Nishiyama Y, Fuchimoto S, Orita K
First Department of Surgery, Okayama University Medical School.
Jpn J Cancer Res. 1989 Apr;80(4):366-72. doi: 10.1111/j.1349-7006.1989.tb02321.x.
This investigation was undertaken in order to assess both the preventive and antiproliferative effects of tumor necrosis factor (TNF) in a hepatic metastasis model, by means of inoculation of mouse colon-26 tumor cells into the portal vein via the superior mesenteric vein in male CDF1 mice, aged 5 weeks. Continuous 10-day administration of natural human TNF-alpha (nHuTNF-alpha) following the tumor cell inoculation caused no reduction but rather an increase in the number of hepatic metastases. However, pretreatment with this preparation daily for 10 days before the inoculation caused a remarkable decrease in the number of hepatic metastases. This prophylactic effect was reversed by the intravenous administration of anti-asialo GM1 antibody 24 h before the inoculation. The result of immunoperoxidase staining of liver specimens suggested that organ-associated natural killer cells might play a role in the metastatic inhibition. An apparent antiproliferative effect on metastatic liver tumors was also recognized following injection of nHuTNF-alpha from the 10th day after the inoculation. Thus, TNF appears to have important effects upon the host immune system, acting against liver metastases.
本研究旨在通过将小鼠结肠26肿瘤细胞经肠系膜上静脉接种至5周龄雄性CDF1小鼠的门静脉，在肝转移模型中评估肿瘤坏死因子（TNF）的预防和抗增殖作用。在接种肿瘤细胞后连续10天给予天然人TNF-α（nHuTNF-α），并未使肝转移灶数量减少，反而使其增加。然而，在接种前每天用该制剂预处理10天，则导致肝转移灶数量显著减少。接种前24小时静脉注射抗去唾液酸GM1抗体可逆转这种预防作用。肝脏标本免疫过氧化物酶染色结果提示，器官相关自然杀伤细胞可能在转移抑制中发挥作用。接种后第10天起注射nHuTNF-α后，对转移性肝肿瘤也有明显的抗增殖作用。因此，TNF似乎对宿主免疫系统有重要作用，可对抗肝转移。
