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Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. A well-established in vitro cell model is required to determine the therapeutic mechanism of BPH inflammation. In this study, we attempted to establish an immortalized human prostate stromal cell line by transfecting with HPV-16 E6/E7 and designated as ihPSC. No significant difference was found in fibroblast-like morphology between primary hPSC and ihPSC. The ihPSC possessed a significantly higher cell proliferation rate than primary hPSC. The prostate-specific markers and proteins including cytoskeleton (α-SMA and vimentin) and smooth muscle (calponin), especially the androgen receptor (AR) were also examined in ihPSC, almost identical to the primary hPSC. To create an in vitro model featuring chronic prostatic inflammation, ihPSC was stimulated with IFN-γ+IL-17 and then treated with the high molecular weight hyaluronic acid hylan G-F 20 as an alternative strategy for inhibiting BPH inflammation. Hylan G-F 20 could dose-dependently diminish the inflammation-induced proliferation in ihPSC. The enhanced expressions of inflammatory molecules including IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), inducible nitrogen oxide synthase (iNOS), and Toll-like receptor 4 (TLR4) were all abolished by hylan G-F 20. For inflammatory signaling, hylan G-F 20 can also diminish the IFN-γ+IL-17-increased expression of iNOS and p65 in ihPSC. These findings suggest that ihPSC could provide a mechanism-based platform for investigating prostate inflammation. The hylan G-F 20 showed strong anti-inflammatory effects by decreasing inflammatory cytokines and signalings in the ihPSC, indicating its therapeutic potentials in BPH treatment in the future. [ABSTRACT FROM AUTHOR]

Objective: We investigated the overall and age-specific risks of developing breast and endometrial cancer among women with diabetes in a population-based cohort study. Methods: Women with diabetes (n = 319310) and age-matched controls (n = 319308), selected from ambulatory care claims and beneficiary registry in 2000, respectively were linked to the in-patient claims (2000–2008) to identify admissions due to breast (ICD-9-CM: 174) and endometrial (ICD-9-CM: 182) cancer. The person-year approach with Poisson assumption was used to estimate the incidence density rate. The age-specific hazard ratios (HRs) of above malignancies in relation to diabetes with multivariate Cox proportional hazard regression. Results: The overall incidence density rate of breast and endometrial cancer was estimated at 1.21 and 0.21 per 10,000 patient-years, respectively, for diabetes. The corresponding figures for controls were lower at 1.00 and 0.14 per 10,000 patient-years. Compared with the controls, the covariate adjusted HR for breast and endometrial cancer was 1.42 (95% confidence interval (CI) 1.34–1.50) and 1.71 (95% CI 1.48–1.97), respectively in women with diabetes. Elderly (> = 65 years) diabetes had the highest HR (1.61) of breast cancer, while the highest HR (1.85) of endometrial cancer was observed in diabetes aged < = 50 years. Conclusions: Diabetes may significantly increase the risks of breast and endometrial cancer in all age stratifications. Health education for strict adherence of cancer screening program in women with diabetes is essential. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the survival outcomes and prognostic factors of patients with advanced hepatocellular carcinoma (HCC) who underwent stereotactic ablative radiotherapy (SABR). Methods: This retrospective study evaluated patients with advanced HCC who underwent SABR between December 2007 and July 2015. All patients had Barcelona Clinic Liver Cancer stage C disease and Child–Turcotte–Pugh (CTP) class A–B function. In-field control (IFC), overall survival (OS), prognostic factors, and toxicity were evaluated. Results: In this study of 89 patients, the 3-year IFC rate was 78.1%, and the 1-year and 3-year OS rates were 45.9% and 24.3%, respectively. The multivariate analysis revealed that CTP class, the presence of main portal vein tumor thrombosis, and the presence of extrahepatic spread were independent predictors of OS. The expected median OS values among patients with ≥2, 1, and 0 predictors were 4.2, 8.6, and 26.4 months, respectively (p <0.001). Conclusions: SABR may be useful for patients with advanced HCC, and patient selection could be based on the CTP classification, main portal vein tumor thrombosis, and extrahepatic spread. [ABSTRACT FROM AUTHOR]

Purpose: Gemcitabine-based chemotherapy remains one of the standards in management of metastatic breast cancer. However, intrinsic and acquired resistance to gemcitabine inevitably occurs. The aims of this study were to assess the efficacy of the combination of src inhibition and gemcitabine in gemcitabine-resistant breast cancer cells. Methods and Results: By using colony formation, sphere forming, flow cytometry, cell counting kit-8 and transwell assays, 231/GEM-res (gemcitabine-resistant) cell line, which was 10 times more resistant, was shown to have elevated drug tolerance, enhanced proliferative and self-renewal abilities, compared with its parental cells. Inhibition of src by both saracatinib (AZD0530) and siRNA could partially reverse gemcitabine resistance and attenuate resistance-associated anti-apoptosis, migration and stem cell capacities. In addition, the combination of src inhibition and gemcitabine had synergistic antitumor effects. Western blot analysis revealed up-regulation of pro-apoptotic protein BAX, along with the down-regulation of anti-apoptotic proteins (BCL-XL, Survivin), migration associated proteins (p-FAK, MMP-3) and cancer stem cell (CSC) markers (CD44, Oct-4), which was probably mediated by AKT/c-Jun pathway. Conclusion: In highly gemcitabine-resistant 231 cells, src inhibition can synergize with gemcitabine, reverse drug resistance, inhibit tumor growth/metastasis/stemness of cancer stem cells, possibly via the AKT/c-Jun pathway. [ABSTRACT FROM AUTHOR]

Although proton magnetic resonance spectroscopy (1H-MRS) is a common method for the evaluation of intracranial meningiomas, controversy exists regarding which parameter of 1H-MRS best predicts the histopathological grade of an intracranial meningioma. In this study, we evaluated the results of pre-operative 1H-MRS to identify predictive factors for high-grade intracranial meningioma. Thirteen patients with World Health Organization (WHO) grade II-III meningioma (confirmed by pathology) were defined as high-grade; twenty-two patients with WHO grade I meningioma were defined as low-grade. All patients were evaluated by 1H-MRS before surgery. The relationships between the ratios of metabolites (N-acetylaspartate [NAA], creatine [Cr], and choline [Cho]) and the diagnosis of high-grade meningioma were analyzed. According to Mann-Whitney U test analysis, the Cho/NAA ratio in cases of high-grade meningioma was significantly higher than in cases of low-grade meningioma (6.34 ± 7.90 vs. 1.58 ± 0.77, p<0.05); however, there were no differences in age, Cho/Cr, or NAA/Cr. According to conditional inference tree analysis, the optimal cut-off point for the Cho/NAA ration between high-grade and low-grade meningioma was 2.409 (sensitivity = 61.54%; specificity = 86.36%). This analysis of pre-operative 1H-MRS metabolite ratio demonstrated that the Cho/NAA ratio may provide a simple and practical predictive value for high-grade intracranial meningiomas, and may aid neurosurgeons in efforts to design an appropriate surgical plan and treatment strategy before surgery. [ABSTRACT FROM AUTHOR]

Introduction: Bladder cancer (BC) is one of the most common urologic malignancies and it is urgently needed to identify novel potential prognostic biomarkers for predicting prognosis and progression of patients with BC in clinical practice. Previous research has revealed that long noncoding RNAs (lncRNAs) played critical roles in BC, and may serve as novel potential prognostic biomarkers in patients with BC. Therefore, we conducted this meta-analysis to clarify the prognostic potential of lncRNAs in BC patients. Methods: A comprehensive search was performed in PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI). According to the predefined exclusion and inclusion criteria, a total of 9 recently published articles comprising 13 lncRNAs and 666 BC patients were included into this meta-analysis. We analyzed the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the relationship between lncRNAs expression and survival outcomes. We also analyzed the odds ratio (ORs) and 95% confidence intervals (CIs) to assess the association between lncRNAs expression and clinicopathological characteristics, including histological grade, gender, multifocality, tumor size, and tumor stage. Results: Our results revealed that high lncRNAs expression was associated with shorter overall survival in Asian BC patients (pooled HR = 2.32, 95% CI: 1.35–4.00, P = 0.002, random-effect). High lncRNAs expression levels were significantly associated with histological grade (G2-G3 vs. G1: OR = 3.857, 95%CI: 1.293–11.502, P = 0.015, random-effect). Conclusions: In summary, this meta-analysis has demonstrated that lncRNAs could be used as potential prognostic markers for BC and high lncRNAs expression could predict poor prognosis among Asian BC patients. [ABSTRACT FROM AUTHOR]

Purpose: The rising incidence and life expectancy associated with prostate cancer (PCa) has led to increasing interest in predicting the risk of second primary malignancies (SPMs) among PCa survivors, although data regarding SPMs after PCa are controversial. Methods: We identified 30,964 patients from the National Health Insurance Research Database in Taiwan who had newly diagnosed PCa between 2000 and 2010. Each patient was randomly frequency-matched with an individual without PCa, based on age, comorbidity, and index year. Competing-risks regression models were used to estimate subhazard ratios (SHRs) of SPMs development associated with PCa. The Bonferroni adjustment was used in multiple comparisons. Results: Men with PCa had a trend of lower risk of developing overall SPMs compared to those without PCa (adjusted SHR = 0.94, 99.72% confidence interval [CI] = 0.89–1.00, p = 0.06). The risks of lung and liver cancer were significantly lower. In contrast, these patients had a significantly higher risk of thyroid cancer. There is a trend for a higher risk of developing SPMs in the urinary bladder and rectum/anus. Further analyses indicated that PCa patients who received radiation therapy (RT) had an increased risk of overall SPMs, hematologic malignancies, esophageal cancer, liver cancer, lung cancer, and urinary bladder cancer compared with those who did not receive RT. Conclusion: Men with PCa tended to have a lower risk of SPMs, but a significantly higher risk of subsequent thyroid cancer. Continued cancer surveillance is required among PCa survivors, especially in specific sites and in individuals who received RT. [ABSTRACT FROM AUTHOR]

Warburg effect, one of the hallmarks for cancer cells, is characterized by metabolic switch from mitochondrial oxidative phosphorylation to aerobic glycolysis. In recent years, increased expression level of pyruvate kinase M2 (PKM2) has been found to be the culprit of enhanced aerobic glycolysis in cancer cells. However, there is no agent inhibiting aerobic glycolysis by targeting PKM2. In this study, we found that Oleanolic acid (OA) induced a switch from PKM2 to PKM1, and consistently, abrogated Warburg effect in cancer cells. Suppression of aerobic glycolysis by OA is mediated by PKM2/PKM1 switch. Furthermore, mTOR signaling was found to be inactivated in OA-treated cancer cells, and mTOR inhibition is required for the effect of OA on PKM2/PKM1 switch. Decreased expression of c-Myc-dependent hnRNPA1 and hnRNPA1 was responsible for OA-induced switch between PKM isoforms. Collectively, we identified that OA is an antitumor compound that suppresses aerobic glycolysis in cancer cells and there is potential that PKM2 may be developed as an important target in aerobic glycolysis pathway for developing novel anticancer agents. [ABSTRACT FROM AUTHOR]