Association between Serum Gastrin Levels, Gastric Acid Secretion and Age in Early Gastric Cancer

Miyaji, Masao; Ogoshi, Kyoji; Tajima, Tomoo; Mitomi, Toshio

doi:10.1159/000218044

Cited by 11 publications

(8 citation statements)

References 10 publications

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“…In addition, G17DT or Gastrimmune, which has been shown to exert strong therapeutic effects towards primary as well as metastatic colorectal cancers, is currently under phase III clinical trials for treatment of GI-related cancers (Watson and Gilliam, 2001). A link between hypergastrinemia and gastric cancer (particularly those with neuroendocrine differentiation) has been suggested in other studies as well (Miyaji et al, 1997;Qvigstad et al, 2002). These conflicting reports indicate the need for further studies to establish a direct link between the gastrin pathway and tumorigenesis.…”

Section: Introductionmentioning

confidence: 97%

Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

et al. 2004

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Gastrin and its precursors promote proliferation in different gastrointestinal cells. Since mature, amidated gastrin (G-17) can induce cyclin D1, we determined whether G-17-mediated induction of cyclin D1 transcription involved Wnt signaling and CRE-binding protein (CREB) pathways. Our studies indicate that G-17 induces protein, mRNA expression and transcription of the G 1 -specific marker cyclin D1, in the gastric adenocarcinoma cell line AGSE (expressing the gastrin/cholecystokinin B receptor). This was associated with an increase in steadystate levels of total and nonphospho b-catenin and its nuclear translocation, indicating the activation of the Wnt-signaling pathway. In addition, G-17-mediated increase in cyclin D1 transcription was significantly attenuated by axin or dominant-negative (dn) T-cell factor 4(TCF4), suggesting crosstalk of G-17 with the Wnt-signaling pathway. Mutational analysis indicated that this effect was mediated through the cyclic AMP response element (CRE) (predominantly) and the TCF sites in the cyclin D1 promoter, which was also inhibited by dnCREB. Furthermore, G-17 stimulation resulted in increased CRE-responsive reporter activity and CREB phosphorylation, indicating an activation of CREB. Chromatin immunoprecipitation studies revealed a G-17-mediated increase in the interaction of b-catenin with cyclin D1 CRE, which was attenuated by dnTCF4 and dnCREB. These results indicate that G-17 induces cyclin D1 transcription, via the activation of b-catenin and CREB pathways.

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Section: Introductionmentioning

confidence: 97%

Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

et al. 2004

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“…( 7 ) In addition, it has been well‐documented that hypergastrinemia was associated with tumor growth in human gastric cancer patients. ( 8 )…”

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confidence: 99%

Gene expression profiling in a mouse model of Helicobacter‐induced gastric cancer

Takaishi

Wang²

2007

Cancer Science

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We have previously reported that a synergistic interaction between hypergastrinemia and Helicobacter felis (H. felis) infection accelerates gastric carcinogenesis in mice, but the precise mechanism for this interaction has not been clarified. Consequently, we undertook an oligonucleotide cDNA microarray study to investigate changes in gene expression in this model system. Nevertheless, the possible mechanisms by which this infectious organism is able to promote gastric cancer have not been elucidated for the most part. Data derived from both animal models as well as human studies have pointed to host immune responses, particularly strong T-helper (Th)1 immune responses, as critical to the development of gastric atrophy and intestinal metaplasia, preneoplastic conditions strongly associated with progression to cancer. (4,5) However, more recent studies in mice have also suggested a role for hypergastrinemia in the pathogenesis of gastric cancer. Hypergastrinemic mice (INS-GAS mice) developed by our group showed spontaneous development of gastric atrophy, metaplasia and adenocarcinoma which could be markedly accelerated by concurrent Helicobacter infection. (6) Kanda et al. also recently reported their gastrin transgenic mice (ACT-GAS mice) showed gastric mucosal hypertrophy and eventually gastric cancer, which was significantly regressed by cyclooxygenase-2 inhibitor celecoxib.(7) In addition, it has been well-documented that hypergastrinemia was associated with tumor growth in human gastric cancer patients.These data suggest the notion that elevations in circulating amidated gastrin might directly promote gastric atrophy and preneoplasia as well as neoplasia of the stomach in a susceptible host. A direct role for amidated gastrin in gastric carcinogenesis has been confirmed in recent studies by our group with the CCK2/gastrin receptor antagonist, YF476, which was shown to inhibit the development of atrophy and cancer in Helicobacterinfected INS-GAS mice.(9) Nevertheless, the relevant downstream targets of gastrin, and the mechanism of synergy between amidated gastrin and Helicobacter infection, has not been defined.The high throughput cDNA microarray represents a powerful tool for analyzing molecular events in cancer progression. This technology has been applied to study of the gene expression patterns in both human tissues and animal models of gastric cancer.(10-12) For example, we have recently reported in Helicobacter felis-infected C57BL/6 mice the gene expression profile of spasmolytic-polypeptide expressing metaplasia (SPEM), a precancerous lesion associated with gastric neoplasia in both rodent and human gastric fundus, and identified 11 SPEM-specific transcripts.(13) However, previous studies did not distinguish and characterize expression profiles based on Helicobacter infection status or serum gastrin levels. Other microarray studies have focused primarily on Helicobacter-treated gastric cancer cell lines, (14) but these in vitro experiments could not correlate the expression of specific genes with can...

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“…Duodenal ulceration occurs in patients with high acid secretion, 1-5 gastrooesophageal reflux disease and its complications in patients with normal 6 or high levels of acid secretion, [7][8][9] gastric ulceration in patients with moderately reduced secretion 10 and gastric cancer in patients with profoundly reduced or absent acid secretion. [11][12][13][14] The level of acid secretion is thought to have a role in the aetiology of these common upper gastrointestinal diseases. Increased gastric acid secretion and duodenal acid load predispose to duodenal ulceration as shown by the Zollinger-Ellison syndrome.…”

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confidence: 99%

Gastric histology, serological markers and age as predictors of gastric acid secretion in patients infected withHelicobacter pylori

et al. 2006

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Background: Acid secretion is intimately associated with most upper gastrointestinal diseases. Helicobacter pylori infection is a major environmental factor modifying acid secretion. Aim: To study the association between the pattern of H pylori gastritis and gastric secretory function in a large number of subjects without specific upper gastrointestinal disease. Methods and materials: Maximal acid output (MAO) was measured in 255 patients with dyspepsia showing normal endoscopy. Activity and severity of gastritis, atrophy and H pylori infection were assessed in body and antral biopsies. The correlations of histological parameters as well as age, sex, height, weight, smoking, serum gastrin, pepsinogen I and II, and their ratio with MAO were determined. Multiple linear regression was used to show the best possible predictors of MAO. Results: Negative relationships: Body atrophy and body-combined (active and chronic) inflammatory scores showed a potent inverse correlation with MAO (correlation coefficients (CC) 0.59 and 0.50, respectively). Body:antral chronic gastritis ratio and body:antral combined inflammation ratio (both with CC = 0.49) and age (CC = 0.44) were also inversely correlated with MAO. Intestinal metaplasia at both antral and body sites had negative relationships with acid output with CC = 0.23 and 0.20, respectively. Positive relationships: Serum pepsinogen I, body H pylori density:combined inflammation ratio and pepsinogen I:II ratio with CC of 0.38, 0.38 and 0.30, respectively, correlated with MAO. The H pylori density: combined inflammation of both antrum and body positively correlated with MAO (CC = 0.29 and 0.38, respectively). Male sex and patient height also positively correlated with acid output. Modelling showed that body combined inflammatory score, body atrophy, age and serum pepsinogen I are independent predictors of acid output (R 2 = 0.62). Conclusion: Combination of body gastritis, body atrophy, age and serum pepsinogen I can be used as predictors of acid-secretory state in populations infected with H pylori.

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Association between Serum Gastrin Levels, Gastric Acid Secretion and Age in Early Gastric Cancer

Cited by 11 publications

References 10 publications

Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

Gene expression profiling in a mouse model of Helicobacter‐induced gastric cancer

Gastric histology, serological markers and age as predictors of gastric acid secretion in patients infected withHelicobacter pylori

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