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)

The authors conducted a phase II study of somatostatin analogue in 18 patients with extensive stage small cell lung cancer (four with previous treatment, 14 without previous treatment). Patients received 2,000 mg subcutaneously thrice daily. They were required to have an Eastern Cooperative Oncology Group performance score of 0-2 and acceptable pretreatment biochemical parameters. No patient responded to treatment. The median time to progression was 44 days. The median survival was 106 days. Toxicity related to treatment consisted of mild diarrhea and anorexia. Somatostatin analogue is not active as a single agent in the treatment of extensive-stage small cell lung cancer.
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PMID:Phase II study of high-dose somatostatin analogue in patients either previously treated or untreated who have extensive-stage small cell lung cancer. 1002 72

The hypothalamic satiety peptide CART (cocaine and amphetamine regulated transcript) is expressed at high levels in anorectic rat glucagonomas but not in hypoglycemic insulinomas. However, a non-anorectic metastasis derived from the glucagonoma retained high CART expression levels and produced circulating CART levels comparable to that of the anorectic tumors. Moreover, distinct glucagonoma lines derived by stable HES-1 transfection of the insulinoma caused severe anorexia but retained low circulating levels of CART comparable to that of insulinoma bearing or control rats. Islet tumor associated anorexia and circulating CART levels are thus not correlated, and in line with this peripheral administration of CART (5-50 mg/kg) produced no effect on feeding behavior. In the rat two alternatively spliced forms of CART mRNA exist and quantitative PCR revealed expression of both forms in the hypothalamus, in the different islet tumors, and in the islets of Langerhans. Immunocytochemistry as well as in situ hybridization localized CART expression to the somatostatin producing islet D cell. A potential endocrine/paracrine role of islet CART remains to be clarified.
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PMID:The hypothalamic satiety peptide CART is expressed in anorectic and non-anorectic pancreatic islet tumors and in the normal islet of Langerhans. 1021 34

To evaluate the neuroendocrinological dysfunction in anorexia nervosa, plasma somatostatin, glucose, insulin, and growth hormone were monitored in ten patients with anorexia nervosa in the active and refeeding (remission) phases of the disorder and in nine age-matched healthy control subjects. Somatostatin levels were significantly higher in the anorectic patients in both the active and refeeding phases than in the controls at baseline (mean+/-SD 27.4 +/-5.5 and 31.1+/-2.6 vs 21.3+/-1.9 pg/ml; p<0.001), and significantly higher in the anorectic patients in the active phase compared to the refeeding phase and to the controls in response to a mixed meal (p<0.05). Insulin levels were significantly lower in the anorectic patients in both the active and refeeding phases compared to the controls at baseline (9.3+/-1.1, 7.6+/-1.0 vs 14.7+/-3.5 microU/ml; p<0.0001) and after a mixed meal (p<0.05). An attenuated glucose response discriminated the anorectic patients in the active state from the same patients in the refeeding state and the controls (p<0.0001). There was no significant difference in growth hormone response between the anorectic patients and the controls. These findings suggest that there is an augmented response of somatostatin and an attenuated response of insulin to mixed meal stimulation in active anorexia. The diminished insulin response persists during the refeeding phase. It seems that central and peripheral alterations in endocrine function occur in anorexia nervosa.
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PMID:Neuroendocrinological response to standardized mixed meal in female anorectic patients during active and refeeding phases. 1071 66

Five callitrichids (three common marmosets -Callithrix jacchus -, a black tufted-eared marmoset -C. penicillata-, and a saddle-back tamarin -Saguinus fuscicollis) were diagnosed with islet hyperplasia by histopathology and immunohistochemistry. All were privately-owned, unrelated callitrichids ranging from 2- to 4-year-old. Relevant findings were anorexia (3/5), vomiting (2/5), ptyalism (1/5), polyuria/polydipsia (1/5), respiratory distress (1/5), hyperglycemia (2/3) and glycosuria (1/1); hyperglycemia and glycosuria were associated with pregnancy in a common marmoset and resolved after reducing simple carbohydrates in diet. All five animals died, three of them after few premonitory signs; in two cases, other concurrent diseases unrelated to islet hyperplasia were considered the cause of death. Additional animals from two facilities had high weight (4), physical obesity (3), polyuria/polydipsia/polyphagia/uriposia (1), hyperglycemia (1), and/or glycosuria (2). Pathologic findings in the deceased callitrichids were: islet hyperplasia (5/5); hemosiderosis (5/5); lipomatosis (4/5) of several tissues (atria, 3/5; pancreas, gall bladder, intestine, esophagus, and thyroid, 2/5; liver, 1/5); pancreatic necrosis or steatonecrosis, and/or acute pancreatitis (3/5); and vacuolation of hepatocytes and renal tubular cells most likely consistent with hepatorenal lipidosis (2/5). The islets of Langerhans were more numerous and larger than in a control, and morphologically normal in all cases, except in a common marmoset that had a few cells with a foamy cytoplasm and shrunken hyperchromatic or picknotic nucleus. Insulin (5/5), glucagon (3/5), and somatostatin (3/5) immunohistochemistry revealed that most cells stained positively for insulin diffusely in their cytoplasm (5/5) (staining restricted to the vascular pole of b-cells in the control). These findings suggest that obesity, insulin resistance and/or type II diabetes may be implicated and thus a prospective study on these diseases in callitrichids is necessary to determine their etiopathogenesis.
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PMID:Islet hyperplasia in callitrichids. 1214 99

Growth hormone (GH) secretion declines with aging in mammals, including humans. Defective pituitary function does not play a major role in this event. Rather, age-related changes involving the function of specific hypothalamic peptides for GH regulation, GH-releasing hormone (GHRH) and somatostatin (SS), appear to be the fundamental factors. Experimental evidence indicates that GHRH synthesis is impaired with aging in the rat hypothalamus, and that a relative hyperfunction of the SS-ergic system is present. In the elderly, systemic, short-term administration of GHRH enhances GH secretion and increases the formation of the GH-dependent peptide IGF-1. In old dogs, a combination of GHRH and clonidine (CLO), an alpha(2)-adrenoceptor agonist, reportedly acting via GHRH stimulation and SS inhibition, is the most effective stimulus to rejuvenate the apulsatile GH secretion. Discovery of GH secretagogues (GHSs), a series of peptydil and non-peptydil synthetic molecules endowed with a strong GH-releasing activity, the cloning of a GHS receptor (GHS-R), present in the hypothalamus and the pituitary, the isolation of the endogenous ligand of GHS-R, ghrelin, a 28-amino acid peptide whose main source is the stomach, pose the issue for the physiologic role of the GHS/ghrelin system and forces revision of our current understanding of GH regulation in different GH deficiency (GHD) states, including aging. GHSs are very effective for enhancing GH secretion in old subjects, but long-term studies are needed to assess their safety and the real biological impact of GHS replacement therapy in aging. Therapeutic use of GHSs can also be envisaged to restore, via GH-independent mechanisms, functional, and structural age-related alterations, such as anorexia, sexual dysfunction, cardiovascular damage, bone loss.
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PMID:GH-related and extra-endocrine actions of GH secretagogues in aging. 1239 95

Ghrelin is a 28-amino-acid peptide predominantly produced by the stomach, while substantially lower amounts derive from other tissues including the pancreas. It is a natural ligand of the GH secretagogue (GHS) receptor (GHS-R1a) and strongly stimulates GH secretion, but acylation in serine 3 is needed for its activity. Ghrelin also possesses other endocrine and nonendocrine actions reflecting central and peripheral GHS-R distribution including the pancreas. The wide spectrum of ghrelin activities includes orexigenic effect, control of energy expenditure, and peripheral gastroenteropancreatic actions. Circulating ghrelin levels mostly reflect gastric secretion as indicated by evidence that they are reduced by 80% after gastrectomy and even after gastric by-pass surgery. Ghrelin secretion is increased in anorexia and cachexia but reduced in obesity, a notable exception being Prader-Willi syndrome. The negative association between ghrelin secretion and body weight is emphasized by evidence that weight increase and decrease reduces and augments circulating ghrelin levels in anorexia and obesity, respectively, and agrees with the clear negative association between ghrelin and insulin levels. In fact, ghrelin secretion is increased by fasting whereas it is decreased by glucose load as well as during euglycemic clamp but not after arginine or free fatty acid load in normal subjects; in physiological conditions, however, the most remarkable inhibitory input on ghrelin secretion is represented by somatostatin as well as by its natural analog cortistatin that concomitantly reduce beta-cell secretion. This evidence indicates that the endocrine pancreas plays a role in directly or indirectly modulating ghrelin secretion.
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PMID:Ghrelin and the endocrine pancreas. 1461 Feb 95

Normal circadian variations in vasoactive intestinal polypeptide, somatostatin, cholecystokinin and pancreatic polypeptide were measured to determine if these alter with aging and to identify gastrointestinal regulatory hormones that might control the dramatic diurnal variation in the gastric cytoprotective trefoil protein TFF2. Plasma pancreatic polypeptide concentrations showed a marked diurnal rhythm (p < 0.0001). Basal and postprandial pancreatic polypeptide concentrations increased with age (p < 0.01). The timing of the diurnal rhythm was consistent with pancreatic polypeptide inhibiting TFF2 secretion and there was a negative association between pancreatic polypeptide and TFF2 concentrations (p < 0.002). The much higher pancreatic polypeptide concentrations in older people will induce increased satiety that may contribute to 'anorexia of ageing'. These results identify potential therapies for treatment of gastric mucosal morbidity and age-associated loss of appetite.
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PMID:Human pancreatic polypeptide has a marked diurnal rhythm that is affected by ageing and is associated with the gastric TFF2 circadian rhythm. 1635 55

Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.
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PMID:Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide. 1750 6

The distribution and density of gastric endocrine cells in Balb/c mice bearing CT-26 carcinoma cells were studied immunohistochemically employing specific antisera against serotonin, somatostatin, glucagon, gastrin, cholecystokinin (CCK)-8 and human pancreatic polypeptide (hPP). The animals were divided into two groups, a non-implanted sham group and a CT-26 carcinoma cell-implanted group. Samples were collected from two regions of the stomach (fundus and pylorus) at 28 days after implantation of the medium or the CT-26 cells (1x10(5) cells/mouse). Five of the 6 types of immunoreactive (IR) cells were identified, with only the hPP IR cells not being detected. The regional distribution of the gastric endocrine cells in the CT-26 implanted group was similar to that of the non-implanted sham group. However, the endocrine cells were significantly decreased in the CT-26-implanted group as compared to those of the non-implanted sham group. Serotonin- and somatostatin-IR cells in the fundus and pylorus , and gastrin- and CCK-8-IR cells in the pylorus of the CT-26 implanted groups were significantly decreased compared to those of the sham group. In addition, glucagon-IR cells were restricted only to the fundus of the sham animals. hPP-IR cells were not detected in either the T-26 implanted- or the non-implanted group. Since endocrine cells are the anatomical units responsible for the production of gut hormones, a change in their density may reflect a change in their capacity to produce such hormones. Implantation of the tumor cell mass induced severe quantitative changes in gastric endocrine cell density, an abnormality which may contribute to the development of gastrointestinal symptoms, such as anorexia and indigestion, frequently encountered in cancer patients.
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PMID:Changes in gastric endocrine cells in Balb/c mice bearing CT-26 carcinoma cells: an immunohistochemical study. 1721 38

A 72-year-old woman visited a clinic for anorexia and general fatigue but no particular abnormality was detected by routine examination at that time. Thereafter, she experienced gradually increasing dyspnea and chest X ray showed right pleural effusion. Idiopathic chylothorax was diagnosed due to the milky effusion with a high concentration of triglyceride (2618 mg/dl) and no apparent causative disease. Irrespective of treatments including dietary restriction, drainage of the pleural space, and somatostatin injections, her effusion did not reduce. The leakage of lymph fluid from the right posterior mediastinum was identified by lymphatic scintigraphy and she was successfully treated with surgical ligation of the thoracic ducts.
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PMID:[Case of idiopathic chylothorax successfully treated with surgical ligation of thoracic ducts]. 1801 31


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