Fumio Sakashita

Vascular endothelial growth factor protects hepatoma cells against oxidative stress‐induced cell death

Background:  The aim of the present study was to examine coordination of the vascular endothelial growth factor (VEGF) and VEGF receptor (Flk‐1) system and to study control of VEGF expression by oxidative stress, which is considered a model for chronic liver disease.

Challenge for a better combination with basic evidence

Abstract5-Fluorouracil (5-FU) has been the most widely accepted and studied chemotherapeutic agent, and many combination chemotherapeutic regimens have been reported. However, until recently, a standard regimen for metastatic gastric cancer had not been established. The combination of S-1 and cisplatin is a good candidate as a standard first-line regimen for metastatic gastric cancer. On the other hand, interest in biochemical modulation has become wide spread recently. The low level of dihydropyrimidine denhydrogenase (DPD), thymidylate synthase (TS) activities, and a high level of orotate phosphoribosyl-transferase (OPRT) activity enhance the antitumor effect of 5-FU and S-1. Docetaxel is one of the agents that modulate these enzyme expressions and activities. Moreover, the response rate of combination therapy of docetaxel and S-1 for metastatic gastric cancer was 56.3% and median survival time was 14.3 months in a phase II study, showing it to be a good candidate for a new standard regimen for gastric cancer. A phase III collaborative study, START (S-1 and Taxotere for advanced gastric cancer randomized phase III trial), is now under way in Japan and Korea.

Clinicopathological features of hepatocellular carcinoma evaluated by vascular endothelial growth factor expression

Aim:  To evaluate the significance of the expression of vascular endothelial growth factor (VEGF), its correlation with clinicopathological variables were studied in the tissue of hepatocellular carcinoma (HCC) and surrounding liver.

Identification of an immune tolerance reaction in response to pretreatment with frozen pancreatic tissue in islet cell transplantation in rats.

Objectives: Whereas transplantation of insulin-secreting pancreatic islets may provide long-term control of glucose metabolism in patients with diabetes mellitus, transplant rejection remains a problem. In this study, we tried pretreatment with frozen pancreatic tissue in a rat model of islet cell transplantation to determine whether induction of immune tolerance is feasible. Methods: Isolated islet cells from Wistar rats were transplanted into the spleen of recipient rats that were sensitized and rats that were not sensitized with frozen pancreatic tissue. Spleens were analyzed histologically and then examined immunohistochemically for expression of insulin, a pancreas-specific gene. With the use of cDNA primers for proinsulin, RT-PCR was performed to detect islet cells in the spleen. Results: Although islet cells were present in spleens at posttransplantation day (PTD) 1, islet cell clusters in recipients without pretreatment were markedly destroyed on PTD 14 on histologic examination. In contrast, islet cell clusters in recipients sensitized with frozen pancreatic tissue appeared similar to those at PTD 1 even at PTD 14. Proinsulin gene expression was found to be specific to pancreatic tissue. In recipients sensitized with frozen pancreatic tissue, proinsulin gene expression was identified in recipient spleens, even at PTD 14, whereas it was undetected in the absence of pretreatment. In recipients transplanted with islet cells and treated simultaneously with frozen pancreatic tissue, proinsulin gene expression was completely eliminated. The immunohistologic study also showed the presence of insulin-producing islet cells in the spleens of rats sensitized with frozen pancreatic tissue. Conclusions: Inhibition of the immune reaction in transplant rejection may be mediated by pretreatment with frozen donor tissue.