Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane receptors for luteinizing hormone-releasing hormone (LH-RH), somatostatin, and prolactin (PRL) were investigated in the Dunning R-3327H rat prostate adenocarcinoma specimens after in vivo treatment with microcapsules of the agonist [D-Trp6]LH-RH and the somatostatin analog RC-160. The LH-RH receptors showed a low-binding affinity (Kd = 54 nM) and high capacity (Bmax = 12.0 pmol/mg). Treatment with the [D-Trp6]LH-RH decreased the binding affinity (Kd = 0.52 microM). Specific somatostatin receptors, with Kd = 1.3 nM and Bmax = 543 fmol/mg, were also found. Treatment with [D-Trp6]LH-RH lowered Bmax to 44 fmol/mg, and administration of RC-160 reduced Kd to 30 nM. After the combined treatment with the two analogs, Kd and Bmax were decreased. Specific PRL receptors (Kd = 0.72 nM; Bmax = 161 fmol/mg) were also detected. Treatment with either analog reduced Bmax by 50%, but a much greater reduction of PRL binding capacity was revealed after in vitro dissociation of the bound endogenous PRL by MgCl2. The dramatic fall in the total number of PRL receptors after combination treatment with both analogs could be partially responsible for the decrease in the weight and volume of prostate tumors. The findings support the concept that analogs of LH-RH and somatostatin can inhibit tumors directly through their own respective receptors. One of several mechanisms of the antineoplastic activity of these analogs could be the elimination of tumor growth-promoting effect of PRL by the reduction of the total number of PRL receptors.
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PMID:Receptors for prolactin, somatostatin, and luteinizing hormone-releasing hormone in experimental prostate cancer after treatment with analogs of luteinizing hormone-releasing hormone and somatostatin. 289 78

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

The growth-inhibiting effects of the long-acting somatostatin analogue Sandostatin on the transplanted Dunning R3327-H androgen-sensitive rat prostate tumor were investigated. Recipient animals were male Copenhagen x Fischer F1 rats (N = 36). When mean tumor volume reached 700 mm3 (20 weeks following transplantation), the rats were divided into four groups: control; Sandostatin (100 micrograms/kg s.c. twice a day); castrate; castrate/Sandostatin. Tumor size was assessed by magnetic resonance imaging 21, 42, 63, 105, and 138 days subsequently. Administration of Sandostatin was interrupted between days 43 and 62. As assessed by transplant volume, Sandostatin caused a moderate (up to 50%) but highly significant (P less than 0.001) suppression of tumor growth in the intact rats; the effect was reversed when drug administration was stopped. In the castrates, in which tumor growth was markedly less than in intact rats, no significant effect of Sandostatin was seen. Analysis of the tumor growth rate demonstrated that Sandostatin led to a 19% reduction (P less than 0.05) in growth rate in intact rats and a 9% decrease (not significant) in castrates. These findings extend previous reports of partial suppression of various types of tumors in vivo with Sandostatin and other somatostatin analogues. Their relevance with regard to the possible use of Sandostatin in the treatment of prostatic carcinoma in humans is discussed.
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PMID:Partial inhibition of the growth of transplanted dunning rat prostate tumors with the long-acting somatostatin analogue sandostatin (SMS 201-995). 289 58

The effects of gastrin, proglumide (a gastrin receptor antagonist), and somatostatin on growth of human colon adenocarcinoma cell lines CX1, X56, and HT29 were examined in two experimental models. Nude mice bearing xenografts of colon cancer CX1 or X56 were treated for 14-25 days subcutaneously with saline, pentagastrin (0.5 or 1.0 mg/kg), proglumide (250 or 500 mg/kg), or somatostatin 14 (33, 100, or 300 micrograms/kg) twice daily. Tumor volume, weight, protein, and deoxyribonucleic acid were measured. HT29 cells were grown in vitro and the effects of gastrin 17, proglumide, and somatostatin on growth were evaluated by cell counts or [3H]thymidine incorporation. The larger dose of pentagastrin significantly increased tumor growth in the nude mouse (p less than 0.005) and gastrin induced a biphasic effect on deoxyribonucleic acid synthesis in tissue culture with significant increases of up to 39% (p less than 0.025). Somatostatin alone significantly inhibited tumor growth in two of the cell lines and also inhibited the gastrin-induced growth. Proglumide had no effect by itself but significantly inhibited gastrin-stimulated growth. These findings suggest that growth of some human colon cancers may be hormone-dependent.
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PMID:Effects of gastrin, proglumide, and somatostatin on growth of human colon cancer. 290 11

We have examined the effects of the somatostatin analogue (SMS 201-995) in 10 patients with gastrinoma syndrome. Four had hepatic metastases, one had a tumor in a peripancreatic lymph node, two had resectable intrahepatic and intraduodenal gastrinomas, and in three the primary tumor was not found. Acutely, SMS 201-995 decreased acid secretion and restored the BAO/MAO ratio to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized in eight of eight patients. Suppression of endogenous gastrin restored responsiveness to exogenous gastrin. Treatment for up to 12 months with SMS 201-995 controlled symptoms in six of eight patients, suppressed serum gastrin in three of five, and suppressed acid secretion in three of three patients. Treatment with SMS 201-995 in three patients for 5 months decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted in two of three patients 48 hours after withdrawal of SMS. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 12 months did not inhibit tumor growth or decrease gastrin levels. SMS treatment arrested progression of tumor growth only in patients who had a reduction in gastrin and gastric acid secretion. We conclude that SMS may be useful in the management of gastrinoma patients by decreasing hypersecretion of gastrin and gastric acid and, over a longer term, may even change tumor capacity to release gastrin and gastric acid secretion. SMS may thus be useful as a palliative agent and as an adjunct to conventional treatment of the gastrinoma syndrome. SMS does not appear to shrink tumor mass in patients with very high basal gastrin levels.
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PMID:Somatostatin analogue (SMS 201-995) in patients with gastrinomas. 290 62

Daily injections of somatostatin into mice with myeloid leukemia retarded the tumor growth. This myeloid leukemia is an insulin-dependent tumor (in that it grows more slowly in hypoinsulinemic diabetic mice than in nondiabetic animals). Since somatostatin decreased the level of immunoreactive insulin in mice with myeloid leukemia, and since the treatment with insulin abrogated the antileukemic effect of somatostatin, we attribute retarded growth of this leukemia to decreased secretion of insulin, caused by somatostatin.
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PMID:Somatostatin suppresses growth of murine myeloid leukemia in vivo. 611 Apr 47

We have recently reported the establishment of 16 series of calcitonin-producing transplantable rat medullary thyroid carcinoma. In the present study, these tumor series have been evaluated for the presence of somatostatin-like immunoreactivity. Each of the series contained detectable levels of both peptides. Immunoreactive somatostatin varied from less than 1 ng/mg of protein to almost 500 ng/mg of protein. The range of immunoreactive calcitonin was 0.3 to 30 micrograms/mg of protein. Although somatostatin-like immunoreactivity was always less than that of calcitonin, the levels in certain series were as high as those found in neural or endocrine tissues used for in vitro studies of somatostatin elaboration. No significant correlation was found between tissue levels of these two peptides. Two tumor lines were generated by initiation of tumor growth with cells from primary monolayer cultures. Levels of both immunoreactive calcitonin and somatostatin significantly differed from those of the parent lines, which were maintained by serial passage of tissue fragments only. Plasma somatostatin-like immunoreactivity assessed in two tumor series with high (149 ng/mg of protein) and low (1.5 ng/mg of protein) tissue levels was 3100 and 50 pg/ml, respectively. Gel filtration chromatography of tissue and blood extracts showed a predominant peak (greater than 90%) of immunoreactive somatostatin eluting at the position of the native hormone. Three other peaks were resolved in the tissue extract with estimated molecular weights of 14,000, 8,700, and 5,000. The high level of somatostatin-like immunoreactivity and the presence of multiple large forms suggest that certain tumor lines will prove valuable for studies of somatostatin biosynthesis and secretion.
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PMID:Tumor and plasma somatostatin-like immunoreactivity in transplantable rat medullary thyroid carcinoma. 611 Apr 76

Murine mammary aplastic carcinoma, when it is passed from one alloxan-diabetic animal to another, after several passages becomes conditioned to hypoinsulinemia by secreting its own substance(s) immunologically cross-reactive with insulin (SICRI). Although not cytotoxic, the total daily dose of 2.5 mg of synthetic linear somatostatin per one kg body mass, administered in three or more portions, retards tumor growth in normoinsulinemic mice and the proliferation of tumors preconditioned by three serial passages in diabetics. After the first passage, somatostatin treatment has no effect on the already slow growth of the unconditioned tumor. Somatostatin-reduced tumor proliferation is accompanied by the strong suppression of insulin and SICRI levels, respectively; this effect is completely abolished by the administration of modest doses of crystalline insulin. It is concluded that somatostatin retards tumor growth by diminution of plasma levels of insulin and SICRI, respectively.
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PMID:Somatostatin-reduced proliferation of murine aplastic carcinoma conditioned to diabetes. 612 80

Using animal models of acinar and ductal pancreatic cancer, we investigated the effect of analogs of hypothalamic hormones on tumor growth. In Wistar/Lewis rats bearing the acinar pancreatic tumor DNCP-322, chronic administration of [L-5-Br-Trp8]somatostatin-14 significantly decreased tumor weights and volume. Somatostatin-28 and the cyclic hexapeptide analog of somatostatin cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) failed to influence the growth of this tumor. The agonistic analog of luteinizing hormone-releasing hormone [D-Trp6]LH-RH also significantly decreased tumor weight and volume in this model and reduced testosterone levels and the weights of the ventral prostate and tests. In Syrian hamsters bearing ductal type of pancreatic carcinoma, chronic administration of [L-5-Br-Trp8]somatostatin diminished tumor weights and volume. The percentage change in tumor volume was significantly decreased when compared to control animals. In one experiment, cyclic hexapeptide of somatostatin also inhibited growth of this tumor. [D-Trp6]LH-RH, given twice daily or injected in the form of microcapsules for constant controlled release, significantly decreased tumor weight and volume and suppressed serum testosterone levels. Hamsters castrated 4 days after transplantation of the pancreatic tumors showed a significant decrease in weight and volume of these tumors. This suggests that pancreatic cancers may, at least in part, be sex hormone sensitive. [D-Trp6]LH-RH may decrease the growth of pancreatic carcinomas by suppressing androgens. Somatostatin analogs reduce the growth of pancreatic ductal and acinar cancers, probably by inhibiting the release or stimulatory action of gastrointestinal hormones on tumor cells (or both). Inhibition of animal models of pancreatic tumors by chronic administration of somatostatin analogs and [D-Trp6]LH-RH suggests that these compounds should be considered for the development of a new hormonal therapy for cancer of the pancreas.
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PMID:Inhibition of growth of pancreatic carcinomas in animal models by analogs of hypothalamic hormones. 614 60

We have examined the ability of a number of neuropeptides to increase tyrosine hydroxylase (TH) activity in the superior cervical ganglion in vitro. Secretin and vasoactive intestinal peptide (VIP) both increased TH activity, whereas angiotensin II, bombesin, bradykinin, cholecystokinin octapeptide, insulin, luteinizing hormone-releasing hormone, [D-Ala2, Met5]enkephalinamide, motilin, neurotensin, somatostatin, and substance P produced no effects. Secretin and VIP increased TH activity with an EC50 of 5 nM and 0.5 microM, respectively. The effects of these peptides were not altered by prior decentralization of the ganglia, by addition of hexamethonium (3 mM) and atropine (6 microM), or by lowering the concentration of calcium in the medium to 0.1 mM. Addition of carbachol (3 microM) potentiated the effects of both secretin and VIP on TH activity. Several gastrointestinal peptides with structural similarities to secretin and VIP were examined for their ability to increase TH activity. Glucagon, gastric inhibitory peptide and human pancreatic tumor growth hormone-releasing factor produced no effect at a concentration of 10 microM, while PHI increased enzyme activity.
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PMID:Acute stimulation of ganglionic tyrosine hydroxylase activity by secretin, VIP and PHI. 614 16


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