ObjectiveThis double-blind, placebo-controlled phase 3 study was designed to compare efficacy and safety of abiraterone acetate + prednisone (abiraterone) to prednisone alone in chemotherapy-naïve, asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients from China, Malaysia, Thailand and Russia.MethodsAdult chemotherapy-naïve patients with confirmed prostate adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade 0–1, ongoing androgen deprivation (serum testosterone <50 ng/dL) with prostate specific antigen (PSA) or radiographic progression were randomized to receive abiraterone acetate (1000 mg, QD) + prednisone (5 mg, BID) or placebo + prednisone (5 mg, BID), until disease progression, unacceptable toxicity or consent withdrawal. Primary endpoint was improvements in time to PSA progression (TTPP).ResultsTotally, 313 patients were randomized (abiraterone: n = 157; prednisone: n = 156); and baseline characteristics were balanced. At clinical cut-off (median follow-up time: 3.9 months), 80% patients received treatment (abiraterone: n = 138, prednisone: n = 112). Median time to PSA progression was not reached with abiraterone versus 3.8 months for prednisone, attaining 58% reduction in PSA progression risk (HR = 0.418; p < 0.0001). Abiraterone-treated patients had higher confirmed PSA response rate (50% vs. 21%; relative odds = 2.4; p < 0.0001) and were 5 times more likely to achieve radiographic response than prednisone-treated patients (22.9% vs. 4.8%, p = 0.0369). Median survival was not reached. Most common (≥10% abiraterone vs. prednisone-treated) adverse events: bone pain (7% vs. 14%), pain in extremity (6% vs. 12%), arthralgia (10% vs. 8%), back pain (7% vs. 11%), and hypertension (15% vs. 14%).ConclusionInterim analysis confirmed favorable benefit-to-risk ratio of abiraterone in chemotherapy-naïve men with mCRPC, consistent with global study, thus supporting use of abiraterone in this patient population.

Vitamin D has important biological functions including modulation of the immune system and anti-cancer effects. There was no conclusive finding of the impact of serum vitamin D level on bladder cancer risk. A systemic review and meta-analysis was performed to assess the impact of serum 25-hydroxyvitamin D level on bladder cancer risk. The pooled relative risk (RR) with 95% confidence interval (95%CI) was used to assess the impact of serum 25-hydroxyvitamin D level on bladder cancer risk. A total of 89,610 participants and 2238 bladder cancer cases were finally included into the meta-analysis. There was no obvious heterogeneity among those included studies (I(2) = 0%). Meta-analysis total included studies which showed that a high serum 25-hydroxyvitamin D level could obviously decrease risk of bladder cancer (RR = 0.75, 95%CI 0.65-0.87, P < 0.001). In addition, the pooled RRs were not significantly changed by excluding any single study. The findings from the meta-analysis suggest an obvious protective effect of vitamin D against bladder cancer. Individuals with higher serum 25-hydroxyvitamin D levels suffer from less risk of subsequent bladder cancer.

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Background: Higher tumor expression of CD44, a marker of cancer stem cells (CSCs), is associated with poor overall survival (OS) in various cancers. However, the association between CD44 and poor OS remains inconsistent in glioma. We aimed to evaluate the potential predictive role of CD44 for prognosis of glioma patients in a meta-analysis. Methods: Observational studies comparing OS of glioma patients according to the level of CD44 were identified through searching PubMed, Embase, and Cochrane’s Library databases. Meta-analyses were performed with a random- or fixed-effect model according to the heterogeneity. Subgroup analyses were performed to evaluate the influences of study characteristics. Results: Eleven retrospective cohort studies were included. Results showed that increased CD44 expression in tumor predicted poor OS in glioma patients (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.02–1.97, P=0.04). Subgroup analyses showed that higher tumor CD44 expression significantly predicted poor OS in patients with World Health Organization (WHO) stages II–III glioma (HR: 2.99, 95% CI: 1.53–5.89, P=0.002), but not in patients with glioblastoma (HR: 1.26, 95% CI: 0.76–2.08, P=0.47; P for subgroup difference = 0.03). Results were not statistically different between subgroups according to patient ethnicity, sample size, CD44 detection method, CD44 cutoff, HR estimation, univariate or multivariate analysis, or median follow-up durations (P-values for subgroup difference all &gt;0.10). Conclusion: Higher tumor expression of CD44 may predict poor survival in patients with glioma, particularly in those with WHO stage II–III glioma.

Clear cell renal cell carcinoma (ccRCC) is a common urologic malignancy. Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) has been suggested as serving pivotal roles in tumorigenesis. However, the clinical significance and biological role of CCAT2 in ccRCC remains elusive. The purpose of this study is to identify the function of CCAT2 in ccRCC and its possible molecular mechanism. Expression of CCAT2 was analyzed in 61 ccRCC tissues and two ccRCC cell lines (786-O and ACHN) by quantitative reverse transcription polymerase chain reaction. The functional roles of CCAT2 in ccRCC were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, Transwell assay, and flow cytometric analysis. The influence of CCAT2 on tumorigenesis was monitored by in vivo mice xenograft model. The activation of Wnt/β-catenin signaling pathway was evaluated by the TOP/FOP Wnt luciferase reporter assay and western blot assay. CCAT2 expression was markedly higher in ccRCC cell lines and tissues, being positively associated with tumor size and tumor stage in ccRCC patients. Patients with higher CCAT2 expression had a markedly poorer overall survival than did patients with low CCAT2 expression. Knocking down CCAT2 expression led to reduced cell proliferation and increased apoptosis of ccRCC cells in vitro as well as the activation of Wnt/β-catenin signaling pathway, and CCAT2 overexpression remarkably enhanced these oncogenic properties. In vivo mice xenograft model also showed that knocking CCAT2 expression inhibited the growth of ccRCC xenografts. In conclusion, these results indicated that CCAT2 may play a critical role in ccRCC progression and will be further considered as a biomarker for predicting the survival of ccRCC patients and a potential therapeutic target for ccRCC intervention.

BackgroundProstate cancer has become a serious threat to the life of patients. microRNAs are small non-coding RNA molecules that regulate the growth and apoptosis of cells. We aimed to investigate the regulation and mechanism of microRNA (miR-143) in the proliferation and apoptosis of prostate cancer LNCap cells.Material/MethodsmiR-143 and control scramble miRNA were synthesized and respectively transfected into LNCap cells. The proliferation and apoptosis were detected by MTT assay, flow cytometry, and caspase-3 activity assay. The intracellular expression of Bcl-2 was determined by Western blot. Further, LNCap cells were transfected with small interfering RNA (siRNA) targeting Bcl-2 (siBcl-2) or plasmid expressing Bcl-2, followed by transfection of miR-143 or control miRNA. Bcl-2 expression was detected by Western blot, and cell apoptosis was measured by caspase-3 activity assay.ResultsTransfection of miR-143 significantly inhibited the proliferation of LNCap cells (P=0.0073), increased the percentage of externalized phosphatidylserine (P=0.0042), activated the caspase-3 (P=0.0012), and decreased the expression of Bcl-2 (P=0.012) when compared with the control miRNA group. The expression of Bcl-2 was significantly reduced after siBcl-2 transfection. The apoptosis in the siBcl-2+miR-143 group was significantly increased compared with that in the miR-143 group (P=0.036), whereas there was no significant difference in the apoptosis between the siBcl-2+miRNA and miRNA groups. The expression of Bcl-2 was obviously higher after the transfection of Bcl-2-expressing plasmid. The apoptosis in Bcl-2+miR-143 group was significantly reduced compared with the miR-143 group (P=0.031), whereas no significant difference in the apoptosis was detected between the miRNA and Bcl-2+miRNA groups.ConclusionsTransfection of miR-143 induces the apoptosis of prostate cancer LNCap cells by down-regulating Bcl-2 expression, suggesting that Bcl-2 might be a potential therapeutic target for prostate cancer.

An experimental analysis of the distribution and thickness of the bulk nonlinearity induced in poled silica is reported. The second-order susceptibility decreases exponentially from the anodic interface. Maker fringe patterns showing a double structure are interpreted in relation to the presence of two nonlinear profiles, one concentrated near the anodic surface and another extending into the bulk of the sample. The Maker fringe theory is properly generalized and a double fitting technique reproducing well the experimental results is used to characterize the induced nonlinearities. The dependence of the second-harmonic signal on the poling temperature is given, which is different from that of sol-gel silica.