Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bombesin, a 14-amino acid peptide, exhibits direct and indirect effects on the gastrointestinal tract, including release of hormones, stimulation of pancreatic, gastric, and intestinal secretion and intestinal motility. Cholecystokinin (CCK) and gastrin, two of the hormones released by bombesin, have been shown to play a role in maintaining the growth of normal gastrointestinal mucosa as well as in eliciting trophic responses in normal and neoplastic tissue. We studied the effects of chronic bombesin treatment on the growth of a human ductal pancreatic adenocarcinoma (SKI) xenografted into nude mice, and on the growth of the normal nude mouse pancreas. Thirteen nude mice were implanted with SKI tumor and divided into two groups. Mice received 0.1 ml intraperitoneal injections of either bombesin (20 micrograms/kg) or the vehicle alone three times per day. Tumor areas were measured twice weekly until death (week 8), at which time the tumors and the host pancreas were excised, weighed, and assayed for protein, RNA, and DNA content. Significant inhibition of tumor growth was found in the bombesin-treated group at weeks 4, 5, 6, 7, and 8. Tumor area and weight at death (day 57) were significantly less in the bombesin-treated group (48 and 46%) as compared with control. We observed similar inhibition of tumor DNA (39%), RNA (38%), and protein (43%) content compared with controls. In contrast, bombesin significantly increased the weight (64%), protein (81%), and DNA (73%) content of the mouse pancreas compared with controls. We conclude that bombesin acts concurrently as both a trophic agent for normal host pancreas and a growth inhibitory agent in xenografted pancreatic cancer tissue.
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PMID:Bombesin inhibits growth of human pancreatic adenocarcinoma in nude mice. 283 42

Signs and symptoms of Cushing's syndrome developed rapidly after total gastrectomy in a 37-yr-old man with a metastatic gastrin-secreting islet cell carcinoma. Argyrophilic tumor cells in a lymph node removed during operation immunostained for gastrin and ACTH. Treatment for more than 6 months with the somatostatin analog SMS 201-995 (300 micrograms/day) greatly reduced serum gastrin levels and normalized plasma ACTH and cortisol levels and urinary cortisol excretion, and the signs and symptoms of Cushing's syndrome disappeared. The size of the primary tumor in the head of the pancreas, which had grown rapidly before SMS 201-995 therapy, stabilized after 6 months of treatment with the analog. We conclude that SMS 201-995 can reduce ACTH as well as gastrin secretion from islet cell carcinomas as well as control tumor growth.
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PMID:Successful treatment with SMS 201-995 of Cushing's syndrome caused by ectopic adrenocorticotropin secretion from a metastatic gastrin-secreting pancreatic islet cell carcinoma. 284 25

The effects of gastrin, proglumide (a gastrin receptor antagonist), and somatostatin on growth of human colon adenocarcinoma cell lines CX1, X56, and HT29 were examined in two experimental models. Nude mice bearing xenografts of colon cancer CX1 or X56 were treated for 14-25 days subcutaneously with saline, pentagastrin (0.5 or 1.0 mg/kg), proglumide (250 or 500 mg/kg), or somatostatin 14 (33, 100, or 300 micrograms/kg) twice daily. Tumor volume, weight, protein, and deoxyribonucleic acid were measured. HT29 cells were grown in vitro and the effects of gastrin 17, proglumide, and somatostatin on growth were evaluated by cell counts or [3H]thymidine incorporation. The larger dose of pentagastrin significantly increased tumor growth in the nude mouse (p less than 0.005) and gastrin induced a biphasic effect on deoxyribonucleic acid synthesis in tissue culture with significant increases of up to 39% (p less than 0.025). Somatostatin alone significantly inhibited tumor growth in two of the cell lines and also inhibited the gastrin-induced growth. Proglumide had no effect by itself but significantly inhibited gastrin-stimulated growth. These findings suggest that growth of some human colon cancers may be hormone-dependent.
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PMID:Effects of gastrin, proglumide, and somatostatin on growth of human colon cancer. 290 11

We have examined the effects of the somatostatin analogue (SMS 201-995) in 10 patients with gastrinoma syndrome. Four had hepatic metastases, one had a tumor in a peripancreatic lymph node, two had resectable intrahepatic and intraduodenal gastrinomas, and in three the primary tumor was not found. Acutely, SMS 201-995 decreased acid secretion and restored the BAO/MAO ratio to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized in eight of eight patients. Suppression of endogenous gastrin restored responsiveness to exogenous gastrin. Treatment for up to 12 months with SMS 201-995 controlled symptoms in six of eight patients, suppressed serum gastrin in three of five, and suppressed acid secretion in three of three patients. Treatment with SMS 201-995 in three patients for 5 months decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted in two of three patients 48 hours after withdrawal of SMS. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 12 months did not inhibit tumor growth or decrease gastrin levels. SMS treatment arrested progression of tumor growth only in patients who had a reduction in gastrin and gastric acid secretion. We conclude that SMS may be useful in the management of gastrinoma patients by decreasing hypersecretion of gastrin and gastric acid and, over a longer term, may even change tumor capacity to release gastrin and gastric acid secretion. SMS may thus be useful as a palliative agent and as an adjunct to conventional treatment of the gastrinoma syndrome. SMS does not appear to shrink tumor mass in patients with very high basal gastrin levels.
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PMID:Somatostatin analogue (SMS 201-995) in patients with gastrinomas. 290 62

Eight patients with stomach cancer are described who had also a striking glandular hyperplasia of the fundic mucosa adjacent and remote from the tumor. Five of the eight patients were young women (30 to 37 years of age). The tumors were poorly differentiated carcinomas and six of the eight patients have died of their disease. None of the patients had clinical evidence of endocrine dysfunction including the Zollinger-Ellison syndrome. Immunohistochemistry revealed cells with endocrine differentiation in five of eight tumors, and in two tumors gastrin producing cells were found. Five of seven patients showed increased numbers of antral G-cells. In two patients numerous endocrine (chromogranin-positive) cells were present in the fundic mucosa, specific products of which could not be identified with the antigens tested. No satisfactory explanation exists for this coincidence and its apparent predominance in young female patients. It may be that endocrine substances are responsible for this fundic hyperplasia and that they may also act as promotors of tumor growth.
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PMID:Coincidence of fundic glandular hyperplasia and carcinoma of the stomach. 291 Apr 42

Gastrin has been shown to stimulate the growth of carcinogenic-induced colon cancer in animals, and some human colon cancers grown in vitro or as xenografts in nude mice. We determined fasting plasma gastrin levels in control subjects and patients with adenomatous polyps or adenocarcinoma of the colon to determine whether abnormal levels occurred in either patient group. Blood samples were obtained from 73 patients undergoing colonoscopy, primarily for evaluation of Hemoccult-positive stools. Fasting plasma gastrin was significantly greater in patients with adenomatous polyps (24.2 +/- 5.7 pM, N = 25) or colon cancer (84.5 +/- 28.5 pM, N = 20) than in controls (9.9 +/- 0.9 pM, N = 28). Elevations were due to gastrin values greater than control mean + 2 SD in nine patients with polyps (19.5-150.2 pM) and eight with cancer (20.7-403.2 pM). None of the patients had identifiable causes (drugs, prior surgery) for elevated gastrin levels. Our results indicate that elevated plasma gastrin occurs in subgroups of patients with adenomatous polyps or adenocarcinoma of the colon. The cause and potential role of elevated gastrin for polyp and tumor growth in these patients is not known.
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PMID:Elevated gastrin levels in patients with colon cancer or adenomatous polyps. 291 35

This study deals with the effect of four types of COOH-terminal cholecystokinin (CCK) fragments on the growth of xenotransplantable human gastric cancer (SC-6-JCK, a poorly differentiated adenocarcinoma) whose growth has been promoted by pentagastrin. The growth of the tumor was inhibited using daily s.c. injections of CCK-octapeptide (CCK-8) and glutaryl-CCK-8 at a dose of 500 micrograms/kg body weight. After 30 days of treatment with CCK-8 or glutaryl-CCK-8, a significant decrease was observed in the tumor weight (P less than 0.05) and the tumor size P less than 0.01) in comparison with those of the control. But treatment with CCK-12 and pyroglutamyl-CCK-8 did not produce inhibition of tumor growth. Furthermore the correlation between the effect of CCK-8 on the normal rise in tumor cyclic adenosine 3':5'-monophosphate (cAMP) levels caused by pentagastrin injection and tumor growth was studied. The increase of cAMP by a single i.p. injection of pentagastrin at a dose of 20 micrograms/mouse was significantly inhibited by pretreatment with CCK-8 at concentrations equimolar to pentagastrin (P less than 0.05), while cAMP in the tumor was slightly elevated by a single i.p. injection of CCK-8 alone. Also in the in vitro study, CCK-8 inhibited the increase of cAMP and the activation of cAMP-dependent protein kinase which was stimulated by pentagastrin. These results suggest that proliferation of gastrin-dependent human gastric cancers may be suppressed by CCK in competition with gastrin.
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PMID:Cholecystokinin inhibition of tumor growth and gastrin-stimulated cyclic adenosine 3':5'-monophosphate metabolism in human gastric carcinoma in nude mice. 300 May 84

We recently reported trophic response of transplantable mouse colon cancer cells (MC-26) to pentagastrin, in vivo, and demonstrated gastrin receptors on MC-26 cells, in vitro. In the present study, growth of MC-26 cells in mice, in response to pentagastrin, was studied in relation to binding kinetics and capacity of gastrin receptor. Gastrin receptor levels on mouse fundic and colonic membranes and on MC-26 cellular membranes were determined before MC-26 cell inoculation and designated as Day 0 levels. Four groups of mice were next inoculated with MC-26 cells and given injections of either pentagastrin (treated) or normal saline (control) for 10 or 15 days. At the end of the treatment periods, body, tumor, fundic, and colon weights were noted and gastrin receptor measured. tumor and fundic weights increased significantly within 15 days of pentagastrin treatment, compared to control values. In control (non-pentagastrin treated) mice, the binding affinity of gastrin receptor on tumor membranes was significantly decreased and associated with the complete loss of high-affinity gastrin receptor (Kd = less than 0.5 nM) by Day 15 of tumor growth. On the other hand, both the binding affinity and gastrin receptor levels of tumor membranes were maintained at Day 0 values by pentagastrin treatment. Endogenous gastrin was therefore ineffective in maintaining high-affinity gastrin receptor on control tumors. A significant number of low-affinity gastrin-binding sites (Kd = less than 2 nM) appeared in control tumors by Day 15, which could reflect rapid dedifferentiation or conformational changes of gastrin receptor in the absence of high levels of normal regulatory hormones. These studies demonstrate that the trophic effects of gastrin on MC-26 cells are probably mediated by its regulation and maintenance of the binding affinity and capacity of gastrin receptor on the cancer cells, in vivo.
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PMID:Role of gastrin and gastrin receptors on the growth of a transplantable mouse colon carcinoma (MC-26) in BALB/c mice. 300

Gastrin is trophic for normal gastric and colonic mucosa. We examined the potential trophic effects of chronic gastrin administration on the growth of mouse colon adenocarcinoma (MC-26). Thirty-three mice bearing transplantable MC-26 colon cancers were treated with varying doses (125, 250, or 500 micrograms/kg/day) of pentagastrin. Significant increases in tumor weight and DNA content were observed. Fundic mucosal weight and DNA content in these mice showed a dose-related trophic response. The weight of control fundic mucosa was 10 mg and rose to 20, 45, and 65 mg with increasing doses of gastrin. The DNA content of control fundic mucosa was 155 micrograms and rose to 220, 340, and 480 micrograms as the dose of gastrin was increased. Pentagastrin stimulated growth of the MC-26 colon cancer, but the threshold for gastrin-stimulated tumor growth was different from that of normal mucosal growth. The hyperplastic response of the fundic mucosa was increased by increasing gastrin doses; whereas, colon cancer hyperplasia was maximal at the lowest dose tested (125 micrograms/kg/day) and did not increase further with increasing doses of hormone. Mice bearing gastrin-stimulated tumors died at a significantly greater rate than did mice with untreated tumors (80% of control mice and none of the treated mice were alive at day 55). The effects of gastrin treatment on the growth of MC-26 colon cancer persist after treatment is discontinued; mice with tumors that were treated with gastrin for either 7 or 14 days and in which the treatment was stopped were all dead by 35 or 28 days, respectively, after the end of treatment.
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PMID:Gastrin stimulates growth of colon cancer. 395 54

Within the physiological range of other known releasing factors, human pancreatic tumor growth hormone releasing factor (hpGRF) is specific for GH release. Data concerning hpGRF action on cAMP and GH are consistent with the concept of cAMP acting as a second messenger for this releasing factor. hpGRF-stimulated GH release is Ca++ dependent. Exogenous hpGRF40 does not alter the interdigestive gastric motility or secretion of gastrin and motilin in dogs, while large doses of hpGRF stimulate somatostatin release into the hepatic portal blood of the rat. Significant GRF activity as determined by a rat pituitary perifusion system is confined within the median eminence and the arcuate nucleus, though detectable but insignificant GRF activity is present in other area of the hypothalamus and cortex in the rat. GRF activity is present in the ovine brain as well as in the gut. Both tissues contain large (between 4000-5000 daltons) and small (but possibly larger than 1000 daltons) m.w. GRF materials. GRF appears to be structurally different between species and more than one GRF may be present within the same species. One of the ovine brain peptides with GH-releasing activity was partially characterized as His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr- Lys-Arg-Try-Asn-Lys-Glu-Met- Ala-Lys--which is similar to rat GRF and porcine VIP having His at the N-terminus. Another peptide with GRF activity which eluted earlier on reverse phase HPLC and later on cation exchange chromatography has also been obtained in a pure form.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone releasing factors in the brain and the gut: chemistry, actions, and localization. 620 12


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