Balkwill F R
Imperial Cancer Research Fund, London, U.K.
Prog Growth Factor Res. 1992;4(2):121-37. doi: 10.1016/0955-2235(92)90027-f.
TNF is a cytokine whose diverse actions are dependent on the local microenvironment. As a member of the cytokine network, TNF plays an important role in infection and inflammation, but excessive and deregulated production can contribute to disease processes. Likewise in malignant disease, TNF may have a role in cancer therapy and contribute to host response against tumours, but it may also be involved in the progression and spread of the cancer. In experimental models, recombinant TNF can induce significant haemorrhagic necrosis, localised to the tumour vasculature and specific tumour immunity. Although the historical background and preclinical data are promising, systemic therapy with TNF in human cancer has proved highly toxic and is inactive against all tumour types so far tested. Local therapy, particularly isolated limb perfusion, has resulted in complete and long lasting tumour regressions with necrotic activity confined solely to the tumour vascular bed. However, in several animal models, TNF contributes to malignant progression and there is evidence that TNF may have autocrine or paracrine actions in human ovarian cancer.
肿瘤坏死因子（TNF）是一种细胞因子，其多样的作用取决于局部微环境。作为细胞因子网络的一员，TNF在感染和炎症中发挥重要作用，但过量且失调的产生会促成疾病进程。同样在恶性疾病中，TNF可能在癌症治疗中发挥作用，并有助于宿主对肿瘤的反应，但它也可能参与癌症的进展和扩散。在实验模型中，重组TNF可诱导显著的出血性坏死，局限于肿瘤血管系统和特异性肿瘤免疫。尽管历史背景和临床前数据很有前景，但TNF在人类癌症中的全身治疗已证明毒性极高，且对目前测试的所有肿瘤类型均无活性。局部治疗，尤其是孤立肢体灌注，已导致肿瘤完全且持久消退，坏死活性仅局限于肿瘤血管床。然而，在几种动物模型中，TNF促成恶性进展，并且有证据表明TNF可能在人类卵巢癌中具有自分泌或旁分泌作用。
