Gastrins ; metabolism ; Gonadal Steroid Hormones ; metabolism ; Growth Hormone ; metabolism ; Hormones ; metabolism ; Humans ; Liver Diseases ; metabolism ; Thyroid Hormones ; metabolism

The ontogeny and distribution of gastrin- and serotonin-immunoreactive (IR) cell in the proventriculus of chicks (Gallus gallus domestica, n = 60) in different growth periods was examined immunohistochemically using antisera specific to gastrin and serotonin. Gastrin and serotonin-IR cells were detected in chick proventriculus. Gastrin-IR cells were first evident after 12 days of incubation in lamina epithelialis and compound glands, while serotonin-IR cells were observed only in compound glands at that same time. Gastrin-IR and serotonin-IR cells increased in frequency on incubation day 14 and 16, respectively. Towards the end of incubation, gastrin- and serotonin-IR cell numbers decreased. In adult chicken, both IR cells were present but not lower numbers. The observations demonstrate the presence of gastrin- and serotonin-IR cells in the proventriculus of developing chicks in temporally changing frequencies.
Animals ; Chick Embryo/*metabolism ; Endocrine Cells/cytology/metabolism ; Gastrins/*metabolism ; Gene Expression Regulation, Developmental/physiology ; Proventriculus/*embryology/*metabolism ; Serotonin/*metabolism

OBJECTIVES: Helicobacter pylori infection induces selective reduction of the number of antral D-cells and results in abnormal regulation of serum gastrin secretion. The purpose of this study was to investigate the relationship between H. pylori infection and the numbers of G-cells and D-cells. METHODS: The numbers of antral G-cells and D-cells, the ratio of G-cells to D-cells and fasting serum gastrin concentrations were compared between 37 patients with (29 with duodenal ulcers and 8 with gastric ulcers) and 33 without H. pylori infection (22 with duodenal ulcers and 11 with gastric ulcers). Serum gastrin concentrations were measured using the radioimmunoassay technique. Antral mucosal biopsy specimens were examined using immunohistochemical staining with antibodies specific for gastrin and somatostatin and the numbers of G-cells and D-cells per gastric gland were counted. RESULTS: Fasting serum gastrin concentrations were significantly higher in patients with H. pylori infection compared to patients without infection (80.3 +/- 23.5 vs 47.6 +/- 14.1 pg/ml, p < 0.001). The number of G-cells per gastric gland was similar in infected and uninfected patients (7.1 +/- 3.1 vs 7.3 +/- 3.9, respectively, p > 0.5). The number of D-cells was significantly lower in patients with H. pylori infection than in uninfected patients in both duodenal and gastric ulcer patients (1.3 +/- 0.4 vs 2.5 +/- 1.6, respectively, p < 0.001). The ratio of G-cells to D-cells was also significantly higher in infected patients compared with uninfected patients for both gastric and duodenal ulcers (5.7 +/- 2.7 vs 3.5 +/- 1.9, respectively, p < 0.001). CONCLUSIONS: These results strongly suggest that Helicobacter pylori infection induces reduction of the number of antral D-cells. The resulting relative hypofunction of the inhibitory action of D-cells against G-cells may be responsible for increased serum gastrin secretion.
Case-Control Studies ; D Cells/pathology ; D Cells/metabolism ; G Cells/pathology ; G Cells/metabolism ; Gastrins/metabolism ; Gastrins/blood ; Gastritis/pathology ; Gastritis/metabolism* ; Helicobacter Infections/pathology ; Helicobacter Infections/metabolism* ; Helicobacter pylori* ; Human ; Somatostatin/metabolism

OBJECTIVETo examine the correlation between the mRNA and proteins expressions of gastrin(GAS), and the association of protein expression of GAS with apoptosis index(AI) and apoptosis regulation gene Fas/FasL, caspases in colorectal cancer.

METHODSThe expressions of GAS mRNA in tumor tissues of 79 cases with colorectal cancer were detected by nested RT-PCR. Cell apoptosis was detected by molecular biology in situ apoptosis detecting technic(TUNEL). Protein expressions of GAS, Fas/FasL, and caspases were detected by immunohistochemical staining (SP method).

RESULTSThe positive correlation was found between the mRNA and proteins expressions of GAS(rGAS=0.99, P<0.01). The mRNA and protein expressions of GAS in well and moderately differentiated cancers were significantly lower than those in poorly differentiated cancers (chi(2)(high vs low)=10.47, 10.23, P<0.01, chi(2)(middle vs low)=6.68, 4.95, P<0.05). The mRNA and protein expressions of GAS in papillary and tubular adenocarcinomas were significantly lower than those in mucinous adenocarcinomas, signet-ring cell carcinoma and undifferentiated carcinoma (chi(2)(papillary vs mucinous and signet-ring)=4.80, 6.22, chi(2)(papillary vs undifferentiation)=5.44, 8.43, chi(2)(tubular vs mucinous and signet-ring)=4.40, 4.38, chi(2)(tubular vs undifferentiation)=4.92, 6.43, P<0.05, respectively). The mRNA and protein expressions of GAS in Dukes' stages A, B were significantly lower than those in Dukes stages C, D (chi(2)=4.84, 4.45, P<0.01). The AI in GAS high and moderate expression groups of colorectal cancer were significantly lower than that in low expression group (q(high vs low)=6.71, q(middle vs low)=4.60, P<0.01). The positive expression rate of FasL was significantly different among GAS high, moderate and low expression groups of colorectal cancer (chi(2)=9.35, P<0.01). The positive expression rate of FasL in GAS high and moderate expression groups was higher than that in low expression group (chi(2)high vs low=6.24, chi(2)(middle vs low)=4.74, P<0.05).

CONCLUSIONSGAS plays an important role in the regulation of cell apoptosis in colorectal carcinoma, whose mechanism may be related to the aberrant expression of Fas/FasL. GAS will be one of the indicators of the biological behavior in colorectal carcinoma.

Adult ; Aged ; Caspases ; metabolism ; Colorectal Neoplasms ; metabolism ; pathology ; Fas Ligand Protein ; metabolism ; Female ; Gastrins ; metabolism ; Humans ; Male ; Middle Aged ; RNA, Messenger ; metabolism ; Young Adult ; fas Receptor ; metabolism

OBJECTIVETo investigate the effect of gastrin on invasiveness of human colon cancer cells and the role of gastrin receptor-focal adhesion kinase (FAK) signal transduction pathway in this proess.

METHODSpCR3.1/GR vector expressing gastrin receptor was transfected into a colorectal cancer cell line Colo320 with lipofectamine 2000, and screened by G418. The expression levels of gastrin receptor of the parental cell line Colo320 and the transfected cell line Colo320/GR were assayed by RT-PCR. On the other hand, antisense oligonucleotide of FAK was used to block its expression. The mock transfected Colo320 and sense oligonucleotide Colo320 cells were used as controls. Colo320 and Colo320/GR cells were treated with increasing doses (0 approximately 100 nmol/L) of gastrin. Invasiveness of Colo320 and Colo320/GR cells was determined by Boyden chamber. Phosphorylation of focal adhesion kinase (FAK) tyr-397 was examined by immunoprecipitation and Western-blot.

RESULTSRT-PCR results showed that the Colo320/GR cells had an mRNA level four times as high as that of Colo320 cells. Western blot showed that FAK tyr397 phosphorylation of Colo320 cells was apparently decreased. Colo320 and Colo320/GR cells showed a dose-dependent response to gastrin on invasiveness and phosphorylation of FAK tyr-397. Invasiveness of Colo320 cells reached its climax when concentration of gastrin was 100 nmol/L, and FAK tyr-397 phosphorylation was marked when concentration of gastrin was 10 nmol/L, but the latter decreased when gastrin concentration was increased to 100 nmol/L. Colo320/GR cells had the same tendency as Colo320 cells, but showed an even stronger invasiveness and a higher level of FAK tyr-397 phosphorylation than Colo320 cells. Before gastrin stimulation, the invasiveness of Colo320 cells transfected with antisense oligonucleotides and the controls showed no difference. After gastrin stimulation, the increase in invasiveness was much less than that in the controls.

CONCLUSIONGastrin can evidently promote invasiveness of Colo320 cells via gastrin-gastrin receptor-FAK signal transduction pathway.

Cell Line, Tumor ; Colorectal Neoplasms ; pathology ; Focal Adhesion Protein-Tyrosine Kinases ; metabolism ; Gastrins ; pharmacology ; Humans ; Neoplasm Invasiveness ; Signal Transduction

OBJECTIVETo study the expression of gastrin(GAS) and gastrin releasing peptide(GRP) in patients with gastric cancer and investigate the clinical significance.

METHODSThe expression of GAS and GRP in sixty patients with gastric cancer was detected by using tissue chip technique and immunohistochemical methods.

RESULTSThe positive rates of GAS and GRP were 30.0% and 11.7% respectively in 60 cases with gastric cancer. The positive rates of GAS and GRP were higher in moderately and poorly differentiated cancers than those in well differentiated cancer (P< 0.05). The positive rates of GAS and GRP were significantly higher in mucinous adenocarcinoma and signet-ring cell carcinoma than those in other types of gastric cancer (P< 0.05). The positive expression of GAS and GRP in gastric cancer was correlated with lymph node metastasis (P< 0.05).

CONCLUSIONTissue chip technique is a feasible,rapid,economic and accurate approach for screening clinical tissue specimens on a large scale.

Adult ; Aged ; Female ; Gastrin-Releasing Peptide ; metabolism ; Gastrins ; metabolism ; Humans ; Immunohistochemistry ; methods ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Protein Array Analysis ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo explore the effects of gastrin on the expression of 1,25(OH)2D3-membrane associated rapid response steroid (1,25D3-MARRS) binding protein in rat intestinal epithelium.

METHODSSD rats received intraperitoneal injections of gastrin, omeprazole or physiological saline. The protein expression of 1,25D3-MARRS binding protein in SD rat intestinal was determined with Western blotting and immunohistochemistry, and its mRNA levels determined by RT-PCR. The serum calcium and phosphate levels in the rats were also detected.

RESULTSImmunohistochemistry showed that 1,25D3-MARRS binding protein was expressed mainly in the nuclei, cytoplasm and membrane of the intestinal epithelial cells. Both the protein and mRNA expression levels of 1,25D3-MARRS binding protein were up-regulated after treatments with gastrin and omeprazole (P<0.05), but the serum calcium and phosphate concentrations showed no obvious increase.

CONCLUSION1,25D3-MARRS binding protein, which is widely expressed with versatile functionalities, is regulated by gastrin and shows high potentials in the study of gastrointestinal diseases.

Animals ; Calcitriol ; metabolism ; Epithelial Cells ; drug effects ; metabolism ; Gastrins ; pharmacology ; Intestines ; cytology ; drug effects ; Male ; Protein Disulfide-Isomerases ; metabolism ; Rats ; Rats, Sprague-Dawley

The regional distributions and relative frequencies of some gastrointestinal endocrine cells in the three portions (cecum, colon and rectum) of the large intestinal tract of C57BL/6 mice were examined with immunohistochemical method using 7 types of specific antisera against chromogranin A (CGA), serotonin, somatostatin, human pancreatic polypeptide (HPP), glucagon, gastrin and cholecyctokinin (CCK)-8. In this study, all 3 types of immunoreactive (IR) cells were identified. Most of these IR cells in the large intestinal portion were generally spherical or spindle in shape (open-typed cell) while cells with a round shape (close-typed cell) were found in the intestinal gland. Their relative frequencies varied according to each portion of the large intestinal tract. CGA-IR cells were found throughout the whole large intestinal tract but were most predominant in the colon. Serotonin-IR cells were detected throughout the whole large intestinal tract and showed highest frequency in the colon. Peculiarly, glucagon-IR cells were restricted to the colon with a low frequency. However, no somatostatin-, HPP-, gastrin- and CCK-8-IR cells were found in the large intestinal tract. In conclusion, some peculiar distributional patterns of large intestinal endocrine cells were identified in C57BL/6 mice.
Animals ; Chromogranin A ; Chromogranins/metabolism ; Enteroendocrine Cells/*metabolism/physiology ; Female ; Gastrins/metabolism ; Glucagon/metabolism ; Immunohistochemistry/veterinary ; Intestine, Large/*cytology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pancreatic Polypeptide/metabolism ; Serotonin/metabolism ; Sincalide/metabolism ; Somatostatin/metabolism

OBJECTIVETo study the clinicopathological features of gastric neuroendocrine tumors.

METHODSTwenty cases were reviewed. The specimens were formalin-fixed, paraffin-embedded and immunostained by S-P method.

RESULTSAmong the twenty cases, one case was carcinoid, three were malignant carcinoids, six had small cell carcinomas and ten had mixed extocrine--endocrine carcinomas. Immunohistological examination of tumor cells found 80% positive for S-100, NSE (85%), CgA (50%), SY (50%), gastrin (30%), serotonin (65%), AE1/AE3 (50%), and CEA (80%).

CONCLUSIONSIn the WHO classification, there are five histological types in endocrine tumors of gastrointestinal tract. They are carcinoid, malignant carcinoid, small cell carcinoma, mixed exocrine--endocrine carcinoma and tumor-like lesions. But some cases in our paper were so different that they could not be classified. The gastric endocrine tumors are different from intestinal endocrine tumors and in classification, treatment and prognosis.

Adult ; Aged ; Carcinoembryonic Antigen ; metabolism ; Carcinoid Tumor ; metabolism ; pathology ; Carcinoma, Small Cell ; metabolism ; pathology ; Female ; Gastrins ; metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neuroendocrine Tumors ; metabolism ; pathology ; Phosphopyruvate Hydratase ; metabolism ; Prognosis ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the expression of gastrin in human gastric cancer cell line SGC-7901 and the effects of gastrin-17 and anti-gastrin mAb on its growth.

METHODSThe expression of gastrin was determined by immunohistochemistry with anti-gastrin mAb prepared by our group. In a series of experiments, the growth of SGC-7901 cells was evaluated by MTT assay on cells grown in serum-free medium and treated with gastrin-17 and/or anti-gastrin mAb.

RESULTSImmunohistochemical examination of SGC-7901 cells revealed a specific gastrin immunoreactivity. Gastrin-17 significantly stimulated cell growth at the concentrations of 1 x 10(-9) mol/L approximately 1 x 10(-5) mol/L in a dose-dependent manner. The growth of SGC-7901 cells treated with anti-gastrin mAb, either alone or in combination with gastrin-17 (1 x 10(-7) mol/L), was significantly inhibited.

CONCLUSIONGrowth of human gastric cancer cells SGC-7901 can be stimulated in an autocrine fashion. The gastrin-stimulated growth of gastric cancer cells can be blocked by anti-gastrin mAb bound specifically with gastrin. Further study on the significance of anti-gastrin mAb in designing immunotherapy targeting to gastrin or gastrin receptor is warranted.

Antibodies, Monoclonal ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Gastrins ; biosynthesis ; genetics ; immunology ; Humans ; Receptor, Cholecystokinin B ; biosynthesis ; genetics ; Stomach Neoplasms ; metabolism ; pathology