Watanabe N, Niitsu Y, Umeno H, Kuriyama H, Neda H, Yamauchi N, Maeda M, Urushizaki I
Dept. of Internal Medicine, Sapporo Medical College.
Gan To Kagaku Ryoho. 1987 Dec;14(12):3337-43.
Effects of human recombinant TNF on the tumor blood vessels and on the thrombus formation were investigated in relation to its mode of antitumor action against Meth-A sarcoma transplanted in BALB/c mice. The extent of the blood vessel lesion was evaluated by using transparent chamber placed in the mouse skin. Bleeding, hyperemia and congestion were observed at 1-2h, 4-6h and 24h after TNF (1 X 10(4)U/mouse) administration, respectively. In contrast, no histological changes in the normal blood vessels were observed microscopically following TNF injection. Thrombus formation was evoked in the tumor vessels 4h after TNF injection. However, when thrombus formation was prevented by heparin, no difference was observed among antitumor action of TNF against Meth-A fibrosarcoma necrotic response and the rate of complete cure. These results suggest that the direct effects of TNF causing lesions in the tumor blood vessels plays an important role in its antitumor action.
研究了重组人肿瘤坏死因子(TNF)对肿瘤血管及血栓形成的影响,并探讨了其对BALB/c小鼠移植的Meth-A肉瘤的抗肿瘤作用机制。通过置于小鼠皮肤的透明小室评估血管损伤程度。分别在给予TNF(1×10⁴U/小鼠)后1-2小时、4-6小时和24小时观察到出血、充血和淤血。相反,注射TNF后,显微镜下未观察到正常血管的组织学变化。TNF注射后4小时,肿瘤血管中诱发血栓形成。然而,当用肝素阻止血栓形成时,TNF对Meth-A纤维肉瘤的抗肿瘤作用、坏死反应和完全治愈的比例之间未观察到差异。这些结果表明,TNF导致肿瘤血管损伤的直接作用在其抗肿瘤作用中起重要作用。