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)

This review addresses means for improving treatment results in small cell and non-small cell lung cancer. In small cell lung cancer lactate dehydrogenase and neuron-specific enolase seem to be important prognostic factors that may reflect not only tumor load but also growth rate. Chemotherapy seems to induce or select differentiated cells in small cell lung cancer, which focuses attention on other treatment modalities such as drugs, which can induce terminally differentiated nonproliferating cells. Scheduling of chemotherapy may improve survival, especially in extensive disease patients. Exciting new techniques for tumor targeting by a radiolabelled somatostatin-analogue and radiolabelled murine anti-epidermal growth factor are reported. The possible adverse effect of heterologous blood transfusions on survival after surgery of stage I and II non-small cell lung cancer remains a very important subject for investigation to solve the essential question whether the need for transfusion or the transfusion itself is the adverse prognostic factor. A possible improvement of survival of non-small cell lung cancer patients by chemotherapy should be investigated in patients with an excellent performance score and a small tumor load, eg, stage IIIa and IIIb patients. Neoadjuvant chemotherapy in such patients may improve survival but a better and especially more uniform design of the trials is urgently needed. Finally, the development of techniques to palliate terminally ill patients quickly and easily by reopening a closed bronchial lumen should be encouraged.
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PMID:Therapy for small cell and non-small cell lung cancer. 131 20

We have detected somatostatin receptors (SSR) by autoradiography in 3/4 established small cell lung cancer (SCLC) cell lines but not in two non-SCLC cell lines. The growth of 1/3 SSR positive SCLC cell lines was significantly inhibited by the long-acting somatostatin analogue octreotide (SMS 201-995, Sandostatin) 10(-9) M. We treated 20 SCLC patients with octreotide 250 micrograms three times daily for 1 week prechemotherapy (six patients) or at relapse after chemotherapy (14). Octreotide was well tolerated, and serum insulin-like growth factor-I levels were suppressed to 62 +/- 7% of pre-treatment levels. However there was no evidence of anti-tumour activity measured by tumour bulk or serum levels of neuron-specific enolase. In one patient metastatic skin nodules were shown to be SSR positive before and at the end of 2 weeks octreotide. Despite this the patient had progressive disease, and tumour cells obtained by fine needle aspirate before and after treatment showed no growth inhibition when cultured with octreotide immediately or following establishment as a cell line. In summary we saw little correlation between SSR expression and growth inhibition by octreotide, either in vitro or clinically.
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PMID:Experimental and clinical studies with somatostatin analogue octreotide in small cell lung cancer. 165 81

Two endocrinologically active octapeptide analogues (BIM-23014 C and BIM-23034) of somatostatin (SRIF) containing either an N- or C-terminal 3-(2-naphthyl)-D-Ala residue were examined for their ability to inhibit the in vitro receptor binding, clonal growth, and vasoactive intestinal peptide (VIP)-stimulated cyclic AMP formation in human small cell lung cancer cell (SCLC) line NCI-H345. Both SRIF peptides inhibited [125I]SRIF(Tyr11)-14 binding with IC50 values in the low nM range. Colony formation in the in vitro SCLC growth assay was also inhibited in the same concentration range, as was VIP-stimulated cyclic AMP formation. Therefore, octapeptide analogues of SRIF function as SCLC SRIF receptor agonists.
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PMID:Octapeptide analogues of somatostatin inhibit the clonal growth and vasoactive intestinal peptide-stimulated cyclic AMP formation in human small cell lung cancer cells. 168 16

Biopsy specimens obtained from eight patients with lung cancer were tested for content of somatostatin receptors by autoradiography. Somatostatin receptors were detected in two of three patients with small cell lung cancer (SCLC) but in none of five patients with non-small cell lung cancer (NSCLC) including adenocarcinoma (two), squamous cell carcinoma (two), and bronchoalveolar carcinoma (one). In those with SCLC, specific somatostatin receptor binding was evidenced only in tumor foci and not in surrounding stroma or normal lung parenchyma. Further tissue characterization by immunoperoxidase staining with the pancytokeratin monoclonal antibody, mAB-lu-5, revealed labeling to all of the NSCLC but to none of the SCLC specimen. Selective immunoreactivity was detected in both the SCLC and the NSCLC specimen to chromogranin and neuron-specific enolase (NSE) whereas none of the specimen had detectable immunostaining to somatostatin, bombesin, serotonin, adrenocorticotropic hormone, neurofilament, calcitonin, and synaptophysin. The identification of somatostatin receptors in primary human lung cancer may have a bearing on the biology of this disease and perhaps on the clinical application of somatostatin analogues in patients with SCLC.
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PMID:Identification of somatostatin receptors in human small cell lung carcinoma. 217 45

Production and secretion of neuroendocrine peptides by small cell lung cancer (SCLC) has been detected in the past years. Most recently the role of bombesin as an autocrine/paracrine growth modifier has been demonstrated. We used the soft agarose clonogenic assay to evaluate the influence of other neuroendocrine peptides on the in vitro proliferation of SCLC cell lines. Neuroendocrine peptides tested were adrenocorticotropic hormone, arginine vasopressin, calcitonin, glucagon, kassinin, neurotensin, physalaemin, somatostatin, and substance P. Experiments were carried out in serum-free and serum-supplemented media with and without serum-free incubation periods. Our results indicated that the amphibian undecapeptide physalaemin inhibits the clonal and mass culture growth of SCLC cell lines at picomolar concentrations. All other neuroendocrine peptides failed to influence SCLC growth in the test systems used. These results suggest a growth regulating effect of physalaemin and a potential new form of neuroendocrine peptide therapy for SCLC.
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PMID:In vitro growth inhibition of human small cell lung cancer by physalaemin. 243 62

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

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.
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PMID:Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects. 283 87

The effects of somatostatin (SRIF) on small cell lung cancer (SCLC) cell line NCI-H345 was investigated. SRIF had no effects on the basal cAMP levels or the secretion rate of bombesin-like peptides. VIP (1 microM) increased the cAMP levels approximately 10-fold and the secretion rate of bombesin-like peptides 3-fold. SRIF and its analogues inhibited the increase in the cAMP levels and the secretion rate of bombesin-like peptides caused by VIP. The order of peptide potency was (D-Trp8)SRIF > SRIF-28 = (Tyr11)SRIF > SRIF. These data suggest that functional SRIF receptors may be present on SCLC cells.
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PMID:Somatostatin inhibits the secretion of bombesin-like peptides from small cell lung cancer cells. 290 12

Growth hormone (GH)-releasing activity has been detected in extracts of carcinoid and pancreatic islet tumors from three patients with GH-secreting pituitary tumors and acromegaly. Bioactivity was demonstrated in 2 N acetic acid extracts of the tumors using dispersed rat adenohypophyseal cells in primary monolayer culture and a rat anterior pituitary perifusion system. The GH-releasing effect was dose responsive and the greatest activity was present in the pancreatic islet tumor. Small amounts of activity were also found in two other tumors (carcinoid and small cell carcinoma of lung) unassociated with GH hypersecretion. Each of the tumors contained somatostatin-like immunoreactivity but the levels did not correlate with the net biologic expression of the tumor. Sephadex G-75 gel filtration indicated the GH-releasing activity to have an apparent molecular size of slightly greater than 6,000 daltons. The GH-releasing activity was adsorbed onto DEAE-cellulose at neutral pH and low ionic strength, from which it could be eluted by increasing ionic strength. The GH-releasing activity was further purified by high pressure liquid chromatography using an acetonitrile gradient on a cyanopropyl column to yield a preparation that was active at 40 ng protein/ml. Partially purified GH-releasing activity, from which most of the bioactive somatostatin had been removed, increased GH release by pituitary monolayer cultures to five times base line. Enzymatic hydrolysis studies revealed that the GH-releasing activity was resistant to carboxypeptidase, leucine-aminopeptidase, and pyroglutamate-amino-peptidase but was destroyed by trypsin and chymotrypsin, indicating that internal lysine and/or arginine and aromatic amino acid residues are required for biologic activity and that the NH2-terminus and CO9H-terminus are either blocked or not essential. The results provide an explanation for the presence of GH-secreting tumors in some patients with the multiple endocrine neoplasia syndrome, type I, and warrant the addition of GH-releasing activity to the growing list of hormones secreted by tumors of amine precursor uptake and decarboxylation cell types.
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PMID:Partial purification and characterization of a peptide with growth hormone-releasing activity from extrapituitary tumors in patients with acromegaly. 624 40

To further investigate the antineoplastic efficacy and safety of somatostatin analogues, 2 trials were performed. Octreotide, SMS 201-995 (Sandostatin), was escalated in doses ranging from 1,500 micrograms to 6,000 micrograms daily in 14 patients with carcinoid. Somatuline, (BIM 23014C, Angiopeptin, Lanreotide) was given in doses ranging from 2,250 micrograms to 9,000 micrograms daily to 13 neuroendocrine patients (6 carcinoid, 2 atypical carcinoid, 3 pancreatic islet cell and 2 small cell lung cancer patients). All patients successfully completed dose escalations without significant adverse effects and were evaluable for toxicity. The dose limiting side-effect of octreotide was the injection volume. No dose limiting adverse effects have been observed with somatuline. Carcinoid syndrome symptoms were better controlled with higher octreotide doses. Thirteen patients were evaluable for octreotide's antitumor efficacy with a partial response observed in 4 (31%), stable disease in 2 and progressive disease in 7 patients. Radiographic changes of increased tumor necrosis occurred in 5 patients and was independent of response. Somatuline resulted in a partial response in 4 patients (2 carcinoids, 1 gastrinoma and 1 small cell lung cancer) (31%), stable disease in 1 atypical carcinoid, and progressive disease in 8 (4 carcinoid, 1 atypical carcinoid, 2 islet cell and 1 multi-drug resistant small cell lung cancer). Six of the 8 carcinoid patients had radiographic changes of increased necrosis. Dose escalation of somatostatin analogues is well tolerated and may be associated with antitumor activity in some neuroendocrine neoplasms.
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PMID:Somatostatin analogue phase I trials in neuroendocrine neoplasms. 768 64


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