SYNERGISTIC EFFECT OF METHIONINE-DEPLETING TOTAL PARENTERAL-NUTRITION WITH 5-FLUOROURACIL ON HUMAN GASTRIC-CANCER - A RANDOMIZED, PROSPECTIVE CLINICAL-TRIAL
SYNERGISTIC EFFECT OF METHIONINE-DEPLETING TOTAL PARENTERAL-NUTRITION WITH 5-FLUOROURACIL ON HUMAN GASTRIC-CANCER - A RANDOMIZED, PROSPECTIVE CLINICAL-TRIAL
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DOI：
10.1111/j.1349-7006.1995.tb03082.x
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发表时间：
1995-05-01
期刊：
影响因子：
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通讯作者：
TAKAHASHI, H
中科院分区：
文献类型：
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作者：
GOSEKI, N;YAMAZAKI, S;TAKAHASHI, H
在荷瘤大鼠和胃肠道癌临床试验中，输注AO-90氨基酸溶液（缺乏L-蛋氨酸和L-半胱氨酸）作为唯一氮源的蛋氨酸消耗全肠外营养（Met消耗TPN）与J-氟尿嘧啶（5-FU）显示出协同效应。在这项研究中，Met耗竭TPN与5-FU对胸苷酸合成酶（TS）活性的影响进行了检查，并评价了这种治疗对人胃癌的组织学影响。14例进展期胃癌患者术前随机分为两组，AO-90组7例，术前给予去甲硫氨酸TPN 7 d，同时持续静脉注射5-FU（500 mg/人/d，共4.0g/人）。另7例接受常规含L-甲硫氨酸的TPN +5-FU（对照组）。所有患者均行胃切除术，未发生这些治疗引起的并发症。切除材料进行TS动力学检查，并进行组织病理学评估的抗癌效果。AO-90组的标本显示出明显的癌变性，而对照组几乎没有观察到影响。AO-90组肿瘤组织游离TS活性较对照组降低（P=0.0165），TS抑制率较对照组升高（P=0.0243）。Met耗尽TPN似乎在人类胃癌中发挥着5-FU生物调节剂的作用。
Methionine-depleting total parenteral nutrition (Met-depleting TPN), infusing AO-90 amino acid solution (lacking both L-methionine and L-cysteine) as a sole nitrogen source, showed synergistic effects with J-fluorouracil (5-FU) in tumor-bearing rats and in clinical trials with gastrointestinal tract cancers. In this study, the effect of Met-depleting TPN with 5-FU upon thymidylate synthase (TS) activity was examined, and the histological effect of this treatment on human gastric cancer was evaluated. Fourteen preoperative advanced gastric cancer patients were divided randomly into two groups, Seven cases were given Met-depleting TPN for 7 days before surgery with continuous intravenous administration of 5-FU (500 mg/body per day; total 4.0 g/body) (AO-90 group). The other 7 received conventional L-methionine-containing TPN with 5-FU (control group). All patients underwent gastrectomy without complications due to these treatments. Resected materials were examined for TS kinetics, and the anti-cancer effect was also assessed histopathologically. The specimens in the AO-90 group showed marked degeneration of cancer, while almost no effect was seen in the control group. The free TS activity of carcinoma tissue in the AO-90 group was decreased and the TS inhibition rate was increased in comparison with the control group (P=0.0165 and P=0.0243, respectively). Met-depleting TPN appears to play a role as a biomodulator of 5-FU in human gastric cancer.