MELANIN SYNTHESIS AND CONTROL OF MALIGNANT MELANOMA

恶性黑色素瘤提供了一些特殊的属性，通过导弹方法提供了改善诊断和化疗的机会。a）黑色素和黑素体的合成，即，黑素生成专门发生在黑素细胞中，并且在肿瘤对应物恶性黑素细胞中大大升高; B）黑素体在结构上由基质蛋白和酪氨酸酶组成，后者将酪氨酸转化为多巴和多巴醌以形成黑素分类; c）结构蛋白在恶性黑色素瘤中变得显著异常;和B）从酪氨酸到黑色素的代谢途径是不可逆的，因此阻止酪氨酸酶底物掺入代谢聚合物黑色素中。针对黑素细胞特有的黑素体结构基质蛋白，我们成功地建立了抗黑素体的单克隆抗体，从而成功地建立了检测恶性黑色素瘤早期病变和评估恶性黑色素瘤患者预后的免疫诊断工具。其次，通过化学修饰酪氨酸酶底物的黑色素前体，我们成功地将合成化合物定位在黑色素瘤细胞中，从而破坏它们。因此，我们的项目提供了，通过解剖我们的恶性黑素细胞的特定生物学特性，一个独特的研究方向a）早期实验室诊断，和B）恶性黑色素瘤的合理化疗。具体而言，我们能够表征黑素细胞的生物成分，并开发实验结果的实际应用，以更好地管理患者护理。

Malignant melanoma offers some particular attributes that provide opportunities for improved diagnosis and chemotherapy by a guided missile approach. This proposal is based upon the following observations; a) the synthesis of melanin and melanosomes, i.e., melanogenesis, occurs exclusively in melanocytes and is greatly elevated in the neoplastic counterpart, malignant melanocytes; b) melanosomes consist structurally of matrix protein anc tyrosinase, the latter of which categorizes the conversion of tyrosine to dopa and dopaquinone to form melanin; c) the structural protein becomes markedly aberrant in malignant melanoma; and b) the metabolic pathway from tyrosin to melanin is irreversible thus permittin incorporation of tyrosinase substrate into metabolically polymer melanin. To the melanosomal structural matrix proteins specifically of unique to the malignant melamocyte, we were able to establish monoclonal antibodies against melanosomes and thereby we have succeeded to establish the improved immunodiagnostic tools to detect early lesion of malignant melanoma and estimate the prognosis of malignant melanoma patients. Secondly, by chemically modifying the melanin precursors of tyrosinase substrate, we succeeded to localize synthetic compounds in melanoma cells and thereby destroy them. Thus, our project provided, by dissecting our specific specific biological properties of the malignant melanocyte, a unique research directed a) early laboratory diagnosis, and b) rational chemotherapy of malignant melanoma. Specifically, we were able to characterize the biological component of the melanocyte and to develop practical application of experimental result for better management of patient care.