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Indian Journal of Cancer 2023Postoperative pancreatic fistula (POPF) is the most feared complication following pancreatic resection. Octreotide, a synthetic somatostatin analog, has been widely used... (Review)
Review
Postoperative pancreatic fistula (POPF) is the most feared complication following pancreatic resection. Octreotide, a synthetic somatostatin analog, has been widely used by pancreatic surgeons worldwide after pancreatic resections, often as per surgeon's discretion, to prevent POPF especially in cases at high risk of developing POPF. We herein analyze the data available till date of the subject. A PubMed search with keywords "somatostatin OR octreotide OR somatostatin analogues AND postoperative pancreatic fistula" was made. Further filters were applied in the search "Clinical Trial, Meta-Analysis, Randomized Controlled Trial, Systematic Review, from 1990 - 2021," and the 68 results thus obtained were analyzed and included in this narrative review. There is considerable heterogeneity among the studies assessing the role of octreotide in the prevention of POPF making data comparison difficult, and hence results remain inconclusive. Most of the earlier studies used different definitions of POPF and other complications; included patients with varied pancreatic pathologies such as cancer, chronic pancreatitis, and benign lesions; surgical techniques such as pancreaticoduodenectomy, distal pancreatectomy, and other procedures; use of somatostatin and its analogs such as octreotide, lanreotide, pasireotide, and vapreotide; varied surgeon and institutional volume; and so on. Besides, pancreatic surgery is per se a complex surgical procedure and has its own inherent biases related to patient and the pancreas itself affecting the overall outcome. Data indicate favorable role of newer somatostatin analogs, and further studies are urgently needed. The question about the efficacy of prophylactic octreotide to reduce POPF after pancreaticoduodenectomy remains open to debate.
Topics: Humans; Octreotide; Pancreas; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Factors; Somatostatin; Treatment Outcome
PubMed: 37530235
DOI: 10.4103/ijc.IJC_280_21 -
Archives of Medical Science : AMS 2020The extreme health and economic problems in the world due to the SARS-CoV-2 infection have led to an urgent need to identify potential drug targets for treating...
INTRODUCTION
The extreme health and economic problems in the world due to the SARS-CoV-2 infection have led to an urgent need to identify potential drug targets for treating coronavirus disease 2019 (COVID-19). The present state-of-the-art tool-based screening was targeted to identify drug targets among clinically approved drugs by uncovering SARS-CoV-2 helicase inhibitors through molecular docking analysis.
MATERIAL AND METHODS
Helicase is a vital viral replication enzyme, which unwinds nucleic acids and separates the double-stranded nucleic acids into single-stranded nucleic acids. Hence, the SARS-CoV-2 helicase protein 3D structure was predicted, validated, and used to screen the druggable targets among clinically approved drugs such as protease inhibitor, nucleoside reverse transcriptase inhibitor, and non-nucleoside reverse transcriptase inhibitors, used to treat HIV infection using molecular docking analysis.
RESULTS
Interaction with SARS-CoV-2 helicase, approved drugs, vapreotide (affinity: -12.88; score: -9.84 kcal/mol), and atazanavir (affinity: -11.28; score: -9.32 kcal/mol), approved drugs for treating AIDS-related diarrhoea and HIV infection, respectively, are observed with significantly low binding affinity and MOE score or binding free energy. The functional binding pockets of the clinically approved drugs on SARS-CoV-2 helicase protein molecule suggest that vapreotide and atazanavir may interrupt the activities of the SARS-CoV-2 helicase.
CONCLUSIONS
The study suggests that vapreotide may be a choice of drug for wet lab studies to inhibit the infection of SARS-CoV-2.
PubMed: 32399096
DOI: 10.5114/aoms.2020.94567 -
Saudi Pharmaceutical Journal : SPJ :... Dec 2018Cancer may be difficult to target, however, if cancer targeted this provides the chance for a better and more effective treatment. uantum dots (Qdots) coated vapreotide...
Cancer may be difficult to target, however, if cancer targeted this provides the chance for a better and more effective treatment. uantum dots (Qdots) coated vapreotide (VAP) as a somatostatin receptors (SSTRs) agonist can be efficient targeting issue since may reduce side effects and increase drug delivery to the target tissue. This study highlights the active targeting of cancer cells by cells imaging with improving the therapeutic outcomes. VAP was conjugated to Qdots using amine-to-sulfhydryl crosslinker. The synthesized Qdots-VAP was characterized by determination of size, measuring the zeta-potential and UV fluorometer. The cellular uptake was studied using different cell lines. Finally, the Qdots-VAP was injected into a rat model. The results showed a size of 479.8 ± 15 and 604.88 ± 17 nm for unmodified Qdots and Qdots-VAP respectively, while the zeta potential of particles went from negative to positive charge which proved the conjugation of VAP to Qdots. The fluorometer recorded a redshift for Qdots-VAP compared with unmodified Qdots. Moreover, cellular uptake exhibited high specific binding with cells which express SSTRs using confocal microscopy and flow cytometry (17.3 MFU comparing to 3.1 MFU of control, P < 0.001). Finally, an study showed a strong accumulation of Qdots-VAP in the blood cells (70%). In conclusion, Qdots-VAP can play a crucial role in cancer diagnosis and treatment of blood cells diseases when conjugated with VAP as SSTRs agonist.
PubMed: 30532637
DOI: 10.1016/j.jsps.2018.07.004 -
Neuropsychopharmacology : Official... Jul 2017Altered brain somatostatin functions recently appeared as key elements for the pathogenesis of stress-related neuropsychiatric disorders. The hippocampus exerts an...
Altered brain somatostatin functions recently appeared as key elements for the pathogenesis of stress-related neuropsychiatric disorders. The hippocampus exerts an inhibitory feedback on stress but the mechanisms involved remain unclear. We investigated herein the role of hippocampal somatostatin receptor subtypes in both stress response and behavioral emotionality using C57BL/6, wild type and sst or sst knockout mice. Inhibitory effects of hippocampal infusions of somatostatin agonists on stress-induced hypothalamo-pituitary-adrenal axis (HPA) activity were tested by monitoring peripheral blood and local hippocampus corticosterone levels, the latter by using microdialysis. Anxiolytic and antidepressant-like effects were determined in the elevated-plus maze, open field, forced swimming, and stress-sensitive beam walking tests. Hippocampal injections of somatostatin analogs and sst or sst but not sst or sst receptor agonists produced rapid and sustained inhibition of HPA axis. sst agonists selectively produced anxiolytic-like behaviors whereas both sst and sst agonists had antidepressant-like effects. Consistent with these findings, high corticosterone levels and anxiety were found in sstKO mice and depressive-like behaviors observed in both sstKO and sstKO strains. Both hippocampal sst and sst receptors selectively inhibit stress-induced HPA axis activation but mediate anxiolytic and antidepressive effects through distinct mechanisms. Such results are to be accounted for in development of pathway-specific somatostatin receptor agents in the treatment of hypercortisolism (Cushing's disease) and stress-related neuropsychiatric disorders.
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Behavior, Animal; Corticosterone; Emotions; Hippocampus; Hypothalamo-Hypophyseal System; Male; Mice; Mice, Knockout; Octreotide; Pituitary-Adrenal System; Receptors, Somatostatin; Somatostatin; Stress, Psychological
PubMed: 27986975
DOI: 10.1038/npp.2016.281 -
Journal of Clinical Gastroenterology 2017Data on acute variceal hemorrhage (AVH) in the United States is limited and the best method to stratify risk is not clear. Taking advantage of a prospective US cohort... (Observational Study)
Observational Study
GOALS/BACKGROUND
Data on acute variceal hemorrhage (AVH) in the United States is limited and the best method to stratify risk is not clear. Taking advantage of a prospective US cohort study, we aimed to (1) describe clinical outcomes of AVH and their predictors; (2) compare predictors of 6-week mortality.
STUDY
Prospective 15-center US cohort of patients with cirrhosis presenting with endoscopically proven AVH, all of whom received antibiotics, vapreotide (a somatostain analog) infusion and endoscopic band ligation. Patients were enrolled between August 2006 and April 2008. Primary outcome was 6-week mortality. Secondary outcome was 5-day treatment failure. The prognostic value of Child-Turcotte-Pugh (CTP) class, Model for End-stage Liver Disease (MELD) score and a recent recalibrated MELD were compared.
RESULTS
Seventy eligible patient were enrolled; 18 (26%) patients died within 6-weeks of index bleed. Demographic, clinical, and laboratory data were compared between survivors and nonsurvivors. Multivariate models showed that admission CTP or the MELD score (separately) were independent predictors of survival. The discriminative values of CTP (area under receiver operating characteristic: 0.75) and MELD (area under receiver operating characteristic: 0.79) were good and not significantly different (P=0.27). However, calibration (correlation between observed and predicted mortality) test was significantly better for CTP than for MELD, with the recently described recalibrated MELD model having the worst agreement. Predicted mortality for CTP-A was <10%, CTP-B 10% to 30%; and CTP-C >33%.
CONCLUSIONS
AVH mortality of 26% in the United States is in the upper range limit compared with recent series but may be due to inclusion of patients with more advanced cirrhosis. CTP score has the best overall performance in the prediction of 6-week mortality and is best at stratifying risk.
Topics: Decision Support Techniques; Disease Progression; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Predictive Value of Tests; Risk Assessment; Risk Factors; Time Factors; Treatment Failure; United States
PubMed: 27779613
DOI: 10.1097/MCG.0000000000000733 -
Oncotarget Apr 2016Malignant brain glioma is the most lethal and aggressive type of cancer. Surgery and radiotherapy cannot eliminate all glioma stem cells (GSCs) and blood-brain barrier...
Malignant brain glioma is the most lethal and aggressive type of cancer. Surgery and radiotherapy cannot eliminate all glioma stem cells (GSCs) and blood-brain barrier (BBB) restricts the movement of antitumor drugs from blood to brain, thus leading to the poor prognosis with high recurrence rate. In the present study, the targeting conjugates of cholesterol polyethylene glycol polyethylenimine (CHOL-PEG2000-PEI) and D-a-tocopheryl polyethylene glycol 1000 succinate vapreotide (TPGS1000-VAP) were newly synthesized for transporting drugs across the BBB and targeting glioma cells and GSCs. The multifunctional targeting vinorelbine plus tetrandrine liposomes were constructed by modifying the targeting conjugates. The studies were undertaken on BBB model, glioma cells, GSCs, and glioma-bearing mice. In vitro results showed that multifunctional targeting drugs-loaded liposomes with suitable physicochemical property could enhance the transport drugs across the BBB, increase the intracellular uptake, inhibit glioma cells and GSCs, penetrate and destruct the GSCs spheroids, and induce apoptosis via activating related apoptotic proteins. In vivo results demonstrated that multifunctional targeting drugs-loaded liposomes could significantly accumulate into brain tumor location, show the specificity to tumor sites, and result in a robust overall antitumor efficacy in glioma-bearing mice. These data suggested that the multifunctional targeting vinorelbine plus tetrandrine liposomes could offer a promising strategy for treating brain glioma.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzylisoquinolines; Brain Neoplasms; Cell Line, Tumor; Glioma; Liposomes; Mice; Mice, Inbred ICR; Molecular Targeted Therapy; Neoplastic Stem Cells; Random Allocation; Vinblastine; Vinorelbine
PubMed: 27029055
DOI: 10.18632/oncotarget.8360 -
Neuroimmunomodulation 2013Vapreotide, a synthetic analog of somatostatin, has analgesic activity most likely mediated through the blockade of neurokinin-1 receptor (NK1R), the substance P...
OBJECTIVES
Vapreotide, a synthetic analog of somatostatin, has analgesic activity most likely mediated through the blockade of neurokinin-1 receptor (NK1R), the substance P (SP)-preferring receptor. The ability of vapreotide to interfere with other biological effects of SP has yet to be investigated.
METHODS
We studied the ability of vapreotide to antagonize NK1R in three different cell types: immortalized U373MG human astrocytoma cells, human monocyte-derived macrophages (MDM) and a human embryonic kidney cell line, HEK293. Both U373MG and MDM express endogenous NK1R while HEK293 cells, which normally do not express NK1R, are stably transformed to express human NK1R (HEK293-NK1R).
RESULTS
Vapreotide attenuates SP-triggered intracellular calcium increases and nuclear factor-κB activation in a dose-dependent manner. Vapreotide also inhibits SP-induced interleukin-8 and monocyte chemotactic protein-1 production in HEK293-NK1R and U373MG cell lines. Vapreotide inhibits HIV-1 infection of human MDM in vitro, an effect that is reversible by SP pretreatment.
CONCLUSIONS
Our findings indicate that vapreotide has NK1R antagonist activity and may have a potential application as a therapeutic intervention in HIV-1 infection.
Topics: Analgesics; Aprepitant; Calcium; Cell Line; Chemokine CCL2; Cytokines; Dose-Response Relationship, Drug; Drug Interactions; Gene Expression Regulation; Humans; Macrophages; Morpholines; NF-kappa B; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Receptors, Somatostatin; Signal Transduction; Somatostatin; Substance P; Transfection; gag Gene Products, Human Immunodeficiency Virus
PubMed: 23921645
DOI: 10.1159/000350468 -
The Journal of Biological Chemistry Sep 2013Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine...
Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine and bleeding disorders, cancer, and diarrhea, with gastrointestinal side effects of constipation, abdominal pain, and nausea. How endogenous agonists and drugs differentially regulate neuronal SSTR2A is unexplored. We evaluated SSTR2A trafficking in murine myenteric neurons and neuroendocrine AtT-20 cells by microscopy and determined whether agonist degradation by endosomal endothelin-converting enzyme 1 (ECE-1) controls SSTR2A trafficking and association with β-arrestins, key regulators of receptors. SST-14, SST-28, and peptide analogs (octreotide, lanreotide, and vapreotide) stimulated clathrin- and dynamin-mediated internalization of SSTR2A, which colocalized with ECE-1 in endosomes and the Golgi. After incubation with SST-14, SSTR2A recycled to the plasma membrane, which required active ECE-1 and an intact Golgi. SSTR2A activated by SST-28, octreotide, lanreotide, or vapreotide was retained within the Golgi and did not recycle. Although ECE-1 rapidly degraded SST-14, SST-28 was resistant to degradation, and ECE-1 did not degrade SST analogs. SST-14 and SST-28 induced transient interactions between SSTR2A and β-arrestins that were stabilized by an ECE-1 inhibitor. Octreotide induced sustained SSTR2A/β-arrestin interactions that were not regulated by ECE-1. Thus, when activated by SST-14, SSTR2A internalizes and recycles via the Golgi, which requires ECE-1 degradation of SST-14 and receptor dissociation from β-arrestins. After activation by ECE-1-resistant SST-28 and analogs, SSTR2A remains in endosomes because of sustained β-arrestin interactions. Therapeutic SST analogs are ECE-1-resistant and retain SSTR2A in endosomes, which may explain their long-lasting actions.
Topics: Animals; Arrestins; Aspartic Acid Endopeptidases; Cell Line, Tumor; Endosomes; Endothelin-Converting Enzymes; Enteric Nervous System; Female; Gastrointestinal Agents; Golgi Apparatus; Male; Metalloendopeptidases; Mice; Neurons; Octreotide; Protein Transport; Proteolysis; Rats; Rats, Sprague-Dawley; Receptors, Somatostatin; Somatostatin; Somatostatin-28; beta-Arrestins
PubMed: 23913690
DOI: 10.1074/jbc.M113.496414 -
Alimentary Pharmacology & Therapeutics Jun 2012Vasoactive medications such as vasopressin, somatostatin and their analogues (terlipressin, vapreotide and octreotide) are commonly used for the treatment of acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vasoactive medications such as vasopressin, somatostatin and their analogues (terlipressin, vapreotide and octreotide) are commonly used for the treatment of acute variceal bleeding. However, the risks and benefits of these interventions are not well understood.
AIM
To undertake a meta-analysis of the efficacy of vasoactive medications in patients having acute variceal bleeds.
METHODS
Randomised controlled trials (RCTs) of vasopressin, somatostatin and their analogues, administered to patients with acute variceal bleeds were identified based on systematic searches of nine electronic databases and multiple sources of grey literature.
RESULTS
The search identified 3011 citations, and 30 trials with a total of 3111 patients met eligibility criteria. The use of vasoactive agents was associated with a significantly lower risk of 7-day mortality (RR 0.74; 95% CI 0.57-0.95; P = 0.02; I(2) = 0%; moderate quality of evidence), and a significant improvement in haemostasis (RR 1.21, 95% CI 1.13-1.30; P < 0.001; I(2) = 28%; very low quality of evidence), lower transfusion requirements (pooled mean difference -0.70 units of blood transfused, 95% CI -1.01 to -0.38; P < 0.001; I(2) = 82%; moderate quality of evidence), and a shorter duration of hospitalisation (pooled mean difference -0.71 days; 95% CI -1.23 to -0.19; P = 0.007; I(2) = 0%; low quality of evidence). Studies comparing different vasoactive agents did not show a difference in efficacy, although the quality of evidence was very low.
CONCLUSIONS
The use of vasoactive agents was associated with a significantly lower risk of acute all-cause mortality and transfusion requirements, and improved control of bleeding and shorter hospital stay. Studies comparing different vasoactive medications failed to demonstrate a difference in efficacy.
Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemostatics; Humans; Lypressin; Octreotide; Randomized Controlled Trials as Topic; Somatostatin; Terlipressin; Vasopressins
PubMed: 22486630
DOI: 10.1111/j.1365-2036.2012.05088.x