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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.

用模拟DiAcSpm和DiAcSpd的亲和配体亲和纯化了兔抗N^1，N^8-二乙酰精脒（DiAcSpd）和N^1，N^8-二<12>乙酰精胺（DiAcSpm）的抗体。Ant i-DiAcSpm抗体与N^1-乙酰亚精胺的交叉反应性仅为约0.03%。建立了一种用于测定尿中diAcSpm的竞争性ELISA系统，使用这种高度DiAcSpm选择性抗体。用ELISA法测定尿中DiAcSpm的浓度，结果表明：（1）除极早期的睾丸癌和肾癌外，大多数睾丸癌和肾癌患者尿中DiAcSpm的浓度均较高;另一方面，在膀胱癌的情况下，DiAcSpm值经常保持在正常范围内（健康人的平均值± 2S.D.）。即使是晚期病人(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，即使在一些病例中PSA值仍然较高，患者的预后也是有利的。相比之下，当治疗后DiAcSpm仍然升高时，患者的预后很差，即使治疗明显有效并暂时导致部分缓解。这些结果强烈表明，DiAcSpm作为前列腺癌预后的良好指标，并且在这方面比PSA更有效。