Yang R, Liu Q, Rescorla F J, Grosfeld J L
Department of Surgery, Indiana University School of Medicine, Indianapolis, USA.
Surgery. 1995 Oct;118(4):768-72; discussion 772-4. doi: 10.1016/s0039-6060(05)80048-0.
The aim of this study is to investigate whether regional infusion of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) could improve the therapeutic results of hepatic artery ligation (HAL) on liver cancer in a rat model.
Morris hepatoma 3924A was implanted intrahepatically in 50 ACI rats. Two weeks after tumor implantation, 40 rats underwent hepatic artery cannulation and ligation. The cannula was connected to an infusion port implanted subcutaneously. Animals were then divided into four groups of 10 each to receive seven daily intraarterial injections of IFN-gamma 100,000 IU/rat/day (HAL + IFN group), TNF-alpha 30 micrograms/rat/day (HAL + TNF group), IFN + TFN (HAL + IFN + TNF group), or normal saline solution (HAL group). The remaining 10 rats received a laparotomy only and served as untreated controls. Tumor volume, viable tumor area, and histopathology were assessed after 3 weeks.
The tumor growth was significantly retarded in the HAL group compared with the controls (tumor volume 683 +/- 245 mm3 vs 2424 +/- 596 mm3, p < 0.05 ANOVA). HAL + TNF (221 +/- 93 mm3) and HAL + IFN + TNF groups (74 +/- 31 mm3), but not the HAL + IFN group (493 +/- 164 mm3), were much more effective than the HAL group in controlling tumor growth (p < 0.05). HAL + IFN + TNF achieved the best tumor control resulting in a 60% tumor-free rate (p < 0.05 vs all other groups).
These data suggest that HAL combined with regional infusion of TNF-alpha and IFN-gamma significantly reduces tumor growth in a rat liver model. This attractive concept of combined modality therapy may have utility in the clinical setting in instances of unresectable liver cancer.
本研究旨在探讨在大鼠模型中，局部输注肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）是否能改善肝动脉结扎术（HAL）对肝癌的治疗效果。
将Morris肝癌3924A植入50只ACI大鼠的肝脏内。肿瘤植入两周后，40只大鼠接受肝动脉插管和结扎。插管连接至皮下植入的输注端口。然后将动物分为四组，每组10只，分别接受为期7天的每日动脉内注射，剂量为100,000 IU/大鼠/天的IFN-γ（HAL + IFN组）、30微克/大鼠/天的TNF-α（HAL + TNF组）、IFN + TFN（HAL + IFN + TNF组）或生理盐水溶液（HAL组）。其余10只大鼠仅接受剖腹手术，作为未治疗的对照。3周后评估肿瘤体积、存活肿瘤面积和组织病理学。
与对照组相比，HAL组的肿瘤生长明显受到抑制（肿瘤体积683±245立方毫米对2424±596立方毫米，方差分析p<0.05）。HAL + TNF组（221±93立方毫米）和HAL + IFN + TNF组（74±31立方毫米），而非HAL + IFN组（493±164立方毫米），在控制肿瘤生长方面比HAL组更有效（p<0.05）。HAL + IFN + TNF实现了最佳的肿瘤控制，无瘤率达到60%（与所有其他组相比p<0.05）。
这些数据表明，HAL联合局部输注TNF-α和IFN-γ可显著降低大鼠肝脏模型中的肿瘤生长。这种联合治疗模式的有吸引力的概念可能在不可切除肝癌的临床情况下有用。
