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International Journal of Molecular... Sep 2019Hepatocellular carcinoma, one of the most dreaded complications of cirrhosis, is a frequent cancer with high mortality. Early primary liver cancer can be treated by... (Review)
Review
Hepatocellular carcinoma, one of the most dreaded complications of cirrhosis, is a frequent cancer with high mortality. Early primary liver cancer can be treated by surgery or ablation techniques, but advanced hepatocellular carcinoma remains a challenge for clinicians. Most of these patients have underlying cirrhosis, which complicates or even precludes treatment. Therefore, efficacious treatments without major side effects are welcomed. Initial results of treatment of advanced hepatocellular carcinoma with somatostatin analogues were promising, but subsequent trials have resulted in conflicting outcomes. This might be explained by different patient populations, differences in dosage and type of treatment and differences in somatostatin receptor expression in the tumor or surrounding tissue. It has been shown that the expression of somatostatin receptors in the tumor might be of importance to select patients who could benefit from treatment with somatostatin analogues. Moreover, somatostatin receptor expression in hepatocellular carcinoma has been shown to correlate with recurrence, prognosis, and survival. In this review, we will summarize the available data on treatment of primary liver cancer with somatostatin analogues and analyze the current knowledge of somatostatin receptor expression in hepatocellular carcinoma and its possible clinical impact.
Topics: Animals; Antineoplastic Agents, Hormonal; Carcinoma, Hepatocellular; Clinical Trials as Topic; Humans; Liver Neoplasms; Somatostatin; Treatment Outcome
PubMed: 31569719
DOI: 10.3390/ijms20194811 -
Current Opinion in Endocrinology,... Aug 2013Recently developed agents treat Cushing's disease by inhibiting ACTH secretion from corticotrope tumors or antagonizing cortisol action. (Review)
Review
PURPOSE OF REVIEW
Recently developed agents treat Cushing's disease by inhibiting ACTH secretion from corticotrope tumors or antagonizing cortisol action.
RECENT FINDINGS
The dopamine agonist cabergoline and the somatostatin agonist pasireotide target ACTH secretion. Each has low rates of normalization of urine-free cortisol (UFC), about 40% at doses of 1-7 mg weekly and 20% at doses of 600 or 900 μg twice daily, respectively. Cabergoline, an oral agent, has a relatively benign side-effect profile, primarily asthenia. Small trials suggest that combination therapy with ketoconazole increases effectiveness. Pasireotide, a parenteral agent, is associated with types and rates of adverse events similar to those seen with other somatostatin agonists (diarrhea, nausea, cholelithiasis), except for glucose intolerance, which occurs more frequently (∼75%). It may be most effective when UFC is less than two-fold normal. A few case reports suggest that pasireotide or cabergoline may control tumor size and ACTH secretion from macroadenomas. Retinoic acid must be evaluated further. The glucocorticoid antagonist mifepristone ameliorates glucose intolerance but may not normalize other Cushingoid features.
SUMMARY
These novel approaches provide options for treatment of patients in whom surgery has failed or is not possible, and those who decline adrenalectomy or radiation therapy.
Topics: Cabergoline; Dopamine Agonists; Drug Therapy, Combination; Ergolines; Humans; Hydrocortisone; Pituitary ACTH Hypersecretion; Somatostatin
PubMed: 23807605
DOI: 10.1097/MED.0b013e3283631809 -
Digestive Surgery 2015The use of somatostatin analogues (SAs) following pancreaticoduodenectomy (PD) is controversial. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of somatostatin analogues (SAs) following pancreaticoduodenectomy (PD) is controversial.
METHOD
Literature databases were searched systematically for relevant articles. A meta-analysis of all randomized controlled trials (RCTs) evaluating prophylactic SAs in PD was performed.
RESULTS
Fifteen RCTs involving 1,352 patients were included. There was a towards reduced incidences of pancreatic fistulas (p = 0.26), clinically significant pancreatic fistulas (p = 0.08), and bleeding (p = 0.05) in prophylactic SAs group. In subgroup analyses, prophylactic somatostatin significantly reduced the incidence of pancreatic fistulas(p = 0.02), with a nonsignificant trend toward reduced incidence of clinically significantly pancreatic fistulas (p = 0.06).Pasireotide significantly reduced the incidence of clinically significantly pancreatic fistulas (p = 0.03). Octreotide had no influence on the incidence of pancreatic fistulas.
CONCLUSION
The current best evidence suggests prophylactic treatment with somatostatin or pasireotide has a potential role in reducing the incidence of pancreatic fistulas, while octreotide had no influence on the incidence of pancreatic fistulas.High-quality RCTs assessing the role of somatostatin and pasireotide are required for further verification.
Topics: Gastrointestinal Agents; Humans; Models, Statistical; Octreotide; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Postoperative Hemorrhage; Somatostatin; Treatment Outcome
PubMed: 25872003
DOI: 10.1159/000381032 -
Cardiology 2020Somatostatin inhibits intestinal motility and hormonal secretion and is a potent arterial vasoconstrictor of the splanchnic blood flow. It is unknown if somatostatin...
BACKGROUND
Somatostatin inhibits intestinal motility and hormonal secretion and is a potent arterial vasoconstrictor of the splanchnic blood flow. It is unknown if somatostatin concentrations are associated with central hemodynamic measurements in patients with advanced heart failure (HF).
METHODS
A prospective study of HF patients with a left ventricular ejection fraction (LVEF) <45% referred to right heart catheterization (RHC) for evaluation for heart transplantation (HTX) or left ventricular assist device (LVAD).
RESULTS
Fifty-three patients were included with mean LVEF 18 ± 8% and majority in NYHA-class III-IV (79%). Median plasma somatostatin concentration was 18 pmol/L. In univariable regression analysis, log(somatostatin) was associated with increased central venous pressure (CVP; r2 = 0.14, p = 0.003) and a reduced cardiac index (CI; r2 = 0.15, p = 0.004). When adjusted for selected clinical variables (age, gender, LVEF, eGFR and BMI), log(somatostatin) remained a significant predictor of CVP (p = 0.044). Increased somatostatin concentrations predicted mortality in multivariable models (hazard ratio: 5.2 [1.2-22.2], p = 0.026) but not the combined endpoint of death, LVAD implantation or HTX.
CONCLUSIONS
Somatostatin concentrations were associated with CVP and CI in patients with HF. The pathophysiological mechanism may be related to congestion and/or hypoperfusion of the intestine. Somatostatin was an independent predictor of mortality in advanced HF.
Topics: Heart Failure; Humans; Prospective Studies; Somatostatin; Stroke Volume; Ventricular Function, Left
PubMed: 33027795
DOI: 10.1159/000510284 -
Asian Pacific Journal of Cancer... 2014Carcinoid crisis is a life-threatening syndrome of neuroendocrine tumors (NETs) characterized by dramatic blood pressure fluctuation, arrhythmias, and bronchospasm. In... (Review)
Review
BACKGROUND
Carcinoid crisis is a life-threatening syndrome of neuroendocrine tumors (NETs) characterized by dramatic blood pressure fluctuation, arrhythmias, and bronchospasm. In the era of booming anti-tumor therapeutics, this has become more important since associated stresses can trigger carcinoid crisis. Somatostatin analogues (SSTA) have been recommended for prophylactic administration before intervention procedures for functioning NETs. However, the efficacy is still controversial. The aim of this article is to review efficacy of SSTA for preventing carcinoid crisis.
MATERIALS AND METHODS
PubMed, Cochrane Controlled trials Register, and EMBASE were searched using 'carcinoid crisis' as a search term combining terms with 'somatostatin'; 'octreotide'; 'lanreotide' and 'pasireotide' until December 2013.
RESULTS
Twenty-eight articles were retrieved with a total of fifty-three unique patients identified for carcinoid crisis. The most common primary sites of NETs were the small intestine and respiratory tract. The triggering factors for carcinoid crisis included anesthesia/ surgery (63.5%), interventional therapy (11.5%), radionuclide therapy (9.6%), examination (7.7%), medication (3.8%), biopsy (2%) and spontaneous (2%). No randomized controlled trials (RCTs) were identified and two case-control studies were included to assess the efficacy of SSTA for preventing carcinoid crisis by meta-analysis. The overall pooled risk of perioperative carcinoid crisis was similar despite the prophylactic administration of SSTA (OR 0.44, 95% CI: 0.14 to 1.35, p=0.15).
CONCLUSIONS
SSTA was not helpful for preventing carcinoid crisis based on a meta-analysis of retrospective studies. Attentive monitoring and careful intervention are essential. Future studies with better quality are needed to clarify any effect of SSTA for preventing carcinoid crisis.
Topics: Humans; Intestine, Small; Malignant Carcinoid Syndrome; Neuroendocrine Tumors; Octreotide; Peptides, Cyclic; Respiratory System; Somatostatin
PubMed: 25169508
DOI: 10.7314/apjcp.2014.15.16.6679 -
Scientific Reports Oct 2022Somatostatin, a growth hormone-release inhibiting peptide, exerts antiproliferative and antiangiogenic effects on tumor cells. However, the short half-life of...
Somatostatin, a growth hormone-release inhibiting peptide, exerts antiproliferative and antiangiogenic effects on tumor cells. However, the short half-life of somatostatin limits its application in human therapy, and long-acting somatostatin fusion protein is also limited by its severe terminal degradation. Therefore, oncolytic virus delivery system was introduced to express somatostatin fusion protein and the anti-tumor effects of both somatostatin and oncolytic virus were combined to destroy tumor tissues. Here, a vaccinia VG9/(SST-14)-HSA recombinant was constructed by replacing somatostatin fusion gene into TK locus of attenuated VG9 strain via homologous recombination. Results showed that vaccinia VG9/(SST-14)-HSA possessed a combined anti-tumor effect on sstr-positive tumor cells in vitro. In the tumor burden models, BALB/c mice with complete immunity are most suitable for evaluating tumor regression and immune activation. Complete tumor regression was observed in 3 out of 10 mice treated with vaccinia VG9/TK or VG9/(SST-14)-HSA, and the survival of all mice in both groups was significantly prolonged. Besides, vaccinia VG9/(SST-14)-HSA is more effective in prolonging survival than VG9/TK. Vaccinia VG9/(SST-14)-HSA exerts a combined anti-tumor efficacy including the oncolytic ability provided by the virus and the anti-tumor effect contributed by (SST-14)-HSA, which is expected to become a potent therapeutic agent for cancer treatment.
Topics: Animals; Growth Hormone; Humans; Mice; Mice, Inbred BALB C; Neoplasms; Oncolytic Virotherapy; Receptors, Somatostatin; Somatostatin; Vaccinia; Vaccinia virus
PubMed: 36207478
DOI: 10.1038/s41598-022-21506-8 -
Signal Transduction and Targeted Therapy May 2023Seizures due to cortical dysplasia are notorious for their poor prognosis even with medications and surgery, likely due to the widespread seizure network. Previous...
Seizures due to cortical dysplasia are notorious for their poor prognosis even with medications and surgery, likely due to the widespread seizure network. Previous studies have primarily focused on the disruption of dysplastic lesions, rather than remote regions such as the hippocampus. Here, we first quantified the epileptogenicity of the hippocampus in patients with late-stage cortical dysplasia. We further investigated the cellular substrates leading to the epileptic hippocampus, using multiscale tools including calcium imaging, optogenetics, immunohistochemistry and electrophysiology. For the first time, we revealed the role of hippocampal somatostatin-positive interneurons in cortical dysplasia-related seizures. Somatostatin-positive were recruited during cortical dysplasia-related seizures. Interestingly, optogenetic studies suggested that somatostatin-positive interneurons paradoxically facilitated seizure generalization. By contrast, parvalbumin-positive interneurons retained an inhibitory role as in controls. Electrophysiological recordings and immunohistochemical studies revealed glutamate-mediated excitatory transmission from somatostatin-positive interneurons in the dentate gyrus. Taken together, our study reveals a novel role of excitatory somatostatin-positive neurons in the seizure network and brings new insights into the cellular basis of cortical dysplasia.
Topics: Humans; Seizures; Interneurons; Hippocampus; Somatostatin; Dentate Gyrus
PubMed: 37193687
DOI: 10.1038/s41392-023-01404-9 -
Drug Design, Development and Therapy 2016Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates.... (Comparative Study)
Comparative Study Review
Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%-70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%-90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR®), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to be established. Lastly, novel therapies and new potential delivery modalities (oral octreotide) are summarized.
Topics: Acromegaly; Animals; Delayed-Action Preparations; Drug Delivery Systems; Drug Design; Humans; Octreotide; Somatostatin
PubMed: 26811671
DOI: 10.2147/DDDT.S77999 -
Journal of Gastrointestinal and Liver... Dec 2020Molecular predictive biomarkers represent an essential tool for the future of personalized oncotherapy. Gastro- entero-pancreatic neuroendocrine neoplasms are a... (Review)
Review
Molecular predictive biomarkers represent an essential tool for the future of personalized oncotherapy. Gastro- entero-pancreatic neuroendocrine neoplasms are a heterogeneous group of epithelial tumors with a steady increase in incidence and prevalence. Their effective management depends on early diagnosis, personalized risk stratification, and monitoring response to therapy. A crucial element is identifying accurate biomarkers to predict/monitor therapeutic responses, assess drug resistance, and quantify residual disease in a reproducible and less invasive way. Taking into consideration their role in cell differentiation, cell proliferation, apoptosis and tumor development, microRNAs have gained interest as potential prognostic markers and treatment response predictors in neuroendocrine neoplasms. This review is the first to summarize the available data on the possible role of microRNAs in evaluating the efficacy of somatostatin analogs treatment in gastro- entero-pancreatic neuroendocrine neoplasms. Although the literature is scarce, the let-7 family targeting phosphoinositide 3 kinase - protein kinase B 1 - mammalian target of rapamycin signaling pathway might represent a promising biomarker with potential clinical benefit, but further research is required before their eventual clinical application. Furthermore, the ambiguous molecular mechanisms of neuroendocrine proliferation and the undefined signaling pathway of somatostatin analogs should encourage future research in this field that may lead to a different clinical approach to neuroendocrine disease.
Topics: Digestive System Neoplasms; Humans; MicroRNAs; Neuroendocrine Tumors; Precision Medicine; Somatostatin
PubMed: 33331339
DOI: 10.15403/jgld-2866 -
Annals of Surgery Mar 1991Somatostatin is a naturally occurring cyclic tetradecapeptide that inhibits release of growth hormone and all gastrointestinal hormones. The beneficial effect of... (Review)
Review
Somatostatin is a naturally occurring cyclic tetradecapeptide that inhibits release of growth hormone and all gastrointestinal hormones. The beneficial effect of somatostatin in the treatment of certain hypersecretory disorders of hormone excess in well recognized; however its clinical usefulness has been limited in the past by its extremely short plasma half-life. The development of long-acting somatostatin analogues has provided clinically useful agents for treatment of hormone-producing tumors. In addition to well-known inhibiting effects on hormone release and actions, recent studies using experimental tumor models have demonstrated an antiproliferative effect of somatostatin and its analogues on growth of a variety of neoplasms. The exact role of somatostatin analogues in cancer therapy has yet to be established; however studies suggest that these agents could provide a useful and relatively nontoxic adjuvant therapy in the treatment of certain tumors. In this review, the oncologic application of somatostatin and possible mechanism of action are examined and current clinical and experimental studies are summarized.
Topics: Breast Neoplasms; Endocrine System Diseases; Humans; Lung Neoplasms; Male; Neoplasms; Pancreatic Neoplasms; Prostatic Neoplasms; Somatostatin
PubMed: 1671812
DOI: 10.1097/00000658-199103000-00002