The gut microbiome-prostate cancer crosstalk is modulated by dietary polyunsaturated long-chain fatty acids.

The gut microbiota modulates response to hormonal treatments in prostate cancer (PCa) patients, but whether it influences PCa progression remains unknown. Here, we show a reduction in fecal microbiota alpha-diversity correlating with increase tumour burden in two distinct groups of hormonotherapy naïve PCa patients and three murine PCa models. Fecal microbiota transplantation (FMT) from patients with high PCa volume is sufficient to stimulate the growth of mouse PCa revealing the existence of a gut microbiome-cancer crosstalk. Analysis of gut microbial-related pathways in mice with aggressive PCa identifies three enzymes responsible for the metabolism of long-chain fatty acids (LCFA). Supplementation with LCFA omega-3 MAG-EPA is sufficient to reduce PCa growth in mice and cancer up-grading in pre-prostatectomy PCa patients correlating with a reduction of gut Ruminococcaceae in both and fecal butyrate levels in PCa patients. This suggests that the beneficial effect of omega-3 rich diet is mediated in part by modulating the crosstalk between gut microbes and their metabolites in men with PCa.

The role of metformin, statins and diet in men on active surveillance for prostate cancer.

PURPOSE OF REVIEW: A sound scientific basis has been emerging on the anti-neoplastic role of metformin, statins and dietary interventions. However, evidence in prostate cancer patients remains mixed owing to an absence of completed randomized trials. This overview examines the rationale for metformin, statins and dietary intervention for secondary prevention in men on active surveillance by summarizing current evidence base and biological mechanisms in influencing cancer progression and mortality. METHODS: A comprehensive literature search was performed to identify studies that evaluated the role of metformin, statins and diet in the secondary prevention of prostate cancer as well as those that described the anti-cancer mechanisms of these agents. The search included Pubmed, MEDLINE, EMBASE and Cochrane library from inception till August 2021. RESULTS: A total of 14 trials on metformin, 21 trials on statins and 13 trials on dietary measures were evaluated. Majority were observational population-based cohort studies or meta-analysis of them. Three ongoing prospective randomized controlled trials were also reported. Overall, mixed results were obtained. CONCLUSIONS: The role of metformin and statins remains promising with several trials showing reduced rates of progression and cancer specific mortality. Combination therapy strategies have also been evaluated in more advanced patients showing synergism. Dietary interventions especially fruits, vegetables and fish intake has shown some benefit albeit with mixed results for others like legumes, red meat, coffee and multivitamins. Several ongoing randomized trials will provide stronger evidence in the future for secondary prevention.

Tomato and Olive Bioactive Compounds: A Natural Shield against the Cellular Effects Induced by ß-Hexachlorocyclohexane-Activated Signaling Pathways.

The ß-isomer of hexachlorocyclohexane (ß-HCH) is a globally widespread pollutant that embodies all the physicochemical characteristics of organochlorine pesticides, constituting an environmental risk factor for a wide range of noncommunicable diseases. Previous in vitro studies from our group disclosed the carcinogenic potential of ß-HCH, which contributes to neoplastic transformation by means of multifaceted intracellular mechanisms. Considering the positive evidence regarding the protective role of natural bioactive compounds against pollution-induced toxicity, micronutrients from olive and tomato endowed with the capability of modulating ß-HCH cellular targets were tested. For this purpose, the solution obtained from a patented food supplement (No. EP2851080A1), referred to as Tomato and Olive Bioactive Compounds (TOBC), was administered to the androgen-sensitive prostate cancer cells LNCaP and different biochemical and cellular assays were performed to evaluate its efficiency. TOBC shows a dose-dependent significant chemoprotection by contrasting ß-HCH-induced intracellular responses such as STAT3 and AhR activation, disruption of AR signaling, antiapoptotic and proliferative activity, and increase in ROS production and DNA damage. These experimental outcomes identified TOBC as a suitable functional food to be included in a diet regimen aimed at defending cells from ß-HCH negative effects, recommending the development of tailored enriched formulations for exposed individuals.

Dietary tomato inhibits angiogenesis in TRAMP prostate cancer but is not protective with a Western-style diet in this pilot study.

Prostate cancer (PCa) remains the second most diagnosed cancer worldwide. Higher body weight is associated with chronic inflammation, increased angiogenesis, and treatment-resistant tumor phenotypes. Dietary tomato reduces PCa risk, which may be due to tomato inhibition of angiogenesis and disruption of androgen signaling. This pilot study investigated the interplay between tomato powder (TP), incorporated into control (CON) and obesogenic (OB) diets, and PCa tumor growth and blood perfusion over time in a transgenic model of PCa (TRAMP). Ultrasound microvessel imaging (UMI) results showed good agreement with gold-standard immunohistochemistry quantification of endothelial cell density, indicating that this technique can be applied to non-invasively monitor tumor blood perfusion in vivo. Greater body weight was positively associated with tumor growth. We also found that TP significantly inhibited prostate tumor angiogenesis but that this inhibition differentially affected measured outcomes depending on CON or OB diets. TP led to reduced tumor growth, intratumoral inflammation, and intratumoral androgen-regulated gene expression (srd5a1, srd5a2) when incorporated with the CON diet but greater tumor growth and intratumoral gene expression when incorporated with the OB diet. Results from this study show that protective benefits from dietary tomato are lost, or may become deleterious, when combined with a Western-style diet.

Vulpinic acid as a natural compound inhibits the proliferation of metastatic prostate cancer cells by inducing apoptosis.

BACKGROUND: Lichen secondary metabolites have drawn considerable attention in recent years due to the limitations of current treatment options. Vulpinic acid (VA) obtained from Letharia vulpina lichen species exerts a remarkable cytotoxic effect on different cancer types. However, the therapeutic efficacy of VA in metastatic prostate cancer (mPC) cells has not been investigated. In the present study, we aimed to identify VA-mediated cytotoxicity in PC-3 mPC cells compared with control cells. METHODS AND RESULTS: After identifying the cytotoxic concentrations of VA, VA induced apoptosis was analyzed by Annexin V, cell cycle, acridine orange and propidium iodide staining and RT-PCR analysis. Our findings showed that VA significantly decreased the viability of PC-3 cells (p < 0.01) and caused a considerable early apoptotic effects through G0/G1 arrest, nuclear blebbing and the activation of particularly initiator caspases. CONCLUSIONS: Therefore, VA may be a potential treatment option for mPC patients. However, the underlying molecular mechanisms of VA-induced apoptosis with advanced analysis should be further investigated.

Long chain omega-3 fatty acids and their oxidized metabolites are associated with reduced prostate tumor growth.

INTRODUCTION: Cancer has been associated with increased oxidative stress and deregulation of bioactive oxylipins derived from long-chain polyunsaturated fatty acids (LC-PUFA) like arachidonic acid (AA). There is a debate whether ω-3 LC-PUFA could promote or prevent prostate tumor growth through immune modulation and reduction of oxidative stress. Our aim was to study the association between enzymatically or non-enzymatically produced oxidized-LC-PUFA metabolites and tumor growth in an immune-competent eugonadal and castrated C57BL/6 male mice injected with TRAMP-C2 prostate tumor cells, fed with ω-3 or ω-6 LC-PUFA-rich diets. MATERIALS AND METHODS: Tumor fatty acids were profiled by gas chromatography and 26 metabolites derived from either AA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were assessed by liquid chromatography-mass spectrometry. RESULTS: The enriched ω-3 diet did not reduce oxidative stress overall in tumors but favored the formation of ω-3 rather than ω-6 derived isoprostanoids. We discovered that EPA and its oxidized-derivatives like F3-isoprostanes and prostaglandin (PG)F3α, were inversely correlated with tumor volume (spearman correlations and T-test, p<0.05). In contrast, F2-isoprostanes, adrenic acid, docosapentaenoic acid (DPAω-6) and PGE2 were positively correlated with tumor volume. Interestingly, F4-neuroprostanes, PGD2, PGF2α, and thromboxane were specifically increased in TRAMP-C2 tumors of castrated mice compared to those of eugonadal mice. DISCUSSION: Decreasing tumor growth under ω-3 diet could be attributed in part to increased levels of EPA and its oxidized-derivatives, a reduced level of pro-angiogenic PGE2 and increased levels of F4-neuroprostanes and resolvins content in tumors, suspected of having anti-proliferative and anti-inflammatory effects.

Medication utilization evaluation of androgen deprivation therapy for prostate cancer in Taiwan.

Prostate cancer is one of the most common cancer in males. Both the incidence and the mortality rates of prostate cancer show an increasing trend. Androgen deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer. The aim of our study was to show the epidemiology of prostate cancer and the proportion of patients utilizing ADT.This study used Taiwan's National Health Insurance Research Database (NHIRD) and identified the patients who had been diagnosed with prostate cancer (International Classification of Disease (ICD)-10: C61) and followed up between Jan 1, 2008 and Dec 31, 2015. The ADT drugs used by prostate cancer patients were recorded: Gonadotropin-releasing hormone (GnRH) agonists; GnRH antagonist; estrogen analogs and androgen receptor antagonist.A total of 25,233 patients with newly diagnosed prostate cancer in 2008-2014 were enrolled. The utilization of ADT increased from more than 7,000 person-time in 2008 to more than 50,000 person-time in 2014. Cyproterone acetate was the most commonly used drug in 2008-2015, but its proportion of utilization, which was the highest in stage 2 cancer, dropped from 43% in 2008 to 15% in 2015. Bicalutamide was the second most used drug from 2008 to 2015, but its utilization was not different for different stages.The incidence rate of prostate cancer increased in the study period and medical expenditure also increased in ADT treatment. Health insurance benefits for various ADT drugs should be further evaluated.

Dose-Dependent Increases in Ellagitannin Metabolites as Biomarkers of Intake in Humans Consuming Standardized Black Raspberry Food Products Designed for Clinical Trials.

SCOPE: Black raspberry (BRB) phytochemicals demonstrate anti-carcinogenic properties in experimental models, including prostate cancer. Two BRB foods, a confection and nectar, providing a consistent and reproducible product for human clinical studies are designed and characterized. METHODS AND RESULTS: Men with clinically localized prostate cancer are sequentially enrolled to a control group or one of four intervention groups (confection or nectar, 10 or 20 g dose; n = 8 per group) for 4 weeks prior to prostatectomy. Primary outcomes include: safety, adherence, and ellagitannin metabolism. Adherence to the intervention is >96%. No significant (≥grade II) toxicities are detected. Urinary urolithins (A, B, C, and D) and dimethyl ellagic acid (DMEA) quantified by Ultra high performance liquid chromatography tandem mass spectroscopy (UPLC/MS/MS) indicate a dose-dependent excretion yet heterogeneous patterns among men. Men in the BRB confection groups have greater urinary excretion of the microbial urinary metabolites urolithin A and DMEA, suggesting that this food matrix provides greater colonic microflora exposure. CONCLUSION: Fully characterized BRB confections and nectar are ideal for food-based large phase III human clinical studies. BRB products provide a bioavailable source of BRB phytochemicals, however large inter individual variation in polyphenol metabolism suggests that host genetics, microflora, and other factors are critical to understanding bioactivity and metabolism.

A Randomized Controlled Trial of a 6-Month Low-Carbohydrate Intervention on Disease Progression in Men with Recurrent Prostate Cancer: Carbohydrate and Prostate Study 2 (CAPS2).

PURPOSE: Both weight loss and low-carbohydrate diets (LCD) without weight loss prolong survival in prostate cancer models. Few human trials have tested weight loss or LCD on prostate cancer. EXPERIMENTAL DESIGN: We conducted a multi-site randomized 6-month trial of LCD versus control on PSA doubling time (PSADT) in patients with prostate cancer with biochemical recurrence (BCR) after local treatment. Eligibility included body mass index (BMI) ≥ 24 kg/m2 and PSADT 3 to 36 months. The LCD arm was instructed to eat [Formula: see text]20 g/carbs/day; the control arm instructed to avoid dietary changes. Primary outcome was PSADT. Secondary outcomes included weight, lipids, glucose metabolism, and diet. RESULTS: Of 60 planned patients, the study stopped early after an interim analysis showed futility. Twenty-seven LCD and 18 control patients completed the study. At 6 months, although both arms consumed similar protein and fats, the LCD arm reduced carbohydrates intake (-117 vs. 8 g, P < 0.001) and lost weight (-12.1 vs. -0.50 kg, P < 0.001). The LCD arm reduced HDL, triglycerides, and HbA1c with no difference in total cholesterol or glucose. Mean PSADT was similar between LCD (21 months) and control (15 months, P = 0.316) arms. In a post hoc exploratory analysis accounting for prestudy PSADT, baseline PSA, primary treatment, and hemoconcentration, PSADT was significantly longer in LCD versus control (28 vs. 13 months, P = 0.021) arms. Adverse events were few, usually mild, and returned to baseline by 6 months. CONCLUSIONS: Among BCR patients, LCD induced weight loss and metabolic benefits with acceptable safety without affecting PSADT, suggesting LCD does not adversely affect prostate cancer growth and is safe. Given exploratory findings of longer PSADT, larger studies testing LCD on disease progression are warranted.

Impact of a low FODMAP diet on the amount of rectal gas and rectal volume during radiotherapy in patients with prostate cancer - a prospective pilot study.

BACKGROUND: Small inter- and intrafractional prostate motion was shown to be a prerequisite for precise radiotherapy (RT) of prostate cancer (PCa) to achieve good local control and low rectal toxicity. As rectal gas and rectal volume are known to have a relevant effect on prostate motion, this study aims to reduce these parameters by using a Low FODMAP Diet (LFD) and to show feasibility of this intervention. METHODS: We compared a prospective intervention group (IG, n = 25) which underwent RT for PCa and whose patients were asked to follow a LFD during RT with a retrospective control group (CG, n = 25) which did not get any dietary advice. In the planning CT scan and all available cone beam CT scans rectal gas was classified based on a semiquantitative score (scale from 1 to 5) and rectal volume was measured. Furthermore, patients' compliance was evaluated by a self-assessment questionnaire. RESULTS: Clinical and treatment characteristics were well balanced between both groups. A total of 266 (CG, 10.6 per patient) and 280 CT scans (IG, 11.2 per patient), respectively, were analysed. The frequency distribution of gas scores differed significantly from each other (p < .001) with the IG having lower scores. Rectal volume was smaller in the IG (64.28 cm3, 95% CI 60.92-67.65 cm3, SD 28.64 cm3) than in the CG (71.40 cm3, 95% CI 66.47-76.32 cm3, SD 40.80 cm3) (p = .02). Mean intrapatient standard deviation as a measure for the variability of rectal volume was 22 cm3 in the IG and 23 cm3 in the CG (p = .81). Patients' compliance and contentment were satisfying. CONCLUSIONS: The use of a LFD significantly decreased rectal gas and rectal volume. LFD was feasible with an excellent patients' compliance. However, prospective trials with a larger number of patients and a standardized evaluation of gastrointestinal toxicity and quality of life are reasonable. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00012955. Registered 29 August 2017 - Retrospectively registered, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012955.

Effect of a Behavioral Intervention to Increase Vegetable Consumption on Cancer Progression Among Men With Early-Stage Prostate Cancer: The MEAL Randomized Clinical Trial.

Importance: Guidelines endorsing vegetable-enriched diets to improve outcomes for prostate cancer survivors are based on expert opinion, preclinical studies, and observational data. Objective: To determine the effect of a behavioral intervention that increased vegetable intake on cancer progression in men with early-stage prostate cancer. Design, Setting, and Participants: The Men's Eating and Living (MEAL) Study (CALGB 70807 [Alliance]) was a randomized clinical trial conducted at 91 US urology and medical oncology clinics that enrolled 478 men aged 50 to 80 years with biopsy-proven prostate adenocarcinoma (International Society of Urological Pathology grade group = 1 in those <70 years and ≤2 in those ≥70 years), stage cT2a or less, and serum prostate-specific antigen (PSA) level less than 10 ng/mL. Enrollment occurred from January 2011 to August 2015; 24-month follow-up occurred from January 2013 to August 2017. Interventions: Patients were randomized to a counseling behavioral intervention by telephone promoting consumption of 7 or more daily vegetable servings (MEAL intervention; n = 237) or a control group, which received written information about diet and prostate cancer (n = 241). Main Outcomes and Measures: The primary outcome was time to progression; progression was defined as PSA level of 10 ng/mL or greater, PSA doubling time of less than 3 years, or upgrading (defined as increase in tumor volume or grade) on follow-up prostate biopsy. Results: Among 478 patients randomized (mean [SD] age, 64 [7] years; mean [SD] PSA level, 4.9 [2.1] ng/mL), 443 eligible patients (93%) were included in the primary analysis. There were 245 progression events (intervention: 124; control: 121). There were no significant differences in time to progression (unadjusted hazards ratio, 0.96 [95% CI, 0.75 to 1.24]; adjusted hazard ratio, 0.97 [95% CI, 0.76 to 1.25]). The 24-month Kaplan-Meier progression-free percentages were 43.5% [95% CI, 36.5% to 50.6%] and 41.4% [95% CI, 34.3% to 48.7%] for the intervention and control groups, respectively (difference, 2.1% [95% CI, -8.1% to 12.2%]). Conclusions and Relevance: Among men with early-stage prostate cancer managed with active surveillance, a behavioral intervention that increased vegetable consumption did not significantly reduce the risk of prostate cancer progression. The findings do not support use of this intervention to decrease prostate cancer progression in this population, although the study may have been underpowered to identify a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT01238172.

Subcapsular orchiectomy versus total orchiectomy and LHRH analogue in the treatment of hormone-sensitive metastatic prostate cancer: a different perspective in evaluation of the psychosocial effects.

PURPOSE: We aimed to compare total orchiectomy, subcapsular orchiectomy, and luteinizing hormone-releasing hormone (LHRH) analogue treatment in patients with hormone-sensitive metastatic prostate cancer in terms of efficacy of androgen deprivation treatment (ADT), patient satisfaction, health-related quality of life (HRQoL), development of phantom testis syndrome (PTS), and post-traumatic stress disorder (PTSD). METHOD: Among 272 patients treated between July 2015 and January 2019, 189 patients were enrolled in this prospective, cohort study and the patients were divided into three groups: group I, bilateral total orchiectomy (n 66); group II, bilateral subcapsular orchiectomy (n 63); and group III, LHRH analogue treatment (n 60). The adequacy of ADT was routinely monitored every 3 months and clinical parameters were evaluated. After 6 to 36 months following ADT, questionnaires were used to evaluate PTS, PTSD, and HRQoL during outpatient visits. The patient satisfaction was questioned as yes/no. RESULTS: Adequate castration was provided with all three treatments, while the presence and frequency of PTS and severity of PTSD were lower, and patient satisfaction related to ADT and all components of HRQoL were better in patients undergoing subcapsular orchiectomy than those undergoing total orchiectomy. All findings except for PTS were similar in patients undergoing subcapsular orchiectomy and LHRH analogue treatment. In analysis of all patients, total incidence of PTS was 43.4% and PTSD was reported to be 48.7%. A strong relationship was found between PTSD and phantom testis pain (r 0.621, p < 0.001). CONCLUSIONS: Subcapsular orchiectomy has less psychosocial side effects than total orchiectomy and is similar to LHRH analogue treatment. It can be a reliable, cheaper, and fast-acting alternative to LHRH analogue treatment.

Dietary Glycemic Index and Glycemic Load and the Risk of Prostate Cancer: An Updated Systematic Review and Dose-Response Meta-Analysis.

A meta-analysis in 2015 revealed no significant association between glycemic index (GI), glycemic load (GL), and prostate cancer. Moreover, until now, no study has examined the dose-response association of GI, GL, and prostate cancer yet. The online databases were searched by two independent researchers for relevant publications up to Jan. 2019, using relevant keywords. Nine studies including five prospective and four case-control studies were included in the current systematic review and meta-analysis. These studies have included 290,911 individuals. We found a significant positive dose-response association between dietary GI and prostate cancer (Pnonlinearity = 0.03). Comparing individuals in the highest category of GI with those in the lowest category, no significant association was found between GI and prostate cancer (combined effect size: 1.08, 95% CI: 0.97-1.19, P = 0.17). Furthermore, no significant association was seen between dietary GL and prostate cancer in both dose-response analysis and when comparing the highest versus lowest categories of GL (combined effect size: 1.03, 95% CI: 0.91-1.16, P = 0.65). In conclusion, we found a significant positive dose-response association between dietary GI and prostate cancer. However, significant association was not seen for dietary GL.

Impact of oxidative stress SNPs and dietary antioxidant quality score on prostate cancer.

Purpose: To analyse the relation between antioxidant genotypes and Dietary Antioxidant Quality score (DAQs) effect on prostate cancer (PCa) risk and aggressiveness in a Spanish population.Methods: Men (N = 155 patients and 152 controls) with PSA values >4 ng/ml were enrolled in the project. DAQs were used considering the daily recommended intake for Spanish people (DRI). Genotyping of 5 SNPs rs662 (PON1), rs10432782 (SOD1), rs4880 (SOD2), rs17650792 (GPX1) and rs1001179 (CAT) were included for the analysis.Results: rs17650792 was statistically significant between case and controls subjects. When comparing D´Amico risk, we found that rs662 (CC), rs10432782 (G allele) and rs17650792 (GG) confer a protection. When testing SNP-antioxidant nutrients interactions, we found an intake of vitamin A and rs100179 (T carriers) and selenium and rs17650792 (G carriers) confers a protection of being in low risk classification.Conclusions: We reported by the first time a correlation between rs662 (PON1) and PCa aggressiveness.

Sulforaphane Bioavailability and Chemopreventive Activity in Men Presenting for Biopsy of the Prostate Gland: A Randomized Controlled Trial.

Previous studies suggest compounds such as sulforaphane (SFN) derived from cruciferous vegetables may prevent prostate cancer development and progression. This study evaluated the effect of broccoli sprout extract (BSE) supplementation on blood histone deacetylase (HDAC) activity, prostate RNA gene expression, and tissue biomarkers (histone H3 lysine 18 acetylation (H3K18ac), HDAC3, HDAC6, Ki67, and p21). A total of 98 men scheduled for prostate biopsy were allocated into either BSE (200 µmol daily) or a placebo in our double-blind, randomized controlled trial. We used nonparametric tests to evaluate the differences of blood HDAC activity and prostate tissue immunohistochemistry biomarkers between treatment groups. Further, we performed RNA-Seq analysis on the prostate biopsies and identified 40 differentially expressed genes correlated with BSE treatment, including downregulation of two genes previously implicated in prostate cancer development, AMACR and ARLNC1. Although urine and plasma SFN isothiocyanates and individual SFN metabolites were statistically higher in the treatment group, our results did not show a significant difference in HDAC activity or prostate tissue biomarkers. This study indicates BSE supplementation correlates with changes in gene expression but not with several other prostate cancer biomarkers. More research is required to fully understand the chemopreventive effects of BSE supplementation on prostate cancer.

Title Changes in the Mineral Composition of Rat Femoral Bones Induced by Implantation of LNCaP Prostate Cancer Cells and Dietary Supplementation.

Prostate cancer (PCa) is the second most frequent cancer in men and the fifth most common cause of death worldwide, with an estimated 378,553 deaths in 2020. Prostate cancer shows a strong tendency to form metastatic foci in the bones. A number of interactions between cancer cells attacking bones and cells of the bone matrix lead to destruction of the bone and growth of the tumour. The last few decades have seen increased interest in the precise role of minerals in human health and disease. Tumour cells accumulate various minerals that promote their intensive growth. Bone, as a storehouse of elements, can be a valuable source of them for the growing tumour. There are also reports suggesting that the presence of some tumours, e.g., of the breast, can adversely affect bone structure even in the absence of metastasis to this organ. This paper presents the effect of chronic dietary intake of calcium, iron and zinc, administered in doses corresponding maximally to twice their level in a standard diet, on homeostasis of selected elements (Ca, K, Zn, Fe, Cu, Sr, Ni, Co, Mn and Mo) in the femoral bones of healthy rats and rats with implanted cancer cells of the LNCaP line. The experiment was conducted over 90 days. After the adaptation period, the animals were randomly divided into four dietary groups: standard diet and supplementation with Zn, Fe and Ca. Every dietary group was divided into experimental group (with implanted cancer cells) and control group (without implanted cancer cells). The cancer cells (LnCaP) were implanted intraperitoneally in the amount 1 × 106 to the rats at day 90 of their lifetime. Bone tissue was dried and treated with microwave-assisted mineral digestation. Total elemental content was quantified by ICP-MS. Student's t-test and Anova or Kruskal-Wallis tests were applied in order to compare treatment and dietary groups. In the case of most of the diets, especially the standard diet, the femoral bones of rats with implanted LNCaP cells showed a clear downward trend in the content of the elements tested, which may be indicative of slow osteolysis taking place in the bone tissue. In the group of rats receiving the standard diet, there were significant reductions in the content of Mo (by 83%), Ca (25%), Co (22%), Mn (13%), K (13%) and Sr (9%) in the bone tissue of rats with implanted LNCaP cells in comparison with the control group receiving the same diet but without LNCaP implantation. Supplementation of the rat diet with calcium, zinc and iron decreased the frequency of these changes relative to the standard diet, which may indicate that the diet had an inhibitory effect on bone resorption in conditions of LNCaP implantation. The principal component analysis (PCA) score plot confirms the pronounced effect of implanted LNCaP cells and the standard diet on bone composition. At the same time, supplementation with calcium, zinc and iron seems to improve bone composition. The microelements that most often underwent quantitative changes in the experimental conditions were cobalt, manganese and molybdenum.

Epigallocatechin-3-gallate Enhances the Efficacy of MicroRNA-34a Mimic and MicroRNA-93 Inhibitor Co-transfection in Prostate Cancer Cell Line.

The potential role of microRNAs (miRNA or MIR) as therapeutic molecules has moved them from basic research to the field of cancer therapy. High expression of miR-93 and low expression of miR-34a have previously been indicated in prostate cancer (PC), which is the second leading cause of cancer-related death in men. Androgen receptor (AR) and prostate-specific antigen (PSA) play key roles in the initiation and progression of this cancer. Therefore, this study aimed to investigate the effects of the transfection and co-transfection of miR-34a mimic and miR-93 inhibitor with or without epigallocatechin-3-gallate (EGCG) on prostate cancer cell line and also to evaluate their effects on the expression of AR, PSA. Human lymph node carcinoma of the prostate (LNCaP) cells were treated with miR-34a mimic or/and miR-93 inhibitor with or without EGCG. Gene or protein expressions were assessed by real-time PCR or western blotting of lysates. The transfection with miR-34a mimics significantly reduced the mRNA expression of AR (p=0.0016), and PSA (p=0.038) compared to the control. Also, the miR-93 inhibitor led to a decrease in the mRNA expression of AR (p=0.0057) and PSA (p>0.05) compared to the control group. Furthermore, the co-transfection, along with EGCG, caused more decrease in both the AR (p<0.001) and the PSA (p=0.003) expression compared with the co-transfection without EGCG. Our study indicates that the reduced expression of AR and PSA in PC cells followed by treatment with miR-34a mimic and miR-93 inhibitor and their combination with EGCG as a natural substance may be a promising therapeutic way for controlling the growth of these malignant cells.

Impact of the antifermentative diet during radiotherapy for prostate cancer in elderly, SÃO Paulo, Brazil.

OBJECTIVE: Assess the impact of the antifermentative diet on the dietary intake and body composition of elderly prostate cancer patients in radiotherapy. METHODS: Observational and prospective study involving 45 men aged 60 years or older, receiving radiotherapy for prostate cancer treatment. The dietary intake was assessed at four times during radiotherapy: onset (TPre), between the 11th and 16th day (T1), between the 24th and 28th day (T2), and on the last day (TLast). The body composition was assessed before and on the last day of radiotherapy, by means of the body weight and height, mid-arm circumference, triceps and subscapular skin folds, phase angle, resistance, and reactance. The data were statistically treated, considering a 5% significance level. RESULTS: The intake of energy, dietary fibers, and some nutrients decreased during the radiotherapy (p < 0.05). The intake of vitamins E, B1, B2, and folate, of the minerals calcium, magnesium, potassium, sodium, and phosphorus, and of the amino acid leucine dropped when the four assessment times were compared (p < 0.05). As regards the body composition, an impact was observed at the end of the radiotherapy, with lower body weight, arm circumference, subscapular cutaneous fold, phase angle and reactance (p < 0.05). CONCLUSION: The antifermentative diet negatively influenced the food consumption and body composition of elderly patients submitted to radiotherapy for prostate cancer.

Effects of a nutrition intervention on acute and late bowel symptoms and health-related quality of life up to 24 months post radiotherapy in patients with prostate cancer: a multicentre randomised controlled trial.

PURPOSE: Radiotherapy to the prostate gland and pelvic lymph nodes may cause acute and late bowel symptoms and diminish quality of life. The aim was to study the effects of a nutrition intervention on bowel symptoms and health-related quality of life, compared with standard care. METHODS: Patients were randomised to a nutrition intervention (n = 92) aiming to replace insoluble fibres with soluble and reduce intake of lactose, or a standard care group (n = 88) who were recommended to maintain their habitual diet. Bowel symptoms, health-related quality of life and intake of fibre and lactose-containing foods were assessed up to 24 months after radiotherapy completion. Multiple linear regression was used to analyse the effects of the nutrition intervention on bowel symptoms during the acute (up to 2 months post radiotherapy) and the late (7 to 24 months post radiotherapy) phase. RESULTS: Most symptoms and functioning worsened during the acute phase, and improved during the late phase in both the intervention and standard care groups. The nutrition intervention was associated with less blood in stools (p = 0.047), flatulence (p = 0.014) and increased loss of appetite (p = 0.018) during the acute phase, and more bloated abdomen in the late phase (p = 0.029). However, these associations were clinically trivial or small. CONCLUSIONS: The effect of the nutrition intervention related to dietary fibre and lactose on bowel symptoms from pelvic RT was small and inconclusive, although some minor and transient improvements were observed. The results do not support routine nutrition intervention of this type to reduce adverse effects from pelvic radiotherapy.

Assessing the nutritional needs of men with prostate cancer.

BACKGROUND: Nutrition is important for prostate cancer (PC) survivorship care to help achieve a healthy weight, reduce treatment side effects and reduce the risk of developing other chronic diseases. We aimed to advance the understanding of the nutritional needs of men with PC and services that could be potentially implemented to address them. METHODS: We conducted a needs assessment of nutrition services for men with PC drawing on four perspectives; 1) patient evaluation of a nutrition education session in British Columbia (BC), 2) survey of BC health professionals, 3) an environmental scan of existing nutrition services across Canada and 4) a scoping literature review. RESULTS: Patients expressed a need for more nutrition information and a desire for additional nutrition services. More than 60% of health professionals believed there is a need for more nutrition services for men with PC, and reported the focus should be on weight management or management of PC progression. The environmental scan revealed few existing services for men with PC across Canada, most were inclusive of multiple cancers and not tailored for men with PC. Eighteen completed studies were identified in the scoping literature review. The majority provided combined diet and exercise programs with various formats of delivery such as individual, group and home-based. Overall, 78% of studies reported improvements in one or more of the following measures: dietary intake/ diet quality, body composition, self-efficacy, quality of life, fatigue, practicing health behavior goals and physical function/ exercise. Four studies assessed feasibility, adherence or satisfaction with all reporting positive findings. CONCLUSION: Despite the high prevalence of PC in Canada, and the perceived need for more support by patients and health professionals, there are limited nutrition services for men with PC. Evidence from the literature suggests nutrition services are effective and well-accepted by men with PC. Our findings define a need for standardized nutrition services for men with PC that assess and meet long term nutritional needs. Our findings also provide insight into the type and delivery of nutrition services that may help close the gap in care for men with PC.