Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous studies have reported diverse effects of gut-derived regulatory peptides on growth of the normal pancreas, pancreatic neoplasms induced experimentally in animals, and pancreatic cancer cell lines, but the results of these investigations are rather controversial. The stimulatory effect of epidermal growth factor (EGF) on cell proliferation of pancreatic cell lines is well established. Whether this action can be modulated by somatostatin is not clear. Furthermore, it is not certain whether another regulatory peptide, cholecystokinin (CCK), affects the proliferation of these cells. In the present study we investigated the presence of CCK-A and CCK-B, as well as somatostatin-2 (SSTR2) receptors by RT-PCR, and studied the actions of EGF, CCK and octreotide on DNA synthesis in the human pancreatic adenocarcinoma cell line Capan-2. Octreotide, a long-acting somatostatin analogue was used as somatostatin agonist. Cells were cultured in RPMI-1640 medium. They were incubated in serum free medium containing 0.2% BSA in the absence (control) or the presence of the peptides. [3H]-thymidine incorporation into DNA was measured after 48 h of incubation. By means of RT-PCR analysis we were able to demonstrate SSTR2 expression, but not CCK-A or CCK-B receptor mRNA in Capan-2 cells. DNA synthesis evaluated by [3H]-thymidine incorporation was found to be increased by 45.2 +/- 5.6% in response to EGF (10(-8) M) and decreased by 11.7 +/- 2.6% to octreotide (10(-8) M) compared to controls (P < 0.01). The increase in [3H]-thymidine incorporation was significantly lower when EGF treatment was combined with octreotide administration (10.1 +/- 2.5% over control). In the concentration range of 10(-11)-10(-8) M, CCK did not alter significantly the incorporation of [3H]-thymidine into DNA in Capan-2 cells. In conclusion, these data support a role for EGF as a growth factor for the human pancreatic cancer cell Capan-2. Somatostatin may play an important role in regulating cell proliferation in Capan-2 cells both under basal, and growth factor-stimulated conditions. Our results suggest, however, that CCK receptors are not expressed, and CCK does not affect cell proliferation in this transformed pancreatic cell line.
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PMID:Inhibitory effect of a long-acting somatostatin analogue on EGF-stimulated cell proliferation in Capan-2 cells. 1076 90

Somatostatin is a neuropeptide produced by neuroendocrine, inflammatory and immune cells in response to different stimuli. Somatostatin inhibits various cellular functions including secretions, motility and proliferation. Its action is mediated by five specific somatostatin receptors (sst1-sst5) which belong to the G protein-coupled receptor family. The five receptors bind the natural peptide with high affinity but only sst2, sst5 and sst3 bind the short synthetic analogues used to treat patients with neuroendocrine tumors. The five receptors are expressed in various normal and tumor cells, the expression of each receptor being receptor subtype and cell-type specific. In neuroendocrine tumors, sst2 is highly expressed whereas in advanced pancreatic adenocarcinoma as well as high-grade colorectal carcinomas, its expression is lost. Each receptor subtype is coupled to different signal transduction pathways through G protein-dependent and -independent mechanisms. The synthesis of selective agonists for each receptor and the recent development of genetic animal models with selective deletion of receptor subtype provide tools for establishing some of the biological roles of the receptors. sst1, 2 and 5 mediate inhibition of GH secretion whereas sst2 and sst5 mediate inhibition of glucagon secretion and insulin secretion, respectively.
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PMID:Somatostatin receptors. 1094 Jun 84

Duct cell adenocarcinomas may produce neuroendocrine markers such as pancreatic polypeptide, gastrin and gastrin releasing hormones. A 53 year old patient, with a history of insulin dependent diabetes, was found to have a pancreatic mass which was later pathologically demonstrated to be a duct cell adenocarcinoma. The tumor produced elevated circulating neuroendocrine markers specifically gastrin and pancreatic polypeptides. An 111In Octreotide imaging showed definite uptake of Octreotide by the tumor. The patient was subsequently treated with Somatostatin analog which resulted in the reduction of some of the circulating endocrine markers. The patient had essentially six months of asymptomatic clinical remission but then she relapsed. Octreotide scanning could be useful for selected patients with pathologic diagnosis of duct cell adenocarcinoma, because some tumors may have neuroendocrine features and can be imaged, and might even respond to Somatostatin analog therapy.
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PMID:Pancreatic duct cell carcinoma with positive 111In Octreotide uptake. 1096 25

We report two cases of primary large cell neuroendocrine carcinoma (LCNEC) of the gallbladder, which, to the best of our knowledge, represent the first description of this entity. One of the tumors consisted entirely of LCNEC, whereas the second tumor was composed of LCNEC and the more common intestinal-type adenocarcinoma. Both tumors were morphologically similar to their pulmonary counterpart and were characterized by large cells with prominent nucleoli, coarse chromatin, and a high mitotic rate. The cells showed an organoid growth pattern with rosette formation and frequent areas of necrosis. Panendocrine markers were expressed in a variable proportion of tumor cells in both cases, and one of the cases also showed focal positivity for type 2 somatostatin receptors. One of the tumors followed a rapidly fatal course despite aggressive surgical treatment and chemotherapy administration, and the second patient is still alive and disease-free 12 months after surgery. The description of these two cases of LCNEC of the gallbladder is significant for two reasons. From an academic standpoint, we now know that all the neuroendocrine tumors described in other organs can arise de novo in the gallbladder. More importantly, however, the recognition of this rare tumor type carries important clinical implications in regard to the use of chemotherapeutic agents and supplemental treatments (for example, somatostatin analogs).
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PMID:Large cell neuroendocrine carcinoma of the gallbladder: report of two cases. 1102 6

The authors give an overview on the clinical treatment results of pancreatic carcinoma with somatostatin analogs including octreotide, lanreotide and vapreotide. Numerous preclinical studies provided solid evidence that the growth of ductal pancreatic adenocarcinoma can successfully be inhibited using such synthetic analogs via direct (apoptosis-inducing) and various indirect mechanisms. In the clinical practice their role still remains contradictory. Monotherapy did not result in a prolongation of the survival, however, in 15-20% of patients the progression of the process has been halted for several months accompanied by a significant improvement of the clinical condition without notable side effects. Combination of octreotide with tamoxifen yielded a survival benefit in addition to the stabilization of the general condition, although reduction of the tumor mass has not been documented. Despite the modest results these finding reinforce the responsiveness of the pancreatic ductal cancer to the hormonal manipulations and further studies on optimization of the effects are of worth. While in the majority of cases the somatostatin receptors have been lost, hormonal control of the pancreatic cancer could be achieved by combination treatment modalities.
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PMID:[Somatostatin analogs in the treatment of pancreatic cancer: utopia or feasible alternative?]. 1108 87

We report a patient with insulinoma associated with Zollinger-Ellison syndrome. A 67-year-old woman was first admitted to our hospital for an abdominal mass. Abdominal computed tomography (CT) revealed a large pancreatic tumor, which was then diagnosed as an unresectable pancreatic adenocarcinoma. At the age of 71, she presented symptoms of hypoglycemia. Fasting blood glucose was 21 mg/dl and plasma immunoreactive insulin level was 846 microU/ ml. Plasma gastrin, glucagon, vasoactive intestinal polypeptide and somatostatin levels were all normal. At the age of 73, hypoglycemic attacks occurred more frequently and she was admitted to our hospital. Abdominal CT scan showed multiple liver metastases. Chemotherapy with 5-fluorouracil and doxorubicin was performed. Three months later, she had an emergency laparotomy because of a perforated duodenal ulcer. Plasma gastrin level was 1,960 pg/ml at that time. Gastric hypersecretion was well controlled with a proton pump inhibitor (lansoprazole) but she died of widespread cancer dissemination 8 years after her first admission. On autopsy, histologic examination revealed a mixed acinar-endocrine carcinoma of the pancreas. Immunohistochemical stains were positive for insulin, gastrin, and alpha1-antitrypsin.
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PMID:Insulinoma with subsequent association of Zollinger-Ellison syndrome. 1139 7

We report a case of a human gastric composite tumor occurring seven years after a partial gastrectomy for a low grade B cell MALT lymphoma. Histological examination of the tumor revealed two intimately intermingled components: 1. A moderately to poorly differentiated tubulo-acinar adenocarcinoma with signet-ring cells; and 2. Isolated or clustered small neuroendocrine cells without atypia expressing chromogranin A, somatostatin and/or glucagon, serotonin (5-HT) and, the 5-HT2B receptors. In addition to immunohistochemical detection, the presence of 5-HT2B receptors was shown pharmacologically through [125I]-DOI binding. Since 5-HT2B receptors have been demonstrated to have autocrine functions and, mitogenic and transforming properties, these results suggest a role of 5-HT in neuroendocrine malignant transformation. On the other hand, the expression of somatostatin and the detection by reverse transcriptase polymerase chain reaction (RT-PCR) of somatostatin receptor subtypes 2, 3, and 5, which have been shown to be involved in tumor regression, might account for the long evolution of this case (> 5 yr). This case illustrates the importance of local humoral modulation in tumor growth. Moreover, ultrastructural results favor a unique origin of the tumor cells from one amphicrine cell type.
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PMID:Histological, immunohistochemical, ultrastructural and biochemical study of human gastric composite tumor: expression of the serotonin-2B receptor by the neuroendocrine component. 1147 72

Colonic carcinoma was induced in male Sprague-Dawley rats by injecting them with 1,2-dimethylhydrazine dihydrochloride. Control rats were injected with EDTA solution. Tissue specimens of colon from four groups of animals: (i) rats without tumour, (ii) with dysplasia and lymphoid hyperplasia, (iii) with colonic adenocarcinoma, and (iv) controls, were investigated. The colonic endocrine cells were detected by immunocytochemistry and quantified by computerised image analysis. Peptide YY (PYY)- and serotonin-immunoreactive cells were found in the colon of all the groups investigated. There were few somatostatin- or enteroglucagon-immunoreactive cells and no pancreatic polypeptide (PP)-immunoreactive cells in the colon of any of the groups studied. The density of PYY-immunoreactive cells increased significantly in rats with dysplasia and lymphoid hyperplasia and in rats with colon carcinoma. There was no statistically significant difference as regards cell secretory index (CSI) or nuclear area of PYY-immunoreactive cells in any of treated groups examined. Nor was there any statistically significant difference between all treated animal groups and controls, as regards cell density, CSI, or nuclear area of serotonin-immunoreactive cells. The present observations in an animal model of human colon carcinoma support the assumption that neuroendocrine peptides in the gut are involved in the carcinogenesis of colorectal carcinoma. However, The nature of the changes in the colonic endocrine cells observed here differed from those in patients with colon carcinoma, possibly due to a difference between the response of young rats to an induced colon carcinoma and a spontaneously developed carcinoma in elderly humans, or due to a species difference.
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PMID:Colonic endocrine cells in rats with chemically induced colon carcinoma. 1151 Sep 74

Somatostatin and its analogs have been included in experimental treatment protocols for advanced pancreatic adenocarcinoma based on their known antisecretory and antiproliferative properties. Somatostatin receptor type 2 (sstr2A) mediates antiproliferative actions of somatostatin and has the strongest affinity to the therapeutically used somatostatin analog--octreotide. We investigated localization of sstr2A in 27 pancreatic adenocarcinomas in relation to tumor histological features and neuroendocrine differentiation confirmed by immunoreactivity for chromogranin A (CgA), chromogranin B (CgB), or somatostatin. Immunoreactivity for sstr2A generally coincided with tumor neuroendocrine differentiation demonstrated by staining for CgA and was present on the cell membranes of pancreatic islet cells and endocrine cells occasionally present in the wall of normal pancreatic ducts. Thirteen pancreatic adenocarcinomas contained cells immunoreactive for sstr2A in numbers ranging from occasional single cells, cell clusters, or carcinoma duct segments. In two cases, cells immunoreactive for sstr2A and CgA represented more than 30 and 10% of the total tumor cell population (case 1 and 15, respectively). Case 1 fulfills the diagnostic criteria of mixed ductal endocrine carcinoma. We conclude that immunohistochemical staining for a generic neuroendocrine marker such as CgA would facilitate identification of a subgroup of pancreatic adenocarcinomas expressing sstr2A receptors. Future studies need to evaluate the responsiveness of these tumors to somatostatin analogue treatment.
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PMID:Somatostatin type 2A receptor immunoreactivity in human pancreatic adenocarcinomas. 1157 80

A 76-year-old man with chronic obstructive pulmonary disease and a smoking history had a 2-cm solitary pulmonary nodule that was likely to be malignant. He underwent Tc-99m-labeled somatostatin receptor-binding peptide SPECT. A computed tomographic-guided transthoracic needle biopsy performed before the SPECT was nondiagnostic. SPECT showed increased uptake of the tracer by the nodule, which was subsequently found to be adenocarcinoma by surgical resection. Differentiation of malignant from benign nodules by Tc-99m-labeled somatostatin imaging may be a reasonable approach in patients at high risk for cancer and concurrently at increased risk for complications from invasive diagnostic procedures or surgical resection.
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PMID:Tc-99m-labeled somatostatin receptor-binding peptide imaging for a pulmonary nodule. 1159 41


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