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)

Novel, powerful and long-acting inhibitors of gastric acid secretion include second generation H2-blockers and so-called proton pump inhibitors, such as omeprazole. Gastric carcinoids were found to develop in experimental animals as a consequence of continuous long-term administration of several of these highly effective anti secretory drugs. This unwanted side effect is now thought to reflect the fact (1) that pharmacological blockade of acid secretion results in hypergastrinaemia, and (2) that long-standing hypergastrinaemia gives rise to hyperplasia of certain endocrine cells, the so-called ECL cells, in the gastric mucosa. The carcinoids that develop in the rat stomach after lifelong treatment with antisecretagogues arise from the ECL cells. The proposed sequence of events is acid blockade--hypergastrinaemia--ECL cell hyperplasia--carcinoid. This concept, referred to as the gastrin hypothesis, maintains that the ECL cell hyperplasia (and possibly the carcinoids) is a consequence of long-term continuous hypergastrinaemia.
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PMID:Proposed mechanism of induction of gastric carcinoids: the gastrin hypothesis. 212

Ten patients with hepatic metastases from islet cell tumors or carcinoid tumors had clinical symptoms from hormonal secretion and/or pain related to the mass effect of neoplastic liver involvement. Hepatic arterial embolization (HAE) using radiographically guided catheters to inject thrombogenic material was applied to the right and/or left hepatic arteries separately 5 to 7 days apart. All ten patients improved within days of the procedure as confirmed by a decrease in measurable hormone levels (gastrin, adrenocorticotropin, and 5-hydroxy indole acetic acid) or by a decrease in tumor size and improved symptoms. Three patients underwent repeated reembolization from two to four times over nine to 50-month intervals for symptom control. Complications of and indications for HAE in these patients are discussed. It appears to be an effective treatment for dealing with the hormonal syndromes and local symptoms related to the hepatic metastases of hormone-secreting tumors.
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PMID:Hepatic arterial embolization for metastatic hormone-secreting tumors. Technique, effectiveness, and complications. 216 Dec 78

The effect of an octapeptide analogue of somatostatin, octreotide, on tumor blood flow was evaluated with angiography in eight patients with hepatic endocrine tumors; one patient had primary intrahepatic gastrinoma, two patients had hepatic metastases from gastrinomas, two patients had VIPomas (vasoactive intestinal polypeptide-secreting tumor), and three patients had carcinoid tumors. Octreotide caused a marked decrease in tumor blood flow in two patients with gastrinomas and two with VIPomas. One patient could not be evaluated due to the lack of a tumor blush on a control angiogram. In patients with carcinoid tumors, octreotide caused a slight reduction in blood flow through the tumors in two patients, while there was no change in one patient. Octreotide markedly decreased gastrin and gastric acid secretion in two of three patients with gastrinomas, lowered VIP and stopped the diarrhea in patients with VIPomas, and controlled symptoms in two of three patients with carcinoid tumors. The vasoactive effect of octreotide on hepatic endocrine tumors may be a direct action on tumor blood supply or secondary to inhibition of the endocrine tumor cell secretion and consequent decreased blood flow.
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PMID:Effect of somatostatin analogue (octreotide) on blood flow to endocrine tumors metastatic to the liver: angiographic evaluation. 217 Oct 15

A case of signet-ring cell carcinoid of the gallbladder is reported. The tumour diffusely infiltrated the gallbladder wall and extensively ulcerated the mucosa. Neoplastic nests were composed of numerous signet-ring cells mixed with clear endocrine cells. The latter expressed chromogranin A, gastrin and somatostatin and contained neurosecretory granules. The diagnostic problem of differentiating between signet-ring cell carcinomas and composite adenocarcinoma-carcinoid tumours is discussed.
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PMID:Signet-ring cell carcinoid of the gallbladder. 217 77

Newer potent and long-acting inhibitors of acid secretion, such as the proton pump inhibitor omeprazole, are becoming available for general use. These drugs promise to control acid-peptic disease effectively in patients who do not respond adequately to conventional short-acting H2-receptor antagonists. The safety of chronic administration of these drugs has come into question, however. Lifelong profound inhibition of acid secretion in rats induced by superpotent inhibitors of acid secretion or subtotal fundectomy is associated with the development of carcinoid tumors of enterochromaffin-like (ECL) cells in the gastric corpus. Available evidence supports a role of gastrin, which becomes chronically elevated in animals subjected to prolonged and profound hypochlorhydria. In humans, hypergastrinemic states such as Zollinger-Ellison syndrome and atrophic gastritis are associated with an increased risk of ECL-cell carcinoid tumors. Such observations have raised concern that humans may also be susceptible to carcinoid tumor formation in response to potent inhibitors of acid secretion. To date, however, no cases of carcinoid tumor have been attributed to the use of omeprazole in humans. If achlorhydric doses are not used, significant hypergastrinemia can be avoided while effectiveness of treatment is maintained. Such measures should minimize any risk of ECL-cell carcinoid tumors in humans taking potent long-term antisecretory drugs.
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PMID:The gastrin hypothesis. Implications for antisecretory drug selection. 224 96

Eighty-four carcinoids of the colon and rectum were studied with emphasis on prognostic features, immunohistochemical characteristics, and pitfalls in diagnosis. Follow-up data were available on 35 patients. Tumors with adenocarcinomatous components, or those resembling small cell carcinomas of the lung, were excluded. Eighty-one tumors were in the rectum and three tumors were in the distal sigmoid colon. Neuron-specific enolase, chromogranin, and Leu-7 were positive in 87%, 58%, and 53% of the tumors, respectively. Hormones were positive in the following percentages: serotonin, 45%; pancreatic polypeptide, 46%; glucagon, 10%; gastrin, 3%; somatostatin, 3%; adrenocorticotrophic hormone, 1%; cholecystokinin, 0%; calcitonin, 0%; and insulin, 0%. Many tumors elaborated more than one hormone. Fifty-five percent of the tumors were argyrophil and 28% were argentaffin. Carcinoembryonic antigen was present in 24% of the tumors; 82% of the tumors contained prostatic acid phosphatase. Three patients had liver metastases; their tumors ulcerated, invaded muscularis propria, and had more than 2 mitoses per 10 high-power fields (HPF). One patient with a 2.5-cm tumor without mitoses had regional lymph node metastases. All non-metastasizing tumors had less than one mitosis in 10 HPF. We conclude that large bowel carcinoid tumors are essentially limited to the rectum and sigmoid, that they are indolent if mitotically inactive and smaller than 2 cm, and that most show production of a selected group of endocrine markers.
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PMID:Rectal and colonic carcinoids. A clinicopathologic study of 84 cases. 229 59

Six cases of primary hepatic carcinoid tumors were studied with combined immunocytochemical and electron microscopic techniques. Positive tumor immunostaining with PHE5, LK2H10, neuron-specific enolase (NSE), serotonin, gastrin, and insulin antibodies was observed. At the ultrastructural level, cytoplasmic dense granules were seen in all the cases tested. This finding supports a putative origin of these carcinoids found in the liver from a pluripotential stem cell. The clinical course and follow-up of these cases suggests that this unusual hepatic neoplasm has a more favorable prognosis than other forms of hepatic cancer.
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PMID:A clinicopathologic study of primary hepatic carcinoid tumors. 230 69

Three monoclonal IgG 2a antibodies were produced after immunization of mice with dispersed cells from a human mid-gut carcinoid tumor. Acetone-fixed cryosections of 57 primary and metastatic mid-gut carcinoid tumors as well as 2 hind-gut (rectal) carcinoids showed a conspicuous immunoreaction while a thymic carcinoid was essentially unstained with the antibodies. The 3 antibodies yielded a similar pattern of immunostaining. The immunoreaction comprised more than 95% of the carcinoid tumor cells, and it was more uniform and intense in primary tumors than in mesenteric, hepatic, and ovarian metastases of the mid-gut carcinoid tumors. Immunofluorescence studies on suspended carcinoid tumor cells showed that the antibodies bound to the surface membrane of the cells. The antibodies immunostained enterocytes of the small and large bowel, intestinal metaplasia of the stomach mucosa as well as colorectal adenocarcinomas. Endocrine pancreatic tumors producing vasoactive intestinal polypeptide, gastrin, somatostatin, and/or pancreatic polypeptide as well as the epithelium of pancreatic ducts were also stained with the antibodies, whereas a large number of other normal and abnormal human tissues, including benign and malignant insulinomas, were unreactive. The findings indicate that the antibodies recognize differentiation antigens on the carcinoid tumor cell surface preserved also on endocrine and nonendocrine cells of the normal bowel mucosa. The restricted tissue reactivity of the antibodies suggests that they may constitute useful tools in the histological characterization of carcinoid tumors. Further studies may reveal if they are applicable for immunolocalization and perhaps even immunotherapy of these neoplasms.
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PMID:Monoclonal antibodies raised against mid-gut carcinoid tumor cells. 236 42

7 gastrinomes and 1 gastrin-producer complex carcinoma-carcinoid tumor were examined by light and electron microscopical-method and by immunohistochemical method. In six cases, the tumor was in the pancreas or in the wall of duodenum; in two cases its localisation was of extra-gastroenteropancreatic (liver, lymph node). All patients developed Zollinger-Ellison syndrome, three patients bled and one had diarrhea. One patient had other tumors, besides gastrinome, which were characteristic of MEN-I syndrome. By immunohistochemical methods all tumors proved to be gastrin and neuron-specific-enolase positive. In four cases somatostatin positivity, in some cases glucagon, pancreatic polypeptide, S-100 protein, keratin and carcinoembryonal antigen positivity were detected. Relation could not be detected between other polypeptide hormones, produced besides gastrin, and biological behaviour of tumor and clinical symptoms.
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PMID:[Gastrinoma and carcinoma-carcinoid tumor causing Zollinger-Ellison syndrome]. 238 29

The concomitant occurrence of neuropeptide-reactive endometrial carcinoma and ileal carcinoid tumor represents an observation that has been unreported until now. We have seen two patients with this rare combination of tumors. The endometrial carcinomas in these cases manifested focal immunoreactivity for neuron-specific enolase; in addition, one contained rare cells showing positive staining for gastrin, and the other displayed focal content of substance P. The carcinoid tumors seen in each case demonstrated immunocytochemical positivity for neuron-specific enolase and vasoactive intestinal polypeptide, and one also exhibited immunoreactivity for gastrin. Whether this association of neoplasms represents a syndromic complex or a coincidence is a matter of speculation at present.
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PMID:Concomitant neuropeptide-producing endometrial carcinomas and ileal carcinoid tumors. 242 Jan 66


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