The Effect of TRA-8 on Ovarian Cancer Tissue
Death Receptor-Mediated Apoptosis and Therapy Strategies in Ovarian Cancer
調査の概要
状態
条件
詳細な説明
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.
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Alabama
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Birmingham、Alabama、アメリカ、35294
- University of Alabama
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Patients must have suspected ovarian cancer and must be a candidate for surgery.
- Patients must have provided a signed consent form.
- Patients must have extra tumor at the time of surgery that is appropriate for tumor slicing.
- Patients must be at least 19 years of age.
- Patients must have histologically confirmed epithelial carcinoma of the ovary or of extra-ovarian origin, any histologic subtype or stage.
Exclusion Criteria:
- Patients who have received any prior therapy for ovarian cancer.
研究計画
研究はどのように設計されていますか?
デザインの詳細
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Presence of TRA-8 apoptosis
時間枠:At the time of surgery
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Apoptosis properties of TRA-8 will be analyzed in tissue collected from surgery using tissue slice technology.
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At the time of surgery
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Presence of apoptosis regulatory proteins
時間枠:At the time of surgery
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The presence of apoptosis regulatory properties will be analyzed in tissue collected from surgery using multiplex proteomic technology.
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At the time of surgery
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協力者と研究者
捜査官
- 主任研究者:Tong Zhou, M.D.、University of Alabama at Birmingham
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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卵巣がんの臨床試験
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