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The Journal of Physical Chemistry. B Aug 2012Octreotide, a potent somatostatin (SST) analogue, is used as an antiproliferative drug in numerous endocrine tumors. Previous NMR investigations, basically performed in...
Octreotide, a potent somatostatin (SST) analogue, is used as an antiproliferative drug in numerous endocrine tumors. Previous NMR investigations, basically performed in DMSO, had evidenced a type-II' β-turn structure for this cyclic peptide. However, apart a few incomplete studies by circular dichroism, a systematic analysis of the structural behavior of octreotide in aqueous solution as a function of concentration and ionic strength was still lacking. Here, we report the chemical synthesis and purification of octreotide for optical spectroscopic purposes accompanied by its structural analysis. Furthermore, we have used octreotide as a short size, well-defined model compound for analyzing the CD and Raman markers of a type-II' β-turn. CD data collected in the 25-250 μM range revealed the general trend of octreotide to undergo a disordered toward ordered structural transition upon increasing concentration. Especially, the β-turn CD markers could be characterized above 50 μM by a negative band at ~202 nm flanked by a shoulder at ~218 nm. On the basis of Raman spectra recorded as a function of concentration (1-20 mM), we could assign the markers at ~1678 and ~1650 cm(-1) in the amide I region, and at ~1303, ~1288, and ~1251 cm(-1) in the amide III region, to the type-II' β-turn structure. The stability of the intermolecular antiparallel β-sheet formed in octreotide could be confirmed by the rigidity of the disulfide bridge which adopts a preferential gauche-gauche-gauche rotamer along the -Cβ-S-S-Cβ- moiety of the linked cysteines. The present analysis permits a better understanding of the differences between the structural features of SST-14 and its routinely used analogue, octreotide.
Topics: Amino Acid Sequence; Chromatography, High Pressure Liquid; Circular Dichroism; Models, Molecular; Octreotide; Protein Structure, Secondary; Spectrometry, Mass, Electrospray Ionization; Spectrum Analysis, Raman
PubMed: 22793173
DOI: 10.1021/jp3036428 -
The Quarterly Journal of Nuclear... Feb 2010The use of somatostatin (SS) analogues in humans takes advantage by the availability of many related chemical forms that can be used for receptor therapy and, after... (Review)
Review
The use of somatostatin (SS) analogues in humans takes advantage by the availability of many related chemical forms that can be used for receptor therapy and, after radiolabelling, for diagnostic imaging and radionuclide therapy. The first proposed radiocompound, yet clinically widely diffuse, has been (111)In-octreotide (OCT), followed by positron emission tomography (PET) and beta emitter tracers. The main field of clinical applications is in neuroendocrine tumours (NET), starting by the demonstration of SS receptors (SSR) on the majority of NET, particularly on gastroenteropancreatic (GEP) tumours. Uptake of SS analogues can also be due to a SSR expression on non malignant cells when activated, as lymphocytes, macrophages, fibroblasts , vascular cells. Because of this uptake clinical indications can be found also in active benign diseases, as Grave's ophthalmopathy, rheumatoid arthritis, histiocitosis, sarcoidosis, idiopatic pulmonary fibrosis. Moreover, these cells can also determine the OCT in vivo uptake in tumours non expressing in vitro SSR, as non-snall cell lung cancer (NSCLC). Because of a different kinetic respect to SCLC a differential histotype diagnosis could be obtained. Starting from this premise OCT can also allows radioguided surgery in tumours non expressing SSR. Finally a relevant clinical role can be defined in the a priori recruitment and as marker of therapeutic efficacy in all the therapeutic strategies utilizing SSR, both in malignant and benign diseases.
Topics: Biological Transport; Humans; Neoplasms; Octreotide; Radionuclide Imaging; Receptors, Somatostatin; Somatostatin
PubMed: 20168284
DOI: No ID Found -
Praxis Mar 1995
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Expert Opinion on Drug Safety Nov 2010Octreotide analogs are used in the treatment of neuroendocrine tumors and are investigated as treatment options in many diseases. These agents mimic somatostatin effect...
Octreotide analogs are used in the treatment of neuroendocrine tumors and are investigated as treatment options in many diseases. These agents mimic somatostatin effect which is inhibitory to pancreatic hormones. The most common side effects are biliary dysfunction and gastroenterologic disorders. Pancreatic insufficiency is a common adverse effect of this medication which is explained by the direct inhibition of pancreatic hormones responsible for stimulating the production and excretion of pancreatic enzymes. This side effect is misdiagnosed leading to increasing octreotide analog dosage, and eventually more pancreatic insufficiency and cost of treatment. We report our experience with pancreatic insufficiency developing in neuroendocrine tumor patients treated with octreotide analogs, reviewing the pathogenesis of this side effect. This common but underpublished condition is easy to diagnose and treat.
Topics: Adult; Aged; Aged, 80 and over; Diagnostic Errors; Diarrhea; Exocrine Pancreatic Insufficiency; Female; Gastrointestinal Agents; Humans; Male; Middle Aged; Octreotide; Receptors, Serotonin; Time Factors
PubMed: 20662741
DOI: 10.1517/14740338.2010.510130 -
American Journal of Surgery Nov 1991The long-acting somatostatin analogue, octreotide, has recently been made available for clinical use in the United States. This novel synthetic peptide possesses a broad... (Review)
Review
The long-acting somatostatin analogue, octreotide, has recently been made available for clinical use in the United States. This novel synthetic peptide possesses a broad spectrum of physiologic actions primarily involving the inhibition of a variety of gastrointestinal and endocrine functions. Such actions have been utilized in the management of a variety of surgical disorders. Current understanding of the indications and efficacy of this agent in the treatment of surgical disease is reviewed.
Topics: Amino Acid Sequence; Gastrointestinal Diseases; Humans; Molecular Sequence Data; Neoplasms, Hormone-Dependent; Octreotide; Pancreatic Diseases
PubMed: 1951921
DOI: 10.1016/0002-9610(91)90273-g -
Drug and Therapeutics Bulletin Mar 1991
Topics: Endocrine Gland Neoplasms; Humans; Octreotide
PubMed: 1935602
DOI: No ID Found -
Digestive Diseases and Sciences Nov 2000We investigated the effect of octreotide in the treatment of severe acute pancreatitis in a case-control study. Experimental and clinical studies on the effect of... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
We investigated the effect of octreotide in the treatment of severe acute pancreatitis in a case-control study. Experimental and clinical studies on the effect of octreotide in the treatment of acute pancreatitis have shown controversial results. Since January 1992, we have been conducting a prospective randomized study on the effect of octreotide in severe acute pancreatitis, in three hospitals in Israel. The entering criteria included three or more of the Ranson prognostic signs and CT findings of severe pancreatitis. Patients were randomly assigned to conservative treatment either with or without octreotide (0.1 mg subcutaneously three times a day). The end points of the study included: complication rate (ARDS, sepsis, renal failure, pseudocyst, fistula, and abscess), length of hospital stay, and mortality. From January 1992 to December 1996, 60 patients entered the study. After evaluating the files, 10 patients were excluded due to failure to meet the entering criteria, incomplete data, or incorrect diagnosis. Of the remaining 50 patients, 25 were assigned to octreotide (treatment group) and 25 to conservative treatment only (control group). The two groups matched with regard to age, sex, etiology, and severity of the disease. The complication rate was lower in the treatment group with regard to sepsis (24% vs 76%, P = 0.0002) and ARDS (28% vs 56%, P = 0.04). The hospital stay was shorter in the treatment group (20.6 vs 33.1 days, P = 0.04). Two patients died in the treatment group and eight in the control group (P < 0.019). These results suggest that octreotide may have a beneficial effect in the treatment of severe acute pancreatitis.
Topics: Adult; Aged; Case-Control Studies; Female; Humans; Injections, Subcutaneous; Length of Stay; Male; Middle Aged; Octreotide; Pancreatitis, Acute Necrotizing; Survival Rate; Treatment Outcome
PubMed: 11215748
DOI: 10.1023/a:1026679106463 -
Annals of Oncology : Official Journal... 2001Neuroendocrine tumors are rare, occurring in less than 1% of the population. They are divided clinically into functionally active or non-active tumors. Functionally... (Review)
Review
Neuroendocrine tumors are rare, occurring in less than 1% of the population. They are divided clinically into functionally active or non-active tumors. Functionally active tumors produce a variety of substances (mainly peptides or serotonin) that are responsible for symptoms and sometimes can lead to the death of the patient independently from tumor proliferation. The most important compounds that can control symptoms in these patients are somatostatin analogs. Native somatostatin is not suitable for long-term clinical application due to its short half-life. Therefore, synthetic drugs were developed with improved pharmacokinetic characteristics. The best-characterized analog, octreotide, has been successfully applied to patients with functioning tumors. Octreotide can ameliorate symptoms in 30%-70% of the patients, mainly through a direct inhibitory effect on hormone production from the tumors. There is little or no effect on tumor growth during octreotide therapy; clinical responses were recorded in only 10%-30% of the patients. Recently, significant improvement in the management of the disease has been demonstrated with long-acting repeatable (LAR) octreotide. This new formulation requires only one monthly intramuscolar injection, and shows better acceptability and patient compliance to therapy. Data available to date show superimposable results of both standard octreotide and LAR octreotide in controlling symptoms, lowering hormone and tumor marker levels, and in reducing tumor growth. The availability of long-acting molecules have permitted the exploration of high-dose therapy in increasing tumor shrinkage and prolonging survival. Although there is a clear dose-response trend, the published data are not conclusive and further investigations are needed. The possible lack of cross-resistance between LAR octreotide and a different analog, Lanreotide, is a very stimulating finding and this might lead to the development of new therapeutical strategies in the management of neuroendocrine tumors.
Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Clinical Trials as Topic; Delayed-Action Preparations; Dose-Response Relationship, Drug; Humans; Injections, Subcutaneous; Neuroendocrine Tumors; Octreotide; Peptides, Cyclic; Somatostatin; Survival Analysis
PubMed: 11762334
DOI: 10.1093/annonc/12.suppl_2.s105 -
Hepato-gastroenterology 2000To assess the value of octreotide in the control of acute bleeding esophageal varices, in a prospective randomized study. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND/AIMS
To assess the value of octreotide in the control of acute bleeding esophageal varices, in a prospective randomized study.
METHODOLOGY
One hundred and ninety-seven patients admitted for variceal bleeding confirmed at endoscopy were recruited and divided into two groups: group I (n = 111) with endoscopic stigmata of recent bleeding; and group II (n = 86) with active bleeding at emergency endoscopy. Patients in group I were randomized to receive a continuous infusion of octreotide (n = 58) or emergency sclerotherapy (n = 53). Patients in group II were assigned to sclerotherapy (n = 42) or to sclerotherapy plus octreotide (n = 44). At the end of the period of study (48 hours), patients were submitted to sclerotherapy or band ligation until variceal obliteration was achieved.
RESULTS
In group I, octreotide was found to be as effective as sclerotherapy regarding hemostasis at 48 hours and on day 7 after the index bleeding episode. Transfusion needs were not significantly different for the two treatment modalities. In group II, the association of octreotide with sclerotherapy was significantly better than sclerotherapy alone either in controlling acute active bleeding (P < 0.001) or in achieving hemostasis at 48 hours (P < 0.01). Transfusion needs were significantly fewer in patients treated with this therapeutic association as compared to sclerotherapy alone.
CONCLUSIONS
These results suggest that octreotide infusion is effective in the treatment of variceal bleeding. In patients with recent bleeding, octreotide infusion is as effective as emergency sclerotherapy. In active variceal bleeding, it is a valuable adjuvant treatment in association with emergency sclerotherapy.
Topics: Acute Disease; Emergencies; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Octreotide; Prospective Studies; Sclerotherapy
PubMed: 11100339
DOI: No ID Found -
Digestion 1999
Topics: Gastrointestinal Agents; Hormones; Humans; Octreotide
PubMed: 10357619
DOI: 10.1159/000051473