Guggulsterone, a plant-derived inhibitor of NF-TB, suppresses CDX2 and COX-2 expression and reduces the viability of esophageal adenocarcinoma cells.

Background/aims: Induction by bile acid of caudal type homeobox 2 (CDX2) and cyclooxygenase-2 (COX-2) expression via nuclear factor-κB (NF-κB) activation is a critical event in the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Guggulsterone (GS) is a plant sterol that inhibits NF-κB activity. Here, we evaluated whether GS has either or both chemopreventive or therapeutic effects against EAC.

Guggulsterone suppresses bile acid-induced and constitutive caudal-related homeobox 2 expression in gut-derived adenocarcinoma cells.

Background: Guggulsterone, a plant polyphenol guggulipid, has several antitumour effects and acts as an antagonist for the farnesoid X receptor. Although bile acids induce caudal-related homeobox 2 (CdX2), a transcription factor essential for intestinal development and gut tumourigenesis, the effects of guggulsterone on regulation of CdX2 in the gut are unknown.

Materials And Methods: Regulation of CdX2 expression by treatment with bile acids and/or guggulsterone was analysed by immunoblot analysis in human gut-derived adenocarcinoma, Bic-1 cells.

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.

Serum pepsinogens as an early diagnostic marker of H. pylori eradication.

Background/aims: Helicobacter pylori (H. pylori) eradication increases the serum pepsinogen I/ pepsinogen II ratio and the percentage change in pepsinogen I/pepsinogen II ratios is a useful marker of H. pylori eradication.

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.

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.

Dual therapy with high doses of rabeprazole and amoxicillin versus triple therapy with rabeprazole, amoxicillin, and metronidazole as a rescue regimen for Helicobacter pylori infection after the standard triple therapy.

Backgrounds And Aims: Development of safe and effective rescue regimens for eradication failure of Helicobacter pylori infection by standard regimens is an urgent task. We designed the prospective study to compare the efficacy of two rescue regimens after eradication failure by the standard triple therapy.

Methods: One hundred and thirty-two patients in whom eradication of H.

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)-1beta and tumor necrosis factor (TNF)-alpha with susceptibility to peptic ulcer diseases and gastric cancer in Japan.

Methods: The IL-1beta-511/-31 and TNF-alpha-308/-857/-863/-1031 genotypes were determined in Helicobacter pylori-positive patients with gastritis only (n = 164), gastric ulcers (n = 110), duodenal ulcers (n = 94), or gastric cancers (n = 105), and in H.

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.

Background: Gastrointestinal 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.

Outcome of radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication therapy.

Backgrounds And Aims: Most low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas respond to eradication of H. pylori, however, some are refractory. The effectiveness of radiotherapy for MALT lymphoma refractory to H.

EGF rapidly translocates tight junction proteins from the cytoplasm to the cell-cell contact via protein kinase C activation in TMK-1 gastric cancer cells.

Tight junctions are commonly disrupted in cancer cells, including gastric cancer. Various growth factors have been reported to affect the localization of tight junction-associated proteins such as ZO-1 and occludin. We investigated the effect of epidermal growth factor (EGF), a growth factor that is often overexpressed in gastric cancer, and fetal bovine serum (FBS) on the localization of ZO-1 and occludin in a gastric cancer cell line.

Alteration of intracellular histamine H2 receptor cycling precedes antagonist-induced upregulation.

Long-term administration of a histamine H2 receptor (H2R) antagonist (inverse agonist) induces upregulation of H2R in parietal cells, which may be relevant to the rebound hypersecretion of gastric acid that occurs after withdrawal of treatment. The mechanisms underlying this effect are unknown. We hypothesized that the H2R upregulation could be related to receptor trafficking and used H2R-green fluorescent protein (H2R-GFP) to test the hypothesis.

Cell-cycle-dependent efficacy of photodynamic therapy with ATX-S10(Na).

Photodynamic therapy (PDT) is a useful strategy for treating various cancers. Details of the mechanisms of PDT have not been made clear yet. We intended to study the efficacy of PDT in relation to the cell cycle.

Comparison of an increased dosage regimen of rabeprazole versus a concomitant dosage regimen of famotidine with rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome P450 2C19 genotypes.

Background And Objective: A concomitant dosage regimen of a histamine 2 receptor antagonist with a proton pump inhibitor (PPI) effectively decreases the incidence of nocturnal acid breakthrough, which is one of the problems encountered when acid-related diseases are treated with a PPI alone. We compared the effectiveness of an increased dosage regimen of rabeprazole with that of a concomitant dosage regimen of rabeprazole with famotidine, relative to cytochrome P450 (CYP) 2C19 genotype status, on nocturnal acid inhibition.

Methods: Fifteen Helicobacter pylori-negative volunteers, consisting of 5 homozygous extensive metabolizers (EMs), 6 heterozygous EMs, and 4 poor metabolizers (PMs) of CYP2C19, took 20 mg rabeprazole, 40 mg rabeprazole, and 20 mg rabeprazole plus 20 mg famotidine at bedtime (at 10 PM) for 8 days.

Different dosage regimens of rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome P450 2C19 genotype status.

Objective: For the treatment of gastroesophageal reflux disease, intragastric pH should be lower than 4.0 for no more than 4 hours a day (<16.7%).

Potential usefulness of detecting cyclooxygenase 2 messenger RNA in feces for colorectal cancer screening.

Background & Aims: Cyclooxygenase 2 (COX-2) is overexpressed frequently in aerodigestive tumors, especially in colorectal tumors. Therefore, it may be a suitable biomarker for colorectal cancer (CRC) screening. We performed a pilot study of whether detecting COX-2 expression in fecal RNA enables us to discriminate between patients with and without CRC.

Congenital absence of the portal vein complicating hepatic tumors.

Congenital absence of the portal vein (CAPV) is a rare malformation that is often accompanied by other anomalies such as cardiac and skeletal malformations and/or hepatic tumors. We describe here a case of CAPV complicating hepatic tumors in a 16-year-old Japanese girl. Abdominal ultrasonography revealed a hyperechoic tumor in the liver and dilatation of the portal vein that appeared to be connected directly with the inferior vena cava.

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.

High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin.

Background/aims: Some patients are refractory to the usual triple therapy for eradication of Helicobacter pylori, consisting of a proton pump inhibitor, amoxicillin and clarithromycin, so there needs to be an alternative strategy for retreatment after failure to eradicate the infection.

Methodology: The study group comprised 17 H. pylori-positive patients who had failed to clear H.

A Japanese case of familial Mediterranean fever with family history demonstrating a mutation in MEFV.

We describe a 17-year-old woman with a family history of FMF who suffered from recurrent fever accompanied by pains in the left chest and abdomen. During a five-year period she experienced attacks about once every six months. The metaraminol provocative test was positive.

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.

Transient leukopenia and anaphylatoxin production during granulocyte apheresis as treatment for ulcerative colitis.

It is well known that transient leukopenia due to activation of the alternative pathway of the complement system accompanies hemodialysis when cellulose acetate dialyzers are used. However, it has not been evaluated whether leukopenia also occurs during granulocyte apheresis (GCAP) as treatment for ulcerative colitis, in which an extracorporeal column is filled with cellulose acetate beads in order to remove circulating leukocytes. The aim of the present study was to evaluate whether transient leukopenia and activation of the alternative pathway of the complement system were observed during GCAP.