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1.
OXER1 mediates testosterone-induced calcium responses in prostate cancer cells.
Panagiotopoulos, AA, Kalyvianaki, K, Serifoglou, B, Konstantinou, E, Notas, G, Castanas, E, Kampa, M
Molecular and cellular endocrinology. 2022;:111487
Abstract
In prostate cancer, calcium homeostasis plays a significant role in the disease's development and progression. Intracellular calcium changes are an important secondary signal, triggered by a variety of extracellular stimuli, that controls many cellular functions. One of the main events affecting calcium is androgen signaling. Indeed, via calcium changes, androgens regulate cell processes like cell growth, differentiation and motility. In the present work we explored the nature of the receptor involved in calcium response induced by membrane-acting testosterone in prostate cancer cells. We report that testosterone, independently of the presence of the classical androgen receptor, can rapidly increase intracellular calcium from calcium stores, through the oxoeicosanoid receptor 1 (OXER1) and a specific signaling cascade that triggers calcium release from the endoplasmic reticulum. These findings reveal for the first time the receptor involved in the rapid calcium changes induced by androgens. Moreover, they further support the notion that androgens, even in the absence of AR, can still exert specific effects that regulate cancer cell fate.
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2.
Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response.
Ashrafizadeh, M, Paskeh, MDA, Mirzaei, S, Gholami, MH, Zarrabi, A, Hashemi, F, Hushmandi, K, Hashemi, M, Nabavi, N, Crea, F, et al
Journal of experimental & clinical cancer research : CR. 2022;(1):105
Abstract
Prostate cancer is a leading cause of death worldwide and new estimates revealed prostate cancer as the leading cause of death in men in 2021. Therefore, new strategies are pertinent in the treatment of this malignant disease. Macroautophagy/autophagy is a "self-degradation" mechanism capable of facilitating the turnover of long-lived and toxic macromolecules and organelles. Recently, attention has been drawn towards the role of autophagy in cancer and how its modulation provides effective cancer therapy. In the present review, we provide a mechanistic discussion of autophagy in prostate cancer. Autophagy can promote/inhibit proliferation and survival of prostate cancer cells. Besides, metastasis of prostate cancer cells is affected (via induction and inhibition) by autophagy. Autophagy can affect the response of prostate cancer cells to therapy such as chemotherapy and radiotherapy, given the close association between autophagy and apoptosis. Increasing evidence has demonstrated that upstream mediators such as AMPK, non-coding RNAs, KLF5, MTOR and others regulate autophagy in prostate cancer. Anti-tumor compounds, for instance phytochemicals, dually inhibit or induce autophagy in prostate cancer therapy. For improving prostate cancer therapy, nanotherapeutics such as chitosan nanoparticles have been developed. With respect to the context-dependent role of autophagy in prostate cancer, genetic tools such as siRNA and CRISPR-Cas9 can be utilized for targeting autophagic genes. Finally, these findings can be translated into preclinical and clinical studies to improve survival and prognosis of prostate cancer patients.
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3.
Prostate-specific Membrane Antigen PET in Prostate Cancer.
Lawhn-Heath, C, Salavati, A, Behr, SC, Rowe, SP, Calais, J, Fendler, WP, Eiber, M, Emmett, L, Hofman, MS, Hope, TA
Radiology. 2021;(2):248-260
Abstract
Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals are playing a large role at the time of initial staging and biochemical recurrence for localizing prostate cancer, as well as in other emerging clinical settings. PSMA PET has demonstrated increased detection rate compared with conventional imaging and has been shown to change management plans in a substantial percentage of cases. The aims of this narrative review are to highlight the development and clinical impact of PSMA PET radiopharmaceuticals, to compare PSMA to other agents such as fluorine 18 fluciclovine and carbon 11 choline, and to highlight some of the individual PSMA PET agents that have contributed to the advancement of prostate cancer imaging.
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4.
The Association of Nighttime Fasting Duration and Prostate Cancer Risk: Results from the Multicase-Control (MCC) Study in Spain.
Palomar-Cros, A, Espinosa, A, Straif, K, Pérez-Gómez, B, Papantoniou, K, Gómez-Acebo, I, Molina-Barceló, A, Olmedo-Requena, R, Alguacil, J, Fernández-Tardón, G, et al
Nutrients. 2021;(8)
Abstract
Nighttime fasting has been inconclusively associated with a reduced risk of cancer. The purpose of this study was to investigate this association in relation to prostate cancer risk. We examined data from 607 prostate cancer cases and 848 population controls who had never worked in night shift work from the Spanish multicase-control (MCC) study, 2008-2013. Through an interview, we collected circadian information on meal timing at mid-age. We estimated odds ratios (OR) and 95% confidence intervals (CI) with unconditional logistic regression. After controlling for time of breakfast, fasting for more than 11 h overnight (the median duration among controls) was associated with a reduced risk of prostate cancer compared to those fasting for 11 h or less (OR = 0.77, 95% 0.54-1.07). Combining a long nighttime fasting and an early breakfast was associated with a lower risk of prostate cancer compared to a short nighttime fasting and a late breakfast (OR = 0.54, 95% CI 0.27-1.04). This study suggests that a prolonged nighttime fasting duration and an early breakfast may be associated with a lower risk of prostate cancer. Findings should be interpreted cautiously and add to growing evidence on the importance of chrononutrition in relation to cancer risk.
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5.
Vaccinium myrtillus L. extract and its native polyphenol-recombined mixture have anti-proliferative and pro-apoptotic effects on human prostate cancer cell lines.
Del Bubba, M, Di Serio, C, Renai, L, Scordo, CVA, Checchini, L, Ungar, A, Tarantini, F, Bartoletti, R
Phytotherapy research : PTR. 2021;(2):1089-1098
Abstract
Vaccinium myrtillus berry extract (VME) and a recombined standard mixture (RSM) of its main native phenolic compounds were investigated for cell growth inhibition and pro-apoptotic activity on hormone-dependent (LNCaP) and hormone-independent (PC3 and DU-145) prostate cancer (PCa) cell lines. Normal prostate epithelial cells (PrEC) were also studied in comparison. VME hindered anchorage-dependent PCa cell proliferation in a dose-dependent manner, that is, at 1/800 (v/v) dilution for LNCaP and PC3, and 1/100 (v/v) dilution for DU-145 (corresponding to 14.15 and 113.2 μg cyanidin-3-O-glucoside equivalents per ml of culture medium), respectively. VME had a growth inhibitory effect towards PrEC at the same dilution of DU-145 cells although the IC50 values indicated that PrEC are more resistant than PCa cell lines. VME also reduced the anchorage-independent growth of PCa cells. The study of the apoptotic profile (i.e., non-apoptotic, early apoptotic, late apoptotic and necrotic cells) evidenced that the apoptotic rate (early+late) was statistically higher in all three cell lines exposed to VME compared to control. Anchorage-dependent and anchorage-independent growth inhibition of RSM was very similar to that displayed by VME. Moreover, RSM exerted its growth inhibitory effect also under hypoxia, the latter representing a biological condition known to sustain PCa proliferation and aggressiveness.
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6.
Cardiorespiratory fitness is not associated with reduced risk of prostate cancer: A cohort study and review of the literature.
Kunutsor, SK, Voutilainen, A, Laukkanen, JA
European journal of clinical investigation. 2021;(8):e13545
Abstract
BACKGROUND Cardiorespiratory fitness (CRF) has a strong inverse relationship with several chronic disease outcomes, including some cancers. The association between CRF and prostate cancer is controversial. We aimed to assess the prospective association of CRF with prostate cancer risk using a cohort study and review of the literature. MATERIAL AND METHODS Cardiorespiratory fitness was assessed using a respiratory gas exchange analyser during exercise testing in 2204 cancer-free middle-aged men. Hazard ratios (HRs) with 95% confidence interval (CIs) were estimated. We corrected for within-person variability in CRF levels using repeat measurements. RESULTS During a median follow-up of 24.9 years, 216 prostate cancer cases occurred. The age-adjusted regression dilution ratio of CRF was 0.58 (95% CI: 0.53-0.64). The HR (95% CI) of prostate cancer per 1 standard deviation increase in CRF in age-adjusted analysis was 1.10 (0.95-1.27). The association remained consistent after further adjustment for several risk factors (HR 1.13; 95% CI 0.96-1.33). The corresponding adjusted HRs were 1.24 (95% CI: 0.87-1.77) and 1.28 (95% CI: 0.87-1.88), respectively, when comparing the extreme tertiles of CRF levels. Previous studies mostly reported no evidence of an association or an increased risk of prostate cancer in relation to high CRF. Studies reporting positive associations had short-term follow-up durations (<10 years). CONCLUSIONS Primary data and a review of previous studies suggest that elevated CRF is not associated with reduced prostate cancer risk. Previous findings of significant evidence of associations could be attributed to increased screening and detection as well as reverse causation bias.
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7.
Gut microbial differences in breast and prostate cancer cases from two randomised controlled trials compared to matched cancer-free controls.
Smith, KS, Frugé, AD, van der Pol, W, Caston, NE, Morrow, CD, Demark-Wahnefried, W, Carson, TL
Beneficial microbes. 2021;(3):239-248
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Abstract
Implicated in several chronic diseases, the gastrointestinal microbiome is hypothesised to influence carcinogenesis. We compared faecal microbiota of newly diagnosed treatment-naïve overweight and obese cancer patients and matched controls. Cases were enrolled in presurgical weight-loss trials for breast (NCT02224807) and prostate (NCT01886677) cancers and had a body mass index (BMI) ≥25 kg/m2. Cancer-free controls were matched 1:1 by age (±5 years), race, gender, and BMI (±5 kg/m2). All participants provided faecal samples; isolated bacterial DNA were PCR amplified at the V4 region of the 16S rRNA gene and analysed using the QIIME pipeline. Tests compared cases versus controls, then separately by gender. Microbial alpha-diversity and beta-diversity were assessed, and relative abundance of Operational Taxonomic Units (OTU's) were compared at the genus level, with false discovery rate (FDR) correction. 22 overweight and obese cancer patients were matched with 22 cancer-free controls, with an average BMI of 30.5±4.3 kg/m2, age 54.4±5.3 years, and 54.5% were black. Fourteen matches were made between breast cancer cases and healthy female controls, and 8 matches were made with prostate cancer cases and healthy male controls. Comparison of all cases and controls revealed no differences in alpha diversity, though prostate cancer patients had higher Chao1 (P=0.006) and Observed Species (P=0.036) than cancer-free males. Beta-diversity metrics were significantly different between cases and controls (P<0.03 for all tests in whole sample and in men), though only unweighted Unifrac was different in women (P=0.005). Kruskal Wallis tests indicated significant differences among 16 genera in all matches, 9 in female, and 51 in male. This study suggests the faecal microbiota of treatment-naive breast and prostate cancer patients differs from controls, though larger samples are needed to substantiate these findings. Trial registration: NIH Clinical Trials, NCT01886677, NCT02224807, registered 26 June 2013, 25 Aug 2014 (respectively) - retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01886677; https://clinicaltrials.gov/ct2/show/NCT02224807.
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Low Carbohydrate Diets and Estimated Cardiovascular and Metabolic Syndrome Risk in Prostate Cancer.
Freedland, SJ, Howard, LE, Ngo, A, Ramirez-Torres, A, Csizmadi, I, Cheng, S, Mack, A, Lin, PH
The Journal of urology. 2021;(6):1411-1419
Abstract
PURPOSE A low carbohydrate diet (LCD) was shown to suggestively slow prostate cancer (PC) growth. In noncancer patients, LCDs improve metabolic syndrome (MetS) without weight loss. However, concerns about negative impact on cardiovascular disease (CVD) risk remain. The objective of this secondary analysis is to determine the impact of an LCD on risk of MetS and estimated CVD risk in patients with PC. MATERIALS AND METHODS Pooled data were analyzed from 2 randomized trials testing LCD vs control on 1) preventing insulin resistance after starting hormone therapy (CAPS1) and 2) slowing PC growth in recurrent PC after failed primary treatment (CAPS2). Both trials included a usual care control vs LCD intervention in which patients were instructed to limit carbohydrate intake to ≤20 gm/day, and in CAPS1 only, to walk for ≥30 minutes/day for ≥5 days/week. MetS components (hypertension, high triglycerides, low high-density lipoprotein cholesterol, central obesity and diabetes), 10-year CVD risk estimated using the Framingham Score with either body mass index (BMI) or lipids, and remnant cholesterol were compared between arms using mixed models adjusting for trial. RESULTS LCD resulted in a significantly reduced risk of MetS (p=0.004) and remnant cholesterol (p <0.001). Moreover, LCD resulted in significantly lower estimated CVD risk using BMI (p=0.002) over the study with no difference in estimated CVD risk using lipids (p=0.14). CONCLUSIONS LCD resulted in a significantly reduced risk of MetS and remnant cholesterol, and a significantly lower estimated CVD risk using BMI. By comparison, there was no difference in estimated CVD risk using lipids. Study limitations include small sample size, short followup, and inability to distinguish effects of carbohydrate restriction and weight loss. Long-term studies are needed to confirm this finding.
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9.
Public interest in dietary supplements for prostate cancer prevention.
Patel, DN, Kuhlmann, P, Lin, PH, Freedland, SJ
Prostate cancer and prostatic diseases. 2021;(1):58-60
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10.
Differences in the Central Energy Metabolism of Cancer Cells between Conventional 2D and Novel 3D Culture Systems.
Ikari, R, Mukaisho, KI, Kageyama, S, Nagasawa, M, Kubota, S, Nakayama, T, Murakami, S, Taniura, N, Tanaka, H, Kushima, RP, et al
International journal of molecular sciences. 2021;(4)
Abstract
The conventional two-dimensional (2D) culture is available as an in vitro experimental model. However, the culture system reportedly does not recapitulate the in vivo cancer microenvironment. We recently developed a tissueoid cell culture system using Cellbed, which resembles the loose connective tissue in living organisms. The present study performed 2D and three-dimensional (3D) culture using prostate and bladder cancer cell lines and a comprehensive metabolome analysis. Compared to 3D, the 2D culture had significantly lower levels of most metabolites. The 3D culture system did not impair mitochondrial function in the cancer cells and produce energy through the mitochondria simultaneously with aerobic glycolysis. Conversely, ATP production, biomass (nucleotides, amino acids, lipids and NADPH) synthesis and redox balance maintenance were conducted in 3D culture. In contrast, in 2D culture, biomass production was delayed due to the suppression of metabolic activity. The 3D metabolome analysis using the tissueoid cell culture system capable of in vivo cancer cell culture yielded results consistent with previously reported cancer metabolism theories. This system is expected to be an essential experimental tool in a wide range of cancer research fields, especially in preclinical stages while transitioning from in vitro to in vivo.