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Bcl-2 family protein is an important factor in regulating apoptosis and is associated with cancer. The anti-apoptotic proteins of Bcl-2 family, such as Bcl-2, are overexpression in numerous tumors, and contribute to cancer formation, development, and therapy resistance. Therefore, Bcl-2 is a promising target for drug development, and several Bcl-2 inhibitors are currently undergoing clinical trials. In this study, we carried out a QSAR-based virtual screening approach to develop potential Bcl-2 inhibitors from the SPECS database. Surface plasmon resonance (SPR) binding assay was performed to examine the interaction between Bcl-2 protein and the screened inhibitors. After that, we measured the anti-tumor activities of the 8 candidate compounds, and found that compound M1 has significant cytotoxic effect on breast cancer cells. We further proved that compound M1 downregulated Bcl-2 expression and activated apoptosis by inducing mitochondrial dysfunction. In conclusion, we identified a novel Bcl-2 inhibitor by QSAR screening, which exerted significant cytotoxic activity in breast cancer cells through inducing mitochondria-mediated apoptosis. [ABSTRACT FROM AUTHOR]

Previous studies have shown that alterations of cytokines might play a role in the pathogenesis of adenomyosis. This study aims to investigate the expression of interleukin-37 (IL-37), an anti-inflammatory cytokine, in the eutopic and ectopic endometria of patients with adenomyosis. Endometrial specimens were collected from 30 women with adenomyosis and 20 without adenomyosis. The gene and protein expression of IL-37 was measured using a quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Compared with the control endometria, the protein expression level and gene level of IL-37 was significantly lower in both the ectopic and eutopic endometria of patients with adenomyosis. The gene and protein expressions of IL-37 in ectopic endometria were lower than those in eutopic endometria of patients with adenomyosis. Our results suggest that there was a low level of IL-37 in the eutopic and ectopic endometria of patients with adenomyosis, and an abnormal inflammatory response might occur in the endometria of patients with adenomyosis. [ABSTRACT FROM PUBLISHER]

Objective: To investigate the role of Stat1 gene in the proliferation and chemotherapeutic sensitivity of cervical cancer HeLa cells., Methods: The protein expression of Stat1 in the Hela cells exposed to gradient concentrations of cisplatin (DDP) was detected by Western blotting with or without small interfering RNA (siRNA)-mediated Stat1 gene silencing. The effect of Sata1 silencing on the sensitivity to DDP and cell proliferation of the cells was tested using MTT assay and BrdU assay, and the expression of c-Myc was detected by Western blotting in the cells treated with siRNA and DDP., Results: The expression of Stat1 in Hela cells exposed to DDP increased with the DDP concentrations, reaching 1.5 folds of the baseline at a DDP concentration of 5 mg/L and 2 folds at 10 mg/L. Stat1-siRNA effectively reduced Stat1 expression in Hela cells, promoted the cell proliferation, and enhanced the expression of c-Myc; DDP inhibited the cell growth and down-regulated c-Myc expression. Stat1-siRNA rescued DDP-induced inhibition of cell growth and c-Myc down-regulation., Conclusion: The expression of Stat1 is associated with DDP sensitivity in cervical cancer cells, and Stat1 silencing can increase the sensitivity to DDP and c-Myc expression of the cells.

Objective: A patient was admitted for menopause for 2 years and abnormal vaginal bleeding and abdominal pain for 2 months. Gynecological examination revealed uterine atrophy without abnormal findings in the bilateral adnexa. CA125 and CEA levels were normal. The patient underwent laparoscopically assisted vaginal hysterectomy with bilateral salpingo-oophorectomy. Pathological examination of the surgical specimens revealed synchronous primary cancers stage Ia in both the endometrium and the right fallopian tube. The patient then received 6 cycles of chemotherapy with oxaliplatin combined with docetaxel given intravenously and remained alive without evidence of recurrence. Synchronous primary endometrial and fallopian tube cancer is a rare clinical entity, and laparoscopic surgery with postoperative chemotherapy can be considered for stage I patients.

Objective: To determine whether the infertile patients with polycystic ovarian syndrome (PCOS) is related to dysregulation of peritoneal fluid and serum leptin concentration, and to investigate the relationship between the leptin and some endocrine hormones in PCOS., Methods: Twenty subjects with PCOS and 20 control women were included in the study. Peritoneal fluid and serum concentration of leptin, insulin, insulin-antibody, testosterone (T), estrogen (E(2)), and progestogen (P) were measured by radioimmunoassay (RIA)., Results: Peritoneal fluid concentrations of leptin, insulin, T and insulin-antibody in PCOS patients were significantly higher than those of the control group (P<0.05). There was no statistically significant difference in peritoneal fluid E(2) and P between PCOS and the control group (P>0.05). The serum concentrations of leptin and T in PCOS were significantly higher than those of the control group (P<0.05), but the levels of insulin, E(2), P and insulin-antibody were not significantly different between the 2 groups (P>0.05). With the BMI> or =23 kg/m(2) subgroup in PCOS patients, the peritoneal fluid and serum concentrations of leptin, insulin and T were significantly higher than those of BMI 23 kg/m(2) subgroup (P<0.01). There was no significant difference in E(2)and insulin-antibody between the 2 subgroups (P>0.05). Pearson correlation analysis indicated that peritoneal fluid and serum leptin levels were positively correlated with BMI, insulin, T and insulin-antibody, but negatively correlated with E(2), with no significant correlation with P. Multiple stepwise regression analysis indicated that the factors that influenced the peritoneal fluid and serum leptin levels were BMI, insulin, T and E(2) ordinally., Conclusion: Peritoneal fluid and serum leptin concentration and insulin,T, Ins-antibody level are abnormal in PCOS patients. Leptin may play an important role in the pathogenesis of PCOS. BMI is the main factor to correlate with leptin.