[Strategy of treatment for gastric cancer with peritoneal metastasis].

In advanced gastric cancer with peritoneal metastasis, adjuvant chemotherapy after primary tumor resection showed considerably poor prognosis with a median survival time of only 232 days. So, we changed the strategy that we start systemic chemotherapy at the earliest opportunity without resecting the primary tumor for gastric cancer patients who were diagnosed peritoneal metastasis by laparotomy or staging laparoscopy. Eleven cases of gastric cancer with peritoneal metastasis were administered systemic chemotherapy first including S-1+paclitaxel (PTX). The regimen of chemotherapy of two weeks administration of S-1 (80 mg/m2/day)followed by one week rest and injections of PTX (50mg/m2) at day 1 and 8 for 21 days as one course. Five of eleven cases were performed S-1+PTX as the first-line, the other six cases as the second-line. In some cases, this therapy led to transient responses. Ultimately, most of them showed progressive disease. However, two of eleven cases showed a complete response in the peritoneal metastasis and could receive radical operation for gastric cancer. Both patients were still alive without any relapse at the time of this report. The median survival time of eleven cases of gastric cancer with peritoneal metastasis performed the systemic chemotherapy first with this regimen was 464 days. The survival was considerably prolonged (p=0. 0500), compared to 232 days in postoperative cases.

Significance of apoptosis induced by tumor necrosis factor-alpha and/or interferon-gamma against human gastric cancer cell lines and the role of the p53 gene.

PURPOSE: The expression of the p53 gene in target cells plays an important role in the induction of apoptosis by tumor necrosis factor (TNF)-Alpha and interferon (IFN)-Gamma. We herein present a study suggesting the existence of a caspase-independent pathway from p53 via insulin-like growth factor binding protein 3 (IGF-BP3) which acts as an apoptosis induction mechanism. METHODS: MKN-45 (wild-type p53) or MKN-28 (mutant-type p53) was cultured with TNF-Alpha or IFN-Gamma either alone or together. After 24 and 48 h, the apoptotic index (AI) was determined by Hoechst staining and then compared. To clarify whether the mechanism of apoptosis is induced by TNF-Alpha and/or IFN-Gamma, apoptosis-related genes were examined by a cDNA on microarray analysis and a Western blot analysis. RESULTS: (1) The AI for MKN-45 increased at 48 h in the presence of TNF-Alpha or IFN-Gamma alone. (2) In the case of combination treatment using TNF-Alpha and IFN-Gamma, the AI for MKN-45 was higher than those in the groups with a single treatment. (3) A cDNA microarray analysis showed that IGF-BP3, the TNF superfamily, and caspase 1 were all upregulated after treatment with the combination of TNF-Alpha and IFN-Gamma. (4) A Western blot analysis of MKN-45 showed a reaction with an anti-IGF-BP3 antibody. CONCLUSIONS: These results suggest that the induction mechanism underlying apoptosis induced by TNF-Alpha and IFN-Gamma might therefore involve the caspase-independent pathway via IGF-BP3.