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Zhong Zhang - One of the best experts on this subject based on the ideXlab platform.
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factors affecting the serum Gastrin 17 level an evidence based analysis of 3906 serum samples among chinese
Journal of Digestive Diseases, 2007Co-Authors: Yue-hua Gong, Xu Guang Wang, Meng Zhang, Zhong Zhang, Yuan YuanAbstract:OBJECTIVE: To investigate the influence of gender, age, site of lesion, disease type and Helicobacter pylori (H. pylori) infection on the human serum Gastrin-17 level and to study the diagnostic value of serum Gastrin-17 in gastric precancerous lesions and gastric cancer. METHODS: Serum Gastrin-17 and serum H. pylori IgG antibody were detected by the ELISA method. The different gastric disease groups were confirmed by endoscopy and histopathology. RESULTS: Among the 3906 serum samples according to the gender, age, site of lesion and the data of different gastric disease groups, the serum Gastrin-17 level was markedly higher in people ≥60 years old than that in younger age groups. The serum Gastrin-17 level increased progressively in the following order: healthy control group, nonatrophic gastritis group, gastric ulcer group, and the serum Gastrin-17 level was higher in the atrophic gastritis with dysplasia group than that without it, the lowest level being in the gastric cancer group. Among the 2946 serum samples matched with the site of the lesion, the serum Gastrin-17 level was higher in those with antral diseases than in those with gastric corpus diseases. Among the 3805 serum samples matched with the H. pylori infection data, the serum Gastrin-17 level was higher in the H. pylori-positive group than in the H. pylori-negative group. CONCLUSIONS: In people over 60 years of age, the serum Gastrin-17 level tends to increase. In subjects with precancerous gastric lesions, it may increase significantly with the progression of gastric disease, and ultimately decrease in gastric cancer. Serum Gastrin-17 is a good biomarker to differentiate benign from malignant gastric diseases. The site of the gastric lesions is an important factor affecting the serum Gastrin-17 level, whereas H. pylori infection is usually associated with its increment.
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Factors affecting the serum Gastrin 17 level: an evidence‐based analysis of 3906 serum samples among Chinese
Journal of Digestive Diseases, 2007Co-Authors: Zhong Zhang, Yue-hua Gong, Xu Guang Wang, Meng Zhang, Yuan YuanAbstract:OBJECTIVE: To investigate the influence of gender, age, site of lesion, disease type and Helicobacter pylori (H. pylori) infection on the human serum Gastrin-17 level and to study the diagnostic value of serum Gastrin-17 in gastric precancerous lesions and gastric cancer. METHODS: Serum Gastrin-17 and serum H. pylori IgG antibody were detected by the ELISA method. The different gastric disease groups were confirmed by endoscopy and histopathology. RESULTS: Among the 3906 serum samples according to the gender, age, site of lesion and the data of different gastric disease groups, the serum Gastrin-17 level was markedly higher in people ≥60 years old than that in younger age groups. The serum Gastrin-17 level increased progressively in the following order: healthy control group, nonatrophic gastritis group, gastric ulcer group, and the serum Gastrin-17 level was higher in the atrophic gastritis with dysplasia group than that without it, the lowest level being in the gastric cancer group. Among the 2946 serum samples matched with the site of the lesion, the serum Gastrin-17 level was higher in those with antral diseases than in those with gastric corpus diseases. Among the 3805 serum samples matched with the H. pylori infection data, the serum Gastrin-17 level was higher in the H. pylori-positive group than in the H. pylori-negative group. CONCLUSIONS: In people over 60 years of age, the serum Gastrin-17 level tends to increase. In subjects with precancerous gastric lesions, it may increase significantly with the progression of gastric disease, and ultimately decrease in gastric cancer. Serum Gastrin-17 is a good biomarker to differentiate benign from malignant gastric diseases. The site of the gastric lesions is an important factor affecting the serum Gastrin-17 level, whereas H. pylori infection is usually associated with its increment.
Yuan Yuan - One of the best experts on this subject based on the ideXlab platform.
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factors affecting the serum Gastrin 17 level an evidence based analysis of 3906 serum samples among chinese
Journal of Digestive Diseases, 2007Co-Authors: Yue-hua Gong, Xu Guang Wang, Meng Zhang, Zhong Zhang, Yuan YuanAbstract:OBJECTIVE: To investigate the influence of gender, age, site of lesion, disease type and Helicobacter pylori (H. pylori) infection on the human serum Gastrin-17 level and to study the diagnostic value of serum Gastrin-17 in gastric precancerous lesions and gastric cancer. METHODS: Serum Gastrin-17 and serum H. pylori IgG antibody were detected by the ELISA method. The different gastric disease groups were confirmed by endoscopy and histopathology. RESULTS: Among the 3906 serum samples according to the gender, age, site of lesion and the data of different gastric disease groups, the serum Gastrin-17 level was markedly higher in people ≥60 years old than that in younger age groups. The serum Gastrin-17 level increased progressively in the following order: healthy control group, nonatrophic gastritis group, gastric ulcer group, and the serum Gastrin-17 level was higher in the atrophic gastritis with dysplasia group than that without it, the lowest level being in the gastric cancer group. Among the 2946 serum samples matched with the site of the lesion, the serum Gastrin-17 level was higher in those with antral diseases than in those with gastric corpus diseases. Among the 3805 serum samples matched with the H. pylori infection data, the serum Gastrin-17 level was higher in the H. pylori-positive group than in the H. pylori-negative group. CONCLUSIONS: In people over 60 years of age, the serum Gastrin-17 level tends to increase. In subjects with precancerous gastric lesions, it may increase significantly with the progression of gastric disease, and ultimately decrease in gastric cancer. Serum Gastrin-17 is a good biomarker to differentiate benign from malignant gastric diseases. The site of the gastric lesions is an important factor affecting the serum Gastrin-17 level, whereas H. pylori infection is usually associated with its increment.
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Factors affecting the serum Gastrin 17 level: an evidence‐based analysis of 3906 serum samples among Chinese
Journal of Digestive Diseases, 2007Co-Authors: Zhong Zhang, Yue-hua Gong, Xu Guang Wang, Meng Zhang, Yuan YuanAbstract:OBJECTIVE: To investigate the influence of gender, age, site of lesion, disease type and Helicobacter pylori (H. pylori) infection on the human serum Gastrin-17 level and to study the diagnostic value of serum Gastrin-17 in gastric precancerous lesions and gastric cancer. METHODS: Serum Gastrin-17 and serum H. pylori IgG antibody were detected by the ELISA method. The different gastric disease groups were confirmed by endoscopy and histopathology. RESULTS: Among the 3906 serum samples according to the gender, age, site of lesion and the data of different gastric disease groups, the serum Gastrin-17 level was markedly higher in people ≥60 years old than that in younger age groups. The serum Gastrin-17 level increased progressively in the following order: healthy control group, nonatrophic gastritis group, gastric ulcer group, and the serum Gastrin-17 level was higher in the atrophic gastritis with dysplasia group than that without it, the lowest level being in the gastric cancer group. Among the 2946 serum samples matched with the site of the lesion, the serum Gastrin-17 level was higher in those with antral diseases than in those with gastric corpus diseases. Among the 3805 serum samples matched with the H. pylori infection data, the serum Gastrin-17 level was higher in the H. pylori-positive group than in the H. pylori-negative group. CONCLUSIONS: In people over 60 years of age, the serum Gastrin-17 level tends to increase. In subjects with precancerous gastric lesions, it may increase significantly with the progression of gastric disease, and ultimately decrease in gastric cancer. Serum Gastrin-17 is a good biomarker to differentiate benign from malignant gastric diseases. The site of the gastric lesions is an important factor affecting the serum Gastrin-17 level, whereas H. pylori infection is usually associated with its increment.
Eizo Kaneko - One of the best experts on this subject based on the ideXlab platform.
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effects of helicobacter pyloriinfection on gastric acid secretion and serum Gastrin levels in mongolian gerbils
Gut, 2001Co-Authors: Misako Takashima, Takahisa Furuta, Hiroyuki Hanai, Haruhiko Sugimura, Eizo KanekoAbstract:BACKGROUND AND AIMS Body gastritis caused by Helicobacter pylori infection appears to inhibit gastric acid secretion. The aim of this study was to determine the effects of H pylori infection on gastric acid secretion and clarify its mechanisms with reference to interleukin 1β (IL-1β). METHODS (1) Mongolian gerbils were inoculated orally with H pylori . Before, six, and 12 weeks after inoculation, serum Gastrin levels, gastric acid output, and IL-1β mRNA levels in the gastric mucosa were determined. Pathological changes were also determined according to the updated Sydney system. (2) Effects of recombinant human IL-1 receptor antagonist (rhIL-1ra) on gastric acid output and serum Gastrin levels were also determined. RESULTS (1) Scores for activity and inflammation of gastritis and serum Gastrin levels were significantly increased, and gastric acid output was significantly decreased six and 12 weeks after inoculation with H pylori. IL-1β mRNA levels in the gastric mucosa were also elevated six and 12 weeks after inoculation with H pylori . (2) Acid output and serum Gastrin levels in the infected groups returned to control levels after rhIL-1ra injection. CONCLUSIONS Gastric acid secretion is decreased and serum Gastrin levels are increased in Mongolian gerbils infected with H pylori . This change in gastric acid secretion appears to be mediated by IL-1β induced by H pylori infection.
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effects of helicobacter pylori infection on gastric acid secretion and serum Gastrin levels in mongolian gerbils
Gut, 1998Co-Authors: Misako Takashima, Takahisa Furuta, Hiroyuki Hanai, Haruhiko Sugimura, Eizo KanekoAbstract:Background and aims—Body gastritis caused by Helicobacter pylori infection appears to inhibit gastric acid secretion. The aim of this study was to determine the eVects of H pylori infection on gastric acid secretion and clarify its mechanisms with reference to interleukin 1‚ (IL-1‚). Methods—(1) Mongolian gerbils were inoculated orally with H pylori. Before, six, and 12 weeks after inoculation, serum Gastrin levels, gastric acid output, and IL-1‚ mRNA levels in the gastric mucosa were determined. Pathological changes were also determined according to the updated Sydney system. (2) EVects of recombinant human IL-1 receptor antagonist (rhIL-1ra) on gastric acid output and serum Gastrin levels were also determined. Results—(1) Scores for activity and inflammation of gastritis and serum Gastrin levels were significantly increased, and gastric acid output was significantly decreased six and 12 weeks after inoculation with H pylori. IL-1‚ mRNA levels in the gastric mucosa were also elevated six and 12 weeks after inoculation with H pylori. (2) Acid output and serum Gastrin levels in the infected groups returned to control levels after rhIL-1ra injection. Conclusions—Gastric acid secretion is decreased and serum Gastrin levels are increased in Mongolian gerbils infected with H pylori. This change in gastric acid secretion appears to be mediated by IL-1‚ induced by H pylori infection. (Gut 2001;48:765‐773)
Jens F Rehfeld - One of the best experts on this subject based on the ideXlab platform.
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acute effects of n terminal proGastrin fragments on gastric acid secretion in man
Physiological Reports, 2017Co-Authors: Jens P Goetze, Carsten P. Hansen, Jens F RehfeldAbstract:We previously identified an N-terminal fragment of proGastrin in human antrum and plasma, where it circulates in high concentrations. In this study, we examined the effects of N-terminal proGastrin fragments on gastric acid secretion by infusion in healthy individuals. Increasing doses of proGastrin fragment 1-35 were infused intravenously during constant gastric acid stimulation by Gastrin-17. In addition, the effects of proGastrin fragment 1-35, fragment 6-35, and fragment 1-19 on Gastrin-17 stimulated acid secretion were tested. The Gastrin-17 stimulated acid secretion decreased 30% after administration of a high dose of proGastrin fragment 1-35 (P < 0.05). In extension, a 1-h infusion of fragment 1-35 also decreased gastric acid output. In contrast, fragment 6-35 did not affect acid secretion, and a single infusion of Gastrin-17 alone did not reveal fading of gastric acid output during the time course of the experiments. The results show that N-terminal fragments of proGastrin may acutely affect Gastrin-stimulated gastric acid secretion in vivo. Structure-function analysis suggests that the N-terminal pentapeptide of proGastrin is required for the effect.
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Impact of Assay Epitope Specificity in Gastrinoma Di-
2016Co-Authors: Jens Peter Goetze, Jens F RehfeldAbstract:The antral hormone Gastrin regulates gastric acid secre-tion and growth of the gastric mucosa (1). As a result of the elaborate cellular maturation process of proGastrin, the antral G cells release a mixture of different acid-stimulatory Gastrins and other precursor fragments to the circulation (2). This mixture comprises Gastrin-71,-52,-34,-17,-14, and-6, all of which are carboxyamidated and circulate in an O-sulfated and nonsulfated form. The dominant Gastrin forms in serum from healthy humans are amidated Gastrin-34 and-17 [for a review, see Ref. (3)]. In cases of increased Gastrin synthesis, however, as seen in patients with hypo- and achlorhydric gastritis and gas-trin-producing tumors, i.e., Gastrinomas, the serum or plasma pattern molecular pattern changes to larger mo-lecular forms and more incompletely processed precur-sors (4–6). Hence, only little Gastrin-17 may be present i
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An evaluation of chromogranin A versus Gastrin and proGastrin in Gastrinoma diagnosis and control
Biomarkers in medicine, 2014Co-Authors: Jens F Rehfeld, Linda Bardram, Linda Hilsted, Jens P GoetzeAbstract:Aim: The value of chromogranin A (CgA) versus Gastrin and proGastrin in diagnosis and control of Gastrinoma patients is not settled because the peptides circulate as variable mixtures. We have addressed this complexity using defined sequence-specific assays. Patients & methods: Six assays were applied to plasma from 40 Gastrinoma patients to measure α-amidated Gastrins, glycine-extended Gastrins, the total proGastrin product, and assays for CgA sequence (340–348) and the ‘total’ CgA product. Results: The Gastrin/proGastrin parameters did not add to the diagnosis beyond that of α-amidated Gastrins, except in one patient. All Gastrin parameters correlated otherwise closely. The CgA results differed. Thus, 11 patients had normal CgA concentrations. By contrast, all total CgA concentrations were elevated but correlated only moderately to Gastrin. Conclusion: Assays measuring α-amidated Gastrins have high diagnostic value except for singular patients in whom only proGastrin was elevated. By contrast, CgA measu...
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the zollinger ellison syndrome and mismeasurement of Gastrin
Gastroenterology, 2011Co-Authors: Jens F Rehfeld, Jens P Goetze, Linda Bardram, Linda Hilsted, Marie Helene Gingras, Pierre PoitrasAbstract:Background & Aims Zollinger–Ellison syndrome (ZES) is characterized by hypersecretion of gastric acid, severe peptic ulcerations in the upper small intestine, and diarrhea. It is usually diagnosed by measuring increased levels of Gastrin in plasma. Methods We examined the accuracy of commercial kits to measure Gastrin (7 radioimmunoassays and 5 enzyme-linked immunosorbent assays), using plasma from 40 patients suspected or known to have ZES. Each sample was analyzed using the 12 kits and a reference assay that measures bioactive Gastrin in plasma, irrespective of size and amino acid derivatization. Known concentrations of peptides with identical sequences to circulating Gastrins were also assessed by all assays. Molecular patterns in plasma from patients with ZES were examined by chromatography and monitored by kits that measure false-low or false-high concentrations of Gastrin. Results Failure to diagnose Gastrinomas has serious consequences. Four kits found false-low concentrations of Gastrin in 20% to 80% of the patients. Specificity assessment showed that the antibodies used in these kits bound only Gastrin-17. Three kits found false-high concentrations of Gastrin, because the reagents had increased reactions to sulfated Gastrins or to unspecific factors in plasma. Thus, only 5 of 12 kits tested accurately measure plasma concentrations of Gastrin. Conclusions Seven of 12 tested commercial kits inaccurately measure plasma concentrations of Gastrin; these assays used antibodies with inappropriate specificity that were insufficiently validated. Misdiagnosis of Gastrinoma based on lack of specificity of assays for Gastrin results in ineffective or inappropriate therapy for patients with ZES.
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Influence of COX-2 Inhibition by Rofecoxib on Serum and Tumor ProGastrin and Gastrin Levels and Expression of PPARγ and Apoptosis-Related Proteins in Gastric Cancer Patients
Digestive diseases and sciences, 2003Co-Authors: Peter C. Konturek, Jens F Rehfeld, Artur Hartwich, Monika Zuchowicz, Władysław Bielański, Joanna Kania, Eckhart G. HahnAbstract:Cyclooxygenase-2 (COX-2) expression and certain growth hormones, such as Gastrin, have been related to gastric carcinogenesis, but little is known about the factors that enhance this COX-2 expression and whether specific blockade of this enzyme has any influence on tumor growth and progression. Our objective was to determine the influence of a specific COX-2 inhibitor, rofecoxib (Vioxx), on serum and tumor levels of Gastrin and its precursor, proGastrin, as well as on tumor gene expression of COX-2, peroxisome proliferator-activated receptor gamma (PPARγ), and apoptosis-related proteins (Bax and Bcl-2, caspase-3, and survivin). Twenty-four gastric cancer (GC) patients entered this study and were examined twice, once before and then following a 14-day treatment with Vioxx at a dose of 25 mg twice daily. For comparison, 48 age- and sex-matched healthy controls and 24 similarly matched Helicobacter pylori (Hp)-positive subjects were enrolled and treated with Vioxx as GC patients. Serum levels of anti-Hp and anti-CagA antibodies as well as IL-8 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA), while serum and tumor contents of proGastrin and amidated Gastrin were determined by specific RIA. Tumor gene and protein expressions of COX-2, PPARγ, Bax and Bcl-2, caspase-3, and survivin were determined by RT-PCR and western blot. The overall Hp and CagA seropositivity in 24 GC patients was significantly higher (82% and 47%) than in 48 controls (61% and 22%) but not in 24 Hp-infected subjects (100% and 38%). Serum IL-8 and TNF-α values were significantly higher in GC patients than in controls without GC or Hp-infected controls. Median serum proGastrin and Gastrin levels were found to be significantly higher in GC than in controls without GC and in Hp-positive subjects. Treatment of GC patients with Vioxx resulted in a significant decrease in plasma and tumor contents of both proGastrin and Gastrin, and this was accompanied by the increment in tumor expression of COX-2, PPARγ, Bax, and caspase-3 with a concomitant reduction in Bcl-2 and survivin expression. We conclude that: (1) GC patients show significantly higher Hp and CagA seropositivity than age- and sex-matched controls, but not Hp-positive subjects, indicating that infection with cytotoxic Hp is linked to GC. (2) Serum proGastrin and Gastrin levels are signficantly higher in GC patients than in matched controls, confirming that both Gastrins may be implicated in gastric carcinogenesis. (3) GC patients exhibit significantly higher levels of IL-8 and TNF-α than non-GC controls and Hp-positive subjects, probably reflecting more widespread gastritis in GC. (4) COX-2, PPARγ, Bcl-2, and survivin were overexpressed in gastric tumor, but the inhibition of COX-2 activity by Vioxx resulted in a significant reduction in serum and tumor levels of proGastrin and Gastrin and serum IL-8 and TNF-α levels, suggesting that Gastrin and proinflammatory cytokines could mediate the up-regulation of COX-2 in gastric cancerogenesis. (5) Vioxx also enhanced expression of COX-2, PPARγ, Bax, and caspase-3, while inhibiting the expression of Bcl-2 and survivin, suggesting that COX-2 blockade might be useful in chemoprevention against cancer possibly due to enhancement of the PPAR-γ and proapoptotic proteins-dependent apoptosis and the reduction in proGastrin/Gastrin-induced promotion of tumor growth.
Graham J. Dockray - One of the best experts on this subject based on the ideXlab platform.
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Gastrin Receptor Pharmacology
Current Gastroenterology Reports, 2012Co-Authors: Graham J. Dockray, Andrea Varro, Andy Moore, D. Mark PritchardAbstract:C-terminally amidated Gastrins act at cholecystokinin-2 receptors (CCK2R), which are normally expressed by gastric parietal and enterochromaffin-like (ECL) cells and smooth muscle; there is also extensive expression in the CNS where the main endogenous ligand is cholecystokinin. A variety of neoplasms express CCK2R, or splice variants, including neuroendocrine, pancreatic, medullary thyroid and lung cancers. Other products of the Gastrin gene (proGastrin, the Gly-Gastrins) may stimulate cell proliferation but are not CCK2R ligands. Depending on the cell type, stimulation of CCK2R evokes secretion, increases proliferation and cell migration, inhibits apoptosis, and controls the expression of various genes. These effects are mediated by increased intracellular calcium and activation of protein kinase C, MAPkinase and other protein kinase cascades. There has been recent progress in developing CCK2R ligands that can be used for imaging tumours expressing the receptor. New antagonists have also been developed, and there is scope for using these for suppression of gastric acid and for treatment of neuroendocrine and other CCK2R-expressing tumours.
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Gastrin: old hormone, new functions
Pflügers Archiv, 2005Co-Authors: Graham J. Dockray, Rod Dimaline, Andrea VarroAbstract:It is exactly a century since the gastric hormone Gastrin was first described as a blood-borne regulator of gastric acid secretion. The identities of the main active forms of the hormone (the “classical Gastrins”) and their cellular and molecular sites of action in regulating acid secretion have all attracted sustained attention. However, recent work on peptides derived from the Gastrin precursor that do not stimulate acid secretion (“non-classical Gastrins”), together with studies on mice over-expressing the gene, or in which the Gastrin gene has been deleted, suggest hitherto unsuspected roles in regulating cell proliferation, migration, and differentiation. Moreover, microarray and proteomic studies have identified previously unsuspected target genes of the classical Gastrins. Some of the newer actions have implications for our understanding of the progression to cancer in oesophagus, stomach, pancreas and colon, all of which have recently been linked in one way or another to dysfunctional signalling involving products of the Gastrin gene. The present review focuses on recent progress in understanding the biology of both classical and non-classical Gastrins.
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clinical endocrinology and metabolism Gastrin
Best Practice & Research Clinical Endocrinology & Metabolism, 2004Co-Authors: Graham J. DockrayAbstract:: The gastric hormone Gastrin stimulates gastric acid secretion and epithelial cell proliferation. Multiple active products are generated from the precursor, preproGastrin, including the well-characterized amidated Gastrins acting at the cholecystokinin-2 (CCK-2, or Gastrin-CCK(B)) receptor, and others that may be growth factors in a range of cancers. Plasma concentrations of the amidated Gastrins are elevated as a consequence of Gastrin-secreting tumours (Gastrinomas) and in conditions in which the normal inhibition of the antral G-cell by acid is depressed, for example chronic atrophic gastritis and prolonged treatment with proton pump inhibitors. There may also be increased Gastrin release in Helicobacter pylori infection. Provocative tests for the diagnosis of Gastrinoma include the secretin and calcium infusion tests. HyperGastrinaemia is associated with enterochromaffin-like (ECL) cell proliferation; the factors that determine progression to ECL cell dysplasia and gastric ECL cell carcinoid tumours are discussed. Several strategies for inhibiting the effects of Gastrin are under evaluation, and their potential application is discussed.
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Identification of plasminogen activator inhibitor-2 as a Gastrin-regulated gene: Role of Rho GTPase and menin.
Gastroenterology, 2002Co-Authors: Andrea Varro, Rod Dimaline, Elaine Hemers, Debbie Archer, Adelina Pagliocca, Chris Haigh, Suhail Ahmed, Graham J. DockrayAbstract:Abstract Background & Aims: The gastric hormone Gastrin regulates acid secretion, gene expression, and the functional development and cellular composition of the gastric mucosa. Using a gene array, we sought to identify major, novel, Gastrin-regulated genes. Methods: A cancer gene array was probed with samples from the gastric cancer cell line AGS, expressing the Gastrin-cholecystokinin B receptor and stimulated with Gastrin. The expression of Gastrin-regulated genes was further characterized by Western blots and enzyme-linked immunosorbent assay in tissue and blood of hyperGastrinemic patients. Gene expression was studied using promoter-luciferase reporter constructs. Results: Plasminogen activator inhibitor 2 (PAI-2) was identified as a major, previously unknown target of Gastrin in the gastric cancer cell line AGS. The relevance was confirmed by showing elevated tissue and plasma PAI-2 in hyperGastrinemic patients (pernicious anemia and multiple endocrine neoplasia type 1). PAI-2 promoter-luciferase constructs showed that Gastrin stimulated expression via pathways involving Gα and Gβγ subunits, protein kinase C, RhoA, and the transcription factors CREB and AP1. The tumor suppressor menin inhibited transcription. In addition, Gastrin stimulated expression in adjacent cells via a paracrine mechanism involving protein kinase C and RhoA but not CREB. Conclusions: A gene array showed PAI-2 to be a novel Gastrin-regulated gene, stimulated in part through CREB and AP-1 and inhibited by the tumor suppressor menin. GASTROENTEROLOGY 2002;123:271-280
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Gastrin deficiency results in altered gastric differentiation and decreased colonic proliferation in mice
Gastroenterology, 1997Co-Authors: Theodore J. Koh, Graham J. Dockray, Andrea Varro, Alan S Kopin, James R Goldenring, Susumu Ito, Hiroshi Mashimo, Timothy C WangAbstract:Background & aims Gastrin is a peptide hormone important in the regulation of both acid secretion and differentiation of oxyntic mucosal cells of the stomach. To further elucidate the role of Gastrin in the growth and development of the gastrointestinal tract, we have generated mice that are deficient in Gastrin. Methods Gastrin-deficient mice were generated through targeted gene disruption. Gastric and colonic architecture were determined by routine histology and immunohistochemical techniques. Proliferation was assessed by 5-bromo-2'-deoxyuridine incorporation. Results Targeted disruption of the Gastrin gene resulted in mice incapable of expressing Gastrin messenger RNA (mRNA) or producing Gastrin peptide. This deficiency led to a marked change in gastric architecture, with a decrease in number of parietal and enterochromaffin-like cells and an increase in number of mucous neck cells. There was no difference in the proliferation labeling index of the stomach in Gastrin-deficient mice (3.04% +/- 0.33%) compared with wild-type littermates (3.15% +/- 0.18%). The colon of Gastrin-deficient mice seemed normal histologically, although there was a decreased proliferation labeling index (2.97% +/- 0.52%) compared with wild-type littermates (4.71% +/- 0.44%; P Conclusions Gastrin is important in regulating the differentiation of the gastric mucosa and is a trophic factor for the colonic mucosa.
