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)

Somatostatin receptors have been characterized on biopsy specimens from small-cell lung carcinoma (SCLC) and on cultured human SCLC cells. We recently described the in vivo visualization of various somatostatin receptor-positive tumors, such as carcinoids and endocrine pancreatic tumors, after injection of 123I-Tyr-3-octreotide, a radiolabeled somatostatin analog. In the present study, this imaging procedure using 123I-Tyr-3-octreotide is reported in 11 patients with lung tumors. In five of eight patients with SCLC (63%), we were able to demonstrate tumor deposits using 123I-Tyr-3-octreotide scintigraphy. Unexpected metastases were found in two patients. In one of three patients with SCLC in whom tumor was not visualized, nonvisualization may have been caused by tumor necrosis and recent radiotherapy. In one of two patients with malignant small-cell tumors as described by Askin, the neoplasm was visualized. Like SCLC, these tumors are thought to derive from neuroendocrine cells. In one patient, a squamous-cell carcinoma and a bronchial adenoma were not visualized. We conclude that in the majority of patients with SCLC, the tumor and its metastases can be visualized using 123I-Tyr-3-octreotide scintigraphy. However, the value of this new technique in terms of specificity and sensitivity requires further studies in a larger group of patients.
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PMID:Radioiodinated somatostatin analog scintigraphy in small-cell lung cancer. 165 97

Sixteen primary human lung tumours were analysed for their content of somatostatin receptors using receptor autoradiography with somatostatin-28 and somatostatin octapeptide analogues as radio-ligands. Two out of 4 small-cell lung carcinomas were somatostatin receptor-positive, with a high density of homogeneously distributed receptors on tumour tissue only. Somatostatin receptors were characterized in one of the tumours in homogenate binding assay as saturable, high-affinity binding sites (KD = 0.53 nM) with a number of sites (Bmax) equivalent to 189 fmoles/mg protein. These sites were specific for somatostatin, since only biologically active somatostatin analogues but not unrelated peptides showed high-affinity binding. Both receptor-positive patients had limited disease; furthermore, the small-cell lung carcinoma patient with the longest survival was receptor-positive, while the one with the shortest survival was receptor-negative. None of the 12 non-small-cell lung carcinomas (5 squamous carcinomas, 7 adenocarcinomas) contained somatostatin receptors. For comparison, epidermal growth factor receptors were found in all non-small-cell lung carcinomas. Neuroendocrine features (synaptophysin, chromogranin, neuron-specific enolase, protein gene product 9.5) were present in all small-cell lung carcinomas but absent in non-small-cell lung carcinomas. Given the receptor-mediated action of somatostatin in other neuroendocrine tumours, these data may have a bearing on the clinical application of somatostatin analogues in patients with small-cell lung carcinomas.
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PMID:Somatostatin receptors are present in small-cell but not in non-small-cell primary lung carcinomas: relationship to EGF-receptors. 196 52

Four human small cell lung carcinomas, NCI-H69, NCI-N417, NCI-H345, LX-1, and a non-small cell lung carcinoma, H-165, implanted s.c. as tumor xenografts in athymic nude mice, were treated with Somatuline (BIM-23014C), an endocrinologically potent octapeptide analogue of somatostatin. All tumors responded, although in varying degrees, with percentage of test/control values ranging from 3 to 88. Somatuline administered as a perilesional infusion effectively inhibited xenograft growth inducing prolonged remissions. When treatment was terminated, some tumors regrew, suggesting antimitogenic activity rather than cytocidal. Absence of observable systemic or local toxicity during prolonged treatment would support this conclusion and suggest the feasibility of long term maintenance therapy with a resultant extended survival.
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PMID:Response of human lung tumor xenografts to treatment with a somatostatin analogue (Somatuline). 197 71

Dynamic studies of growth hormone (GH) secretion were performed in two patients with ectopic GHRH syndrome. Patient 1 (female, 33 years old) had a growth hormone releasing hormone (GHRH) producing carcinoid of the lung with clinical features of acromegaly while patient 2 (50 years old male) had small cell carcinoma of the lung without acromegaly. Insulin hypoglycemia stimulated GH secretion in both patients (i.e. from a basal level of 10 mU/l to 48 mU/l in patient 1, while the respective values in patient 2 were 5 mU/l and 61 mU/l), TRH acutely stimulated GH in both patients. Synthetic GHRH 1-29 (KABI) i.v. bolus 100 micrograms did not stimulate GH release in either patient (i.e. basal GH 14 mU/l and peak 18 mU/l (patient 1); basal GH 4.6 mU/l and peak 8.8 mU/l (patient 2). It is concluded that: 1. prolonged pituitary exposure to GHRH is associated with chronic GH hypersecretion with or without clinical acromegaly; 2. GH response to TRH may be mediated at the pituitary level and results from prolonged exposure to GHRH; 3. the discordant response of GH after GHRH and insulin induced hypoglycemia might suggest the involvement (at least partially) of somatostatin in the mechanism of GH release after hypoglycemia and after GHRH.
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PMID:Discordance between growth hormone responses after growth hormone-releasing hormone (GHRH) and insulin hypoglycemia in ectopic GHRH syndrome. 211 55

Large cell neuroendocrine (LCNE) carcinomas of the lung are a newly recognized, highly aggressive and frequently misdiagnosed entity. We report a case of stage I LCNE lung carcinoma initially misdiagnosed as large cell undifferentiated carcinoma or poorly differentiated adenocarcinoma. The tumor was very extensively necrotic and its neuroendocrine differentiation was only demonstrable with immunohistochemical staining with PHE-5 monoclonal antibody and with antisera against synaptophysin and calcitonin. ACTH, somatostatin and neurofilaments were not demonstrable. The clinical course was ominous and the patient died within 17 months. The reason for this rapid fatal outcome could be ascribed either to the neuroendocrine phenotype of the tumor, or to the extensive necrosis, or both.
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PMID:Large cell neuroendocrine carcinoma of the lung. 255 26

A series of heptapeptide somatostatin (SRIF) analogs containing mercaptopropionic acid (Mpa) and based on the parent structure Mpa-Tyr-[D]Trp-Lys-Val-Cys-Thr-NH2 were synthesized by solid-phase methodologies and assayed for their effects on rat growth hormone (GH) secretion and their ability to displace [125I]Tyr11-SRIF bound to various tissues in vitro. Structural modifications consisted primarily of aromatic substitutions for Thr. All analogs were less potent than SRIF in inhibiting GH secretion in vitro from 4-day primary cultures of rat pituitary cells (0.04-21% that of SRIF). Higher GH inhibitory potencies were observed in an acute 15 min in vivo potency assay probably reflecting increases in plasma half-life of the analogs as compared to native SRIF. All analogs had extremely low binding affinity for rat cerebral cortex (0.05-4% that of SRIF), while binding potency for rat pancreas ranged from 3-130% of SRIF. Several analogs exhibited enhanced binding to human small cell lung carcinoma cells (SCLC; NCI-H69) as compared to SRIF. One of these, containing Phe at the C-terminus, exhibited an affinity 3.5 X greater than SRIF itself and was further tested for possible effects on the proliferation of SCLC and rat pancreatic tumor cells (AR42J) in vitro. The proliferation of both tumor types was inhibited 32 and 60%, respectively (p less than 0.01). The data suggest that SRIF and certain analogs may have a direct action on proliferating tumors independent of endocrine effects and that the anti-tumor activity of SRIF analogs can be further dissociated from the other actions of native SRIF, thereby providing for potentially more selective therapeutic analogs.
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PMID:Novel heptapeptide somatostatin analog displays anti-tumor activity independent of effects on growth hormone secretion. 257 97

Small-cell lung carcinoma (SCLC) is characterized by a consensus deletion in the short arm of chromosome 3. Using a panel of cell lines and somatic cell hybrids containing various rearrangements involving chromosome 3, we have localized the erbA beta sequence (which codes for a thyroid hormone receptor) to the region 3p21----3p25 which overlaps the consensus deletion in SCLC. Moreover, we have shown by Southern blot analysis that at least one copy of the erbA beta sequence is deleted in all six SCLCs so far studied. Normalized ratios of hybridization intensities of the erbA beta probe to intensities of probes for somatostatin (3q28) and raf(3p24-25) ranged from 0.28 to 0.56 and 0.32 to 0.71, respectively, in the six tumors and tumor lines. In view of the importance of the role these genes are known or suspected to play in biological regulation, our results suggest that the erbA beta sequence is a candidate for a recessive oncogene involved in the genesis of SCLC.
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PMID:erbA-related sequence coding for DNA-binding hormone receptor localized to chromosome 3p21-3p25 and deleted in small cell lung carcinoma. 289 38

Plasma samples from 21 patients with small cell carcinoma of the lung were screened for pancreatic polypeptide, somatostatin, motilin, and vasoactive intestinal polypeptide. One patient had severe impairment of both renal and liver function. In the 20 remaining subjects vasoactive intestinal polypeptide concentrations were normal, and only two patients had increased concentrations of somatostatin. Increases in pancreatic polypeptide were detected more commonly (7/20), but these may have been non-specific age related increases. The major finding was high concentrations of motilin (greater than 496 pg/ml) in 17 of 20 patients. Plasma motilin was subsequently assayed in 16 more patients with lung cancer, including 10 patients with non-small cell carcinoma of the lung. At concentrations over 900 pg/ml plasma motilin appears to be a tumour marker for small cell carcinoma of the lung with acceptable sensitivity (59%) and specificity (78%). The origin of increased plasma motilin in small cell carcinoma of the lung was investigated. Bombesin (gastrin releasing peptide), a peptide known to stimulate the release of motilin in man, was, as in previous studies, detected in tumour but not in plasma, except in one patient out of 21. Immunohistochemical studies failed to detect motilin antigen in biopsy samples. Motilin tumour content was found to be low in tumour tissue from three patients with small cell carcinoma of the lung who had appreciable hypermotilinaemia and from three patients with non-small cell carcinoma of the lung who had either normal or slightly raised plasma motilin concentrations. The stimulus to motilin secretion in patients with small cell carcinoma of the lung remains unclear.
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PMID:Increased plasma motilin concentrations in small cell carcinoma of the lung. 289 80

An endocrinologically-potent octapeptide analogue of somatostatin (SRIF), 3-(2-naphthyl)-D-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (BIM-23014 C), was examined for its ability to inhibit the in vitro and in vivo growth of the human small cell lung carcinoma (SCLC) line, NCI-H69. When cultured cells were implanted into athymic nude mice, treatment (500 micrograms/injection, twice daily) resulted in a prolongation of lag time for the appearance of measurable tumors, and there was a marked inhibition of the growth rate. Indeed, peptide injection in the region of the tumor resulted in a complete regression of the NCI-H69 tumors. Withdrawal of BIM-23014 C treatment resulted in an acceleration of tumor growth indicating an antiproliferative rather the oncolytic action. A similar inhibition of tumor growth was also observed when solid tumors obtained from the first implantation were used as the donor tissues. In cell culture, the proliferation in the presence of a low concentration (10nM) of BIM-23104 C was also significantly retarded suggesting a direct mechanism of action.
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PMID:In vitro and in vivo inhibition of human small cell lung carcinoma (NCI-H69) growth by a somatostatin analogue. 289 54

Continuous cell lines have been established from a variety of biopsy and postmortem species of tumor from patients with small-cell carcinoma of the lung (SCCL) and have been maintained over several years. The medium from the cultures has been assayed for peptide, glycoprotein, and steroid hormones. Significant amounts of 14 hormones including calcitonin, adrenocorticotropin (ACTH), parathormone, luteinizing hormone, chorionic gonadotropin, glucagon, growth hormone, somatostatin, prolactin, beta-endorpin, lipotropin, oxytocin-neurophysin, vasopressin-neurophysin, and estradiol have been demonstrated. Up to ten different hormones have been produced by a single cell line. Most produce ACTH and all evaluated so far produce estradiol. These studies indicate that cells from SCCL have a potential for producing a wide variety of hormones and that this characteristic can be maintained for prolonged periods of culture in vitro.
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PMID:Hormone production by cultures of small-cell carcinoma of the lung. 626 22


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