Yuan-Chieh Yang

Isolation and characterization of human gastric cell lines with stem cell phenotypes.

Aim:  The aim of this study was to develop an in vitro human gastric stem and/or progenitor cell model that may be used to study the mechanism of gastric carcinogenesis induced by Helicobacter pylori infection.

Amoxicillin resistance with β‐lactamase production in Helicobacter pylori

Background  Amoxicillin‐resistant Helicobacter pylori with minimal inhibitory concentration (MIC) ≥ 256 mg L−1 was isolated from a gastritis patient. The aims were to investigate the mechanism of high‐level amoxicillin resistance in H. pylori.

Rabeprazole Can Overcome the Impact of CYP2C19 Polymorphism on Quadruple Therapy

Objectives:  The prospective study was designed to clarify the impact of CYP2C19 on quadruple therapies and survey the efficacies of rabeprazole‐based quadruple therapy for Helicobacter pylori infection after failure of standard triple therapies.

Effects of arecoline in relaxing human umbilical vessels and inhibiting endothelial cell growth.

Abstract This study investigated the effects of arecoline, an active ingredient of the areca nut, on the tone of human umbilical arteries and veins and on the eNOS expression and cell proliferation of human umbilical vein endothelial cells (HUVECs). We found that arecoline relaxes the human umbilical artery and vein rings in a concentration-dependent manner; the higher the concentration of arecoline, the greater the relaxation of the rings. However, the relaxation decreases after the endothelium was removed or pretreated with L-NAME, a nitric oxide synthase inhibitor. Moreover, arecoline increases in a dose-dependent way the cGMP levels of human umbilical arteries and veins. In HUVECs, arecoline also increases the eNOS expression. Therefore, the relaxant effects of arecoline on the umbilical artery and vein rings were endothelium-dependent through the NO-cGMP systems. In addition, arecoline at higher doses (100–1000 μM) inhibits endothelial cell proliferation; the exposure toarecoline (100–1000 μM) for 24 and 48 h induces G2/M cell cycle arrest of HUVECs. Our results indicate that arecoline would decrease vascular tone, in part mediated by NO. Higher doses of arecoline inhibit endothelial cell growth, which suggest that long-term use or high doses of areca nut might induce endothelial dysfunction and associated diseases.

A tumorigenic homeobox (HOX) gene expressing human gastric cell line derived from putative gastric stem cell.

Goal Study the mechanism of gastric tumor development. Background We have generated and characterized a novel human gastric cell line, KMU-CS12 (CS12), from an immortal cell line, KMU-CSN (CSN; formerly named as GI2CS−) which was derived from putative human gastric stem cell/progenitor cell clone, KMU-GI2. Study The characterization of the CS12 cell line includes gene expression by immunocytochemical staining, cell proliferation and differentiation potential, cyotogenetic analysis by Giemsa banding and spectral karyotype analysis (SKY), and tumorigenicity in immune-deficient congenic inbred, nude mice (BALB/cAnN-Foxn1nu/CrlNarl). The Agilent Human 1A oligo-array and RT-PCR were also employed to analyze the expression of homeobox (HOX) genes. Results The CS12 gastric cell line showed cancer cell phenotypes, i.e. the ability of anchorage-independent growth high frequency (44%) and to the expression of Oct-4, a transcription factor expressed in embryonic stem cells and many types of cancer cells, and tumor development in immune deficient mice. SKY analysis indicated a characteristic duplication of the short arm of chromosome 7 to chromosome 12. Agilent Human 1A oligo-array analysis showed that the expression of 1145 genes was upregulated while that of 890 genes was downregulated in CS12 cells. RT-PCR revealed that homeobox genes (HOXA4, HOXA5, HOXA7, HOXA9, and HOXA13) were highly expressed in CS12 cells in culture, as well as tumor tissues developed by CS12 cells in immunodeficient mice for six to eight weeks. Conclusion Except for the duplication of the short arm of Chromosome 7 on Chromosome12, the karyotype of the tumorigenic CS12 cells is similar to the parental GI2 cells which are non-tumorigenic and normal in karyotype. This chromosomal change could be the cause for the high expression of HOXA genes and tumorigenicity of these cells found in this study. Thus HOXA genes might play an important role in gastric carcinogenesis.

17β-estradiol inhibits mesenchymal stem cells-induced human AGS gastric cancer cell mobility via suppression of CCL5- Src/Cas/Paxillin signaling pathway.

Gender differences in terms of mortality among many solid organ malignancies have been proved by epidemiological data. Estrogen has been suspected to cast a protective effect against cancer because of the lower mortality of gastric cancer in females and the benefits of hormone replacement therapy (HRT) in gastric cancer. Hence, it suggests that 17β-estradiol (E2) may affect the behavior of cancer cells. One of the key features of cancer-related mortality is metastasis. Accumulating evidences suggest that human bone marrow mesenchymal stem cells (HBMMSCs) and its secreted CCL-5 have a role in enhancing the metastatic potential of breast cancer cells. However, it is not clear whether E2 would affect HBMMSCs-induced mobility in gastric cancer cells. In this report, we show that CCL-5 secreted by HBMMSCs enhanced mobility in human AGS gastric cancer cells via activation of Src/Cas/Paxillin signaling pathway. Treatment with specific neutralizing antibody of CCL-5 significantly inhibited HBMMSCs-enhanced mobility in human AGS gastric cancer cells. We further observe that 17β-estradiol suppressed HBMMSCs-enhanced mobility by down-regulating CCL5-Src/Cas/paxillin signaling pathway in AGS cells. Collectively, these results suggest that 17β-estradiol treatment significantly inhibits HBMMSCS-induced mobility in human AGS gastric cancer cells.