Biomedical subjects

Seishiro Watanabe

Publications and source records attributed to Seishiro Watanabe.

43 records · Page 3Linked to original sources

PubMed2002

Expression of p57(KIP2) in hepatocellular carcinoma: relationship between tumor differentiation and patient survival.

Cyclins, cyclin-dependent kinases (CDK), and CDK inhibitors (CKI) are frequently altered in neoplasm. p57(KIP2) is a member of the KIP (kinase inhibitory protein) family of CKI and is a potential tumor suppressor gene. p27(KIP1) is the most extensively studied KIP family member with respect to the clinical significance in human neoplasms. However, the clinical significance of p57(KIP2) expression in patients with human cancers, including hepatocellular carcinoma (HCC), remains unknown. This study examined whether p57(KIP2) expression has any impact on clinical behavior of HCC including prognosis. We examined an expression of p57(KIP2) by immunohistochemistry in 101 cases of various liver diseases, including 59 HCC. The p57(KIP2) expression in HCC was analyzed in association with the pathohistologic stage, differentiation, proliferating cell nuclear antigen (PCNA) expression status and several histopathologic factors of possible prognostic value, and patient survival. Immunohistochemical analysis revealed the frequent loss of p57(KIP2) in HCC, especially in moderately and poorly differentiated HCC. By Kaplan-Meier analysis, overall survival was significantly correlated with p57(KIP2) expression and PCNA, and multivariate analysis showed p57(KIP2) was an independent prognostic factor. When the status of p57(KIP2) and PCNA were combined, cases positive for p57(KIP2) and with a low expression of PCNA had a significantly better prognosis than those negative for p57KIP2 and/or with a high expression of PCNA. These data indicate that loss of p57(KIP2) is a frequent event in HCC, especially in poorly differentiated HCC, suggesting that p57(KIP2) might play a role in the differentiation of HCC. In addition, p57(KIP2) expression status is an independent prognostic factor for patients with HCC, and the loss of p57(KIP2) is correlated with poor prognosis. New therapeutic options might be provided by the combination of the loss of p57(KIP2) and expression of PCNA.

Adult↗

PubMed2002

Enhanced expression of Bcl-2 in lymphocytes infiltrating into the liver of patients with primary biliary cirrhosis.

The Bcl-2 family proteins are important regulators of apoptosis and have been implicated in the occurrence of autoimmune diseases. There have been reports that Bcl-2-positive lymphocytes play important roles in pathogenesis of at least some types of autoimmune diseases, including autoimmune hepatitis. In this study, we examined the role of Bcl-2-positive lymphocytes in the development of primary biliary cirrhosis (PBC). The expression of Bcl-2 in lymphocytes infiltrating into the liver was evaluated from liver biopsy specimens of 25 patients with PBC (stage I/II/III/IV, 11/3/8/3) and 24 controls with chronic hepatitis B (CH-B) or chronic hepatitis C (CH-C). Bcl-2 expression in lymphocytes infiltrating into the liver was investigated by immunohistochemistry using a monoclonal antibody to Bcl-2 with an avidin-biotin complex system. Significant overexpression of Bcl-2 in lymphocytes infiltrating into the liver was observed in the early stage of PBC, especially in areas of destructed bile ducts. Most of Bcl-2-positive cells were CD45RO-positive helper T-cells visualized by the double staining method. These results suggest that Bcl-2-positive helper T-cells may have important roles in the pathogenesis of PBC.

Adult↗

PubMed2002

Enhancing and suppressing effects of dexamethasone on transgene expression in vitro.

Gene therapy is becoming an important treatment modality against various diseases including cancer, genetic disorders, infectious diseases and inflammatory diseases. For achieving successful gene therapy, it is extremely important to control the expression of a transduced therapeutic gene. However, there have been few studies examining the effect of glucocorticoid on transgene expression. We demonstrate here that the synthetic glucocorticoid dexamethasone significantly affected transgene expression in vitro. Bone marrow cells freshly prepared from rats and murine fibroblasts were infected with retroviruses carrying the neomycin phosphotransferase gene under the transcriptional control of the retroviral long terminal repeat promoter and the reporter lacZ gene under the transcriptional control of the simian virus 40 (SV40) early promoter. Retrovirus-infected cells were selected by G418. When retrovirus-infected bone marrow cells were cultured in the presence of dexamethasone, lacZ expression was markedly decreased. This suppressive effect of dexamethasone on transgene expression in bone marrow cells appeared to be mediated by a methylation-independent mechanism, because the suppressive effect was also observed in bone marrow cells that were supposed to contain a considerable number of methylated cells. In marked contrast, when retrovirus-infected fibroblasts were cultured in the presence of dexamethasone, lacZ expression was significantly increased. The enhancing and suppressing effects of dexamethasone on transgene expression were considered to be independent on promoter types, because the SV40 early promoter used to control lacZ expression does not contain a glucocorticoid-responsive element. Therefore, the different effects of dexamethasone on transgene expression appeared to be dependent on cell types. These results indicate that dexamethasone may play an important role for achieving successful gene therapy. Furthermore, these observations may also have important implications for future clinical applications of gene therapy.

3T3 Cells↗

PubMed2002

Combination therapy of percutaneous ethanol injection and radiofrequency ablation against hepatocellular carcinomas difficult to treat.

Radiofrequency ablation (RFA) is an effective modality for the treatment of hepatocellular carcinoma (HCC), because it can induce large coagulated necrosis in a few sessions. We have recently reported that the combination therapy of percutaneous ethanol injection (PEI) with RFA (PEI-RFA) created enhancement of coagulated necrosis compared with RFA alone. In the present study, we adopted PEI-RFA for the treatment of HCCs located in the regions that are difficult to treat with RFA alone. Five patients with biopsy-proven HCC and liver cirrhosis underwent PEI-RFA therapy. In these patients, HCCs were located beside the gallbladder, inferior vena cava or portal vein or kidney, or immediately under the diaphragm. Prior to RFA, 99.5% ethanol was injected into the region of HCC located in the regions where RFA energy appears to be difficult to reach. In all cases, HCC was totally coagulated by PEI-RFA. Injecting ethanol prior to RFA therapy caused no major side effects. These results indicate that PEI-RFA may be effective for the treatment of HCCs located in the regions that are difficult to treat with RFA alone as well as large-sized HCCs.

Administration, Cutaneous↗

PubMedDate not supplied

Aldehyde dehydrogenase-2 genotypes and HLA haplotypes in Japanese patients with esophageal cancer.

The aim of this study was to examine how aldehyde dehydrogenase-2 (ALDH2) genotypes and human leukocyte antigen (HLA) haplotypes contribute to the risk for esophageal cancer. We examined ALDH2 genotypes and HLA haplotypes in 29 Japanese patients with esophageal cancer. The ratio of patients who experienced current or former intense vasodilatation upon consuming alcohol (flushing type) was much higher in individuals with the inactive form of ALDH2 encoded by the ALDH2(2)/2(2) or ALDH2(1)/2(2) genotype than in those with the active form of ALDH2 encoded by the ALDH2(1)/2(1) genotype. The ratio of inactive ALDH2 was significantly higher in patients with esophageal cancer than in control normal subjects, suggesting that alcoholics with inactive ALDH2 were susceptible to esophageal cancer. HLA haplotypes A24, A26, B54, B61 and DR9 were prevalent in patients with esophageal cancer (82.8, 24.1, 34.5, 37.9 and 44.8%, respectively). HLA haplotype of A24 and inactive ALDH2 were simultaneously found in 58.6% of patients with esophageal cancer. Furthermore, we found other primary malignancies in 6 of 29 (20.7%) patients with esophageal cancer, and 4 of these 6 patients had both the inactive form of ALDH2 and the HLA A24 haplotype. The present study showed the high prevalence of the inactive form of ALDH2 and HLA haplotypes A24, A26, B54, B61 and DR9 in Japanese patients with esophageal cancer. Therefore, the examination of genotypes of ALDH2 loci and HLA haplotypes may allow the early detection of esophageal cancer in the Japanese population.

Adult↗

PubMedDate not supplied

Conversion from external nasobiliary drainage to internal drainage using endoscopically available scissor forceps.

Endoscopic nasobiliary drainage may cause undue stress, such as pharyngeal discomfort. We converted external drainage to internal drainage by cutting the external drainage tube with endoscopically available scissor forceps. Endoscopic nasobiliary drainage tubes were cut in the vicinity of the papilla using scissor forceps in 4 patients. The drainage tube was successfully cut in all patients. The tube was left for short-term internal drainage in 3 patients until the operation or endoscopic treatment was performed. The remaining patient with pancreatic head cancer was followed as an outpatient and the tube stent was occluded 62 days after cutting. Although further studies using a larger number of patients are needed, our procedure is thought to be beneficial to patients undergoing endoscopic nasobiliary drainage.

Aged↗

PubMedDate not supplied

Effect of an aldose reductase inhibitor on esophageal dysfunction in diabetic patients.

BACKGROUND/AIMS: Disorders of the digestive tract in diabetic patients are mainly ascribed to disorders of the vagus nerve. Although aldose reductase inhibitors (ARIs) have been shown to be effective against diabetic peripheral neuropathy, their effectiveness on diabetic digestive neuropathy remains to be evaluated. The aim of the present study is to examine the effect of an ARI on the esophageal dysfunction in diabetic patients by monitoring pH and motility of the esophagus. METHODOLOGY: Eight type 2 diabetic patients with peripheral neuropathy were administered with the ARI epalrestat (150 mg/day) for 90 days, and esophageal pH and motility were monitored before and after the ARI treatment. RESULTS: Parameters related to the gastroesophageal acid reflux and the esophageal motility, such as % time of pH<4, DeMeester score, duration of the longest reflux episode, reflux episodes longer than 5 min, ratios of peristaltic waves with the amplitude greater than 25 mmHg and ratios of effective peristalsis were remarkably improved by the ARI treatment. CONCLUSIONS: Because the present study clearly demonstrated the effectiveness of an ARI on the esophageal dysfunction in diabetic patients, ARI may be useful for the treatment of diabetic digestive disorders.

Aged↗