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허혈-재관류에 의한 신장조직 손상에서 Cobalt Chloride의 조직 보호작용에 관한 연구
Brief ischemic periods before sustained ischemia known as ischemic preconditioning, have been shown to protect several organs, including the kidney, from ischemia-reperfusion( I-R ) injury. Cobalt chloride (COCL) has hypoxia-mimetic effects by inhibiting degradation of HIF-1α, which is a master regulator of genes activated by low oxygen tension. Herne oxygenase-1(HO-1), an inducible heat shock protein, is known to have cytoprotective effects against ischemic injury. This study evaluated the efficacy of COCL in a bilateral renal I-R injury model of male Sprague-Dawley rats. I-R renal injury was induced by 45 min clamping of both renal arteries. Rats in the sham(n=6) and I-R control groups(n=8) had been drinking tap water, whereas rats in the sham(n=6) and COCL treated I-R groups(n=9) had been drinking water containing 2 mM COCL from day -10 to day 1. The serum levels of creatinine, AST, LDH, and the renal tubular necrosis score based on light microscopic examination in each group were measured 24 hrs after surgery. The levels of renal gene expressions of HO-1, TGF-β, MCP-1, TNF-α, endeothelin-1, iNOS, Bcl-2 and Fas were measured by competitive RT-PCR. The serum level of creatinine 24 hrs after surgery was 2.6±1.1(mean±SD) mg/dL in I-R COCL treated group, significantly lower than that in I-R control group(4.8±1.6 mg/dL, p<0.05). The tubular necrosis score of I-R COCL treated group was also significantly lower than that of I-R control group(p<0.01). The renal gene expression of HO-1 was significantly upregulated in the COCL treated sham group compared to sham operated control rats. The HO-1 protein signal of kidney in the COCL treated I-R group measured by Western blot was also significantly higher than the level of I-R control group(p<0.05). The expressions of TGF-β, MCP-1, TNF-α, endothelin-1 and Fas genes in the kidneys of COCL treated I-R rats were significantly lower than those of I-R control rats(all, p<0.05). The level of Bcl-2 gene expression of kidneys in COCL treated I-R rats was significantly higher than the level of I-R control rats (p<0.05). In conclusion, it is speculated that the pretreatment of COCL in I-R injured rat model attenuates ischemic renal injury and at least in part, upregulation of renal HO-1 is involved in this mechanism.
Background: To find out effectiveness of multimodality treatments based on induction chemotherapy(CTx) in patients with clinical stage ⅢA NSCLC Methods: From 1997 to 2002, 74 patients with clinical stage ⅢA NSCLC underwent induction CTx at the hospital of Chungnam National University. Induction CTx included above two cycles of cisplatin-based regimens(ectoposide, gemcitabine, vinorelbine, or taxol) followed by tumor evaluation. In 30 complete resection group, additional 4500-5000cGy radiotherapy(RTx) was delivered in 15 patients with pathologic nodal metastasis. 29 out of 44 patients who were unresectable disease, refusal of operation, and incomplete resection were followed by 60-70Gy RTx in local treatment. Additional 1-3 cycle CTx were done in case of induction CTx responders in both local treatment groups. Results: Induction CTx response rate were 44.6%(complete remission 1.4% & partial response 43.2%) and there was no difference of response rate by regimens(p=0.506). After induction chemotherapy, only 33 out of resectable 55 ones(including initial resectable 37 patients) were performed by surgical treatment because of 13 refusal of surgery by themselves and 9 poor predicted reserve lung function. There were 30(40.5%) patients with complete resection, 2(2.6%) persons with incomplete resection, and 1(1.3%) person with open & closure. Response rate in 27 ones with chest RTx out of non-operation group was 4.8% CR and 11.9% PR. In complete resection group, relapse free interval was 13.6 months and 2 year recur rate was 52%. In non-complete resection(incomplete resection or non-operation) group, disease progression free interval was 11.2 months and 2 year disease progression rate was 66.7%. Median survival time of induction CTx 74 patients with ⅢA NSCLC was 25.1months. When compared complete resection group with non-complete resection group, the median survival time was 31.7 and 23.4months(p=0.024) and the 2-year overall survival rate was 80% and 41% . In the complete resection group, adjuvant postoperative RTx subgroup significantly improved the 2-year local control rate(0% vs. 40%, p= 0.007) but did not significantly improve overall survival(32.2months vs. 34.9months, p=0.48). Conculusion: Induction CTx is a possible method in the multimodality treatments, especially followed by complete resection, but overall survival by any local treatment(surgical resection or RTx) was low. Additional studies should be needed to analysis data for appropriate patient selection, new chemotherapy regimens and the time when should RTx be initiated.