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 role of endoscopic ultrasound (EUS) in the evaluation of entero-pancreatic endocrine tumours has evolved in conjunction with advances in other imaging methods. The high spatial resolution of this technique allows the detection of very small lesions and their precise anatomical localisation. In patients with biochemically proven insulinoma, EUS can be effectively used as a first line investigation, with a sensitivity of 94%. Combined with thin section CT, the sensitivity rises to 100%. There is also high sensitivity in diagnosing intrapancreatic gastrinomas but lower for those arising in the duodenal wall which require detailed duodenal evaluation at surgery. EUS in conjunction with Somatostatin Receptor Scanning (SRS) has a combined sensitivity of 93% for gastrinomas. EUS is recommended for screening of asymptomatic patients with genetically proven MEN1. There is a limited role for EUS guided biopsy in pancreatic endocrine tumours.
Best Pract Res Clin Endocrinol Metab 2005 Jun
PMID:Endoscopic ultrasound in the localisation of pancreatic islet cell tumours. 1576 94

Over the last decade somatostatin receptor scintigraphy using various derivatives of long-acting somatostatin analogues has gained its place in the management of pancreatic islet-cell tumours. Scintigraphy is based on the high-affinity binding of such somatostatin analogues to receptors over-expressed by these tumour types. Following the introduction of (111)In-DTPA-D-Phe(1)-octreotide, clinical studies with radiolabelled DOTA-Tyr(3)-octreotide and DOTA-Tyr(3)-octreotate derivatives have shown considerable improvement of imaging results with increased tumour uptake. One of the newer developments, (68)Ga-labelled DOTA-Tyr(3)-octreotide, has shown promising results in patients with pancreatic islet-cell tumours, based on the high-affinity binding to the somatostatin receptor subtype 2 in combination with positron emission tomography (PET) technology. Other peptides--such as ligands for the gastrin/CCK2 receptors or vasoactive intestinal peptide (VIP)--have also been studied for imaging pancreatic cell tumours. Whereas small-sized gastrinoma, somatostatinoma, glucagonoma, carcinoid and VIPoma are frequently detected by somatostatin receptor scintigraphy, insulinoma may escape detection due to reduced receptor expression. Following peptide receptor scintigraphy, a change in patient management is reported in up to 30% of patients. When labelled with (90)Y or (177)Lu, some somatostatin analogues have been applied to patients in advanced stages of the disease. Despite positive response data in 50% of patients, long-term results and survival rates are lacking.
Best Pract Res Clin Endocrinol Metab 2005 Jun
PMID:Nuclear medicine in the detection and management of pancreatic islet-cell tumours. 1576 96

Carcinoid tumours belong to the family of neuroendocrine tumours with a capacity to take up and concentrate amines and precursors as well as peptides, and can thereby be detected by nuclear medicine techniques. These rare tumours are difficult to diagnose at earlier stages because of small size and multiplicity. Computed tomography (CT) and magnetic resonance imaging (MRI) are mostly of benefit for detection of larger primary tumours (1-3 cm) and liver and lymph-node metastases. A majority of carcinoid tumours express somatostatin receptors, particularly receptor type 2, and thus somatostatin receptor scintigraphy (SRS) can be used for detection and staging of carcinoid tumours. The detection rate of carcinoid tumours has been reported to be somewhere between 80 and 100% in different studies. The scintigraphy gives a good staging of the disease and detection of unexpected tumour sites, which were not determined by conventional imaging. This method also indicates content of somatostatin receptors, which might indicate efficacy of treatment with octreotide or other somatostatin analogues. Another new non-invasive technique for detection of carcinoid tumours is positron emission tomography (PET). The biological substance for study can be labelled for radioactive imaging with radionuclears, such as (11)C, (15)O and (18)F, with emission of positrons. More than 95% of patients studied displayed high tracer uptake from PET with (11)C-5HTP (5-hydroxytryptophan), which is significantly higher compared to both computer tomography and somatostatin receptor scintigraphy. MIBG has been used for decades to visualize carcinoid tumours, because MIBG is concentrated in the endocrine cells. It was initially developed to detect phaeochromocytomas of the adrenal with reported high sensitivity (87%) and specificity as high as 99%. The method can be used when other methods fail to localize carcinoid tumours and particularly when treatment with (131)I-MIBG is being considered. Tumour-targeted treatment for malignant carcinoid tumour is still investigational, but has become of significant interest with the use of radiolabelled somatostatin analogues. Since a majority of carcinoid tumours present somatostatin receptors and can therefore be visualized in vivo by using radiolabelled somatostatin analogues, it seems logical to try to target these tumours with radioactive substances, not only for visualization but also for treatment. (111)Indium-DTPA-octreotide has been used as the first tumour-targeted treatment, with rather low response rates (in the order of 10-20%) and no significant tumour shrinkage. The second radioactive analogue which has been applied in the clinic is (90)yttrium-DOTA-Tyr3-octreotide, which has given partial and complete remissions in 20-30% of patients. The most significant side-effects have been kidney dysfunction, thrombocytopenia and liver toxicity. The most recent compound is (177)lutetium-DOTA-Tyr3-octreotate, which has been applied by the Rotterdam group and has been reported to give partial remission in about 40% of the patients. In the near future, combined treatment with both (90)yttrium and (177)lutetium coupled to a somatostatin analogue might come into clinical trials. (177)Lutetium may be more effective for smaller tumours whereas (90)yttrium may be more effective for larger tumours.
Best Pract Res Clin Endocrinol Metab 2005 Jun
PMID:Nuclear medicine in the detection, staging and treatment of gastrointestinal carcinoid tumours. 1576

Somatostatin is a neuropeptide that acts as an endogenous inhibitor of various cellular functions including endocrine and exocrine secretions and the proliferation of normal and tumour cells. Its action is mediated by a family of G-protein-coupled receptors (sst1-sst5) that are widely distributed in normal and tumour cells. Gastroenteropancreatic endocrine tumours express multiple somatostatin receptors, sst2 being clearly predominant. These receptors represent the molecular basis for the clinical use of somatostatin analogues in the treatment of endocrine tumours and their in vivo localisation. This review covers current knowledge in somatostatin receptor biology and signalling.
Best Pract Res Clin Gastroenterol 2005 Aug
PMID:Endocrine tumours of the gastrointestinal tract. Somatostatin receptors as tools for diagnosis and therapy: molecular aspects. 1618 26

Hepatic metastases are frequent in patients with gastroentero-pancreatic (GEP) endocrine tumours; their presence significantly influences overall prognosis. Surgery, although the treatment of choice for hepatic metastases, is frequently impossible due to disease extent. Systemic chemotherapy in patients with diffuse and/or progressive liver metastases yields disappointing results especially in patients with metastases from midgut origin. In addition, in patients with carcinoid syndrome, the efficacy of somatostatin analogues wanes due to disease progression and development of tachyphylaxis. Locoregional strategies with vascular occlusion inducing ischemia in these highly vascular GEP tumours are indeed other options and may be performed using either surgical or radiological techniques (e.g. surgical ligation of the hepatic artery, transient hepatic ischemia, or sequential hepatic arterialization). Trans-catheter arterial chemoembolization is efficacious in both the control of hormonal symptoms and yields reliable objective tumour responses. Treatments aimed at regional destruction either alone or in combination with surgery include radiofrequency ablation and cryotherapy and may also be considered in certain circumstances.
Best Pract Res Clin Gastroenterol 2005 Aug
PMID:Chemoembolization and other ablative therapies for liver metastases of gastrointestinal endocrine tumours. 1618 29

Peptide receptor radionuclide therapy is a new treatment modality for patients with inoperable or metastasised neuroendocrine gastroenteropancreatic tumours. After the successful implementation of somatostatin receptor scintigraphy in daily clinical practice, the next logical step was to increase the radiation dose of the administered radiolabelled somatostatin analogue in an attempt to induce tumour shrinkage. Since then, an increasing number of patients has been successfully treated with this approach, resulting in a substantial numbers of patient with objective tumour shrinkage. Serious side-effects have been rare. This article reviews the effectiveness of the different radiolabelled somatostatin analogues used, the currently known side-effects and the survival data available. Furthermore, clinical issues, including indication and timing of therapy, are discussed. Finally, important directions for future research are briefly mentioned to illustrate that, although the currently available results already suggest a favourable outcome compared with other systemic therapies, new strategies are being developed to increase efficacy.
Best Pract Res Clin Gastroenterol 2005 Aug
PMID:Endocrine tumours of the gastrointestinal tract. Peptide receptor radionuclide therapy. 1618 30

Somatostatin analogues have been the mainstay of symptomatic management of patients with neuroendocrine tumours (NETs) for two decades with the main mechanism of action being inhibition of peptide release. Evidence base for interferon use is perhaps less clear. It may contribute to symptom control by abrogating peptide release, and there is some evidence that it has an anti-proliferative action. Combination of somatostatin analogues and interferon provides symptom control, mainly by effecting a reduction in the amount of circulating, physiologically active, peptide hormones. Treatment can also provide disease stabilisation in a proportion of patients. In a minority of patients treatment may lead to partial response.
Best Pract Res Clin Gastroenterol 2005 Aug
PMID:Endocrine tumours of the gastrointestinal tract. Biotherapy for metastatic endocrine tumours. 1618 31

Gastric endocrine tumours (gastric carcinoids) usually grow from enterochromaffin-like (ECL) cells. Three types of tumour may be distinguished on the basis of the background gastric pathology: type I, which develops in atrophic body gastritis (ABG); type II, which is associated with multiple endocrine neoplasia and Zollinger-Ellison syndrome; and the sporadic type III, which is not associated with any background pathology. This classification plays a major role in determining the optimal approach to these diseases. In fact, type I carcinoids can be considered to be benign lesions, with exceptional risk of metastases. Type II, in contrast, may be associated with distant metastases, which are also common in type III carcinoids. The therapeutic approach is based mainly on endoscopic excision and somatostatin analogues in types I and II, or on surgical resection in type III. Both types I and II grow under the stimulus of hypergastrinaemia through a well-described sequence. However, gastrin is sufficient to cause ECL cell hyperplasia and dysplasia, but not transformation, which is due to menin defects in MEN-I patients, or to other unknown alterations in ABG. Several other candidates--including Bcl2, p53 and MMP9--have been linked with carcinoid initiation and progression. The biology of type III tumours which are not associated with hypergastrinaemia is still poorly understood.
Best Pract Res Clin Gastroenterol 2005 Oct
PMID:Endocrine tumours of the stomach. 1625 92

(Neuro-)endocrine tumours of the gastrointestinal tract are also called 'carcinoids'. (Neuro-)endocrine midgut tumours can be categorized according to their clinical behaviour. Most tumours are non-functioning. Functioning tumours are responsible for the carcinoid syndrome. The carcinoid syndrome is almost uniquely associated with midgut carcinoids. Symptoms of the carcinoid syndrome are caused by an excess of biogenic amines, peptides and other factors in the circulation. The typical symptoms of the carcinoid syndrome are diarrhoea, flushing, and carcinoid heart disease. Carcinoid heart disease involves the tricuspid and pulmonary valves and the endocardium. Serum chromogranin A and urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA) are biochemical markers. Carcinoid tumours express large numbers of high-affinity somatostatin receptors. These can bind the currently available octapeptide somatostatin analogues. In inoperable patients, biotherapy with somatostatin analogues and interferon-alpha is the treatment of choice. Somatostatin analogues and interferon-alpha significantly improve symptoms.
Best Pract Res Clin Gastroenterol 2005 Oct
PMID:Tumours of the midgut (jejunum, ileum and ascending colon, including carcinoid syndrome). 1625 95

Midgut carcinoids originating in the small intestine are the most common cause of the carcinoid syndrome. These tumours typically progress slowly and have an extended disease course, and although they often present with metastases at diagnosis, surgical treatment has become increasingly important for their management. Surgery should include efforts to remove mesenteric metastases, which may cause severe long-term abdominal complications with typical fibrotic intestinal entrapment and small-bowel ischaemia due to compression of mesenteric vessels. Attempts should also be made to surgically remove or ablate liver metastases, since this may provide considerable palliation of the carcinoid syndrome. For patients with the carcinoid syndrome surgery is combined with continuous biotherapy with long-acting somatostatin analogues, which may alleviate symptoms and stabilize disease or slow progression. Favourable survival and appreciable quality of life can be expected with this combined treatment, even in patients with advanced midgut carcinoids.
Best Pract Res Clin Gastroenterol 2005 Oct
PMID:Midgut carcinoid tumours: surgical treatment and prognosis. 1625 96


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