报告从医药行业事件分析、竞争环境、竞争对手、行业数据等几个方面进行了分析评论。

报告从政策环境、市场行情、厂商动态、科技研发、国际资讯、行业数据、分析评论等几个方面对医药行业进行了分析评论。

报告从政策环境、市场行情、厂商动态、科技研发、国际资讯、行业数据、分析评论等几个方面对医药行业进行了分析评论。

报告从医药行业事件分析、竞争环境、竞争对手、行业数据等几个方面进行了分析评论。

报告从政策环境、市场行情、厂商动态、科技研发、国际资讯、行业数据、分析评论等几个方面对医药行业进行了分析评论。

报告从医药行业事件分析、竞争环境、竞争对手、行业数据等几个方面进行了分析评论。

报告从产业动态、产业分析、技术趋势、企业跟踪、地方动向等几个方面对生物科技产业进行了分析评论。

Following treatment with chemotherapeutic agents, responsive ovarian cancer cells undergo apoptotic cell death. Several groups have shown that the apoptotic protease, caspase 2 (C2), is an essential activator of cell death in ovarian cancer cells treated with cisplatin and we have found, by knock-down of C2 in ovarian cancer cells, that C2 is also required for responsiveness to microtubule perturbing agents such as paclitaxel. Work from our laboratory has demonstrated that C2 is normally controlled by the metabolic status of the cell in that high levels of flux through the pentose phosphate pathway (PPP) prevents activation of C2 . This inhibition is exerted through phosphorylation of C2 at a specific residue that is catalyzed by calcium-calmodulin-dependent kinase II (CaMKII). CaMKII is activated by the product of the PPP, NADPH, through its ability to support fatty acid synthesis. The precise mechanism by which fatty acid synthesis activates CaMKII is not yet known. Because ovarian cancers exhibit increased glucose uptake and increased fatty acid synthesis, we hypothesized that susceptibility of ovarian cancers to front-line chemotherapeutic agents, reflect, at least in part, the metabolic status of the cells and, consequently, the phosphorylation state of caspase 2. We have found that inhibition of PPP operation and interference with fatty acid synthesis sensitizes ovarian cancer cells to a range of chemotherapeutic agents that depend upon C2 for cell death.

The metabolic consequences of obesity may be critical in the development of ovarian cancer (OC), resulting in biologically different cancers than those that arise in leaner women. This may occur through aberrant modulation of mTOR signaling, given that alterations in this pathway are common in both obesity and OC. Thus, obese OC patients may derive increased benefit from chemotherapeutic agents related to inhibition of this pathway, such as mTOR inhibitors (everolimus) or metformin. We have demonstrated that the obese state can promote tumor progression in the KpB mouse model of OC. The ovarian tumors that arose in the obese mice were genomically and metabolically different from those that arose in non-obese mice. Metformin was found to be more efficacious in the obese versus non-obese KpB mice, suggesting that obesity may be a biomarker for response to this agent. For our in vitro studies, metformin and everolimus were found to be more effective in the inhibition of proliferation and induction of apoptosis under low versus high glucose concentrations. We postulate that OC cells deprived of glucose have blunted proliferative capacity, rendering them more susceptible to metformin and everolimus, and that a high glucose environment may overall enhance proliferative capacity.

Project 1. We will determine the early molecular changes in STIC and their biological significance in developing high-grade serous carcinoma. marker selection and sample preparation will begin in the next coming months. Project 2. We will evaluate whether the presence of a STIC is associated with different clinical manifestations and/or outcome compare to those patients in whom a STIC was not identified. Molecular profiling will be initiated after quality control checking. Project 3. We will identify the early molecular changes that precede the development of STICs using gene expression analysis of morphologically normal FTE from high-risk women compared to FTE from normal control specimens and use an in vitro system and a mouse model to generate a molecularly defined carcinoma resembling HGSC from FTE and OSE using oncogenes expressed in ovarian carcinoma. Project 4 We plan to if the statin drugs are effective in preventing STIC formation and suppress tumor progression in the OVGP1 mouse model that spontaneously develops STIC and neoplasms.. Project 5. With the data and cases piling up, we will be able to address the molecular and epidemiologic profile of putative precursor lesions including STIC in the fallopian tubes and ovaries from women at high-risk for ovarian cancer. Also, a pilot study will be performed to determine the most cost-effective way to prepare the tissue sections for studies related to study early tumor development in ovarian cancer. This information will be shared with science community.