RESUMO
A 65-year-old man was referred to our hospital for evaluation of his huge abdominal tumor. He was diagnosed as having a gastrointestinal stromal tumor arising from the stomach. Seven months after surgery, multiple liver metastases and mesenteric dissemination occurred. He was medicated with STI571, which works by blocking proliferation of malignant cells with expression of c-kit. The tumors shrank and serum lactate dehydrogenase and alkaline phosphatase concentrations fell to below the normal limit three months later. STI571 was effective medicine for the metastatic gastrointestinal stromal tumor for six months in this case.
Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Cuidados Paliativos , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Idoso , Benzamidas , Biópsia por Agulha , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Evolução Fatal , Humanos , Mesilato de Imatinib , Imuno-Histoquímica , Masculino , Estadiamento de Neoplasias , Medição de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND AIMS: Interferon (IFN)-gamma and tumor necrosis factor (TNF) are predominant cytokines produced in the gastric mucosa of patients with Helicobacter pylori-infected gastritis. Several studies reported that IFN-gamma and TNF induced the synergistic effect on many cell lines. We attempted to clarify the apoptotic activity and the synergistic effect of IFN-gamma and TNF on the gastric epithelial cell, and whether IFN-gamma relates to soluble TNF receptors (sTNF-R) release from the gastric epithelial cell. METHODS: On the gastric epithelial cell line MKN45, cytotoxic and apoptotic effects of IFN-gamma and TNF were examined. Next, sTNF-R released in response to IFN-gamma and the protective effect of sTNF-R against the cytotoxic activity of TNF and IFN-gamma were examined by blocking the release of sTNF-R with a serine protease inhibitor such as phenylmethylsulfonyl fluoride. RESULTS: Interferon-gamma significantly decreased cell viability, but TNF decreased it only slightly. Interferon-gamma and TNF did not make a synergistic effect on cell viability and apoptosis. Interferon-gamma and TNF induced sTNF-R release from gastric epithelial cells. Phenylmethylsulfonyl fluoride significantly inhibited shedding of sTNF-R and a synergistic effect of TNF and IFN-gamma on apoptosis was observed. CONCLUSION: These results suggest that sTNF-R released by IFN-gamma regulate the injury on the gastric epithelial cell line induced by TNF.