Control of Eye Melanoma Metastasis

描述（由申请人提供）：本研究的长期目标是 以确定可用于人体试验的化合物， 眼黑色素瘤转移。尽管原发性眼部疾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，眼黑色素瘤通常作为微转移扩散到肝脏， 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 随着微转移的增加， 诸如干扰素（IFN）的药物减少微转移的数量。 此外，有证据表明，原发性眼部黑色素瘤产生 血管抑制素，一种抑制血管生成的化合物， 微转移到血管化转移。本提案的目的是 测试免疫和抗血管生成/抗黑色素瘤的机制 侵袭剂在扩散至肝脏的眼黑色素瘤小鼠模型中的作用 并导致微转移，可能会发展成转移。肌内 (IM)在去核前注射IFN α-2b， 皮下（SC）注射血管抑素后立即给予 摘除含有黑色素瘤的眼睛干扰素会消除 通过增强宿主NK反应来抑制微转移。干扰素和血管抑素 将阻止微转移进展为转移， 抗血管生成。血管抑制素将通过抗黑色素瘤 入侵效应

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.