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METABOLISM OF DIACETYLPOLYAMINES AND CONTROL OF CELL PROLIFERATION

二乙酰多胺的代谢和细胞增殖的控制

基本信息

批准号：
09670141
负责人：
KAWAKITA Masao
金额：
$ 0.83万
依托单位：
TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670141/
关键词：
Polyamine Diacetylspermine Diacetylspermicine ELISA Anti-polyamine antibody Tumor marker

项目摘要

Antibodies specific toN^1, N^8-diacetylspermidine (DiAcSpd) AndN^1, N^<12>-diacetylspermine (DiAcSpm) were reised in rabbits and were affinity-pufified, using affinity-1 igands mimicking DiAcSpm and DiAcSpd. Cross-reactivity of Ant i-DiAcSpm antibody with N^1-acetylspermidine was only about 0.03%. A competitive ELISA system for the determination of urinary diAcSpm was developed, using this highly DiAcSpm-selective antibody. The ELISA system allowed accurate determination of DiAcSpm concentrations as low as 10-20 nM and the values obtained by this procedure coinceded very well with those determined by HPLC.Determination of the amount of DiAcSpm in the urine of patients with urogenital malignancies revealed several points as follows : (1) The DiAcSpm levels were high inmost testicular and renal cancer cases except for those at very early stages. On the other hand, in cases of bladder cancer, DiAcSpm values frequently stayed within the normal range (mean for healthy persons + 2S.D.) even with patients at advanced stages. (2) The DiAcSpm levels after treatments of prostate cancer were well correlated with the patients' prognosis. In cases where DiAcSpm was low and stationary after treatments, the prognosis of patients turned out to be favorable even though the PSA value remained high in several cases. In contrast, when DiAcSpm remained elevated after a treatment, prognosis of the patient was poor, even if the treatment had been apparently effective and had temporarily led to partial remission. These results strongly suggest that DiAcSpm serves as a good indicator of the prognosis of prostate cancer, and that it works much better than PSA in this respect.

特异于N^1，N^8-二乙酰精胺(DiAcSpd)和N^1，N^12-二乙酰精胺(DiAcSpm)的抗体在兔子中重新制备并使用模拟DiAcSpm和DiAcSpd的亲和力1配体进行亲和纯化。 Anti i-DiAcSpm 抗体与 N^1-乙酰亚精胺的交叉反应性仅为约 0.03%。使用这种高度 DiAcSpm 选择性的抗体，开发了一种用于测定尿液 diAcSpm 的竞争性 ELISA 系统。 ELISA 系统可以准确测定低至 10-20 nM 的 DiAcSpm 浓度，并且通过该程序获得的值与 HPLC 测定的值非常吻合。对泌尿生殖系统恶性肿瘤患者尿液中 DiAcSpm 含量的测定揭示了以下几点：（1）除了非常早期的病例外，大多数睾丸癌和肾癌病例中 DiAcSpm 水平较高。另一方面，在膀胱癌病例中，即使是晚期患者，DiAcSpm 值也经常保持在正常范围内（健康人平均值 + 2S.D.）。 (2)前列腺癌治疗后DiAcSpm水平与患者预后密切相关。在治疗后 DiAcSpm 较低且稳定的病例中，尽管在一些病例中 PSA 值仍然很高，但患者的预后良好。相反，当治疗后 DiAcSpm 仍然升高时，即使治疗明显有效并暂时导致部分缓解，患者的预后也很差。这些结果强烈表明 DiAcSpm 可以作为前列腺癌预后的良好指标，并且在这方面它比 PSA 效果更好。