Ilan Bruchim

In vitro metformin anti-neoplastic activity in epithelial ovarian cancer

OBJECTIVEnMetformin, a commonly used drug in the treatment of type II diabetes, may reduce cancer risk and improve cancer prognosis. We evaluated its effect on epithelial ovarian cancer cell lines.nnnMETHODSnThe OVCAR-3 and OVCAR-4 cell lines were exposed to metformin with and without cisplatin. Cytotoxicity assays were performed in triplicates using the Alamar colorimetric assay. Levels of total and phosphorylated AMPK, p70S6K and S6K were evaluated by Western blotting following exposure to metformin.nnnRESULTSnMetformin induces dose- and time-dependent growth inhibition of OVCAR-3 and OVCAR-4 cell lines. Metformin potentiated the effect of cisplatin in vitro. Metformin growth inhibition was partly abolished by the AMPK inhibitor, compound C. Western blotting demonstrated that metformin at cytotoxic concentrations, induced AMPK phosphorylation and decreased p70S6K and S6K phosphorylation, suggesting the mechanism for its anti-proliferative action.nnnCONCLUSIONnMetformin significantly inhibits the growth of ovarian cancer cell lines and potentiates cisplatin. Further pre-clinical studies are being conducted to determine the applicability of metformin in the treatment of ovarian cancer.

Advancing Women’s Cancer Care

Prognostic Model for FIGO Stage I Epithelial Ovarian Cancer The choice to give adjuvant chemotherapy to patients with stage I epithelial ovarian cancer is currently based on the substage (IC) and grade (G2–3) of the disease. At the opening plenary session, Dr. Andreas Obermair from Brisbane, Australia, introduced a new prognostic index (ECO-1) for stratifying patients with surgical stage I epithelial ovarian cancer. The ECO-1 score is based on points assigned for preoperative CA125 1 30 (3 points), advanced age at diagnosis (3 points), substage IC (1 point) and grade 2 or 3 (1 point). Based on retrospective data from 600 patients, ECO-1 scores of 0–1, 3–6 and 7–8 corresponded to 5-year survival rates of 97, 89 and 73%, respectively (p ! 0.0001). The authors concluded that patients with ECO-1 scores ̂ 2 have a very good prognosis and, confirming results of previous trials, likely obtain no additional survival benefit from adjuvant chemotherapy.

New Aspects in Gynecologic Oncology

a complete pelvic and para-aortic lymph node (LN) dissection had a signifi cant longer operating time (median operating time: 300 vs. 210 min, p ! 0.001); greater number of transfusion rate (72 vs. 59%, p ! 0.006), and greater postoperative morbidity (p = 0.014). Therefore, despite the evidence that pelvic and aortic LNs are frequent sites of metastases in patients with advanced ovarian cancer, the value of lymphadenectomy in optimally intraperitoneal cytoreduced patients is not established in this RCT. Lymphadenectomies delay recurrence but have no demonstrable survival benefi ce.