Effect of TRA-8 anti-DR5 monoclonal antibody in combination with chemotherapy in an ex vivo human ovarian cancer model
2008
14695 Background: It has been previously demonstrated that TRA-8 anti-DR5 monoclonal antibody induces apoptosis in primary human ovarian cancer (Gynecol Oncol 105:291–298, 2007). The purpose of this study was to evaluate the cytotoxicity of TRA-8 in combination with carboplatin and paclitaxel utilizing the same ex vivo three-dimensional tissue slice technique. Methods: Primary epithelial ovarian cancer tissue from 18 patients was obtained at the time of cytoreductive surgery. The Krumdieck tissue slicer was used to prepare 5 mm slices. 300 μm thick slices were incubated in media and treated with TRA-8, carboplatin, paclitaxel, or a combination of TRA-8 plus carboplatin and paclitaxel for 24–48 hours. To evaluate cytotoxicity, ATP levels were assessed using a luminescence-based ATP assay and compared to untreated control slices. Results: The average patient age was 63 years-old (range 48–84). Fourteen patients (78%) were Caucasian and 4 (22%) were African American. Sixteen (89%) tumor specimens were papill...
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