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 described on the membrane of neoplastic cells derived from the APUD system and their expression has also been demonstrated on small cell lung cancer (SCLC) in vitro and in vivo. 21 patients with SCLC were studied using 111In-octreotide (111In-OCT) scintigraphy. Scintigraphic examinations were performed following intravenous (i.v.) injection of 111 MBq 111In-OCT with whole-body scintigraphy and planar scintigraphy of the thorax as well as the SPET technique. No short-term side effects were described following 111In-OCT administration. We studied the 111In-OCT biodistribution in 3 patients with serial scintigraphies at 1, 5 and 24 h. We used the 5 h as standard scanning time for the following 18 patients. The scintigraphic results were compared with those of other conventional diagnostic procedures. 111In-OCT detected 86% (48/56) of the lesions already known at the time of scintigraphy. It was positive in all 20 SCLC patients and negative in one lung adenocarcinoma. 111In-OCT showed high sensitivity for mediastinal metastases (94%) and good sensitivity for bone metastases (75%) and abdominal lymph node metastases (71%). 111In-OCT did not detect two liver metastases. 111In-OCT detected five unknown lesions which were confirmed by other diagnostic examinations. 111In-OCT was also effective in cancer patients with low levels of NSE. Our study shows that 111In-OCT scintigraphy is a reliable, non-invasive technique to detect primary SLCL and its locoregional or distant metastases. The clinical utility of receptor status characterisation obtained with 111In-OCT scintigraphy should be evaluated by means of an appropriate prospective study.
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PMID:Somatostatin receptor imaging of small cell lung cancer (SCLC) by means of 111In-DTPA octreotide scintigraphy. 771 23

We evaluated octreotide scintigraphy in 81 untreated patients who were suspected of having bronchial carcinoma. Octreotide scintigraphy visualized the primary tumour in all of 40 patients with non-small-cell lung carcinoma (non-SCLC), and all of 26 patients with SCLC. In the remaining patients, other bronchial disease and metastases from extrapulmonary carcinomas were also visualized. Mediastinal lymph node involvement and distant metastases were recognized in 5 of 15 and 1 of 7 patients with non-SCLC, respectively. In vitro, none of the non-SCLCs were shown to bear somatostatin receptors. We postulate that the visualization of non-SCLC during octreotide scintigraphy is caused by binding of labelled octreotide to activated leucocytes or to proliferating neuroendocrine cells around the tumours. In patients with SCLC, radiologically suspected lymph node involvement was visualized for 21 of 25 sites. Distant metastases, especially to the liver and abdomen, were missed for 14 of 20 sites, most probably because no laxatives were administered and single photon emission tomography of the abdomen was not performed. The failure to recognize liver metastases is most probably due to a comparable uptake of radioactivity by the surrounding normal liver tissue. In 15 of 26 patients, previously unrecognized tumour sites were suggested during octreotide scintigraphy, leading to a downstaging of 5 of 14 patients with limited disease. Unexpected cerebral metastases were suggested in five patients with either limited or extensive disease. In all four of these for whom follow-up was available, cerebral metastases became manifest 5-8 months after octreotide scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The value of octreotide scintigraphy in patients with lung cancer. 782 21

Experimental evidence suggests that somatostatin analogues may have a role to play in the management of lung tumours. We evaluated membrane preparations of nine small cell lung cancer (SCLC) cell lines and of tumour samples from 3 patients with non-small cell lung cancer (NSCLC), 1 patient with an atypical carcinoid and another with a bronchial carcinoid for the presence of specific binding sites for RC-160, a potent growth inhibitory octapeptide analogue of somatostatin. Specific binding was noted on six of nine SCLC lines. Radio-receptor assay on the cell line NCI H 69 showed evidence of two specific binding sites for RC-160, one with high affinity and the other with low affinity. Binding sites were also found on all five tumour samples. Scatchard analysis indicated the presence of a single class of receptors with high affinity in each case. Histological assessment of the resected specimens before binding assay showed them to be comprised of tumour cells and necrotic tissue, stroma and/or inflammatory cells. Therefore, the specific binding of RC-160 may be to tissues other than the tumour cells. In 3 patients, from whom the tumour samples were obtained, radiolabelled somatostatin analogue scintigraphy using [111In] pentetreotide was performed prior to surgery. In all cases, the radiolabel localised the disease. This study demonstrates the presence of specific binding sites for RC-160 in SCLC. Furthermore, the detection of specific binding in vitro and in vivo in NSCLC and intrapulmonary carcinoids demonstrates that these tumours contain cells which express specific binding sites for somatostatin. These results suggest that RC-160 may have a role to play as a therapeutic agent in lung cancer.
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PMID:Somatostatin receptor expression in lung cancer. 783 44

The somatostatin receptor subtype 2 (SSTR2) was detected in a wide range of human and rat tumors using in vitro receptor binding ([125I]MK-678), receptor gene expression analysis, and immunoblotting techniques. The highest receptor concentrations were observed in the rat AR42J pancreatic and human small cell lung cancer (SCLC) cell lines, NCI-H69 and NCI-H345, with much lower levels detected in breast, prostate, melanoma, and hepatic tumors. Several human pancreas tumors were devoid of SSTR2. For all tumors showing detectable [125I]MK-678 binding, SSTR2 receptor mRNA was expressed. Furthermore, a mRNA transcript corresponding to a truncated isoform of SSTR2 was detected at low levels in the human SCLC NCI-H69 cell line, and likely represents a human homologue of rodent SSTR2B. Immunoblotting analysis using the SSTR2-specific antibody, 2e3, detected multiple immunoreactive protein species, including a predominant 150-kDa molecule, which could be blocked by the SSTR2-derived 2e3 peptide. Somatostatin (SRIF) peptides with high SSTR2 affinity and antiproliferative properties were potent inhibitors of [125I]MK-678 binding to several tumor types, suggesting that they may exert antitumor effects via the SSTR2 receptor.
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PMID:Detection of somatostatin receptor subtype 2 (SSTR2) in established tumors and tumor cell lines: evidence for SSTR2 heterogeneity. 785 74

The mechanism of ectopic adrenocorticotrophic hormone (ACTH) secretion was examined by studies on the effects of corticotropin-releasing hormone (CRH), dexamethasone, interleukin (IL)-1 beta and 2, somatostatin, calcium ionophore A23187, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 8-bromo-cAMP on pro-opiomelanocortin (POMC) expression and ACTH secretion from a human small cell lung cancer cell line COR-L103. None of these agents except TPA and A23187 had any effect on ACTH secretion from the cell line in short (0-8 hrs) or long term (1-4 days) cultures. In long term cultures, 1-100 nM TPA stimulated ACTH secretion dose-dependently, whereas 500nM A23187 inhibited ACTH secretion completely. When the cells were incubated with 10nM TPA plus 500 nM A23187, the inhibitory action of A23187 on ACTH secretion was suppressed by TPA. These results suggest that the mechanisms of ACTH secretion by COR-L103 cells and normal pituitary cells are different.
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PMID:Calcium ionophore A23187 inhibits ACTH secretion from a human small cell lung cancer cell line, COR-L103. 785 71

Lung carcinoma is the most common cause of death in the western world and is increasing particularly among women. Despite significant developments in our understanding of the molecular biology of this disease our ability to treat the various subtypes of lung cancer has been at a relative standstill for the past decade. Novel approaches to the therapy of lung tumours are required. Recent work has evaluated the potential role of somatostatin and its analogues in the treatment of lung cancer. Experimental evidence has demonstrated that lung tumours, in particular small cell lung cancer (SCLC), may express somatostatin. The significance of this expression has not yet been evaluated. Somatostatin receptors have been demonstrated on between 50-75% of SCLC cell lines and fresh tumour samples studied to date. Using radiolabelled somatostatin analogues SCLC tumours may be detected and localised in patients through scintigraphic imaging techniques. Studies have shown that SCLC cell line clonal proliferation may be inhibited in vitro with somatostatin analogues suggesting that the somatostatin receptors are functional. In-vivo growth inhibition studies have likewise yielded encouraging results with growth inhibition of somatostatin receptor positive SCLC xenografts and receptor negative SCLC and non-small cell lung cancer cell line xenografts. These latter result suggests that somatostatin analogues may inhibit tumour growth by indirect as well as direct means. These findings have laid the ground for formal clinical trials in the future.
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PMID:Somatostatin and the lung. 791 18

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In-pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.
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PMID:A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome. Assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide. 792 88

Somatostatin (SS) acts as a universal endocrine off-swich, and also inhibits the growth of neuroendocrine tumors through its specific receptors. Small cell lung cancer (SCLC) demonstrates some neuroendocrine characteristics and has been proposed as a candidate for treatment with SS and its analogues. In the present study, we investigated the expression of somatostatin receptor (SSTR) subtype (SSTR1 and SSTR2) mRNA in various human lung cancer cell lines by the sensitive reverse-transcription-PCR method and Southern blotting. The levels of expression of SSTR1 mRNA were higher in both SCLC and squamous cell carcinoma than in adenocarcinoma cell lines. Interestingly, SSTR1 gene expression was independent of that of SSTR2 in each SCLC cell line, although the expression of both genes showed a positive correlation in non-SCLC cells. Membranes from a cell line exhibiting highest expression of SSTR2 gene bound SS and its analogue, octreotide, with moderate affinity. These findings may provide useful information for the future clinical application of SS and its analogues for the treatment of lung cancer.
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PMID:Gene expression of somatostatin receptor subtypes, SSTR1 and SSTR2, in human lung cancer cell lines. 796 60

Human small cell lung cancer (SCLC) is a neuroendocrine tumour with a very poor prognostic. Receptors for somatostatin-14 and its synthetic analogue BIM23014 (Lanreotide) were characterized in 3 human SCLC xenografts (SCLC-6, SCLC-10 and SCLC-75) transplanted in nude mice. The binding activity of both iodinated ligands was tested by cross-linking assay. One major complex of 57kDa was identified by both ligands in all 3 tumours. Two other minor complexes were only detected by the natural ligand: 90kDa in all 3 tumours and 70kDa in 2 out of the 3 tumours (SCLC-6 and SCLC-75). Analysed by Northern hybridization, the expression of the gene encoding for the receptor subtype I was detected in all 3 tumours whereas the expression of the receptor subtype II was only detected in 2 out of the 3 tumours (SCLC-6 and SCLC-75). No receptor subtype III transcript was observed. The relative quantification of the detected messengers and of the cross-linked complexes determined by densitometry suggested that SCLC-6 contained a large amount of somatostatin receptors. SCLC-6 growing in nude mice was used to evaluate the antiproliferative effect of BIM23014. BIM23014 (250 micrograms, b.i.d. for 5 days) significantly inhibited tumor growth and had an additive effect with cis-platinum (1.5 mg/kg/day for 2 days) when given concomitantly. Values of the relative tumour volume as compared to control were: BIM23014 alone 57%, cis-platinum alone 57% and BIM23014 + cis-platinum: 78%. These experimental data suggest that BIM23014 given alone or in combination with cis-platinum could have a therapeutic potential in the treatment of somatostatin receptor positive SCLCs.
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PMID:Characterization of somatostatin receptors and growth inhibition by the somatostatin analogue BIM23014 in small cell lung carcinoma xenograft: SCLC-6. 801 59

Several native peptides can regulate tumour cell proliferation. After binding to specific membrane receptors they have the ability to stimulate or inhibit directly cell growth. Peptides can also control the regulation of endocrine or paracrine growth factor secretion. Agonist and antagonist molecules have been synthesized for therapeutic purposes. Hypothalamic neuropeptides are used in oncology. GnRH agonists lead to biochemical castration which is useful in treatment of hormone-dependent tumours (breast and prostate). Somatostatin analogues are beneficial in the treatment of gut neuroendocrine tumours and have demonstrated an antitumoural effect in experimental studies. Cytostatic agents, such as Gastrin Releasing Peptide antagonists, may be of interest as an adjuvant to chemotherapy or surgery in small cell lung cancer and other malignancies. The role of peptides in antigenic presentation, cell proliferation control and the metastatic process suggests a new therapeutic potential for these compounds. Progress in biotechnology could provide specific tools to screen new molecules and increase the understanding of mechanisms of action. Improvement in drug delivery techniques will allow for more convenient routes of administration.
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PMID:Therapeutic use and perspectives of synthetic peptides in oncology. 810 Jul 10


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