TUMOR-GROWTH STIMULATION AFTER PARTIAL-HEPATECTOMY CAN BE REDUCED BY TREATMENT WITH TUMOR-NECROSIS-FACTOR-ALPHA

TUMOR-GROWTH STIMULATION AFTER PARTIAL-HEPATECTOMY CAN BE REDUCED BY TREATMENT WITH TUMOR-NECROSIS-FACTOR-ALPHA
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DOI:
10.1002/bjs.1800820144
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发表时间:
1995-01-01
影响因子:
9.6
通讯作者:
IJZERMANS, JNM
IJZERMANS, JNM
中科院分区:
医学1区
文献类型:
--
作者:
SLOOTER, GD;MARQUET, RL;IJZERMANS, JNM

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本研究调查了部分肝切除术是否能增强大鼠结肠癌实验性肝转移的生长,以及重组人肿瘤坏死因子(TNF)α治疗是否能减少这种生长增加。在近交系WAG大鼠中切除35%或70%的肝脏,并进行假手术对照(每组5至8只动物)。手术后立即将5x 10(5)CC 531结肠肿瘤细胞注射到门静脉中。28天后,处死动物并计数肝转移瘤的数量。35%的肝切除术导致肝转移的中位数显著增加(28个,对照组为3个),而70%的切除引起过度生长,始终导致超过100个肝转移,所有动物的湿肝重量显著增加。在70%肝切除术或假手术后,以160 μ g/kg的剂量每周三次静脉注射TNF-α。这对假手术大鼠的肿瘤发展只有轻微的影响,但在部分肝切除术后非常有效(平均45个肝转移灶)。这些观察结果证实了以前的研究结果,即手术切除术可能作为一把“双刃剑”,通过激发休眠肿瘤细胞的生长,并表明TNF-α的辅助治疗可能对转移瘤切除术的患者有益。
This study investigated whether partial hepatectomy enhances the growth of experimental liver metastases of colonic carcinoma in rats and whether treatment with recombinant human tumour necrosis factor (TNF) alpha can reduce this increased growth. Resection of 35 or 70 per cent of the liver was performed in inbred WAG rats, with sham-operated controls (five to eight animals per group). Immediately after surgery 5x10(5) CC531 colonic tumour cells were injected into the portal vein. After 28 days the animals were killed and the number of liver metastases counted. A 35 per cent hepatectomy induced a significant increase in the median number of liver metastases (28 versus 3 in controls), whereas a 70 per cent resection provoked excessive growth, consistently leading to more than 100 liver metastases and a significantly increased wet liver weight in all animals. TNF-alpha was given intravenously to rats following 70 per cent hepatectomy or sham operation in a dose of 160 mu g/kg three times per week. This had only a marginal effect on tumour development in sham-operated rats but was very effective following partial hepatectomy (median 45 liver metastases). These observations confirm previous findings that surgical metastasectomy may act as a 'double-edged sword' by provoking outgrowth of dormant tumour cells and suggest that adjuvant treatment with TNF-alpha may be of benefit in patients undergoing resection of metastases.