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)

Because of its widespread distribution within the nervous system and the gastro-enteropancreatic (GEP) system and its diverse physiological inhibitory actions on various gastrointestinal functions, including endocrine and exocrine secretion, motility, liver and splanchnic blood flow and absorption, native somatostatin has been viewed as a possible therapy for many diseases. However, its short duration of action and consequent limited clinical usefulness have been overcome with the availability of Sandostatin, a long-acting, synthetic octapeptide analogue of the naturally occurring hormone. Sandostatin represents a significant advance in the treatment of GH and TSH secreting pituitary tumours and GEP endocrine tumours (carcinoid tumour, VIPoma, glucagonoma, insulinoma, and gastrinoma). Preclinical in vitro and animal studies have shown the antineoplastic activity of the compound. Moreover, because of a possible direct effect on somatostatin receptor-positive endocrine tumour cells and indirect effect whereby Sandostatin lowers GH, IGF-1 and numerous gastrointestinal peptides, Sandostatin may prove useful as an adjunctive therapy in cancer patients. In vivo labelling of somatostatin receptor-positive tumours with radiolabelled somatostatin analogues now allows localisation of such tumours and their metastases. Moreover, targeted irradiation of these tumours by beta particle emitting isotopes attached to such somatostatin analogues may become possible. The use of Sandostatin in acute oesophageal variceal bleeding, pancreatic pseudocysts, gastrointestinal and pancreatic external fistulae, short bowel syndrome, dumping syndrome and AIDS-related refractory hypersecretory diarrhea has provided encouraging results. Preliminary reports indicate efficacy of Sandostatin in psoriasis, autonomic neuropathy (postprandial and orthostatic hypotension) and its ability to reduce height velocity in tall adolescents. The ultimate role of Sandostatin as a therapeutic agent in these disorders is being explored in prospective clinical trials.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Future medical prospects for Sandostatin. 198 Jul 78

Suramin is a polyanionic compound which has been used in the treatment of trypanosomiasis and acquired immunodeficiency syndrome (AIDS), while preliminary success has been reported in the treatment of cancer. However, suramin also causes adrenal insufficiency. We have previously reported that suramin selectively inhibited corticotropin (ACTH)-stimulated corticosterone release by dispersed adrenal cells in a dose-dependent manner via a direct interaction with the ACTH molecule. The present study was undertaken in order to investigate the effect of suramin on hormone release by dispersed rat anterior pituitary cells. Suramin at a concentration of 100 microM inhibited both basal and secretagogue-stimulated ACTH release by cells cultured in minimal essential medium (MEM) only, while it had no effect on ACTH release by cells cultured in MEM + 10% fetal calf serum (FCS) or MEM + 0.1% bovine serum albumin (BSA). In addition, suramin also caused a parallel decrease of prolactin (PRL) and growth hormone (GH) release by cells cultured in MEM only, suggesting a toxic, rather than a selective effect of suramin on anterior pituitary cells cultured in MEM only. In addition, suramin potentiated the effect of thyrotropin-releasing hormone (TRH) on PRL release by cells cultured in MEM + 10% FCS and suppressed the inhibitory effect of dopamine (DA) on PRL release by cells cultured in MEM + 10% FCS and in MEM + 0.1% BSA. Comparable suppressive effects of suramin on growth hormone-releasing hormone (GHRH)-stimulated and somatostatin (SRIH)-inhibited GH release were found in cells cultured in MEM + 0.1% BSA but not in cells cultured in MEM + 10% FCS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of suramin on hormone release by cultured rat anterior pituitary cells. 198 Aug 98

Somatostatin analogues have been suggested as possible therapy for human pancreatic cancer. This paper investigates the effect of the somatostatin analogue SMS 201-995 (Sandoz) in the Syrian golden hamster model of nitrosamine-induced pancreatic carcinogenesis. Step-wise increasing doses of i.v. SMS 201-995 suppressed pancreatic juice output from a median basal value of 212 mg/kg body wt/h (Q1:Q3 = 121:334) to a median basal value of 70 mg/kg body wt/h during infusion of 5 micrograms/kg body wt/h of SMS 201-995 (Q1:Q3 = 64:102, P less than 0.05). Chronic s.c. injection of 5 and 10 micrograms/kg body wt SMS 201-995 twice daily for 3 days each week, did not affect pancreatic wet wt or pancreatic total DNA content after 1 or 6 weeks of treatment when compared to controls. The most interesting and unexpected finding in our study was that SMS 201-995 seemed to promote pancreatic carcinogenesis when administered in low dosage. More SMS 201-995 treated animals receiving 5 micrograms/kg body wt developed invasive pancreatic adenocarcinoma than controls after 15 weeks of carcinogen (4/10 animals versus 0/10, P less than 0.05, Fisher's exact test) and pancreatic involvement by tumour was more extensive (17/75 pancreatic blocks affected versus 0/71, P less than 0.001). When carcinoma in situ and microcarcinomata were analysed with invasive lesions, animals injected with 5 micrograms/kg body wt SMS 201-995 were still significantly more affected than controls (33/75 blocks versus 9/71, P less than 0.001). Hamsters injected with the higher SMS 201-995 dose (10 micrograms/kg body wt) did not show any increase in malignancy over the controls. These results suggest that the effect of SMS 201-995 on pancreatic carcinogenesis in the Syrian hamster is complex and varies with dose administered. Further work is required before its use on man can be justified.
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PMID:The effect of the somatostatin analogue SMS 201-995 on experimental pancreatic carcinogenesis in the Syrian golden hamster. 204 91

PTH and calcitonin are the two major hormones controlling calcium metabolism. Recently two new substances related to these hormones have been isolated: calcitonin gene related peptide (CGRP) and PTH-related protein (PTHrP). CGRP is a potent vasodilator and stimulant of intestinal secretion while PTHrP is probably the agent responsible for humoral hypercalcaemia of malignancy. We report here a patient with a prostatic tumour presenting with vasodilation, diarrhoea and hypercalcaemia. Our investigations revealed that the primary prostatic and liver secondary tumour contained CGRP, calcitonin and PTHrP. Most of the immunoreactive CGRP in the tumour and plasma co-eluted with the biologically active form of CGRP. The circulating levels of CGRP correlated with the presence of the diarrhoea. PTHrP concentration in the tumours was one of the highest reported for any tumour although previous studies may have utilized less than optimal extraction procedures. The somatostatin analogue, octreotide (SMS 201-995), did not reduce the plasma CGRP or the diarrhoea, a finding similar to that seen in patients with medullary thyroid carcinoma and high plasma CGRP. The hypercalcaemia was also unaffected by octreotide administration. This is the first report of a prostatic tumour associated with over-production of calcitonin, PTHrP and CGRP. The major life-threatening effects of this unusual case of prostatic carcinoma were diarrhoea and hypercalcaemia. Both these effects could be tentatively ascribed to newly discovered substances, CGRP and PTHrP. With the greater availability of assays to measure CGRP and PTHrP in plasma, a detailed examination of the incidence of over-production of these substances in various cancers will be possible.
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PMID:Production of calcitonin gene related peptide, calcitonin and PTH-related protein by a prostatic adenocarcinoma. 206 Jan 48

Twelve patients with rectal carcinoma were treated for 2 weeks with the somatostatin analogue SMS 201.995. Effects of this therapy were assessed using serum marker concentration, Ki67 and gastrin-immunoreactivity of the primary tumour. In four out of 12 patients, a significant decrease in Ki67 immunoreactivity was seen during SMS 201.995 treatment while in the remaining eight patients there was no significant change in Ki67 expression. Four patients had elevated pretreatment serum carcinoembryonic antigen (CEA) levels. In two of these four patients, serum CEA levels fell modestly during SMS 201.995 therapy. This is the first clinical evidence that a somatostatin analogue can inhibit the growth of some colorectal cancers.
Br J Cancer 1991 Jun
PMID:The effect of long acting somatostatin analogue SMS 201.995 therapy on tumour kinetic measurements and serum tumour marker concentrations in primary rectal cancer. 206 53

The effect of enprostil and the somatostatin analogue SMS 201 995 on the growth of a clonal variant of the human gastric adenocarcinoma cell line, MKN45, was studied. The derived cell line grew twice as fast as MKN45 when grown as a xenograft line in nude mice. However, it did not respond trophically to gastrin either in vitro or in vivo (unlike MKN45) although it possessed the same number of gastrin receptors as the parental line. Gastrin production by the cell line during in vitro culture was twice that of MKN45; thus, the cell line was denoted MKN45G. When MKN45G was grown as xenografts in nude mice (n = 10/group), enprostil (20 micrograms/kg/day) significantly inhibited tumour growth when administered continuously by an osmotic mini-pump from day 1 to day 7 of a 20-day experiment, and induced tumour regression when administered from day 7 to day 14. Enprostil reduced postprandial serum gastrin levels when administered from day 7 to day 14 and prevented gastrin release by MKN45 in vitro. SMS 201 995 at doses of 25 and 240 micrograms/kg/day induced tumour regression when administered from day 1 to day 7 and the former dose reduced post-prandial serum gastrin levels at day 5. Gastrin release by MKN45G was not affected by SMS 201 995 in vitro, thus its effect may not be mediated directly via gastrin, requiring interaction between other hormones or growth factors in the in vivo situation.
Int J Cancer 1990 Jan 15
PMID:The effect of the E2 prostaglandin enprostil, and the somatostatin analogue SMS 201 995, on the growth of a human gastric cell line, MKN45G. 210 79

Pulmonary blastoma is an infrequent malignant neoplasm, so called because of its resemblance to fetal lung. The original description outlined the components as variable mixtures of epithelial and stromal elements. More recently, a variant displaying almost exclusively epithelial differentiation has been described. We report our findings in a case of pulmonary blastoma with predominance of epithelial cells, forming tubular structures and large morules. The architectural arrangement of the morules was remarkably similar to normal bronchial neuroepithelial bodies. Moreover, their immunohistochemical profiles were also very similar, including the expression of cytokeratins, chromogranin, neuron-specific enolase, synaptophysin, gastrin, calcitonin, bombesin, somatostatin and serotonin.
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PMID:Pulmonary blastoma with neuroendocrine differentiation in cell morules resembling neuroepithelial bodies. 212 6

In view of advancements in treatment of certain hormone-dependent cancers with analogues of luteinizing hormone-releasing hormone (LH-RH), this study was undertaken to establish the presence and characteristics of receptors for [D-Trp6]LH-RH on the membranes of human endometrial cancer. Specific binding of [125I,D-Trp6]LH-RH was demonstrated in membrane preparations from 24 of 31 (77%) endometrial carcinomas and from 3 of 13 (23.1%) nonmalignant human endometrial specimens. Ligand binding was dependent on temperature, time, and plasma membrane concentration in a fashion expected of a peptide hormone. Mathematical analysis of the binding data showed that interaction of [125I,D-Trp6]LH-RH with the binding sites was consistent with the presence of a single class of high affinity, noncooperative receptors (Kd 9.88 +/- 4.59 x 10(-9) M; Bmax 0.70 +/- 0.14 x 10(-12) mol/mg membrane protein). The rates of association and dissociation were calculated to be 6.5 x 10(6) M-1 min-1 and 0.021 min-1, respectively. [125I,D-Trp6]LH-RH binding was not displaced by either unlabeled somatostatin or epidermal growth factor, but was displaced completely by native LH-RH. Using 125I-epidermal growth factor, specific, high-affinity receptors were also detected in membranes from 22 of 26 (85%) endometrial cancers and in all of 6 nonmalignant endometrial specimens (Kd 0.42 +/- 0.12 x 10(-9) M; Bmax 0.30 +/- 0.15 x 10(-12) mol/mg membrane protein). The potential functional role of the receptors for [D-Trp6]LH-RH in human endometrial carcinoma is not clear, but this finding provides a rationale for the use of therapeutic approaches based on LH-RH analogues in this malignancy.
Cancer Res 1990 Mar 15
PMID:Detection and partial characterization of receptors for [D-Trp6]-luteinizing hormone-releasing hormone and epidermal growth factor in human endometrial carcinoma. 215 60

The binding of 125I-Tyr4 bombesin was investigated on plasma membranes of 8 human breast cancer cell lines and 2 long-term cultures of normal human breast epithelial cells. Scatchard plots were compatible with high-affinity, single-site class of receptors in 3 cell lines (KD of 0.75 x 10(-9) and 10(-9) M, Bmax of 0.75 x 10(-13) and 9.7 x 10(-13) M/mg protein in MDA-MB231 and in T47D cells, respectively) while no binding was observed in 5 other cell lines and normal epithelial cells. The neuropeptide and its structural analogues (natural or synthetic) inhibited the binding of 125I-Tyr4 bombesin in the following order of potency: gastrin-releasing peptide (GRP, EC50 = 1.7 x 10(-10) M) greater than BIM 26159 greater than bombesin, Tyr4 bombesin greater than BIM 26147 greater than litorin greater than neuromedin C. In contrast, 125I-Tyr4 bombesin binding was not displaced by neuromedin B, somatostatin, bradykinin and insulin. In agreement with our binding data, SDS-PAGE of the complex 125I-Tyr4 bombesin-receptor covalently linked by ethylene glycol-bis succinimidyl succinate (EGS) identified after autoradiography a single band with a molecular weight of 75,000, which disappeared in the presence of bombesin in excess. No transcription of either GRP or neuromedin B mRNA could be shown in tumor or normal cells. Exogenous gastrin-releasing peptide had no effect on growth of the cell lines when a serum-free medium was used, implicating that in breast cancer cell lines this receptor does not mediate growth but has a functional role.
Int J Cancer 1990 Aug 15
PMID:Characterization, in some human breast cancer cell lines, of gastrin-releasing peptide-like receptors which are absent in normal breast epithelial cells. 216 13

Somatostatin (SS) receptor status was investigated in the tumor tissues from 62 patients with carcinoid tumors and 15 patients with islet cell carcinomas using receptor autoradiography techniques with two different iodinated somatostatin analogues as radioligands, a [Leu8, DTrp22, Tyr25]somatostatin-28 and a somatostatin octapeptide, Tyr3-octreotide. The carcinoid tumors were either primaries (n = 32) or metastases (n = 43), sampled as surgical specimens or as small needle liver biopsies. Fifty-four of 62 carcinoid patients had SS receptor-positive tumors (87%). All 15 islet cell carcinoma patients had positive tumors (4 primaries, 11 metastases), i.e., 3 vipomas, 3 insulinomas, 2 glucagonomas, 1 gastrinoma, 2 polyfunctional tumors, and 4 nonfunctioning tumors. Saturation and competition experiments on tissue sections revealed saturable, high affinity binding sites pharmacologically specific for bioactive SS analogues. In a majority of the tumors, the receptors were densely distributed and were always homogeneously found in the whole tumor. All except two tumors were labeled with both radioligands. Multiple liver metastases (n = 16) from three different patients were all shown to contain a comparable amount of receptors. SS receptors could be demonstrated even in very small tissue samples of liver metastases obtained by percutaneous liver biopsies (mean weight, 6.8 mg). The majority of the eight SS receptor-negative carcinoids were mainly bronchial carcinoids (n = 5), usually poorly differentiated. On the contrary, SS receptor-positive cases were never found to be anaplastic. All tumors except one from patients pretreated with octreotide (3 days to 3.8 years) were SS receptor positive. In the majority of carcinoids or islet cell carcinomas, the SS receptor status correlated with the in vivo biochemical response (hormone inhibition) to octreotide. These data demonstrate (a) the high prevalence of SS receptors in the primary tumors of both carcinoids and islet cell carcinomas, (b) their presence in metastases as well, (c) their continuous expression even during long term octreotide therapy, (d) the possibility of measuring SS receptors in percutaneous needle liver biopsies, and (e) the evidence of their functionality. This study therefore suggests that tumoral SS receptors may be the likely molecular basis for octreotide action and may be an important parameter for predicting the therapeutic efficacy of SS analogues in carcinoids and islet cell carcinomas.
Cancer Res 1990 Sep 15
PMID:Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. 216 86


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