The Effect of TRA-8 on Ovarian Cancer Tissue
The goal of this study is to determine the apoptosis-inducing efficacy of TRA-8 in patient ovarian cancer tissues using a tissue slice technology. In addition, we want to evaluate the expression of apoptosis regulatory proteins using multiplex proteomic technology and its correlation with TRA-8-induced cytotoxicity in patient ovarian cancer tissues.
|Study Design:||Observational Model: Cohort
Time Perspective: Cross-Sectional
|Official Title:||Death Receptor-Mediated Apoptosis and Therapy Strategies in Ovarian Cancer|
- Presence of TRA-8 apoptosis [ Time Frame: At the time of surgery ] [ Designated as safety issue: No ]Apoptosis properties of TRA-8 will be analyzed in tissue collected from surgery using tissue slice technology.
- Presence of apoptosis regulatory proteins [ Time Frame: At the time of surgery ] [ Designated as safety issue: No ]The presence of apoptosis regulatory properties will be analyzed in tissue collected from surgery using multiplex proteomic technology.
|Study Start Date:||August 2008|
|Study Completion Date:||January 2013|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Ovarian cancer remains highly lethal, with an estimated 25,580 new cases and 16,090 death per year in the US. The most common ovarian cancers arise from the surface epithelium of the ovary. Approximately 75% of patients with advanced-stage cancer are surgically incurable. While chemotherapy is a critical component of treatment, the pre-existing and induced chemoresistance of ovarian cancer cells is a major obstacle in treatment of patients with advanced disease. Novel strategies to enhance the established therapeutic Defective apoptosis has been proposed as one of the major mechanisms that lead to malignant transformation and resistance to therapeutics. Defective apoptosis may result from increased growth stimulation (oncogenes), decreased growth inhibition (tumor suppressor genes) or imbalanced apoptosis regulation. Alterations of the Bcl-2 family proteins have been reported to be associated with chemotherapy resistance in ovarian cancer cells.(1) Increased anti-apoptosis protein, Bcl-XL, may play a role in preventing apoptosis of ovarian cancer cells in response to chemotherapy. Conversely, high levels of pro-apoptosis protein, Bax, are associated with a favorable response to therapy. The role of these and other apoptotic regulatory proteins in sensitivity/resistance mechanisms to chemotherapy in patient's ovarian cancer cells are just beginning to be elucidated.
Precision cut tumor slices will be prepared from fresh primary ovarian tumor specimens using the Krumdieck tissue slicer, followed by ex vivo TRA-8 cytotoxicity assays on the tumor slices. Tumor-derived tissue slices may be used immediately in short term assays with no need to isolate or expand tumor cells, thus avoiding potential problems in maintaining cell viability or selecting variant cells during tumor dispersion or longer periods of in vitro cell culture. Demonstration of TRA-8-induced apoptosis using primary ovarian tumors in ex vivo tumor slice cytotoxicity assays can strengthen the rationale for this therapy in this tumor type and may be used to select patients who would most likely benefit from TRA-8 therapy. The sensitivity of ovarian patient tumors to TRA-8, paclitaxel, and carboplatin will be evaluated in tumor slice cytotoxicity assays as single agents and in combination. Slices from different treatment conditions will be paraffin-embedded or frozen for immunohistochemical evaluation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00711932
|United States, Alabama|
|University of Alabama|
|Birmingham, Alabama, United States, 35294|
|Principal Investigator:||Tong Zhou, M.D.||University of Alabama at Birmingham|