Tomazic V J, Farha M, Loftus A, Elias E G
Department of Surgery, University of Maryland, School of Medicine, Baltimore 21201.
J Immunol. 1988 Jun 1;140(11):4056-61.
The experiments presented were designed first to determine the effects of rTNF on the methylcholanthrene-induced fibrosarcoma (FSA-1) in C3H/JSed mice and second to determine whether the observed effects are the result of direct action by rTNF on the tumor or whether rTNF acts as a mediator of other effector mechanisms. Mice received syngeneic FSA-1 fibrosarcoma cells either s.c. or i.v. in order to evaluate growth of transplantable solid tumor or lung metastases, respectively. The range of dosages, from 10(2) to 2 x 10(5) U of rTNF, was administered i.v. at different intervals after the tumor cell injection. Early injection of 10(3) to 10(4) U of rTNF reduced the growth of s.c. injected tumor and the number of lung metastases in i.v. injected mice. In both cases, survival of mice was also prolonged. However, in vitro treatment of FSA-1 tumor cells with rTNF did not result in the reduction of their proliferating activity after injection into mice, although direct cytostatic and moderate cytotoxic activity of rTNF in vitro was demonstrated. To identify whether other cellular mechanisms are involved in the effects observed in vivo, the anti-tumor activity of rTNF-treated spleen cells was evaluated in vitro using a 75Se release assay. Whereas nontreated spleen cells demonstrated very low cytotoxic activity in this system, the cells from rTNF-treated mice showed marked increase in the cytotoxicity against syngeneic tumor cells. These results suggest that the anti-tumor activity of rTNF represents a combination of its direct effect on tumor cells and indirect effects involving host immune mechanisms.
所呈现的实验首先旨在确定重组肿瘤坏死因子（rTNF）对C3H/JSed小鼠中甲基胆蒽诱导的纤维肉瘤（FSA - 1）的影响，其次旨在确定所观察到的影响是rTNF对肿瘤的直接作用结果，还是rTNF作为其他效应机制的介导物。小鼠分别通过皮下或静脉注射同基因FSA - 1纤维肉瘤细胞，以分别评估可移植实体瘤的生长或肺转移情况。在肿瘤细胞注射后的不同时间间隔，静脉注射剂量范围为10²至2×10⁵单位的rTNF。早期注射10³至10⁴单位的rTNF可减少皮下注射肿瘤的生长以及静脉注射小鼠的肺转移数量。在这两种情况下，小鼠的存活时间也得以延长。然而，尽管rTNF在体外具有直接的细胞抑制和适度的细胞毒性活性，但用rTNF对FSA - 1肿瘤细胞进行体外处理后，在将其注射到小鼠体内后并未导致其增殖活性降低。为了确定体内观察到的效应是否涉及其他细胞机制，使用⁷⁵Se释放试验在体外评估了rTNF处理的脾细胞的抗肿瘤活性。在该系统中，未处理的脾细胞显示出非常低的细胞毒性活性，而来自rTNF处理小鼠的细胞对同基因肿瘤细胞的细胞毒性显著增加。这些结果表明，rTNF的抗肿瘤活性代表了其对肿瘤细胞的直接作用和涉及宿主免疫机制的间接作用的组合。
