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)

Prolonged and severe diarrhoea after alcohol celiac plexus block is a rare, but life-threatening, complication if not recognized. This type of diarrhoea may be considered an autonomic neuropathy due to sympathetic denervation. A 65-year-old pancreatic cancer patient developed serious diarrhoea after celiac plexus block which was unresponsive to traditional treatment such as loperamide, dyphenoxylate and opioids. Subcutaneous octreotide, 0.1 mg twice a day, achieved a complete resolution of the symptom. This drug was maintained at the same dosage and was well tolerated for 4 months until death. Octreotide, an analogue of somatostatin, reduces diarrhoea by suppression of intestinal motility and secretion and offers a useful option in the treatment of this complication of celiac plexus block.
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PMID:Octreotide in the treatment of diarrhoea induced by coeliac plexus block. 765 45

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

The effect of somatostatin analog RC-160 on the growth of CFPAC-1 human pancreatic cancer cells in vitro was investigated. RC-160 effectively inhibited the proliferation of CFPAC-1 cells in culture, inducing a time- and dose-dependent decrease in the number of treated cells. A significant suppression of cell growth was observed after 48 and 72 hr of the exposure to (1 microM) RC-160, the cell number being decreased by 38% and 46%, respectively. RC-160 was more potent than SS-14 or SMS201-995 in inhibiting the growth of CFPAC-1 cells, and after 48-hr treatment the cell number decreased by 49% for RC-160 compared with 12% for SS-14 and 27% for SMS201-995. Binding experiments demonstrated that specific receptors for somatostatin were present on CFPAC-1 cells. SS-14 showed a high binding affinity for [125I]-Tyr11-SS-14 receptors on CFPAC-1 cells. Scatchard analysis indicated the presence of 2 classes of somatostatin binding sites on the cells, one with high binding affinity and low capacity and the other with low binding affinity and high capacity. RC-160 could bind to somatostatin receptors on these cells with an affinity similar to SS-14 but significantly higher than that of SMS201-995. Radioimmunoassay of intracellular cAMP showed that RC-160 could powerfully inhibit forskolin-stimulated cAMP production in CFPAC-1 cells. Addition of forskolin to the cultures increased cAMP concentrations in the cellular lysate of treated cells. RC-160 attenuated or nullified in a dose-dependent manner the cAMP production stimulated by forskolin. Our observations indicate that somatostatin analog RC-160 inhibits the proliferation of CFPAC-1 human pancreatic cancer cells in vitro and that this effect may involve the intracellular cAMP pathway.
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PMID:Somatostatin analog RC-160 inhibits growth of CFPAC-1 human pancreatic cancer cells in vitro and intracellular production of cyclic adenosine monophosphate. 786 Jan 45

Nude mice bearing xenografts of the MIA PaCa-2 human pancreatic cancer cell line were treated with sustained-release formulations (microcapsules) of luteinizing hormone releasing hormone (LH-RH) agonist [D-Trp6]-LH-RH, somatostatin analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2), or combination of both analogues. Other groups of mice received daily subcutaneous injections of LH-RH antagonist SB-75 [Ac-D-Nal(2)',D- Phe(4Cl)2,D-Pal(3)3,D-Cit6,D-Ala10-LH-RH] or bombesin antagonist RC-3095. At necropsy, in mice given microcapsules releasing 25 micrograms/day of [D-Trp6]-LH-RH, tumor weight and volume were decreased, but not significantly, as compared with control mice. Microcapsules of RC-160, releasing 25 micrograms/day, significantly reduced tumor volume, percentage change in tumor volume, and tumor weight. Combination of RC-160 and [D-Trp6]-LH-RH inhibited tumor growth to a somewhat greater extent than RC-160 alone. Bombesin antagonist RC-3095, at a dose of 25 micrograms/day, did not influence the growth of tumors. In mice receiving 100 micrograms/day of antagonist SB-75, there was a significant decrease in tumor weight and volume and a significant reduction in the weight of ovaries and uteri. Specific binding of [125I]RC-160 and [125I][D-Trp6]-LH-RH, but not [125I]Tyr4-bombesin, was found on MIA PaCa-2 cells in culture. [D-Trp6]-LH-RH, SB-75, and RC-160 inhibited the growth of MIA PaCa-2 cells in vitro. Neither bombesin nor RC-3095 influenced the growth of MIA PaCa-2 cells in cultures. The results indicate that the LH-RH antagonist SB-75 could be tried for treatment of pancreatic cancer. Our findings confirm the efficacy of somatostatin analogue RC-160 in inhibiting the growth of pancreatic cancers and suggest that the combination of RC-160 and agonist [D-Trp6]-LH-RH might possibly increase the therapeutic response.
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PMID:Somatostatin analogue RC-160 and LH-RH antagonist SB-75 inhibit growth of MIA PaCa-2 human pancreatic cancer xenografts in nude mice. 809 55

Exocrine pancreas carcinoma is still diagnosed at a relatively late stage, so that only a few cases can be cured by surgery. Therefore, it is desirable that an effective medical therapy be found first to stall the development of the disease and second to improve the life conditions of patients. On the basis of recent discoveries, a new therapeutic approach seems to derive from hormone manipulation. The growth of pancreatic carcinoma appears to be stimulated by various factors, such as Epidermal Growth Factor (EGF) and Insulin-like Growth Factor I (IGF-I), and by various hormones, such as androgens and cholecystokinin. Several studies performed on cell lines and on animal models of pancreatic carcinoma demonstrated an antitumoral effect of certain antihormones and of somatostatin. Taking such studies as a premise, the first clinical studies were finally started in patients suffering from nonoperable pancreatic cancer. Results are still partial and contradictory, but such research is certainly worthy of further study along the lines already taken.
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PMID:Hormonal therapy of pancreatic carcinoma. Rationale and perspectives. 810 83

Between 1986 and 1991 35 partial duodenopancreatectomies have been performed in the Clinic for visceral surgery of the University of Berne. 17 for adenocarcinoma of the pancreas and 18 for miscellaneous malignant or semimalignant pathologies such as ampullary or duodenal carcinomas, cystadenomas and distal bile duct carcinomas. The mortality was 5%. Postoperative complication was observed in 50% of cases. Leak at the pancreaticojejunal anastomosis was the most common surgical complication but healed under conservative treatment with somatostatin within few days in 5 of 6 cases. The median survival for patients with adenocarcinoma of the pancreas is 550 days, for patients with other pathologies 1200 days with some long-term survival in ampullary carcinomas. These results show on one hand that this kind of surgery can be realized with acceptable morbidity and mortality rate, on the other hand that further clinical trials in systemic adjuvant treatment are indicated especially in pancreatic cancer to improve the disappointing long-term results.
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PMID:[Whipple's operation for tumors of the pancreatic head and periampullar area]. 810 69

Prognosis in patients with advanced pancreatic cancer is dismal. There has been no effective therapy for these patients so far. Somatostatin and its analogues have been proven to be potent inhibitors of experimental pancreatic cancer. Tumor inhibition is supposed to be mediated directly by somatostatin-binding sites or indirectly by suppression of growth factors. In two trials the value of the new somatostatin analogue octreotide in a low-dose (3 x 100 micrograms/day) and a high-dose (3 x 2,000 micrograms/day) protocol was evaluated in patients with advanced pancreatic cancer. Median survival of the patients with a low-dose protocol was 3 months. However, the treatment of pancreatic cancer with a high-dose protocol revealed a median survival of 6 months and stable disease in 4/10 patients. According to quality of life scoring 4 patients showed values comparable to healthy controls. Octreotide therapy with a high-dose protocol is a promising experimental therapeutic approach to advanced pancreatic cancer.
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PMID:Role of octreotide in the treatment of pancreatic cancer. 813 37

Octreotide (SMS 201-995), a long-acting somatostatin analogue, has been shown to decelerate growth of human pancreatic cancer in vitro and in vivo. We analyzed the efficacy of octreotide treatment in 22 patients (14 men, 8 women) with histologically verified ductal pancreatic cancer. All patients had advanced tumor stages (stage III: 13 patients; stage IV: 9 patients). Octreotide was given by self-administered subcutaneous injection (3 x 100 micrograms/day). When there was evidence of tumor progression, the dose of octreotide was increased to 3 x 200 micrograms/day. A monthly follow-up, including clinical status, CT scan or ultrasonography, and tumor marker carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 determination was carried out. There were no severe side effects apart from slight burning sensation at the injection site. No partial or complete remission was seen. Eighteen patients showed tumor progression with a median survival time of 17 weeks (range 3-42 weeks). In three patients a "no change" evaluation with a median survival time of 46 weeks (range 40-68 weeks) was registered. In these three patients the serum tumor markers CA 19-9 and CEA did not show an increase to more than twice the baseline value during this time. One patient discontinued the octreotide treatment because of tumor progression. The results of the analysis indicate that low-dose octreotide treatment is not effective in patient suffering from advanced tumor stages of pancreatic cancer.
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PMID:Low-dose octreotide treatment is not effective in patients with advanced pancreatic cancer. 830 89

Somatostatin exerts diverse effects in various tissues upon binding its specific membrane receptors. Recently, we have cloned three different somatostatin receptor subtypes. Here we report the sequence and functional expression of a fourth and a fifth human somatostatin receptor subtype, termed hSSTR4 and hSSTR5, respectively. The hSSTR4 encodes a protein of 388 amino acids and the hSSTR5 is a protein of 364 amino acids. There is 42-60% identity among the amino acid sequences of the five human somatostatin receptor subtypes identified to date. RNA blotting studies reveal that the hSSTR4 is expressed as a single transcript of 4.8 kb in MIA PaCa-2 cells, a cell line derived from human pancreatic cancer while the hSSTR5 is undetectable in the tissues examined. The hSSTR4 and hSSTR5 transiently expressed in COS1 cells exhibit specific binding to somatostatin-14 with IC50 values of 1.6 and 0.16 nM, respectively. We also have characterized the binding affinity of various somatostatin analogues to the hSSTR4 and hSSTR5. The rank of the potency of the analogues are: somatostatin-14 = somatostatin-28 >> RC-160 >> SMS201-995 for the hSSTR4 and somatostatin-28 > somatostatin-14 >> RC-160 > SMS201-995 for the hSSTR5. These results suggest that diverse actions of somatostatin are mediated by at least five somatostatin receptor subtypes with potentially different function.
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PMID:Cloning, functional expression and pharmacological characterization of a fourth (hSSTR4) and a fifth (hSSTR5) human somatostatin receptor subtype. 837 20

Five somatostatin receptor subtypes (sst1 to sst5) have been cloned. We demonstrated previously that sst2 and sst5 mediate the antiproliferative effect of the somatostatin analogues octreotide and vapreotide. Using reverse transcription-PCR, we investigated gene expression of the five receptors in 47 human normal and cancerous tissues or cell lines from pancreatic and colorectal origin. mRNAs of somatostatin receptor subtypes were detected in 98% of samples, with more than two mRNA subtypes being expressed in 55% of cases. sst1, sst4, and sst5 were heterogeneously expressed in both normal and cancerous tissues; sst3 was rarely or not expressed. sst2 was present in normal pancreatic tissues but was absent in exocrine pancreatic carcinomas and their metastases. sst2 mRNAs were detected in normal colon, sporadic polyadenomas, and 50% of Dukes' stage B and 20% of Dukes' stage C carcinomas but were undetectable in Dukes' stage D carcinomas, hepatic metastases, and adenomas from familial adenomatous polyposis. The loss of sst2 expression could represent a growth advantage in these tumors and provide an explanation for the lack of therapeutic effect of somatostatin analogues in such adenocarcinomas. A subtyping of somatostatin receptors should be carried out before considering a somatostatin analogue treatment in patients with colorectal or pancreatic cancer.
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PMID:Loss of sst2 somatostatin receptor gene expression in human pancreatic and colorectal cancer. 862 Apr 99


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