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)

A 67-year-old man presented with a pulmonary atypical carcinoid tumor with marked elevation of the serum alpha-fetoprotein (AFP) level to 181,000 ng/ml and no hepatic metastases. Immunohistochemistry revealed AFP-positive fine granules, sparsely distributed in some cells. The proportion of the concanavalin A nonbinding subfraction was 33.7%. Light microscopy revealed hyaline globules within or outside the clear and reticular cytoplasm of a few cells. These were ultrastructurally electron-dense materials similar to the hyaline bodies observed in yolk sac tumors. The Grimelius silver method stained only a few cells and very few cells showed a positive Masson-Fontana reaction. Electron microscopy revealed secretory granules measuring 220 nm on the average in scattered cells. Immunohistochemical studies showed 5-hydroxytryptophan in many cells and 5-hydroxytriptamine or serotonin in only a few cells. As for polypeptide hormones, gastrin was detected and in autopsy specimens carcinoembryonic antigen (CEA) immunoreactive cells were observed. Past case reports on the coexistence of carcinoid tumors and adenocarcinomas in the digestive tract suggest that the tumor cells in our case are also derived from primitive or stem cells of endodermal origin and expressed unusual differentiation in the course of treatment.
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PMID:Pulmonary atypical carcinoid tumor with marked alphafetoprotein production and features of an adenocarcinoma differentiation. 246 82

In order to compare histologic subtypes and endocrine profiles, immunohistochemical and silver stains were performed on 120 appendiceal carcinoids. Forty-three were predominantly insular; 21 were mixed insular, glandular, and trabecular; 33 were goblet cell; 17 were tubular; and five were clear cell carcinoids. Insular, mixed, and clear cell carcinoids were generally diffusely argentaffin and positive for chromogranin, neuron-specific enolase (NSE), and serotonin. Occasional tumors of insular or mixed patterns had scattered cells that stained weakly for glucagon, calcitonin, adrenocorticotrophic hormone (ACTH), somatostatin, cholecystokinin (CCK), human pancreatic polypeptide (HPP), or gastrin. Most had S-100-positive sustentacular cells. Less than half were positive for carcinoembryonic antigen (CEA). Many were cytokeratin-positive, but often focally. Goblet cell carcinoids contained few endocrine cells, but these were strongly argentaffin and positive for serotonin in nearly all, and positive for HPP in almost a third. Tubular carcinoids lacked argentaffinity and serotonin but were diffusely and strongly positive for glucagon. All goblet cell and tubular carcinoids were diffusely positive for CEA and cytokeratin. Somatostatin stained strongly in a single tumor, which had psammoma bodies and was in a patient with neurofibromatosis. In all groups, argentaffinity correlated with serotonin positivity, and argyrophilia with chromogranin positivity, although the latter was somewhat more sensitive. We conclude that among appendiceal carcinoids, the endocrine content varies according to histologic subtype.
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PMID:Appendiceal carcinoids: correlation of histology and immunohistochemistry. 247 45

We have measured gastrin receptors (GR) in surgical specimens from 67 patients with primary colon cancers in order to determine the clinical significance of GR in colon cancer. GR analysis was performed on these specimens, and 22 cancers (32.8%) had no detectable GR. Thirty-eight cancers (56.7%) had high-affinity (Kd less than 1.0 nM) levels of GR. Seven cancers (10.4%) had only low-affinity GR (Kd greater than 1.0 nM). Twenty patients (29.9%) had cancers with GR greater than 10 fmol/mg protein. Mean GR content was significantly greater (11.8 +/- 2.9 fmol/mg protein) in Dukes' Stage A and B cancers when compared to Stage C and D cancers (6.2 +/- 1.6 fmol/mg protein). A significantly greater percentage (52.4%) of patients in the early stages (A and B) had tumors with greater than 10 fmol/mg protein compared to patients with more advanced (C and D) cancers (19.6%). GR content did not correlate with histological differentiation, patient age, or preoperative carcinoembryonic antigen levels. No difference in the GR content was noted between left and right colon cancers or in patients of different sex or race. GR content of normal colon mucosa correlated with the GR content of colon cancers from the same surgical specimen, suggesting that these tumors maintain their normal complement of GR. In the early period of follow-up, 12 of 43 (28%) Stage C and D patients with GR less than 10 fmol/mg protein have died, whereas all 8 Stage C and D patients with GR greater than 10 fmol/mg protein are alive. GR content of colon cancers may have prognostic significance and may identify a group of patients with colon cancer that may benefit from hormonal therapy with antigastrin drugs.
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PMID:Clinical significance of gastrin receptors in human colon cancers. 291 Apr 67

A human gastric carcinoma cell line TMK-1 was established in vitro by the soft agar method from SC-6-JCK, a poorly differentiated adenocarcinoma xenotransplanted in nude mice. TMK-1 cells had a doubling time of approximately 35 hr and showed carcinoembryonic antigen (CEA), alpha 1-antitrypsin and secretory component immunoreactivity. Ultrastructurally, the tumor cells were characterized by numerous mitochondria, tubulovesicles and intracytoplasmic canaliculi filled with abundant microvilli. The growth of TMK-1 cells was promoted by 10nM human gastrin (G-17), 2 microM tetragastrin or 2 microM pentagastrin, among which human gastrin showed the most effective growth promotion. Moreover, incorporation of [3H]thymidine into TMK-1 cells was stimulated by gastrin in a dose-dependent manner. The content of cyclic adenosine 3',5'-monophosphate (cAMP) in TMK-1 cells was increased by gastrin treatment but decreased to the control level within 10 min. cAMP-dependent protein kinase was also activated by gastrin administration.
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PMID:Growth-promoting effect of gastrin on human gastric carcinoma cell line TMK-1. 300 17

Immunoreactivity for endocrine peptides (serotonin, gastrin, somatostatin, insulin, corticotropin, calcitonin, neurotensin, vasoactive intestinal peptide, and bombesin), cytoskeletal proteins (high and low molecular weight keratins), and tumor differentiation markers (chromogranin, neuron-specific enolase, carcinoembryonic antigen, S100 protein, and Grimelius stain) was sought on nine cervical and one vaginal poorly differentiated small-cell carcinoids. Dense-core secretory granules were ultrastructurally identified in all cases (seven of ten) in which tissue was available for electron microscopy. Immunoreactivity for endocrine secretory products was rarely noted, and only in a minority cell population (serotonin in two of ten). The majority of the tumors exhibited immunoreactivity for low molecular weight keratin (AE1/AE3 in eight of ten; CAM 5.2 in seven of nine), and three of ten tumors focally expressed high molecular weight keratin. Among the markers of neuroendocrine differentiation, neurospecific enolase was more frequently expressed (ten of ten) than chromogranin (five of ten) or argyrophilia (three of ten). Carcinoembryonic antigen was present in eight of ten tumors. S100 protein was absent in all cases. In summary, poorly differentiated small-cell carcinoids of the lower female genital tract, similarly to other small-cell endocrine tumors, occasionally exhibit focal glandular and squamoid differentiation, and only relatively infrequently or focally express immunohistochemically detectable endocrine secretory products, chromogranin, and argyrophilia.
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PMID:Endocrine and tumor differentiation markers in poorly differentiated small-cell carcinoids of the cervix and vagina. 302 70

The gastrointestinal hormone gastrin has been shown to stimulate the growth of normal colonic mucosa. To examine for a possible role of gastrin in the proliferation of cultured colon tumor cells, we have studied the effects of two gastrin receptor antagonists, proglumide and benzotript, and of antibodies to gastrin. We find that proglumide (50% effective concentration, 2 to 5 mM) and benzotript (50% effective concentration, 0.4 to 0.8 mM) inhibit the monolayer growth of six human colon cancer cell lines. Addition of exogenous gastrin abrogated the growth-inhibitory effect of proglumide. The anchorage-independent growth of colon carcinoma cells was also inhibited by the two gastrin antagonists. Also, a dose-dependent increase in carcinoembryonic antigen secretion was observed upon treatment with proglumide and benzotript in three cell lines examined. Half-maximal inhibition of labeled gastrin binding was observed at concentrations of 0.4 mM benzotript and 8.6 mM proglumide. In addition, antigastrin antiserum added to HCT 116 cells adapted to growth in serum-free medium resulted in a concentration-dependent inhibition of cellular proliferation. These data suggest that gastrin may function as an autocrine growth factor in colon carcinoma.
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PMID:Antiproliferative effects of gastrin receptor antagonists and antibodies to gastrin on human colon carcinoma cell lines. 319 91

Seventeen patients 40 yr of age and less with gastric carcinoma were studied retrospectively. Clinicopathological findings and survival data were collected on all patients. Immunohistochemistry for serotonin, gastrin, somatostatin, carcinoembryonic antigen, beta-human chorionic gonadotropin, and alpha-fetoprotein was performed and the results correlated with pathological and survival data. Patients were divided into two groups according to the presence or absence of endocrine markers in their tumors. The group with endocrine immunoreactivity tended to present with less advanced disease and had longer survival than the group without endocrine immunoreactivity (p less than 0.05). Although the number of patients in the study is too small to reach definite conclusions, our results are interesting in light of current knowledge of the pathobiology of gastric carcinoma and have important implications for future investigations.
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PMID:Gastric carcinoma in the young: a clinicopathological and immunohistochemical study. 352 36

A series of six ovarian strumal carcinoids was examined. The presence of thyroid follicular epithelium was conclusively proved by the presence of follicular cells immunohistochemically positive for thyroglobulin, and by the ultrastructural identification of non-neuroendocrine cells with features of thyroid epithelium lining the follicles. Progressive replacement of thyroid epithelial cells by carcinoid cells accounts for the predominance of neuroendocrine granule-containing cells and the scarcity of thyroid epithelial cells lining many of the follicles. A variety of neuroendocrine hormones and other immunoreactive substances was demonstrated within carcinoid cells, including somatostatin (five cases), chromogranin (five cases), serotonin (five cases), glucagon (four cases), insulin (two cases), and gastrin (one case). Only one case contained calcitonin-positive cells. None were carcinoembryonic antigen-positive or had amyloid deposits. The carcinoid element in five cases stained positively for prostatic acid phosphatase. While strumal carcinoid shares some features with medullary carcinoma of the thyroid gland, it has sufficient differences to warrant a separate designation.
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PMID:Strumal carcinoids of the ovary. An immunohistologic and ultrastructural study. 355 74

The prevalence of gastric carcinoid in fundic atrophic gastritis is probably greater than previously recognized. To help elucidate the clinicopathology of this syndrome, we report a series of 11 patients with solitary or multicentric carcinoid tumors. In these patients, basal gastrin levels and density of fundic mucosal endocrine cells were greater than that for patients with uncomplicated fundic atrophic gastritis (p = 0.02 and p = 0.002, respectively). The polypoid tumors, of which the largest measured 30 mm, frequently showed characteristic endoscopic features. They were all situated in the fundic mucosa, which showed micronodular endocrine cell hyperplasia. Small, endoscopically evident tumorlets, or "early carcinoids," limited to the lamina propria were observed in some patients. These lesions may represent intermediate stages between micronodules and invasive carcinoids, all of which infiltrated at least into the muscularis mucosae of the gastric wall. Although some consistent characteristics features were noted, there were structural variations. The cells were argyrophil but nonargentaffin and did not stain with conventional mucus stains. They did not stain significantly for carcinoembryonic antigen (CEA). The secretory product of these tumors remains to be identified. Ultrastructurally, some tumors were mainly composed of enterochromaffinlike (ECL) cells, but in other tumors most of the cells could not be classified.
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PMID:Gastric carcinoid associated with the syndrome of hypergastrinemic atrophic gastritis. A prospective analysis of 11 cases. 359 60

A morphologic, histochemical, and immunocytochemical study of 20 cases of pure gastrointestinal carcinoids, adenocarcinomas, and mixed neoplasms composed of both elements, so-called composite carcinoma-carcinoid tumors (CCC), was undertaken in order to correlate the morphologic patterns with the immunocytochemical localization of carcinoembryonic antigen (CEA), serotonin, and a battery of polypeptide hormones (calcitonin, glucagon, insulin, gastrin, somatostatin, and adrenocorticotropin [ACTH]). Paraffin sections from five pure carcinoids, seven pure adenocarcinomas, and eight CCC from the stomach, small bowel, appendix, and colon were studied with mucicarmine, silver impregnation stains, and a peroxidase-anti-peroxidase technic. Of the eight CCC, all were mucin positive, four were argyrophilic, and three were argentaffin positive. CEA was present in all eight, serotonin in seven, and calcitonin in one. No other neurohormonal peptides were demonstrated. The distribution of serotonin and CEA generally corresponded to the morphologic pattern, but discordance was observed in two cases, i.e., serotonin was not always localized to areas of carcinoid and CEA not always confined to areas of carcinoma. All five pure carcinoids demonstrated intracytoplasmic localization of serotonin, whereas none contained intracytoplasmic CEA. In two cases, CEA was present within acinar lumens only. The seven colonic adenocarcinomas were argyrophil and argentaffin negative. All contained CEA within the cytoplasm and in gland lumens. None contained serotonin. None of the neurohormonal peptides was localized in either pure adenocarcinomas or carcinoids. This study reveals that among gastrointestinal neoplasms displaying morphologic patterns of adenocarcinoma and carcinoid, immunocytochemical localization of CEA and serotonin confirms their bidirectional differentiation and justifies the designation "composite carcinoma-carcinoid."
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PMID:Composite carcinoma-carcinoid tumors of the gastrointestinal tract. A morphologic, histochemical, and immunocytochemical study. 389 86


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