Involvement of the CXC chemokines Mig and IP-10 in response to M. bovis BCG in mice

The non-ELR-containing CXC chemokines Mig and IP-10 have been shown to function as chemotactic cytokines for activated T lymphocytes. In this study, we examined the potential involvement of Mig and IP-10 in antimycobacterial response of mice immunized or infected with M. bovis BCG. The accumulation of Mig and IP-10 mRNA in resident peritoneal monocytes (RPMPHI) was slightly reduced by stimulation with vBCG, and the degree was greater for 24 hr culture even though IFN-gamma was added. Expression of Mig, IP-10, and IFN-gamma in 24 hr delayed-type hypersensitivity (DTH) response was stronger in vBCG-immune mice than in the non-immune. The increase of DTH measured by foot-pad thickness appears to be clearly related to the levels of chemokines Mig and IP10 messages and those of IFN-gamma and IL-12. Stimulation with vBCG for 2 days decreased or completely dropped the levels of Mig message in non-immune or immune splenocytes, respectively, whereas IP-10 message was slightly decreased in 2 days culture. Moreover, messages for IL-12 (p40) showed similar kinetics for Mig. The levels of Mig and IP-10 mRNA during the course of infection with BCG were not readily changed in lungs, livers, and spleens from BCG-infected mice. Although there was no obvious changes of Mig and IP-10 messages in the target organs during infection process, we found that the infection progressed over the first 3 wk before being contained by the emerging immune response suggested from detectable amount of IFN-gamma mRNA around this time. In view of selectivity of chemokines Mig and IP-10 for activated T cells, these data suggest that chemokine Mig and IP-10, especially in collaboration with IL-12 and IFN-gamma, may play a role as T cell recruiters in immune response against mycobacterial infection.

Radiotherapy in Incompletely Resected Gastric Cancers / 대한방사선종양학회지

PURPOSE: Although local recurrence rates of stomach cancer after radical surgery have been eported in the range of 30-70%, the role of postoperative adjuvant therapy has not been established. We report the result of radiotherapy in resected stomach cancer with positive surgical margin to elucidate the role of postoperative radiotherapy. MATERIALS AND METHODS: From June 1991 to August 1996, twenty five patients with positive surgical margins after radical gastrectomy were treated with postoperative radiotherapy and chemotherapy. Median dose of radiation was 55.8Gy and the range was 44.6-59.4Gy. Second cycle of chemotherapy was delivered concurrently with radiation and total number of six cycles were delivered. Twenty three had adenocarcinoma and the other two had leiomyosarcoma. The numbers of patients with stage IB, II, IIIA, IIIB, and IV were 1, 2, 11, 10 and 1 respectively. Positive margins at distal end of the stomach were in 17 patients and proximal in 5. The other three patients had positive margin at the sites of adjacent organ invasion. Minimum and median follow-up periods were 12 months and 18 months, respectively. RESULTS: Twenty-four of 25 patients received prescribed radiation dose and RTOG grade 3 toxicity of UGI tract was observed in 3, all of which were weight loss more than 15% of their pretreatment weight. But hematemesis, melena, intestinal obstruction or grade 4 toxicity were not found. Locoregional failure within the radiation field was observed in 7 patients, and distant metastasis in 10 patients. Sites of locoregional recurrences involve anastomosis/ remnant stomach in 3, tumor bed/duodenal stump in 3, regional lymph node in 1 patient. Peritoneal seeding occurred in 6, liver metastases in 2, and distant nodes in 2 patients. Four year disease specific survival rate was 40% and disease free survival was 48%. Median survival was 35 months and median disease free survival time was 26 months. Stages and radiation dose were not significant prognostic factors for locoregional failures. CONCLUSION: Although all patients in this study had positive surgical margins, locoregional failure rate was 28%, and 4 year disease specific survival rate was 40%. Considering small number of patients and relatively short follow-up period, it is not certain that postoperative radiotherapy lowered locoregional recurrences, but we could find a possibility of the role of postoperative radiotherapy in patients with high risk factors.