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)

Eleven continuous cultures of human pulmonary small cell carcinoma cells were examined, and eight were shown to secrete quantities of somatostatin-like immunoreactivity (SRIF-LI) ranging from 0.07-27 ng/ml culture medium/4 days, SRIF-LI was also found in a 2-N acetic acid extract of one of three human pulmonary small cell carcinomas obtained at autopsy as well as in the extract of a solid tumor resulting from inoculation of nude, athymic mice with SRIF-LI-producing, cultured small cell carcinoma cells. The SRIF-LI produced by one continuous cell line, DMS 53, was characterized in terms of its immunological, chromatographic, and biological properties. SRIF-LI from DMS 53 culture media and lysed cells was heat stable and exhibited parallel displacement to synthetic SRIF standard in a double antibody RIA. DMS 53 SRIF-LI was quantitatively retained on an immunoaffinity column of sheep anti-SRIF-Sepharose 4B under neutral conditions and could be eluted with 2 N acetic acid. Gel filtration chromatography of immunoaffinity-purified SRIF-LI revealed multiple molecular weight forms, the largest of which had an apparent molecular weight of 10,000-12,000 daltons and may represent a precursor form. This high molecular weight SRIF-LI form was resistant to exposure to denaturing conditions (8 M urea or 4 M urea plus 0.5% mercaptoethanol), suggesting the absence of noncovalent and/or disulfide linkages. A low molecular weight form coeluted with synthetic SRIF. Additional evidence for the identity of this form with the tetradecapeptide was provided by highly specific reverse phase high performance liquid chromatography. The rate of degradation of high molecular weight SRIF-LI by the cultures was markedly reduced in comparison to that of the SRIF monomer, resulting in a preferential accumulation of high molecular weight SRIF-LI in 4-day culture medium. Bioactivity of DMS 53 SRIF-LI was assessed in 4-day primary monolayer cultures of rat adenohypophyseal cells where 10(-10)-10(-9) M synthetic SRIF elicited a linear log-dose suppression of 5 X 10(-4) M synthetic SRIF elicited a linear log-dose suppression of 5 X 10(-4) M dibutyryl cAMP-stimulated rat GH release. Immunoaffinity-purified SRIF-LI from DMS 53 lysed cells and 1-h serum-free incubation medium, which consisted predominantly of monomeric SRIF, was equipotent to synthetic SRIF, SRIF-LI from 4-day culture medium consisted mostly of the high molecular weight form and exhibited a reduced bioassay potency ratio relative to synthetic SRIF of 0.73 (95% confidence limits, 0.99-0.53). Chromatographically purified high molecular weight SRIF-LI had significant bioactivity with a bioassay to immunoassay ratio of 0.19 (95% confidence limits, 0.33-0.09). The demonstration of ectopic SRIF, production by human pulmonary small cell carcinoma is consistent with the proposed derivation of this tumor from a cell type in the amine precursor uptake and decarboxylation cell series.
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PMID:Ectopic production of somatostatin-like immuno- and bioactivity by cultured human pulmonary small cell carcinoma. 610 52

Neuroblastoma is the most common extracranial solid tumor of children. Neuroblastoma tumors derive from the neural crest and synthesize neurotransmitters including the neuropeptide somatostatin. This study was designed to characterize somatostatin receptors both in primary neuroblastoma tumors and in two neuroblastoma cell lines, SKNSH and IMR32. Somatostatin receptors were identified in 6 of 7 Stage I and II compared to 7 of 19 Stage III and IV tumors. Down-regulation of somatostatin receptor binding was observed in five tumors during disease progression. A lack of high affinity binding of somatostatin was identified as a poor prognostic indicator; negative binding correlated with advanced disease and death. Somatostatin receptor binding was observed in the IMR32 cell line, but not in the SKNSH cell line. IMR32 cells demonstrated a single class of high affinity binding sites for both somatostatin and a synthetic analogue, octreotide (Kd 0.16 +/- 0.05 nM and 0.89 +/- 0.23 nM, respectively). Somatostatin and octreotide inhibited both vasoactive intestinal peptide-mediated and forskolin-mediated cyclic AMP accumulation in IMR32 cells. Somatostatin and octreotide inhibition of signal transduction was attenuated by pretreatment of the cells with pertussis toxin. Octreotide inhibited proliferation of IMR32 cells by 70% in a 6-day culture. In contrast, octreotide did not exhibit high affinity binding in SKNSH cells and had no effect on cyclic AMP accumulation or on proliferation in SKNSH cells. Together, these data indicate that octreotide interacts with high affinity somatostatin receptors to modulate signal transduction and regulate proliferation in neuroblastoma cell lines. These data also suggest that somatostatin receptor expression may be an independent prognostic factor in primary neuroblastoma tumors.
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PMID:Characterization of somatostatin receptors on human neuroblastoma tumors. 812 88

We report a case of a 56-year-old male with a primary large cell neuroendocrine renal carcinoma. Grossly, the left kidney was enlarged by a solid tumor that measured 145 x 125 x 100 mm. Histologically, the tumor consisted of large cells with a moderate to abundant amount of eosinophilic cytoplasm. The nuclei were irregular, some of them with finely or coarsely granular chromatin, others with vesicular chromatin and prominent nucleoli. The tumor cells showed multiple mitotic figures (up to 32 mitoses/10 HPF). In some areas, the tumor cells were arranged in solid sheets; however, the predominant pattern was solid-alveolar, trabecular and cribriform. Large areas of tumor necrosis were found. Immunohistochemically, the tumor cells were positive for synaptophysin, CD56 and CD57. Cytokeratin AE1/AE3, vimentin and CD10 were positive only focally. Chromogranin showed weak cytoplasmic positivity in rare tumor cells. Cytokeratin CAM5.2, cytokeratin 34betaE12, BerEP 4, EMA, TTF-1, cytokeratin 7, cytokeratin 20, calretinin, serotonin, somatostatin, gastrin, calcitonin, glukagon and insulin were negative. Primary large cell neuroendocrine carcinoma of the kidney is a rare tumor. To the best of our knowledge, only 3 cases of a tumor of this type have been reported to date.
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PMID:Primary large cell neuroendocrine carcinoma of the kidney. 1957 58

Somatostatin receptors (sstrs) are G-protein-coupled receptors that mediate various physiological effects when activated by the neuropeptide somatostatin or its synthetic analogs. In addition to the well-documented antisecretory effects of sstr(2)-preferential somatostatin analogs octreotide and lanreotide, ligand binding to sstr initiates an inhibitory action on tumor growth. This effect may result from both indirect actions (suppression of growth factors and growth-promoting hormones [e.g., GH/IGF-1 axis] and inhibition of angiogenesis) and direct actions (activation of antigrowth activities [e.g., apoptosis]). As solid tumor cells express multiple sstrs, there is a rationale to evaluate the potential antitumor effects of pasireotide (SOM230), a multireceptor-targeted somatostatin analog with high binding affinity for sstr(1-3) and sstr(5). Pasireotide reduces systemic IGF-1 levels more potently than currently available somatostatin analogs and has been well tolerated in clinical trials.
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PMID:Somatostatin receptors in non-neuroendocrine malignancies: the potential role of somatostatin analogs in solid tumors. 2173 59

A 50-year-old woman presented for evaluation of an enlarging right cardiophrenic angle mass. Two years prior she complained of intermittent nausea, diarrhea, and flushing. Initial chest radiography and computed tomography (CT) suggested a pericardial cyst. Due to the onset of increasing dyspnea on exertion, lower extremity edema, and weight gain repeat CT was performed revealing a solid tumor. An Indium-111 octreotide scan showed somatostatin activity limited to the pericardiac mass. Histology after resection confirmed the diagnosis of peripheral bronchial carcinoid. The traditional differential diagnosis for a right cardiophrenic angle mass was misleading in this patient.
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PMID:Peripheral Bronchial Carcinoid Tumor Presenting as a Right Cardiophrenic Angle Mass. 2730 75

Neuroendocrine tumors (NETs) are rare in childhood. Neuroblastoma is the most common pediatric extracranial solid tumor, occurring >90% in children younger than 5 years of age. Pheochromocytoma and paraganglioma are rare NETs, causing hypertension in 0.5-2% of hypertensive children. Gastroenteropancreatic NETs can occur in children and are classified into carcinoids and pancreatic tumors. Nuclear medicine procedures have an essential role both in the diagnosis and treatment of NETs. Metaiodobenzylguanidine (MIBG) labeled with radioiodine has a well-established role in diagnosis as well as therapeutic management of the neuroblastoma group of diseases. During recent decades, establishing the abundant expression of somatostatin receptors by NETs first led to scintigraphy with somatostatin analogs (i.e. Tc/In-octreotide) and, later, with the emergence of positron-emitting labeled agents (i.e. Ga-DOTATATE/DOTATOC/DOTANOC) PET scans with significantly higher detection efficiency became available. Therapy with somatostatin analogs labeled with beta emitters such as Lu-177 and Y-90, known as peptide receptor radionuclide therapy, is a promising new option in the management of patients with inoperable or metastasized NETs. In this article, pediatric NETs are briefly reviewed and the role of radioactive agents in the detection and treatment of these tumors is discussed.
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PMID:A review of pediatric neuroendocrine tumors, their detection, and treatment by radioisotopes. 3304