Prostate cancer is the most common form of cancer affecting men in the Western world. Risk factors include ageing, genetics, recurrent inflammation, lifestyle and diet intake, related to an increase of oxidative stress. Prostate cancer risk is also associated with exposure to carcinogen such as polycyclic aromatic hydrocarbons (PAHs), originated from the incomplete combustion of carbon-containing fuels like tobacco, wood, diesel, or charbroiled meat. Although numerous studies have associated the effect of PAHs to tumour development, few investigations have associated its effects to cancer progression. Considering that prostate cancer patients don’t die from localized prostate cancer but from advanced disease, we are interested in investigating whether PAHs may potentially influence prostate cancer progression and how this could be related to an increase in oxidative stress. Likewise we evaluated the effect of PAHs (pyrene, benzo(a) pyrene, chrysene and benzo(k)fluoranthene) on cell growth and in the expression of molecules involved in cancer me- tastization such as the vascular endothelial growth factor (VEGF) and hypoxia inducible factor (HIF) using prostate- derived cell lines from localized adenocarcinoma (HPV10), bone metastasis (PC3) and in non-neoplastic prostate epi- thelium cells. Moreover...

INTRODUÇÃO: Os pacientes submetidos a transplante renal estão sujeitos a um risco muito aumentado para câncer, porém inexistem dados concretos quanto a maior chance de tumor de próstata nesses pacientes. Neste estudo, avaliou-se a freqüência de câncer de próstata em transplantados renais comparada à de pacientes-controle, bem como a sua relação com etnia, antecedentes familiares, toque prostático, níveis de PSA e aos esquemas de imunossupressão nos pacientes transplantados renais. MÉTODOS: Neste estudo caso-controle realizado entre agosto de 2004 e junho de 2006 comparou-se a freqüência de câncer de próstata entre pacientes transplantados renais (n=119) há mais de um ano e pacientes do grupo-controle (n=184), bem como as variáveis: etnia, idade, presença de antecedentes familiares, escore internacional de sintomas prostáticos, toque retal, níveis de PSA e índice de massa corpórea (IMC). Os pacientes com PSA e/ou toque retal alterado foram submetidos à biópsias prostáticas guiadas por ultra-som transretal. As comparações das freqüências entre os dois grupos deram-se através das variáveis: idade, etnia, presença de antecedentes familiares, toque suspeito e valores de PSA>2,5ng/mL e >4,0ng/mL. Avaliou-se também a relação entre os tipos e doses de imunossupressor e presença de câncer. RESULTADOS: Não houve maior freqüência de tumor de próstata em transplantados (6...

Objectives: To verify prostate cancer prevalence in non-symptomatic men between 50 and 70 years old as well as cancer characteristics. Material and Methods: 2815 non-symptomatic men had total PSA and digital rectal examination performed between March 1998 and April 1998. Racial distribution was: 2331 Caucasians (83.9%), 373 Blacks (13.4%) and 75 Asiatic (2.7%). PSA was normal in 2554 (91.4%), 4 to 10 in 177 (6.3%) and greater than 10 in 64 (2.3%). DRE was normal in 2419 (86.3%), suspicious in 347 (12.4%) and characteristic for cancer in 37 (1.3%). Men with abnormal DRE and/or PSA had transrectal prostate biopsy indicated. Results: 461 biopsies were done and 78 tumors was detected (prevalence = 2.8%). Prevalence was progressively higher with age (p < 0.001), PSA level (p < 0.0001) and DRE findings (p = 0.0216). Cancer prevalence in Blacks was 1.65 times higher than in Caucasians (p > 0.05) and 94.9% of detected tumors were moderately or poorly differentiated. Sensibility, specificity, positive predictive value, negative predictive value and total accuracy for PSA were respectively: 66.6%; 89.7%; 51.7%; 94.2% and 86.5%. For DRE, the respective values were: 49.1%; 79.4%; 50.9%; 78.3% and 70.3%. Conclusions: prostate cancer prevalence in the studied population (2.8%) was similar to that of other countries populations. Cancer prevalence in blacks was 1.65 times higher than in Caucasians (difference was not statistically significant). Cancer prevalence becomes higher with aging. The association of DRE and PSA is of paramount importance for cancer diagnosis. The great majority of detected tumors (94.9%) was moderately and poorly differentiated. Brazil probably needs regional studies to better characterize prostate cancer epidemiology due to population heterogeneity.

INTRODUCTION: Monocarboxylate transporter 2 (MCT2) is a transmembrane protein involved in the transport of monocarboxylates such as pyruvate and lactate. In a previous study we described overexpression of MCT2 in prostate carcinoma raising the hypothesis of using MCT2 as a possible biomarker in prostate cancer. With the present study we aimed to compare the pattern of expression of MCT2 and alpha-methylacyl-CoA racemase (AMACR), in prostate carcinoma, PIN lesions, non-neoplastic prostate tissue, and normal prostate and compare their sensitivity and specificity. Also, we wanted to evaluate the value of using MCT2 in combination with AMACR and the negative markers 34βE12 or p63 to detect prostate cancer. METHODS: A total of 349 cases, including prostate carcinoma, non-neoplastic prostate tissue and PIN lesions, from radical prostatectomies were examined by immunohistochemistry for AMACR, MCT2, p63, and 34βE12, using tissue microarrays (TMAs). Normal prostate from radical cystoprostatectomy was also studied. RESULTS: Our study revealed that MCT2, similarly to AMACR, was consistently expressed in prostate cancer regardless of the Gleason score. In combination with AMACR and p63 or 34βE12, MCT2 helped to improve the diagnosis of prostate carcinoma. Also...

Prostate cancer is relatively unique to man. There is no naturally occurring prostate cancer in the mouse. Pre-clinical studies involve the establishment of a genetically engineered mouse prostate cancer model with features close to those of the human situation. A new knock-in mouse adenocarcinoma prostate (KIMAP) model was established, which showed close-to-human kinetics of tumor development. In order to determine if the similar kinetics is associated with heterogeneous tumor architecture similar to the human situation, we utilized a new mouse histological grading system (Gleason analogous grading system) similar to the Gleason human grading system and flow cytometry DNA analysis to measure and compare the adenocarcinoma of the KIMAP model with human prostate cancer. Sixty KIMAP prostate cancer samples from 60 mice were measured and compared with human prostate cancer. Flow cytometry DNA analysis was performed on malignant prostate tissues obtained from KIMAP models. Mice with prostate cancer from KIMAP models showed a 53.3% compound histological score rate, which was close to the human clinical average (50%) and showed a significant correlation with age (P = 0.001). Flow cytometry analyses demonstrated that most KIMAP tumor tissues were diploid...

Objective: To examine whether fish and fish oil consumption across the lifespan is associated with a lower risk of prostate cancer. Design: The study was nested among 2268 men aged 67–96 years in the AGES-Reykjavik cohort study. In 2002 to 2006, dietary habits were assessed, for early life, midlife and later life using a validated food frequency questionnaire. Participants were followed for prostate cancer diagnosis and mortality through 2009 via linkage to nationwide cancer- and mortality registers. Adjusting for potential confounders, we used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for prostate cancer according to fish and fish oil consumption. Results: Among the 2268 men, we ascertained 214 prevalent and 133 incident prostate cancer cases, of which 63 had advanced disease. High fish consumption in early- and midlife was not associated with overall or advanced prostate cancer. High intake of salted or smoked fish was associated with a 2-fold increased risk of advanced prostate cancer both in early life (95% CI: 1.08, 3.62) and in later life (95% CI: 1.04, 5.00). Men consuming fish oil in later life had a lower risk of advanced prostate cancer [HR (95%CI): 0.43 (0.19, 0.95)], no association was found for early life or midlife consumption. Conclusions: Salted or smoked fish may increase risk of advanced prostate cancer...

Purpose Glycine N-methyltransferase (GNMT) affects genetic stability by regulating the ratio of S-adenosylmethionine to S-adenosylhomocysteine, by binding to folate, and by interacting with environmental carcinogens. In Taiwanese men, GNMT was found to be a tumor susceptibility gene for prostate cancer. However, the association of GNMT with prostate cancer risk in other ethnicities has not been studied. It was recently reported that sarcosine, which is regulated by GNMT, increased markedly in metastatic prostate cancer. We hereby explored the association of GNMT polymorphisms with prostate cancer risk in individuals of European descent from the Health Professionals Follow-up Study (HPFS). Methods: A total of 661 incident prostate cancer cases and 656 controls were identified from HPFS. The GNMT short tandem repeat polymorphism 1 (STRP1), 4-bp insertion/deletion polymorphisms (INS/DEL) and the single nucleotide polymorphism rs10948059 were genotyped to test for their association with prostate cancer risk. Results: The rs10948059 T/T genotype was associated with a 1.62-fold increase in prostate cancer risk (95% confidence interval (CI): 1.18, 2.22) when compared with the C/C genotype. The STRP1 ≥16GAs/≥16GAs genotype was associated with decreased risk of prostate cancer when compared with the <16GAs/<16GAs genotype (odds ratio (OR) = 0.68; 95% CI: 0.46...

The global economic downturn has been associated with increased unemployment in many countries. Insights into the impact of unemployment on specific health conditions remain limited. We determined the association between unemployment and prostate cancer mortality in members of the Organisation for Economic Co-operation and Development (OECD). We used multivariate regression analysis to assess the association between changes in unemployment and prostate cancer mortality in OECD member states between 1990 and 2009. Country-specific differences in healthcare infrastructure, population structure, and population size were controlled for and lag analyses conducted. Several robustness checks were also performed. Time trend analyses were used to predict the number of excess deaths from prostate cancer following the 2008 global recession. Between 1990 and 2009, a 1% rise in unemployment was associated with an increase in prostate cancer mortality. Lag analysis showed a continued increase in mortality years after unemployment rises. The association between unemployment and prostate cancer mortality remained significant in robustness checks with 46 controls. Eight of the 21 OECD countries for which a time trend analysis was conducted, exhibited an estimated excess of prostate cancer deaths in at least one of 2008...

Le cancer de la prostate est le cancer le plus fréquemment diagnostiqué chez les hommes canadiens et la troisième cause de décès relié au cancer. Lorsque diagnostiqué à un stade précoce de la maladie, le cancer de la prostate est traité de manière curative par chirurgie et radiothérapie. Par contre, les thérapies actuelles ne peuvent éradiquer la maladie lorsqu’elle progresse à des stades avancés. Ces thérapies, comme la chimiothérapie et l’hormonothérapie, demeurent donc palliatives. Il est primordial d’optimiser de nouvelles thérapies visant l’élimination des cellules cancéreuses chez les patients atteints des stades avancés de la maladie. Une de ces nouvelles options thérapeutiques est l’immunothérapie. L’immunothérapie du cancer a fait des progrès considérables durant les dernières années. Cependant, les avancements encourageants obtenus lors d’essais précliniques ne se sont pas encore traduits en des résultats cliniques significatifs. En ce qui concerne le cancer de la prostate, les résultats négligeables suivants des interventions immunothérapeutiques peuvent être causés par le fait que la plupart des études sur le microenvironnement immunologique furent effectuées chez des modèles animaux. De plus la majorité des études sur l’immunologie tumorale humaine furent effectuées chez des patients atteints d’autres cancers...

Study Type – Diagnostic (validating cohort) Level of Evidence 1b What’s known on the subject? and What does the study add? Scientists have found a number of genetic factors that increase prostate cancer risk, including heritable mutations in the genes BRCA1 and BRCA2. These mutations are not common but can have major impact, as a BRCA2 mutation increases risk by up to seven-fold while a BRCA1 mutation is thought to double risk in men under 65. The IMPACT study aims to determine whether targeted screening in men with a known BRCA1 or BRCA2 mutation would lead to earlier diagnosis of prostate cancers. This data from the IMPACT study adds to the increasing evidence that BRCA mutation carriers develop more aggressive disease. Although these are early results, it appears that PSA screening is more accurate at predicting potentially aggressive prostate cancer among men at higher risk of the disease due to a genetic predisposition than general population screening. This study provides support for continued screening in men with genetic mutations. OBJECTIVE: To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls)...

Prostate cancer remains one of the leading causes of cancer related morbidity and mortality in Australian men. The androgen receptor (AR) is an intracellular transcription factor that mediates the biological actions of circulating androgens to drive the growth and survival of prostate cancer cells. However, current treatment options for non-localised, advanced stage prostate cancer invariably fail, which is a consequence of continued AR signalling during all stages of disease progression. Therefore, understanding the regulatory mechanisms of AR action is essential for the development of more effective therapies. Molecular regulation of the AR can occur during the process of protein maturation. This includes the incorporation of tetratricopeptide repeat (TPR) containing co-chaperones into the heat shock protein 90 (Hsp90) molecular chaperone complex, which collectively acts to generate AR proteins capable of high affinity ligand binding, nuclear translocation and gene regulation. The co-chaperone small glutamine-rich TPR containing protein alpha (SGTA) acts to restrict AR nuclear translocation and thereby regulate AR transcriptional activity. The clinical implications of SGTA are evident by a decline in protein levels with prostate cancer progression. The loss of SGTA may therefore disrupt the regulatory process of AR cytoplasmic retention...

BACKGROUND Cancer-related fatigue is the most common, distressing complaint reported by cancer patients and the most frequently reported long-term side effect of treatment for prostate cancer. Despite this, cancer-related fatigue has not received serious attention from health professionals or researchers, particularly in relation to men with prostate cancer. It is important for healthcare professionals to understand effective non-pharmacological interventions for treating cancer-related fatigue. OBJECTIVE To synthesize the best available evidence on the effectiveness of non-pharmacological interventions for managing cancer-related fatigue in men with prostate cancer who are undergoing or have completed treatment. INCLUSION CRITERIA : TYPES OF PARTICIPANTS This review considered men with prostate cancer (regardless of staging, any previous treatment or co morbidities), aged 18 years and over who were undergoing any treatment, or had completed any treatment for prostate cancer within the previous 12 months. TYPES OF INTERVENTIONS This review considered non-pharmacological interventions, including exercise, diet modification, counselling, education, and cognitive behavioral therapy, using other non-pharmacological interventions or standard care as comparators. TYPES OF OUTCOMES Fatigue...

Prostate cancer remains the second leading cause of cancer related death in Australian males, with approximately 28000 Australian men being diagnosed in 2007 and more than 3000 deaths as a result of this disease. The probability of patient survival from prostate cancer is greatly diminished when the disease has spread outside of the confines of the prostate. Disease spread, or the potential for spread, also determines the therapy received by the patient, be it surgical removal, chemotherapy, radiotherapy, or hormonal therapy, or any of these in combination. The advent of serum PSA testing has allowed for both earlier and increased detection of prostate cancer over the past 20 years. Despite this, the mortality rate for prostate cancer has remained relatively constant. Moreover, it is thought that increased detection may lead to over diagnosis and over treatment of indolent disease in up to 50% of cases, burdening patients who would not actually die from prostate cancer. Central to this issue is that there is no accurate means of predicting, at the time of diagnosis, the likelihood of prostate cancer becoming aggressive and metastasising, and thus identifying the patient population that would benefit most from more aggressive treatment. The prostate is a glandular structure composed of secretory epithelial cells embedded in a stroma containing smooth muscle cells...

BACKGROUND: Individual studies have suggested that some circulating fatty acids are associated with prostate cancer risk, but have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease. METHODS: Principal investigators of prospective studies on circulating fatty acids and prostate cancer were invited to collaborate. Investigators provided individual participant data on circulating fatty acids (weight percent) and other characteristics of prostate cancer cases and controls. Prostate cancer risk by study-specific fifths of 14 fatty acids was estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. RESULTS: Five thousand and ninety-eight case patients and 6649 control patients from seven studies with an average follow-up of 5.1 (SD = 3.3) years were included. Stearic acid (18:0) was inversely associated with total prostate cancer (odds ratio [OR] Q5 vs Q1 = 0.88, 95% confidence interval [CI] = 0.78 to 1.00, P trend = .043). Prostate cancer risk was, respectively, 14% and 16% greater in the highest fifth of eicosapentaenoic acid (20:5n-3) (OR = 1.14, 95% CI = 1.01 to 1.29, Ptrend = .001) and docosapentaenoic acid (22:5n-3) (OR = 1.16...

Curcumin is a component of the Indian spice turmeric that has shown anti-cancer activity across a range of models. This includes prostate cancer, the most commonly diagnosed cancer in Australia. While much of the current literature relates to epithelial cells, there is no information regarding curcumin activity or resistance in prostate fibroblasts. With curcumin recently entering clinical trials for prostate cancer and being increasingly used as a dietary supplement, it is critical to gain an understanding of curcumin action and potential resistance in these cells, given their reported contribution to cancer progression. Furthermore, with drug resistance being a major setback to cancer therapy, it is also important to investigate curcumin-based combination strategies to enhance efficacy and avoid the development of resistance. The aims of this thesis were therefore to comparatively investigate mechanisms of curcumin action in prostate cancer cells and fibroblasts, to explore the potential for curcumin resistance to occur in prostate fibroblasts and to examine the ability of curcumin to re-sensitise prostate cancers resistant to drozitumab, a monoclonal antibody against death receptor 5 (DR5). Curcumin inhibited prostate cancer cell and fibroblast viability...

BACKGROUND: Epigenetic alterations are common in prostate cancer, yet how these modifications contribute to carcinogenesis is poorly understood. We investigated whether specific histone modifications are prognostic for prostate cancer relapse, and whether the expression of epigenetic genes is altered in prostate tumorigenesis. METHODS: Global levels of histone H3 lysine-18 acetylation (H3K18Ac) and histone H3 lysine-4 dimethylation (H3K4diMe) were assessed immunohistochemically in a prostate cancer cohort of 279 cases. Epigenetic gene expression was investigated in silico by analysis of microarray data from 23 primary prostate cancers (8 with biochemical recurrence and 15 without) and 7 metastatic lesions. RESULTS: H3K18Ac and H3K4diMe are independent predictors of relapse-free survival, with high global levels associated with a 1.71-fold (P < 0.0001) and 1.80-fold (P = 0.006) increased risk of tumor recurrence, respectively. High levels of both histone modifications were associated with a 3-fold increased risk of relapse (P < 0.0001). Epigenetic gene expression profiling identified a candidate gene signature (DNMT3A, MBD4, MLL2, MLL3, NSD1, and SRCAP), which significantly discriminated nonmalignant from prostate tumor tissue (P = 0.0063) in an independent cohort. CONCLUSIONS: This study has established the importance of histone modifications in predicting prostate cancer relapse and has identified an epigenetic gene signature associated with prostate tumorigenesis. IMPACT: Our findings suggest that targeting the epigenetic enzymes specifically involved in a particular solid tumor may be a more effective approach. Moreover...

Introduction: Au Canada, le cancer de la prostate est le cancer le plus fréquemment diagnostiqué chez les hommes et le plus mortel après les cancers du poumon et du côlon. Il y a place à optimiser le traitement du cancer de la prostate de manière à mettre en œuvre une médecine personnalisée qui s’adapte aux caractéristiques de la maladie de chaque patient de façon individuelle. Dans ce mémoire, nous avons évalué la réponse aux dommages de l’ADN (RDA) comme biomarqueur potentiel du cancer de la prostate. Les lésions potentiellement oncogènes de l'ADN déclenche une cascade de signalisation favorisant la réparation de l'ADN et l’activation des points de contrôle du cycle cellulaire pour préserver l’intégrité du génome. La RDA est un mécanisme central de suppression tumorale chez l’homme. La RDA joue un rôle important dans l’arrêt de la prolifération des cellules dont les génomes sont compromis, et donc, prévient la progression du cancer en agissant comme une barrière. Cette réponse cellulaire détermine également comment les cellules normales et cancéreuses réagissent aux agents utilisés pour endommager l'ADN lors du traitement du cancer comme la radiothérapie ou la chimiothérapie, en plus la présence d...

Background: As the long-term efficacy of stereotactic body radiation therapy (SBRT) becomes established and other prostate cancer treatment approaches are refined and improved, examination of quality of life (QOL) following prostate cancer treatment is critical in driving both patient and clinical treatment decisions. We present the first study to compare QOL after SBRT and radical prostatectomy, with QOL assessed at approximately the same times pre- and post-treatment and using the same validated QOL instrument. Methods: Patients with clinically localized prostate cancer were treated with either radical prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at baseline, 1, 6, 12, 24, and 36 months. Differences in patient characteristics between the two groups were assessed using Chi-squared tests for categorical variables and t-tests for continuous variables. Generalized estimating equation (GEE) models were constructed for each EPIC scale to account for correlation among repeated measures and used to assess the effect of treatment on QOL. Results: The largest differences in QOL occurred in the first 1–6 months after treatment...

Changqing Wu; Prostate cancer is one of the most common cancers in men. However, the incidence of clinical prostate cancer varies widely between ethnic populations and countries. Epidemiological studies have shown that higher intake of soy foods can lower risk of prostate cancer. Soy isoflavones, such as daidzein, genistein, and their sugar conjugates, daidzin and genistin, are considered to be major bioactive compounds in soy and provide chemoprotection of prostate cancer. The majority of studies to assess the anticancer efficacy of soy products for prostate cancer (PCa) have been performed using purified bioactive compounds such as daidzein and genistein at pharmacological concentrations for short periods using androgen independent PCa cells such as PC-3 or androgen sensitive PCa cells such as LNCaP. However, attention has been drawn to the safety of using high levels of soy isoflavones in humans and the limited effect of individual soy isoflavones and these studies cannot reflect the real effects that soy may induce through diets. Currently, little is known about the bioavailability of isoflavones from whole soy foods and their bioactivities after cooking and digestion. The objectives of this study include: 1) examine the antiproliferative and apoptotic effects of high-dose (25 to 200 μM) individual soy isoflavones...