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)

The presence of somatostatin receptors has been demonstrated in various endocrine tumors as well as in normal tissues. We recently have cloned five human somatostatin receptor subtypes (SSTR1-SSTR5). These mRNAs are expressed in a tissue-specific manner. In this study, we have determined the somatostatin receptor subtypes expressed in various endocrine tumors using a reverse transcriptase polymerase chain reaction method. In two cases of glucagonoma and its metastatic lymph nodes in one case, all the SSTR subtype mRNAs except SSTR5 mRNA were expressed. In four cases of insulinoma, SSTR1 and SSTR4 mRNAs were detected, but SSTR2 mRNA was not detected in one case and SSTR3 mRNA was not detected in two cases, indicating a heterogeneous expression of SSTR subtypes in insulinomas. Interestingly, SSTR3 mRNA, which is highly expressed in rat pancreatic islets, is not expressed in normal human pancreatic islets, while SSTR1, SSTR2, and SSTR4 mRNAs are expressed. In three cases of pheochromocytoma, SSTR1 and SSTR2 mRNAs were detected, showing an expression pattern identical to that of normal adrenal gland. In a carcinoid, SSTR1 and SSTR4 mRNAs were detected. We have also found that human SSTR2 shows a high affinity for SMS 201-995, which has been used clinically for the treatment of endocrine tumors. Since SMS 201-995 was effective in the treatment of a patient with glucagonoma in which SSTR2 mRNA was present, but had no effect in a patient with carcinoid in which SSTR2 mRNA was not detected, this study suggests that the efficacy of SMS 201-995 may depend, at least in part, on the expression of SSTR2 in tumors.
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PMID:Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors. 813 73

Meta-iodobenzylguanidine (MIBG) is an effective imaging agent for neuroblastoma and pheochromocytoma in children, MIBG is concentrated by the neurosecretory granules of normal and neoplastic tissues of neural crest origin. The typical normal scintigraphic uptake pattern of MIBG includes the salivary glands, lung, myocardium, liver, gastrointestinal tract, and contents of the urinary bladder. When MIBG is labeled with iodine-123 (123I), the adrenal glands often are seen. The sensitivity and specificity of MIBG imaging is extremely high in both neuroblastoma and pheochromocytoma. MIBG may detect extensive bone and bone marrow involvement in neuroblastoma, in the absence of findings on bone marrow aspiration and biopsy, plain radiographs, and bone scintigraphy. MIBG labeled with 131I has been used with moderate success in the palliation of advanced neuroblastoma and pheochromocytoma. Early therapeutic intervention in advanced neuroblastoma is promising. Current controversies in the application of MIBG include (1)131I versus 123I as a label for imaging studies: Although improved image quality and reduced absorbed radiation dose are achieved with [123I]MIBG imaging, is it actually more efficacious in the detection of neuroblastoma? (2) Use of bone scintigraphy in neuroblastoma: Given the small number of false-negative MIBG scans for bone involvement, can the bone scan be dropped as a routine study in the follow-up of neuroblastoma? (3) Other new imaging agents: Is there a role for labeled monoclonal antibodies, somatostatin analogs, and magnetic resonance imaging of marrow in the routine follow-up of neuroblastoma? (4) Iodine-125 MIBG therapy in neuroblastoma: Is the improved energy deposition of 125I at extremely short range useful in the ablation of micrometastases? (5) Early therapy with MIBG in neuroblastoma: Is there a role for MIBG therapy in the initial therapeutic regimens of children with advanced neuroblastoma? Twelve years after the initial report of its use in humans, MIBG has become an important imaging agent in pediatric neural tumors, one that is used routinely and efficaciously in many centers. In the next few years we will continue to learn more about its use, particularly in the therapy of advanced neural crest tumors.
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PMID:Meta-iodobenzylguanidine in children. 837 96

Somatostatin (SS) is a neuropeptide that is distributed in various regions of the CNS, where it may act as a neurotransmitter or neuromodulator. SS produces multiple effects in the CNS through interactions with membrane receptors. In particular, SS inhibits various secretory responses in different cell types. In the present study, we have investigated the effects of exogenous application of SS on the intracellular free Ca2+ concentration ([Ca2+]i) in PC12 cells, a rat pheochromocytoma cell line. SS did reduce the magnitude of the secondary, maintained Ca2+ influx brought about by K+ depolarization. Similar effects were obtained with the application of SS analogues, such as D-Trp8-SS, D-Trp8-D-Cys14-SS, CGP-23996, and SMS-201995. In addition, treatment with cyclo-SS, a SS antagonist, did not alter [Ca2+]i. Experiments with selective blockers of different voltage-dependent Ca2+ channels, such as methoxyverapamil (D600) and omega-conotoxin GVIA, demonstrated that the effects of SS on [Ca2+]i were mediated by voltage-dependent Ca2+ channels of the L type. Control experiments with a membrane potential indicator, i.e., the fluorescent dye bisoxonol, excluded that SS influenced the level of the membrane potential. SS effects on PC12 cells suggest the possibility that this neuropeptide plays a role in the modulation of cell functional activity by altering Ca2+ influx.
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PMID:Effects of somatostatin on intracellular calcium concentration in PC12 cells. 859 17

Adrenomedullin is a novel hypotensive adrenal polypeptide originally isolated from a human pheochromocytoma and is structurally related to calcitonin gene-related peptide and islet amyloid polypeptide. Using immunocytochemistry, the occurrence of adrenomedullin in the adrenal gland and gastro-entero-pancreatic region in the rat was examined and its effect on insulin secretion from isolated rat islets was determined. Adrenomedullin-like immunoreactivity occurred in noradrenaline- and adrenaline-producing cells in the adrenal gland. Gastrointestinal endocrine cells, with increased density distally, displayed adrenomedullin-like immunoreactivity; these cells constituted a subpopulation of the enterochromaffin (serotonin-containing) cells. Co-localization of adrenomedullin with somatostatin, glicentin, gastrin/cholecystokinin, peptide YY or islet amyloid polypeptide was not encountered. Adrenomedullin-immunoreactive cells were not observed in the pancreatic islets. At 1, 10 and 100 nmol/l, adrenomedullin stimulated insulin release from isolated rat islets in the presence of 3.3 mmol/l glucose (P < 0.05) and at 100 nmol/l, the peptide potentiated insulin secretion also in the presence of 8.3 mmol/l glucose (P < 0.05). These findings suggest that, besides being an adrenal hypotensive peptide, adrenomedullin may be a gut hormone with a potential insulinotropic function.
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PMID:Adrenomedullin: localization in the gastrointestinal tract and effects on insulin secretion. 879 72

In 10 patients with histologically proven neuroendocrine tumors (4 carcinoids, 4 pheochromocytomas, 1 medullary thyroid cancer and 1 Merkel tumor) the results of radiolabeled metaiodobenzylguanidine (MIBG) and somatostatin analogs were compared. A total of 24 tumor lesions was detected on standard imaging studies. MIBG scintigraphy correctly localized 12 (50%) of these lesions which were observed in 5 patients (4 with pheochromocytoma and 1 with carcinoid tumor). Scintigraphy using labeled somatostatin analogs correctly localized 21 (87%) lesions which occurred in 8 patients (4 with carcinoid, 2 with pheochromocytoma, 1 with medullary thyroid cancer and 1 with Merkel tumor). Concordant scintigraphic results were obtained in 1 patient with carcinoid and 2 with pheochromocytoma. In conclusion, although this series was limited, our results suggest that MIBG is more accurate than somatostatin analogs in imaging pheochromocytoma. Conversely, somatostatin analogs are more accurate than MIBG in detecting other neuroendocrine tumors such as carcinoids.
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PMID:Comparison of labeled MIBG and somatostatin analogs in imaging neuroendocrine tumors. 900 75

Radiolabeled somatostatin analogs have shown uptake in a variety of tumors. These include carcinoid, Merkel cell carcinoma, pheochromocytoma, islet cell tumor, and other tumors with somatostatin receptors. Radiolabeled somatostatin analog imaging with Indium-111-DTPA-pentetreotide permits whole body imaging, providing a new safe and effective means for detection of primary tumors and metastatic foci in neoplasms with somatostatin receptors. This imaging modality is helpful in screening the entire body as well as evaluating questionable foci of disease identified by conventional imaging modalities. This case report demonstrates the utility of computed tomography (CT) and radiolabeled somatostatin imaging as complementary modalities in the workup of a patient with metastatic carcinoid tumor.
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PMID:Metastatic carcinoid tumor imaged with CT and a radiolabeled somatostatin analog: a case report. 906 82

Endocrine neoplasms are rare tumors that have traditionally been imaged with ultrasound, CT, magnetic resonance imaging, and angiography. Additional imaging modalities are now available. Endoscopic ultrasound is a new imaging approach to islet cell tumors of the pancreas, in which they typically appear round, homogeneous, and slightly hypoechoic compared with the pancreatic parenchyma. Carcinoid tumors can now be localized with 111In octreotide scintigraphy, which binds to the somatostatin receptors in the tumor. Pheochromocytomas have a distinctive appearance on magnetic resonance imaging, but important advances have occurred using 131I metaiodobenzylguanidine (MIBG). 131I MIBG scanning has a high diagnostic accuracy in detecting pheochromocytoma, with sensitivity greater than 90%. The various tumors and recent advances in their imaging are discussed.
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PMID:Imaging advances in the diagnosis of endocrine neoplasia. 946 83

A 74-year-old male suffering from Recklinghausen's fibromatosis (NvR) is reported. He presented with weight loss, cholestasis, endocrine and exocrine pancreatic insufficiency. These symptoms were caused by a neuroendocrine tumor of the ampulla of Vater containing somatostatin. The tumor induced an obstruction of both the common bile and the pancreatic duct. In addition to this uncommon tumor, a silent pheochromocytoma was found. The patient was treated by endoscopic papillotomy, substitution of pancreatic enzymes and additional enteral nutrition. After recovery no progression of the disease was observed over one year. A review of the literature shows that patients with neurofibromatosis are at high risk for periampullar tumors. In particular, somatostatin-rich carcinoids were previously documented. Pheochromocytomas are also quite prevalent in NvR. However the combination of NvR, pheochromocytoma and somatostatin-rich neuroendocrine tumors of the duodenum has only been reported a few times. An explanation for the high prevalence of neuroendocrine tumors in NvR might be the loss of neurofibromin, a tumor suppressor protein, which is the main product of the neurofibromatosis-l-gene.
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PMID:[A rare combination of pheochromocytoma ans somatostatin-rich neuroendocrine tumor of Vater's papilla (carcinoid) in a patient with von Recklinghausen neurofibromatosis]. 957 7

We describe a 42-year-old man with von Hippel-Lindau disease and islet cell tumor of the pancreas. He had retinal and cerebellar hemangioblastomas. His sister had pheochromocytoma. A pancreatic tumor was detected by ultrasonography at his periodical medical checkup. Contrast enhanced computed tomography and abdominal angiography revealed a hypervascular tumor in the pancreatic head. Histological examination of the resected tumor revealed characteristics of islet cell tumor of the pancreas, which was positive for chromogranin-A, S-100 protein, and pancreatic polypeptide, but was negative for insulin, gastrin, glucagon, somatostatin, vasoactive intestinal peptide, serotonin, and adrenocorticotropic hormone.
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PMID:Islet cell tumor in von Hippel-Lindau disease. 961 66

Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [111In-DTPA-d-Phe1]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq 99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [111In-DTPA-d-Phe1]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using 99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for 99mTc(V)-DMSA and [111In-DTPA-D-Phe1]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node metastasis located in the upper mediastinum. Somatostatin receptor scintigraphy only demonstrated tumour sizes more than 1 cm in diameter. These preliminary results suggest that the combination of metabolic [99mTc(V)-DMSA] and receptor ([111In-DTPA-D-Phe1]-pentetreotide) imaging is more sensitive for tumour localization in patients with recurrent MTC than the use of only one radiopharmaceutical. However, neither 99mTc(V)-DMSA nor [111In-DTPA-D-Phe1]-pentetreotide is specific for MTC and false-positive scintigraphic findings have to be considered. Furthermore, somatostatin receptor scintigraphy cannot visualize small tumour sites (<1 cm). Further studies are needed to evaluate the role of combined metabolic and receptor imaging in the management of patients with recurrent MTC.
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PMID:Comparison of metabolic and receptor imaging in recurrent medullary thyroid carcinoma with histopathological findings. 1004 54


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