Goseki N, Endo M
First Department of Surgery, School of Medicine, Tokyo Medical and Dental University, Japan.
Tohoku J Exp Med. 1990 Jul;161(3):227-39. doi: 10.1620/tjem.161.227.
As an adjunct to cancer chemotherapy, we had succeeded in creating the methionine depletion in vivo, using the technique of total parenteral nutrition (TPN) by infusing an amino acid solution devoid of methionine and cysteine, as sole nitrogen source (Met-deplet. TPN). In Experiment 1, we demonstrated that the marked depletion of thiol was induced both in the liver and tumor tissues by Met-deplet. TPN in Sato lung carcinoma (SLC)-bearing rats. Then in Experiment 2, we also confirmed the presence of the enhancing effect on nimustine hydrochloride (ACNU) in Met-deplet. TPN to SLC. The tumor proliferation was inhibited significantly by Met-deplet. TPN even in conjunction with a small dose of ACNU, which showed no anti-tumor effect on the rats treated with methionine-containing amino acid solution, without apparent increase of the side effects in comparison with those in the control groups. On the other hand, to determine the carcinostatic effect on tumor-bearing animals, not only the size of the tumor but also its components, especially the percentage of necrotic tumor tissue (necrotic index), were considered to be important.
作为癌症化疗的辅助手段，我们通过全胃肠外营养（TPN）技术，输注不含蛋氨酸和半胱氨酸的氨基酸溶液作为唯一氮源（蛋氨酸缺乏的TPN），成功在体内造成了蛋氨酸缺乏。在实验1中，我们证明了蛋氨酸缺乏的TPN可使荷佐藤肺癌（SLC）大鼠的肝脏和肿瘤组织中的硫醇显著减少。然后在实验2中，我们还证实了蛋氨酸缺乏的TPN对SLC中盐酸尼莫司汀（ACNU）有增强作用。蛋氨酸缺乏的TPN即使与小剂量ACNU联合使用，也能显著抑制肿瘤增殖，而含蛋氨酸的氨基酸溶液对大鼠无抗肿瘤作用，且与对照组相比，副作用没有明显增加。另一方面，为了确定对荷瘤动物的抗癌作用，不仅要考虑肿瘤的大小，还要考虑其成分，特别是坏死肿瘤组织的百分比（坏死指数），这一点很重要。
