Background: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. Patients and methods: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 Â 10 3 /ml received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.

Background: Epithelial-to-mesenchymal transition (EMT) plays a prominent role in tumorigenesis. Metformin exerts antitumorigenic effects in various cancers. This study investigated the mechanisms of metformin in TGF-β1-induced Epithelial-to-mesenchymal transition (EMT) in cervical carcinoma cells. Methods: cells were cultured with 10 ng/mL TGF-β1 to induce EMT and treated with or without metformin. Cell viability was evaluated by CCK-8 (Cell Counting Kit 8, CCK-8) assay; apoptosis were analyzed by flow cytometry; cell migration was evaluated by wound-healing assay. Western blotting was performed to detect E-cadherin, vimentin, signal transducer and activator of transcription 3 (STAT3), snail family transcriptional repressor 2 (SNAIL2), phosphorylation of p70s6k (p-p70s6k) and -Pyruvate kinase M2 (PKM2) Results: TGF-β1 promoted proliferation and migration, and it attenuated apoptosis compared with cells treated with metformin with or without TGF-β1 in cervical carcinoma cells. Moreover, metformin partially abolished TGF-β1-induced EMT cell proliferation and reversed TGF-β1-induced EMT. In addition, the anti-EMT effects of metformin could be partially in accord with rapamycin, a specific mTOR inhibitor. Metformin decreased the p-p70s6k expression and the blockade of mTOR/p70s6k signaling decreased PKM2 expression. Conclusion: Metformin abolishes TGF-β1-induced EMT in cervical carcinoma cells by inhibiting mTOR/p70s6k signaling to down-regulate PKM2 expression. Our study provides a novel mechanistic insight into the anti-tumor effects of metformin.

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Overexpression and overactivation of Stat3 was found in EOC tissues, and the constitutive activation of Stat3 signaling pathway may play an important role in the invasion and prognosis of EOC.

We aimed to investigate the risk factors for cervical intraepithelial neoplasia (CIN) in Jiexiu, Shanxi Province, China. Twenty thousand eligible married women (age: 18-65 years) were administered with a questionnaire on potential risk factors for CIN and underwent liquid based Pap test. All women with abnormal cytological results underwent colposcopy with biopsy. Based on the biopsy pathology results, women were then assigned to either study group (with CIN) or control group (negative for histological results and volunteered to participate in the follow up study). The women in both study group and control group underwent vaginal microflora detection and dietary survey. The potential risk factors were analyzed by using ordinal logistic regression. Among the 20,000 women ne 1,438 women (7.19%) had cytologic abnormalities and 410 (2.05%) women were diagnosed histologically with CIN lesions, including 317 (1.58%) with CIN1, 93 (0.50%) with CIN2/3and 11 (55/100,000) with squamous cell carcinoma (SCC). The average daily dietary folate intake was significantly lower in the study group (344.61±153.07μg) than in the control group (371.50±166.58μg; P<0.001). Multivariate analysis demonstrated that age of 56-65 years, farming as the husband's occupation, unwashing the vulva after sexual intercourse, and low self-reported folate intake were positively associated with CIN development and might have contribution to the increased CIN incidence in this population. These findings may provide help to develop the strategies to reduce the risk of cervical cancer in China.