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Biosynthesis of Eumelanin in Melanoma and Biochemical Markers of Melanoma

黑色素瘤中真黑素的生物合成及黑色素瘤的生化标志物

基本信息

批准号：
63570484
负责人：
ITO Shosuke
金额：
$ 1.34万
依托单位：
Fujita Health University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570484/
关键词：
Melanin Malignant melanoma Dopa HPLC ドーパ

项目摘要

1. Simplified method for preparing enmelanin-related metabolites Dopachrome solution, firepared by chemical oxidation of dopa, was kept under different pH to yield 5,6DHI and 5,6DHI2C. Treatment with diazomethane afforded their O-methyl derivatives. This enabled us to obtain standard compounds necessary for the following research.2. Importance of enmelanin-related metabolites as biochemical markers of melanoma (1) Excretion of melanin-related metabolites was examined in mice bearing B16 melanoma. In early stage of tumor progression, the increase of 5H6MI2C was found to be more pronounced than of 5-S-CD, a commonly used marker. (2) Correlation among the contents of melanin-related metabolites in tumor, serum, and urine was examined in mice bearing B16 melanoma. Good correlation was found between serum indoles (5H6MI2C + 6H5MI2C) or 5-S-CD and tumor weight (r = 0.92, 0.89, respectively). Urinary metabolites did not show a significant correlation. These results suggest that melanin-related metabolites in serum may better reflect progression of melanoma than those in urine. (3) High levels of glucronide and sulfate conjugates of indoles were found in urine of a melanoma patient. Only sulfate conjugates were detected in urine of melanoma-bearing mice.Serum and urine samples from healthy subjects and melanoma patients will be analyzed for indoles and 5-S-CD to compare their usefulness in early diagnosis and prognosis of melanoma.

1. 采用多巴化学氧化法制备的Dopachrome溶液，在不同的pH条件下，得到5,6dhi和5,6dh2c。用重氮甲烷处理得到它们的邻甲基衍生物。这使我们能够得到下列研究所必需的标准化合物。黑色素相关代谢物作为黑色素瘤生化标志物的重要性(1)在B16黑色素瘤小鼠中检测了黑色素相关代谢物的排泄。在肿瘤进展的早期，5H6MI2C的升高比5-S-CD（一种常用的标志物）更为明显。(2)检测B16黑色素瘤小鼠肿瘤、血清和尿液中黑色素相关代谢物含量的相关性。血清吲哚（5H6MI2C + 6H5MI2C）或5-S-CD与肿瘤重量有较好的相关性（r分别为0.92、0.89）。尿代谢物无显著相关性。这些结果表明血清中的黑色素相关代谢物可能比尿液中的代谢物更好地反映黑色素瘤的进展。(3)在黑色素瘤患者的尿液中发现了高水平的葡萄糖醛酸和吲哚硫酸盐缀合物。在黑色素瘤小鼠尿液中只检测到硫酸盐缀合物。将对健康受试者和黑色素瘤患者的血清和尿液样本进行吲哚和5-S-CD分析，比较它们在黑色素瘤早期诊断和预后中的作用。