-01-01

Full Text Available Upregulated gene 11 (URG11, a new gene upregulated by hepatitis B virus X protein, is involved in the development and progression of several tumors, including liver, stomach, lung, and colon cancers. However, the role of URG11 in prostate cancer remains yet to be elucidated. By determined expression in human prostate cancer tissues, URG11 was found significantly upregulated and positively correlated with the severity of prostate cancer, compared with that in benign prostatic hyperplasia tissues. Further, the mRNA and protein levels of URG11 were significantly upregulated in human prostate cancer cell lines (DU145, PC3, and LNCaP, compared with human prostate epithelial cell line (RWPE-1. Moreover, by the application of siRNA against URG11, the proliferation, migration, and invasion of prostate cancer cells were markedly inhibited. Genetic knockdown of URG11 also induced cell cycle arrest at G1/S phase, induced apoptosis, and decreased the expression level of β-catenin in prostate cancer cells. Overexpression of URG11 promoted the expression of β-catenin, the growth, the migration, and invasion ability of prostate cancer cells. Taken together, this study reveals that URG11 is critical for the proliferation, migration, and invasion in prostate cancer cells, providing the evidence of URG11 to be a novel potential therapeutic target of prostate cancer.

Influence of radiotherapy on node-positive prostate cancer treated with androgen ablation

Energy Technology Data Exchange (ETDEWEB)

Sands, M Elizabeth; Pollack, Alan; Zagars, Gunar K

1995-01-01

Purpose: Patients with node-positive prostate cancer that is regionally localized (T1-4, N1-3, M0) have a relatively poor prognosis when a single-treatment modality such as radical surgery, definitive radiotherapy, or androgen ablation is used. While promising results using radical surgery and androgen ablation have been reported, there are no data to support an analogous approach using local radiotherapy and androgen ablation. In this retrospective review, the outcome after local radiotherapy and early androgen ablation (XRT/HORM) was compared to early androgen ablation alone (HORM). Methods and Materials: Between 1984 and 1992 there were 181 patients treated with HORM and 27 patients treated with XRT/HORM at the University of Texas M. D. Anderson Cancer Center. The nodal status of all patients was established pathologically by lymph node dissection, which was terminated after frozen section confirmation of involvement. In the majority of cases androgen ablation was by orchiectomy. The median dose to the prostate in XRT/HORM group was 66 Gy. The median follow-up was 45 months; 49 months for the HORM group and 25 months for the XRT/HORM group. Results: The distribution of prognostic factors between the HORM and XRT/HORM groups was similar, with the exception of tumor grade. There was a significantly larger proportion of high grade tumors in the HORM group. In terms of actuarial disease outcome, at 4 years the results of patients in the HORM group were significantly worse, including a rising prostate specific antigen (PSA) of 53%, any disease progression of 32%, a rising PSA or disease progression of 55%, and local progression of 22%. None of the patients in the XRT/HORM group failed biochemically or clinically. To determine the impact of grade on these findings, the analyses were repeated, using only those with grade 2 tumors. A similar pattern was evidenced with significantly worse actuarial outcome at 4 years for the HORM group using the endpoints of a rising PSA

Microenvironment-Programmed Metastatic Prostate Cancer Stem Cells (mPCSCs)

Science.gov (United States)

2015-10-01

with meta- static prostate cancer and serum prostate- specific antigen levels of < 10 ng/mL. BJU Int. 2005; 96:303–307. 59. Davis JN, Wojno KJ...renewal in vivo. As an example, in a recent study, prostate- specific antigen (PSA)-positive (PSAþ) and PSA/lo human prostate cancer cells were...In addition, transgene inser- tion of Cre recombinase under the control of a specific pro - moter may alter the function of the endogenous locus via

Implications of false-positive results for future cancer screenings.

Science.gov (United States)

Taksler, Glen B; Keating, Nancy L; Rothberg, Michael B

2018-06-01

False-positive cancer screening results may affect a patient's willingness to obtain future screening. The authors conducted logistic regression analysis of 450,484 person-years of electronic medical records (2006-2015) in 92,405 individuals aged 50 to 75 years. Exposures were false-positive breast, prostate, or colorectal cancer screening test results (repeat breast imaging or negative breast biopsy ≤3 months after screening mammography, repeat prostate-specific antigen [PSA] test ≤3 months after PSA test result ≥4.0 ng/mL or negative prostate biopsy ≤3 months after any PSA result, or negative colonoscopy [without biopsy/polypectomy] ≤6 months after a positive fecal occult blood test). Outcomes were up-to-date status with breast or colorectal cancer screening. Covariates included prior screening history, clinical information (eg, family history, obesity, and smoking status), comorbidity, and demographics. Women were more likely to be up to date with breast cancer screening if they previously had false-positive mammography findings (adjusted odds ratio [AOR], 1.43 [95% confidence interval, 1.34-1.51] without breast biopsy and AOR, 2.02 [95% confidence interval, 1.56-2.62] with breast biopsy; both Pfalse-positive PSA testing were more likely to be up to date with colorectal cancer screening (AOR, 1.22 [P = .039] without prostate imaging/biopsy and AOR, 1.60 [P = .028] with imaging/biopsy). Results were stronger for individuals with more false-positive results (all P≤.005). However, women with previous false-positive colorectal cancer fecal occult blood test screening results were found to be less likely to be up to date with breast cancer screening (AOR, 0.73; Pfalse-positive breast or prostate cancer screening test were more likely to engage in future screening. Cancer 2018;124:2390-8. © 2018 American Cancer Society. © 2018 American Cancer Society.

Urologists' and GPs' knowledge of hereditary prostate cancer is suboptimal for prostate cancer counseling: a nation-wide survey in The Netherlands.

NARCIS (Netherlands)

Cremers, R.G.H.M.; Asperen, C. van; Kil, P.; Vasen, H.; Wiersma, T.; Oort, I.M. van; Kiemeney, L.A.

2012-01-01

A family history of prostate cancer (PCa) is an established risk factor for PCa. In case of a positive family history, the balance between positive and adverse effects of prostate-specific antigen (PSA) testing might be different from the general population, for which the European Randomized Study

Relative Risks for Lethal Prostate Cancer Based on Complete Family History of Prostate Cancer Death.

Science.gov (United States)

Albright, Frederick S; Stephenson, Robert A; Agarwal, Neeraj; Cannon-Albright, Lisa A

2017-01-01

There are few published familial relative risks (RR) for lethal prostate cancer. This study estimates RRs for lethal prostate cancer based on comprehensive family history data, with the goal of improving identification of those men at highest risk of dying from prostate cancer. We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry and death certificates to estimate relative risks (RR) for death from prostate cancer based upon family history. Over 600,000 male probands were analyzed, representing a variety of family history constellations of lethal prostate cancer. RR estimates were based on the ratio of the observed to the expected number of lethal prostate cancer cases using internal rates. RRs for lethal prostate cancer based on the number of affected first-degree relatives (FDR) ranged from 2.49 (95% CI: 2.27, 2.73) for exactly 1 FDR to 5.30 (2.13, 10.93) for ≥3 affected FDRs. In an absence of affected FDRs, increased risk was also significant for increasing numbers of affected second-degree or third degree relatives. Equivalent risks were observed for similar maternal and paternal family history. This study provides population-based estimates of lethal prostate cancer risk based on lethal prostate cancer family history. Many family history constellations associated with two to greater than five times increased risk for lethal prostate cancer were identified. These lethal prostate cancer risk estimates hold potential for use in identification, screening, early diagnosis, and treatment of men at high risk for death from prostate cancer. Prostate77:41-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Overexpression of the A Disintegrin and Metalloproteinase ADAM15 is linked to a Small but Highly Aggressive Subset of Prostate Cancers

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Christoph Burdelski

2017-04-01

Full Text Available The A Disintegrin and Metalloproteinase (ADAM family of endopeptidases plays a role in many solid cancers and includes promising targets for anticancer therapies. Deregulation of ADAM15 has been linked to tumor aggressiveness and cell line studies suggest that ADAM15 overexpression may also be implicated in prostate cancer. To evaluate the impact of ADAM15 expression and its relationship with key genomic alterations, a tissue microarray containing 12,427 prostate cancers was analyzed by immunohistochemistry. ADAM15 expression was compared to phenotype, prognosis and molecular features including TMPRSS2:ERG fusion and frequent deletions involving PTEN, 3p, 5q and 6q. Normal prostate epithelium did not show ADAM15 staining. In prostate cancers, negative, weak, moderate, and strong ADAM15 staining was found in 87.7%, 3.7%, 5.6%, and 3.0% of 9826 interpretable tumors. Strong ADAM15 staining was linked to high Gleason grade, advanced pathological tumor stage, positive nodal stage and resection margin. ADAM15 overexpression was also associated with TMPRSS2:ERG fusions and PTEN deletions (P < .0001 but unrelated to deletions of 3p, 5q and 6q. In univariate analysis, high ADAM15 expression was strongly linked to PSA recurrence (P < .0001. However, in multivariate analyses this association was only maintained if the analysis was limited to preoperatively available parameters in ERG-negative cancers. The results of our study demonstrate that ADAM15 is strongly up regulated in a small but highly aggressive fraction of prostate cancers. In these tumors, ADAM15 may represent a suitable drug target. In a preoperative scenario, ADAM15 expression measurement may assist prognosis assessment, either alone or in combination with other markers.

Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

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Wayland Hsiao

2009-01-01

Full Text Available HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs and corresponding 95% confidence intervals (CI. The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5. In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients.

Association between HIV status and Positive Prostate Biopsy in a Study of U.S. Veterans

Science.gov (United States)

Hsiao, Wayland; Anastasia, Katrina; Hall, John; Goodman, Michael; Rimland, David; Ritenour, Chad W. M.; Issa, Muta M.

2009-01-01

HIV infection is associated with increased incidence of malignancies, such as lymphomas and testicular cancers. We reviewed the relationship between HIV infection and prostate cancer in a contemporary series of prostate biopsy patients. The study is a retrospective analysis of consecutive prostate biopsies performed at a VA Medical Center. The indications for performing a prostate biopsy included an abnormal digital rectal examination and/or an elevated PSA. Patients were categorized according to their HIV status, biopsy results, and various demographic and clinical characteristics. Univariate and multivariate analyses compared distributions of HIV status, and various clinical and demographic characteristics. The adjusted measures of association between HIV status and positive biopsy were expressed as odds ratios (ORs) and corresponding 95% confidence intervals (CI). The likelihood of positive biopsy was significantly higher among 18 HIV-positive patients compared to patients with negative HIV tests (adjusted OR = 3.9; 95% CI: 1.3–11.5). In analyses restricted to prostate cancer patients, HIV-positive patients were not different from the remaining group with respect to their prostate cancer stage, PSA level, PSA velocity, PSA density, or Gleason grade. There is an association between HIV infection and prostate biopsy positive for carcinoma in a population referred for urologic workup. Further confirmation of this association by prospective studies may impact the current screening practices in HIV patients. PMID:19219374

Prognostic Significance of TMPRSS2-ERG Fusion Gene in Prostate Cancer

Czech Academy of Sciences Publication Activity Database

Kulda, V.; Topolčan, O.; Kučera, R.; Kripnerová, M.; Srbecká, K.; Hora, M.; Hes, O.; Klečka, J.; Babuška, V.; Rousárová, M.; Benson, Veronika; Pesta, M.

2016-01-01

Roč. 36, č. 7 (2016), s. 4787-4793 ISSN 0250-7005 Institutional support: RVO:61388971 Keywords : Prostate cancer * TMPRSS2-ERG * PSA Subject RIV: FD - Oncology ; Hematology Impact factor: 1.937, year: 2016

Chronic inflammation of the prostate type IV with respect to risk of prostate cancer

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Antonio B. Porcaro

2014-09-01

Full Text Available Background: Chronic inflammatory infiltrate (CII might be involved in prostate cancer (PCA and benign hyperplasia (BPH; however, its significance is controversial. Chronic inflammatory prostatitis type IV is the most common non cancer diagnosis in men undergoing biopsy because of suspected PCA. Objective: To evaluate potential associations of coexistent CII and PCA in biopsy specimens after prostate assessment. Design, setting, and participants: Between January 2007 and December 2008, 415 consecutive patients who underwent prostate biopsy were retrospectively evaluated. The investigated variables included Age (years and PSA (ug/l; moreover, CII+, glandular atrophy (GA+, glandular hyperplasia (GH+, prostate Intraepithelial neoplasm (PIN+, atypical small acinar cell proliferation (ASAP+ and PCA positive cores (P+ were evaluated as categorical and continuous (proportion of positive cores. Outcome measurements and statistical analysis: Associations of CII+ and PCA risk were assessed by statistical methods. Results and limitations: In the patient population, a biopsy core positive for PCA was detected in 34.2% of cases and the rate of high grade PCA (HGPCA: bGS ! 8 resulted 4.82%. CII+ significantly and inversely associated with a positive biopsy core P+ (P < 0.0001; OR = 0.26 and HGPCA (P = 0.0005; OR = 0.05. Moreover, the associations indicated that patients with coexistent CII+ on needle biopsy were 74% less likely to have coexistent PCA than men without CII+ as well as 95% less likely to have HGPCA in the biopsy core than men without coexistent CII+. There were limits in our study which was single centre and included only one dedicated pathologist. Conclusions: There was an inverse association of chronic inflammation of the prostate type IV and risk of PCA; moreover, HGPCA was less likely to be detected in cancers associated with coexistent CII. In prostate microenvironment, prostate chronic inflammation may be protective; however, its role in

Antibody Responses to Prostate-Associated Antigens in Patients with Prostatitis and Prostate Cancer

Science.gov (United States)

Maricque, Brett B.; Eickhoff, Jens C.; McNeel, Douglas G.

2010-01-01

Background An important focus of tumor immunotherapy has been the identification of appropriate antigenic targets. Serum-based screening approaches have led to the discovery of hundreds of tumor-associated antigens recognized by IgG. Our efforts to identify immunologically recognized proteins in prostate cancer have yielded a multitude of antigens, however prioritizing these antigens as targets for evaluation in immunotherapies has been challenging. In this report, we set out to determine whether the evaluation of multiple antigenic targets would allow the identification of a subset of antigens that are common immunologic targets in patients with prostate cancer. Methods Using a phage immunoblot approach, we evaluated IgG responses in patients with prostate cancer (n=126), patients with chronic prostatitis (n=45), and men without prostate disease (n=53). Results We found that patients with prostate cancer or prostatitis have IgG specific for multiple common antigens. A subset of 23 proteins was identified to which IgG were detected in 38% of patients with prostate cancer and 33% patients with prostatitis versus 6% of controls (pprostate and prostate cancer, and suggest that IgG responses to a panel of commonly recognized prostate antigens could be potentially used in the identification of patients at risk for prostate cancer or as a tool to identify immune responses elicited to prostate tissue. PMID:20632317

Co-Targeting Prostate Cancer Epithelium and Bone Stroma by Human Osteonectin-Promoter-Mediated Suicide Gene Therapy Effectively Inhibits Androgen-Independent Prostate Cancer Growth.

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Shian-Ying Sung

Full Text Available Stromal-epithelial interaction has been shown to promote local tumor growth and distant metastasis. We sought to create a promising gene therapy approach that co-targets cancer and its supporting stromal cells for combating castration-resistant prostate tumors. Herein, we demonstrated that human osteonectin is overexpressed in the prostate cancer epithelium and tumor stroma in comparison with their normal counterpart. We designed a novel human osteonectin promoter (hON-522E containing positive transcriptional regulatory elements identified in both the promoter and exon 1 region of the human osteonectin gene. In vitro reporter assays revealed that the hON-522E promoter is highly active in androgen receptor negative and metastatic prostate cancer and bone stromal cells compared to androgen receptor-positive prostate cancer cells. Moreover, in vivo prostate-tumor-promoting activity of the hON-522E promoter was confirmed by intravenous administration of an adenoviral vector containing the hON-522E promoter-driven luciferase gene (Ad-522E-Luc into mice bearing orthotopic human prostate tumor xenografts. In addition, an adenoviral vector with the hON-522E-promoter-driven herpes simplex virus thymidine kinase gene (Ad-522E-TK was highly effective against the growth of androgen-independent human prostate cancer PC3M and bone stromal cell line in vitro and in pre-established PC3M tumors in vivo upon addition of the prodrug ganciclovir. Because of the heterogeneity of human prostate tumors, hON-522E promoter-mediated gene therapy has the potential for the treatment of hormone refractory and bone metastatic prostate cancers.

Usefulness of transrectal ultrasound in diagnosing prostate cancer: comparison with digital rectal examination, prostate-specific antigen and prostate-specific antigen density

International Nuclear Information System (INIS)

Yoon, Jung Hwan; Kim, Bo Hyun; Choi, Sang Hee; Kim, Seung Hoon; Choi, Han Yong; Chai, Soo Eung; Yoon, Hye Kyung; Lee, Soon Jin; Choo, In Wook; Kim, Bo Kyung

1998-01-01

To determine the usefulness of transrectal ultrasonography (TRUS) in diagnosing prostate cancer by comparing the sensitivity, specificity, accuracy, and positive and negative predictive values of TRUS with those of serum prostate-specific antigen (PSA), prostate-specific antigen density (PSAD) and digital rectal examination (DRE). Two hundred and ten consecutive patients underwent TRUS-guided prostate biopsy due to elevated PSA and/or abnormal findings on TRUS or DRE. The TRUS findings were analyzed and correlated with pathological diagnosis. PSAD was calculated by dividing the serum PSA level by the prostate volume calculated on TRUS. The sensitivity, specificity, accuracy, and positive and negative predictive values of TRUS were compared with those of PSA, PSAD and DRE. Using ROC curve analysis, the combinations of these diagnostic methods were also evaluated for the determination of efficacy in diagnosing prostate cancer. The sensitivity and specificity of serum PSA (cut-off level, 4ng/ml), PSAD (cut-off level, 0.15ng/ml/cm 3 ), DRE, and TRUS were 96%/17%, 96%/37%, 72%/62%, and 89%/68%, respectively. On TRUS, the sensitivity and specificity of low echoic lesions and those of irregular outer margin were 89%/69%, and 60%/90%, respectively. TRUS was statistically more accurate than other diagnostic methods. Of the combinations of diagnostic methods, TRUS and PSAD were most accurate. TRUS demonstrated lower sensitivity but higher specificity than PSA or PSAD. Although it is an accurate modality for the diagnosis of prostate cancer, it cannot be used as a confirmative test due to its relatively low positive predictive value. A combination of diagnostic methods and random biopsy is needed in patients in whom prostate cancer is suspected.=20

Outcomes following negative prostate biopsy for patients with persistent disease after radiotherapy for prostate cancer

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Jacob H. Cohen

2010-02-01

Full Text Available PURPOSE: When faced with biochemical recurrence after definitive radiotherapy for prostate cancer, clinicians must determine whether the recurrence is local or systemic. Post radiotherapy prostate biopsies to detect persistent local disease are difficult to interpret histopathologically and are subject to sampling error. Our study examines outcomes for patients with a negative prostate biopsy performed for rising prostate-specific antigen (PSA levels after prostate radiation. MATERIALS AND METHODS: We performed a retrospective review of 238 prostate cancer patients with a negative biopsy following definitive radiotherapy. Seventy-five of these patients had biochemical recurrence at the time of biopsy. A negative biopsy was defined as the absence of prostate cancer without radiation-treatment effect in the specimen. RESULTS: Patients underwent biopsy at a mean of 41 months after the completion of radiation. They had a mean PSA of 6. Patients were followed for an average of 63 months. Thirty-two patients (43% developed metastasis, and 11 (15% died of prostate cancer despite a negative post-radiation biopsy. Five of nine patients (56% with sequential biopsies had a positive second biopsy. CONCLUSIONS: Patients with PSA recurrence and a negative post-radiation biopsy have a high chance of persistent local disease, progression, and death from prostate cancer. Furthermore, an initial negative biopsy does not rule-out local recurrence. Patients with biochemical recurrence after radiotherapy for prostate cancer need to be evaluated earlier for local recurrence.

Reduction of Racial Disparities in Prostate Cancer

Science.gov (United States)

2008-12-01

African Americans and whites revealed increased risks among men who reported a history of gonorrhea or syphilis or who had positive serology for...cancer, of 1.49 to 2.64 for syphilis, and 1.16 to 1.50 for gonorrhea .16 The meta-analysis also found an association be- tween prostate cancer and...tients with prostatitis include Chlamydia trachoma- tis, Ureaplasma, Mycoplasma, Neisseria gonorrhea , Pseudomonas, Escherichia coli, and

Prostate cancer - epidemiology, etiology, diagnostics, clinical symptoms, screening

International Nuclear Information System (INIS)

Ondrus, D.

2006-01-01

Prostate cancer presents a real important medical and social problem at present. It is one of the most common malignancy in males. In global point of view it means permanent incidence increase of this disease. Despite improvement of prostate cancer diagnosis and complex treatment mortality does not decreased significantly. Knowledge of etiological factors are relatively limited. Important factors are: genetic disposition, age, life style, race, positive familial history, circulated androgens. Diagnostics is well known, based on routine clinical methods: digital rectal examination, measurement of PSA a transrectal ultrasound. Benefit of prostate cancer screening is until now unclear, controversial. (author)

Prostate Cancer Foundation News

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... Finding a Doctor Treatment Options Side Effects Managing Prostate Cancer Treatment Related Side Effects Clinical Trials Patient Resources Guides Videos Prostate Cancer FAQs Information by Stage Newly Diagnosed with Prostate ...

[Epigenetics of prostate cancer].

Science.gov (United States)

Yi, Xiao-Ming; Zhou, Wen-Quan

2010-07-01

Prostate cancer is one of the most common malignant tumors in males, and its etiology and pathogenesis remain unclear. Epigenesis is involved in prostate cancer at all stages of the process, and closely related with its growth and metastasis. DNA methylation and histone modification are the most important manifestations of epigenetics in prostate cancer. The mechanisms of carcinogenesis of DNA methylation include whole-genome hypomethylation, aberrant local hypermethylation of promoters and genomic instability. DNA methylation is closely related to the process of prostate cancer, as in DNA damage repair, hormone response, tumor cell invasion/metastasis, cell cycle regulation, and so on. Histone modification causes corresponding changes in chromosome structure and the level of gene transcription, and it may affect the cycle, differentiation and apoptosis of cells, resulting in prostate cancer. Some therapies have been developed targeting the epigenetic changes in prostate cancer, including DNA methyltransferases and histone deacetylase inhibitors, and have achieved certain desirable results.

Treatment planning aids in prostate cancer: friend or foe?

International Nuclear Information System (INIS)

Malone, Shawn; Donker, Remco; Dahrouge, Simone; Eapen, Libni; Aref, Ibrahim; Perry, Gad; Szanto, Janos

2001-01-01

Background: Rectal barium is commonly used as a treatment planning aid for prostate cancer to delineate the anterior rectal wall. Previous research at the Ottawa Regional Cancer Centre demonstrated that retrograde urethrography results in a systematic shift of the prostate. We postulated that rectal barium could also cause prostate motion. Purpose: The study was designed to evaluate the effects of rectal barium on prostate position. Methods and Materials: Thirty patients with cT1-T3 prostate cancer were evaluated. Three fiducial markers were placed in the prostate. During simulation, baseline posterior-anterior and lateral films were taken. Repeat films were taken after rectal barium opacification. The prostate position (identified by the fiducials) relative to bony landmarks was compared before and after rectal barium. Films were analyzed using PIPsPro software. Results: The rectal barium procedure resulted in a significant displacement of the prostate in the anterior and superior direction. The mean displacement of the prostate measured on the lateral films was 3.8 mm (SD: 4.4 mm) in the superior direction and 3.0 mm (SD: 3.1) in the anterior direction. Conclusions: Rectal barium opacification results in a systematic shift of the prostate. This error could result in a geographic miss of the target; therefore, alternate methods of normal tissue definition should be used

Imaging and prostate cancer

International Nuclear Information System (INIS)

Schwartz, Lawrence H.

1996-01-01

The use of imaging in evaluating patients with prostate cancer is highly dependent upon the purpose of the evaluation. Ultrasound, Computed Tomography, Magnetic Resonance Imaging, TC-99m Bone Scanning, and Positron Emission Tomography may all be utilized for imaging in prostate cancer. The utility of each of these modalities depends upon the intended purpose: for instance, screening, staging, or evaluating for progression of disease in patients with prostate cancer. Transrectal ultrasound is performed by placing a 5MHz to 7.5 MHz transducer in the rectum and imaging the prostate in the coronal and sagittal planes. Prostate cancer generally appears as an area of diminished echogenocity in the peripheral zone of the prostate gland. However, up to 24% of prostate cancers are isoechoic and cannot be well distinguished from the remainder of the peripheral zone. In addition, the incidence of malignancy in a lesion judged to be suspicious on ultrasound is between 20% and 25%. Therefore, while ultrasound is the least expensive of the three cross sectional imaging modalities, its relatively low specificity precludes it from being used as a screening examination. Investigators have also looked at the ability of ultrasound to evaluate the presence and extent of extracapsular spread of prostate cancer. The RDOG (Radiology Diagnostic Oncology Group) multi-institutional cooperative trial reported a disappointing overall accuracy of ultrasound of 58% for staging prostate cancer. The accuracy was somewhat higher 63%, for patients with advanced disease. The other cross-sectional imaging modalities available for imaging the prostate include Computed Tomography and Magnetic Resonance Imaging. Computed Tomography is useful as an 'anatomic' imaging technique to detect lymph node enlargement. It is not sensitive in detecting microscopic nodal involvement with tumor, or tumor in non-enlarged pelvic lymph nodes. The primary prostate neoplasm is generally the same attenuation as the normal

The Danish Prostate Cancer Database

DEFF Research Database (Denmark)

Nguyen-Nielsen, Mary; Høyer, Søren; Friis, Søren

2016-01-01

variables include Gleason scores, cancer staging, prostate-specific antigen values, and therapeutic measures (active surveillance, surgery, radiotherapy, endocrine therapy, and chemotherapy). DESCRIPTIVE DATA: In total, 22,332 patients with prostate cancer were registered in DAPROCAdata as of April 2015......AIM OF DATABASE: The Danish Prostate Cancer Database (DAPROCAdata) is a nationwide clinical cancer database that has prospectively collected data on patients with incident prostate cancer in Denmark since February 2010. The overall aim of the DAPROCAdata is to improve the quality of prostate cancer...... care in Denmark by systematically collecting key clinical variables for the purposes of health care monitoring, quality improvement, and research. STUDY POPULATION: All Danish patients with histologically verified prostate cancer are included in the DAPROCAdata. MAIN VARIABLES: The DAPROCAdata...

Prostate Cancer Biorepository Network

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-14-2-0185 TITLE: Prostate Cancer Biorepository Network PRINCIPAL INVESTIGATOR: Jonathan Melamed, MD CONTRACTING ORGANIZATION...AND SUBTITLE 5a. CONTRACT NUMBER Prostate Cancer Biorepository Network 5b. GRANT NUMBER W81XWH-14-2-0185 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...infrastructure and operations of the Prostate Cancer Biorepository Network (PCBN). The aim of the PCBN is to provide prostate researchers with high-quality

The biology and natural history of prostate cancer: a short introduction.

Science.gov (United States)

Holmberg, Lars; Van Hemelrijck, Mieke

2014-01-01

This chapter aims to serve as a quick glance outlining an overall picture of mainstream thoughts, and to serve as a point of departure for more thorough discussions. The introduction of PSA testing has immensely complicated research in prostate cancer epidemiology and biology and added new clinical and biological domains. As for many cancers, age and ethnic origin are the strongest known risk factors. While migrant studies imply that environment and/or personal life style is important, epidemiological studies have failed to establish any strong leads. Despite the known androgen dependence of prostate cancer, there is little to support that circulating levels of androgens, estrogens or 5-alpha-reductase are associated with risk of developing the disease. However, a consistent finding is a positive association with levels of Insulin-like Growth Factor-1 (IGF-1). Prostate cancer is one of the cancers most strongly related to inherited susceptibility, even when taking into account that family history of prostate cancer triggers PSA testing among relatives. A number of somatic genetic alterations (amplifications, deletions, point mutations, translocations) are associated with prostate cancer risk. Findings for alterations in FASN, HPN, AMACR and MYC have been fairly consistent. Recent research shows that the notion of "hormone-independent prostate cancer" has to be revised: most prostate cancers remain dependent on androgen receptor signalling also after progression despite traditional androgen deprivation therapy. Traditional markers of stage and type of disease still play a major role for prognostication and treatment decisions. Prostate cancer is one of the few cancers where patients have been recommended watchful waiting or active surveillance. This provides opportunities for studies of natural history of the disease. The understanding of prostate cancer aetiology and natural history has progressed slowly. However, the current situation is positively challenging and

The link between benign prostatic hyperplasia and prostate cancer

DEFF Research Database (Denmark)

Ørsted, David Dynnes; Bojesen, Stig E

2013-01-01

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

The influence of prostate-specific antigen density on positive and negative predictive values of multiparametric magnetic resonance imaging to detect Gleason score 7-10 prostate cancer in a repeat biopsy setting.

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Hansen, Nienke L; Barrett, Tristan; Koo, Brendan; Doble, Andrew; Gnanapragasam, Vincent; Warren, Anne; Kastner, Christof; Bratt, Ola

2017-05-01

To evaluate the influence of prostate-specific antigen density (PSAD) on positive (PPV) and negative (NPV) predictive values of multiparametric magnetic resonance imaging (mpMRI) to detect Gleason score ≥7 cancer in a repeat biopsy setting. Retrospective study of 514 men with previous prostate biopsy showing no or Gleason score 6 cancer. All had mpMRI, graded 1-5 on a Likert scale for cancer suspicion, and subsequent targeted and 24-core systematic image-fusion guided transperineal biopsy in 2013-2015. The NPVs and PPVs of mpMRIs for detecting Gleason score ≥7 cancer were calculated (±95% confidence intervals) for PSAD ≤0.1, 0.1-0.2, ≤0.2 and >0.2 ng/mL/mL, and compared by chi-square test for linear trend. Gleason score ≥7 cancer was detected in 31% of the men. The NPV of Likert 1-2 mpMRI was 0.91 (±0.04) with a PSAD of ≤0.2 ng/mL/mL and 0.71 (±0.16) with a PSAD of >0.2 ng/mL/mL (P = 0.003). For Likert 3 mpMRI, PPV was 0.09 (±0.06) with a PSAD of ≤0.2 ng/mL/mL and 0.44 (±0.19) with a PSAD of >0.2 ng/mL/mL (P = 0.002). PSAD also significantly affected the PPV of Likert 4-5 mpMRI lesions: the PPV was 0.47 (±0.08) with a PSAD of ≤0.2 ng/mL/mL and 0.66 (±0.10) with a PSAD of >0.2 ng/mL/mL (P prostate cancer, not only in men with negative mpMRI, but also in men with equivocal imaging. Surveillance, rather than repeat biopsy, may be appropriate for these men. Conversely, biopsies are indicated in men with a high PSAD, even if an mpMRI shows no suspicious lesion, and in men with an mpMRI suspicious for cancer, even if the PSAD is low. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Prostate stromal cells express the progesterone receptor to control cancer cell mobility.

Science.gov (United States)

Yu, Yue; Lee, Jennifer Suehyun; Xie, Ning; Li, Estelle; Hurtado-Coll, Antonio; Fazli, Ladan; Cox, Michael; Plymate, Stephen; Gleave, Martin; Dong, Xuesen

2014-01-01

Reciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cancer cells to grow and metastasize. Our previous work showed that the progesterone receptor (PR) was expressed specifically in prostate stromal fibroblasts and smooth muscle cells. However, the expression levels of PR and its impact to tumor microenvironment in prostate tumors are poorly understood. Immunohistochemistry assays are applied to human prostate tissue biopsies. Cell migration, invasion and proliferation assays are performed using human prostate cells. Real-time PCR and ELISA are applied to measure gene expression at molecular levels. Immunohistochemistry assays showed that PR protein levels were decreased in cancer associated stroma when compared with paired normal prostate stroma. Using in vitro prostate stromal cell models, we showed that conditioned media collected from PR positive stromal cells inhibited prostate cancer cell migration and invasion, but had minor suppressive impacts on cancer cell proliferation. PR suppressed the secretion of stromal derived factor-1 (SDF-1) and interlukin-6 (IL-6) by stromal cells independent to PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1 or IL-6 to conditioned media from PR positive stromal cells counteracted the inhibitory effects of PR to cancer cell migration and invasion. Decreased expression of the PR in cancer associated stroma may contribute to the elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor progression.

Prostate stromal cells express the progesterone receptor to control cancer cell mobility.

Directory of Open Access Journals (Sweden)

Yue Yu

Full Text Available Reciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cancer cells to grow and metastasize. Our previous work showed that the progesterone receptor (PR was expressed specifically in prostate stromal fibroblasts and smooth muscle cells. However, the expression levels of PR and its impact to tumor microenvironment in prostate tumors are poorly understood.Immunohistochemistry assays are applied to human prostate tissue biopsies. Cell migration, invasion and proliferation assays are performed using human prostate cells. Real-time PCR and ELISA are applied to measure gene expression at molecular levels.Immunohistochemistry assays showed that PR protein levels were decreased in cancer associated stroma when compared with paired normal prostate stroma. Using in vitro prostate stromal cell models, we showed that conditioned media collected from PR positive stromal cells inhibited prostate cancer cell migration and invasion, but had minor suppressive impacts on cancer cell proliferation. PR suppressed the secretion of stromal derived factor-1 (SDF-1 and interlukin-6 (IL-6 by stromal cells independent to PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1 or IL-6 to conditioned media from PR positive stromal cells counteracted the inhibitory effects of PR to cancer cell migration and invasion.Decreased expression of the PR in cancer associated stroma may contribute to the elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor progression.

Risk factors for the onset of prostatic cancer: age, location, and behavioral correlates

Directory of Open Access Journals (Sweden)

Leitzmann MF

2012-01-01

Full Text Available Michael F Leitzmann1, Sabine Rohrmann21Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany; 2Institute of Social and Preventive Medicine, University of Zurich, Zurich, SwitzerlandAbstract: At present, only three risk factors for prostate cancer have been firmly established; these are all nonmodifiable: age, race, and a positive family history of prostate cancer. However, numerous modifiable factors have also been implicated in the development of prostate cancer. In the current review, we summarize the epidemiologic data for age, location, and selected behavioral factors in relation to the onset of prostate cancer. Although the available data are not entirely consistent, possible preventative behavioral factors include increased physical activity, intakes of tomatoes, cruciferous vegetables, and soy. Factors that may enhance prostate cancer risk include frequent consumption of dairy products and, possibly, meat. By comparison, alcohol probably exerts no important influence on prostate cancer development. Similarly, dietary supplements are unlikely to protect against the onset of prostate cancer in healthy men. Several factors, such as smoking and obesity, show a weak association with prostate cancer incidence but a positive relation with prostate cancer mortality. Other factors, such as fish intake, also appear to be unassociated with incident prostate cancer but show an inverse relation with fatal prostate cancer. Such heterogeneity in the relationship between behavioral factors and nonadvanced, advanced, or fatal prostate cancers helps shed light on the carcinogenetic process because it discerns the impact of exposure on early and late stages of prostate cancer development. Inconsistent associations between behavioral factors and prostate cancer risk seen in previous studies may in part be due to uncontrolled detection bias because of current widespread use of prostate-specific antigen

Prostatic specific antigen for prostate cancer detection

Directory of Open Access Journals (Sweden)

Lucas Nogueira

2009-10-01

Full Text Available Prostate-specific antigen (PSA has been used for prostate cancer detection since 1994. PSA testing has revolutionized our ability to diagnose, treat, and follow-up patients. In the last two decades, PSA screening has led to a substantial increase in the incidence of prostate cancer (PC. This increased detection caused the incidence of advanced-stage disease to decrease at a dramatic rate, and most newly diagnosed PC today are localized tumors with a high probability of cure. PSA screening is associated with a 75% reduction in the proportion of men who now present with metastatic disease and a 32.5% reduction in the age-adjusted prostate cancer mortality rate through 2003. Although PSA is not a perfect marker, PSA testing has limited specificity for prostate cancer detection, and its appropriate clinical application remains a topic of debate. Due to its widespread use and increased over-detection, the result has been the occurrence of over-treatment of indolent cancers. Accordingly, several variations as regards PSA measurement have emerged as useful adjuncts for prostate cancer screening. These procedures take into consideration additional factors, such as the proportion of different PSA isoforms (free PSA, complexed PSA, pro-PSA and B PSA, the prostate volume (PSA density, and the rate of change in PSA levels over time (PSA velocity or PSA doubling time. The history and evidence underlying each of these parameters are reviewed in the following article.

Prostatic specific antigen for prostate cancer detection.

Science.gov (United States)

Nogueira, Lucas; Corradi, Renato; Eastham, James A

2009-01-01

Prostate-specific antigen (PSA) has been used for prostate cancer detection since 1994. PSA testing has revolutionized our ability to diagnose, treat, and follow-up patients. In the last two decades, PSA screening has led to a substantial increase in the incidence of prostate cancer (PC). This increased detection caused the incidence of advanced-stage disease to decrease at a dramatic rate, and most newly diagnosed PC today are localized tumors with a high probability of cure. PSA screening is associated with a 75% reduction in the proportion of men who now present with metastatic disease and a 32.5% reduction in the age-adjusted prostate cancer mortality rate through 2003. Although PSA is not a perfect marker, PSA testing has limited specificity for prostate cancer detection, and its appropriate clinical application remains a topic of debate. Due to its widespread use and increased over-detection, the result has been the occurrence of over-treatment of indolent cancers. Accordingly, several variations as regards PSA measurement have emerged as useful adjuncts for prostate cancer screening. These procedures take into consideration additional factors, such as the proportion of different PSA isoforms (free PSA, complexed PSA, pro-PSA and B PSA), the prostate volume (PSA density), and the rate of change in PSA levels over time (PSA velocity or PSA doubling time). The history and evidence underlying each of these parameters are reviewed in the following article.

Prostatic intraepithelial neoplasia-like ductal prostatic adenocarcinoma: A case suitable for active surveillance?

Directory of Open Access Journals (Sweden)

Soroush Rais-Bahrami

2017-01-01

Full Text Available In contrast to typical prostatic ductal adenocarcinoma, prostatic intraepithelial neoplasia (PIN-like ductal adenocarcinoma is a rare variant of prostate cancer with low-grade clinical behavior. We report a case of a 66-year-old African-American male with an elevated serum prostate-specific antigen who underwent multiparametric prostate magnetic resonance imaging (MRI and MRI/ultrasound fusion-guided biopsies. Pathology demonstrated low-volume Gleason score 3 + 3 = 6 (Grade Group 1, acinar adenocarcinoma involving one core and PIN-like ductal adenocarcinoma on a separate core. Herein, we discuss the potential role of active surveillance for patients with this rare variant of prostate cancer found in the era of advanced imaging with multiparametric MRI for prostate cancer.

Other biomarkers for detecting prostate cancer.

Science.gov (United States)

Nogueira, Lucas; Corradi, Renato; Eastham, James A

2010-01-01

Prostate-specific antigen (PSA) has been used for detecting prostate cancer since 1994. Although it is the best cancer biomarker available, PSA is not perfect. It lacks both the sensitivity and specificity to accurately detect the presence of prostate cancer. None of the PSA thresholds currently in use consistently identify patients with prostate cancer and exclude patients without cancer. Novel approaches to improve our ability to detect prostate cancer and predict the course of the disease are needed. Additional methods for detecting prostate cancer have been evaluated. Despite the discovery of many new biomarkers, only a few have shown some clinical value. These markers include human kallikrein 2, urokinase-type plasminogen activator receptor, prostate-specific membrane antigen, early prostate cancer antigen, PCA3, alpha-methylacyl-CoA racemase and glutathione S-transferase pi hypermethylation. We review the reports on biomarkers for prostate cancer detection, and their possible role in the clinical practice.

Targeting Quiescence in Prostate Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0413 TITLE: Targeting Quiescence in Prostate Cancer PRINCIPAL INVESTIGATOR: Laura Buttitta CONTRACTING...Quiescence in Prostate Cancer 5a. CONTRACT NUMBER Targeting uiescence in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0413 5c. PROGRAM ELEMENT NUMBER 6...NOTES 14. ABSTRACT A major problem in prostate cancer is finding and eliminating the non-proliferating or “quiescent” cancer cells. This is because early

The role of serum prostate specific antigen assayed by TRFIA in diagnosis of prostate cancer

International Nuclear Information System (INIS)

Deng Yongmei; Zhang Jinshan; Li Min

2002-01-01

The authors evaluate the diagnostic value of serum free prostate specific antigen (F-PSA), total-PSA(T-PSA) and free/total (F/T) PSA ratio in differentiation between benign and malignant prostatic diseases. Serum samples were measured by time-resolved fluoroimmunoassay (TRFIA), there were 86 patients whose T-PSA levels were limited within 2-20 ng/mL, from the results of prostate biopsies after operation, the patients were classified into two groups: the group with prostate hyperplasia (68 patients) and the group with prostate cancer (18 patients). The serum F-PSA and T-PSA of the two groups were analysed and compared, and the F/T PSA ratio was calculated. Results were: 1) the means of F-PSA and T-PSA were not significantly different between patients with prostate hyperplasia (BPH) and with prostate cancer (P>0.05), but the mean of F/T PSA ratio for prostate cancer was significantly lower than that for BPH (P<0.001); 2) sensitivity, specificity and positive predictive value for prostate cancer detection at a cutoff value of 0.18 for the F/T PSA ratio were 85%, 72.5% and 43.6%, respectively. Conclusion is the F/T PSA ratio may be used in differentiation prostate cancer from BPH, and when T-PSA level is within the range of 2-20 ng/mL, selecting 0.18 as the cutoff value has great clinical value

Combination of Autoantibody Signature with PSA Level Enables a Highly Accurate Blood-Based Differentiation of Prostate Cancer Patients from Patients with Benign Prostatic Hyperplasia.

Directory of Open Access Journals (Sweden)

Petra Leidinger

Full Text Available Although an increased level of the prostate-specific antigen can be an indication for prostate cancer, other reasons often lead to a high rate of false positive results. Therefore, an additional serological screening of autoantibodies in patients' sera could improve the detection of prostate cancer. We performed protein macroarray screening with sera from 49 prostate cancer patients, 70 patients with benign prostatic hyperplasia and 28 healthy controls and compared the autoimmune response in those groups. We were able to distinguish prostate cancer patients from normal controls with an accuracy of 83.2%, patients with benign prostatic hyperplasia from normal controls with an accuracy of 86.0% and prostate cancer patients from patients with benign prostatic hyperplasia with an accuracy of 70.3%. Combining seroreactivity pattern with a PSA level of higher than 4.0 ng/ml this classification could be improved to an accuracy of 84.1%. For selected proteins we were able to confirm the differential expression by using luminex on 84 samples. We provide a minimally invasive serological method to reduce false positive results in detection of prostate cancer and according to PSA screening to distinguish men with prostate cancer from men with benign prostatic hyperplasia.

Biomarkers in Prostate Cancer Epidemiology

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Mudit Verma

2011-09-01

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

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

Science.gov (United States)

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

Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients

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Ahmed Abdel-Hady

2017-03-01

CONCLUSION: Our findings emphasise that only malignant and pre-malignant cells and not benign cells from the prostate stain positive. ERG expression may offer a simpler, accurate and less costly alternative for evaluation of ERG fusion status in PCa.

Prostate cancer staging

Science.gov (United States)

... this page: //medlineplus.gov/ency/patientinstructions/000397.htm Prostate cancer staging To use the sharing features on this ... trials you may be able to join How Prostate Cancer Staging is Done Initial staging is based on ...

Prostate Cancer Screening

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

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

Science.gov (United States)

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.

The Early Prostate Cancer program: bicalutamide in nonmetastatic prostate cancer

DEFF Research Database (Denmark)

Iversen, Peter; Roder, Martin Andreas; Røder, Martin Andreas

2008-01-01

The Early Prostate Cancer program is investigating the addition of bicalutamide 150 mg to standard care for localized or locally advanced, nonmetastatic prostate cancer. The third program analysis, at 7.4 years' median follow-up, has shown that bicalutamide 150 mg does not benefit patients...

Elevated Prostate Health Index (phi) and Biopsy Reclassification During Active Surveillance of Prostate Cancer.

Science.gov (United States)

Andreas, Darian; Tosoian, Jeffrey J; Landis, Patricia; Wolf, Sacha; Glavaris, Stephanie; Lotan, Tamara L; Schaeffer, Edward M; Sokoll, Lori J; Ross, Ashley E

2016-07-01

The Prostate Health Index (phi) has been FDA approved for decision-making regarding prostate biopsy. Phi has additionally been shown to positively correlate with tumor volume, extraprostatic disease and higher Gleason grade tumors. Here we describe a case in which an elevated phi encouraged biopsy of a gentleman undergoing active surveillance leading to reclassification of his disease as high risk prostate cancer.

Glycogen synthase kinase-3 inhibitors suppress the AR-V7-mediated transcription and selectively inhibit cell growth in AR-V7-positive prostate cancer cells.

Science.gov (United States)

Nakata, Daisuke; Koyama, Ryokichi; Nakayama, Kazuhide; Kitazawa, Satoshi; Watanabe, Tatsuya; Hara, Takahito

2017-06-01

Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system. The effects of a glycogen synthase kinase-3 (GSK3) inhibitor, LY-2090314, on endogenous AR-V7 signaling were evaluated in an AR-V7-positive cell line, JDCaP-hr, by quantitative reverse transcription polymerase chain reaction. The relationship between AR-V7 signaling and β-catenin signaling was assessed using RNA interference. The effect of LY-2090314 on cell growth in various prostate cancer cell lines was also evaluated. We identified GSK3 inhibitors as transcriptional suppressors of AR-V7 using a high-throughput screen with an AR-V7 reporter system. LY-2090314 suppressed the reporter activity and endogenous AR-V7 activity in JDCaP-hr cells. Because silencing of β-catenin partly rescued the suppression, it was evident that the suppression was mediated, at least partially, via the activation of β-catenin signaling. AR-V7 signaling and β-catenin signaling reciprocally regulate each other in JDCaP-hr cells, and therefore, GSK3 inhibition can repress AR-V7 transcriptional activity by accumulating intracellular β-catenin. Notably, LY-2090314 selectively inhibited the growth of AR-V7-positive prostate cancer cells in vitro. Our findings demonstrate the potential of GSK3 inhibitors in treating advanced prostate cancer driven by AR splice variants. In vivo evaluation of AR splice variant-positive prostate cancer models will help illustrate the overall significance of GSK3 inhibitors in treating prostate cancer. © 2017 Wiley Periodicals, Inc.

Case of prostate cancer with anterior localization multiparametric MRI study

International Nuclear Information System (INIS)

Georgiev, A.

2016-01-01

Prostate cancer most often originates from acinar epithelium. Most of the clinically palpable carcinomas are located predominantly in the rear/dorzo-lateraI zones of the gland, but the tumors in the transition zone anatomical may spread to the periphery. The detection of a neoplastic process in the front parts of the gland is rare and poses difficulties in diagnosis. We present a rare case of anterior location of prostate carcinoma with invasion of bladder, blood vessels and seminal vesicles. At present, diagnosis of prostate cancer in most men is demonstrated by elevated serum levels of prostate-specific antigen (PSA), or positive rectal examination or ultrasonography. Multi parametric MR study is a promising method for detecting prostate cancer. When used in conjunction with PSA values and rectal examination, MRI is increasingly accepted as a standard for the diagnosis and characterization of prostate carcinoma. Key words; Prostate Cancer. Anterior Localization. Multi Parametric MRI

Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

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Pascoe Abigail C

2012-03-01

Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

Clinical Usefulness of Implanted Fiducial Markers for Hypofractionated Radiotherapy of Prostate Cancer

International Nuclear Information System (INIS)

Choi, Young Min; Ahn, Sung Hwan; Lee, Hyung Hwan; Lee, Hyung Sik; Hur, Woo Joo; Yoon, Jin Han; Kim, Tae Hyo; Kim, Soo Dong; Yun, Seong Guk

2011-01-01

To assess the usefulness of implanted fiducial markers in the setup of hypofractionated radiotherapy for prostate cancer patients by comparing a fiducial marker matched setup with a pelvic bone match. Four prostate cancer patients treated with definitive hypofractionated radiotherapy between September 2009 and August 2010 were enrolled in this study. Three gold fiducial markers were implanted into the prostate and through the rectum under ultrasound guidance around a week before radiotherapy. Glycerin enemas were given prior to each radiotherapy planning CT and every radiotherapy session. Hypofractionated radiotherapy was planned for a total dose of 59.5 Gy in daily 3.5 Gy with using the Novalis system. Orthogonal kV X-rays were taken before radiotherapy. Treatment positions were adjusted according to the results from the fusion of the fiducial markers on digitally reconstructed radiographs of a radiotherapy plan with those on orthogonal kV X-rays. When the difference in the coordinates from the fiducial marker fusion was less than 1 mm, the patient position was approved for radiotherapy. A virtual bone matching was carried out at the fiducial marker matched position, and then a setup difference between the fiducial marker matching and bone matching was evaluated. Three patients received a planned 17-fractionated radiotherapy and the rest underwent 16 fractionations. The setup error of the fiducial marker matching was 0.94±0.62 mm (range, 0.09 to 3.01 mm; median, 0.81 mm), and the means of the lateral, craniocaudal, and anteroposterior errors were 0.39±0.34 mm, 0.46±0.34 mm, and 0.57±0.59 mm, respectively. The setup error of the pelvic bony matching was 3.15±2.03 mm (range, 0.25 to 8.23 mm; median, 2.95 mm), and the error of craniocaudal direction (2.29±1.95 mm) was significantly larger than those of anteroposterior (1.73±1.31 mm) and lateral directions (0.45±0.37 mm), respectively (p< 0.05). Incidences of over 3 mm and 5 mm in setup difference among the

From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

International Nuclear Information System (INIS)

Thobe, Megan N.; Clark, Robert J.; Bainer, Russell O.; Prasad, Sandip M.; Rinker-Schaeffer, Carrie W.

2011-01-01

Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies

From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

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Thobe, Megan N. [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States); Clark, Robert J. [Department of Molecular Pathogenesis and Molecular Medicine, The University of Chicago, Chicago, IL 60637 (United States); Bainer, Russell O. [Department of Human Genetics, The University of Chicago, Chicago, IL 60637 (United States); Prasad, Sandip M.; Rinker-Schaeffer, Carrie W., E-mail: crinkers@uchicago.edu [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States)

2011-01-27

Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.

Total antioxidant intake and prostate cancer in the Cancer of the Prostate in Sweden (CAPS) study. A case control study

International Nuclear Information System (INIS)

Russnes, Kjell M.; Möller, Elisabeth; Wilson, Kathryn M.; Carlsen, Monica; Blomhoff, Rune; Smeland, Sigbjørn; Adami, Hans-Olov; Grönberg, Henrik; Mucci, Lorelei A.; Bälter, Katarina

2016-01-01

The total intake of dietary antioxidants may reduce prostate cancer risk but available data are sparse and the possible role of supplements unclear. We investigated the potential association between total and dietary antioxidant intake and prostate cancer in a Swedish population. We used FFQ data from 1499 cases and 1112 controls in the population based case–control study Cancer of the Prostate in Sweden (CAPS). The ferric reducing antioxidant potential (FRAP) assay was used to assess the total antioxidant capacity (TAC) of diet and supplements. We calculated odds ratios (ORs) for the risk of prostate cancer across quintiles of antioxidant intake from all foods, from fruit and vegetables only, and from dietary supplements using unconditional logistic regression. Coffee comprised 62 % of the dietary antioxidant intake, tea 4 %, berries 4 %, chocolate 2 %, and boiled potatoes 2 %. In total 19 % and 13 % of the population took multivitamins and supplemental Vitamin C respectively, on a regular basis. Antioxidant intake from all foods and from fruits and vegetables separately measured by the FRAP assay was not associated with prostate cancer risk. For antioxidant intake from supplements we found a positive association with total, advanced, localized, high grade and low grade prostate cancer in those above median supplemental TAC intake of users compared to non-users (Adjusted ORs for total prostate cancer: 1.37, 95 % CI 1.08–1.73, advanced: 1.51, 95 % CI 1.11–2.06, localized: 1.36. 95 % CI 1.06–1.76, high grade 1.60, 95 % CI 1.06–2.40, low grade 1.36, 95 % CI 1.03–1.81). A high intake of coffee (≥6 cups/day) was associated with a possible risk reduction of fatal and significantly with reduced risk for high grade prostate cancer, adjusted OR: 0.45 (95 % CI: 0.22–0.90), whereas a high intake of chocolate was positively associated with risk of total, advanced, localized and low grade disease (adjusted OR for total: 1.43, 95 % CI 1.12–1.82, advanced: 1

Comparison of sonographic features in benign prostate hyperplasia and prostate cancer

International Nuclear Information System (INIS)

Choi, Won Young; Hong, Hyun Sook; Kang, Eun Young; Seol, Hae Young; Suh, Won Hyuck

1988-01-01

Transrectal sonography of prostate was sensitive to textural changes produced by both benign prostate hyperplasia (BPH) and prostate cancers. During recent 4 years, twenty cases of BPH and twenty cases of prostate cancers proven histologically were analyzed in their sonographic features, retrospectively, by using transrectal prostate sonography and suprapubic prostate sonography. The results were as follows: 1. Mean weights of BPH and prostate cancers was 40.4g and 47.6g, respectively. 2. Sonographic features of BPH revealed isoechogenecity in 11 cases, homogeneity in 18 cases, well defined capsular margins in 19 cases, and calcification in 16 cases. 3. Sonographic features of prostate cancers revealed mixed echogenecity in 14 cases, inhomogeneity in 15 cases, poorly defined capsular margin in 14 cases, and calcifications in 13 cases. 4. Authors concluded that prostate sonography were valuable diagnostic modality in the differentiation of BPH and prostate cancers.

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

Science.gov (United States)

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

2016-07-01

High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010-2012. During follow-up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high-grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log-PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer-free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: -2.1 to -1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI-categories of 25 prostate cancer risk although results were indicative of a positive association to incidence rates of high-grade disease and an inverse association to incidence of low-grade disease. However, findings regarding risk are limited by the short follow-up time. In conclusion, BMI was inversely associated to PSA-levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA-levels. © 2016 UICC.

Development of a Nomogram Model Predicting Current Bone Scan Positivity in Patients Treated with Androgen-Deprivation Therapy for Prostate Cancer

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Gotto, Geoffrey T.; Yu, Changhong; Bernstein, Melanie; Eastham, James A.; Kattan, Michael W.

2014-01-01

Purpose: To develop a nomogram predictive of current bone scan positivity in patients receiving androgen-deprivation therapy (ADT) for advanced prostate cancer; to augment clinical judgment and highlight patients in need of additional imaging investigations. Materials and methods: A retrospective chart review of bone scan records (conventional 99mTc-scintigraphy) of 1,293 patients who received ADT at the Memorial Sloan-Kettering Cancer Center from 2000 to 2011. Multivariable logistic regression analysis was used to identify variables suitable for inclusion in the nomogram. The probability of current bone scan positivity was determined using these variables and the predictive accuracy of the nomogram was quantified by concordance index. Results: In total, 2,681 bone scan records were analyzed and 636 patients had a positive result. Overall, the median pre-scan prostate-specific antigen (PSA) level was 2.4 ng/ml; median PSA doubling time (PSADT) was 5.8 months. At the time of a positive scan, median PSA level was 8.2 ng/ml; 53% of patients had PSA <10 ng/ml; median PSADT was 4.0 months. Five variables were included in the nomogram: number of previous negative bone scans after initiating ADT, PSA level, Gleason grade sum, and history of radical prostatectomy and radiotherapy. A concordance index value of 0.721 was calculated for the nomogram. This was a retrospective study based on limited data in patients treated in a large cancer center who underwent conventional 99mTc bone scans, which themselves have inherent limitations. Conclusion: This is the first nomogram to predict current bone scan positivity in ADT-treated prostate cancer patients, providing high predictive accuracy. PMID:25386410

Development of a nomogram model predicting current bone scan positivity in patients treated with androgen-deprivation therapy for prostate cancer

Directory of Open Access Journals (Sweden)

Michael eKattan

2014-10-01

Full Text Available Purpose: To develop a nomogram predictive of current bone scan positivity in patients receiving androgen-deprivation therapy (ADT for advanced prostate cancer; to augment clinical judgment and highlight patients in need of additional imaging investigations.Materials and Methods: A retrospective chart review of bone scan records (conventional 99mTc-scintigraphy of 1,293 patients who received ADT at the Memorial Sloan-Kettering Cancer Center from 2000 to 2011. Multivariable logistic regression analysis was used to identify variables suitable for inclusion in the nomogram. The probability of current bone scan positivity was determined using these variables and the predictive accuracy of the nomogram was quantified by concordance index.Results: In total, 2,681 bone scan records were analyzed and 636 patients had a positive result. Overall, the median pre-scan prostate-specific antigen (PSA level was 2.4 ng/ml; median PSA doubling time (PSADT was 5.8 months. At the time of a positive scan, median PSA level was 8.2 ng/ml; 53% of patients had PSA <10 ng/ml; median PSADT was 4.0 months. Five variables were included in the nomogram: number of previous negative bone scans after initiating ADT, PSA level, Gleason grade sum, and history of radical prostatectomy and radiotherapy. A concordance index value of 0.721 was calculated for the nomogram. This was a retrospective study based on limited data in patients treated in a large cancer centre who underwent conventional 99mTc bone scans, which themselves have inherent limitations. Conclusions: This is the first nomogram to predict current bone scan positivity in ADT-treated prostate cancer patients, providing high predictive accuracy.

Is Preoperative Neutrophil Lymphocyte Ratio a Reliable Prognostic Parameter for Localized Prostate Cancer?

Directory of Open Access Journals (Sweden)

Tümay İpekçi

2017-12-01

Full Text Available Objective: In spite of all efforts, prostate cancer is still the 2nd highest cause of cancer-related deaths in men. For this reason new developments are needed in diagnosis, treatment and follow-up of prostate cancer. Neutrophil/lymphocyte (N/L ratio is a cheap and effective parameter used for research into many solid tumors; but there are not enough studies on the reliability of this parameter in prostate cancer. In this study we researched the efficacy of N/L ratio in localized prostate cancer. Materials and Methods: Between March 9, 2012 and April 23, 2017, the data of 140 patients who underwent radical prostatectomy with localized prostate cancer were screened retrospectively. The patients’ ages, preoperative prostate specific antigen (PSA and N/L ratio, pathologic stage, pathologic Gleason score, tumor volume, lymph node involvement, surgical margin positivity and presence or absence of 3rd month biochemical recurrence were noted. The correlations between N/L ratio with age, PSA, pathologic parameters, surgical margin positivity and biochemical recurrence were investigated. Results: The mean age of patients was 63.0±5.9 years, mean PSA value was 10.8±8.5 ng/mL and mean N/L ratio was 2.5±1.9. There was no correlation found between N/L ratio and PSA, pathologic stage, Gleason score, lymph node involvement, tumor volume, surgical margin positivity and biochemical recurrence (p>0.05. Conclusion: In our study investigating 140 patients with localized prostate cancer, we did not identify any correlation between N/L ratio and PSA, surgical stage and Gleason score, surgical margin positivity, and 3rd month biochemical recurrence. When the literature is investigated, it appears that N/L ratio is effective for metastatic prostate cancer. To provide a more accurate judgment of the role of N/L ratio in localized prostate cancer, there is a need for new studies with broader patient series.

Positive and negative mood in men with advanced prostate cancer undergoing androgen deprivation therapy: considering the role of social support and stress.

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Benedict, Catherine; Dahn, Jason R; Antoni, Michael H; Traeger, Lara; Kava, Bruce; Bustillo, Natalie; Zhou, Eric S; Penedo, Frank J

2015-08-01

Advanced prostate cancer patients often undergo androgen deprivation therapy (ADT). Advanced disease and adverse ADT side effects are often debilitating and negatively impact mood. Social support has been shown to mitigate detrimental effects of stress on mood. This study sought to characterize positive and negative mood in this select patient population and determine whether social support moderated relations between stress and mood. Participants (N = 80) completed the Interpersonal Support Evaluation List, Perceived Stress Scale, and Derogatis Affect Balance Scale at a single time point. Hierarchical regression models evaluated relations among social support, stress, and mood controlling for relevant covariates. Standard moderation analyses were performed. Participants reported higher levels of negative and positive mood compared with published means of localized prostate cancer patients. Overall, mood was more positive than negative. Stress levels were comparable to cancer populations with recurrent disease. Moderated regression analyses showed that social support partially buffered the effects of stress on positive mood; men with high stress and low support reported the lowest levels of positive mood. The model with negative mood as the dependent measure did not support moderation; that is, the relationship between stress and negative mood did not differ by level of social support. Among individuals living with advanced prostate cancer, social support may be an important factor that sustains positive mood in the presence of stress. Future work should examine the extent to which social support prospectively impacts health-related quality of life by promoting positive mood. Limitations include cross-sectional design, which precludes causal inferences. Copyright © 2014 John Wiley & Sons, Ltd.

Childhood height increases the risk of prostate cancer mortality

DEFF Research Database (Denmark)

Aarestrup, J; Gamborg, M; Cook, M B

2015-01-01

cancers. Cox proportional hazards regressions were performed. RESULTS: 630 men had prostate cancer recorded as the underlying cause of death. Childhood height at age 13years was positively associated with prostate cancer-specific mortality (hazard ratio [HR]per z-score=1.2, 95% confidence interval [CI]: 1.1-1.3......). Associations were significant at all other childhood ages. Growth analyses showed that height at age 13years had a stronger association with prostate cancer-specific mortality than height at age 7, suggesting the association at age 7 is largely mediated through later childhood height. The tallest boys at age...... 13years had a significantly worse survival, but only when restricted to a diagnosis at years of age (HRz-score of 1=1.7, 95% CI: 1.3-2.4). These associations were significant at all other childhood ages. Childhood BMI was not associated with prostate cancer mortality or survival. CONCLUSION...

Improved detection of localized prostate cancer using co-registered MRI and {sup 11}C-acetate PET/CT

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Jambor, Ivan, E-mail: ivjamb@utu.fi [Department of Diagnostic Radiology, University of Turku, Turku (Finland); 2nd Department of Radiology, Comenius University and St. Elisabeth Oncology Institute, Bratislava (Slovakia); Turku PET Centre, University of Turku, Turku (Finland); Borra, Ronald, E-mail: ronald.borra@tyks.fi [Department of Diagnostic Radiology, University of Turku, Turku (Finland); Turku PET Centre, University of Turku, Turku (Finland); Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku (Finland); Kemppainen, Jukka, E-mail: Jukka.Kemppainen@tyks.fi [Turku PET Centre, University of Turku, Turku (Finland); Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku (Finland); Lepomaeki, Virva, E-mail: Virva.Lepomaki@tyks.fi [Turku PET Centre, University of Turku, Turku (Finland); Parkkola, Riitta, E-mail: Riitta.Parkkola@tyks.fi [Department of Diagnostic Radiology, University of Turku, Turku (Finland); Turku PET Centre, University of Turku, Turku (Finland); Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku (Finland); Dean, Kirsti, E-mail: Kirsti.Dean@tyks.fi [Department of Diagnostic Radiology, University of Turku, Turku (Finland); Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku (Finland); Alanen, Kalle, E-mail: Kalle.Alanen@tyks.fi [Department of Pathology, Turku University Hospital, Turku (Finland); Arponen, Eveliina, E-mail: Eveliina.Arponen@utu.fi [Turku PET Centre, University of Turku, Turku (Finland); Nurmi, Martti, E-mail: Martti.Nurmi@tyks.fi [Department of Surgery, Division of Urology, Turku University Hospital, Turku (Finland); Aronen, Hannu J., E-mail: Hannu.Aronen@tyks.fi [Department of Diagnostic Radiology, University of Turku, Turku (Finland); Medical Imaging Centre of Southwest Finland, Turku University Hospital, Turku (Finland); and others

2012-11-15

Objectives: We aimed to study the ability of contrast enhanced MRI at 1.5 T and {sup 11}C-acetate PET/CT, both individually and using fused data, to detect localized prostate cancer. Methods: Thirty-six men with untreated prostate cancer and negative for metastatic disease on pelvic CT and bone scan were prospectively enrolled. A pelvic {sup 11}C-acetate PET/CT scan was performed in all patients, and a contrast enhanced MRI scan in 33 patients (6 examinations using both endorectal coil and surface coils, and 27 examinations using surface coils only). After the imaging studies 10 patients underwent prostatectomy and 26 were treated by image guided external beam radiation treatment. Image fusion of co-registered PET and MRI data was performed based on anatomical landmarks visible on CT and MRI using an advanced in-house developed software package. PET/CT, MRI and fused PET/MRI data were evaluated visually and compared with biopsy findings on a lobar level, while a sextant approach was used for patients undergoing prostatectomy. Results: When using biopsy samples as method of reference, the sensitivity, specificity and accuracy for visual detection of prostate cancer on a lobar level by contrast enhanced MRI was 85%, 37%, 73% and that of {sup 11}C-acetate PET/CT 88%, 41%, 74%, respectively. Fusion of PET with MRI data increased sensitivity, specificity and accuracy to 90%, 72% and 85%, respectively. Conclusions: Fusion of sequentially obtained PET/CT and MRI data for the localization of prostate cancer is feasible and superior to the performance of each individual modality alone.

Daily variations in the position of the prostate bed in patients with prostate cancer receiving postoperative external beam radiation therapy

International Nuclear Information System (INIS)

Kupelian, Patrick A.; Langen, Katja M.; Willoughby, Twyla R.; Wagner, Thomas H.; Zeidan, Omar A.; Meeks, Sanford L.

2006-01-01

Purpose: The aim of this study was to evaluate the extent of the variation in the position of the prostate bed with respect to the bony anatomy. Methods and Materials: Four patients were treated to 70 Gy in 35 fractions. Before each fraction, a megavoltage computed tomography (CT) of the prostate bed was obtained, resulting in a total of 140 CT studies. Retrospectively, each CT scan was aligned to the simulation kilovoltage scan based on bony anatomy and the prostate bed. The difference between the 2 alignments was calculated for each scan. Results: The average differences (±1 SD) between the two alignments were 0.06 ± 0.37, 0.10 ± 0.86, and 0.39 ± 1.27 mm in the lateral, longitudinal (SI), and vertical (AP) directions, respectively. Laterally, there was no difference ≥3 mm. The cumulative frequency of SI differences were as follows; ≥3 mm: 3%, ≥4 mm: 1%, and ≥5 mm: 1% (maximum: 5 mm). The cumulative frequency of AP differences were as follows; ≥3 mm: 7%, and ≥4 mm: 3% (maximum: 4 mm). Conclusion: In patients with prostate cancer receiving postoperative radiotherapy, the prostate bed motion relative to the pelvic bony anatomy is of a relatively small magnitude. Significant motion (≥3 mm) is infrequent. However, small differences between the prostate bed and the bony anatomy still exist. This might have implications on treatment margins when daily alignment on bony anatomy is performed

Epigenetic modifications in prostate cancer.

Science.gov (United States)

Ngollo, Marjolaine; Dagdemir, Aslihan; Karsli-Ceppioglu, Seher; Judes, Gaelle; Pajon, Amaury; Penault-Llorca, Frederique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique J

2014-01-01

Prostate cancer is the most common cancer in men and the second leading cause of cancer deaths in men in France. Apart from the genetic alterations in prostate cancer, epigenetics modifications are involved in the development and progression of this disease. Epigenetic events are the main cause in gene regulation and the three most epigenetic mechanisms studied include DNA methylation, histone modifications and microRNA expression. In this review, we summarized epigenetic mechanisms in prostate cancer. Epigenetic drugs that inhibit DNA methylation, histone methylation and histone acetylation might be able to reactivate silenced gene expression in prostate cancer. However, further understanding of interactions of these enzymes and their effects on transcription regulation in prostate cancer is needed and has become a priority in biomedical research. In this study, we summed up epigenetic changes with emphasis on pharmacologic epigenetic target agents.

Issues reporting PSA in prostate cancer

International Nuclear Information System (INIS)

Lange, Paul H.

1996-01-01

The National Cancer Institute Prostate; Lung; Colon; Ovarian Cancer Screening (PLCO) project is a multi-center trial developed to investigate the effectiveness of DRE and PSA testing in the early detection and outcome of patients with prostate cancer. Accordingly, the Prostate Cancer Intervention versus Observation Trial (PIVOT) has been launched and is a randomized trial comparing radical prostatectomy versus expectant management for ALCaP. PSA: Initially PSA was thought to be of little value for diagnosis because 20% of men undergoing radical prostatectomy have 'normal' PSA and patients with apparently only symptomatic BPH have 'elevated' levels as follows: 4-10 ng/ml (Tandem-R) - 20%, >10 ng/ml -3%. Yet, PSA has looked attractive as a diagnostic tool in many studies; for example, when PSA was used in a screening approach as the first test which then drove further evaluation (Catalona, Brawer). It was shown that the positive predictive value for PSA's between 4 and 10 is approximately 20% and > 10 approximately 55%. The value of serial PSA's (velocity) is unknown but is under intense study: one major issue is determination of what represents a significant rise (details to be presented). Studies have also revealed that a DRE and PSA are important for optimal results. About 18% of clinically detectable cancers are only DRE positive while about 25 - 30% are only PSA positive. When both a DRE and PSA are used together, very few clinically apparent cancers are missed (3-5%). Recent ROC curves suggest that 4 ng/ml is reasonable. Recently, PSA values for men without apparent cancer were stratified by age, and taking the 2SD, age specific reference values were generated as follows: age 40-49 (0-2.5 ng/ml), 50-59 (0-3.5), 60-69 (0-4.5), 70-70 (0-6.5). Finally, there is the issue about different PSA assays regarding the compatabilities/reliability of the upper limit of normal and serial values. Much of the confusion is because there is no international PSA standard and

Precision medicine for advanced prostate cancer.

Science.gov (United States)

Mullane, Stephanie A; Van Allen, Eliezer M

2016-05-01

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

Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

Science.gov (United States)

Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

2010-01-01

The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

The transcription factor ERG increases expression of neurotransmitter receptors on prostate cancer cells

International Nuclear Information System (INIS)

Kissick, Haydn T.; On, Seung T.; Dunn, Laura K.; Sanda, Martin G.; Asara, John M.; Pellegrini, Kathryn L.; Noel, Jonathan K.; Arredouani, Mohamed S.

2015-01-01

The TMPRSS2-ERG gene fusion occurs in about half of prostate cancer (PCa) cases and results in overexpression of the transcription factor ERG. Overexpression of ERG has many effects on cellular function. However, how these changes enhance cell growth and promote tumor development is unclear. To investigate the role of ERG, LNCaP and PC3 cells were transfected with ERG and gene expression and metabolic profile were analyzed. Our data show that expression of ERG induces overexpression of many nicotinicacetylcholine receptors (nAChRs). In addition, metabolic profiling by LC-MS/MS revealed elevated production of several neurotransmitters in cells expressing ERG. Consistently, treatment of ERG-expressing cells with nicotine induced elevated calcium influx, GSK3β (Ser9) phosphorylation and cell proliferation. Finally, we show that PCa patientswho are smokers have larger tumors if their tumors are TMPRSS2-ERG gene fusion positive. Collectively, our data suggest that ERG sensitizes prostate tumor cells to neurotransmitter receptor agonists like nicotine. The online version of this article (doi:10.1186/s12885-015-1612-3) contains supplementary material, which is available to authorized users

Prostate cancer

DEFF Research Database (Denmark)

Chabanova, Elizaveta; Balslev, Ingegerd; Logager, Vibeke

2011-01-01

To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data.......To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data....

Guidelines for primary radiotherapy of patients with prostate cancer

International Nuclear Information System (INIS)

Boehmer, Dirk; Maingon, Philippe; Poortmans, Philip; Baron, Marie-Helene; Miralbell, Raymond; Remouchamps, Vincent; Scrase, Christopher; Bossi, Alberto; Bolla, Michel

2006-01-01

Background and purposes: The appropriate application of 3-D conformal radiotherapy, intensity modulated radiotherapy or image guided radiotherapy for patients undergoing radiotherapy for prostate cancer requires a standardisation of target delineation as well as clinical quality assurance procedures. Patients and methods: Pathological and imaging studies provide valuable information on tumour extension. In addition, clinical investigations on patient positioning and immobilisation as well as treatment verification data offer an abundance of information. Results: Target volume definitions for different risk groups of prostate cancer patients based on pathological and imaging studies are provided. Available imaging modalities, patient positioning and treatment preparation studies as well as verification procedures are collected from literature studies. These studies are summarised and recommendations are given where appropriate. Conclusions: On behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology Group this article presents a common set of recommendations for external beam radiotherapy of patients with prostate cancer

On cribriform prostate cancer

OpenAIRE

Kweldam, Charlotte

2018-01-01

markdownabstractThis general aim of the thesis is to study the clinical relevance, interobserver reproducibility, and genetics of cribriform growth in prostate cancer. More specifically, the aims and outline of this thesis are • To study the metastatic potential of modified Gleason score 3+3 prostate cancer in radical prostatectomies. (Chapter 2) • To examine the prognostic value of individual Gleason grade 4 patterns in prostate cancer in radical prostatectomy and diagnostic biopsy specimens...

Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer.

Science.gov (United States)

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

2017-07-01

To examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study. The study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7. First, we evaluated whether the addition of PHI improves the performance of currently available risk calculators (the Prostate Cancer Prevention Trial [PCPT] and European Randomised Study of Screening for Prostate Cancer [ERSPC] risk calculators). We also designed and internally validated a new PHI-based multivariable predictive model, and created a nomogram. Of 728 men undergoing biopsy, 118 (16.2%) had aggressive prostate cancer. The PHI predicted the risk of aggressive prostate cancer across the spectrum of values. Adding PHI significantly improved the predictive accuracy of the PCPT and ERSPC risk calculators for aggressive disease. A new model was created using age, previous biopsy, prostate volume, PSA and PHI, with an area under the curve of 0.746. The bootstrap-corrected model showed good calibration with observed risk for aggressive prostate cancer and had net benefit on decision-curve analysis. Using PHI as part of multivariable risk assessment leads to a significant improvement in the detection of aggressive prostate cancer, potentially reducing harms from unnecessary prostate biopsy and overdiagnosis. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Epigenetic Regulation in Prostate Cancer Progression.

Science.gov (United States)

Ruggero, Katia; Farran-Matas, Sonia; Martinez-Tebar, Adrian; Aytes, Alvaro

2018-01-01

An important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers. Key players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency. As such, epigenetic dysregulation represents a driving mechanism in the reprograming of prostate cancer cells as they lose AR-imposed identity. Chromatin integrity and accessibility for transcriptional regulation are key features altered in cancer progression, and particularly relevant in nuclear hormone receptor-driven tumors like prostate cancer. Understanding how chromatin remodeling dictates prostate development and how its deregulation contributes to prostate cancer onset and progression may improve risk stratification and treatment selection for prostate cancer patients.

Diagnostic Accuracy of Robot-Guided, Software Based Transperineal MRI/TRUS Fusion Biopsy of the Prostate in a High Risk Population of Previously Biopsy Negative Men

Directory of Open Access Journals (Sweden)

Malte Kroenig

2016-01-01

Full Text Available Objective. In this study, we compared prostate cancer detection rates between MRI-TRUS fusion targeted and systematic biopsies using a robot-guided, software based transperineal approach. Methods and Patients. 52 patients received a MRIT/TRUS fusion followed by a systematic volume adapted biopsy using the same robot-guided transperineal approach. The primary outcome was the detection rate of clinically significant disease (Gleason grade ≥ 4. Secondary outcomes were detection rate of all cancers, sampling efficiency and utility, and serious adverse event rate. Patients received no antibiotic prophylaxis. Results. From 52 patients, 519 targeted biopsies from 135 lesions and 1561 random biopsies were generated (total n=2080. Overall detection rate of clinically significant PCa was 44.2% (23/52 and 50.0% (26/52 for target and random biopsy, respectively. Sampling efficiency as the median number of cores needed to detect clinically significant prostate cancer was 9 for target (IQR: 6–14.0 and 32 (IQR: 24–32 for random biopsy. The utility as the number of additionally detected clinically significant PCa cases by either strategy was 0% (0/52 for target and 3.9% (2/52 for random biopsy. Conclusions. MRI/TRUS fusion based target biopsy did not show an advantage in the overall detection rate of clinically significant prostate cancer.

Metastasis in urothelial carcinoma mimicking prostate cancer metastasis in Ga-68 prostate-specific membrane antigen positron emission tomography-computed tomography in a case of synchronous malignancy

International Nuclear Information System (INIS)

Gupta, Manoj; Choudhury, Partha Sarathi; Gupta, Gurudutt; Gandhi, Jatin

2016-01-01

Prostate cancer is the second most common cancer in man. It commonly presents with urinary symptoms, bone pain, or diagnosed with elevated prostate-specific antigen.(PSA) levels. Correct staging and early diagnosis of recurrence by a precise imaging tool are the keys for optimum management. Molecular imaging of prostate cancer with Ga-68 prostate-specific membrane antigen.(PSMA), positron emission tomography-computed tomography.(PET-CT) has recently received significant attention and frequently used with a signature to prostate cancer-specific remark. However, this case will highlight the more cautious use of it. A-72-year-old male treated earlier for synchronous double malignancy.(invasive papillary urothelial carcinoma right ureter and carcinoma prostate) presented with rising PSA.(0.51.ng/ml) and referred for Ga-68 PSMA PET-CT, which showed a positive enlarged left supraclavicular lymph node. Lymph node biopsy microscopic and immunohistochemistry examination revealed metastatic carcinoma favoring urothelial origin. Specificity of PSMA scan to prostate cancer has been seen to be compromised in a certain situation mostly due to neoangiogenesis, and false positives emerged in renal cell cancer, differentiated thyroid cancer, glioblastoma, breast cancer brain metastasis, and paravertebral schwannomas. Understanding the causes of false positive will further enhance the confidence of interpretating PSMA scans

Prostate cancer and inflammation: the evidence

Science.gov (United States)

Sfanos, Karen S; De Marzo, Angelo M

2014-01-01

Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk. PMID:22212087

MRI diagnosis for prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Tamada, Tsutomu; Nagai, Kiyohisa; Imai, Shigeki; Kajihara, Yasumasa; Jo, Yoshimasa; Tanaka, Hiroyoshi; Fukunaga, Masao (Kawasaki Medical School, Kurashiki, Okayama (Japan)); Matsuki, Takakazu

1998-01-01

Recently, in Japan, both the Westernization of life styles and the advent of an aged-society have led to an increase in the incidence of prostate cancer. In making a localizing diagnosis of prostate cancer, magnetic resonance imaging (MRI), which has excellent contrast resolution, and transrectal ultrasonography, are used clinically, and their usefulness is being established. MRI is employed in the diagnosis of prostate cancer to detect tumors, and to determine the stage of such tumors. For the visualization of prostate cancer by MRI, T2-weighted axial images are used exclusively. After becoming familiar with normal prostate images, it is important to evaluate the localization of a tumor, and the invasion of the capsule and seminal vesicles. Future applications of new techniques for MRI will undoubtedly be found. In this paper, the present state of MRI diagnosis of prostate cancer at Kawasaki Medical School Hospital will be reviewed. (author)

MRI diagnosis for prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Tamada, Tsutomu; Nagai, Kiyohisa; Imai, Shigeki; Kajihara, Yasumasa; Jo, Yoshimasa; Tanaka, Hiroyoshi; Fukunaga, Masao [Kawasaki Medical School, Kurashiki, Okayama (Japan); Matsuki, Takakazu

1998-12-31

Recently, in Japan, both the Westernization of life styles and the advent of an aged-society have led to an increase in the incidence of prostate cancer. In making a localizing diagnosis of prostate cancer, magnetic resonance imaging (MRI), which has excellent contrast resolution, and transrectal ultrasonography, are used clinically, and their usefulness is being established. MRI is employed in the diagnosis of prostate cancer to detect tumors, and to determine the stage of such tumors. For the visualization of prostate cancer by MRI, T2-weighted axial images are used exclusively. After becoming familiar with normal prostate images, it is important to evaluate the localization of a tumor, and the invasion of the capsule and seminal vesicles. Future applications of new techniques for MRI will undoubtedly be found. In this paper, the present state of MRI diagnosis of prostate cancer at Kawasaki Medical School Hospital will be reviewed. (author)

Prostate-specific membrane antigen-based imaging in prostate cancer: impact on clinical decision making process.

Science.gov (United States)

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.

Baldness, benign prostate hyperplasia, prostate cancer and androgen levels.

Science.gov (United States)

Faydaci, Gökhan; Bilal, Eryildirim; Necmettin, Penpegül; Fatih, Tarhan; Asuman, Orçun; Uğur, Kuyumcuoğlu

2008-12-01

We evaluated the pattern of baldness and serum androgen levels in patients with benign prostate hyperplasia (BPH) and prostate cancer. BPH, prostate cancer and androgenic alopecia (AA) were somehow androgen dependent and affect large population of elderly men. A total of 152 patients, 108 patients with BPH and 44 patients with prostate cancer were included in the study. We measured serum total, free and bioavailable testosterone, FSH, LH, prolactin, estradiol, albumin and SHBG levels. Baldness classification was based on Norwood's classification and we categorised baldness as vertex and frontal baldness. The frequency of AA in BPH and prostate cancer groups were not different. We looked for some correlation between the two groups with respect to AA and hormone levels. We did not find any correlation between AA and total testosterone, free testosterone, bioavailable testosterone or SHBG levels in both groups. This prospective study with selected small group of patients showed that there is no difference of male pattern baldness in BPH and prostate cancer patients and also there is no correlation between pattern of baldness and serum androgen levels.

Familial prostate cancer has a more aggressive course than sporadic prostate cancer after treatment for localized disease, mainly due to a higher rate of distant metastases

International Nuclear Information System (INIS)

Kupelian, Patrick A.; Klein, Eric A.; Suh, John H; Kupelian, Varant A.

1997-01-01

Purpose: We had already established that familial prostate cancer, defined as prostate cancer diagnosed in a father or brother, was an independent predictor of biochemical failure after treatment for localized disease. Our aim was to determine whether differences in outcome could be observed with respect to clinical failures (either local or distant) between the two forms of prostate cancer. Methods: Of the 1685 consecutive cases with localized prostate carcinoma treated between 1986 and 1996, patients with the following were excluded from the present study: no pretreatment Prostatic Specific Antigen (iPSA) level (n=54), no biopsy Gleason score (bGS) (n=25), adjuvant or neoadjuvant treatment (n=234), no available follow-up PSA level (n=30). We also excluded 617 patients who did not have a minimum of 3 years potential follow-up. The analysis was performed on 725 cases. Radiotherapy (RT) was the primary treatment in 330 patients and radical prostatectomy (RP) in 395 patients. Five percent had clinical stage T3 disease (n=37). Positive family history was defined as the presence of prostate cancer in a first degree relative (father or brother). The outcomes of interest were biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), local relapse-free survival (locRFS), distant relapse-free survival (dRFS). We used proportional hazards to analyze the effect of family history and other potential confounding variables (i.e. age, race, treatment modality, stage, biopsy GS, and iPSA levels) on treatment outcome. We included pathologic findings (extracapsular extension, seminal vesicle involvement, surgical margin involvement, and lymph node metastases) in a separate analysis for RP patients. Results: The median follow-up was 45 months. Eight percent of all cases (n=57) had a positive family history. The 5-year bRFS rates for patients with negative and positive family history were 54% and 38%, respectively (p<0.001). The 5-year cRFS rates for patients

The clinical value of MR elastography in the diagnosis of prostate cancer

International Nuclear Information System (INIS)

Chen Min; Li Saying; Wang Wenchao; Zhao Weifeng; Yang Zhenghan; Liu Ming; Zhou Cheng

2010-01-01

Objective: To investigate the clinical value of MR elastography in the diagnosis of prostate cancer at 3.0 T, and to assess the elasticity and viscosity of prostate cancer and benign prostatic diseases. Methods: Eight patients (63±7 years old) with 12 foci of prostate cancer and 10 patients (59±3 years old) with 14 foci of prostatitis in the peripheral zone were evaluated by MR elastography. MR elastography was performed by transmitting low-frequency longitudinal mechanical waves of 100 Hz into prostate with a transducer placed above the pubic bones. The phase images were reconstructed to acquire viscoelastic mapping. t test was used to compare the mean elasticity and viscosity of prostate cancer and prostatitis. The correlation of elasticity and Gleason scores between prostate cancer and prostatitis were also retrospectively analyzed with Pearson Correlation. Results: The mean elasticity and viscosity were significantly higher in prostate cancer [(6.55±0.47) kPa, (6.56±0.99) Pa·s, respectively] than in prostatitis [(1.99±0.66) kPa, (2.13±0.21) Pa·s, respectively], and the difference was statistically significant (t=19.392, 16.372; P<0.01). In 8 patients with prostate cancer, the Gleason scores were 5 (2 cases), 6 (3 cases), 7 (2 cases) and 8 (1 case), respectively. The mean elasticity for the cases with different Gleason scores was 5.83, 6.02, 7.45 and 8.05 kPa, respectively. There was a positive correlation between Gleason scores and elasticity of the prostate cancer(r=0.913, P<0.01) in this study. Conclusion: MR elastography can be used to visualize the difference in stiffness between prostate cancer and benign prostatic disease, it is a new imaging method with great potential in grading of prostate cancer. (authors)

The future perspectives in transrectal prostate ultrasound guided biopsy

Directory of Open Access Journals (Sweden)

Sung Il Hwang

2014-12-01

Full Text Available Prostate cancer is one of the most common neoplasms in men. Transrectal ultrasound (TRUS-guided systematic biopsy has a crucial role in the diagnosis of prostate cancer. However, it shows limited value with gray-scale ultrasound alone because only a small number of malignancies are visible on TRUS. Recently, new emerging technologies in TRUS-guided prostate biopsy were introduced and showed high potential in the diagnosis of prostate cancer. High echogenicity of ultrasound contrast agent reflect the increased status of angiogenesis in tumor. Molecular imaging for targeting specific biomarker can be also used using ultrasound contrast agent for detecting angiogenesis or surface biomarker of prostate cancer. The combination of TRUS-guided prostate biopsy and ultrasound contrast agents can increase the accuracy of prostate cancer diagnosis. Elastography is an emerging ultrasound technique that can provide the information regarding tissue elasticity and stiffness. Tumors are usually stiffer than the surrounding soft tissue. In two types of elastography techniques, shearwave elastography has many potential in that it can provide quantitative information on tissue elasticity. Multiparametric magnetic resonance imaging (MRI from high resolution morphologic and functional magnetic resonance (MR technique enables to detect more prostate cancers. The combination of functional techniques including apparent diffusion coefficient map from diffusion weighted imaging, dynamic contrast enhanced MR and MR spectroscopy are helpful in the localization of the prostate cancer. MR-ultrasound (US fusion image can enhance the advantages of both two modalities. With MR-US fusion image, targeted biopsy of suspicious areas on MRI is possible and fusion image guided biopsy can provide improved detection rate. In conclusion, with recent advances in multiparametric-MRI, and introduction of new US techniques such as contrast-enhanced US and elastography, TRUS-guided biopsy

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

Science.gov (United States)

Cooper, Colin S; Eeles, Rosalind; Wedge, David C; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, ZSofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; O'Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Warren, Anne Y; Foster, Christopher S; Stratton, Michael R; Whitaker, Hayley C; McDermott, Ultan; Brewer, Daniel S; Neal, David E

2015-04-01

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

The value of magnetic resonance imaging and ultrasonography (MRI/US)-fusion biopsy platforms in prostate cancer detection: a systematic review

NARCIS (Netherlands)

Gayet, M.; Aa, A. van der; Beerlage, H.P.; Schrier, B.P.; Mulders, P.F.A.; Wijkstra, H.

2016-01-01

Despite limitations considering the presence, staging and aggressiveness of prostate cancer, ultrasonography (US)-guided systematic biopsies (SBs) are still the 'gold standard' for the diagnosis of prostate cancer. Recently, promising results have been published for targeted prostate biopsies (TBs)

Ultrasonography and prostate-specific antigen (PSA) in differential diagnosis of prostate cancer and benign prostatic hyperplasia

International Nuclear Information System (INIS)

Mechev, D.S.; Shcherbyina, O.V.; Yatsik, V.Yi.; Gladka, L.Yu.

2003-01-01

The purpose of the work is analysis of diagnostic possibilities of transrectal ultrasonography and PSA in differential diagnosis of prostate cancer and benign prostatic hyperplasia. 142 patients have been investigated by transrectal ultrasonography. he transrectal ultrasonography and PSA are sensible tests in diagnosis of prostate cancer and in differential diagnosis of benign prostatic hyperplasia and prostate cancer

Dosimetric effects of the prone and supine positions on image guided localized prostate cancer radiotherapy

International Nuclear Information System (INIS)

Liu Bei; Lerma, Fritz A.; Patel, Shilpen; Amin, Pradip; Feng Yuanming; Yi, B.-Y.; Yu, Cedric

2008-01-01

Purpose: To compare target coverage and doses to rectum and bladder in IMRT of localized prostate cancer in the supine versus prone position, with the inclusion of image guidance. Materials and methods: Twenty patients with early stage localized prostate carcinoma who received external beam radiotherapy in the supine and prone positions underwent approximately 10 serial CT examinations in their respective treatment position in non-consecutive days, except for one patient who was treated prone but serially imaged supine. The prostate, bladder and rectum were contoured on all CT scans. A PTV was generated on the first scan of each patient's CT series by expanding the prostate with a 5 mm margin and an IMRT plan was created. The resultant IMRT plan was then applied to that patient's remaining serial CT scans by aligning the initial CT image set with the subsequent serial CT image sets using (1) skin marks, (2) bony anatomy and (3) center of mass of the prostate. The dosimetric results from these three alignments were compared between the supine and prone groups. To account for the uncertainties associated with prostate delineation and intra-fractional geometric changes, a fictional 'daily PTV' was generated by expanding the prostate with a 3 mm margin on each serial CT scan. Thus, a more realistic target coverage index, V95, was quantified as the fraction of the daily PTV receiving at least 95% of the prescription dose. Dose-volume measures of the organs at risk were also compared. The fraction of the daily PTV contained by the initial PTV after each alignment method was quantified on each patient's serial CT scan, and is defined as PTV overlap index. Results: As expected, alignment based on skin marks yielded unacceptable dose coverage for both groups of patients. Under bony alignment, the target coverage index, V95, was 97.3% and 93.6% for prone and supine patients (p < 0.0001), respectively. The mean PTV overlap indices were 90.7% and 84.7% for prone and supine

Antibiotic and anti-inflammatory use and the risk of prostate cancer

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Bent Stephen

2009-04-01

Full Text Available Abstract Background Prostate inflammation or infection may increase the risk of prostate cancer. Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs are used to treat prostatitis and urinary tract infections (UTIs. The objective of our study was to assess whether their use decreases the risk of prostate cancer. Methods We conducted a case-control study among men with incident prostate cancer (N = 65 cases and without prostate cancer (N = 195 controls at the San Francisco Veteran Affairs medical center (VAMC between June 1996 and June 2006. Cases were all patients who had prostate biopsies positive for cancer. We matched controls to cases on age group and race at a 3:1 ratio, and each matched pair was given an identical index date. Total antibiotic, aspirin, and NSAID use (number of prescriptions was computed for each participant by drug type and was restricted to a fill date at least 1 year before the index date. Logistic regression was used for analysis. We adjusted for the matching variables (age group and race and potential confounders (years of VAMC enrollment and number of clinic visits. Results Neither total antibiotic use nor total anti-inflammatory use reduces the risk of prostate cancer (P > 0.05. Conclusion Our analysis did not reveal a relation between use of antibiotics, aspirin, or NSAIDs and the risk of prostate cancer.

Baseline prostate-specific antigen measurements and subsequent prostate cancer risk in the Danish Diet, Cancer and Health cohort

DEFF Research Database (Denmark)

Larsen, Signe Benzon; Brasso, Klaus; Iversen, Peter

2013-01-01

Although prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer.......Although prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer....

Immunotherapy in metastatic prostate cancer

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Susan F Slovin

2016-01-01

Full Text Available Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit.

Perioperative Search for Circulating Tumor Cells in Patients Undergoing Prostate Brachytherapy for Clinically Nonmetastatic Prostate Cancer

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Hideyasu Tsumura

2017-01-01

Full Text Available Despite the absence of local prostate cancer recurrence, some patients develop distant metastases after prostate brachytherapy. We evaluate whether prostate brachytherapy procedures have a potential risk for hematogenous spillage of prostate cancer cells. Fifty-nine patients who were undergoing high-dose-rate (HDR or low-dose-rate (LDR brachytherapy participated in this prospective study. Thirty patients with high-risk or locally advanced cancer were treated with HDR brachytherapy after neoadjuvant androgen deprivation therapy (ADT. Twenty-nine patients with clinically localized cancer were treated with LDR brachytherapy without neoadjuvant ADT. Samples of peripheral blood were drawn in the operating room before insertion of needles (preoperative and again immediately after the surgical manipulation (intraoperative. Blood samples of 7.5 mL were analyzed for circulating tumor cells (CTCs using the CellSearch System. While no preoperative samples showed CTCs (0%, they were detected in intraoperative samples in 7 of the 59 patients (11.8%; preoperative vs. intraoperative, p = 0.012. Positive CTC status did not correlate with perioperative variables, including prostate-specific antigen (PSA at diagnosis, use of neoadjuvant ADT, type of brachytherapy, Gleason score, and biopsy positive core rate. We detected CTCs from samples immediately after the surgical manipulation. Further study is needed to evaluate whether those CTCs actually can survive and proliferate at distant sites.

Role of transurethral resection of the prostate in the management of prostate cancer

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Szollosi Attila

2016-06-01

Full Text Available Introduction: Prostate cancer is the second most diagnosed cancer in men, after lung cancer. The gold standard procedure in prostate cancer (PCa diagnosis is the ultrasound guided prostate biopsy. Transurethral resection of the prostate (TURP used in solving the bladder outlet obstruction, can have a role in detection of PCa. The aim of this retrospective study is to examine the role of transurethral resection of the prostate in the diagnosis and therapy of prostate cancer.

Blood lipids and prostate cancer

DEFF Research Database (Denmark)

Bull, Caroline J; Bonilla, Carolina; Holly, Jeff M P

2016-01-01

Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL...... into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL.......95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk...

Cryotherapy for prostate cancer

Science.gov (United States)

... this page: //medlineplus.gov/ency/patientinstructions/000907.htm Cryotherapy for prostate cancer To use the sharing features ... first treatment for prostate cancer. What Happens During Cryotherapy Before the procedure, you will be given medicine ...

Risk of biochemical recurrence and positive surgical margins in patients with pT2 prostate cancer undergoing radical prostatectomy

DEFF Research Database (Denmark)

Røder, Martin Andreas; Thomsen, Frederik Birkebæk; Berg, Kasper Drimer

2014-01-01

BACKGROUND AND OBJECTIVE: To investigate risk factors associated with positive surgical margins (PSM) and biochemical recurrence (BR) in organ confined tumors (pT2) after radical prostatectomy (RP) for localized prostate cancer (PCa). METHODS: Between 1995 and 2011, 1,649 patients underwent RP...

MR imaging of the prostate; MRT der Prostata

Energy Technology Data Exchange (ETDEWEB)

Asbach, P.; Haas, M.; Hamm, B. [Charite Campus Benjamin Franklin, Klinik fuer Radiologie, Berlin (Germany)

2015-12-15

Prostate cancer is the most common form of cancer in men in Germany; however, there is a distinct difference between incidence and mortality. The detection of prostate cancer is based on clinical and laboratory testing using serum prostate-specific antigen (PSA) levels and transrectal ultrasound with randomized biopsy. Multiparametric MR imaging of the prostate can provide valuable diagnostic information for detection of prostate cancer, especially after negative results of a biopsy prior to repeat biopsy. In addition the use of MR ultrasound fusion-guided biopsy has gained in diagnostic importance and has increased the prostate cancer detection rate. The prostate imaging reporting and data system (PI-RADS) classification has standardized the reporting of prostate MRI which has positively influenced the acceptance by urologists. (orig.) [German] Das Prostatakarzinom ist in Deutschland die haeufigste Krebserkrankung des Mannes, wobei ein deutlicher Unterschied zwischen Inzidenz und Mortalitaet besteht. Die Detektion des Prostatakarzinoms basiert auf klinischer und laborchemischer Untersuchung (prostataspezifisches-Antigen[PSA]-Wert) sowie der transrektalen Ultraschalluntersuchung mit randomisierter Biopsie. Die multiparametrische MR-Tomographie kann zur Detektion des Prostatakarzinoms, insbesondere bei negativer Biopsie vor einer erneuten Biopsie wertvolle diagnostische Informationen liefern. Zudem wird zunehmend die MRT-Ultraschall-Fusionsbiopsie in der Diagnostik eingesetzt, wodurch die Detektionsrate des Prostatakarzinoms deutlich gesteigert werden kann. Mit Einfuehrung der PI-RADS-Klassifikation (Prostate Imaging-Reporting and Data System) konnte zudem eine Standardisierung der Befundung erreicht werden, was die Akzeptanz der MRT der Prostata in der Urologie erhoeht hat. (orig.)

The 4q27 locus and prostate cancer risk

International Nuclear Information System (INIS)

Tindall, Elizabeth A; Hoang, Hoa N; Southey, Melissa C; English, Dallas R; Hopper, John L; Giles, Graham G; Severi, Gianluca; Hayes, Vanessa M

2010-01-01

Chronic inflammation is considered to be implicated in the development of prostate cancer. In this study we are the first to investigate a potential association between variants in an autoimmune related region on chromosome 4q27 and prostate cancer risk. This region harbors two cytokine genes IL-2 and the recently described IL-21. We genotyped six variants previously associated with autoimmune disease (namely rs13151961, rs13119723, rs17388568, rs3136534, rs6822844 and rs6840978) and one functional IL-2 promoter variant (rs2069762) for possible association with prostate cancer risk using the Australian Risk Factors for Prostate Cancer case-control Study. Overall, our results do not support an association between the seven variants at position 4q27 and prostate cancer risk. Per allele odds ratios (ORs) were not significantly different from 1 (all P-values = 0.06). However, we found suggestive evidence for a significant association between the presence of the rs13119723 variant (located in a protein of unknown function) and men with a family history of prostate cancer in first-degree relatives (P-value for interaction 0.02). The per allele OR associated with this variant was significantly higher than 1 (2.37; 95% C.I. = 1.01-5.57). We suggest that genetic variation within the chromosome 4q27 locus might be associated with prostate cancer susceptibility in men with a family history of the disease. Furthermore, our study alludes to a potential role of unknown protein KIAA1109 in conferring this risk

Vitamin D in prostate cancer

Directory of Open Access Journals (Sweden)

Donald L Trump

2018-01-01

Full Text Available Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.

Vitamin D in prostate cancer.

Science.gov (United States)

Trump, Donald L; Aragon-Ching, Jeanny B

2018-04-13

Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.

Vitamin D in prostate cancer

Science.gov (United States)

Trump, Donald L; Aragon-Ching, Jeanny B

2018-01-01

Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited. PMID:29667615

Childhood Height and Birth Weight in Relation to Future Prostate Cancer Risk

DEFF Research Database (Denmark)

Cook, Michael B; Gamborg, Michael; Aarestrup, Julie

2013-01-01

Adult height has been positively associated with prostate cancer risk. However, the exposure window of importance is currently unknown and assessments of height during earlier growth periods are scarce. In addition, the association between birth weight and prostate cancer remains undetermined. We...

FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer.

Science.gov (United States)

Davidsson, Sabina; Andren, Ove; Ohlson, Anna-Lena; Carlsson, Jessica; Andersson, Swen-Olof; Giunchi, Francesca; Rider, Jennifer R; Fiorentino, Michelangelo

2018-01-01

The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (T regs ). In the present study we evaluated the prevalence of T reg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4 + T regs and CD8 + T regs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of T regs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. In men with prostate cancer, similarly high numbers of stromal CD4 + T regs were identified in PAH and tumor, but CD4 + T regs were less common in PIN. Greater numbers of epithelial CD4+ T regs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4 + T regs in the normal prostatic tissue counterpart. Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4 + T regs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established. © 2017 The Authors. The Prostate Published by Wiley Periodicals Inc.

Human Prostate Cancer Hallmarks Map

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

2016-01-01

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

Prostate ultrasound: back in business!

Science.gov (United States)

Crisan, Nicolae; Andras, Iulia; Radu, Corina; Andras, David; Coman, Radu-Tudor; Tucan, Paul; Pisla, Doina; Crisan, Dana; Coman, Ioan

2017-11-29

The use of grey scale prostate ultrasound decreased after the implementation of magnetic resonance imaging (MRI) for the diagnosis and evaluation of prostate cancer. The new developments, such as multiparametric ultrasound and MRI-ultrasound fusion technology, renewed the interest for this imaging method in the assessment of prostate cancer. The purpose of this paper was to review the current role of prostate ultrasound in the setting of these new applications. A thorough reevaluation of the selection criteria of the patients is required to assess which patients would benefit from multiparametric ultrasound, who wouldbenefit from multiparametric MRI or the combination of both to assist prostate biopsy in order to ensure the balance between overdiagnosis and underdiagnosis of prostate cancer.

Prostate position variability and dose-volume histograms in radiotherapy for prostate cancer with full and empty bladder

International Nuclear Information System (INIS)

Pinkawa, Michael; Asadpour, Branka; Gagel, Bernd; Piroth, Marc D.; Holy, Richard; Eble, Michael J.

2006-01-01

Purpose: To evaluate prostate position variability and dose-volume histograms in prostate radiotherapy with full bladder (FB) and empty bladder (EB). Methods and Materials: Thirty patients underwent planning computed tomography scans in a supine position with FB and EB before and after 4 and 8 weeks of radiation therapy. The scans were matched by alignment of pelvic bones. Displacements of the prostate/seminal vesicle organ borders and center of mass were determined. Treatment plans (FB vs. EB) were compared. Results: Compared with the primary scan, FB volume varied more than EB volume (standard deviation, 106 cm 3 vs. 47 cm 3 ), but the prostate/seminal vesicle center of mass position variability was the same (>3 mm deviation in right-left, anterior-posterior, and superior-inferior directions in 0, 41%, and 33%, respectively, with FB vs. 0, 44%, and 33% with EB). The bladder volume treated with 90% of the prescription dose was significantly larger with EB (39% ± 14% vs. 22% ± 10%; p < 0.01). Bowel loops received ≥90% of prescription dose in 37% (3% with FB; p < 0.01). Conclusion: Despite the larger variability of bladder filling, prostate position stability was the same with FB compared with EB. An increased amount of bladder volume in the high-dose region and a higher dose to bowel loops result from treatment plans with EB

Development and external multicenter validation of Chinese Prostate Cancer Consortium prostate cancer risk calculator for initial prostate biopsy.

Science.gov (United States)

Chen, Rui; Xie, Liping; Xue, Wei; Ye, Zhangqun; Ma, Lulin; Gao, Xu; Ren, Shancheng; Wang, Fubo; Zhao, Lin; Xu, Chuanliang; Sun, Yinghao

2016-09-01

Substantial differences exist in the relationship of prostate cancer (PCa) detection rate and prostate-specific antigen (PSA) level between Western and Asian populations. Classic Western risk calculators, European Randomized Study for Screening of Prostate Cancer Risk Calculator, and Prostate Cancer Prevention Trial Risk Calculator, were shown to be not applicable in Asian populations. We aimed to develop and validate a risk calculator for predicting the probability of PCa and high-grade PCa (defined as Gleason Score sum 7 or higher) at initial prostate biopsy in Chinese men. Urology outpatients who underwent initial prostate biopsy according to the inclusion criteria were included. The multivariate logistic regression-based Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) was constructed with cases from 2 hospitals in Shanghai. Discriminative ability, calibration and decision curve analysis were externally validated in 3 CPCC member hospitals. Of the 1,835 patients involved, PCa was identified in 338/924 (36.6%) and 294/911 (32.3%) men in the development and validation cohort, respectively. Multivariate logistic regression analyses showed that 5 predictors (age, logPSA, logPV, free PSA ratio, and digital rectal examination) were associated with PCa (Model 1) or high-grade PCa (Model 2), respectively. The area under the curve of Model 1 and Model 2 was 0.801 (95% CI: 0.771-0.831) and 0.826 (95% CI: 0.796-0.857), respectively. Both models illustrated good calibration and substantial improvement in decision curve analyses than any single predictors at all threshold probabilities. Higher predicting accuracy, better calibration, and greater clinical benefit were achieved by CPCC-RC, compared with European Randomized Study for Screening of Prostate Cancer Risk Calculator and Prostate Cancer Prevention Trial Risk Calculator in predicting PCa. CPCC-RC performed well in discrimination and calibration and decision curve analysis in external validation compared

Prioritizing genes associated with prostate cancer development

International Nuclear Information System (INIS)

Gorlov, Ivan P; Logothetis, Christopher J; Sircar, Kanishka; Zhao, Hongya; Maity, Sankar N; Navone, Nora M; Gorlova, Olga Y; Troncoso, Patricia; Pettaway, Curtis A; Byun, Jin Young

2010-01-01

The genetic control of prostate cancer development is poorly understood. Large numbers of gene-expression datasets on different aspects of prostate tumorigenesis are available. We used these data to identify and prioritize candidate genes associated with the development of prostate cancer and bone metastases. Our working hypothesis was that combining meta-analyses on different but overlapping steps of prostate tumorigenesis will improve identification of genes associated with prostate cancer development. A Z score-based meta-analysis of gene-expression data was used to identify candidate genes associated with prostate cancer development. To put together different datasets, we conducted a meta-analysis on 3 levels that follow the natural history of prostate cancer development. For experimental verification of candidates, we used in silico validation as well as in-house gene-expression data. Genes with experimental evidence of an association with prostate cancer development were overrepresented among our top candidates. The meta-analysis also identified a considerable number of novel candidate genes with no published evidence of a role in prostate cancer development. Functional annotation identified cytoskeleton, cell adhesion, extracellular matrix, and cell motility as the top functions associated with prostate cancer development. We identified 10 genes--CDC2, CCNA2, IGF1, EGR1, SRF, CTGF, CCL2, CAV1, SMAD4, and AURKA--that form hubs of the interaction network and therefore are likely to be primary drivers of prostate cancer development. By using this large 3-level meta-analysis of the gene-expression data to identify candidate genes associated with prostate cancer development, we have generated a list of candidate genes that may be a useful resource for researchers studying the molecular mechanisms underlying prostate cancer development

Current State of ERG as Biomarker in Prostatic Adenocarcinoma.

Science.gov (United States)

Acs, Balazs; Szarvas, Tibor; Szekely, Nora; Nyirady, Peter; Szasz, A Marcell

2015-01-01

In this review we briefly discuss the possible biomarkers of prostate cancer among them we focus and analyze the relevance of TMPRSS2-ERG fusion gene in line with ERG expression in the diagnosis of prostate cancer. Starting at diagnosis and genetic alterations in prostate carcinomas, we examine the incidence and detection of the most common genetic aberration in this tumor and its protein product as well. We also examined the correlation of clinicopathological factors and prognosis with ERG and the TMPRSS2-ERG fusion oncogene and ERG expression as predictive markers.

Prostate cancer in Denmark

DEFF Research Database (Denmark)

Brasso, K; Friis, S; Kjaer, S K

1998-01-01

To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period.......To review the trends in prostate cancer (PC) incidence and mortality rates in Denmark during a 50-year period....

Cancer/testis antigen SPATA19 is frequently expressed in benign prostatic hyperplasia and prostate cancer.

Science.gov (United States)

Wong, Kah Keng; Hussain, Faezahtul Arbaeyah; Loo, Suet Kee; López, José I

2017-12-01

Spermatogenesis-associated 19 (SPATA19) is a cancer/testis antigen overexpressed in various cancers. However, its protein expression profile in malignant or non-malignant tissues remains unknown. Thus, in this study, we investigated SPATA19 protein expression patterns in a panel of non-malignant human samples and primary prostate cancer (PCa) with or without benign prostatic hyperplasia (BPH) tissues. SPATA19 was absent in all non-malignant tissues investigated (n=14) except testis and prostate tissues. In terms of malignancies, all PCa cases were positive for SPATA19 exhibiting frequency between 20 and 100% (median 85%) with 63 (52.5%) and 57 (47.5%) cases demonstrating weak/moderate and strong intensities, respectively. Thirty-nine PCa cases (32.5%) contained BPH, and all BPH glands were SPATA19 positive (frequency between 20 and 100%; median 90%) with 13 (33.3%) demonstrating strong SPATA19 expression. Higher SPATA19 expression (higher frequency, intensity, or H-score) was not associated with overall survival or disease-specific survival (DFS) in all PCa cases. However, biochemical recurrence (BR) was associated with worse DFS (p = 0.005) in this cohort of 120 patients, and cases with strong SPATA19 intensity were associated with BR (p = 0.020). In conclusion, we showed that SPATA19 protein was frequently expressed in both BPH and PCa glands, and this warrants future investigations on its pathogenic roles in the disease. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Chemotherapeutic prevention studies of prostate cancer

DEFF Research Database (Denmark)

Djavan, Bob; Zlotta, Alexandre; Schulman, Claude

2004-01-01

Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, ie the administration of agents that inhibit 1 or more steps in the natural...... history of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe....

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

Science.gov (United States)

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

2014-04-01

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

[Prostate cancer patients with lymph node metastasis. Outcome in a consecutive group of 59 patients

DEFF Research Database (Denmark)

Roder, M.A.; Reinhardt, S.; Brasso, K.

2008-01-01

INTRODUCTION: The optimal management of prostate cancer patients with lymph node metastasis remains controversial. In this article, the outcome in a consecutive group of patients with newly diagnosed lymph node positive prostate cancer is presented. MATERIALS AND METHODS: In 59 patients...... with histological verified lymph node positive disease but without osseous metastasis, outcome is described by time to biochemical progression, time to metastasis and survival. RESULTS: Median age at diagnosis was 62 years. Median pre-treatment PSA was 21 ng/ml. Endocrine treatment was initiated within median 2...... patients died during follow-up, 15 deaths were attributable to prostate cancer. Estimated median survival was 5.5 years. CONCLUSION: Despite early androgen deprivation therapy, patients with lymph node positive prostate cancer have a grave prognosis with a high risk of progression and disease...

Obesity, body composition, and prostate cancer

Directory of Open Access Journals (Sweden)

Fowke Jay H

2012-01-01

Full Text Available Abstract Background Established risk factors for prostate cancer have not translated to effective prevention or adjuvant care strategies. Several epidemiologic studies suggest greater body adiposity may be a modifiable risk factor for high-grade (Gleason 7, Gleason 8-10 prostate cancer and prostate cancer mortality. However, BMI only approximates body adiposity, and may be confounded by centralized fat deposition or lean body mass in older men. Our objective was to use bioelectric impedance analysis (BIA to measure body composition and determine the association between prostate cancer and total body fat mass (FM fat-free mass (FFM, and percent body fat (%BF, and which body composition measure mediated the association between BMI or waist circumference (WC with prostate cancer. Methods The study used a multi-centered recruitment protocol targeting men scheduled for prostate biopsy. Men without prostate cancer at biopsy served as controls (n = 1057. Prostate cancer cases were classified as having Gleason 6 (n = 402, Gleason 7 (n = 272, or Gleason 8-10 (n = 135 cancer. BIA and body size measures were ascertained by trained staff prior to diagnosis, and clinical and comorbidity status were determined by chart review. Analyses utilized multivariable linear and logistic regression. Results Body size and composition measures were not significantly associated with low-grade (Gleason 6 prostate cancer. In contrast, BMI, WC, FM, and FFM were associated with an increased risk of Gleason 7 and Gleason 8-10 prostate cancer. Furthermore, BMI and WC were no longer associated with Gleason 8-10 (ORBMI = 1.039 (1.000, 1.081, ORWC = 1.016 (0.999, 1.033, continuous scales with control for total body FFM (ORBMI = 0.998 (0.946, 1.052, ORWC = 0.995 (0.974, 1.017. Furthermore, increasing FFM remained significantly associated with Gleason 7 (ORFFM = 1.030 (1.008, 1.052 and Gleason 8-10 (ORFFM = 1.044 (1.014, 1.074 after controlling for FM. Conclusions Our results

Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer; Report From the 2016 Coffey-Holden Prostate Cancer Academy Meeting.

Science.gov (United States)

Miyahira, Andrea K; Roychowdhury, Sameek; Goswami, Sangeeta; Ippolito, Joseph E; Priceman, Saul J; Pritchard, Colin C; Sfanos, Karen S; Subudhi, Sumit K; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2017-02-01

The 2016 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer," was held from June 23 to June 26, 2016, in Coronado, California. For the 4th year in a row, the Prostate Cancer Foundation (PCF) hosted the CHPCA Meeting, a think tank-structured scientific conference, which focuses on a specific topic of critical unmet need on the biology and treatment of advanced prostate cancer. The 2016 CHPCA Meeting was attended by 71 investigators from prostate cancer and other fields, who discussed the biology, study methodologies, treatment strategies, and critical unmet needs concerning metastatic prostate cancer, with the ultimate goal of advancing strategies to treat and eliminate this disease. The major topics of discussion included: the molecular landscape and molecular heterogeneity of metastatic prostate cancer, the role of the metastatic microenvironment, optimizing immunotherapy in metastatic prostate cancer, learning from exceptional responders and non-responders, targeting DNA repair deficiency in advanced prostate cancer, developing and applying novel biomarkers and imaging techniques, and potential roles for the microbiome in prostate cancer. This article reviews the topics presented and discussions held at the CHPCA Meeting, with a focus on the unknowns and next steps needed to advance our understanding of the biology and most effective treatment strategies for metastatic prostate cancer. Prostate 77:123-144, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

Science.gov (United States)

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.

Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer.

Science.gov (United States)

Rhodes, Daniel R; Sanda, Martin G; Otte, Arie P; Chinnaiyan, Arul M; Rubin, Mark A

2003-05-07

Molecular signatures in cancer tissue may be useful for diagnosis and are associated with survival. We used results from high-density tissue microarrays (TMAs) to define combinations of candidate biomarkers associated with the rate of prostate cancer progression after radical prostatectomy that could identify patients at high risk for recurrence. Fourteen candidate biomarkers for prostate cancer for which antibodies are available included hepsin, pim-1 kinase, E-cadherin (ECAD; cell adhesion molecule), alpha-methylacyl-coenzyme A racemase, and EZH2 (enhancer of zeste homolog 2, a transcriptional repressor). TMAs containing more than 2000 tumor samples from 259 patients who underwent radical prostatectomy for localized prostate cancer were studied with these antibodies. Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression, including tumor stage, Gleason score, and prostate-specific antigen (PSA) level. Recurrence was defined as a postsurgery PSA level of more than 0.2 ng/mL. All statistical tests were two-sided. Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer. EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence in a training set of 103 patients (relative risk [RR] = 2.52, 95% confidence interval [CI] = 1.09 to 5.81; P =.021), in a validation set of 80 patients (RR = 3.72, 95% CI = 1.27 to 10.91; P =.009), and in the combined set of 183 patients (RR = 2.96, 95% CI = 1.56 to 5.61; P<.001). EZH2:ECAD status was statistically significantly associated with disease recurrence even after adjusting for clinical parameters, such as tumor stage, Gleason score, and PSA level (hazard ratio = 3.19, 95% CI = 1.50 to 6.77; P =.003). EZH2:ECAD status was statistically significantly associated

CD147 and Prostate Cancer: A Systematic Review and Meta-Analysis.

Directory of Open Access Journals (Sweden)

Fei Peng

Full Text Available Prostate cancer is one of the most common non-cutaneous malignancies in men. We aimed to systemically evaluate the relationship between the expression of CD147 in tissues and the clinicopathological features of prostate cancer.PubMed (1966-2016, EMBASE (1980-2016, the Cochrane Library (1996-2016, Web of Science (1945-2016, China National Knowledge Infrastructure (1982-2016, and the WanFang databases (1988-2016 were searched. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Meta-analysis was performed by using Review Manager 5.3 and Stata 13.0. A total of 12591 prostate cancer patients from 14 studies were included. The results of the meta-analysis showed that there were significant differences in the positive expression rate in the following comparisons: prostatic cancer tissues vs. normal prostate tissues (odds ratio [OR] = 26.93, 95% confidence interval [CI] 7.95-91.20, P < 0.00001, prostatic cancer tissues vs. benign prostatic hyperplasia tissues (OR = 20.54, 95% CI 8.20-51.44, P < 0.00001, high Gleason score vs. low Gleason score (OR = 2.39, 95% CI 1.33-4.27, P = 0.03, TNM III to IV vs. TNM I to II (OR = 9.95, 95% CI 4.96-19.96, P < 0.00001, low or moderate differentiation vs. high differentiation (OR = 8.12, 95% CI 3.69-17.85, P < 0.00001, lymph node metastasis vs. non-lymph node metastasis (OR = 4.31, 95% CI 1.11-16.71, P = 0.03, and distant metastasis vs. non-distant metastasis (OR = 8.90, 95% CI 3.24-24.42, P < 0.00001.The CD147 positive expression rate was closely related to the clinical characteristics of prostate cancer, but more research is needed to confirm the findings owing to the results of the subgroups.

Correlation between PSA, bone scan and Gleason score in patients with prostate cancer

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Mendoza, G.; Cano, R.; Morales, R.; Munoz, L.; Saavedra, P.; Aguilar, C.

2004-01-01

Full text: Prostate cancer is the third most common cancer among Peruvian males. Although radionuclide bone scans (BS) are frequently recommended as part of the staging evaluation for newly diagnosed prostate cancer, most scans are negative for metastases. It has been suggested that a routine bone scan is unnecessary in recently diagnosed prostate cancer if serum PSA is under 10 ng/mL. We hypothesized that Gleason score plus prostate-specific antigen (PSA), could predict for a positive bone scan (better that PSA alone), and that a low - risk group of patients could be identified in whom BS might be omitted. All patients who had both pathologic review of their prostate cancer biopsies and radionuclide BS at our institution from 1/93 to 12/95 were studied. Gleason score, PSA, and bone scan (Soloway Index) were determined in 165 patients. Bivariate analysis using chi (x2) was performed. The mean age of the 165 patients was 71.3 years, 109/165 (66.1%) had a 7-9 Gleason score and only 9/165 (5.5%) were well differentiated prostrate cancer. 82/165 (49.7%) had negative BS. When classifying patients according to their histological grade, the PSA median values were 11.8 ng/mL, 74.8 ng/mL and 116.4 ng/mL in well, median and poorly differentiated prostate cancer respectively. Using a cut off point of 10 ng/mL of PSA, the probability of having a positive BS in Gleason 7, 8 and 9 tumors were 0.109, 0.121 and 0.133 respectively. By using a cut off point of 20 ng/mL of PSA the possibility to have a positive BS in Gleason 7, 8 and 9 tumours were 0.182, 0.206 and 0.224 respectively. Gleason score plus PSA were independent predictors for a positive radionuclide BS in newly diagnosed prostate cancer patients. Considering that most of our patients have Gleason 7-9, the risk of bone metastases despite PSA levels between 10 - 20 ng/mL is not negligible. In our opinion, it is important to continue including bone scan in the staging assessment of prostate cancer. (author)

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

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Rybicki, B A; Kryvenko, O N; Wang, Y; Jankowski, M; Trudeau, S; Chitale, D A; Gupta, N S; Rundle, A; Tang, D

2016-06-01

Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I-III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27-0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15-10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40-6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09-3.35). In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and

Prostate-Specific Antigen-Based Screening for Prostate Cancer: Evidence Report and Systematic Review for the US Preventive Services Task Force.

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Fenton, Joshua J; Weyrich, Meghan S; Durbin, Shauna; Liu, Yu; Bang, Heejung; Melnikow, Joy

2018-05-08

Prostate cancer is the second leading cause of cancer death among US men. To systematically review evidence on prostate-specific antigen (PSA)-based prostate cancer screening, treatments for localized prostate cancer, and prebiopsy risk calculators to inform the US Preventive Services Task Force. Searches of PubMed, EMBASE, Web of Science, and Cochrane Registries and Databases from July 1, 2011, through July 15, 2017, with a surveillance search on February 1, 2018. English-language reports of randomized clinical trials (RCTs) of screening; cohort studies reporting harms; RCTs and cohort studies of active localized cancer treatments vs conservative approaches (eg, active surveillance, watchful waiting); external validations of prebiopsy risk calculators to identify aggressive cancers. One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Prostate cancer and all-cause mortality; false-positive screening results, biopsy complications, overdiagnosis; adverse effects of active treatments. Random-effects meta-analyses were conducted for treatment harms. Sixty-three studies in 104 publications were included (N = 1 904 950). Randomization to PSA screening was not associated with reduced risk of prostate cancer mortality in either a US trial with substantial control group contamination (n = 76 683) or a UK trial with low adherence to a single PSA screen (n = 408 825) but was associated with significantly reduced prostate cancer mortality in a European trial (n = 162 243; relative risk [RR], 0.79 [95% CI, 0.69-0.91]; absolute risk reduction, 1.1 deaths per 10 000 person-years [95% CI, 0.5-1.8]). Of 61 604 men screened in the European trial, 17.8% received false-positive results. In 3 cohorts (n = 15 136), complications requiring hospitalization occurred in 0.5% to 1.6% of men undergoing biopsy after abnormal screening findings. Overdiagnosis was estimated to occur in 20.7% to 50

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

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Wang, K

2014-01-01

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

TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas.

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Lotan, Tamara L; Toubaji, Antoun; Albadine, Roula; Latour, Mathieu; Herawi, Mehsati; Meeker, Alan K; DeMarzo, Angelo M; Platz, Elizabeth A; Epstein, Jonathan I; Netto, George J

2009-03-01

Ductal adenocarcinoma of the prostate is an unusual subtype that may be associated with a more aggressive clinical course, and is less responsive to conventional therapies than the more common prostatic acinar adenocarcinoma. However, given its frequent association with an acinar component at prostatectomy, some have challenged the concept of prostatic ductal adenocarcinoma as a distinct clinicopathologic entity. We studied the occurrence of the TMPRSS2-ERG gene fusion, in 40 surgically resected ductal adenocarcinoma cases, and in their associated acinar component using fluorescence in situ hybridization. A group of 38 'pure' acinar adenocarcinoma cases matched with the ductal adenocarcinoma group for pathological grade and stage was studied as a control. Compared with the matched acinar adenocarcinoma cases, the TMPRSS2-ERG gene fusion was significantly less frequently observed in ductal adenocarcinoma (45 vs 11% of cases, P=0.002, Fisher's exact test). Here, of the ductal adenocarcinoma cases with the gene fusion, 75% were fused through deletion, and the remaining case was fused through translocation. The TMPRSS2-ERG gene fusion was also rare in the acinar component of mixed ductal-acinar tumors when compared with the pure acinar adenocarcinoma controls (5 vs 45%, P=0.001, Fisher's exact test). In 95% of the ductal adenocarcinoma cases in which a concurrent acinar component was analyzed, there was concordance for presence/absence of the TMPRSS2-ERG gene fusion between the different histologic subtypes. In the control group of pure acinar adenocarcinoma cases, 59% were fused through deletion and 41% were fused through translocation. The presence of the TMPRSS2-ERG gene fusion in some cases of prostatic ductal adenocarcinoma supports the concept that ductal adenocarcinoma and acinar adenocarcinoma may be related genetically. However, the significantly lower rate of the gene fusion in pure ductal adenocarcinoma cases underscores the fact that genetic and biologic

Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

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2017-10-01

AWARD NUMBER: W81XWH-16-1-0737 TITLE: Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer 5b. GRANT NUMBER W81XWH...that there exist distinctive molecular correlates of PTEN loss in the context of ETS-negative versus ETS-positive human prostate cancers and that

Epigenetics in prostate cancer.

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Albany, Costantine; Alva, Ajjai S; Aparicio, Ana M; Singal, Rakesh; Yellapragada, Sarvari; Sonpavde, Guru; Hahn, Noah M

2011-01-01

Prostate cancer (PC) is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG) rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a "normal" epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

Prostate Cancer Rates by Race and Ethnicity

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... HPV-Associated Lung Ovarian Skin Uterine Cancer Home Prostate Cancer Rates by Race and Ethnicity Language: English (US) ... Tweet Share Compartir The rate of men getting prostate cancer or dying from prostate cancer varies by race ...

The characteristics and spatial distributions of initially missed and rebiopsy-detected prostate cancers

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Myung-Won You

2016-07-01

Full Text Available Purpose: The purpose of this study was to analyze the characteristics of initially missed and rebiopsy-detected prostate cancers following 12-core transrectal biopsy. Methods: A total of 45 patients with prostate cancers detected on rebiopsy and 45 patients with prostate cancers initially detected on transrectal ultrasound-guided biopsy were included in the study. For result analysis, the prostate was divided into six compartments, and the cancer positive rates, estimated tumor burden, and agreement rates between biopsy and surgical specimens, along with clinical data, were evaluated. Results: The largest mean tumor burden was located in the medial apex in both groups. There were significantly more tumors in this location in the rebiopsy group (44.9% than in the control group (30.1%, P=0.015. The overall sensitivity of biopsy was significantly lower in the rebiopsy group (22.5% vs. 43.4%, P<0.001. The agreement rate of cancer positive cores between biopsy and surgical specimens was significantly lower in the medial apex in the rebiopsy group compared with that of the control group (50.0% vs. 65.6%, P=0.035. The cancer positive rates of target biopsy cores and premalignant lesions in the rebiopsy group were 63.1% and 42.3%, respectively. Conclusion: Rebiopsy-detected prostate cancers showed different spatial distribution and lower cancer detection rate of biopsy cores compared with initially diagnosed cancers. To overcome lower cancer detection rate, target biopsy of abnormal sonographic findings, premalignant lesions and medial apex which revealed larger tumor burden would be recommended when performing rebiopsy.

Prostate cancer outcome in Burkina Faso

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Yameogo Clotaire

2011-09-01

Full Text Available Abstract Introduction African-American black men race is one of non-modifiable risk factors confirmed for prostate cancer. Many studies have been done in USA among African- American population to evaluate prostate cancer disparities. Compared to the USA very few data are available for prostate cancer in Sub-Saharan African countries. The objective of this study was to describe incident prostate cancer (PC diagnosis characteristics in Burkina Faso (West Africa. Methods We performed a prospective non randomized patient’s cohort study of new prostate cancer cases diagnosed by histological analysis of transrectal prostate biopsies in Burkina Faso. Study participants included 166 patients recruited at the urology division of the university hospital of Ouagadougou. Age of the patients, clinical symptoms, digital rectal examination (DRE result, serum prostate-specific antigen (PSA level, histological characteristics and TNM classification were taking in account in this study. Results 166 transrectal prostate biopsies (TRPB were performed based on high PSA level or abnormal DRE. The prostate cancer rate on those TRPB was 63, 8 % (n=106. The mean age of the patients was 71, 5 years (52 to 86. Urinary retention was the first clinical patterns of reference in our institution (55, 7 %, n = 59. Most patients, 56, 6 % (n = 60 had a serum PSA level over than 100 ng/ml. All the patients had adenocarcinoma on histological study of prostate biopsy cores. The majority of cases (54, 7 % n = 58 had Gleason score equal or higher than 7. Conclusion Prostate cancer is diagnosed at later stages in our country. Very high serum PSA level and poorly differentiated tumors are the two major characteristics of PC at the time of diagnosis.

Prevalence of benign prostatic hyperplasia and prostate cancer and its relative factors in Lanzhou

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Zhong Ganping; Wang Jiaji; Yue Zhongjin; Chen Xuehong

2003-01-01

To investigate the benign prostatic hyperplasia (BPH) and prostate cancer in Lanzhou, an investigation of the incidence of BPH and prostate cancer in 1356 male inhabitants over 50 years of age has been carried out including I-PSS, life quality (L), volume of prostate (V) and digital rectal examination. Plasma testosterone (T) and prostate specific antigen (PSA) were assayed in 145 cases. The incidence of BPH was 35.03%, being 41.04% in urban and 30.05% in rural inhabitants. The increase of BPH has been higher in urban inhabitants (P<0.05). The incidence of prostate cancer was 2.05%, being 3.09% in urban and 2.02% in rural inhabitants, the increase of prostate cancer has been higher in urban inhabitants (P< 0.05). A significant increase of prostate specific antigen was noted in prostate cancer patients (P<0.05). Conclusions: The increase of BPH and prostate cancer has been higher in urban inhabitants. The age, diet and residential areas might associate with a higher incidence of BPH and prostate cancer

Tea, coffee and prostate cancer.

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Lee, Andy H; Fraser, Michelle L; Binns, Colin W

2009-02-01

Worldwide, prostate cancer has the second highest incidence of all cancers in males with incidence and mortality being much higher in affluent developed countries. Risk and progression of the disease may be linked to both genetic and environmental factors, especially dietary factors. Tea and coffee are two of the most popular beverages in the world and have been investigated for possible effects on health outcomes, including cancer. However, very little dietary advice for their consumption exists. The evidence for a relationship between coffee or tea consumption and prostate cancer is reviewed in this paper. While current evidence indicates that coffee is a safe beverage, its consumption probably has no relationship with prostate cancer. Tea, especially green tea, has shown some potential in the prevention of prostate cancer. While evidence from epidemiologic studies is currently inconclusive, strong evidence has emerged from animal and in vitro studies. We also consider what level of evidence is required to make recommendations for preventive measures to the public. Although evidence on the relationship between coffee, tea and prostate cancer is not complete, we consider it strong enough to recommend tea as a healthier alternative to coffee.

Bisphenol A and other environmental risk factors for prostate cancer in Hong Kong.

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Tse, Lap Ah; Lee, Priscilla Ming Yi; Ho, Wing Ming; Lam, Augustine Tsan; Lee, Man Kei; Ng, Simon Siu Man; He, Yonghua; Leung, Ka-Sing; Hartle, Jennifer C; Hu, Howard; Kan, Haidong; Wang, Feng; Ng, Chi Fai

2017-10-01

Environmental exposures are contributing factors to prostate cancer etiology, but these remain unclear. We aimed to document the associations between environmental risk factors and prostate cancer in Chinese, with special reference to bisphenol A (BPA). We recruited 431 newly diagnosed prostate cancer cases and 402 age-matched controls from Prince of Wales Hospital in Hong Kong. We obtained each participant's clinical data and epidemiological information on chronic BPA exposure and other environmental risk factors (e.g., dietary habits, occupation and shift work) using a standard questionnaire. A new assessment tool of environmental BPA exposure was developed and replicated. Multiple logistic regression analysis was performed to examine odds ratio (OR) and 95% confidence interval (95% CI) for the association of prostate cancer with a novel cumulative BPA exposure index (CBPAI) and other environmental risk factors. Weekly consumption of deep fried food (OR=1.85, 95% CI: 1.15-2.95) and pickled vegetable (OR=1.87, 95% CI: 1.07-3.28) was significantly associated with excessive prostate cancer risk. Prostate cancer was positively associated with nightshift work (OR=1.76, 95% CI: 1.07-2.89) and it was negatively associated with green tea drinking (OR=0.56, 95% CI: 0.34-0.91). There was a positive exposure-response relationship between CBPAI and prostate cancer, with the greatest and significant risk in the high versus reference category (OR=1.57, 95% CI: 1.01-2.44). Frequent consumption of deep fried food and pickled vegetable, non-habitual green tea drinking and nightshift work are the contributing risk factors to prostate cancer in Hong Kong Chinese. More importantly, this study provides the first epidemiological evidence on carcinogenicity of BPA on the human prostate. Copyright © 2017. Published by Elsevier Ltd.

Development of New Treatments for Prostate Cancer

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

2005-02-01

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

Neuroendocrine differentiation in prostate cancer – a review

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R. Popescu

2015-12-01

Full Text Available Objectives: This review aims to provide practicing clinicians with the most recent knowledge of the biological nature of prostate cancer especially the information regarding neuroendocrine differentiation. Methods: Review of the literature using PubMed search and scientific journal publications. Results: Much progress has been made towards an understanding of the development and progression of prostate cancer. The prostate is a male accessory sex gland which produces a fraction of seminal fluid. The normal human prostate is composed of a stromal compartment (which contains: nerves, fibroblast, smooth muscle cells, macrophages surrounding glandular acins – epithelial cells. Neuroendocrine cells are one of the epithelial populations in the normal prostate and are believed to provide trophic signals trough the secretion of neuropeptides that diffuse and influence surrounding epithelial cells. Prostate cancer is the most frequently diagnosed malignancy in men. In prostate cancer, neuroendocrine cells can stimulate growth of surrounding prostate adenocarcinoma cells (proliferation of neighboring cancer cells in a paracrine manner by secretion of neuroendocrine products. Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer. The detection of neuroendocrine prostate cancer has clinical implications. These patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. Conclusion: This review shows the need to improve our knowledge regarding diagnostic and treatment methods of the Prostate Cancer, especially cancer cells with neuroendocrine phenotype.

New Prostate Cancer Treatment Target

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

The value and limitations of contrast-enhanced transrectal ultrasonography for the detection of prostate cancer

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Zhao, Han-Xue, E-mail: zhaohx861@163.com [Department of Diagnostic Ultrasound, Beijing Tongren Hospital, Capital Medical University, Dong-Jiao-Min-Xiang, Dong Cheng District, Beijing 100730 (China); Xia, Chun-Xia, E-mail: star9901482@163.com [Department of Diagnostic Ultrasound, Beijing Tongren Hospital, Capital Medical University, Dong-Jiao-Min-Xiang, Dong Cheng District, Beijing 100730 (China); Yin, Hong-Xia, E-mail: hongxia_yin79@yahoo.com.cn [Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Dong-Jiao-Min-Xiang, Dong Cheng District, Beijing 100730 (China); Guo, Ning, E-mail: ningguo99@sina.com.cn [Department of Diagnostic Ultrasound, Beijing Tongren Hospital, Capital Medical University, Dong-Jiao-Min-Xiang, Dong Cheng District, Beijing 100730 (China); Zhu, Qiang, E-mail: qzhutrhos@gmail.com [Department of Diagnostic Ultrasound, Beijing Tongren Hospital, Capital Medical University, Dong-Jiao-Min-Xiang, Dong Cheng District, Beijing 100730 (China)

2013-11-01

Objectives: To evaluate the role of contrast-enhanced transrectal ultrasonography (CE-TRUS) for detecting prostate carcinoma. Methods: Sixty-five patients with elevated serum prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE) were assessed using transrectal ultrasound (TRUS) and CE-TRUS. In all the patients, CE-TRUS was performed with intravenous injection of contrast agent (SonoVue, 2.4 ml) before biopsy. The cancer detection rates of the two techniques were compared. False-positive and false-negative findings related to CE-TRUS were analyzed in comparison to the pathological results of biopsy or radical prostatectomy. The targeted biopsy to abnormal CE-TRUS areas was also compared to systematic biopsy. Results: Prostate cancer was detected in 29 of the 65 patients. CE-TRUS showed rapid focal enhancement or asymmetric vessels of peripheral zones in 28 patients; 23 of them had prostate cancer. CE-TRUS had 79.3% sensitivity, compared to 65.5% of TRUS (P < 0.05). There were five false-positive and six false-negative findings from CE-TRUS. Benign prostate hyperplasia, and acute and chronic prostatitis were important causes related to the false-positive results of CE-TRUS. Prostate cancer originating from the transition zone or peripheral zone with lower PSA levels, small-size foci, and moderately or well-differentiated tumor was missed by CE-TRUS. The cancer detection rate of targeted biopsy (75%, 33/44 cores) was significantly higher than one of systematic biopsy (48.2%, 162/336) in those 28 cases (P < 0.05). In addition, no significant correlation was found between the cancer detection rate with CE-TRUS and serum PSA levels. Conclusion: CE-TRUS may improve the detection rate of prostate cancer through targeted biopsy of contrast-enhanced abnormalities. Our findings indicate that systematic biopsies should not be eliminated on the basis of false-positive and false-negative findings related to CE-TRUS.

Prostate-specific antigen density: correlation with histological diagnosis of prostate cancer, benign prostatic hyperplasia and prostatitis

NARCIS (Netherlands)

van Iersel, M. P.; Witjes, W. P.; de la Rosette, J. J.; Oosterhof, G. O.

1995-01-01

To assess the additional value of prostate-specific antigen density in the diagnosis of prostate cancer in patients who undergo prostate biopsies. The study comprised 376 patients with symptoms of prostatism who were undergoing prostate biopsy. Digital rectal examination (DRE) and transrectal

The influence of obesity in patients with prostate cancer - Review of the literature

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Maximilien C. Goris Gbenou

2013-04-01

Full Text Available ABSTRACTRecent studies have demonstrated an association between higher body mass index and increased aggressiveness in prostate cancer.The present narrative review, based on a search of Medline® and Embase® databases from October 1982 to October 2012, explores the relationship between higher body mass index and localized prostate cancer. In particular, the current epidemiological and mechanistic evidence for interactions between obesity and prostate cancer are discussed.Obesity is associated with alterations in androgen levels, decreased sex hormone binding globulin and increased estrogen levels, insulin resistance, hyperglycemia, alterations in plasma lipoprotein levels particularly raised triglycerides and reduced high density lipoprotein, decreased levels of adiponectin, and increased levels of circulating insulin-growth factor- 1, leptin and dietary saturated fats. Obese men have more aggressive prostate cancer with a greater percentage prostate involvement, increased tumor volume and higher-grade disease, enlarged prostates, high prostate-specific antigen levels, increased risk of having positive margins and recurrence.Moreover, there is strong evidence of the beneficial effects of functional foods for the treatment of obesity. Additionally, an increasing number of studies support that obesity-induced inflammation plays an important role in the development of obesity-related pathologies. Despite, the beneficial role of nutriment in prostate cancer control, the use of functional foods in prostate cancer is not recommended for lack of large epidemiological studies.This data supports the hypothesis that obese men have more aggressive prostate cancers and that the obesity is a modifiable risk factor of prostate cancer.Key Words: prostate cancer, metabolic syndrome, obesity, high BMI, risk factor, diet, functional foods.

1H-MRSI of prostate cancer: The relationship between metabolite ratio and tumor proliferation

International Nuclear Information System (INIS)

Wang Xizhen; Wang Bin; Gao Zhiqin; Liu Jingang; Liu Zuoqin; Niu Qingliang; Sun Zhenkui; Yuan Yuxiao

2010-01-01

Purpose: To investigate whether 1H-MRSI can be used to predict the proliferative activity of prostate cancer. Materials and methods: Thirty-eight patients with prostate cancer (PCa) and thirty-three patients with benign prostate hyperplasia (BPH) were included in this study. Patients were examined in supine position using a 1.5 T superconducting magnetic scanner equipped with a pelvic phased-array multi-coil and CSI-3D-PROSTATE sequence. Commercial software was used to acquire and process MR spectroscopic imaging data. Mean (Cho + Cr)/Cit ratios of PCa, BPH, and peripheral zone (PZ) were calculated. Cellularity of PCa was recorded based on hematoxylin and eosin staining. PCNA was detected using immunohistochemical techniques. Results: The mean (Cho + Cr)/Cit ratio of the peripheral zone (0.38 ± 0.09) was lower than that of BPH (0.51 ± 0.19) (P < 0.05). The average value of (Cho + Cr)/Cit ratio of prostate cancer was 3.98 ± 0.12. The (Cho + Cr)/Cit ratio of prostate cancer was higher than that of the peripheral zone and BPH (P < 0.05). The cellularity and PCNA LI of prostate cancer were 12.90 ± 4.07% and 72.1 ± 19.01%, respectively. The (Cho + Cr)/Cit ratio of prostate cancer positively correlated with tumor cellularity (r = 0.582, P = 0.027) and PCNA LI (r = 0.495, P = 0.022). Conclusion: The (Cho + Cr)/Cit ratio of PCa can reveal the differences in proliferative activity between PCa and BPH. MRSIs are therefore able to predict the proliferative rate of variously differentiated prostate cancers.

Prostate cancer and social media.

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Loeb, Stacy; Katz, Matthew S; Langford, Aisha; Byrne, Nataliya; Ciprut, Shannon

2018-04-11

The use of social media is increasing globally and is employed in a variety of ways in the prostate cancer community. In addition to their use in research, advocacy, and awareness campaigns, social media offer vast opportunities for education and networking for patients with prostate cancer and health-care professionals, and many educational resources and support networks are available to patients with prostate cancer and their caregivers. Despite the considerable potential for social media to be employed in the field of prostate cancer, concerns remain - particularly regarding the maintenance of patient confidentiality, variable information quality, and possible financial conflicts of interest. A number of professional societies have, therefore, issued guidance regarding social media use in medicine. Social media are used extensively in other cancer communities, particularly among patients with breast cancer, and both the quantity and type of information available are expected to grow in the future.

Emerging biomarkers in the diagnosis of prostate cancer

Directory of Open Access Journals (Sweden)

Filella X

2018-05-01

Full Text Available Xavier Filella, Esther Fernández-Galan, Rosa Fernández Bonifacio, Laura Foj Department of Biochemistry and Molecular Genetics (CDB, Hospital Clínic, IDIBAPS, Barcelona, Catalonia, Spain Abstract: Prostate cancer (PCa is the second most common cancer in men worldwide. A large proportion of PCa are latent, never destined to progress or affect the patients’ life. It is of utmost importance to identify which PCa are destined to progress and which would benefit from an early radical treatment. Prostate-specific antigen (PSA remains the most used test to detect PCa. Its limited specificity and an elevated rate of overdiagnosis are the main problems associated with PSA testing. New PCa biomarkers have been proposed to improve the accuracy of PSA in the management of early PCa. Commercially available biomarkers such as PCA3 score, Prostate Health Index (PHI, and the four-kallikrein panel are used with the purpose of reducing the number of unnecessary biopsies and providing information related to the aggressiveness of the tumor. The relationship with PCa aggressiveness seems to be confirmed by PHI and the four-kallikrein panel, but not by the PCA3 score. In this review, we also summarize new promising biomarkers, such as PSA glycoforms, TMPRSS2:ERG fusion gene, microRNAs, circulating tumor cells, androgen receptor variants, and PTEN gene. All these emerging biomarkers could change the management of early PCa, offering more accurate results than PSA. Nonetheless, large prospective studies comparing these new biomarkers among them are required to know their real value in PCa detection and prognosis. Keywords: prostate cancer, PSA, PHI, four-kallikrein panel, PCA3, miRNAs

Inflammatory Genetic Markers of Prostate Cancer Risk

International Nuclear Information System (INIS)

Tindall, Elizabeth A.; Hayes, Vanessa M.; Petersen, Desiree C.

2010-01-01

Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk

Inflammatory Genetic Markers of Prostate Cancer Risk

Energy Technology Data Exchange (ETDEWEB)

Tindall, Elizabeth A.; Hayes, Vanessa M. [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia); University of New South Wales, Kensington Campus, Sydney, NSW 2052 (Australia); Petersen, Desiree C., E-mail: dpetersen@ccia.unsw.edu.au [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia)

2010-06-08

Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk.

The relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance

NARCIS (Netherlands)

van Poppel, Hein; Haese, Alexander; Graefen, Markus; de la Taille, Alexandre; Irani, Jacques; de Reijke, Theo; Remzi, Mesut; Marberger, Michael

2012-01-01

OBJECTIVE To evaluate the relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance. PATIENTS AND METHODS Clinical data from two multi-centre European open-label, prospective studies evaluating the clinical utility of the PCA3 assay in guiding initial and repeat biopsy

Evaluation of the ESUR PI-RADS scoring system for multiparametric MRI of the prostate with targeted MR/TRUS fusion-guided biopsy at 3.0 Tesla.

Science.gov (United States)

Roethke, M C; Kuru, T H; Schultze, S; Tichy, D; Kopp-Schneider, A; Fenchel, M; Schlemmer, H-P; Hadaschik, B A

2014-02-01

To evaluate the Prostate Imaging Reporting and Data System (PI-RADS) proposed by the European Society of Urogenital Radiology (ESUR) for detection of prostate cancer (PCa) by multiparametric magnetic resonance imaging (mpMRI) in a consecutive cohort of patients with magnetic resonance/transrectal ultrasound (MR/TRUS) fusion-guided biopsy. Suspicious lesions on mpMRI at 3.0 T were scored according to the PI-RADS system before MR/TRUS fusion-guided biopsy and correlated to histopathology results. Statistical correlation was obtained by a Mann-Whitney U test. Receiver operating characteristics (ROC) and optimal thresholds were calculated. In 64 patients, 128/445 positive biopsy cores were obtained out of 95 suspicious regions of interest (ROIs). PCa was present in 27/64 (42%) of the patients. ROC results for the aggregated PI-RADS scores exhibited higher areas under the curve compared to those of the Likert score. Sensitivity/Specificity for the following thresholds were calculated: 85 %/73 % and 67 %/92 % for PI-RADS scores of 9 and 10, respectively; 85 %/60 % and 56 %/97 % for Likert scores of 3 and 4, respectively [corrected. The standardised ESUR PI-RADS system is beneficial to indicate the likelihood of PCa of suspicious lesions on mpMRI. It is also valuable to identify locations to be targeted with biopsy. The aggregated PI-RADS score achieved better results compared to the single five-point Likert score. • The ESUR PI-RADS scoring system was evaluated using multiparametric 3.0-T MRI. • To investigate suspicious findings, transperineal MR/TRUS fusion-guided biopsy was used. • PI-RADS can guide biopsy locations and improve detection of clinically significant cancer. • Biopsy procedures can be optimised, reducing unnecessary negative biopsies for patients. • The PI-RADS scoring system may contribute to more effective prostate MRI.

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

Science.gov (United States)

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

Epigenetics in Prostate Cancer

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Costantine Albany

2011-01-01

Full Text Available Prostate cancer (PC is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG rich sequence islands within gene promoter regions is widespread during neoplastic transformation of prostate cells, suggesting that treatment-induced restoration of a “normal” epigenome could be clinically beneficial. Histone modification leads to altered tumor gene function by changing chromosome structure and the level of gene transcription. The reversibility of epigenetic aberrations and restoration of tumor suppression gene function have made them attractive targets for prostate cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases.

Vitamins, metabolomics, and prostate cancer.

Science.gov (United States)

Mondul, Alison M; Weinstein, Stephanie J; Albanes, Demetrius

2017-06-01

How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk. Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes. Higher vitamin E serologic status is associated with lower prostate cancer risk, and vitamin E genetic variant data support this. By contrast, controlled vitamin E supplementation trials have had mixed results based on differing designs and dosages. Beta-carotene supplementation (in smokers) and higher circulating retinol and 25-hydroxy-vitamin D concentrations appear related to elevated prostate cancer risk. Our prospective metabolomic profiling of fasting serum collected 1-20 years prior to clinical diagnoses found reduced lipid and energy/TCA cycle metabolites, including inositol-1-phosphate, lysolipids, alpha-ketoglutarate, and citrate, significantly associated with lower risk of aggressive disease. Several active leads exist regarding the role of micronutrients and metabolites in prostate cancer carcinogenesis and risk. How vitamins D and A may adversely impact risk, and whether low-dose vitamin E supplementation remains a viable preventive approach, require further study.

Diagnostic utility of DTI in prostate cancer

International Nuclear Information System (INIS)

Guerses, Bengi; Tasdelen, Neslihan; Yencilek, Faruk; Kilickesmez, N. Ozguer; Alp, Turgut; Firat, Zeynep; Albayrak, M. Selami; Ulug, Aziz M.; Guermen, A. Nevzat

2011-01-01

Purpose: The aim of this study was to compare the diffusion tensor parameters of prostate cancer, prostatitis and normal prostate tissue. Materials and Methods: A total of 25 patients with the suspicion of prostate cancer were included in the study. MRI was performed with 3 T system (Intera Achieva, Philips Medical Systems, The Netherlands). T2 TSE and DTI with ss-EPI were obtained in each subject. TRUS-guided prostate biopsy was performed after the MRI examination. Images were analyzed by two radiologists using a special software system. ROI's were drawn according to biopsy zones which are apex, midgland, base and central zone on each sides of the gland. FA and ADC values in areas of cancer, chronic prostatitis and normal prostate tissue were compared using Student's t-test. Results: Histopathological analysis revealed carcinoma in 68, chronic prostatitis in 67 and was reported as normal in 65 zones. The mean FA of cancerous tissue was significantly higher (p < 0.01) than the FA of chronic prostatitis and normal gland. The mean ADC of cancerous tissue was found to be significantly lower (p < 0.01), compared with non-cancerous tissue. Conclusion: Decreased ADC and increased FA are compatible with the hypercellular nature of prostate tumors. These differences may increase the accuracy of MRI in the detection of carcinoma and to differentiate between cancer and prostatitis.

Diagnostic utility of DTI in prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Guerses, Bengi, E-mail: bengur0@yahoo.com [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Tasdelen, Neslihan [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Yencilek, Faruk [Yeditepe University Medical Faculty, Department of Urology, Istanbul (Turkey); Kilickesmez, N. Ozguer [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Alp, Turgut [Fatih Sultan Mehmet Training and Research Hospital, Division of Urology, Istanbul (Turkey); Firat, Zeynep [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey); Albayrak, M. Selami [Kartal Training and Research Hospital, Division of Urology, Istanbul (Turkey); Ulug, Aziz M. [Yeditepe University Department of Biomedical Engineering, Istanbul (Turkey); The Feinstein Institute for Medical Research, Manhasset, New York (United States); Guermen, A. Nevzat [Yeditepe University Medical Faculty, Department of Radiology, Istanbul (Turkey)

2011-08-15

Purpose: The aim of this study was to compare the diffusion tensor parameters of prostate cancer, prostatitis and normal prostate tissue. Materials and Methods: A total of 25 patients with the suspicion of prostate cancer were included in the study. MRI was performed with 3 T system (Intera Achieva, Philips Medical Systems, The Netherlands). T2 TSE and DTI with ss-EPI were obtained in each subject. TRUS-guided prostate biopsy was performed after the MRI examination. Images were analyzed by two radiologists using a special software system. ROI's were drawn according to biopsy zones which are apex, midgland, base and central zone on each sides of the gland. FA and ADC values in areas of cancer, chronic prostatitis and normal prostate tissue were compared using Student's t-test. Results: Histopathological analysis revealed carcinoma in 68, chronic prostatitis in 67 and was reported as normal in 65 zones. The mean FA of cancerous tissue was significantly higher (p < 0.01) than the FA of chronic prostatitis and normal gland. The mean ADC of cancerous tissue was found to be significantly lower (p < 0.01), compared with non-cancerous tissue. Conclusion: Decreased ADC and increased FA are compatible with the hypercellular nature of prostate tumors. These differences may increase the accuracy of MRI in the detection of carcinoma and to differentiate between cancer and prostatitis.

The study of diagnostic efficacy of MR spectroscopy in prostate cancer

International Nuclear Information System (INIS)

Ye Jintang; Guo Xuemei; Wang Xiaoying; Li Feiyu; Jiang Xuexiang

2009-01-01

Objective: To evaluate the diagnostic efficacy of MRS in prostate cancer based on sextant localization. Methods: There were 110 patients, 54 patients with pathologically confirmed prostate cancer and 56 patients confirmed non-prostate cancer proved by ultrasound guided systemic biopsy. The (choline + creatine) / citrate (CC/C) value in each voxel and ratio of positive voxel (PVR) in sextant localization were measured. The ROC analysis was used to evaluate the diagnostic efficacy of CC/C in single voxel and PVR in sextant localization. Results: There are 1673 and 2426 voxel in prostate cancer and non-prostate cancer respectively. The median of CC/C in cancer sextants was 2.137; the median of CC/C in noncancer sextants was 0.600. The difference of these two groups was statistically significant (Z = -41.7, P < 0.01). The diagnostic sensitivity was 81.4% (1362/1673), the specificity was 83.1% (2018/2426), and the accuracy was 82.4% [(1362 + 2018)/4099] for prostatic cancer with the cutoff point 0.911 of the CC/C value. The median of PVR in cancer sextants and noncancer sextants were 1 and 0 respectively, the difference of PVR was statistically significant ( Z =-11.7, P < 0.01). The diagnostic sensitivity was 77.5% (148/191), the specificity was 76.9% (247/321), and the accuracy was 77.1%[(148 + 247)/512] for prostatic cancer with the cutoff point 0.519 of the PVR. Conclusion: Detecting the cutoff point of the CC/C value in single voxel and the PVR in sextant localization may be valuable in the diagnosis of prostate cancer. (authors)

Prostate cancer trends in Asia.

Science.gov (United States)

Akaza, Hideyuki; Onozawa, Mizuki; Hinotsu, Shiro

2017-06-01

Differences in the incidence and mortality rates for prostate cancer between East and West are clearly defined, with higher rates in the West and lower rates in the East. Treatment methods are generally selected in accordance with general practice guidelines, but the current reality in Asia is that there is not sufficient clinical data to set Asia-specific guidelines for treatment. This leads to a situation whereby for the large part guidelines based on scientific evidence accumulated in Western countries are followed, but from time to time cases are encountered when such guidelines may not be considered to be the most appropriate for the case at hand. Although there is a relatively large volume of clinical evidence relating to endocrine therapy in Asia, the treatment choices and effects differ to those in the West. These regional differences are thought to be due to various factors, including not only differences in genetic background, but also distinct differences in the living and healthcare environments. If the differences between East and West in terms of trends in prostate cancer could be examined, with positive aspects being adopted and negative aspects being improved, this could also be expected to be of use in developing a better treatment strategy for prostate cancer. The exchanging of information on a broader, global level will enable improvements in prevention, diagnosis and treatment of prostate cancer. It is in pursuit of this objective that it is important to promote high-quality clinical trials and joint epidemiological studies in Asia and work to accumulate data that are comparable to data available in Western countries.

Key papers in prostate cancer.

Science.gov (United States)

Rodney, Simon; Shah, Taimur Tariq; Patel, Hitendra R H; Arya, Manit

2014-11-01

Prostate cancer is the most common cancer and second leading cause of death in men. The evidence base for the diagnosis and treatment of prostate cancer is continually changing. We aim to review and discuss past and contemporary papers on these topics to provoke debate and highlight key dilemmas faced by the urological community. We review key papers on prostate-specific antigen screening, radical prostatectomy versus surveillance strategies, targeted therapies, timing of radiotherapy and alternative anti-androgen therapeutics. Previously, the majority of patients, irrespective of risk, underwent radical open surgical procedures associated with considerable morbidity and mortality. Evidence is emerging that not all prostate cancers are alike and that low-grade disease can be safely managed by surveillance strategies and localized treatment to the prostate. The question remains as to how to accurately stage the disease and ultimately choose which treatment pathway to follow.

Psychosocial Consequences of Overdiagnostic of Prostate Cancer

DEFF Research Database (Denmark)

Nielsen, Sigrid Brisson

Psychosocial Consequences of Overdiagnostic of Prostate Cancer Sigrid Brisson Nielsen & John Brodersen Introduction In Denmark there are approximately 4400 men diagnosed with prostate cancer each year and nearly 1200 men dies of this disease yearly. The incidence of prostate cancer has increased...... for the past twenty years and make up 24 % of all cancer incidents in men. However, the mortality of prostate cancer has not changed in line with this increase. Empirical evidence shows that the increase in incidence of prostate cancer in Denmark without an increase in the mortality is mostly caused...... by opportunistic PSA screening in General Practice. It is recommended that men ≥ 60 year old diagnosed with prostate cancer and a Gleason score ≤ 6 are monitored with active surveillance. This is due to the probability of this type of cancer metastasizing is very small as approximately 90 % of them is assumed...

Cadmium burden and the risk and phenotype of prostate cancer

International Nuclear Information System (INIS)

Chen, Yi-Chun; Pu, Yeong S; Wu, Hsi-Chin; Wu, Tony T; Lai, Ming Kuen; Yang, Chun Y; Sung, Fung-Chang

2009-01-01

Studies on the association between prostate cancer and cadmium exposure have yielded conflicting results. This study explored cadmium burden on the risk and phenotype of prostate cancer in men with no evident environmental exposure. Hospital-based 261 prostate cancer cases and 267 controls with benign diseases were recruited from four hospitals in Taiwan. Demographic, dietary and lifestyle data were collected by standardized questionnaires. Blood cadmium (BCd) and creatinine-adjusted urine cadmium (CAUCd) levels were measured for each participant. Statistical analyses measured the prostate cancer risk associated with BCd and CAUCd separately, controlling for age, smoking and institution. BCd and CAUCd levels within cases were compared in relation to the disease stage and the Gleason score. High family income, low beef intake, low dairy product consumption and positive family history were independently associated with the prostate carcinogenesis. There was no difference in BCd levels between cases and controls (median, 0.88 versus 0.87 μg/l, p = 0.45). Cases had lower CAUCd levels than controls (median, 0.94 versus 1.40 μg/g creatinine, p = 0.001). However, cases with higher BCd and CAUCd levels tended to be at more advanced stages and to have higher Gleason scores. The prostate cancer cases with Gleason scores of ≥ 8 had an odds ratio of 2.89 (95% confidence interval 1.25-6.70), compared with patients with scores of 2-6. Higher CAUCd and BCd levels may be associated with advanced cancer phenotypes, but there was only a tenuous association between cadmium and prostate cancer

Cancer of the prostate - role of PSA

International Nuclear Information System (INIS)

Shittu, O.B.

1999-02-01

Since 1979 when prostate specific antigen (PSA), found in the cytoplasm of benign and malignant prostatic cells, was first purified, it has attained world wide popularity in prostate cancer detection. It is also a sensitive test for skeletal meta states from carcinoma of the prostate. Prostate cancer has become the number one cancer in men and constitutes 11% of all cancers. Approximately 50% of men over 50 years have symptoms referable to the lower urinary tract. 50% or more of patients at Ibadan present an advanced stage of the disease and are therefore not curable. Thus, lacking the skill to manage advanced manifestations, early detection and screening programs are the best means to reduce mortality due to prostate cancer

Roswell Park Cancer Institute/Howard University Prostate Cancer Scholars Program

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-14-1-0531 TITLE: Roswell Park Cancer Institute/Howard University Prostate Cancer Scholars Program PRINCIPAL INVESTIGATOR...Roswell Park Cancer Institute/Howard University Prostate Cancer 5a. CONTRACT NUMBER W81XWH-14-1-0531 Cancer Scholars Program 5b. GRANT NUMBER 5c...Prostate Cancer Scholars Program is designed to encourage students from under-represented minority groups to enter graduate training and ultimately

Plant-derived SAC domain of PAR-4 (Prostate Apoptosis Response 4 exhibits growth inhibitory effects in prostate cancer cells

Directory of Open Access Journals (Sweden)

Shayan eSarkar

2015-10-01

Full Text Available The gene Par-4 (Prostate Apoptosis Response 4 was originally identified in prostate cancer cells undergoing apoptosis and its product Par-4 showed cancer specific pro-apoptotic activity. Particularly, the SAC domain of Par-4 (SAC-Par-4 selectively kills cancer cells leaving normal cells unaffected. The therapeutic significance of bioactive SAC-Par-4 is enormous in cancer biology; however, its large scale production is still a matter of concern. Here we report the production of SAC-Par-4-GFP fusion protein coupled to translational enhancer sequence (5′ AMV and apoplast signal peptide (aTP in transgenic Nicotiana tabacum cv. Samsun NN plants under the control of a unique recombinant promoter M24. Transgene integration was confirmed by genomic DNA PCR, Southern and Northern blotting, Real-time PCR and Nuclear run-on assays. Results of Western blot analysis and ELISA confirmed expression of recombinant SAC-Par-4-GFP protein and it was as high as 0.15% of total soluble protein. In addition, we found that targeting of plant recombinant SAC-Par-4-GFP to the apoplast and endoplasmic reticulum (ER was essential for the stability of plant recombinant protein in comparison to the bacterial derived SAC-Par-4. Deglycosylation analysis demonstrated that ER-targeted SAC-Par-4-GFP-SEKDEL undergoes O-linked glycosylation unlike apoplast-targeted SAC-Par-4-GFP. Furthermore, various in vitro studies like mammalian cells proliferation assay (MTT, apoptosis induction assays, and NF-κB suppression suggested the cytotoxic and apoptotic properties of plant-derived SAC-Par-4-GFP against multiple prostate cancer cell lines. Additionally, pre-treatment of MAT-LyLu prostate cancer cells with purified SAC-Par-4-GFP significantly delayed the onset of tumor in a syngeneic rat prostate cancer model. Taken altogether, we proclaim that plant made SAC-Par-4 may become a useful alternate therapy for effectively alleviating cancer in the new era.

Punctuated evolution of prostate cancer genomes.

Science.gov (United States)

Baca, Sylvan C; Prandi, Davide; Lawrence, Michael S; Mosquera, Juan Miguel; Romanel, Alessandro; Drier, Yotam; Park, Kyung; Kitabayashi, Naoki; MacDonald, Theresa Y; Ghandi, Mahmoud; Van Allen, Eliezer; Kryukov, Gregory V; Sboner, Andrea; Theurillat, Jean-Philippe; Soong, T David; Nickerson, Elizabeth; Auclair, Daniel; Tewari, Ashutosh; Beltran, Himisha; Onofrio, Robert C; Boysen, Gunther; Guiducci, Candace; Barbieri, Christopher E; Cibulskis, Kristian; Sivachenko, Andrey; Carter, Scott L; Saksena, Gordon; Voet, Douglas; Ramos, Alex H; Winckler, Wendy; Cipicchio, Michelle; Ardlie, Kristin; Kantoff, Philip W; Berger, Michael F; Gabriel, Stacey B; Golub, Todd R; Meyerson, Matthew; Lander, Eric S; Elemento, Olivier; Getz, Gad; Demichelis, Francesca; Rubin, Mark A; Garraway, Levi A

2013-04-25

The analysis of exonic DNA from prostate cancers has identified recurrently mutated genes, but the spectrum of genome-wide alterations has not been profiled extensively in this disease. We sequenced the genomes of 57 prostate tumors and matched normal tissues to characterize somatic alterations and to study how they accumulate during oncogenesis and progression. By modeling the genesis of genomic rearrangements, we identified abundant DNA translocations and deletions that arise in a highly interdependent manner. This phenomenon, which we term "chromoplexy," frequently accounts for the dysregulation of prostate cancer genes and appears to disrupt multiple cancer genes coordinately. Our modeling suggests that chromoplexy may induce considerable genomic derangement over relatively few events in prostate cancer and other neoplasms, supporting a model of punctuated cancer evolution. By characterizing the clonal hierarchy of genomic lesions in prostate tumors, we charted a path of oncogenic events along which chromoplexy may drive prostate carcinogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts

Directory of Open Access Journals (Sweden)

Dietmar Abraham

2013-09-01

Full Text Available The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF. PlGF is a member of the vascular endothelial growth factor (VEGF family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.

Mitochondrial mutations drive prostate cancer aggression

DEFF Research Database (Denmark)

Hopkins, Julia F.; Sabelnykova, Veronica Y.; Weischenfeldt, Joachim

2017-01-01

Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer...... in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer....

Are food patterns associated with prostate cancer in Jamaican men: a preliminary report.

Science.gov (United States)

Jackson, Maria; Walker, Susan; Simpson, Candace; McFarlane-Anderson, Norma; Bennett, Franklyn

2009-02-10

Morbidity and mortality data highlight prostate cancer as the most commonly diagnosed neoplasm in Jamaican males. This report examines the association between dietary patterns and risk of prostate cancer in Jamaican men. Case-control study of 204 histologically confirmed newly diagnosed prostate cancer cases and 204 individually matched urology clinic controls in Jamaica, 2004 - 2007. Diet was assessed by food frequency questionnaire. Factor analysis yielded four dietary patterns: (i) a "healthy" pattern of vegetables, fruits and peas and beans, (ii) a "carbohydrate" pattern with high loadings for white bread and refined cereals, (iii) "sugary foods and sweet baked products" pattern and (iv) a "organ meat and fast food pattern" with high loadings for high fat dessert, organ meat, fast food and salty snacks.Logistic regressions with the individual dietary patterns controlling for potential confounders showed no association between any of the food patterns and risk of prostate cancer. The healthy pattern showed an inverse non-significant association, whereas the carbohydrate pattern was positively and insignificantly related to prostate cancer. Analysis of all food patterns adjusting for each other revealed no association between food patterns and the risk of prostate cancer. Dietary patterns identified in our sample were not associated with risk of prostate cancer. Further investigations that better define cancer-free subjects and dietary measurements are needed to examine diet and prostate cancer outcomes.

Prostate-specific antigen: does the current evidence support its use in prostate cancer screening?

LENUS (Irish Health Repository)

Duffy, Michael J

2012-02-01

Although widely used, the value of prostate-specific antigen (PSA) in screening asymptomatic men for prostate cancer is controversial. Reasons for the controversy relate to PSA being less than an ideal marker in detecting early prostate cancer, the possibility that screening for prostate cancer may result in the overdetection and thus overtreatment of indolent disease and the lack of clarity as to the definitive or best treatment for men diagnosed with localized prostate cancer. Although the results from some randomized prospective trials suggest that screening with PSA reduces mortality from prostate cancer, the overall benefit was modest. It is thus currently unclear as to whether the modest benefit of reduced mortality outweighs the harms of overdetection and overtreatment. Thus, prior to undergoing screening for prostate cancer, men should be informed of the risks and benefits of early detection. Newly emerging markers that may complement PSA in the early detection of prostate cancer include specific isoforms of PSA and PCA3.

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

Science.gov (United States)

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

2014-01-01

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

Hyaluronan Biosynthesis in Prostate Cancer

National Research Council Canada - National Science Library

McCarthy, James B

2006-01-01

Despite advances in the diagnosis and treatment of prostate cancer in the last several years metastasis represents the major cause of frustration and failure in the successful treatment of prostate cancer patients. Hyaluronan (HA...

Advances in MRI diagnosis of prostate cancer

International Nuclear Information System (INIS)

Zhang Longmin; Liu Ailian

2014-01-01

Prostate cancer is the second most common cancer in the world, and the incidence of prostate cancer in China shows an upward trend. MRI has high soft tissue resolution and multi-dimensional imaging advantages, and it can better show the anatomy of the prostate and adjacent tissue structures. With the development of MR technique, it plays a more and more important role in prostate cancer diagnosis. This review starts from the imaging performance of routine MRI sequence of prostate cancer, and a variety of functional MRI applications in the diagnosis and differential diagnosis of prostate cancer are described in detail, such as MR perfusion-weighted imaging, MR spectroscopy, MR diffusion-weighted imaging, MR diffusion tensor imaging, intravoxel incoherent motion diffusion-weighted imaging, MR susceptibility-weighted imaging. Meanwhile this review introduces that functional MRI has more advantages and can provide more image information than routine MRI sequence. According to a series of semi-quantitative and quantitative data, functional MRI can further provide the blood perfusion of prostate cancer, water molecule diffusion and microcirculation state, metabolism and biochemical composition change information. (authors)

Production of prostate-specific antigen by a breast cancer cell line, Sk-Br-3

International Nuclear Information System (INIS)

Kamali Sarvestani, E.; Ghaderi, A.

2002-01-01

Prostate-specific antigen is a 33-KDa serine protease that is produced predominantly by prostate epithelium. However, it has been shown that about 30-40% of female breast tumors produce prostate-specific antigen and its production is associated with the presence of estrogen and progesterone receptors. We have now developed a new tissue culture system to study prostate-specific antigen production in breast cancer and its association with prognostic factors such as progesterone receptor and c-erbB-2. For this purpose we investigated the ability of prostate-specific antigen production in five different cell lines, including two breast cancer cell lines, Sk-Br-3 and MDA-MB-453. The prostate-specific antigen in tissue culture supernatant and cytoplasm of the Sk-Br-3 cell line was detected by western blotting and immunoperoxidase, respectively. Furthermore, we found lower expression of c-erbB-2 in Sk-Br-3 than non-prostate-specific antigen producer breast cancer cell line, MDA-MB-453. Progesterone receptor was expressed by both prostate-specific antigen-positive and -negative cell lines and only the intensity of staining and the number of positive cells in Sk-Br-3 population was higher than MDA-MB-453. According to our findings prostate-specific antigen can be considered as a good prognostic factor in breast cancer and we suggest that these two cell lines are a good in vitro model to study the relationship of different breast cancer prognostic factors and their regulations

PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

DEFF Research Database (Denmark)

Bouchelouche, Kirsten; Tagawa, Scott T; Goldsmith, Stanley J

2011-01-01

disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Antiprostate-specific membrane antigen RIT demonstrates......Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis...... of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, (18)F-fluorodeoxyglucose (FDG), is not very useful in the imaging of prostate cancer...

Prostate cancer in Brazil and Latin America: epidemiology and screening

Directory of Open Access Journals (Sweden)

Rafael Rocha Tourinho-Barbosa

Full Text Available ABSTRACT Introduction: Prostate cancer is one of the tumors with higher incidence and mortality among men in the World. Epidemiological data are influenced by life expectancy of population, available diagnostic methods, correct collection of data and quality of health services. Screening of the disease is not standardized around the World. Up till now there is no consensus about the risks versus benefits of early detection. There are still missing data about this pathology in Latin America. Objective: to revise current epidemiologic situation and early diagnosis policies of prostate cancer in Brazil and Latin America. Materials and Methods: Medline, Cochrane Library and SciELO databases were reviewed on the subject of epidemiology and screening of prostate cancer. Screening research was performed in websites on national public health organizations and Latin America. Screening recommendations were obtained from those governmental organizations and from Latin American urological societies and compared to the most prominent regulatory agencies and societies of specialists and generalists from around the World. Results: Brazil and Latin America have a special position in relation to incidence and mortality of prostate cancer. In Brazil, it occupies the first position regarding incidence of cancer in men and the second cause of mortality. Central America has the highest rate of mortality of the continent with lower incidence/mortality ratios. Screening recommendations are very distinct, mainly among regulatory organs and urological societies. Conclusion: prostate cancer epidemiology is an important health public topic. Data collection related to incidence and mortality is still precarious, especially in less developed countries. It is necessary to follow-up long term screening studies results in order to conclude its benefits.

Annotating MYC Status in Treatment-Resistant Metastatic Castration-Resistant Prostate Cancer With Gallium-68 Citrate PET

Science.gov (United States)

2017-09-01

which avidly binds to circulating transferrin) labeled transferrin (Tf) can detect MYC-positive prostate cancer tumors, since the transferrin receptor ...Castration-Resistant Prostate Cancer with Androgen Receptor - Axis Imaging. Journal of nuclear medicine : official publication, Society of Nuclear...AWARD NUMBER: W81XWH-16-1-0469 TITLE: Annotating MYC Status in Treatment-Resistant Metastatic Castration- Resistant Prostate Cancer With

Targeting Discoidin Domain Receptors in Prostate Cancer

Science.gov (United States)

2017-08-01

AWARD NUMBER: W81XWH-15-1-0226 TITLE: Targeting Discoidin Domain Receptors in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Rafael Fridman...AND SUBTITLE 5a. CONTRACT NUMBER Targeting Discoidin Domain Receptors in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0226 5c. PROGRAM ELEMENT...response to collagen in prostate cancer. The project’s goal is to define the expression and therapeutic potential of DDRs in prostate cancer. During

Multiparametric MR imaging in diagnosis of chronic prostatitis and its differentiation from prostate cancer

Directory of Open Access Journals (Sweden)

Vivek Kumar Sah

2015-03-01

Full Text Available Chronic prostatitis is a heterogeneous condition with high prevalence rate. Chronic prostatitis has overlap in clinical presentation with other prostate disorders and is one of the causes of high serum prostate specific antigen (PSA level. Chronic prostatitis, unlike acute prostatitis, is difficult to diagnose reliably and accurately on the clinical grounds alone. Not only this, it is also challenging to differentiate chronic prostatitis from prostate cancer with imaging modalities like TRUS and conventional MR Imaging, as the findings can mimic those of prostate cancer. Even biopsy doesn't play promising role in the diagnosis of chronic prostatitis as it has limited sensitivity and specificity. As a result of this, chronic prostatitis may be misdiagnosed as a malignant condition and end up in aggressive surgical management resulting in increased morbidity. This warrants the need of reliable diagnostic tool which has ability not only to diagnose it reliably but also to differentiate it from the prostate cancer. Recently, it is suggested that multiparametric MR Imaging of the prostate could improve the diagnostic accuracy of the prostate cancer. This review is based on the critically published literature and aims to provide an overview of multiparamateric MRI techniques in the diagnosis of chronic prostatitis and its differentiation from prostate cancer.

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

Science.gov (United States)

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 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 cancer may trigger paraneoplastic limbic encephalitis

DEFF Research Database (Denmark)

Jakobsen, Jakob Kristian; Zakharia, Elias Raja; Boysen, Anders Kindberg Fossø

2013-01-01

-Hu antibody test the patient was diagnosed with paraneoplastic limbic encephalitis related to prostate cancer. The patient died within 6 months. We review the literature on prostate cancer-related paraneoplastic limbic encephalitis. High-risk prostate cancer can trigger paraneoplastic limbic encephalitis...

Detection of prostate cancer by an FDG-PET cancer screening program: results from a Japanese nationwide survey

International Nuclear Information System (INIS)

Minamimoto, Ryogo; Senda, Michio; Jinnouchi, Seishi; Terauchi, Takashi; Inoue, Tomio

2014-01-01

The aim of this study was to analyze detection rates and effectiveness of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) cancer screening program for prostate cancer in Japan, which is defined as a cancer-screening program for subjects without known cancer. It contains FDG-PET aimed at detection of cancer at an early stage with or without additional screening tests such as prostate-specific antigen (PSA) and magnetic resonance imaging (MRI). A total of 92,255 asymptomatic men underwent the FDG-PET cancer screening program. Of these, 504 cases with findings of possible prostate cancer in any screening method were analyzed. Of the 504 cases, 165 were verified as having prostate cancer. Of these, only 61 cases were detected by FDG-PET, which result in 37.0% relative sensitivity and 32.8% positive predictive value (PPV). The sensitivity of PET/computed tomography (CT) scanner was higher than that of dedicated PET (44.0% vs. 20.4%). However, the sensitivity of FDG-PET was lower than that of PSA and pelvic MRI. FDG-PET did not contribute to improving the sensitivity and PPV when performed as combined screening. PSA should be included in FDG-PET cancer screening programs to screen for prostate cancer

Plasma tocopherols and risk of prostate cancer in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Science.gov (United States)

Albanes, Demetrius; Till, Cathee; Klein, Eric A; Goodman, Phyllis J; Mondul, Alison M; Weinstein, Stephanie J; Taylor, Philip R; Parnes, Howard L; Gaziano, J Michael; Song, Xiaoling; Fleshner, Neil E; Brown, Powel H; Meyskens, Frank L; Thompson, Ian M

2014-09-01

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed higher prostate cancer incidence in men supplemented with high-dose α-tocopherol. We, therefore, examined whether presupplementation plasma α-tocopherol or γ-tocopherol was associated with overall or high-grade prostate cancer. A stratified case-cohort sample that included 1,746 incident prostate cancer cases diagnosed through June 2009 and a subcohort of 3,211 men was derived from the SELECT trial of 35,533 men. Plasma was collected at entry from 2001 to 2004, and median follow-up was 5.5 years (range, 0-7.9 years). Incidence of prostate cancer as a function of plasma α-tocopherol, γ-tocopherol, and supplementation with α-tocopherol or selenomethionine was estimated by the hazard ratio (HR). Plasma γ-tocopherol was not associated with prostate cancer. Men with higher α-tocopherol concentrations seemed to have risk similar to that of men with lower concentrations [overall HR for fifth (Q5) vs. first quintile (Q1), 1.21; 95 % confidence interval (CI), 0.88-1.66; P-trend = 0.24; in the trial placebo arm, Q5 HR, 0.85; 95% CI, 0.44-1.62; P-trend = 0.66]. We found a strong positive plasma α-tocopherol association among men receiving the trial selenomethionine supplement [Q5 HR, 2.04; 95% CI, 1.29-3.22; P-trend = 0.005]. A positive plasma α-tocopherol-prostate cancer association also seemed limited to high-grade disease (Gleason grade, 7-10; overall Q5 HR, 1.59; 95% CI, 1.13-2.24; P-trend = 0.001; among men receiving selenomethionine, Q5 HR, 2.12; 95% CI, 1.32-3.40; P-trend = 0.0002). Our findings indicate that higher plasma α-tocopherol concentrations may interact with selenomethionine supplements to increase high-grade prostate cancer risk, suggesting a biologic interaction between α-tocopherol and selenium itself or selenomethionine. ©2014 American Association for Cancer Research.

Does Core Length Taken per cc of Prostate Volume in Prostate Biopsy Affect the Diagnosis of Prostate Cancer?

Science.gov (United States)

Deliktas, Hasan; Sahin, Hayrettin; Cetinkaya, Mehmet; Dere, Yelda; Erdogan, Omer; Baldemir, Ercan

2016-08-01

The aim of this study was to determine the minimal core length to be taken per cc of prostate volume for an effective prostate biopsy. A retrospective analysis was performed on the records of 379 patients who underwent a first prostate biopsy with 12 to 16 cores under transrectal ultrasound guidance between September 2012 and April 2015. For each patient, the core length per cc of the prostate and the percentage of sampled prostate volume were calculated, and these values were compared between the patients with and without prostate cancer. A total of 348 patients were included in the study. Cancer was determined in 26.4% of patients. The mean core length taken per cc of prostate and the percentage of sampled prostate volume were determined to be 3.40 ± 0.15 mm/cc (0.26%; range, 0.08-0.63 cc) in patients with cancer and 2.75 ± 0.08 mm/cc (0.20%; range, 0.04-0.66 cc) in patients without cancer (P = .000 and P = .000), respectively. Core length taken per cc of prostate of > 3.31 mm/cc was found to be related to an increase in the rates of prostate cancer diagnosis (odds ratio, 2.84; 95% confidence interval, 1.68-4.78). The rate of cancer determination for core length taken per cc of prostate of  3.31 mm/cc, 41.1%. Core length taken per cc of prostate and the percentage of sampled prostate volume are important morphometric parameters in the determination of prostate cancer. The results of study suggest a core length per cc of the prostate of > 3.31 mm/cc as a cutoff value for quality assurance. Copyright © 2016 Elsevier Inc. All rights reserved.

Employee response to a company-sponsored program of colorectal and prostate cancer screening.

Science.gov (United States)

Myers, R E; Vernon, S W; Carpenter, A V; Balshem, A M; Lewis, P G; Wolf, T A; Hilbert, J; DeFonso, L R; Ross, E A

1997-01-01

Studies done in the mid-1970s documented increased risk for respiratory cancer and leukemia among employees in a chemical company manufacturing plant where chloromethyl ethers were used in production from 1948 to 1971. In the late 1980s, the company informed current and former employees about the results of follow-up studies which showed a moderation of risk of respiratory cancer and leukemia. New data showing elevated rates of mortality from colorectal, prostate, bladder, and pancreatic cancer in the population were also reported. Via mailed correspondence, the company made a no-cost program of colorectal and prostate cancer screening available to employees upon request; and information about bladder and pancreatic cancer was made available. Thirteen percent of employees in the population indicated interest in colorectal and prostate cancer screening (response). Thirty-one percent of these responders were screened (adherence). Multivariate analyses showed that education and length of employment in the plant were positively associated with response. Being white was positively associated with response for younger workers; while among older workers being male was positively associated with response. In terms of adherence, we found that older, more highly educated workers were more likely to have a screening examination. Findings indicate that employee participation in workplace-sponsored colorectal and prostate cancer screening can vary according to worker sociodemographic factors and length of employment in areas of potential exposure.

Multidisciplinary Functional MR Imaging for Prostate Cancer

International Nuclear Information System (INIS)

Kim, Jeong Kon; Jang, Yun Jin; Cho, Gyung Goo

2009-01-01

Various functional magnetic resonance (MR) imaging techniques are used for evaluating prostate cancer including diffusion-weighted imaging, dynamic contrast- enhanced MR imaging, and MR spectroscopy. These techniques provide unique information that is helpful to differentiate prostate cancer from non-cancerous tissue and have been proven to improve the diagnostic performance of MRI not only for cancer detection, but also for staging, post-treatment monitoring, and guiding prostate biopsies. However, each functional MR imaging technique also has inherent challenges. Therefore, in order to make accurate diagnoses, it is important to comprehensively understand their advantages and limitations, histologic background related with image findings, and their clinical relevance for evaluating prostate cancer. This article will review the basic principles and clinical significance of functional MR imaging for evaluating prostate cancer

Epigenetics in Prostate Cancer

OpenAIRE

Albany, Costantine; Alva, Ajjai S.; Aparicio, Ana M.; Singal, Rakesh; Yellapragada, Sarvari; Sonpavde, Guru; Hahn, Noah M.

2011-01-01

Prostate cancer (PC) is the most commonly diagnosed nonskin malignancy and the second most common cause of cancer death among men in the United States. Epigenetics is the study of heritable changes in gene expression caused by mechanisms other than changes in the underlying DNA sequences. Two common epigenetic mechanisms, DNA methylation and histone modification, have demonstrated critical roles in prostate cancer growth and metastasis. DNA hypermethylation of cytosine-guanine (CpG) rich sequ...

Exogenous fatty acid binding protein 4 promotes human prostate cancer cell progression.

Science.gov (United States)

Uehara, Hisanori; Takahashi, Tetsuyuki; Oha, Mina; Ogawa, Hirohisa; Izumi, Keisuke

2014-12-01

Epidemiologic studies have found that obesity is associated with malignant grade and mortality in prostate cancer. Several adipokines have been implicated as putative mediating factors between obesity and prostate cancer. Fatty acid binding protein 4 (FABP4), a member of the cytoplasmic fatty acid binding protein multigene family, was recently identified as a novel adipokine. Although FABP4 is released from adipocytes and mean circulating concentrations of FABP4 are linked with obesity, effects of exogenous FABP4 on prostate cancer progression are unclear. In this study, we examined the effects of exogenous FABP4 on human prostate cancer cell progression. FABP4 treatment promoted serum-induced prostate cancer cell invasion in vitro. Furthermore, oleic acid promoted prostate cancer cell invasion only if FABP4 was present in the medium. These promoting effects were reduced by FABP4 inhibitor, which inhibits FABP4 binding to fatty acids. Immunostaining for FABP4 showed that exogenous FABP4 was taken up into DU145 cells in three-dimensional culture. In mice, treatment with FABP4 inhibitor reduced the subcutaneous growth and lung metastasis of prostate cancer cells. Immunohistochemical analysis showed that the number of apoptotic cells, positive for cleaved caspase-3 and cleaved PARP, was increased in subcutaneous tumors of FABP4 inhibitor-treated mice, as compared with control mice. These results suggest that exogenous FABP4 might promote human prostate cancer cell progression by binding with fatty acids. Additionally, exogenous FABP4 activated the PI3K/Akt pathway, independently of binding to fatty acids. Thus, FABP4 might be a key molecule to understand the mechanisms underlying the obesity-prostate cancer progression link. © 2014 UICC.

Prostate cancer cells induce osteoblastic differentiation via semaphorin 3A.

Science.gov (United States)

Liu, Fuzhou; Shen, Weiwei; Qiu, Hao; Hu, Xu; Zhang, Chao; Chu, Tongwei

2015-03-01

Prostate cancer metastasis to bone is the second most commonly diagnosed malignant disease among men worldwide. Such metastatic disease is characterized by the presence of osteoblastic bone lesions, and is associated with high rates of mortality. However, the various mechanisms involved in prostate cancer-induced osteoblastic differentiation have not been fully explored. Semaphorin 3A (Sema 3A) is a newly identified regulator of bone metabolism which stimulates differentiation of pre-osteoblastic cells under physiological conditions. We investigated in this study whether prostate cancer cells can mediate osteoblastic activity through Sema 3A. We cultured osteoprogenitor MC3T3-E1 cells in prostate cancer-conditioned medium, and analyzed levels of Sema 3A protein in diverse prostate cancer cell lines to identify cell lines in which Sema 3A production showed a positive correlation with osteo-stimulation. C4-2 cells were stably transfected with Sema 3A short hairpin RNA to further determine whether Sema 3A contributes to the ability of C4-2 cells to induce osteoblastic differentiation. Down-regulation of Sema 3A expression decreased indicators of C4-2 CM-induced osteoblastic differentiation, including alkaline phosphatase production and mineralization. Additionally, silencing or neutralizing Sema 3A in C4-2 cells resulted in diminished β-catenin expression in osteogenitor MC3T3-E1 cells. Our results suggest that prostate cancer-induced osteoblastic differentiation is at least partially mediated by Sema 3A, and may be regulated by the β-catenin signalling pathway. Sema 3A may represent a novel target for treatment of prostate cancer-induced osteoblastic lesions. © 2014 Wiley Periodicals, Inc.

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