Prostate Cancer Prevention Research Articles

Plasma Metabolomics for Discovery of Early Metabolic Markers of Prostate Cancer Based on Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry.

Simple SummaryCorrect identification of subjects at high risk is critical in the prevention and early screening of prostate cancer (PCa). Analysis of metabolites in biofluids has shown to be a promising method to identify novel PCa biomarkers. To identify potential biomarkers of PCa, we conducted metabolic profiling of pre-diagnosis plasma metabolite profiles from a large prospective male cohort (n = 418), which included 146 males who developed PCa during a 13-year follow-up and 272 matched controls to investigate the relationship with long-term PCa risk. We show metabolite profiles discriminate males who subsequently developed PCa during the follow-up from matched controls with a high degree of accuracy (AU-ROC 0.92) and highlight 10 metabolites associated with a high risk of PCa. These results suggest that the dysregulation of amino acids and sphingolipid metabolism is associated with future risk of PCa.Background: The prevention and early screening of PCa is highly dependent on the identification of new biomarkers. In this study, we investigated whether plasma metabolic profiles from healthy males provide novel early biomarkers associated with future risk of PCa. Methods: Using the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, we identified plasma samples collected from 146 PCa cases up to 13 years prior to diagnosis and 272 matched controls. Plasma metabolic profiles were characterized using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Results: Orthogonal partial least squares discriminant analysis (OPLS-DA) discriminated PCa cases from controls, with a median area under the receiver operating characteristic curve (AU-ROC) of 0.92 using a 1000-time repeated random sub-sampling validation. Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) identified the top 10 most important metabolites (p < 0.001) discriminating PCa cases from controls. Among them, phosphate, ethyl oleate, eicosadienoic acid were higher in individuals that developed PCa than in the controls during the follow-up. In contrast, 2-hydroxyadenine, sphinganine, L-glutamic acid, serotonin, 7-keto cholesterol, tiglyl carnitine, and sphingosine were lower. Conclusion: Our results support the dysregulation of amino acids and sphingolipid metabolism during the development of PCa. After validation in an independent cohort, these signatures may promote the development of new prevention and screening strategies to identify males at future risk of PCa.

Prostate Cancer Screening in Brazil: a single center experience in the public health system.

ABSTRACTPurpose:Incidence and mortality of prostate cancer (PCa) are still increasing in developing countries. Limited access to the health system or more aggressive disease are potential reasons for this. Ethnic and social differences in developed countries seem to make inappropriate to extrapolate data from other centers. We aim to report the epidemiological profile of a PSA-screened population from a cancer center in Brazil.Materials and Methods:We retrospectively selected 9.692 men enrolled in a PCa prevention program, comprising total PSA level and digital rectal examination at the first appointment, associated with complementary tests when necessary. Men aged over 40 years-old were included after shared decision-making process. Prostate biopsy (TRUS) was performed when clinically suspected for PCa. After the diagnosis, patients underwent appropriate treatment.Results:TRUS was performed in 5.5% of men and PCa incidence was 2.6%. Overall ratio between number of patients who needed to be screened in order to diagnose one cancer was 38.9 patients, with 2.1 biopsies performed to diagnose a cancer. Positive predictive value (PPV) of TRUS biopsy in this strategy was 47.2%, varying from 38.5% (<50 years-old) to 60% (>80 years-old). We evidenced 70 patients (27.9%) classified as low risk tumors, 74 (29.5%) as intermediate risk, and 107 (42.6%) as high-risk disease.Conclusions:PSA-screening remains controversial in literature. In front of a huge miscegenated people and considering the big proportion of high-risk PCa, even in young men diagnosed with the disease, it is imperative to inform patients and health providers about these data particularities in Brazil.

Gut Microbiota-Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signaling.

Excessive intake of animal fat and resultant obesity are major risk factors for prostate cancer. Because the composition of the gut microbiota is known to change with dietary composition and body type, we used prostate-specific Pten knockout mice as a prostate cancer model to investigate whether there is a gut microbiota-mediated connection between animal fat intake and prostate cancer. Oral administration of an antibiotic mixture (Abx) in prostate cancer-bearing mice fed a high-fat diet containing a large proportion of lard drastically altered the composition of the gut microbiota including Rikenellaceae and Clostridiales, inhibited prostate cancer cell proliferation, and reduced prostate Igf1 expression and circulating insulin-like growth factor-1 (IGF1) levels. In prostate cancer tissue, MAPK and PI3K activities, both downstream of the IGF1 receptor, were suppressed by Abx administration. IGF1 directly promoted the proliferation of prostate cancer cell lines DU145 and 22Rv1 in vitro. Abx administration also reduced fecal levels of short-chain fatty acids (SCFA) produced by intestinal bacteria. Supplementation with SCFAs promoted tumor growth by increasing IGF1 levels. In humans, IGF1 was found to be highly expressed in prostate cancer tissue from obese patients. In conclusion, IGF1 production stimulated by SCFAs from gut microbes influences the growth of prostate cancer via activating local prostate MAPK and PI3K signaling, indicating the existence of a gut microbiota-IGF1-prostate axis. Disrupting this axis by modulating the gut microbiota may aid in prostate cancer prevention and treatment. SIGNIFICANCE: These results suggest that intestinal bacteria, acting through short-chain fatty acids, regulate systemic and local prostate IGF1 in the host, which can promote proliferation of prostate cancer cells.

Knowledge of prostate cancer presentation, etiology, and screening practices among women: a mixed-methods systematic review

BackgroundWith the burden of prostate cancer, it has become imperative to exploit cost-effective ways to tackle this menace. Women have demonstrated their ability to recognize early cancer signs, and it is, therefore, relevant to include women in strategies to improve the early detection of prostate cancer. This systematic review seeks to gather evidence from studies that investigated women’s knowledge about (1) the signs and symptoms, (2) causes and risk factors, and (3) the screening modalities of prostate cancer. Findings from the review will better position women in the fight against the late detection of prostate cancer.MethodsThe convergent segregated approach to the conduct of mixed-methods systematic reviews was employed. Five databases, namely, MEDLINE (EBSCOhost), CINAHL (EBSCOhost), PsycINFO (EBSCOhost), Web of Science, and EMBASE (Ovid), were searched from January 1999 to December 2019 for studies conducted with a focus on the knowledge of women on the signs and symptoms, the causes and risk factors, and the screening modalities of prostate cancer.ResultsOf 2201 titles and abstracts screened, 22 full-text papers were retrieved and reviewed, and 7 were included: 3 quantitative, 1 qualitative, and 3 mixed-methods studies. Both quantitative and qualitative findings indicate that women have moderate knowledge of the signs and symptoms and the causes and risk factors of prostate cancer. However, women recorded poor knowledge about prostate cancer screening modalities or tools.ConclusionsModerate knowledge of women on the signs and symptoms and the causes and risk factors of prostate cancer was associated with education. These findings provide vital information for the prevention and control of prostate cancer and encourage policy-makers to incorporate health promotion and awareness campaigns in health policies to improve knowledge and awareness of prostate cancer globally.Systematic review registrationOpen Science Framework (OSF) registration DOI: https://doi.org/10.17605/OSF.IO/BR456

Research advances in the relationship of dietary factors and prostate cancer risk

Prostate cancer is the second most common malignancy in men worldwide. An increasing trend for prostate cancer incidence was observed in China. Enormous studies have been conducted to investigate the association between dietary factors and prostate cancer, however conflicted results were obtained. Red meat, processed meat, and dairy products consumption were reported to be associated with the increased prostate cancer risk, while tomatoes, soybeans and green tea might reduce the risk of prostate cancer occurance. However, no consensus could be reached without strong evidence. Furthermore, further studies are needed to investigate the association between vitamin and mineral supplements and prostate cancer risk. Some studies reported that men with higher dietary inflammatory index scores increased prostate cancer risk. There may be a long susceptible period when dietary factors affect prostate cancer risk, which poses challenges for collecting exposure and the follow-up. Measure bias and detection bias are the main reasons which impair the authenticity of studies on the relationship of dietary factors and prostate cancer risk. Researchers should apply various methods to measure participants' dietary consumption levels and ascertain essential outcomes, such as prostate cancer death. This article reviews updated epidemiological evidences on the association of dietary factors and prostate cancer, aims to benefit future nutritional epidemiology studies focus on the prostate cancer prevention.

Mapping evidence on the distribution of the costs associated with cancer of prostate, cervix, and female breast in the sub-Saharan Africa: protocol for a scoping review

BackgroundDespite the well-documented information on cancer prevention and management, among noncommunicable diseases (NCDs), globally, cancer continues to be the second leading cause of morbidity and mortality with devastating economic consequences. The burden is disproportionately more among developing countries and the extent of evidence available on the economic consequences (direct and indirect costs) of cancer remains unknown in low-income countries particularly in the sub-Saharan region. Understanding the costs of illness is important to inform decision-making on setting up health care policies and informing economic evaluation of interventions.This study aims to map evidence on the distribution of the economic burden (direct and indirect costs) associated with prevention, diagnosis, and treatment of three predominant cancers: prostate, cervix, and female breast in the sub-Saharan Africa.MethodsThis scoping review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR), and will be conducted following Arksey and O’Malley’s framework. We will search PubMed/MEDLINE, Web of Science, CINHAL (via EBSCOhost platform), Science Direct, Cochrane Database of Systematic Reviews, Africa-Wide Information, Google Scholar, and WHO Library. We will perform hand-searching of the reference lists of included studies and other relevant documents.Two reviewers will independently screen all citations, full-text articles, and abstract data.We will include primary studies from all study designs reporting costs associated with prevention, diagnosis and treatment of prostate, cervical, and breast cancers in the sub-Saharan region. Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., thematic analysis) methods. A narrative summary of findings will be presented.DiscussionThis review will map the extent of information available on the economic burden (direct and indirect costs) of prostate, cervical, and breast cancers in the sub-Saharan region. Further guidance for future research in the subject area will be discussed.Systematic review registrationOpen Science Framework

DNA methylome, transcriptome, and prostate cancer prevention by phenethyl isothiocyanate in TRAMP mice.

Epigenetics/epigenomics has been shown to be involved in carcinogenesis. However, how the epigenome would be altered in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and the effect of cancer chemopreventive phytochemical phenethyl isothiocyanate (PEITC) on the epigenome in TRAMP mice are not known. PEITC has been reported to reduce the risk of many cancers including prostate cancer (PCa). In this study, male TRAMP mice were fed a control diet or diet containing 0.05% PEITC from 8 weeks to 16 weeks. The tumor incidence was reduced in the PEITC diet (0/6) as compared with the control diet (6/7). RNA-sequencing (RNA-seq) analyses on nontumor and tumor prostatic tissues revealed several pathways like cell cycle/Cdc42 signaling, inflammation, and cancer-related signaling, were activated in prostate tissues of TRAMP mice but were reversed or attenuated in TRAMP mice fed with PEITC diet. DNA CpG methyl-seq analyses showed that global methylation patterns of prostate samples from TRAMP mice were hugely different from those of wild-type mice. Dietary PEITC partially reversed the global methylation changes during prostatic carcinogenesis. Integration of RNA-seq and DNA methyl-seq analyses identified a list of genes, including Adgrb1 and Ebf4, with an inverse regulatory relationship between their RNA expression and CpG methylation. In summary, our current study demonstrates that alteration of the global epigenome in TRAMP prostate tumor and PEITC administration suppresses PCa carcinogenesis, impacts global CpG epigenome and transcriptome, and attenuates carcinogenic pathways like cell cycle arrest and inflammation. These results may provide insights and epigenetic markers/targets for PCa prevention and treatment in human PCa patients.

Mechanistic Insights into the Link between Obesity and Prostate Cancer.

Obesity is a pandemic of increasing worldwide prevalence. There is evidence of an association between obesity and the risk of prostate cancer from observational studies, and different biologic mechanisms have been proposed. The chronic low-level inflammation within the adipose tissue in obesity results in oxidative stress, activation of inflammatory cytokines, deregulation of adipokines signaling, and increased circulating levels of insulin and insulin-like growth factors (IGF). These mechanisms may be involved in epithelial to mesenchymal transformation into a malignant phenotype that promotes invasiveness, aggressiveness, and metastatic potential of prostate cancer. A thorough understanding of these mechanisms may be valuable in the development of effective prostate cancer prevention strategies and treatments. This review provides an overview of these mechanisms.

Transcriptomic Analysis of LNCaP Tumor Xenograft to Elucidate the Components and Mechanisms Contributed by Tumor Environment as Targets for Dietary Prostate Cancer Prevention Studies.

LNCaP athymic xenograft model has been widely used to allow researchers to examine the effects and mechanisms of experimental treatments such as diet and diet-derived cancer preventive and therapeutic compounds on prostate cancer. However, the biological characteristics of human LNCaP cells before/after implanting in athymic mouse and its relevance to clinical human prostate outcomes remain unclear and may dictate interpretation of biological efficacies/mechanisms of diet/diet-derived experimental treatments. In this study, transcriptome profiles and pathways of human prostate LNCaP cells before (in vitro) and after (in vivo) implanting into xenograft mouse were compared using RNA-sequencing technology (RNA-seq) followed by bioinformatic analysis. A shift from androgen-responsive to androgen nonresponsive status was observed when comparing LNCaP xenograft tumor to culture cells. Androgen receptor and aryl-hydrocarbon pathway were found to be inhibited and interleukin-1 (IL-1) mediated pathways contributed to these changes. Coupled with in vitro experiments modeling for androgen exposure, cell-matrix interaction, inflammation, and hypoxia, we identified specific mechanisms that may contribute to the observed changes in genes and pathways. Our results provide critical baseline transcriptomic information for a tumor xenograft model and the tumor environments that might be associated with regulating the progression of the xenograft tumor, which may influence interpretation of diet/diet-derived experimental treatments.

A comprehensive review on phytochemistry, bioactivity and medicinal value of bioactive compounds of pomegranate (Punica granatum)

Pomegranate (Punica granatum) acts as a therapeutic fruit possessing different bioactive compounds. Different compartments of pomegranate (P. granatum) like seed, peel, juice and leaves are rich in potential bioactive compounds. Pomegranate contains sinapyl, coniferyl, ellagic acid, cinnamic acid, genistein, linoleic acid, anthocyanin, gallic acid, catechin, quercetin, rutin, kaempferol, cyanidin, punicalin, delphinidin, punicalagin, chlorogenic acid, coumaric acid, luteolin and pelletierine alkaloids, flavonoids, anthocyanin and caffeic acid. Pomegranate also exhibits significant anti-oxidative, anti-hypertensive, cardioprotective and anti-diabetic properties and anti-carcinogenic possessions including prevention of prostate cancer; reduction in colon inflammation, prevention of skin tumorigenesis, improvement in renal function and reduction in metastatic melanoma growth. This review summarizes the current available data on the phytochemistry, bioavailability and therapeutic importance of potential bioactive compounds of pomegranate.

Proteomics reveals the function reverse of MPSSS-treated prostate cancer-associated fibroblasts to suppress PC-3 cell viability via the FoxO pathway.

Prostate cancer‐associated fibroblasts (prostate CAFs) are essential components of the tumor microenvironment and can promote tumor progression through their immunosuppressive functions. MPSSS, a novel polysaccharide purified from Lentinus edodes, has been reported to have anti‐tumor activity. MPSSS could also inhibit the immunosuppressive function of prostate CAFs, which has been demonstrated through that the secretome of MPSSS‐treated prostate CAFs could inhibit the proliferation of T cells. However, how the secretome of MPSSS‐treated prostate CAFs influence prostate cancer progression is still unclear. Interestingly, we found that the low molecular weight (3–100kD) secretome of prostate CAFs (lmwCAFS) could promote the growth of PC‐3 cells, while that of MPSSS‐treated prostate CAFs (MT‐lmwCAFS) could inhibit their growth. We carried out comparative secretomic analysis of lmwCAFS and MT‐lmwCAFS to identify functional molecules that inhibit the growth of PC‐3 cells, and proteomic analysis of lmwCAFS‐treated PC‐3 cells and MT‐lmwCAFS‐treated PC‐3 cells to investigate the underlying molecular mechanism. These analyses suggest that TGF‐β3 from MT‐lmwCAFS may inhibit the growth of PC‐3 cells. The validated experiments revealed that TGF‐β3 from MT‐lmwCAFS activated p21 expression in PC‐3 cells by regulating the FoxO pathway thereby inducing G0/G1 cell cycle arrest of PC‐3 cells. Overall, our data demonstrated that MPSSS reversed the ability of prostate CAFs to suppress the cell viability of PC‐3 cells, which might provide a potential therapeutic strategy to prevent prostate cancer progression.

High-dose vitamin D supplementation to prevent prostate cancer progression in localised cases with low-to-intermediate risk of progression on active surveillance (ProsD): protocol of a phase II randomised controlled trial

IntroductionActive surveillance (AS) for patients with prostate cancer (PC) with low risk of PC death is an alternative to radical treatment. A major drawback of AS is the uncertainty whether...

How to interpret the certainty of evidence based on GRADE (Grading of Recommendations, Assessment, Development and Evaluation)

GRADE (Grading of Recommendations, Assessment, Development and Evaluation) is awidely used approach in the fields of medicine and public health to assess the outcome-specific certainty of the evidence in systematic reviews. To make the GRADE approach comprehensible in order to facilitate the reading, understanding and interpretation of GRADE assessments in systematic reviews. Presentation of the procedure of the GRADE approach using the example of aCochrane review on selenium supplements in the prevention of prostate cancer. GRADE provides criteria for rating the certainty of evidence. GRADE's approach to rating the certainty of the evidence is based on afour-level system (high, moderate, low, very low). The GRADE approach classifies bodies of randomized controlled trials as initially starting at high certainty and bodies of observational studies at initially starting at low certainty. By assessing the five domains (risk for bias, inconsistency, indirectness, insufficient precision and publication bias), certainty can be rated down or, in the case of large effects, existing dose-response relationships or plausible confounders, rated up. GRADE is aconsistent and transparent approach for rating the certainty of abody of evidence by offering explicit key questions.

Impact of 5-ALPHA reductase inhibitor use on prostate cancer risk at the time of urology referral.

226 Background: 5-alpha reductase inhibitors (5-ARIs) are commonly used medications for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia. One of the consequences of 5-ARI use is a 50% drop in serum PSA without a concomitant reduction in prostate cancer (PCa) risk. Previous work has suggested that 5-ARI use is associated with worse PCa-specific outcomes. The objective of this study was to evaluate the impact of 5-ARI use on patients’ PCa risk at the time of referral from primary care to urology. Methods: This retrospective cohort study included all men ≥ 40 years who had a PSA resulted between 2018-2019 and were seen in an ambulatory setting. PSA testing was determined through laboratory data in the electronic health record (EHR). Clinical and demographic data were collected for all men. 5-ARI use was determined through orders in the EHR. Men were assigned PCa risk according to both the Prostate Biopsy Collaborative Group (PBCG) and Prostate Cancer Prevention Trial (PCPT) risk calculators. PSA values were doubled for 5-ARI users prior to calculating risk. Referral to urology for PCa risk was determined using the narrative reason for referral associated with the referral order. Results: Between 2018-2019, 91,368 men had a PSA test, including 2,939 5-ARI users, and 88,429 non-users. Uncorrected median PSA and the proportion of men referred to urology for PCa risk were similar between the two groups (p = 0.60 and p = 0.17, respectively). Of men referred to urology for PCa risk, 5-ARI users had similar uncorrected PSA to non-users (p=0.86) but higher risk for high grade PCa once PSA correction was performed, median (IQR) 48% (24%) vs 28% (18%) using the PBCG and 21% (17%) vs 10% (10%) using the PCPT (p &lt; 0.01 for both) (Table). Conclusions: Men taking 5-ARIs have significantly higher risk for high-grade PCa at time of referral to urology than non-users in this cohort. As the unadjusted PSA at referral to urology for PCa risk was the same between 5-ARI users and non-users, this indicates that the effect of 5-ARI use on serum PSA levels is not routinely accounted for when assessing PCa risk. Further study on interventions to account for 5-ARI use when screening for PCa are warranted. [Table: see text]

Androgen deprivation-induced elevated nuclear SIRT1 promotes prostate tumor cell survival by reactivation of AR signaling

The NAD+-dependent deacetylase, Sirtuin 1 (SIRT1) is involved in prostate cancer pathogenesis. However, the actual contribution is unclear as some reports propose a protective role while others suggest it is harmful. We provide evidence for a contextual role for SIRT1 in prostate cancer. Our data show that (i) mice orthotopically implanted with SIRT1-silenced LNCaP cells produced smaller tumors; (ii) SIRT1 suppression mimicked AR inhibitory effects in hormone responsive LNCaP cells; and (iii) caused significant reduction in gene signatures associated with E2F and MYC targets in AR-null PC-3 and E2F and mTORC1 signaling in castrate-resistant ARv7 positive 22Rv1 cells. Our findings further show increased nuclear SIRT1 (nSIRT1) protein under androgen-depleted relative to androgen-replete conditions in prostate cancer cell lines. Silencing SIRT1 resulted in decreased recruitment of AR to PSA enhancer selectively under androgen-deprivation conditions. Prostate cancer outcome data show that patients with higher levels of nSIRT1 progress to advanced disease relative to patients with low nSIRT1 levels. Collectively, we demonstrate that lowering SIRT1 levels potentially provides new avenues to effectively prevent prostate cancer recurrence.

Comparison of Multiparametric Magnetic Resonance Imaging–Targeted Biopsy With Systematic Transrectal Ultrasonography Biopsy for Biopsy-Naive Men at Risk for Prostate Cancer

Magnetic resonance imaging (MRI) with targeted biopsy is an appealing alternative to systematic 12-core transrectal ultrasonography (TRUS) biopsy for prostate cancer diagnosis, but has yet to be widely adopted. To determine whether MRI with only targeted biopsy was noninferior to systematic TRUS biopsies in the detection of International Society of Urological Pathology grade group (GG) 2 or greater prostate cancer. This multicenter, prospective randomized clinical trial was conducted in 5 Canadian academic health sciences centers between January 2017 and November 2019, and data were analyzed between January and March 2020. Participants included biopsy-naive men with a clinical suspicion of prostate cancer who were advised to undergo a prostate biopsy. Clinical suspicion was defined as a 5% or greater chance of GG2 or greater prostate cancer using the Prostate Cancer Prevention Trial Risk Calculator, version 2. Additional criteria were serum prostate-specific antigen levels of 20 ng/mL or less (to convert to micrograms per liter, multiply by 1) and no contraindication to MRI. Magnetic resonance imaging-targeted biopsy (MRI-TB) only if a lesion with a Prostate Imaging Reporting and Data System (PI-RADS), v 2.0, score of 3 or greater was identified vs 12-core systematic TRUS biopsy. The proportion of men with a diagnosis of GG2 or greater cancer. Secondary outcomes included the proportion who received a diagnosis of GG1 prostate cancer; GG3 or greater cancer; no significant cancer but subsequent positive MRI results and/or GG2 or greater cancer detected on a repeated biopsy by 2 years; and adverse events. The intention-to-treat population comprised 453 patients (367 [81.0%] White, 19 [4.2%] African Canadian, 32 [7.1%] Asian, and 10 [2.2%] Hispanic) who were randomized to undergo TRUS biopsy (226 [49.9%]) or MRI-TB (227 [51.1%]), of which 421 (93.0%) were evaluable per protocol. A lesion with a PI-RADS score of 3 or greater was detected in 138 of 221 men (62.4%) who underwent MRI, with 26 (12.1%), 82 (38.1%), and 30 (14.0%) having maximum PI-RADS scores of 3, 4, and 5, respectively. Eighty-three of 221 men who underwent MRI-TB (37%) had a negative MRI result and avoided biopsy. Cancers GG2 and greater were identified in 67 of 225 men (30%) who underwent TRUS biopsy vs 79 of 227 (35%) allocated to MRI-TB (absolute difference, 5%, 97.5% 1-sided CI, -3.4% to ∞; noninferiority margin, -5%). Adverse events were less common in the MRI-TB arm. Grade group 1 cancer detection was reduced by more than half in the MRI arm (from 22% to 10%; risk difference, -11.6%; 95% CI, -18.2% to -4.9%). Magnetic resonance imaging followed by selected targeted biopsy is noninferior to initial systematic biopsy in men at risk for prostate cancer in detecting GG2 or greater cancers. ClinicalTrials.gov Identifier: NCT02936258.

Dietary Factors and Prostate Cancer Development, Progression, and Reduction.

Due to the constantly increasing number of cases, prostate cancer has become one of the most important health problems of modern societies. This review presents the current knowledge regarding the role of nutrients and foodstuff consumption in the etiology and development of prostate malignancies, including the potential mechanisms of action. The results of several in vivo and in vitro laboratory experiments as well as those reported by the clinical and epidemiological research studies carried out around the world were analyzed. The outcomes of these studies clearly show the influence of both nutrients and food products on the etiology and prevention of prostate cancer. Consumption of certain nutrients (saturated and trans fatty acids) and food products (e.g., processed meat products) leads to the disruption of prostate hormonal regulation, induction of oxidative stress and inflammation, and alteration of growth factor signaling and lipid metabolism, which all contribute to prostate carcinogenesis. On the other hand, a high consumption of vegetables, fruits, fish, and whole grain products exerts protective and/or therapeutic effects. Special bioactive functions are assigned to compounds such as flavonoids, stilbenes, and lycopene. Since the influence of nutrients and dietary pattern is a modifiable risk factor in the development and prevention of prostate cancer, awareness of the beneficial and harmful effects of individual food ingredients is of great importance in the global strategy against prostate cancer.

Pomegranate, its Components, and Modern Deliverable Formulations as Potential Botanicals in the Prevention and Treatment of Various Cancers

Cancer is a global multifactorial disease consisting of over 200 types of cancers. It is well recognized that primary prevention is an effective way to fight cancers by using natural polyphenolic anticancer foods, vegetables, and fruits, avoiding exposure to the carcinogenic environment, smoking cessation, and through lifestyle modifications. The present review provides up-todate information on the effects and functions of pomegranate juice and its bioactive components on the most widespread six cancer types. Pomegranate contains important polyphenolic compounds, such as ellagitannins and punicalagin, with strong antioxidant ability for scavenging free radicals and producing metal-chelates in the biological tissues. The in vitro and in vivo studies suggests that antioxidant and anti-inflammation properties of pomegranate constitute have major antimutagenic and antiproliferative activities for regulating gene expression, modulating cellular mechanisms, and limiting the ability of cancers to metastasize. A limited number of clinical studies have suggested that pomegranate ingredients have the potential for the prevention and treatment of cancer, especially colorectal and prostate cancer. In cancer therapy, it remains a clinical dilemma to hit the right target without inducing side effects. The costly anticancer chemotherapies are often associated with drug resistance and serious side effects in vital organs and noncancerous neighboring cells. It appears that the pomegranate-based phytotherapy would be affordable and cost-effective for next-generation non-pharmacologic anticancer remedies with lesser side effects. However, well-designed, randomized, double-blind, and multi-center studies are needed to establish the long-term safety, efficacy, and dose schedules for orally deliverable pomegranate formulations.

Epigenetics/Epigenomics and Prevention of Early Stages of Cancer by Isothiocyanates.

Cancer is a complex disease and cancer development takes 10-50 years involving epigenetics. Evidence suggests that approximately 80% of human cancers are linked to environmental factors impinging upon genetics/epigenetics. Because advanced metastasized cancers are resistant to radiotherapy/chemotherapeutic drugs, cancer prevention by relatively nontoxic chemopreventive "epigenetic modifiers" involving epigenetics/epigenomics is logical. Isothiocyanates are relatively nontoxic at low nutritional and even higher pharmacologic doses, with good oral bioavailability, potent antioxidative stress/antiinflammatory activities, possess epigenetic-modifying properties, great anticancer efficacy in many in vitro cell culture and in vivo animal models. This review summarizes the latest advances on the role of epigenetics/epigenomics by isothiocyanates in prevention of skin, colon, lung, breast, and prostate cancers. The exact molecular mechanism how isothiocyanates modify the epigenetic/epigenomic machinery is unclear. We postulate "redox" processes would play important roles. In addition, isothiocyanates sulforaphane and phenethyl isothiocyanate, possess multifaceted molecular mechanisms would be considered as "general" cancer preventive agents not unlike chemotherapeutic agents like platinum-based or taxane-based drugs. Analogous to chemotherapeutic agents, the isothiocyanates would need to be used in combination with other nontoxic chemopreventive phytochemicals or drugs such as NSAIDs, 5-α-reductase/aromatase inhibitors targeting different signaling pathways would be logical for the prevention of progression of tumors to late advanced metastatic states.

The Effects of Resveratrol on Prostate Cancer through Targeting the Tumor Microenvironment.

Prostate cancer is one of the most common cancers diagnosed in men in the United States and the second leading cause of cancer-related deaths worldwide. Since over 60% of prostate cancer cases occur in men over 65 years of age, and this population will increase steadily in the coming years, prostate cancer will be a major cancer-related burden in the foreseeable future. Accumulating data from more recent research suggest that the tumor microenvironment (TME) plays a previously unrecognized role in every stage of cancer development, including initiation, proliferation, and metastasis. Prostate cancer is not only diagnosed in the late stages of life, but also progresses relatively slowly. This makes prostate cancer an ideal model system for exploring the potential of natural products as cancer prevention and/or treatment reagents because they usually act relatively slowly compared to most synthetic drugs. Resveratrol (RSV) is a naturally occurring stilbenoid and possesses strong anti-cancer properties with few adverse effects. Accumulating data from both in vitro and in vivo experiments indicate that RSV can interfere with prostate cancer initiation and progression by targeting the TME. Therefore, this review is aimed to summarize the recent advancement in RSV-inhibited prostate cancer initiation, proliferation, and metastasis as well as the underlying molecular mechanisms, with particular emphasis on the effect of RSV on TME. This will not only better our understanding of prostate cancer TMEs, but also pave the way for the development of RSV as a potential reagent for prostate cancer prevention and/or therapy.