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)

Using in vivo scintigraphy with the 111In-labeled somatostatin analog octreotide, tumor localizations were demonstrated in 11 of 17 patients (65%) with medullary thyroid carcinoma (MTC). Tumor localizations in the liver in 7 patients, and in the thyroid in 1 patient were not detected on octreotide scintigraphy, most probably because of normal uptake of labeled octreotide in these organs. Specific somatostatin receptors were demonstrated in vitro on all 5 investigated tumors which had also been visualized in vivo, as well as on 1 tumor that was not. Immunohistochemically, somatostatin was present in 1 of 6 tumors that were visualized in vivo, and in neither of 2 tumors that were not. The ratio of serum calcitonin over carcino-embryonic antigen concentrations was significantly higher in patients whose MTCs were visualized during octreotide scintigraphy than in those whose tumors were not. We have formed the following conclusions: 1) In the majority of patients with metastatic MTC, tumor sites can be visualized using octreotide scintigraphy, although this technique is insensitive in detecting liver metastases or intrathyroidal tumor; 2) The visualization of MTC during in vivo somatostatin receptor imaging correlates with the in vitro presence of somatostatin receptors; 3) The immunohistochemical presence of somatostatin in the tumor does not seem to influence the outcome of in vivo somatostatin receptor imaging; and 4) Higher serum calcitonin over carcino-embryonic antigen ratios in patients whose MTC is visualized during octreotide scintigraphy might imply that somatostatin receptors are present on more differentiated MTC.
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PMID:In vivo somatostatin receptor imaging in medullary thyroid carcinoma. 850 Nov 44

Carcinoids, tumors arising from enterochromaffin cells, represent the most common type of gastrointestinal endocrine neoplasm; they are often multiple and may appear anywhere in the gut. Carcinoid tumors may also occur in bronchi and ovaries. Classic symptomatology includes secretory diarrhea, flushing, edema, bronchospasm and cutaneous teleangectasias; however, over 30% of patients with demonstrably elevated serotonin levels may not exhibit any symptoms at all. The diagnosis of carcinoid tumor is typically made by measurement of 24-hour urinary excretion of 5-hydroxyindoloacetic acid. Commonly, tumor localisation is established with CT, US, NMR and arteriography. MIBG scintigraphy is also used to visualize tumors deriving from neuroendocrine cells as carcinoid. These tumors may express somatostatin receptors located on the cell surface. Therefore 111In Octreotide (Octreoscan), a somatostatin analogue, can be employed for tumor localisation. A 32-years-old man with liver metastases secondary to a carcinoid tumor of unknown origin is presented. Classic carcinoid symptoms were absent. Diagnosis was supported by elevated values of urinary 5-hydroxyindolocetic acid and liver fine-needle aspiration. Abdominal US and CT scan detected only liver masses but not the primary tumor. Arteriography was not performed. 131I MIBG and 111I octreotide scans both failed in locating the primary cancer too; only the second tracer showed marked uptake in liver metastases. Beside localization, these two tracers give also informations about the following therapy especially in malignant tumors where local resection isn't an adequate treatment.
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PMID:131I MIBG/111In octreotide mismatch in a patient with liver metastases secondary to a carcinoid of unknown origin. 853 97

Most carcinoid primary tumors are small and do not cause symptoms until complications (e.g. intestinal obstruction) or symptoms and signs of the carcinoid syndrome occur. Therefore in most cases an assessment of the primary tumor and its metastases must be performed. To determine the value of somatostatin receptor scintigraphy (SRS) for localizing carcinoid tumors, we compared the results of SRS with those obtained with computed tomography (CT) and ultrasonography (US) in 22 patients who had not undergone surgery for removal of the primary tumor. We could not find an advantage of SRS over CT and US for detecting the primary lesions. Tumors > 2 cm in diameter were regularly detected using all methods. SRS was not superior to CT or US for the detection of liver metastases. SRS showed the liver metastases in 16 of 18 patients, whereas CT and US detected liver metastases in all patients. For localization of extrahepatic abdominal and extraabdominal metastases (lymph nodes, bone), whole-body SRS showed an advantage over CT and US. We conclude that SRS is not superior to CT or US for localization of primary carcinoid tumors or liver metastases, although it did prove successful for visualizing extrahepatic and extraabdominal tumor spread. Additionally, SRS is useful for identifying receptor-positive metastases that may be treated by somatostatin analogs. Thus SRS should be performed in patients with a known carcinoid tumor, except those with an appendiceal carcinoid measuring < 1 cm in diameter.
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PMID:Value of somatostatin receptor scintigraphy for preoperative localization of carcinoids. 866 12

Carcinoids of the stomach, duodenum, and pancreas are represented by a variety of tumors with variable histologic and clinical features. Multicentric gastric carcinoids and concomitant nonantral argyrophilic hyperplasia are common in chronic atrophic gastritis, more rarely due to a multiple endocrine neoplasia (MEN)-related Zollinger-Ellison syndrome (ZES). These tumors are infrequently associated with metastases and may generally be dealt with by repeated endoscopic fulguration. Sporadic carcinoids tend to be larger, invasive, and more often metastatic, especially in the presence of atypical histology. Small tumors may be removed by endoscopy, but larger lesions need to be surgically excised. In association with metastases a histamine-related atypical carcinoid syndrome may evolve and require treatment with a somatostatin analog. Poorly differentiated neuroendocrine carcinomas of the stomach constitute markedly aggressive tumors that rarely are suitable for radical surgery. Gastrinomas are the most prevalent duodenal carcinoids and a common cause of ZES especially in MEN-I. Despite a marked tendency for regional lymph node dissemination, liver metastases occur late and duodenal gastrinomas are often excisable, thereby offering favorable odds for cure in ZES. Unusual somatostatin-rich carcinoids in the ampulla of Vater relate to von Recklinghausen's disease and may be the cause of obstructive jaundice; depending on their size, these tumors may be removed by local excision or pancreaticoduodenectomy. Gangliocytic paragangliomas are unusual, generally benign lesions of the duodenum. Rare pancreatic tumors with serotonin immunoreactivity may be classified as carcinoids and constitute an unusual cause of the carcinoid syndrome.
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PMID:Management of carcinoid tumors of the stomach, duodenum, and pancreas. 866 14

Long-acting somatostatin analogs, such as octreotide, comprise the therapeutic modality of choice for the symptomatic relief of flush and diarrhea in patients with carcinoid syndrome. The sequelae of gastric acid hypersecretion in patients with gastrin-producing duodenal carcinoids (gastrinoma) are perfectly controlled by proton pump inhibitors. Antiproliferative medical strategies to control the growth of metastatic carcinoid tumors include long-acting somatostatin analogs, interferon alpha, and the combination of the two. However, the success rate is less than 50%, and it is questionable whether true tumor regression can be expected. Controlled prospective studies are mandatory to address the question whether interferon or somatostatin analogs or the combination of the two should be used as first-line medical strategies and if hepatic artery embolization in patients with liver metastases should be performed before beginning medical therapy. Chemotherapy, including etoposide and cisplatin, has been shown to be effective only for purely differentiated neuroendocrine carcinomas and not for slowly growing carcinoids.
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PMID:Medical treatment of metastasizing carcinoid tumors. 866 18

We report a case of left ventricular (LV) myocardial uptake of a labeled somatostatin analog in a patient with a carcinoid tumor of the small bowel. The patient developed liver metastases and a carcinoid syndrome, including right carcinoid heart disease, without right-to-left shunt on contrast ultrasonography or left ventricular myocardial metastases. The basis for visualization of the LV myocardium is probable somatostatin receptor upregulation.
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PMID:Left ventricular myocardial uptake of a labeled somatostatin analog in carcinoid syndrome. 866 61

Recently radiolabeled somatostatin analog, [111In]pentetreotide, was developed and its usefulness for the diagnosis and localization of neuroendocrine tumors has been described. In this paper, we reported the results of [111In]pentetreotide scintigraphy in four patients with gastroenteropancreatic endocrine tumors. Two patients with metastatic gastrinoma, one patient with gastric carcinoid, and one patient suspected with gastrinoma, were injected with 119-156 MBq of [111In]pentetreotide. Planar and SPECT images were obtained 4, 24, and 48 hours postinjection. Both primary and metastatic tumors were well visualized in patients with metastatic gastrinoma. Especially in one patient small liver metastases which were not detected by CT or MRI were imaged. We could not obtain positive images in the other two patients. Four-hour or 24-hr images were better than 48-hr images because of higher count density and lower gut activity. No significant adverse effect were seen in any patient. [111In]pentetreotide scintigraphy is a useful procedure for the localization of gastroenteropancreatic endocrine tumors.
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PMID:[Imaging of somatostatin receptor using 111In-pentetreotide]. 868 86

Octreotide is a synthetic analogue of somatostatin that has clear inhibitory effects on the growth of many animal and human cell lines, including colorectal cell lines both in vitro and in vivo. Colorectal cancer metastatic to the liver is clinically important, both in terms of the number of patients affected and the lack of any effective treatment for the majority of patients. Octreotide inhibits the growth of colorectal liver tumour in a number of experimental models and, in at least three tumour types, inhibits the growth of established micro-metastases. The precise mechanism of action is not known. However, the drug is likely to be most beneficial in the treatment of liver metastases when the tumour burden is relatively small. The available evidence, although experimental, suggests that octreotide may also have a beneficial effect on the development of liver metastases when used as an adjuvant to surgery in colorectal cancer and this area warrants urgent clinical investigation. The cytotoxics which are currently used as an adjuvant to surgery for colorectal cancer have unpleasant side effects which can be life-threatening. There will also be a proportion of patients who have undergone a truly curative resection of their tumour and will thus be treated unnecessarily. The potential benefits of octreotide in the adjuvant setting, although promising, remain speculative, but octreotide has an acceptably low incidence of side effects and can be administered safely for a prolonged period of time.
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PMID:Therapeutic potential of octreotide in the treatment of liver metastases. 882 82

A 59-year-old man presented with painful subcutaneous nodules on the anterior surfaces of the legs. He had received oral antibiotics and supportive care for presumed cellulitis and thrombophlebitis, but had minimal improvement. Five months earlier, he had undergone pancreaticoduodenectomy for acinar pancreatic carcinoma; at that time, the serum level of amylase had been normal, but the level of lipase was elevated. The patient denied fever, rigors, arthritis/arthralgia, or pleuritic pain. His medications included aspirin, furosemide, ranitidine, and nortriptyline. He denied any allergies. Physical examination revealed numerous firm, tender, erythematous and violaceous, subcutaneous nodules on the lower extremities, with marked bilateral pitting edema (Fig. 1). Skin biopsy of a representative lesion revealed septal panniculitis, consistent with erythema nodosum (Fig. 2). None of the characteristic changes of pancreatic fat necrosis was present. The patient was treated with aspirin, 650 mg orally, q 6 h, and indomethacin, 50 mg orally, q 12 h, but he continued to develop new nodules; prednisone, 60 mg orally was begun. Although he reported improvement in symptoms, the nodules failed to respond clinically and older nodules ulcerated along the medical aspect of the right leg (Fig. 3). The complete blood count was normal, except for hemoglobin, 10.9 mg per dL. Routine serum biochemical studies were also normal, except for albumin, 3.1 mg per dL, LDH, 312 U per L, and SGOT, 51 U per L. Serum amylase was 14 U per L (normal per 30 to 115 U per L) and serum lipase was 54,160 U per L (normal 0 to 200 U per L). Chest roentgenogram and tuberculin skin test were negative. A CT scan of the abdomen revealed extensive liver metastases. A second biopsy of the skin and subcutis of a necrotic nodule revealed lobular panniculitis with the characteristic picture seen in pancreatic fat necrosis (Fig. 4). The patient was presumed to have metastatic pancreatic carcinoma and pancreatic fat necrosis. Nodules subsequently developed on the thighs, arms, hands, wrists, and fingers. He developed arthritis and arthralgias of the ankles, wrists, and hands, bilaterally, and the right knee. Aspiration of a right knee effusion revealed numerous neutrophils, but no evidence of infection. Treatment was begun with the somatostatin analog, octreotide, in increasing doses. During this therapy, the lesions did not progress and new lesions did not appear. There was no change in the lipase level. Inadvertently, octreotide was omitted at discharge, but reintroduction of octreotide was associated with lack of further progression of the nodules, according to the patient's spouse; however the patient became progressively debilitated and his abdominal pain worsened, requiring continuous sedation. His condition deteriorated and he died several weeks after hospital discharge.
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PMID:Fat necrosis with features of erythema nodosum in a patient with metastatic pancreatic carcinoma. 883 28

Neuroendocrine gut and pancreatic tumours have provided a diagnostic and therapeutic challenge over the years. These rather slowly growing neoplasms have been assigned a good prognosis but when liver metastases are present the prognosis is not better than that of most other malignant tumours. Despite the development of improved diagnostic procedures many patients are still referred at a stage of the disease too late for surgical cure, at which time medical treatment is warranted. The diagnosis is based on histopathological diagnosis including silver stainings (Grimelius, Masson) and immunohistochemistry for chromogranin A and synaptophysin. Analysis of chromogranin A in the plasma is an important adjunct in the screening for various types of neuroendocrine gut and pancreatic tumours. About 80%-100% of patients with verified neuroendocrine gastrointestinal tumours have elevated circulating levels of this glycoprotein. Depending on clinical symptoms the chromogranin A analysis is supplemented by other peptide hormone analyses as well as urinary 5-HIAA for patients with midgut carcinoid tumours. In the past the localization procedures were based on CT, MRI and ultrasound investigations but in recent years somatostatin receptor scintigraphy (octreoscan) and endoscopic ultrasonography have significantly improved the diagnostic potential. Almost 80% of neuroendocrine gastrointestinal tumours present somatostatin receptor subtype 2 binding 111Indium-labelled octreotide which can be used for staging of the disease, and which also indicates whether or not somatostatin analogues can be used in the treatment of these tumours. Surgery is still a cornerstone in the treatment of neuroendocrine gastrointestinal tumours, even if the patients are beyond cure. Debulking procedures and bypassing operations are important for improving clinical condition and facilitating impending medical treatment, and during the past decade a more aggressive surgical approach has emerged. The medical treatment is based on chemotherapy, and the use of somatostatin analogues and alpha-interferons. Chemotherapy, in particular the combination of streptozotocin with 5-FU or doxorubicin, is still first-line treatment for most endocrine pancreatic tumours, while somatostatin analogues and alpha-interferons are considered first-line for classical midgut carcinoids. Chemotherapy and biotherapy can be combined in many patients, and changes from one medical treatment to another during the course of the disease is mandatory for control of the disease. It is important to realise that most patients with malignant tumours are not cured by medical treatment but that the disease can be controlled for extended periods of time. In the future it will be possible to individualize treatments on the basis of new information about such features of tumour biology as proliferation capacity, expression of adhesion molecules, and growth factors and their receptors.
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PMID:Neuroendocrine gastrointestinal tumours. 883 99


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