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)

Within the physiological range of other known releasing factors, human pancreatic tumor growth hormone releasing factor (hpGRF) is specific for GH release. Data concerning hpGRF action on cAMP and GH are consistent with the concept of cAMP acting as a second messenger for this releasing factor. hpGRF-stimulated GH release is Ca++ dependent. Exogenous hpGRF40 does not alter the interdigestive gastric motility or secretion of gastrin and motilin in dogs, while large doses of hpGRF stimulate somatostatin release into the hepatic portal blood of the rat. Significant GRF activity as determined by a rat pituitary perifusion system is confined within the median eminence and the arcuate nucleus, though detectable but insignificant GRF activity is present in other area of the hypothalamus and cortex in the rat. GRF activity is present in the ovine brain as well as in the gut. Both tissues contain large (between 4000-5000 daltons) and small (but possibly larger than 1000 daltons) m.w. GRF materials. GRF appears to be structurally different between species and more than one GRF may be present within the same species. One of the ovine brain peptides with GH-releasing activity was partially characterized as His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr- Lys-Arg-Try-Asn-Lys-Glu-Met- Ala-Lys--which is similar to rat GRF and porcine VIP having His at the N-terminus. Another peptide with GRF activity which eluted earlier on reverse phase HPLC and later on cation exchange chromatography has also been obtained in a pure form.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone releasing factors in the brain and the gut: chemistry, actions, and localization. 620 12

Administration of human pancreatic tumor growth hormone (GH) releasing factor (hpGRF[1-40]) as a single injection to normal human subjects stimulates the secretion of GH in a dose-responsive manner. In the present studies, hpGRF(1-40) was infused in a graded stepwise manner over a 6-h period in order to determine whether the GH secretory response would be sustained. Normal adult males received four consecutive 90-min infusions of hpGRF(1-40) at doses of 1, 3.3, 10, and 33 ng/kg per min, preceded and followed by a 90-min saline infusion; and the plasma GH responses were compared with those during a separate control infusion. Plasma GH levels were significantly elevated by each hpGRF(1-40) infusion; and dose responsiveness was evident for the lowest three doses. Mean integrated GH secretory rates for the four doses were 1.95, 3.29, 4.29, and 3.65 times those of the respective control study. Plasma GH responses exhibited considerable variability, frequently decreasing during the latter part of each infusion; and at the highest dose, they decreased continuously beginning shortly after the onset of infusion. Episodic GH secretion occurred in individual subjects during each of the infusion periods. The possible contribution of hypothalamic somatostatin secretion to the diminished GH responsiveness was evaluated by determining plasma thyroid stimulating hormone (TSH) levels during the infusions and the TSH responses to thyrotropin-releasing hormone (500 micrograms i.v.) during a separate hpGRF(1-40) infusion of 2 ng/kg per min. Neither basal nor stimulated TSH levels differed between GRF-infused and control groups. The results indicate that GH secretion is dose responsive to hpGRF(1-40) infusions, though the response to hpGRF(1-40) infusions, though the response is complex. The absence of impaired TSH secretion provides evidence against a mediating role of somatostatin. The explanation for the loss of GH responsiveness remains undetermined but could include GRF-induced receptor down-regulation, a postreceptor effect, or, in spite of our negative results, a somatostatin-mediated inhibition.
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PMID:Plasma growth hormone responses to constant infusions of human pancreatic growth hormone releasing factor. Intermittent secretion or response attenuation. 642 98

Since somatostatin analogues have been shown to possess inhibitory activity on prostatic cancer cells in animal models, we studied the clinical effects of the long-acting somatostatin analogue octreotide in the treatment of advanced prostatic cancer. Five patients with metastatic prostatic cancer in relapse under hormonal treatment and with rapidly increasing levels of prostate specific antigen (PSA) received a subcutaneous infusion of octreotide in a dose of 400 to 1,000 micrograms/day for a period of 2 to 6 months. Patients were followed clinically and by monthly measurement of PSA levels. During treatment 3/5 patients showed a temporary halt in rising PSA levels, while another patient had a small decrease. This inhibitory effect however was lost after 1 to 3 months of therapy in 3 patients. The remaining patient died after 4 months before an escape of PSA levels was seen. Side effects consisted of mild diarrhoea in three patients. From this very preliminary data, it appears that octreotide in a dose of 400 to 1,000 micrograms/day may give only a moderate and temporary inhibition of tumor growth in patients with advanced prostatic cancer. Because of the limited effects the study was interrupted prematurely. Since higher doses, other somatostatin-analogues or the combination of LHRH analogues may give better results, further studies are needed to determine the potential therapeutic role of somatostatin-analogues in this group of patients.
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PMID:Octreotide in advanced prostatic cancer relapsing under hormonal treatment. 751 12

The mastomys rodent exhibits a genetic propensity to develop gastric carcinoid tumors. Utilizing acid inhibitory pharmacotherapy (histamine-2 receptor antagonists and proton pump inhibitors), we have demonstrated transformation from normal to neoplastic enterochromaffin-like (ECL) cells in a well-defined fashion over a period of 4 months. In addition, we have demonstrated inhibition of tumor growth with either somatostatin or histamine-1 receptor antagonists (terfenadine and cyproheptadine). In order to define the regulation of growth and secretion of transformed ECL cells, we developed an isolated pure ECL cell system. ECL cells secrete histamine in response to gastrinergic (gastrin), muscarinic (carbachol), and beta-adrenergic (isoproterenol) stimulation. Both cAMP and intracellular calcium-dependent mechanisms are involved in the process of histamine secretion.
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PMID:The mastomys gastric carcinoid: aspects of enterochromaffin-like cell function. 753 69

The place of the long-acting somatostatin analogue octreotide in the management of symptoms in patients with functional gastroenteropancreatic (GEP) tumors and of growth in patients with metastatic disease is reviewed in this report. Numerous studies indicate that octreotide is, currently, the therapeutic principle of first choice in the symptomatic treatment of patients with carcinoid syndrome, Verner-Morrison syndrome and glucagonoma syndrome but not of insulinoma and gastrinoma patients. A beneficial effect on tumor growth has been demonstrated in 40% of patients with metastatic GEP tumor with stabilization of the disease as the most favorable response. However, further studies have to identify subgroups of patients in whom octreotide alone or in combination with alpha-interferon inhibits tumor growth.
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PMID:Management of gastroenteropancreatic endocrine tumors: the place of somatostatin analogues. 769 32

Octreotide is a long-acting somatostatin analog that inhibits cell growth and hormone secretion. It has been successfully used in the management of a variety of endocrine tumors (i.e., acromegaly, carcinoid tumors, gastrinomas). In vitro, octreotide suppresses adenylate cyclase activity, DNA synthesis, and cell growth in cultured thyroid cell lines. Previous studies examining the use of octreotide in the treatment of medullary thyroid cancers, in vivo, report symptomatic improvement from tumor-related hormonal hypersecretion; however, octreotide's ability to suppress tumor growth was limited. In the present study, we examine the efficacy of long-term octreotide administration in six subjects with metastatic thyroid carcinoma, including Hurthle cell (one subject), medullary (one subject) and papillary or mixed papillary/follicular cancer (four subjects). All of the subjects had documented recurrences of their thyroid tumors despite appropriate therapy, and were considered to be untreatable by conventional therapeutic modalities (i.e., radioiodine or surgery). Subjects were monitored while receiving relatively high doses (4 mg daily) octreotide subcutaneously for up to 12 months. Octreotide therapy was very well tolerated; mild gastrointestinal symptoms persisted throughout treatment in one subject. Octreotide did not significantly decrease tumor markers (e.g., thyroglobulin, calcitonin, carcinoembryonic antigen). The carcinomas progressed during treatment, as evidenced by an increase in the size and/or number of metastatic lesions. In summary, in this small series subcutaneous octreotide administration did not appear to be efficacious in the management of advanced thyroid cancers.
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PMID:Octreotide therapy in advanced thyroid cancer. 771 6

We have studied a series of 22 human medullary carcinomas (MCTs), both primary and metastatic, using immunocytochemistry (ICC) to localize calcitonin and somatostatin peptide and in situ hybridization (ISH) to localize calcitonin and somatostatin mRNA. All tumors were positive for calcitonin peptide with ICC, which often showed considerable intercellular heterogeneity, with many cells having undetectable levels of calcitonin. However, calcitonin mRNA localized by ISH was much more uniformly distributed, indicating that MCT tumor cells may retain the capacity to both synthesize and store calcitonin, whereas others lose their storage but not their synthetic capacity. Somatostatin peptide and mRNA were found in tumors from 15 patients. In contrast to the pattern seen with calcitonin, somatostatin mRNA and peptide were usually found in single scattered cells. When correlation was possible, the same cell showed positivity for somatostatin mRNA on ISH and positivity for somatostatin peptide on ICC. However, in one tumor many more cells were positive for mRNA than for peptide, suggesting that only a proportion of cells retained the ability to store the peptide. The variation in cellular content of immunoreactive calcitonin is interpreted as resulting from either an increased tumor growth rate or reduced ability to store peptide in a less differentiated tumor. With somatostatin there was good correlation between mRNA and peptide content, but it occurred in single widely scattered cells, most tumor cells being negative for both peptide and mRNA. It is suggested that somatostatin production might be associated with a reduction in the growth of the cell concerned, either through a differentiation step or through a direct effect of the hormone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of calcitonin and somatostatin peptide and mRNA in medullary thyroid carcinoma. 772 49

Neuroendocrine liver metastases are rare, yet they represent an entity that has attracted much attention lately. The protracted course of neuroendocrine tumors and the hormone origin of their typical incapacitating symptoms constitute a logical basis for well founded and bespoke treatment. Demonstration of the liver secondaries is best done by ultrasonography (US) and contrast-enhanced computed tomography (CT), which on the whole have replaced the invasive angiography techniques. By use of histochemical and molecular biologic methods the exact nature of the tumor can be typified in tissue samples obtained percutaneously, laparoscopically, or surgically. Localization of nonpalpable metastases of the liver is best done by intraoperative US. Surgical removal of liver metastases is curative in some cases and is usually effective in relieving the symptoms. Also, palliative debulking or cytoreductive surgery is often worthwhile as it offers a chance of prolonged survival and symptom relief. Similar benefits are achieved by ischemic therapy preferably by temporary dearterialization, which in our department is done on an outpatient basis using a specially designed (externally controlled) occluder applied during a single laparotomy that includes debulking when appropriate as well as cholecystectomy. Hormonal therapy with somatostatin analogs may be used as a single treatment or in combination with ischemic therapy. It has an ensured symptom-reducing effect, whereas its influence on tumor growth is unsettled. Lately similar effects have been ascribed to human leukocyte interferon. In conclusion the specific characteristics of neuroendocrine tumors and the available treatment arsenal favor an active treatment approach in patients who have developed liver metastases.
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PMID:Neuroendocrine metastases of the liver. 774 Aug 14

Streptozotocin diabetes prevents induction of pancreatic tumors in several animal models, suggesting a pivotal role for islet cell products in the pathogenesis of pancreatic cancer. To test the hypothesis that altered gastrointestinal peptide levels in streptozotocin diabetes influence tumor growth, human pancreatic cancer cells (MIA PaCa-2) were implanted subcutaneously into streptozotocin diabetic nude mice. After 3 weeks, tumors in the control group weighed 43 mg and tumors in the diabetic group weighed 12 mg (P < 0.001). Plasma insulin and IGF-1 levels were significantly decreased in the streptozotocin-treated animals compared to those of control (insulin: 23 microU/ml vs 31 microU/ml, P < 0.001; IGF-1: 254 ng/ml vs 324 ng/ml, P < 0.001). In contrast, somatostatin and glucagon were significantly elevated in the streptozotocin diabetic group relative to control levels (somatostatin: 179 pg/ml vs 54 pg/ml, P < 0.001; glucagon: 290 pg/ml vs 134 pg/ml, P < 0.001). Competitive binding studies revealed specific cell surface receptors for insulin (Kd = 15.5 nM), IGF-1 (Kd = 30.0 nM), and somatostatin (Kd = 2.5 nM) on the MIA PaCa-2 cells. Receptors for glucagon were absent. In an in vitro cell proliferation assay, cell division was promoted by insulin (P < 0.01, max + 11%) and IGF-1 (P < 0.01, max + 10%). Somatostatin inhibited cell division (P < 0.01, max - 18%). No effect was seen with glucagon. The growth of pancreatic cancer, particularly in diabetes, may be influenced by gut peptides in a receptor-dependent fashion.
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PMID:GI hormonal changes in diabetes influence pancreatic cancer growth. 779 56

Recent evidence has shown that endocrine tumors are under an endocrine and an immune regulation, and that biotherapies with interferon or the long-acting somatostatin analog octreotide may be effective in the control of tumor growth and clinical symptomatology. Within the biotherapies of tumors, interleukin-2(IL-2) has appeared to play an essential role in the antitumor immune response. Despite its important antitumor role, very few studies have been carried out to investigate the possible use of IL-2 in the treatment of advanced endocrine tumors. Its potential toxicity would represent the main limiting factor for the clinical experiments with IL-2. Our previous studies have shown that the pineal hormone melatonin (MLT) may amplify the antitumor activity of IL-2, either through immunomodulating mechanisms or through a direct cytostatic activity by inhibiting tumor growth factor production. On this basis, we have performed a phase II pilot study with low-dose IL-2 plus MLT in 14 patients with untreatable endocrine tumors because of disseminated disease, lack of response to previous standard biotherapies or chemotherapies, or tumors for whom no effective therapy is available. Thyroid cancers, carcinoid and endodrine pancreatic tumors were the most frequent neoplasms. IL-2 was given at 3 million IU/day s.c. at 8 p.m. for 6 days/week for 4 weeks, corresponding to one cycle. MLT was given orally at 40 mg/day at 8 p.m. every day. In nonprogressed patients, a second cycle was given after a 21-day rest period. Patients were considered as evaluable when they received at least one complete cycle, and 12 patients were fully evaluable. According to WHO criteria, a partial response was achieved in 3/12 (25%) patients (carcinoid tumor: 1; neuroendocrine lung tumor: 1; pancreatic islet cell tumor: 1). Another patient with gastrinoma had a more than 50% reduction of tumor markers. Toxicity was low in all patients. This preliminary study suggests that low-dose IL-2 immunotherapy in association with the pineal hormone MLT may constitute a new well-tolerated and potentially active therapy of untreatable advanced endocrine tumors.
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PMID:Immunoendocrine therapy with low-dose subcutaneous interleukin-2 plus melatonin of locally advanced or metastatic endocrine tumors. 785 78


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