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Prostate cancer (PCa) is one of the most common health‐related issues in the male individuals of western countries. Icaritin (ICT) is a traditional Chinese herbal medicine that exhibits antitumor efficacy in variety of cancers including PCa. However, the precise function and detailed molecular mechanism of ICT in the regression of PCa remain unclear. Ubiquitin‐conjugating enzyme E2C (UBE2C) is an anaphase‐promoting complex/cyclosome (APC/C)‐specific ubiquitin conjugating enzyme, which acts as an oncogene in PCa progression. The function of ICT in PCa was investigated in transgenic adenocarcinoma mouse prostate (TRAMP) mice using survival analysis, hematoxylin and eosin (HE) staining, TUNEL assay, and immunohistochemistry and in human PCa cell lines using various molecular techniques and functional assays including plasmid construction and transfection. Bioinformatic analyses were performed to identify the interaction between miRNA and UBE2C via the TargetScan algorithm. We demonstrated that ICT inhibited the development and progression of PCa in TRAMP mice by improving the survival rate and tumor differentiation. Furthermore, we found that ICT could significantly inhibit cell proliferation and invasion and induce apoptosis in PCa cells. Consistently, downregulation of UBE2C suppressed the proliferation and invasion of PCa cells. Moreover, a luciferase reporter assay confirmed that UBE2C was a direct target of miR‐381‐3p. Meanwhile, ICT simultaneously downregulated UBE2C expression and upregulated miR‐381‐3p levels in human PCa cells. Altogether, our findings provide a strong rationale for the clinical application of ICT as a potential oncotherapeutic agent against PCa via a novel molecular mechanism of regulating the miR‐381‐3p/UBE2C pathway.

Background and ObjectivesIn previous studies, obesity (measured according to the body mass index) has correlated inconsistently with the risk of biopsy-measured prostate cancer, and specifically high-grade prostate cancer. This meta-analysis aimed to clarify these correlations.MethodsA comprehensive literature search of the MEDLINE and EMBASE databases was conducted for relevant studies published through January 2014. The pooled estimates of odds ratios (OR) and confidence intervals (CI) were computed, and the meta-analysis was performed with the STATA software according to a random effects approach.ResultsA total of 11 studies that included 29,464 individuals were identified. A 5-kg/m2 increase in body mass index was associated with a 15% (OR, 1.15; 95% CI, 0.98–1.34) higher risk of prostate cancer detection and a 37% (OR, 1.37; 95% CI, 1.19–1.57) higher risk of high-grade prostate cancer detection at biopsy. There were no differences among the results of studies conducted in the USA, Europe or Asia. We also found that studies that had adjusted for prostate-specific antigen levels, digital rectal examination results, and prostate volumes obtained positive significant outcomes (OR, 1.27; 95% CI, 1.12–1.44), whereas studies that did not adjust for the above-mentioned confounding variables obtained negative results (OR, 0.92; 95% CI, 0.68–1.25). Moreover, the positive correlation between body mass index and the detection of both prostate cancer and high-grade diseases tended to be stronger as the number of biopsy cores increased.ConclusionThe present meta-analysis demonstrated that a high body mass index correlated positively with prostate cancer detection, especially high-grade prostate cancer detection. The adoption of a modified and possibly more aggressive biopsy strategy was suggested for obese populations.

Background. We aimed to examine whether proinflammatory cytokines participated in prostate cancer (PCa) development and progression promoted by high-fat diet (HFD). Methods. TRAMP (transgenic adenocarcinoma mouse prostate) mice were randomly divided into two groups: normal diet group and HFD group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24th, and 28th week, respectively. Levels of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, and TNF-α, were tested by FlowCytomix. Prostate tissue of TRAMP mice was used for histology study. Results. A total of 13 deaths of TRAMP mice were observed, among which 3 (8.33%) were from the normal diet group and 10 (27.78%) from the HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (P = 0.032). Tumor formation rate at 20th week of age of HFD group was significantly higher than that of normal diet group (P = 0.045). Proinflammatory cytokines levels, including IL-1α, IL-1β, IL-6, and TNF-α, were significantly higher in HFD TRAMP mice. Conclusions. HFD could promote TRAMP mouse PCa development and progression with elevated proinflammatory cytokines levels. Proinflammatory cytokines could contribute to PCa development and progression promoted by HFD.

Obesity is inconsistently related to biochemical recurrence (BCR) of prostate cancer (PCa) in different epidemiological studies. We conducted a systematic review and dose-response meta-analysis of published studies from MEDLINE and EMBASE in order to determine the relationship between body mass index (BMI) and BCR of PCa. We identified a total of 26 studies including 36,927 individuals. Pooled estimates of relative risk (RR) and confidence interval (CI) were computed, and dose-response meta-analysis was subsequently performed. Based on the random-effects approach, a 5 kg/m(2) increase in BMI was associated with 16 % (RR 1.16, 95 % CI 1.08-1.24) higher risk of BCR for entire set of 26 studies. Significantly higher rates of BCR were also observed in radical prostatectomy series (RR 1.17, 95 % CI 1.07-1.28) and external beam radiation therapy series (RR 1.19, 95 % CI 1.10-1.28), while no significant correlation was observed in brachytherapy series (RR 0.91, 95 % CI 0.64-1.28). Different BCR outcomes came out for studies held in USA (RR 1.18, 95 % CI 1.10-1.28), Europe (RR 1.04 95 % CI 0.91-1.17) and Asia (RR 1.83 95 % CI 0.85-3.97), respectively. There was limited evidence of a nonlinear association between BMI and BCR, which showed a critical point of 33 in BMI. The findings from meta-analysis showed that excess BMI was positively correlated with BCR of PCa multifacetedly, indicating good weight control and detailed attention to treating obese patients might improve the prognosis of PCa.

ObjectiveThe risk factors of bladder cancer recurrence after transurethral resection of bladder tumor (TURBt) were poorly understood, especially in Chinese population. This study evaluated the potential risk factors of recurrence based on a Chinese population.Materials and MethodsA total of 698 patients that received TURBt procedure in our institute from 2000 to 2012 were recruited in this study. Clinical information was collected. The patients were followed up according to the schedule recommended by Chinese guideline.ResultsA total of 583 males (83.5%) and 115 females (16.5%) were enrolled in our study. The median follow-up duration was 51.5 months. Gender, chief complain, tumor size, number of lesions, histological grade and chemotherapeutic agents were found significantly associated with patients’ short-term recurrence (less than 1 year) (All p<0.05). In the multivariate analysis, tumor size, number of lesions, histological grade and chemotherapeutic agents were significantly related to patients’ short-term recurrence (less than 1 year) (All p<0.05). A multivariate model based on tumor size, number of lesions, histological grade and chemotherapeutic agents had an AUC of 0.697, which significantly improved the prediction utility for bladder cancer short-term recurrence (less than 1 year) than any single factor In the multivariate Cox regression, tumor size greater than 3 cm, multifocal lesions, worsen histological grade and non-urothelial carcinoma was related to time to recurrence (TR).ConclusionPatients with larger tumor size, multifocal number of lesions, higher tumor grade and who received chemotherapeutic agents other than Epirubicin and Pirarubicin might have higher risks of recurrence less than 1 year. Tumor size, number of lesions, pathology and histological grade might be associated with TR. As Bacille Calmette-Guerin (BCG) is currently not approved for bladder cancer in China, Epirubicin and Pirarubicin might be considered prior to other chemotherapy medications when providing post-operative instillation of chemotherapy.

High-fat diet (HFD) -induced obesity is associated with more aggressive and lethal prostate cancer (PCa) in males, although the exact underlying mechanisms remain unclear. In the present study, transgenic adenocarcinoma of mouse prostate (TRAMP) models fed on an HFD (40% fat) or a control diet (CD; 16% fat) were generated, and cancer differentiation, local invasion and metastasis were compared at 20, 24 and 28 weeks. Mouse sera from each group were collected, and adipokines and cytokines were measured using multiplex immunoassays. HFD-sera and CD-sera were additionally processed into conditioned media (2.5% mixed sera), and in vitro studies were conducted to determine the proliferation, migration and invasion of cancer cells when conditioned media were used for culture. In TRAMP mice, HFD feeding increased body weight and adipose tissue deposition, and promoted the progression of PCa, specifically with regard to poorer differentiation, increased local invasion and metastasis rate. Sera from HFD-fed TRAMP mice contained increased levels of leptin, and a time-dependent increasing trend in the levels of CC chemokine ligand (CCL)3, CCL4, CCL5 and CXC chemokine ligand (CXCL)10 was observed. However, no alterations were detected in the levels of adiponectin, interleukin (IL)-4, IL-5, IL-6, IL-12p70, interferon-γ, tumor necrosis factor-α, CCL2, CCL7, CCL11, CXCL1 and CXCL2. In vitro studies determined that HFD-sera-conditioned medium promoted proliferation, migration and invasion of DU145 cells, as compared with CD-sera-conditioned medium and serum-free medium. In conclusion, the results of the present study suggested that the circulating adipokine and cytokine alterations in response to excess adipose tissue deposition induced by HFD feeding contributed to PCa progression.

A murine monoclonal antibody (mAb), CLD3 (IgG(1),kappa), was generated against hepatocellular carcinoma (HCC). Both immunofluorescence and immunohistochemical assays indicated the reactivity of CLD3 mAb localized at the nucleus and/or cytoplasm of tumorigenic HCC cell lines as well as in liver cancer tissues. By immunoprecipitation and using the matrix-assisted laser desorption/ionization-time of flight mass spectrometry approach, the antigenic specificity of CLD3 was determined to be heterodimeric Ku70 and Ku80 autoantigen, which was confirmed by Western blotting.