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MELANIN SYNTHESIS AND CONTROL OF MALIGNANT MELANOMA

黑色素合成和恶性黑色素瘤的控制

基本信息

批准号：
60480250
负责人：
JIMBOW Kowichi
金额：
$ 4.16万
依托单位：
Sapporo Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1987
项目状态：
已结题

项目摘要

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.

恶性黑色素瘤提供了一些特殊的特征，为通过导弹方法改善诊断和化疗提供了机会。这一建议基于以下观察结果：a)黑色素和黑素小体的合成，即黑色素的合成，仅发生在黑素细胞中，并在肿瘤的对应物恶性黑素细胞中显著升高；b)黑素小体的结构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喹酮以形成黑色素；c)结构蛋白在恶性黑色素瘤中变得明显异常；以及b)从酪氨酸到黑色素的代谢途径是不可逆转的，因此允许酪氨酸酶底物掺入代谢聚合物黑色素中。针对恶性黑素细胞特有的黑素小体结构基质蛋白，我们成功地建立了针对黑素小体的单抗，从而成功地建立了检测恶性黑色素瘤早期病变和估计恶性黑色素瘤患者预后的免疫诊断工具。其次，通过对酪氨酸酶底物的黑色素前体进行化学修饰，我们成功地将合成化合物定位于黑色素瘤细胞，从而摧毁了它们。因此，我们的项目通过解剖我们特定的恶性黑素细胞的特定生物学特性，提供了一项独特的研究，旨在a)早期实验室诊断，b)恶性黑色素瘤的合理化疗。具体地说，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。