YM155 enhances docetaxel efficacy in ovarian cancer.

YM155 (Sepantronium bromide) is a potent small molecule inhibitor of survivin by suppression of survivin expression and shows the promising anticancer activity in many types of cancers. Docetaxel (Taxotere®) is a member of the taxane drugs used in the treatment of a number of cancers in clinic. Despite the therapeutic efficacy of docetaxel is encouraging, the emergent resistance is an urgent issue. In this study, we investigate the effect of YM155 on docetaxel efficacy in ovarian cancer cells. Our data showed that YM155 actively induced cell growth inhibition, cell cycle arrest and apoptosis with downregualtion of survivin in ovarian cancer cells. Moreover, YM155 increased the intracellular ROS levels, and pretreatment with either NAC or GSH partially reversed the YM155-induced ROS accumulation and apoptosis only in the parental A2780 cells, but not in the resistant A2780/Taxol cells. Furthermore, YM155 enhanced docetaxel efficacy to inhibit the growth and induce apoptosis in ovarian cancer cells. Take together, our results suggested that combination of YM155 and docetaxel may be a feasible strategy for the treatment of ovarian cancer.

Crizotinib synergizes with cisplatin in preclinical models of ovarian cancer.

Crizotinib, a small molecule inhibitor of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and c-MET (also called MET or hepatocyte growth factor receptor), has been approved by the Food and Drug Administration for the treatment of patients with advanced non-small cell lung cancer whose tumors have rearrangements in the ALK or ROS1 gene. However, the anticancer effect of crizotinib on ovarian cancer is still unclear. In this study, our data show that crizotinib can actively induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreasing phosphorylation of the downstream signaling effectors AKT and ERK in human ovarian cancer cells. Crizotinib also increases the intracellular reactive oxidative species (ROS) levels, and pretreating with ROS scavenger N-acety-L-cysteine partially reverses crizotinib-induced apoptosis. Moreover, crizotinib can synergistically inhibit ovarian cancer cells growth in vitro and in vivo when combines with cisplatin. Altogether, crizotinib potently potentiates the activity of cisplatin in ovarian cancer, suggesting the synergistic effect of crizotinib and cisplatin may be valuable for ovarian cancer patients' treatment.

Preoperative platelet count improves the prognostic prediction of the FIGO staging system for operable cervical cancer patients.

BACKGROUND: Increased platelet has been identified as an independent and unfavorable prognostic indicator in various cancers including cervical cancer. In our study, the prognostic value of preoperative platelet count combining with FIGO (International Federation of Gynecology and Obstetrics) stage in patients with operable cervical cancer was investigated. METHODS: A large cohort study including 800 operable cervical cancer patients was conducted from May 2005 to December 2012. Cancer-related biomarkers such as platelet count, hematocrit, hemoglobin, RDW was evaluated together with FIGO staging system in stage IA1-IIA2 cervical cancer patients. The prediction validity of platelet together with FIGO stage was then evaluated by receiver operating characteristic (ROC) curve, and the areas under the curve (AUCs) were compared by Z test. RESULTS: Univariate cox proportional hazard analysis demonstrated that hematocrit, platelet count, hemoglobin, FIGO stage, tumor differentiation, PLN (pelvic lymph node metastasis), LVSI (vascular lymph node invasion) were associated with overall survival (OS) and disease free survival (DFS), instead of RDW (red cell distribution width), age and histological subtype. Multivariate analysis demonstrated that preoperative platelet and FIGO stage were independent predictors for OS and DFS in cervical cancer. Furthermore, significant improvements were found after the combination of platelet count and FIGO stage in predicting OS and DFS for cervical cancer patients (P=0.0128 and P=0.0385, respectively). CONCLUSIONS: Combination of platelet count and FIGO stage improved the prediction performance of FIGO staging and provide additional risk stratification for operable cervical cancer patients.

Volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer.

Volasertib (BI 6727), a highly selective and potent inhibitor of PLK1, has shown broad antitumor activities in the preclinical and clinical studies for the treatment of several types of cancers. However, the anticancer effect of volasertib on cervical cancer cells is still unknown. In the present study, we show that volasertib can markedly induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreased protein expressions of PLK1 substrates survivin and wee1 in human cervical cancer cells. Furthermore, volasertib also enhances the intracellular reactive oxidative species (ROS) levels, and pretreated with ROS scavenger N-acety-L-cysteine totally blocks ROS generation but partly reverses volasertib-induced apoptosis. In addition, volasertib significantly potentiates the activity of cisplatin to inhibit the growth of cervical cancer in vitro and in vivo. In brief, volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer, suggesting the combination of volasertib and cisplatin may be a promising strategy for the treatment of patients with cervical cancer.