CURRENT EPIDEMIOLOGICAL KNOWLEDGE ABOUT THE ROLE OF FLAVONOIDS IN PROSTATE CARCINOGENESIS

Numerous experimental studies have demonstrated anticancer action of polyphenolic plant metabolites. However, data about associations between dietary intake of plant-derived flavonoids and prostate cancer risk are still sparse and inconsistent. This minireview compiles the epidemiological findings published to date on the role of flavonoids in prostate tumorigenesis, discusses the reasons of inconsistencies and elicits the promising results for chemoprevention of this malignancy. Long-term consumption of high doses of soy isoflavones can be the reason of markedly lower clinically detectable prostate cancer incidence among Asian men compared to their counterparts in the Western world. The ability to metabolize daidzein to equol, the most biologically active isoflavone, by the certain intestinal bacteria also seems to contribute to this important health benefit. The increasing incidence rate of prostate cancer related to adoption of westernized lifestyle and dietary habits makes the issue of chemoprevention ever more important and directs the eyes to specific food components in the Eastern diet. If further large-scale epidemiological studies will confirm the protective effects of isoflavones against prostate cancer, this could provide an important way for prostate cancer prevention, as diet is a potentially modifiable factor in our behavioral pattern.

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Assessing the Role of Copy Number Variants in Prostate Cancer Risk and Progression using a Novel Genome-Wide Screening Method

10.21236/ada568305 ◽

2012 ◽

Author(s):

Donna Lehman ◽

August Blackburn ◽

Robin Leach

Keyword(s):

Prostate Cancer ◽

Cancer Risk ◽

Copy Number ◽

Screening Method ◽

Copy Number Variants ◽

Prostate Cancer Risk ◽

Genome Wide

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The role of microRNA-572 in the proliferation and chemotherapeutic treatment of prostate cancer

Journal of International Medical Research ◽

10.1177/03000605211014363 ◽

2021 ◽

Vol 49 (5) ◽

pp. 030006052110143

Author(s):

Mingcui Zang ◽

Xun Guo ◽

Manqiu Chen

Keyword(s):

Prostate Cancer ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Prostate Tumorigenesis ◽

Expression Levels ◽

Matrigel Invasion ◽

Tensin Homolog ◽

Docetaxel Treatment ◽

Induced Apoptosis

Objective MicroRNAs (miRNAs) regulate prostate tumorigenesis and progression by involving different molecular pathways. In this study, we examined the role of miR-572 in prostate cancer (PCa). Methods The proliferation rates of LNCaP and PC-3 PCa cells were studied using MTT assays. Transwell migration and Matrigel invasion assays were performed to evaluate cell migration and invasion, respectively. Protein expression levels were examined using western blotting. Docetaxel-induced apoptosis was evaluated by Caspase-Glo3/7 assays. The putative miR-572 binding site in the phosphatase and tensin homolog (PTEN) 3ʹ untranslated region (3ʹ UTR) was assessed with dual-luciferase reporter assays. Additionally, miR-572 expression levels in human PCa tissues were examined by qRT-PCR assays. Results Upregulation of miR-572 promoted proliferation, migration, and invasion of PCa cells. Overexpression of miR-572 decreased sensitivity of PCa cells to docetaxel treatment by reducing docetaxel-induced apoptosis. MiR-572 can regulate migration and invasion in PCa cells. Furthermore, miR-572 could regulate expression of PTEN and p-AKT in PCa cells by directly binding to the PTEN 3ʹ UTR. MiR-572 expression levels were increased in human PCa tissues and associated with PCa stage. Conclusions miR-572 displayed essential roles in PCa tumor growth and its expression level may be used to predict docetaxel treatment in these tumors.

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Role of Platelet-Activating Factor in Cardiovascular Pathophysiology

Physiological Reviews ◽

10.1152/physrev.2000.80.4.1669 ◽

2000 ◽

Vol 80 (4) ◽

pp. 1669-1699 ◽

Cited By ~ 245

Author(s):

Giuseppe Montrucchio ◽

Giuseppe Alloatti ◽

Giovanni Camussi

Keyword(s):

Cardiovascular System ◽

Cell Biology ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Critical Role ◽

Experimental Studies ◽

Platelet Activating Factor ◽

Biologically Active ◽

Endothelial Cell Migration

Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides. PAF acts via a specific receptor that is coupled with a G protein, which activates a phosphatidylinositol-specific phospholipase C. In this review we focus on the aspects that are more relevant for the cell biology of the cardiovascular system. The in vitro studies provided evidence for a role of PAF both as intercellular and intracellular messenger involved in cell-to-cell communication. In the cardiovascular system, PAF may have a role in embryogenesis because it stimulates endothelial cell migration and angiogenesis and may affect cardiac function because it exhibits mechanical and electrophysiological actions on cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure mainly by affecting the renal vascular circulation. In pathological conditions, PAF has been involved in the hypotension and cardiac dysfunctions occurring in various cardiovascular stress situations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic shock syndromes. In addition, experimental studies indicate that PAF has a critical role in the development of myocardial ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of leukocytes in inflamed tissue by promoting adhesion to the endothelium and extravascular transmigration of leukocytes. The finding that human heart can produce PAF, expresses PAF receptor, and is sensitive to the negative inotropic action of PAF suggests that this mediator may have a role also in human cardiovascular pathophysiology.

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CHEK2∗1100delC Mutation and Risk of Prostate Cancer

Prostate Cancer ◽

10.1155/2014/294575 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 24

Author(s):

Victoria Hale ◽

Maren Weischer ◽

Jong Y. Park

Keyword(s):

Prostate Cancer ◽

Current Knowledge ◽

Prostate Cancer Screening ◽

Critical Role ◽

Prostate Cancer Risk ◽

Conclusive Evidence ◽

Increased Risk ◽

History Of ◽

Cancer Studies

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer.CHEK2plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, ofCHEK2on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussedCHEK2∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating thatCHEK2∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer.

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Associations Between Polymorphisms in Genes Related to Oxidative Stress and DNA Repair, Interactions With Serum Antioxidants, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial

Frontiers in Oncology ◽

10.3389/fonc.2021.808715 ◽

2022 ◽

Vol 11 ◽

Author(s):

Zhihong Gong ◽

Mary E. Platek ◽

Cathee Till ◽

Phyllis J. Goodman ◽

Catherine M. Tangen ◽

...

Keyword(s):

Oxidative Stress ◽

Prostate Cancer ◽

Dna Repair ◽

Cancer Prevention ◽

Prostate Cancer Risk ◽

Minor Allele ◽

Cancer Etiology ◽

Lower Serum ◽

Prostate Cancer Prevention

Study of polymorphisms in genes related to the generation and removal of oxidative stress and repair of oxidative DNA damage will lead to new insights into the genetic basis of prostate cancer. In the Prostate Cancer Prevention Trial (PCPT), a double-blind, randomized controlled trial testing finasteride versus placebo for prostate cancer prevention, we intend to investigate the role of oxidative stress/DNA repair mechanisms in prostate cancer etiology and whether these polymorphisms modify prostate cancer risk by interacting with antioxidant status in both placebo and finasteride arms. We evaluated associations of selected candidate polymorphisms in genes in these pathways, and interactions with pre-diagnostic serum antioxidants, and the risk of prostate cancer among 1,598 cases and 1,706 frequency-matched controls enrolled in the PCPT. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable-adjusted logistic regression models. While there were no statistically significant associations observed in the placebo arm, several SNPs were associated with prostate cancer in the finasteride arm. Specifically, APEX1-rs1760944 was associated with increased risk of total prostate cancer (per minor allele: p-trend=0.04). OGG1-rs1052133 was positively (CG/GG vs. CC: OR=1.32, 95% CI: 1.01-1.73) and NOS3-rs1799983 was inversely (per minor allele: p-trend=0.04) associated with risk of low-grade prostate cancer. LIG3-rs1052536 and XRCC1-rs25489 were suggestively associated with reduced risk of high-grade prostate cancer (per minor allele: both p-trend=0.04). In the placebo arm, significant associations were observed among men with higher serum lycopene for APEX1-rs1760944 and NQO1-rs1800566, or higher serum β-cryptoxanthin for ERCC4-rs1800067. In the finasteride arm, stronger associations were observed among men with lower serum lycopene for NOS3-rs1799983, higher serum α-carotene, β-carotene, and β-cryptoxanthin for LIG3-rs1052536, or lower serum retinol for SOD2-rs1799725. These results suggest that germline variations in oxidative stress and DNA repair pathways may contribute to prostate carcinogenesis and that these associations may differ by intraprostatic sex steroid hormone status and be further modified by antioxidant status. Findings provide insights into the complex role of gene, gene-antioxidant and -finasteride interactions in prostate cancer etiology, and thus may lead to the development of preventative strategies.

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The Role of Cancer-Associated Fibroblasts in Prostate Cancer Tumorigenesis

Cancers ◽

10.3390/cancers12071887 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1887 ◽

Cited By ~ 1

Author(s):

Francesco Bonollo ◽

George N. Thalmann ◽

Marianna Kruithof-de Julio ◽

Sofia Karkampouna

Keyword(s):

Prostate Cancer ◽

Molecular Mechanisms ◽

Therapeutic Potential ◽

Current Knowledge ◽

Therapy Resistance ◽

Cancer Associated Fibroblasts ◽

Metastatic Progression ◽

Normal Prostate ◽

Prostate Tumorigenesis

Tumors strongly depend on their surrounding tumor microenvironment (TME) for growth and progression, since stromal elements are required to generate the optimal conditions for cancer cell proliferation, invasion, and possibly metastasis. Prostate cancer (PCa), though easily curable during primary stages, represents a clinical challenge in advanced stages because of the acquisition of resistance to anti-cancer treatments, especially androgen-deprivation therapies (ADT), which possibly lead to uncurable metastases such as those affecting the bone. An increasing number of studies is giving evidence that prostate TME components, especially cancer-associated fibroblasts (CAFs), which are the most abundant cell type, play a causal role in PCa since the very early disease stages, influencing therapy resistance and metastatic progression. This is highlighted by the prognostic value of the analysis of stromal markers, which may predict disease recurrence and metastasis. However, further investigations on the molecular mechanisms of tumor–stroma interactions are still needed to develop novel therapeutic approaches targeting stromal components. In this review, we report the current knowledge of the characteristics and functions of the stroma in prostate tumorigenesis, including relevant discussion of normal prostate homeostasis, chronic inflammatory conditions, pre-neoplastic lesions, and primary and metastatic tumors. Specifically, we focus on the role of CAFs, to point out their prognostic and therapeutic potential in PCa.

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Combination of Peri-Tumoral and Intra-Tumoral Radiomic Features on Bi-Parametric MRI Accurately Stratifies Prostate Cancer Risk: A Multi-Site Study

Cancers ◽

10.3390/cancers12082200 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2200 ◽

Cited By ~ 1

Author(s):

Ahmad Algohary ◽

Rakesh Shiradkar ◽

Shivani Pahwa ◽

Andrei Purysko ◽

Sadhna Verma ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Risk Stratification ◽

Operating Characteristic ◽

Prostate Cancer Risk ◽

Magnetic Resonance Imaging Mri ◽

Validation Set ◽

And Diffusion ◽

Risk Categories

Background: Prostate cancer (PCa) influences its surrounding habitat, which tends to manifest as different phenotypic appearances on magnetic resonance imaging (MRI). This region surrounding the PCa lesion, or the peri-tumoral region, may encode useful information that can complement intra-tumoral information to enable better risk stratification. Purpose: To evaluate the role of peri-tumoral radiomic features on bi-parametric MRI (T2-weighted and Diffusion-weighted) to distinguish PCa risk categories as defined by D’Amico Risk Classification System. Materials and Methods: We studied a retrospective, HIPAA-compliant, 4-institution cohort of 231 PCa patients (n = 301 lesions) who underwent 3T multi-parametric MRI prior to biopsy. PCa regions of interest (ROIs) were delineated on MRI by experienced radiologists following which peri-tumoral ROIs were defined. Radiomic features were extracted within the intra- and peri-tumoral ROIs. Radiomic features differentiating low-risk from: (1) high-risk (L-vs.-H), and (2) (intermediate- and high-risk (L-vs.-I + H)) lesions were identified. Using a multi-institutional training cohort of 151 lesions (D1, N = 116 patients), machine learning classifiers were trained using peri- and intra-tumoral features individually and in combination. The remaining 150 lesions (D2, N = 115 patients) were used for independent hold-out validation and were evaluated using Receiver Operating Characteristic (ROC) analysis and compared with PI-RADS v2 scores. Results: Validation on D2 using peri-tumoral radiomics alone resulted in areas under the ROC curve (AUCs) of 0.84 and 0.73 for the L-vs.-H and L-vs.-I + H classifications, respectively. The best combination of intra- and peri-tumoral features resulted in AUCs of 0.87 and 0.75 for the L-vs.-H and L-vs.-I + H classifications, respectively. This combination improved the risk stratification results by 3–6% compared to intra-tumoral features alone. Our radiomics-based model resulted in a 53% accuracy in differentiating L-vs.-H compared to PI-RADS v2 (48%), on the validation set. Conclusion: Our findings suggest that peri-tumoral radiomic features derived from prostate bi-parametric MRI add independent predictive value to intra-tumoral radiomic features for PCa risk assessment.

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Hormonal Predictors of Prostate Cancer: A Meta-Analysis

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.4.847 ◽

2000 ◽

Vol 18 (4) ◽

pp. 847-847 ◽

Cited By ~ 199

Author(s):

Terrence Shaneyfelt ◽

Rozita Husein ◽

Glenn Bubley ◽

Christos S. Mantzoros

Keyword(s):

Prostate Cancer ◽

Cancer Risk ◽

Confidence Interval ◽

Population Distribution ◽

Serum Insulin ◽

Meta Analysis ◽

Prostate Cancer Risk ◽

Sex Hormone Binding Globulin ◽

Total Testosterone

PURPOSE: Although there is strong circumstantial evidence that androgens are implicated in the etiology of prostate cancer, epidemiologic investigations have failed to demonstrate consistently that one or more steroid hormones are implicated. In contrast, recent epidemiologic studies unequivocally link serum insulin-like growth factor 1 (IGF-1) levels with risk for prostate cancer. METHODS: We have performed the first meta-analysis of all previously published studies on hormonal predictors of risk for prostate cancer. RESULTS: A meta-analysis restricted to studies that performed mutual adjustment for all measured serum hormones, age, and body mass index indicated that men whose total testosterone is in the highest quartile are 2.34 times more likely to develop prostate cancer (95% confidence interval, 1.30 to 4.20). In contrast, levels of dihydrotestosterone and estradiol do not seem to play a role of equal importance. The only study that provides multivariably adjusted sex hormone–binding globulin data indicates that this binding protein is inversely related to prostate cancer risk (odds ratio, 0.46; 95% confidence interval, 0.24 to 0.89). Finally, all three studies that examined the role of serum IGF-1 have consistently demonstrated a positive and significant association with prostate cancer risk that is similar in magnitude to that of testosterone. CONCLUSION: Men with either serum testosterone or IGF-1 levels in upper quartile of the population distribution have an approximately two-fold higher risk for developing prostate cancer.

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