ABSTRACT
BACKGROUND: Since tumor necrosis factor was discovered in 1975, TNF has been well known about its cytotoxic effect on tumor cells in vivo and in vitro. According to the recent improvement of molecular biological techinques, it is possible that exogenous TNF gene is transferred to tumor cells and is expressed in theirs. By virtue of TNF gene transfer, we have expected that TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells in vivo without systemic side effect. The expected mechanisms in which antitumor effects of TNF expressed in TNF-gene-transferred tumor cells are working would be as followings. In the first mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells around (like homicide). In the second mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill themselves (like suicide). In the third mechanism, TNF expressed in TNF-gene-transferred tumor cells would recruit immune effector cells and kill tumor cells indirectly. In the last mechanism, TNF expressed in TNF-gene-transferred tumor cells would augment cytokine such as interferon-γ to kill tumor cells. Among these four mechanisms of antitumor effect, only the second mechanism has not been established yet. Therefore, to elucidate the second mechanism, We performed this study. METHOD: We transferred TNF-α gene to NCI-H2058, a human mesothelioma cell line and WEHI164, a murine fibrosarcoma cell line by using retroviral vector(pLT12SNTNF). And, We determined by using MTT assay whether TNF expressed in TNF-gene-transferred tumor cell lines would kill themselves like suicide or not. Then, if TNF-gene-transferred tumor cell lines would not suicide themselves, 1 would know more about the TNF sensitivity of TNF-gene-transferred tumor cell lines to exogenous TNF also by MTT assay. RESULT: NCI-H2058 and WEHI164 which were sensitive to TNF, became far less sensitive to endogenous and exogenous TNF after being transferred TNF-α gene to. CONCLUSION: TNF-gene-transfer to NCI-H2058 and WEHI164 gaffe them resistance to TNF.
Subject(s)
Humans , Cell Line , Cell Line, Tumor , Fibrosarcoma , Mesothelioma , Necrosis , Retroviridae , Suicide , Tumor Necrosis Factor-alpha , Virtues , ZidovudineABSTRACT
OBJECTIVES: Since Mountain proposed the new staging system of non-small cell lung cancer in 1986, the indications for operation of NSCLC have been extended. However, operative mortality is from 3 to 6%. Therefore it is important to reduce unnecessary operation and to evaluate unresectability of tumor correctly, preoperatively The purpose of this study is to find out the causes of unresectability in patients who were initially thought to be resectable preoperatively. METHODS: By retrospective analysis, 64 patients out of 291 NSCLC patients who were undergone operation for curative resection in Seoul National University Hospital from Jan. of 1987 to Dec. of 1991, ware found to be unresectable at operating roost were selected for this study. Out of 64 patients,42 were evaluable. The analysis was focused on the change of pre- & post-operative staging and the causes of unresectability of tumors. RESULTS: Among B2 patients with unresectable tumor who could be evaluated, preoperative CT finding showed resectable tumors in 55% (23 patients) and suspicious for unresectable tumors in 45% (19 patients). The causes of unresectability were technically unresectable T3 lesions in 7% (3 patients), T4 lesions in 62% (26 patients), N2 lesions in 17% (7 patients) and N3 lesions in 14% (6 patients). CONCLUSION: The major causes of unresectability of NSCLC were pulmonary artery invasions. It is suggested that careful evaluation of mediastinal structure, especially great vessels by additional imaging technique other than CT (like MRI) is indicated in selected NSCLC cases.