Nishiyama Y, Fuchimoto S, Orita K
First Department of Surgery, Okayama University Medical School, Japan.
Acta Med Okayama. 1989 Feb;43(1):17-27. doi: 10.18926/AMO/30895.
We investigated the antitumor effect of purified natural human tumor necrosis factor-beta (nHuTNF-beta) produced by human acute lymphoblastic leukemia BALL-1 cells stimulated with HVJ on pulmonary metastatic tumors of Lewis lung carcinoma (3LL) transplanted into BDF1 mice. nHuTNF-beta showed antiproliferative effects on metastatic tumors in a dose-dependent manner when administered daily for 10 days by the intravenous route. Histological examination of the tumors treated with nHuTNF-beta revealed that the tumor size and number of metastases were much reduced. Lytic cellular changes, including cytoplasmic vacuolation, loosening of the intercellular junction and both cytoplasmic and nuclear swelling, were found, but tumor necrosis was not. These findings indicate a therapeutic effect of Grade IIa according to the histological criteria of Shimosato and Ohboshi. In addition, synergistic augmentation of the antiproliferative effects of nHuTNF-beta by natural murine interferon-alpha/beta (nMu-IFN-alpha/beta) or recombinant murine interferon-gamma (rMuIFN-gamma) was recognized by median effect plot analysis. The results suggested that nHuTNF-beta may well deserve clinical trial as a new immunotherapeutical agent for human cancer.
我们研究了由仙台病毒（HVJ）刺激人急性淋巴细胞白血病BALL-1细胞产生的纯化天然人肿瘤坏死因子-β（nHuTNF-β）对移植到BDF1小鼠体内的Lewis肺癌（3LL）肺转移瘤的抗肿瘤作用。当通过静脉途径连续10天每日给药时，nHuTNF-β对转移瘤显示出剂量依赖性的抗增殖作用。对用nHuTNF-β治疗的肿瘤进行组织学检查发现，肿瘤大小和转移灶数量均显著减少。发现了包括细胞质空泡化、细胞间连接松散以及细胞质和细胞核肿胀在内的溶解性细胞变化，但未发现肿瘤坏死。根据Shimosato和Ohboshi的组织学标准，这些发现表明具有IIa级治疗效果。此外，通过中位效应图分析认识到天然鼠干扰素-α/β（nMu-IFN-α/β）或重组鼠干扰素-γ（rMuIFN-γ）对nHuTNF-β的抗增殖作用有协同增强作用。结果表明，nHuTNF-β作为一种新的人类癌症免疫治疗药物很值得进行临床试验。
