Masayoshi Kajimura

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

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.

A deficiency of gastric interstitial cells of Cajal accompanied by decreased expression of neuronal nitric oxide synthase and substance P in patients with type 2 diabetes mellitus

BackgroundGastrointestinal motility is impaired in patients with diabetes mellitus (DM). Interstitial cells of Cajal (ICC) in the gastrointestinal tract play a central role in gastrointestinal motility. The present study examined whether ICC density, or expression of neuronal nitric oxide synthase (nNOS)- and substance P (SP)-containing nerves in the gastric antrum, were altered in patients with type 2 DM.MethodsParaffin-embedded gastric specimens from 51 controls and 36 male DM patients with gastric cancer were used for immunohistochemistry. Serial sections were stained with Kit and mast cell tryptase-specific antibodies. Fresh-frozen gastric specimens from patients with gastric cancer were used for immunofluorescence. The specimens were stained with antibodies to Kit, nNOS, and SP, and levels of expression of these three markers were compared between controls and DM patients.ResultsICC density in the inner circular muscle layer, but not in the myenteric plexus, was lower in patients with severe DM than in controls in paraffin-embedded specimens. In addition, decreased expression of nNOS and SP accompanied by reduced ICC density was observed in frozen specimens from patients with DM.ConclusionsThese results suggest that lower gastric ICC, nNOS, and SP densities in patients with DM may be associated with the pathogenesis of diabetic gastroparesis.

Different effects of polymorphisms of tumor necrosis factor-alpha and interleukin-1 beta on development of peptic ulcer and gastric cancer

Background and Aim:  In Western countries, polymorphism of pro‐inflammatory cytokine genes is associated with the development of gastric cancer and duodenal ulcer. The aim of this study was to clarify the association of polymorphisms of interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α with susceptibility to peptic ulcer diseases and gastric cancer in Japan.

Effects of interleukin-10 gene polymorphism on the development of gastric cancer and peptic ulcer in Japanese subjects

Background:  Anti‐inflammatory cytokines play an important role in downregulation of inflammation and the prevention of neoplastic disorders. Genetic variations of anti‐inflammatory cytokines are assumed to influence such responses. The aim of the present study was to clarify the association between the IL‐10 polymorphism, one of the representative anti‐inflammatory cytokines, and susceptibility to gastric cancer and peptic ulcer in Japan.

Correlation of EPHA2 overexpression with high microvessel count in human primary colorectal cancer

Evidence suggests that the erythropoietin‐producing hepatocellular (EPH) receptor tyrosine kinases (RTKs) and their ephrin (EFN) ligands are involved in human carcinogenesis. Expression of two of them, EFNA1 ligand and its receptor, EPHA2, has been proposed to contribute to tumor‐induced neovascularization. Colorectal cancers were examined for expressions of EPHA2 and its ligand EFNA1 by semi‐quantitative RT‐PCR, and double‐immunostained for EPHA2 and CD34. Microvessels in the tumors were counted. Double‐staining was also performed in 25 cases of adenoma with focal cancer for comparison. Trends of overexpression of both EPHA2 and EFNA1 was found in tumor tissue compared to the corresponding normal tissue in the same specimen [22/37 (59.5%) and 25/37 (67.5%), respectively; P=0.100 for EPHA2 and P=0.009 for EFNA1]. Overexpression of EPHA2 and EFNA1 was noted more frequently in the early stage than in the late stage [EPHA2, 15/21 (71.4%) vs. 7/16 (43.8%), P=0.007; EFNA1, 15/21 (71.4%) vs. 10/16 (62.5%), P=0.007]. Both EPHA2 and EFNA1 were more frequently overexpressed in smaller tumors (less than 5 cm) than in larger tumors [EPHA2, 15/21 (71.4%) vs. 7/16 (43.8%), P=0.017; EFNA1, 16/21 (76.2%) vs. 8/16 (50%), P=0.001]. Tumors less than 5 cm in diameter and in stages I and II were significantly more likely to overexpress EPHA2 and EFNA1 (P=0.001 for EPHA2, P=0.001 for EFNA1). Microvessel counts (MVCs) after immuno‐staining for CD34 were significantly correlated (r=0.343, P=0.037) with overexpression of EPHA2. EPHA2‐expressing focal cancer also surrounded microvessels in adenomas with focal cancers. These findings suggest an involvement of EPHA2 in colon carcinogenesis, mainly in stages I and II, and probably through their effect on microvessel induction.

Comparison of lansoprazole and famotidine for gastric acid inhibition during the daytime and night-time in different CYP2C19 genotype groups

The acid inhibitory effect of lansoprazole depends on the S‐mephenytoin 4′‐hydroxylase (CYP2C19) genotype status. The effect of famotidine is independent of this genotype.

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.

Fecal Cyclooxygenase 2 Plus Matrix Metalloproteinase 7 mRNA Assays as a Marker for Colorectal Cancer Screening

We previously reported that fecal cyclooxygenase 2 (COX-2) mRNA assay, detecting COX-2 mRNA in feces, is useful for identifying subjects with colorectal cancer (CRC). To further improve the sensitivity, we evaluated the usefulness of the combination of COX-2 mRNA and matrix metalloproteinase 7 (MMP-7) mRNA assays as a marker of CRC. The study cohort included 62 patients with CRC and 29 control patients without colorectal neoplasia. RNA was isolated from routinely collected fecal samples. The expression levels of COX-2 and MMP-7 mRNAs were determined by nested reverse transcription-PCR. PCR conditions were optimized where the specificity of fecal COX-2 and MMP-7 mRNA assay result in 100%. The sensitivity of each fecal assay was 87% [95% confidence interval (95% CI), 76-94%] and 65% (95% CI, 51-76%) for CRC, respectively. The sensitivity of fecal RNA test (either marker being positive) was high for CRC (90%; 95% CI, 80-96%). The sensitivity of the fecal RNA test was also high (93%; 95% CI, 80-98%) in patients with stage I or II who are often cured by surgical resection. The fecal RNA test using COX-2 and MMP-7 mRNAs improved the sensitivity to detect CRC without decreasing the specificity. These results suggest that the fecal RNA test would be a promising approach for CRC screening, although larger clinical investigations are indicated. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1888–93)

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in japanese patients with Helicobacter pylori infection

Background : Cytochrome P450 2C19 (CYP2C19) polymorphism has been associated with the development of lung, liver or oesophageal cancer by detoxification of carcinogen(s) or activation of procarcinogen(s).

Determination of mutations of the 23S rRNA gene of Helicobacter pylori by allele specific primer‐polymerase chain reaction method

Background and Aims:  Susceptibility to clarithromycin of Helicobacter pylori (H. pylori) is caused by single nucleotide polymorphisms (SNPs) of the 23SrRNA gene. Allele specific primer‐polymerase chain reaction (ASP‐PCR) is one of the methods for determining SNPs, which can measure SNPs easily within a short period by PCR amplification alone without digestion with restriction enzymes. The aim of the present study was to develop the ASP‐PCR assay for determining SNPs at positions 2142 and 2143 of the 23S rRNA gene of H. pylori.