MELANIN SYNTHESIS AND CONTROL OF MALIGNANT MELANOMA

恶性黑色素瘤提供了一些特殊的属性，为通过导弹方法改进诊断和化疗提供了机会。这项建议是根据下列意见提出的：A)黑色素和黑素体的合成，即黑色素生成，只发生在黑素细胞中，在肿瘤对应的恶性黑素细胞中大大增加；B)黑素体在结构上由基质蛋白和酪氨酸酶组成，酪氨酸酶将酪氨酸转化为多巴和多巴醌形成黑色素；C)结构蛋白在恶性黑色素瘤中变得明显异常；b)酪氨酸到黑色素的代谢途径是不可逆的，因此允许酪氨酸酶底物掺入代谢聚合黑色素。针对恶性黑素细胞特有的黑素体结构基质蛋白，我们能够建立针对黑素体的单克隆抗体，从而成功建立了改进的免疫诊断工具，用于检测恶性黑素瘤的早期病变和估计恶性黑素瘤患者的预后。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，从而摧毁它们。因此，我们的项目通过剖析恶性黑素细胞的特定生物学特性，为a)早期实验室诊断和b)恶性黑素瘤的合理化疗提供了独特的研究方向。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.