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)

Malignant carcinoid tumours with the carcinoid syndrome has over the years presented a therapeutic challenge. The patients might not only die from tumour progression but also from symptoms relating to hormone overproduction and the specific cardiac disease, e.g. right heart fibrosis and failure. Surgery has been the treatment of choice in local disease, but when liver metastases have developed other treatment procedures must be considered. Conventional chemotherapy has been of little beneficial value, with response rates of only 10-30%, whereas a new somatostatin analogue, octreotid, is effective in controlling clinical symptoms but not tumour progression. Interferon treatment was introduced in 1982 by our group, and we are now presenting treatment results of 130 patients with histologically verified malignant carcinoid tumours and liver metastases. One hundred and eleven patients were treated with a median dose of 6 mega units (MU) of interferon alpha, five times weekly (dose range 3-9 MU), whereas 29 patients received conventional chemotherapy. Forty-seven out of 111 patients (42%) treated with interferon alpha demonstrated a significant biochemical response and 15% demonstrated more than 50% reduction in tumour size. In another 43 (39%) patients stabilization of the carcinoid disease have been noted, whereas 21 (19%) showed progressive disease. The median duration of response was 34 months. Subjective responses with improvement of diarrhoea, flush and/or bronchoconstriction were noticed in 76 patients (68%). The 19 patients treated with chemotherapy demonstrated only 10% biochemical response, lasting for only 3-5 months. The survival analysis demonstrates a median survival of only 8 months in the group of patients treated with chemotherapy, compared to 80+ months (P less than 0.001) in the groups treated with interferon alpha. Interferon adverse reactions of fatigue, weight loss and anaemia were manageable. Neutralizing interferon antibodies were documented in 5-15% of the patients. Interferon alphas are active in patients with malignant carcinoid tumours. Clinical symptoms are significantly reduced following reduction of circulating hormones. Interferon might also have an impact on survival in this group of patients. The side-effects are moderate and managed by dose adjustments.
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PMID:The role of interferons in the management of carcinoid tumours. 183 59

We describe the 4-year follow-up of an endocrine tumour of the pancreas (vipoma-glucagonoma) treated with chemotherapy. To control the endocrine syndrome we used somatostatin 14 by continuous subcutaneous infusion for 1 year, followed by the somatostatin analogue SMS 201-995 administered alone without antitumoral chemotherapy. Under SMS 201-995 (100 micrograms 12-hourly) the endocrine syndrome dramatically improved. This effect persisted for 12 months after which a relative resistance to the drug developed. It was necessary to increase the dosage (300-400 micrograms/24 hours) and to alter the mode of administration (continuous subcutaneous infusion) to obtain a clinical benefit inferior to that obtained during the first year of treatment with SMS 201-995. At present this drug is given combined with recombinant interferon alpha 2A. In spite of computerized tomography, ultrasonography and monitoring of hormone levels we were unable to determine whether or not SMS 201-995 exerted a partial antitumoral effect.
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PMID:[Mixed endocrine tumor of the pancreas (vipoma, glucagonoma). Treatment by somatostatin followed by one of its long-acting analogs]. 289 69

With regard to diabetic retinopathy, in addition to the demonstration by the DCCT study that prevention is achieved by good metabolic control, our present knowledge on physiopathology leads us to imagine three types of possible therapeutic approach; inhibition of glucotoxicity, improvement of capillary flow, blockade of angiogenesis. 1) Inhibition of glucotoxicity Aldose reductase inhibitors can prevent cataract in diabetic or galactosemic rats. The effect of these drugs on retinopathy, evaluated in some clinical trials, remains controversial, suggesting a minor role. Aminoguanidine is an inhibitor of formation of advanced glycosylation end-products (AGE). This compound has been tested on a model of experimental retinopathy in rats. Parallel to the AGE decrease in retina, formation of microaneurysms and loss of endothelial cells in capillaries were delayed. Clinical tolerance allows human application and randomised trials will give further information on this potentially efficient drug. 2) Improvement of capillary flow This objective can be obtained by drugs inhibiting platelet aggregation or improving erythrocyte or leucocyte deformability. Clinical trials using such compounds were not very conclusive. 3) Blockade of angiogenesis Proliferation of new vessels is a rather severe stage of diabetic retinopathy. Angiogenesis is due to factors locally produced (as FGF, TGF and u-PA produced by anoxic tissues), systemic (IGF-1) or released by inflammatory reaction (IL1, TNF alpha and beta). One imagines usage of drugs which inhibit these factors and prevent angiogenesis. At the present time, two approaches have been used in proliferative retinopathy worsening despite panphotocoagulation; analogues of somatostatin and interferon alpha. The promissing results of these pilot studies have to be confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Outlook for the future in the treatment of diabetic retinopathy]. 752 51

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

Gastrointestinal neuroendocrine tumors are slowly growing and metastases are often limited to the liver. As a result of their favorable biological behavior these tumors have a relatively good prognosis even in metastatic stage. Due to a variety of therapeutic options patients with malignant neuroendocrine tumors may survive for extended periods of time up to ten years. Often a combination of different treatments and also alternation between the different therapeutic regimes is needed. A patient with excessive WDHA-syndrome and severe metabolic disturbances due to a pancreatic VIPoma with metastatic spread into the liver and abundant hormonal secretion is presented. Cytotoxic agents (streptozocin, 5-fluorouracil and adriamycin) were able to alleviate clinical symptoms and to control tumor growth for six years. Analogues of somatostatin (octreotide) and interferon alpha had been very useful in controlling clinical symptoms and tumor progress for 18 months. Cytotoxic agents or octreotide were not able, however, to achieve any permanent cure. Eventually, treatment failure occurred with dramatic progression of symptoms and tumor growth, unresponsive to any medical therapy. Consequently, total hepatectomy and liver transplantation together with extirpation of the pancreatic primary tumor was performed and succeeded in providing a normal life to the patient. In our opinion the overall outcome of patients with metastatic VIPoma may be improved best by maintaining the patients on medical therapy until treatment failure occurs. In case of extended hepatic metastases orthotopic liver transplantation might be considered for patients with symptomatic disease who no longer respond to conventional treatment modalities.
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PMID:Metastatic pancreatic VIPoma: deteriorating clinical course and successful treatment by liver transplantation. 957 8

Carcinoid tumours in the intestine are slowly growing neuroendocrine tumours. Patients as a rule report symptoms of the carcinoid syndrome: attacks of diarrhoea and of flushing. When the earliest symptoms manifest themselves, metastases are already present, virtually always localized in the liver. At a late stage, heart failure may occur, difficult to treat and caused by fibrosis of the tricuspid valve in the presence of protractedly raised blood serotonin levels. To diagnose carcinoid tumours, use is made of radioactive substances binding to hormone receptors such as 131I-MIBG and 111-In-octreotide. When multiple metastases exist, only palliative treatment is possible. The drugs used are the somatostatin analog octreotide, interferon alpha, radioactive MIBG and non-radioactive MIBG; these drugs may also be used in combination. The therapies mentioned have approximately the same effect: symptoms improve in 60-80%, while 30-50% show a biochemical response, i.e. decrease of the number of breakdown products in the urine of the hormones produced by the tumour; tumour size decreases in 0-12%.
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PMID:[Carcinoid tumors of the intestines: developments in the Netherlands for diagnosis and palliative treatment]. 1022 Nov 20

Zollinger-Ellison syndrome is characterised by refractory peptic ulcer disease, severe diarrhoea and gastric acid hypersecretion associated with an islet-cell tumour of the pancreas (gastrinoma). The true incidence and prevalence of this rare disease is unknown; in the US, the frequency is one per one million people and the age at presentation varies from 7 to 90 years. Zollinger-Ellison syndrome is sporadic in 62-80% of cases and in 20-38% of cases is associated with multiple endocrine neoplasia type 1 (MEN 1). The diagnosis of Zollinger-Ellison syndrome is certain when the plasma gastrin is >1000 pg/mL and the basal acid output is >15 mEq/h in patients with an intact stomach, >5 mEq/h in gastrectomised patients, or when this hypergastrinemia is associated with a pH <2. The treatment is based on control of gastric acid hypersecretion and of the malignant tumour and its possible metastases. Proton pump inhibitors are the most effective antisecretory drugs and can be administered in the elderly at high dosages without drug-related adverse effects. As an initial therapy, daily dosages of omeprazole 80-100 mg or pantoprazole 40-160 mg are employed. In long-term treatment the doses can be greatly reduced once effective control of the gastric output has been established. Intravenous proton pump inhibitors may be administered when patients cannot take oral therapy, particularly in acute conditions. All sporadic localised gastrinomas should be excised if possible. When liver metastases are also present, their debulking may improve symptoms and survival, and facilitate medical treatment. There is some controversy as to the surgical approach for gastrinomas associated with MEN 1. Somatostatin analogues can be useful in reducing gastric acid hypersecretion, serum gastrin and gastric enterochromaffin-like (ECL) cells and can thus contribute to treating the disease more effectively. Their antiproliferative effect can be used in treating liver metastases. Chemotherapy is not the therapy of choice in patients with gastrinomas and is indicated only in those with malignant progressive disease; interferon alpha, embolisation and chemoembolisation are not advisable for the elderly. The treatment of elderly Zollinger-Ellison syndrome patients, similarly to all elderly oncological patients, should be based on the use of comprehensive geriatric assessment. This will enable the clinician to define the functional status of the elderly person, to decide whether the patient can tolerate surgery and/or the stress of antineoplastic therapy, and finally, to determine whether this patient can tolerate an aggressive treatment for Zollinger-Ellison syndrome or whether the only possible choice is palliative relief of symptoms.
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PMID:Optimal treatment of Zollinger-Ellison syndrome and related conditions in elderly patients. 1465 42

Neuroendocrine tumors of the gastroenteropancreatic (GEP) system are rare neoplasms, characterized by their capacity to synthesize, store, and release hormonal products and biogenic amines. Because of their low incidence, limited data about clinical outcomes and prognostic variables are available. They can present clinical symptoms caused by the products secreted, tumor mass or metastases. Assessment of specific or nonspecific tumor markers offers high sensitivity in establishing diagnosis and can also have prognostic significance. Imaging modalities include endoscopic ultrasonography, computerized tomography, magnetic resonance imaging, and in particular, scintigraphy with somatostatin analogs. The radical treatment of GEP tumors is tumor surgery, but this is rarely possible. Somatostatin analogs have been the treatment of choice in symptomatic patients with GEP tumors. In poorly differentiated tumors or in selected cases of advanced or rapidly growing disease, interferon alpha, chemotherapy, and/or radio-metabolic treatment with radiolabeled somatostatin analogs can be performed. Symptomatic therapy is also helpful.
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PMID:[Diagnostic and therapeutic opportunities in neuroendocrine tumors of the gastroenteropancreatic system]. 1576 86

The application of second derivative tryptophan (Trp) fluorescence spectroscopy to characterize partially unfolded intermediates of proteins relevant to protein formulation was investigated. The second derivatives of the normalized emission scans of N-acetyl tryptophanamide (NATA), single-Trp containing proteins, somatostatin and human serum albumin (HSA), and two-Trp containing proteins previously shown to form partially unfolded intermediates, beta-lactoglobulin (beta Lg) and interferon alpha-2a (IFN alpha 2a), were studied in solution. The second derivative of NATA in water showed three bands at 340, 348 and 367 nm. The 340 nm band showed a blue shift, whereas the intensity of all three bands was affected by a decrease in solution polarity. Second derivative of single-Trp containing proteins, somatostatin and HSA, showed three negative bands, whereas, the second derivative of the two-Trp containing proteins, beta Lg and IFN alpha 2a, showed four bands, two of which lie in the 320-340 nm range. These two bands were attributed to the presence of the Trps in different microenvironments. The characteristic changes in the intensities of these two bands on addition of guanidine hydrochloride (beta Lg) and with a decrease in solution pH (IFN alpha 2a) were related to the presence of partially unfolded intermediates of these proteins. Thus, second derivative Trp fluorescence spectroscopy can be used as an important tool to identify partially unfolded states of proteins during formulation utilizing order of magnitude lower concentrations compared to such other technique as near UV CD.
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PMID:Second derivative tryptophan fluorescence spectroscopy as a tool to characterize partially unfolded intermediates of proteins. 1581 44

Octreotide is one of the somatostatin analogue used for the treatment of endocrine tumors principally to suppress hormone secretion and to inhibit tumor growth. We experienced a case with multiple endocrine neoplasia type 1 who small amount of octreotide dramatically relieved the lumber pain caused by metastatic bone tumor. He had recurrent bronchial carcinoid tumors that metastasized to liver and bones. The spontaneous and radiated pain by bone tumors subsided within a few minutes after the initial injection of octreotide and the effect persisted for several hours. Combination therapy of octreotide and interferon alpha-2b significantly reduced the size of metastatic liver tumors and inhibited further growth of metastatic bone tumors for the last 27 months. The use of octreotide may be a good option for controlling pain by metastatic bone disease and combination therapy of octreotide and interferon alpha-2b is worth to try for patients with inoperable metastatic carcinoid tumor.
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PMID:Octreotide as a rapid and effective painkiller for metastatic carcinoid tumor. 1586 61


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