Papers by Nikunj Gevariya
S1. Chronic long-chain omega-3 (LCω3) treatment blocks prostate cancer cell growth. S2. Tables of... more S1. Chronic long-chain omega-3 (LCω3) treatment blocks prostate cancer cell growth. S2. Tables of differentially expressed genes in tumors of MAG-EPA-supplemented mice. S3. Twenty men supplemented for 4-10 weeks with MAG-EPA or placebo before radical prostatectomy. S4. Stable expression of the ω3 fatty acid desaturase 1 (FAT-1) from c. elegans, which convert ω6 into ω3 fatty acids, hinders prostate cancer cell growth. S5. Cytokine profiling of mouse tumors.
The impact of omega (ω)-3 fatty acids on prostate cancer is controversial in epidemiological stud... more The impact of omega (ω)-3 fatty acids on prostate cancer is controversial in epidemiological studies but experimental studies suggest a protective effect. However, little is known about the mechanism of action. Here, we studied the effects of purified fatty acid molecules on prostate tumor progression using the TRAMP-C2 syngeneic immunocompetent mouse model. Compared with ω-6 or ω-9–supplemented animals, we observed that late-stage prostate tumor growth was reduced with a monoacylglyceride (MAG)-conjugated form of eicosapentaenoic acid (EPA) supplementation, whereas docosahexanenoic acid (DHA) caused an early reduction. MAG–EPA significantly decreased tumor blood vessel diameter (P < 0.001). RNA sequencing analysis revealed that MAG–EPA downregulated angiogenesis- and vascular-related pathways in tumors. We also observed this tissue vascular phenotype in a clinical trial testing MAG–EPA versus a high oleic sunflower oil placebo. Using anti-CD31 IHC, we observed that MAG–EPA reduc...
Cancer Immunology Research
Introduction and Objective: Recently, gut microbiota emerged as an important factor for success o... more Introduction and Objective: Recently, gut microbiota emerged as an important factor for success of immunity-based cancer treatments. However, its steady-state interaction and contribution to developing tumors is largely unexplored in non-intestinal cancers. Our objective was to investigate the connection between prostate tumor and the gut microbiota independently of cancer therapies. Methods: Human fecal samples were obtained from men participating into a phase IIb double-blind randomized controlled trial testing 3g/day of monoglyceride-eicosapentaenoic acid (MAG-EPA) versus placebo for a 4-10 week period before their radical prostatectomy (NCT02333435). A second set of samples were from men taking the same intervention of MAG-EPA or placebo after a PSA increase following their radical prostatectomy (NCT03753334). Short chain fatty acids (SCFA) analysis of patient stool samples between baseline and surgery was performed by gas chromatography coupled with flame ionization detection. ...
clarifiée, suggérant que ce type d'échantillon devrait être utilisé pour les prochaines analyses.... more clarifiée, suggérant que ce type d'échantillon devrait être utilisé pour les prochaines analyses. Dans l'ensemble, mes résultats confirment l'importance des acides gras ω3 pour la prévention de la progression du CaP et appuient une étude plus approfondie de leurs effets sur la réponse immunitaire, l'angiogenèse et la progression tumorale chez les patients atteints de CaP.
Prostaglandins, Leukotrienes and Essential Fatty Acids
Molecular Cancer Research
Nutrients
Dietary omega-3 fatty acids (ω3), particularly long-chain ω3 (LCω3), have protective effects agai... more Dietary omega-3 fatty acids (ω3), particularly long-chain ω3 (LCω3), have protective effects against prostate cancer (PCa) in experimental studies. Observational studies are conflicting, possibly because of the biomarker used. This study aimed at evaluating associations between grade reclassification and ω3 levels assessed in prostatic tissue, red blood cells (RBC), and diet. We conducted a validation cross-sectional study nested within a phase II clinical trial. We identified 157 men diagnosed with low-risk PCa who underwent a first active surveillance repeat prostate biopsy session. Fatty acid (FA) intake was assessed using a food frequency questionnaire and their levels measured in prostate tissue and RBC. Associations were evaluated using logistic regression. At first repeat biopsy session, 39 (25%) men had high-grade PCa (grade group ≥2). We found that high LCω3-eicosapentaenoic acid (EPA) level in prostate tissue (odds ratio (OR) 0.25; 95% (confidence interval (CI) 0.08–0.79; ...
The Prostate, Jan 2, 2018
Several lines of evidence suggest effects of dietary fat on prostate cancer (PCa) development and... more Several lines of evidence suggest effects of dietary fat on prostate cancer (PCa) development and progression. Targeting omega (ω)-3:ω6 fatty acids (FA) ratio could be beneficial against PCa by favorably modulating inflammation. Here, we studied the effects of ω3- and ω6-enriched diets on prostate tumor growth and inflammatory response in androgen-deprived and non-deprived conditions. Immune-competent eugonadal and castrated C57BL/6 mice were injected with TRAMP-C2 prostate tumor cells and daily fed with ω3- or ω6-enriched diet. FA and cytokine profiles were measured in blood and tumors using gas chromatography and multiplex immunoassay, respectively. Immune cell infiltration in tumors was profiled by multicolor flow cytometry. ω3-enriched diet decreased prostate TRAMP-C2 tumor growth in immune-competent eugonadal and castrated mice. Cytokines associated with Th1 immune response (IL-12 [p70], IFN-γ, GM-CSF) and eosinophil recruitment (eotaxin-1, IL-5, and IL-13) were significantly e...
Nutrients, Jul 16, 2019
Dietary omega-3 fatty acids (ω3), particularly long-chain ω3 (LCω3), have protective effects agai... more Dietary omega-3 fatty acids (ω3), particularly long-chain ω3 (LCω3), have protective effects against prostate cancer (PCa) in experimental studies. Observational studies are conflicting, possibly because of the biomarker used. This study aimed at evaluating associations between grade reclassification and ω3 levels assessed in prostatic tissue, red blood cells (RBC), and diet. We conducted a validation cross-sectional study nested within a phase II clinical trial. We identified 157 men diagnosed with low-risk PCa who underwent a first active surveillance repeat prostate biopsy session. Fatty acid (FA) intake was assessed using a food frequency questionnaire and their levels measured in prostate tissue and RBC. Associations were evaluated using logistic regression. At first repeat biopsy session, 39 (25%) men had high-grade PCa (grade group ≥2). We found that high LCω3-eicosapentaenoic acid (EPA) level in prostate tissue (odds ratio (OR) 0.25; 95% (confidence interval (CI) 0.08-0.79; p-trend = 0.03) was associated with lower odds of high-grade PCa. Similar results were observed for LCω3 dietary intake (OR 0.30; 95% CI 0.11-0.83; p-trend = 0.02) but no association for RBC. LCω3-EPA levels in the target prostate tissue are inversely associated with high-grade PCa in men with low-risk PCa, supporting that prostate tissue FA, but not RBC FA, is a reliable biomarker of PCa risk.
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Papers by Nikunj Gevariya