Control of Eye Melanoma Metastasis

控制眼部黑色素瘤转移

• 批准号: 6333632
• 负责人: Hans E. Grossniklaus
• 金额: $ 26.61万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-05 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6333632
• 关键词: SDS polyacrylamide gel electrophoresis; angiostatins; antineoplastics; cancer prevention; dosage; enzyme linked immunosorbent assay; eye neoplasms; fibroblast growth factor; immunocytochemistry; interferon alpha; laboratory mouse; leukocyte activation /transformation; liver neoplasms; melanoma; metastasis; natural killer cells; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; nonhuman therapy evaluation; statistics /biometry

DESCRIPTION (provided by applicant): The long-term goals of this research are to identify compounds that may be used in human trials to prevent and control eye melanoma metastasis. Despite advances in the treatment of primary ocular melanoma, there been no decrease in the mortality rate of this disease. In humans, ocular melanoma often spreads to the liver as micrometastases that have the potential to grow into vascularized metastases and lead to death. There is evidence that downregulation of the natural killer (NK) response is associated with an increase in micrometastases, and upregulation with immunotherapeutic agents such as interferon (IFN) decrease the number of micrometastases. Additionally, there is evidence that primary ocular melanoma produces angiostatin, an anti-angiogenic compound that suppresses growth of micrometastases into vascularized metastases. The objective of this proposal is to test the mechanisms of immunotherapeutic and anti-angiogenic/anti-melanoma invasion agents in a murine model of ocular melanoma that spreads to the liver and causes micrometastases that potentially grow into metastases. Intramuscular (IM) injections of IFN alpha-2b wil1 be given prior to enucleation and subcutaneous (SC) injections of angiostatin will be given just after enucleation of the eyes that contain melanoma. The IFN will eliminate micrometastases by enhancing the host NK response. Both the IFN and angiostatin will prevent the progression of micrometastases into metastases by anti-angiogenesis. Angiostatin will prevent metastases by an anti-melanoma invasion effect.

描述（由申请人提供）：本研究的长期目标是 识别可用于人体试验以预防和控制的化合物 眼部黑色素瘤转移。尽管原发性眼病的治疗取得了进展 黑色素瘤，这种疾病的死亡率没有下降。在 在人类中，眼部黑色素瘤经常以微转移的形式扩散到肝脏 有可能发展成血管化转移并导致死亡。有 有证据表明自然杀伤 (NK) 反应的下调与此相关 随着微转移的增加和免疫治疗的上调 干扰素 (IFN) 等药物可减少微转移的数量。 此外，有证据表明原发性眼部黑色素瘤会产生 血管抑制素，一种抗血管生成化合物，可抑制血管生成 微转移转变为血管化转移。该提案的目标是 测试免疫治疗和抗血管生成/抗黑色素瘤的机制 眼部黑色素瘤扩散至肝脏的小鼠模型中的侵袭剂 并导致可能发展为转移的微转移。肌肉注射 (IM) 在摘除前注射 IFN α-2b 皮下（SC）注射血管抑制素将在 含有黑色素瘤的眼睛被摘除。干扰素将消除 通过增强宿主 NK 反应来抑制微转移。干扰素和血管抑制素 将阻止微转移进展为转移 抗血管生成。血管抑制素可通过抗黑色素瘤预防转移 侵袭作用。