Further, results revealed that AGE alleviated the oxidative stress as evidenced by the stomach antioxidant enzymes (SOD, catalase, GPx, and GR), markers of oxidative stress (TRx, GRx) and Gastrin, a specific marker for gastric cancer and a decreased level of pro-inflammatory markers (NF-kB, TNF-α, IL-6, PGE<sub>2</sub>) which was further confirmed by histopathological analysis.
The same markers were also expressed in a proportion of adenocarcinomas supporting the view that gastrin is important in the development of gastric cancer.
Elevation of gastrin may be the carcinogenic factor for <i>Helicobacter pylori</i> as well as the recently described increased risk of gastric cancer due to proton pump inhibitor treatment.
So far, it has been demonstrated that serum pepsinogens (PGs), and gastrin 17 (G17) are useful for screening individuals at elevated risk to develop atrophic gastritis but they are suboptimal biomarkers to screen individuals for GC.
Although a substantial part of the gastric adenocarcinomas express gastrin and CCKBR, the role of gastrin in tumor development is not completely understood.
We therefore investigated whether serum gastrin or CCK concentrations at baseline were associated with the incidence of gastric non-cardia adenocarcinomas (GNCA), oesophagogastric junctional adenocarcinomas (EGJA) or gastric carcinoid tumours over 24 years of follow-up in a study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish smokers.
We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers-pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)-for identifying high-risk individuals and predicting risk of developing gastric cancer (GC).
The gastrointestinal (GI) peptide gastrin is an important regulator of the secretion and release of gastric acid from stomach parietal cells, and it also plays a vital role in the development and progression of GC.
One uninfected gastric cancer subtype was distinguished by upregulation of 3 genes with neuroendocrine (NE) function (CHGA, GAST, and REG4 encoding chromogranin, gastrin, and the secreted peptide REG4 involved in epithelial cell regeneration), implicating hormonal factors in the pathogenesis of a major class of gastric adenocarcinomas.
We show that gastrin, known to signal through the Gq/G11-coupled CCK2 receptor, induces SIK1 expression in adenocarcinoma cells, and that transcriptional activation of SIK1 is negatively regulated by the Inducible cAMP early repressor (ICER).
Studying menin and its complex interrelationship with gastrin may provide insight into tumor biology at the clinical level and in terms of basic cell biology (eg, the role of the epigenome in neuroendocrine cell proliferation), and lead to potential consideration of other targets that are known candidates for molecular-based therapies in other adenocarcinomas.
We show that NR4A2 is a primary early transient gastrin induced gene in adenocarcinoma cell lines, and that NR4A2 expression is negatively regulated by inducible cAMP early repressor (ICER) and zinc finger protein 36, C3H1 type-like 1 (Zfp36l1), suggesting that these gastrin regulated proteins exert a negative feedback control of NR4A2 activated responses.
We also examined the effects of IL-8 expression in gastric cancer in INS-GAS mice that overexpress gastrin and IL-8Tg mice infected with Helicobacter felis.