Burgers J K, Marshall F F, Isaacs J T
James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
J Urol. 1989 Jul;142(1):160-4. doi: 10.1016/s0022-5347(17)38703-7.
A nude mouse renal subcapsular and subcutaneous implantation xenograft model utilizing the SN12C human renal carcinoma cell line was investigated. In the absence of treatment, renal subcapsular implantation of SN12C resulted in metastatic spread (lung, liver and lymph nodes) and death of all animals. Radical nephrectomy of the tumor-bearing kidney after various periods of tumor implantation demonstrated that surgery alone after 18 days of tumor growth resulted in no statistically significant increase in survival with 100% of the nephrectomized animals succumbing to local recurrence and distant metastases. Recombinant human tumor necrosis factor (rTNF) and VP16 (etoposide), both well known cytotoxic and cytostatic anticancer agents, were tested singly and in combination against this metastatic model of human renal adenocarcinoma. Single agent rTNF or VP16 therapy after radical nephrectomy demonstrated only minimal efficacy with no significant decrease in local recurrence and distant metastases as compared to nephrectomy only control animals. In contrast, the combination of rTNF plus VP16 when given after nephrectomy resulted in a significant decrease in local recurrence and no gross evidence of metastasis in any animal. Subcutaneously growing SN12C tumor nodules were also treated with the same rTNF, VP16 and combination regimens. Regression in tumor size was noted only in the combination treatment group. rTNF or VP16, as single agents, demonstrated only slight growth inhibition that was not statistically significant. These results suggest that by combining TNF plus VP16, a synergistic enhancement of antineoplastic activity against local as well as metastatic human renal cell carcinoma can be produced.
研究了一种利用SN12C人肾癌细胞系的裸鼠肾被膜下和皮下植入异种移植模型。在未进行治疗的情况下，将SN12C植入肾被膜下会导致转移扩散（肺、肝和淋巴结），所有动物死亡。在肿瘤植入不同时间段后对荷瘤肾进行根治性肾切除术表明，肿瘤生长18天后仅进行手术，生存时间无统计学意义的增加，100%接受肾切除术的动物死于局部复发和远处转移。重组人肿瘤坏死因子（rTNF）和VP16（依托泊苷），这两种都是众所周知的细胞毒性和细胞抑制性抗癌药物，分别单独及联合用于该人肾腺癌转移模型。根治性肾切除术后单药使用rTNF或VP16治疗仅显示出最小的疗效，与仅接受肾切除术的对照动物相比，局部复发和远处转移没有显著减少。相比之下，肾切除术后给予rTNF加VP16的联合治疗导致局部复发显著减少，且任何动物均无明显转移迹象。对皮下生长的SN12C肿瘤结节也采用相同的rTNF、VP16及联合治疗方案进行治疗。仅在联合治疗组中观察到肿瘤大小缩小。rTNF或VP16作为单药，仅显示出轻微的生长抑制，无统计学意义。这些结果表明，联合使用TNF和VP16可以产生针对局部及转移性人肾细胞癌的抗肿瘤活性的协同增强作用。
