Angiocidal Effect of Cyclosporine in Cancer Therapy

环孢素在癌症治疗中的杀血管作用

• 批准号: 6873533
• 负责人: DILIP S KITTUR
• 金额: $ 13.07万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-14 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6873533
• 关键词: angiogenesis; cyclosporines; drug screening /evaluation; laboratory mouse; neoplasm /cancer blood supply; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; neoplasm /cancer transplantation; neoplastic growth; nonhuman therapy evaluation; sarcoma; xenotransplantation

DESCRIPTION (provided by applicant): Our application represents a cross fertilization between oncology and transplantation by utilizing cyclosporin A (CyA) as an antiangiogenic agent in the treatment of cancers. Antiangiogenic agents are promising adjuncts in cancer therapy, but their potential has not been fully realized, partly due to a lack of a strong angiocidal effect of these drugs. Our preliminary data in a mouse model of angiogenesis indicates that CyA has angiocidal effects, suggesting that CyA could be a potential antiangiogenic agent in cancer therapy. Our data also indicates that the toxicity of high dose CyA, at which the drug is angiocidal, is principally due to an excess release of Endothelin-1 (ET-1) and is prevented by blockade of the ET-1A receptor on smooth muscle and myocardial cells. Our hypothesis is that high dose CyA will disrupt angiogenesis in tumors due to increase in endothelial cell oxidative stress leading to redistribution of VE-cadherin and loss of endothelial cell-cell contacts. We propose to test this hypothesis in a sarcoma xenograft model and a melanoma isograft model of cancer in mice by administering high dose CyA alone and in combination with a conventional chemotherapeutic agent. Tumor growth, angiogenesis, and drug toxicity will be monitored in these mice to determine if CyA synergizes with the chemotherapeutic agent in the treatment of cancer. Our studies have the potential of discovering a novel, angiocidal effect of a commonly used drug. If successful, these studies will be translated expeditiously into clinical trials for the treatment of cancer.

描述（由申请人提供）：