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 effects of a potent specific gastrin-releasing peptide receptor antagonist, BIM 26226 ([D-F5 Phe6, D-Ala11] bombesin (6-13) OMe), and the long-acting somatostatin analogue, lanreotide (BIM 23014), on the growth of an acinar pancreatic adenocarcinoma growing in the rat or cultured in vitro were investigated. Lewis rats bearing a pancreatic carcinoma transplanted s.c. in the scapular region, were treated with gastrin-releasing peptide (30 microg/kg per day), BIM 26226 (30 and 100 microg/kg per day) and lanreotide (100 microg/kg per day) alone or in combination for 14 successive days. Chronic administration of BIM 26226 and lanreotide significantly inhibited the growth of pancreatic tumours stimulated or not by gastrin-releasing peptide (GRP), as shown by a reduction in tumour volume, protein, ribonucleic acid, amylase and chymotrypsin contents. This effect was more pronounced with 100 microg/kg per day BIM 26226 than with 30 microg/kg per day. However, BIM 26226 and lanreotide, given together, did not exert any additive effect on GRP-treated and -untreated tumours. In cell cultures, both BIM 26226 and lanreotide (10(-6) M) inhibited [3H]thymidine incorporation in tumour cells induced or not by GRP, but no increased effect was observed after combined treatment with both agents. Binding studies showed that BIM 26226 had a high affinity for GRP receptors in tumour cell membranes (IC50 = 6 nM). These results from in vivo and in vitro experiments suggest that BIM 26226 and lanreotide are able to reduce the growth of an experimental acinar pancreatic tumour. Thus, these agents represent interesting steps toward the development of new approaches for treatment of pancreatic carcinomas.
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PMID:Effect of the gastrin-releasing peptide antagonist BIM 26226 and lanreotide on an acinar pancreatic carcinoma. 965 Aug 51

Somatostatin (SST) and its analogues are candidates for use as endocrine agents in the treatment of pancreatic neoplasm. To determine whether the status of SST receptors in the human pancreatic tumors differs from that in the tumor-free pancreata of the human and whether pancreatic adenocarcinoma expresses the same subgroup of SST receptors as found in gastrinomas, this study visualized and characterized SST receptors in human control pancreata (n = 10) as well as pancreatic cancers (n = 12) and gastrinomas (n = 8) with storage phosphor autoradiography. Both pancreatic adenocarcinoma and gastrinoma expressed specific SST receptors. The binding capacity (Bmax, 35.4 +/- 7.6 fmol/mg protein) and the affinity (Kd, 0.32 +/- 0.27 nM) of SST receptors in gastrinomas were significantly higher than in pancreatic cancers (Bmax, 15 +/- 2.5 fmol/mg protein; Kd, 2.16 +/- 0.4 nM). No specific SST receptors were detected in the human control pancreata. Octreotide showed similarly high potencies of inhibition of 125I-SST-28 binding as SST-28 in gastrinomas. Unlike gastrinomas, little competitive binding of 125I-SST-28 was found with octreotide in pancreatic cancers. In conclusion, compared with the control pancreas, an up-regulation of SST receptors was present in both pancreatic cancer and gastrinoma. The subgroup of SST receptors in pancreatic cancers differs from that in gastrinomas.
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PMID:Expression of somatostatin receptors in human pancreatic tumor. 966 24

Long-acting somatostatin analogs have recently become supplemental drugs in the treatment of neurofibroma because of their marked tumor growth inhibitory effect. Somatostatin is currently under extended evaluation in other cancers as a possible supplemental drug to the treatment protocols in use. The mode of action is not known. Somatostatin has been shown to cause glucose intolerance by inhibiting glucose-6-phosphate dehydrogenase (G6PD) in fish liver. Recent data generated in our laboratory indicate that it is this pathway and the transketolase reactions of the pentose cycle (PC) which are directly involved in the ribose synthesis process of pancreatic adenocarcinoma cells. In cell culture, somatostatin alone inhibited glucose carbon recycling through the PC by 5.7%, which was increased to 19.8% in combination with oxythiamine, a competitive inhibitor of transketolase. Oxythiamine produced strong apoptosis in in-vitro hosted tumor cells. We hypothesize that somatostatin- and oxythiamine-induced antiproliferative action is mediated by the inhibition of G6PD, transketolase, or both.
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PMID:Inhibition of the oxidative and nonoxidative pentose phosphate pathways by somatostatin: a possible mechanism of antitumor action. 971 Mar 24

Either radiolabeled Tc-99m- or Re-188-labeled MAG3-4-nitrophenylester or unlabeled Bz-MAG3-4-nitrophenylester was reacted with amines and peptides to follow a pre- or a postconjugate radiolabeling route, respectively. The model compounds were N'-t-butyloxycarbonyl-1,6-diaminohexane (DH-Boc) and a Lys-protected derivative of the somatostatin analog RC-160 (cyclic D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2). In the case of labeling DH-Boc, both the preconjugate labeling and the postconjugate labeling were found by using analytical HPLC to provide identical radiolabeled compounds regardless whether Re-188 or Tc-99m was used. The results are supported by infrared and mass-spectral data obtained from compounds synthesized using stable rhenium. The 188Re- or 99mTc-MAG3-RC-160 somatostatin analog were synthesized following the preconjugate labeling route and subsequent removal of the protecting group. Biodistributions of 188Re-and 99mTc-MAG3-RC-160 were evaluated in normal and tumor-bearing mice, and were similar to those of radioiodinated 131-RC-160. All radiolabeled analogs of RC-160 were rapidly cleared from the blood and were excreted through the hepatobiliary system with very little normal organ uptake. The tumor uptake (PC-3, human prostate adenocarcinoma) of systemically administered Re-188-MAG3-RC160 was very low, and it reached only 0.28% injected dose/g (%IDg) at 24 h postinjection, similar to what was obtained with I-131-RC-160. Intratumor injections resulted in significant tumor retentions (9.3% ID/g at 24 h).
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PMID:188Re- and 99mTc-MAG3 as prosthetic groups for labeling amines and peptides: approaches with pre- and postconjugate labeling. 980 43

For more than two decades, our research group has been studying the pancreatic actions of three groups of regulatory peptides: members of the cholecystokinin/gastrin family, bombesin-like peptides and somatostatin. Investigating these peptides, our work has focused on three particularly interesting aspects: peptidergic regulation of pancreatic enzyme secretion and growth in adult rats, peptidergic control of pancreatic enzyme secretion and growth during postnatal development in rats, and peptidergic regulation of proliferation and differential gene expression in pancreatic adenocarcinoma cells. Our data confirmed that the control of the exocrine function of the pancreas is complex, and that it involves peptides such as the cholecystokinin/gastrin-like peptides, bombesin-like peptides and somatostatin. In these investigations, it became evident that selective peptide receptor agonists, antagonists and monoclonal antibodies raised against peptides are useful tools to identify the role of these bioactive peptides in pancreatic exocrine secretion and cell proliferation.
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PMID:Agonists and antagonists of regulatory peptides as tools to study regulation of pancreatic exocrine secretion, cell proliferation and gene expression. 986 8

The authors report a case of a suspected pure pancreatic polypeptide-secreting neuroendocrine carcinoma of the gallbladder. The tumor was initially interpreted as an adenocarcinoma of the gallbladder, but was found to have a neuroendocrine component after review. The pathology supports the view that a primitive epithelial stem cell can express both epithelial and neuroendocrine characteristics and can differentiate into both an adenocarcinoma and a neuroendocrine carcinoma. Upon recurrence, the tumor produced symptoms due to local growth, but eventually metastasized and led to the death of the patient within 4 years. The patient was treated with chemoembolization followed by the long-acting somatostatin analog octreotide acetate. The high serum level of pancreatic polypeptide may have contributed to cholestasis and cholelithiasis. Earlier measurement of serum hormone levels and identification of high pancreatic polypeptide levels may have suggested the presence of residual tumor and led to closer follow-up, imaging studies, and therapy.
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PMID:Pancreatic polypeptide hypersecretion associated with a neuroendocrine carcinoma of the gallbladder. 989 73

Fourteen patients with metastatic pancreatic adenocarcinoma were treated with the long-acting somatostatin (SST) analogue lanreotide. No objective response was obtained, and the median survival was 4 months (range 1.8-7 months). Pancreatic cancer could not be visualized by means of SST-receptor (R) scintigraphy in our patients. In vitro data also demonstrated absence of SSTR2 expression, suggesting pancreatic cancer not to be a potential target for treatment with SST analogues.
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PMID:Treatment of advanced pancreatic cancer with the long-acting somatostatin analogue lanreotide: in vitro and in vivo results. 1002 26

BACKGROUND: gastric abnormalities are a common feature in patients with primary antibody deficiency. The most important problem is the high incidence of stomach cancer found in these patients. Chronic atrophic gastritis with pernicious anemia is also a common finding that predisposes to gastric adenocarcinoma. The aim of the present study was to identify factors predictive of high risk for developing gastric cancer in patients with primary antibody deficiency. PATIENTS AND METHODS: we studied gastric hormones (gastrin, somatostatin and gastrin-releasing peptide, GRP) in 47 patients (23 children and 24 adults) with primary antibody deficiency. In accordance with the World Health Organization (WHO) classification, patients were diagnosed as having X-linked agammaglobulinemia (Bruton disease) in 13 cases, common variable immunodeficiency in 28, and hypogammaglobulinemia with hyperIgM in 6. Gastric biopsy was performed in 22 patients (16 children and 6 adults). Hormone determinations were carried out by radioimmunoassay. RESULTS: baseline serum gastrin levels were normal or increased compared with controls, but the response to stimulation with a hyperproteic diet was delayed in 18 patients and lower than in controls in 7. In 4 adult patients, all with pernicious anemia, gastric biopsy revealed chronic atrophic gastritis involving the stomach corpus and antrum (type B gastritis). The absence of a normal response of gastrin secretion to stimulation with a hyperproteic diet may be explained by this finding. Serum somatostatin and GRP levels were higher than in controls. No correlations were found between these findings and patient age, type of immunodeficiency or duration of clinical manifestations.
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PMID:Study of gastrointestinal polypeptides controlling gastric acid secretion in patients with primary antibody deficiency. 1021 2

We report the case of a 63-yr-old man who had severe secretory diarrhea associated with colonic adenocarcinoma, with a prominent signet ring cell component and numerous endocrine cells as demonstrated by positive chromogranin-A staining. Improvement in the secretory diarrhea by the somatostatin analog Sandostatin suggested that the diarrhea was related to a functional neuroendocrine tumor within the colonic tumor, the first case to be reported in the literature.
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PMID:Adenocarcinoma of the colon with neuroendocrine features and secretory diarrhea. 1036 49

A 68-year-old man with metastatic brain tumors from adenoendocrine carcinoma of the common bile duct is reported. A common bile duct tumor and a metastatic liver tumor had been resected 6 years and 3 years prior to admission, respectively. Microscopically they showed two components; moderately differentiated tubular adenocarcinoma and neuroendocrine carcinoma. He presented with headache and vomiting and MRI revealed two metastatic brain tumors. They were successfully resected and radiotherapy was carried out. Histological diagnosis of the metastatic brain tumors was neuroendocrine carcinoma, but carbohydrate antigen (CA)-19-9 and carcinoembryonic antigen (CEA)-immunoreactive cells were observed without glandular pattern. Immunohistochemically serotonin and pancreatic polypeptide were detected, but somatostatin was not. As the endocrine cells demonstrated in the normal extrahepatic bile ducts are only somatostatin-containing D cells, these cells are considered to originate as part of a metaplastic process. To our knowledge, this represents the second case of adenoendocrine carcinoma of the common bile duct.
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PMID:Brain metastases from adenoendocrine carcinoma of the common bile duct: a case report. 1037 37


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