Control of Eye Melanoma Metastasis

描述(申请人提供)：这项研究的长期目标是 识别可能用于人体试验的化合物，以预防和控制 眼部黑色素瘤转移。尽管原发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……里面 人类，眼部黑色素瘤通常以微转移的形式扩散到肝脏，这种微转移 有可能发展成血管化转移瘤并导致死亡。的确有 与自然杀伤(NK)反应下调有关的证据 随着微转移的增加，以及免疫治疗的上调 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 血管抑素，一种抑制肿瘤生长的抗血管生成化合物 微转移到血管化转移。这项提议的目标是 检测免疫治疗和抗血管生成/抗黑色素瘤的作用机制 眼部黑色素瘤扩散至肝脏的小鼠模型中的侵袭性物质 并导致微转移，有可能发展为转移。肌内 (M)在摘除眼球前注射干扰素α-2b。 皮下注射血管抑素(SC)后立即进行 摘除含有黑色素瘤的眼睛。干扰素会消除 通过增强宿主NK反应的微转移。干扰素和血管抑素 将通过以下方式防止微转移的进展 抗血管生成。血管抑素将通过一种抗黑色素瘤药物防止转移 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.