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This study investigates the correlation between the oncoprotein Bmi-1 and telomerase activity in ovarian cancer. A real-time polymerase chain reaction (PCR) method is used to detect the messenger RNA (mRNA) expression of Bmi-1 protein in 47 ovarian epithelial cancer cases, and immunohistochemistry is used to detect Bmi-1 protein expression in the tissues. A modified telomeric repeat amplification protocol (TRAP) is used to detect telomerase activity. Western blotting is used to detect the expression of telomerase hTERT in the tissues studied. Compared to normal ovarian epithelial tissue, Bmi-1 protein in the 47 ovarian epithelial cancer cases showed higher expression and was related to pathological grade and clinical stage. Significantly higher Bmi-1 levels were found among different clinocopathological types of the cancer (P<0.05). Grade G3 cases expressed Bmi-1 at a higher rate (93.10%) than did grade G2 cases (61.11%). Expression in phase II and phase III cases was lower (66.67%) than in phase IV (92.31%). In ovarian epithelial cancer tissues, 87.23% (41/47) cases demonstrated positive telomerase activity, whereas no activity was observed in normal tissues. The majority (90.24%) of specimens with positive telomerase activity showed high Bmi-1 expression levels. Spearman correlation analysis indicated that expression of Bmi-1 protein correlated positively with elevated telomerase activity. Bmi-1 protein is highly expressed in ovarian epithelial cancer tissues, and expression correlates with histological grade and clinical phase. Elevated Bmi-1 expression correlates closely with increased telomerase activity and plays a significant role in the pathogenesis of ovarian cancer.

Introduction:We aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating EGFR-mutant leptomeningeal metastases (LMs) from EGFR-mutant NSCLC.Methods: Patients with EGFR-mutant NSCLC with LM who had failed tyrosine kinase inhibitors were recruited. The dose of IP was escalated from 15 mg to 80 mg using an accelerated titration design in a phase 1 study. The recommended dose (RD) determined in phase 1 was used in the phase 2 study. The primary end point was treatment efficacy measured as the clinical response rate. Overall survival and adverse events (AEs) were evaluated as secondary end points. Results:The RD observed in the phase 1 study was 50 mg pemetrexed. A total of 30 cases of LM-NSCLC were enrolled in the phase 2 study, including 14 males and 16 females. Four patients did not survive for 4 weeks and could not be evaluated for efficacy. The clinical response rate was 84.6% (22 of 26). The median overall survival of all patients was 9.0 months (n ¼ 30, 95% confidence interval: 6.6-11.4 mo). Most AEs were mild, and the most frequent AE of any grade was myelosuppression (n ¼ 9, 30%), which returned to normal after symptomatic treatment.Conclusions: This study revealed that 50 mg pemetrexed is the RD which results in few AEs and a good response rate. IP is an effective treatment for patients with EGFRmutant NSCLC-LM who had failed on tyrosine kinase inhibitor.

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The purpose of this study was to examine the relations of hormonal contraceptives and infertility drugs with the risk of venous thromboembolism (VTE), deep vein thrombosis (DVT), pulmonary embolism (PE), ischemic stroke, and cardiovascular disease. The Taiwan National Health Institute Research Database was searched for women who had taken hormonal contraceptives or infertility medications from 2000 to 2010. The two groups were age and index date matched with controls (1:4 ratios). Cox regression analysis was used to examine the risks of VTE, DTE, PE, ischemic stroke, and cardiovascular disease. A total of 32,067 women were included in the hormonal contraceptives group and 4710 in the infertility medications group (matched controls: 127,872 and 18,840, respectively). After adjustment for age, comorbidities, and other confounders, the contraceptives group had a higher risk of VTE (adjusted HR 1.14, 95% CI 1.004 to 1.30) and cardiovascular disease (adjusted HR 1.30, 95% CI 1.26 to 1.34), and lower risk of ischemic stroke (adjusted HR 0.90, 95% CI 0.86 to 0.95). The infertility medications group had a higher risk of VTE (adjusted HR 1.996, 95% CI 1.41 to 2.72) and DVT (adjusted HR 1.86, 95% CI 1.31 to 2.63), and lower risk of ischemic stroke (adjusted HR 0.82, 95% CI 0.68 to 0.99) and cardiovascular disease (adjusted HR 0.83, 95% CI 0.74 to 0.94). Hormonal contraceptives and infertility medications appear to lower the risk of ischemic stroke and increase the risk of VTE; however, their effect on the risk of other types of cardiovascular events varies.

Aims This study was designed to evaluate the protective effects of AMPKα and SIRT1 on insulin resistance in PCOS rats, and to illuminate the underlying mechanisms. Methods An in vitro PCOS model was established by DHEA (6 mg/(100 g•d)), and the rats were randomly divided into the metformin group (MF group, n = 11), the exenatide group (EX group, n = 11), the PCOS group (n = 10), and the normal control group (NC group, n = 10). The MF group was administered MF 300 mg/(kg•d) daily. The EX group was subcutaneously injected EX 10μg/(kg•d) daily. After 4 weeks of continuous administration, fasting blood glucose and serum androgen, luteinizing hormone and other biochemical indicators were measured. Western and Real-time PCR were used to determine the expression of AMPKα and SIRT1 in the ovaries of each group. Results After 4 weeks of drug intervention, compared with untreated PCOS group, EX group and MF group had visibly decreased body weight (222.64 ± 16.57, 218.63 ± 13.18 vs 238.30 ± 12.26 g, P = 0.026), fasting blood glucose (7.71 ± 0.72, 8.17 ± 0.54 vs 8.68 ± 0.47 mmol/L, P < 0.01), HOMA-IR (8.26 ± 2.50, 7.44 ± 1.23 vs 12.66 ± 1.44, P < 0.01) and serum androgen (0.09 ± 0.03, 0.09 ± 0.03 vs 0.53 ± 0.41 ng/ml, P < 0.01) and the expressions of AMPKα and SIRT11 were increased progressively (P < 0.05). Conclusions Both metformin and exenatide can improve the reproductive and endocrine functions of rats with PCOS via the AMPKα-SIRT1 pathway, which may be the molecular mechanism for IR in PCOS and could possibly serve as a therapeutic target.

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The present study aims to clarify whether hyaluronan binding protein 1 (HABP1/p32/C1QBP) is an indicator of peritoneal and lymph node metastasis in epithelial ovarian cancer (EOC), which to the authors' knowledge is not previously reported by others. Western blot analysis demonstrated that HABP1 was highly overexpressed in most metastatic lesions. Of 89 patients whose primary tumors showed high HABP1 expression on immunohistochemical staining, 85 (95.5%) presented peritoneal metastases and 43 (48.3%) had lymph node metastases. Univariate and multivariate logistic regression analyses revealed that HABP1 overexpression correlated with peritoneal dissemination and lymph node metastasis in EOC. The specificity and positive predictive value of HABP1 staining were shown to be better for peritoneal metastasis, while the negative and sensitivity predictive value of HABP1 staining were better for lymph node metastasis. The odds ratio of high versus low staining for peritoneal spread was 9.236 (95% confidence interval (CI), 2.705, 19.316), and that for lymph node metastasis was 8.614 (95% CI, 2.507, 21.039). Furthermore, HABP1 protein may potentially be used alone or in combination with other markers as a predictive marker of EOC patients with lymph node metastasis and/or peritoneal dissemination.