Intestine-specific homeobox (ISX) induces intestinal metaplasia and cell proliferation to contribute to gastric carcinogenesis

Peroxisome proliferator-activated receptorγ(PPARγ) is a nuclear receptor that is important in many physiological and pathological processes, such as lipid metabolism, insulin sensitivity, inflammation, cell proliferation, and carcinogenesis. Several studies have shown that PPARγplays an important role in gastric mucosal injury due toHelicobacter pylori(H. pylori). AsH. pyloriinfection is the main etiologic factor in chronic gastritis and gastric cancer, understanding of the potential roles of PPARγinH. pyloriinfection may lead to the development of a therapeutic target. In this paper, the authors discuss the current knowledge on the role of PPARγinH. pyloriinfection and its related gastric carcinogenesis.

Download Full-text

cagA positive and negative Helicobacter pyloristrains are simultaneously present in the stomach of most patients with non-ulcer dyspepsia: relevance to histological damage

Gut ◽

10.1136/gut.42.6.772 ◽

1998 ◽

Vol 42 (6) ◽

pp. 772-778 ◽

Cited By ~ 59

Author(s):

N Figura ◽

C Vindigni ◽

A Covacci ◽

L Presenti ◽

D Burroni ◽

...

Keyword(s):

Cell Proliferation ◽

Intestinal Metaplasia ◽

Normal Mucosa ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

Glandular Cell ◽

Increased Risk ◽

Molecular Masses ◽

Non Ulcer Dyspepsia ◽

H Pylori

Background/Aims—Infection with Helicobacter pylori strains harbouring the cagA gene (cagA+) is associated with an increased risk of developing peptic ulcer and gastric cancer. The aim of this study was to assess whether H pylori isolates with different cagA status were present in patients with non-ulcer dyspepsia, and whether a variable cagA status is relevant to histological gastric mucosal damage and glandular cell proliferation.Methods—Well separated H pyloricolonies (between 2 and 25) from primary plates, per gastric area, for each of 19 patients with non-ulcer dyspepsia were examined forcagA by hybridisation. Western blotting was used to examine both representative colonies for CagA expression and the patients’ sera for antibody response to CagA. Glandular gastric cell proliferation was assessed immunohistochemically.Results—Of the 747 colonies examined, 45.3% werecagA+. All colonies from four patients werecagA+, and all colonies from two patients werecagA−. In 13 patients (68%) both cagA+ andcagA− colonies were found. CagA expression of isolates corresponded to their cagA status. H pyloristrains with different CagA molecular masses were present in three patients. Results based on all 19 patients studied showed that the prevalence of cagA+ colonies in areas with mucosal atrophy associated or not with intestinal metaplasia (67.9%) was significantly higher than in normal mucosa (44.7%) and mucosa from patients with chronic gastritis (44.0%) (p< 0.001). High levels of cell proliferation were associated with histological atrophy with or without intestinal metaplasia, but not with the possession of cagA by organisms colonising the same mucosal sites.Conclusions—Most patients with non-ulcer dyspepsia are infected by both cagA+ and cagA−H pylori colonies. The cagA status of infecting organisms may play a role in the development of atrophy and intestinal metaplasia.

Download Full-text

Eugenol inhibits cell proliferation via NF-κB suppression in a rat model of gastric carcinogenesis induced by MNNG

Investigational New Drugs ◽

10.1007/s10637-009-9345-2 ◽

2009 ◽

Vol 29 (1) ◽

pp. 110-117 ◽

Cited By ~ 45

Author(s):

P. Manikandan ◽

G. Vinothini ◽

R. Vidya Priyadarsini ◽

D. Prathiba ◽

S. Nagini

Keyword(s):

Cell Proliferation ◽

Rat Model ◽

Gastric Carcinogenesis

Download Full-text

M1634 Overexpression of Retinoic Acid-Regulated Nuclear Matrix-Associated Protein (RAMP) Induces Cell Proliferation in Gastric Cancer: Potential Oncogenic Role of Ramp in Gastric Carcinogenesis

Gastroenterology ◽

10.1016/s0016-5085(08)61804-1 ◽

2008 ◽

Vol 134 (4) ◽

pp. A-386

Author(s):

Julia J. Li ◽

Enders K. Ng ◽

Yu P. Ng ◽

Jun Yu ◽

Joseph J. Sung ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Retinoic Acid ◽

Nuclear Matrix ◽

Gastric Carcinogenesis

Download Full-text

Topographic association of Ki-67 and Bcl-2 expression with H. pylori infection, gastric atrophy, intestinal metaplasia: A role for antralization in gastric carcinogenesis?

Gastroenterology ◽

10.1016/s0016-5085(01)83262-5 ◽

2001 ◽

Vol 120 (5) ◽

pp. A656-A656

Author(s):

G ZHANG ◽

N TALLEY ◽

C HENWOOD ◽

J WYATT ◽

S ADAMS ◽

...

Keyword(s):

Intestinal Metaplasia ◽

Gastric Carcinogenesis ◽

Gastric Atrophy ◽

Ki 67 ◽

H Pylori

Download Full-text

Lgr5 Contributes to Intestinal Metaplasia During Gastric Carcinogenesis: A Meta analysis

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520615666150616123345 ◽

2016 ◽

Vol 16 (9) ◽

pp. 1079-1084

Author(s):

Ye Han ◽

Qiaoming Zhi ◽

Xiaofeng Xue ◽

Bin Yuan ◽

Hong Zhao ◽

...

Keyword(s):

Intestinal Metaplasia ◽

Meta Analysis ◽

Gastric Carcinogenesis

Download Full-text

Cell Proliferation and Inflammation on Biopsy Samples With Multifocal Atrophic Gastritis Before and 1 Year After Helicobacter pylori Eradication

Archives of Pathology & Laboratory Medicine ◽

10.5858/2005-129-1451-cpaiob ◽

2005 ◽

Vol 129 (11) ◽

pp. 1451-1456

Author(s):

Jeannette Guarner ◽

Jeanine Bartlett ◽

Roslyn Seitz ◽

Toni Whistler ◽

Roberto Herrera-Goepfert ◽

...

Keyword(s):

Cell Proliferation ◽

Helicobacter Pylori ◽

T Lymphocytes ◽

Intestinal Metaplasia ◽

Eradication Therapy ◽

Ki 67 ◽

Proliferation Markers ◽

Helicobacter Pylori Eradication ◽

Biopsy Specimens ◽

H Pylori

Abstract Context.—Results of clinical trials that have assessed whether gastric cancer is preventable with Helicobacter pylori eradication therapy remain inconclusive. These trials have used atrophy, intestinal metaplasia, and dysplasia as histopathologic end points that reflect possible preneoplastic lesions. Trial results would be more compelling if cell proliferation and inflammatory markers improved simultaneously with histopathologic lesions. Objective.—To study the presence of cell proliferation markers and type of inflammatory cells in biopsy specimens with gastritis, atrophy, and intestinal metaplasia before and 1 year after H pylori therapy and to determine if immunohistochemistry can be used to study these. Design.—We evaluated 12 subjects with gastritis and 16 with gastritis and multiple foci of atrophy and intestinal metaplasia by using immunohistochemical assays for tumor suppressor protein p53, proliferation marker Ki-67, cell cycle regulator cyclin D1, T and B lymphocytes, macrophages, and TUNEL (terminal deoxynucleotide transferase deoxyuridine triphosphate nick end labeling) assay for apoptosis. The biopsy specimens were selected from a randomized clinical trial that studied improvement of histopathologic gastric lesions after H pylori eradication. Results.—Groups of surface epithelial cells that expressed p53 and Ki-67 were observed more often in subjects with atrophy and intestinal metaplasia compared with those with gastritis alone. T lymphocytes in the lamina propria were frequently observed 1 year after treatment in subjects with atrophy and intestinal metaplasia. Conclusions.—Immunohistochemical assays for cell proliferation and inflammatory cell markers showed different distribution patterns in these gastric biopsy specimens. The presence of T lymphocytes and groups of cells that expressed proliferation markers in subjects with multiple foci of atrophy and intestinal metaplasia needs further study.

Download Full-text