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Hiroyuki Hanai

Publications and source records attributed to Hiroyuki Hanai.

25 records · Page 2Linked to original sources

Expression profile of EFNB1, EFNB2, two ligands of EPHB2 in human gastric cancer.

PURPOSE: We have previously reported that EPHB2 is overexpressed in gastric cancer; however, the expression profiles of its ligands, EFNB1 and EFNB2, are unknown. This study was designed to investigate the expression of EPHB2 and its ligands, EFNB1 and EFNB2, in human gastric cancer. METHODS: Semi-quantitative RT-PCR using (32)P was performed on human gastric cancer tissues and corresponding normal tissues (29 gastric cancer patients). RESULTS: EPHB2 was more highly expressed in tumor tissues than in normal tissues in 21 out of 29 (72.4%), in gastric cancer patients ( P = 0.01); EFNB1 and EFNB2 were highly expressed in 21 out of 29 (72.4%) ( P = 0.037) and 14 out of 29 (48.3%) patients, respectively. The overexpression of EPHB2 was frequently detected in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma [10/13 (76.9%) and 9/14 (64.3%), respectively]. On the other hand, the overexpression of EFNB1 was more frequently detected in poorly differentiated adenocarcinoma than in well-differentiated adenocarcinoma [12/14 (85.7%) and 7/13 (53.8%), respectively. P =0.027]. Elevated levels of EPHB2 and EFNB1 were detected in substantial subsets of early gastric cancers. Genomic alterations to these three genes in gastric cancer specimens were either not found or rarely found except for several rare variations of EPHB2. CONCLUSIONS: These findings suggest that not only the expression of EPHB2, but the expression of its ligand EFNB1 may have some relation with the oncogenesis of gastric cancer.

Base Sequence↗

Curcumin prevents and ameliorates trinitrobenzene sulfonic acid-induced colitis in mice.

BACKGROUND & AIMS: Curcumin is known to have a variety of pharmacologic effects, including antitumor, anti-inflammatory, and anti-infectious activities. The pleiotropic effects of curcumin are attributable at least in part to inhibition of transcriptional factor nuclear factor kappaB (NF-kappaB). However, the effect of curcumin on intestinal inflammation has hitherto not been evaluated. The aim of this study was to determine whether treatment with curcumin prevents and ameliorates colonic inflammation in a mouse model of inflammatory bowel disease. METHODS: Mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis were treated with 0.5%, 2.0%, or 5.0% curcumin in the diet, and changes in body weight together with histologic scores were evaluated. Colonic T-cell subsets were characterized, and NF-kappaB in colonic mucosa was detected by immunohistochemistry. NF-kappaB activity in the colonic mucosa was evaluated using electrophoretic mobility shift assay. Cytokine messenger RNA expression in colonic tissue was assessed by semiquantitative reverse-transcription polymerase chain reaction. RESULTS: Treatment of mice with curcumin prevented and improved both wasting and histopathologic signs of TNBS-induced colonic inflammation. Consistent with these findings, CD4(+) T-cell infiltration and NF-kappaB activation in colonic mucosa were suppressed in the curcumin-treated group. Suppression of proinflammatory cytokine messenger RNA expression in colonic mucosa was also observed. CONCLUSIONS: This study has shown for the first time that treatment with curcumin can prevent and improve murine experimental colitis. This finding suggests that curcumin could be a potential therapeutic agent for the treatment of patients with inflammatory bowel disease.

Animals↗

Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole.

BACKGROUND AND OBJECTIVES: The acid-inhibitory effect of lansoprazole depends on differences in cytochrome P450 (CYP) 2C19 genotypes. We assessed whether therapeutic effects of lansoprazole on gastroesophageal reflux disease (GERD) depended on the CYP2C19 genotype status in relation to the grade of GERD. METHODS: A total of 65 patients with GERD (grades A-D) completed treatment with lansoprazole, by taking 30 mg orally once a day for 8 weeks. The CYP2C19 genotype status of patients was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Before and after treatment, esophageal endoscopy was performed. GERD was considered to be cured on the basis of endoscopic findings at the end of treatment. Plasma lansoprazole levels could be determined at 3 hours after the last 30-mg dose of lansoprazole in the 27 genotyped patients. RESULTS: Cure rates for GERD depended significantly on the CYP2C19 genotype status, as well as the grade of GERD before treatment. Cure rates in the homozygous extensive, heterozygous extensive, and poor metabolizer groups were 45.8%, 67.9%, and 84.6%, respectively. Cure rates in the groups with GERD grade A, grade B, and grade C or D were 85.0%, 60.0%, and 45.0%, respectively. The cure rate in patients with the homozygous extensive metabolizer genotype of CYP2C19 with a GERD grade of C or D was very low (16.7%). Plasma lansoprazole levels in patients with the homozygous extensive metabolizer genotype were the lowest of the 3 groups. CONCLUSIONS: CYP2C19 genotype status, as well as the grade of GERD before treatment, is one of the determinants for the success or failure of treatment of GERD with lansoprazole. The low cure rate in patients with the homozygous extensive metabolizer genotype appeared to be a result of these patients having the lowest plasma lansoprazole levels among the 3 genotype groups.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Should gastric cancer patients more than 80 years of age undergo surgery? Comparison with patients not treated surgically concerning prognosis and quality of life.

This study investigated the performance status, mental status, and prognosis of 24 patients older than 80 years whose gastric cancer had been managed surgically during the past 6 years, and 21 patients who were observed conservatively. The advantages and disadvantages of surgery for elderly patients with gastric cancer is discussed. The 3-year survival rate for patients with advanced gastric cancer was 31% for those surgically treated and 0% for those observed conservatively. The difference is statistically significant. The survival rate for patients with early gastric cancer was 62.5% in the surgical treatment group and 33.3% in the conservative observation group, a difference that is not significant. Decline in performance status and deterioration of mental status after open surgery were slight, and the survival rate for patients treated surgically was significantly higher than for conservatively observed patients, regardless of performance status and whether mental status had deteriorated. On univariate and multivariate analyses, the presence or absence of open surgery and macroscopic classification were the only significant prognostic factors, whereas performance status and the presence or absence of mental deterioration were not significant prognostic factors. These results suggest that surgical treatment should not be discouraged even for patients older than 80 years.

Age Factors↗

Immunohistochemical localization of angiotensin II receptor and local renin-angiotensin system in human colonic mucosa.

Angiotensin II (Ang II) regulates water and sodium transport in renal tubules and gastrointestinal tract. Two types of Ang II receptors have been cloned, but their distributions have not been determined in human colon. In addition, tissue renin-angiotensin systems (RAS) are believed to exist and to regulate local actions in human colon. We studied by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) the presence and localization of Ang II receptors Type 1 (AT(1)), Type 2 (AT(2)), and RAS components [angiotensinogen, renin, and angiotensin-converting enzyme (ACE)] in normal human colon. AT(1) receptors were localized in vessel walls, myofibroblasts, macrophages, and surface epithelium. AT(2) receptors were found in mesenchymal cells and weakly in parts of surface epithelium. Renin and ACE were distributed in vessel walls, mesenchymal cells, and in parts of surface epithelium. Angiotensinogen was also detected by RT-PCR. These findings demonstrated that Ang II receptors and RAS components were present in human colon, suggesting the possibility of its local regulation.

Adult↗