M Katori

Heme oxygenase-1 (HO-1) is induced under a variety of pro-oxidant conditions such as those associated with ischemia-reperfusion injury (IRI) of transplanted organs. HO-1 cleaves the heme porphyrin ring releasing Fe2+, which induces the expression of the Fe2+ sequestering protein ferritin. By limiting the ability of Fe2+ to participate in the generation of free radicals through the Fenton reaction, ferritin acts as an anti-oxidant. We have previously shown that HO-1 protects transplanted organs from IRI. We have linked this protective effect with the anti-apoptotic action of HO-1. Whether the iron-binding properties of ferritin contributed to the protective effect of HO-1 was not clear. We now report that recombinant adenovirus mediated overexpression of the ferritin heavy chain (H-ferritin) gene protects rat livers from IRI and prevents hepatocellular damage upon transplantation into syngeneic recipients. The protective effect of H-ferritin is associated with the inhibition of endothelial cell and hepatocyte apoptosis in vivo. H-ferritin protects cultured endothelial cells from apoptosis induced by a variety of stimuli. These findings unveil the anti-apoptotic function of H-ferritin and suggest that H-ferritin can be used in a therapeutic manner to prevent liver IRI and thus maximize the organ donor pool used for transplantation.

OBJECTIVE: Resective therapeutic strategy for left-sided pancreatic adenocarcinoma is open to debate. The post-resection outcomes and factors influencing post-resection survival for adenocarcinoma of the body and tail of the pancreas were analyzed to determine the effectiveness of surgery. METHODS: A total of 73 patients with adenocarcinoma of the body or tail of the pancreas who underwent resection between 1994 and June 2007 were evaluated for overall survival. RESULTS: Multiple malignancies were present in 34 of 73 patients (47%). Overall 1-, 3- and 5-year survival rates after surgery were 79%, 34%, and 30%, respectively. Presence of symptoms, multiple cancers and level of preoperative tumor marker did not influence post-resection survival. As for tumor characteristics, tumor size, histological tumor differentiation, retroperitoneal invasion, status of residual tumor and UICC staging represented significant prognostic indicators by univariate analysis. Gemcitabine, when administered as an adjuvant settings, strongly worked for improving post-resection outcome (5-year survival rate = 51%). Factors shown to have independent prognostic significance on multivariate analysis were tumor size (<3 vs. >or=3 cm), status of residual tumor (R0 vs. R1, 2), and postoperative administration of gemcitabine. CONCLUSIONS: Appropriate patient selection and accurate surgical technique with postoperative adjuvant therapy could benefit survival of patients with carcinoma of the pancreas body and tail.