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Pasireotide

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https://www.readbyqxmd.com/read/28386722/does-pasireotide-directly-modulate-skeletal-muscle-metabolism
#1
EDITORIAL
Federico Gatto, Tullio Florio
No abstract text is available yet for this article.
April 6, 2017: Endocrine
https://www.readbyqxmd.com/read/28364356/diabetes-in-cushing-disease
#2
REVIEW
G Mazziotti, A M Formenti, S Frara, F Maffezzoni, M Doga, A Giustina
PURPOSE OF REVIEW: This review focuses on the pathophysiological and clinical aspects of diabetes mellitus occurring in patients with Cushing disease (CD). RECENT FINDINGS: Insulin resistance and impairment in insulin secretion are both involved in the pathogenesis of glucocorticoid-induced diabetes. Correction of glucocorticoid excess does not always resolve abnormalities of glucose homeostasis, and correction of hyperglycaemia is specifically required. In fact, insulin resistance may persist even after correction of glucocorticoid excess and diabetes needs to be treated for long term...
May 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28327907/a-randomized-open-label-phase-2-study-of-everolimus-in-combination-with-pasireotide-lar-or-everolimus-alone-in-advanced-well-differentiated-progressive-pancreatic-neuroendocrine-tumors-cooperate-2-trial
#3
M H Kulke, P Ruszniewski, E Van Cutsem, C Lombard-Bohas, J W Valle, W W De Herder, M Pavel, E Degtyarev, J C Brase, L Bubuteishvili-Pacaud, M Voi, R Salazar, I Borbath, N Fazio, D Smith, J Capdevila, R P Riechelmann, J C Yao
Background: Several studies have demonstrated the antitumor activity of first-generation somatostatin analogs (SSAs), primarily targeting somatostatin receptor (sstr) subtypes 2 and 5, in neuroendocrine tumors (NET). Pasireotide, a second-generation SSA, targets multiple sstr subtypes. We compared the efficacy and safety of pasireotide plus everolimus to everolimus alone in patients with advanced, well-differentiated, progressive pancreatic NET (pNET). Patients and methods: Patients were randomized 1:1 to receive a combination of everolimus (10 mg/d, orally) and pasireotide long-acting release (LAR; 60 mg/28 d, intramuscularly) or everolimus alone (10 mg/d, orally); stratified by prior SSA use, and baseline serum chromogranin A and neuron-specific enolase...
March 6, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28323931/in-vitro-head-to-head-comparison-between-octreotide-and-pasireotide-in-gh-secreting-pituitary-adenomas
#4
Federico Gatto, Richard A Feelders, Sanne E Franck, Peter M van Koetsveld, Fadime Dogan, Johan M Kros, Sebastian J C M M Neggers, Aart-Jan van der Lely, Steven W J Lamberts, Diego Ferone, Leo J Hofland
Context: First-generation somatostatin analogs (SSAs), such as octreotide (OCT), are the first line medical therapy for acromegaly. Pasireotide (PAS), a newly developed SSA, has shown promising results in the treatment of acromegaly. Objective: To compare the anti-secretory effect of OCT and PAS in primary cultures of GH-secreting pituitary adenomas (GH-omas). To correlate responses with the adenoma somatostatin receptor (SSTR) profile. Design: The effect of OCT and PAS on GH (and PRL) secretion was tested in 33 GH-oma primary cultures...
March 13, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28306647/pasireotide-for-the-prevention-of-postoperative-pancreatic-fistula-time-to-curb-the-enthusiasm
#5
Laura Maggino, Charles M Vollmer
No abstract text is available yet for this article.
March 16, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28289402/medical-therapy-with-pasireotide-in-recurrent-cushing-s-disease-experience-of-patients-treated-for-at-least-1%C3%A2-year-at-a-single-center
#6
Chris G Yedinak, Sarah Hopkins, Jessica Williams, Aly Ibrahim, Justin Schultz Cetas, Maria Fleseriu
Subcutaneous (SC) injection of pasireotide, a somatostatin analog, is approved for the treatment of adults with Cushing's disease (CD) for whom pituitary surgery was unsuccessful or is not an option. We highlight the symptomatic and biochemical improvement of six patients with recurrent CD treated with pasireotide SC at a single center for at least 1 year. Patients were treated either through commercial use (n = 5) or through the Phase 3 trial (n = 1; http://ClinicalTrials.gov identifier, NCT00434148; study number, B2305)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28286565/everolimus-in-the-management-of-metastatic-neuroendocrine-tumours
#7
REVIEW
David L Chan, Eva Segelov, Simron Singh
Neuroendocrine tumours are increasing in incidence and cause a variety of symptoms. The mammalian target of rapamycin (mTOR) pathway plays a key role in neuroendocrine tumour (NET) pathogenesis, leading to increased lipid synthesis, protein synthesis and cellular growth. Upregulation of this pathway is noted in both hereditary and sporadic NETs. This understanding has led to investigations of mTOR inhibitors as therapy for metastatic NETs. After promising preclinical findings, everolimus, an mTOR inhibitor, was trialled in the RADIANT-1-4 studies on patients with advanced, well differentiated NETs...
January 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28271381/tissue-expression-and-pharmacological-in-vitro-analyses-of-mtor-and-sstr-pathways-in-adrenocortical-carcinoma
#8
Antonina Germano, Ida Rapa, Eleonora Duregon, Arianna Votta, Jessica Giorcelli, Consuelo Buttigliero, Giorgio V Scagliotti, Marco Volante, Massimo Terzolo, Mauro Papotti
New therapies for advanced adrenocortical carcinoma (ACC) are urgently needed, as the majority of the patients experience a rapid and inexorable progression despite surgery and adjuvant mitotane. In vitro data suggest that somatostatin receptors (SSTRs) and mTOR pathway might represent reasonable targets for novel therapies, being involved in functionality and growth of ACC cells. However, in vitro analysis of combination treatments targeting both mTOR and SSTR as compared to mitotane are poorly explored in ACC...
March 7, 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28191290/loss-of-efficacy-of-pasireotide-after-its-re-administration-is-there-a-reason-why
#9
Stylianos Mandanas, Lemonia Mathiopoulou, Maria Boudina, Alexandra Chrisoulidou, Kalliopi Pazaitou-Panayiotou
Pasireotide is a recently approved medical treatment for persistent or recurrent Cushing's disease (CD). However, an escape from the initial successful response has not yet been described. A 42-year-old female presented with several symptoms indicative of hypercortisolism. Biochemical evaluation and imaging were consistent with CD due to a pituitary adenoma. Surgical excision of the adenoma was unsuccessful and gamma-knife radiosurgery was followed. Our patient remained hypercortisolemic thus treatment with pasireotide (900 mg subcutaneously twice daily) was decided...
November 17, 2016: Rare Tumors
https://www.readbyqxmd.com/read/28176162/somatostatin-receptor-ligands-in-the-treatment-of-acromegaly
#10
REVIEW
Monica R Gadelha, Luiz Eduardo Wildemberg, Marcello D Bronstein, Federico Gatto, Diego Ferone
First-generation somatostatin receptors ligands (SRL) are the mainstay in the medical treatment of acromegaly, however the percentage of patients controlled with these drugs significantly varies in the different studies. Many factors are involved in the resistance to SRL. In this review, we update the physiology of somatostatin and its receptors (sst), the use of SRL in the treatment of acromegaly and the factors involved in the response to these drugs. The SRL act through interaction with the sst, which up to now have been characterized as five subtypes...
February 2017: Pituitary
https://www.readbyqxmd.com/read/28170483/diagnosis-and-treatment-of-pituitary-adenomas-a-review
#11
REVIEW
Mark E Molitch
Importance: Pituitary adenomas may hypersecrete hormones or cause mass effects. Therefore, early diagnosis and treatment are important. Observations: Prevalence of pituitary adenomas ranges from 1 in 865 adults to 1 in 2688 adults. Approximately 50% are microadenomas (<10 mm); the remainder are macroadenomas (≥10 mm). Mass effects cause headache, hypopituitarism, and visual field defects. Treatments include transsphenoidal surgery, medical therapies, and radiotherapy...
February 7, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28145031/pasireotide-long-acting-release-treatment-for-diabetic-cats-with-underlying-hypersomatotropism
#12
R Gostelow, C Scudder, S Keyte, Y Forcada, R C Fowkes, H A Schmid, D B Church, S J M Niessen
BACKGROUND: Long-term medical management of hypersomatotropism (HS) in cats has proved unrewarding. Pasireotide, a novel somatostatin analogue, decreases serum insulin-like growth factor 1 (IGF-1) and improves insulin sensitivity in cats with HS when administered as a short-acting preparation. OBJECTIVES: Assess once-monthly administration of long-acting pasireotide (pasireotide LAR) for treatment of cats with HS. ANIMALS: Fourteen cats with HS, diagnosed based on diabetes mellitus, pituitary enlargement, and serum IGF-1 > 1000 ng/mL...
March 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28050766/selective-perioperative-administration-of-pasireotide-is-more-cost-effective-than-routine-administration-for-pancreatic-fistula-prophylaxis
#13
Jason W Denbo, Rebecca S Slack, Morgan Bruno, Jordan M Cloyd, Laura Prakash, Jason B Fleming, Michael P Kim, Thomas A Aloia, Jean-Nicolas Vauthey, Jeffrey E Lee, Matthew H G Katz
BACKGROUND: In a randomized trial, pasireotide significantly decreased the incidence and severity of postoperative pancreatic fistula (POPF). Subsequent analyses concluded that its routine use is cost-effective. We hypothesized that selective administration of the drug to patients at high risk for POPF would be more cost-effective. STUDY DESIGN: Consecutive patients who did not receive pasireotide and underwent pancreatoduodenectomy (PD) or distal pancreatectomy (DP) between July 2011 and January 2014 were distributed into groups based on their risk of POPF using a multivariate recursive partitioning regression tree analysis (RPA) of preoperative clinical factors...
April 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/28045714/how-much-should-we-pay-to-minimize-pancreatic-leak-the-cost-effectiveness-of-pasireotide-in-pancreatic-resection-retracted
#14
Daniel E Abbott, Jeffrey M Sutton, Peter L Jernigan, Alex Chang, Patrick Frye, Shimul A Shah, Daniel P Schauer, Mark H Eckman, Syed A Ahmad, Jeffrey J Sussman
INTRODUCTION: Pasireotide was recently shown to decrease leak rates after pancreatic resection, though the significant cost of the drug may be prohibitive. We conducted a cost-effectiveness analysis to determine whether prophylactic pasireotide possesses a reasonable cost profile by improving outcomes. METHODS: A cost-effectiveness model was constructed to compare pasireotide administration after pancreatic resection versus usual care, populated by probabilities of clinical outcomes from a recent randomized trial and hospital costs (2013 US$) from a university pancreatic disease center...
December 30, 2016: Annals of Surgery
https://www.readbyqxmd.com/read/28008238/communication-practices-and-awareness-of-resources-for-acromegaly-patients-among-endocrinologists
#15
Susan Polanco-Briceno, Daniel Glass, Cindy Plunkett
PURPOSE: This study was designed to assess the awareness and utilization of resources to improve patients' treatment experiences among endocrinologists who currently treat patients with acromegaly. METHODS: A total of 4,280 US endocrinologists were randomly selected from the CMS National Plan and Provider Enumeration System and were invited by mail to participate in a 20-minute online survey. In order to qualify, respondents had to be the primary physician making treatment decisions for at least one patient for their acromegaly...
2016: Patient Preference and Adherence
https://www.readbyqxmd.com/read/27971743/a-cost-effectiveness-analysis-of-pasireotide-long-acting-compared-to-continued-use-of-a-first-line-somatostatin-antagonist-for-the-treatment-of-acromegaly-in-sweden
#16
P Carlqvist, A Wilen-Koort
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27966451/fgfr4-polymorphic-alleles-modulate-mitochondrial-respiration-a-novel-target-for-somatostatin-analog-action-in-pituitary-tumors
#17
Shereen Ezzat, Ri Wang, Melania Pintilie, Sylvia L Asa
We reported that a single nucleotide polymorphism (SNP) at codon 388 of the fibroblast growth factor receptor 4 (FGFR4-Gly388Arg) can result in distinct proteins that alter pituitary cell growth and function. Here, we examined the differential properties of the available therapeutic somatostatin analogs, octreotide and pasireotide, in pituitary tumor cells expressing the different FGFR4 isoforms. Consistent with their enhanced growth properties, FGFR4-R388-expressing cells show higher mitochondrial STAT3 serine phosphorylation driving basal and maximal oxygen consumption rate (OCR) than pituitary cells expressing the more common FGFR4-G388 isoform...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27900635/somatostatin-and-dopamine-receptor-regulation-of-pituitary-somatotroph-adenomas
#18
REVIEW
Anat Ben-Shlomo, Ning-Ai Liu, Shlomo Melmed
Somatostatin and dopamine receptors are expressed in normal and tumoral somatotroph cells. Upon receptor stimulation, somatostatin and the somatostatin receptor ligands octreotide, lanreotide, and pasireotide, and to a lesser extent, dopamine and the dopamine analogs bromocriptine and cabergoline, suppress growth hormone (GH) secretion from a GH-secreting pituitary somatotroph adenoma. Somatostatin and dopamine receptors are Gαi-protein coupled that inhibit adenylate cyclase activity and cAMP production and reduce intracellular calcium concentration and calcium flux oscillations...
November 29, 2016: Pituitary
https://www.readbyqxmd.com/read/27896545/safety-and-tolerability-of-pasireotide-long-acting-release-in-acromegaly-results-from-the-acromegaly-open-label-multicenter-safety-monitoring-program-for-treating-patients-who-have-a-need-to-receive-medical-therapy-access-study
#19
Maria Fleseriu, Elisha Rusch, Eliza B Geer
PURPOSE: Pasireotide long-acting release is a somatostatin analog that is indicated for treatment of patients with acromegaly. This analysis documents the safety of pasireotide long-acting release in patients with acromegaly enrolled in the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734). METHODS: ACCESS is an open-label, multicenter, single-arm, expanded-treatment protocol designed to provide patients access to pasireotide long-acting release pending regulatory approval...
January 2017: Endocrine
https://www.readbyqxmd.com/read/27894193/currently-used-and-investigational-drugs-for-cushing%C3%A2-s-disease
#20
REVIEW
Denis Ciato, Aizhar G Mumbach, Marcelo Paez-Pereda, Günter K Stalla
Cushing's disease (CD) is caused by a corticotroph adenoma of the pituitary gland that secretes excess adrenocorticotropic hormone (ACTH) causing increased morbidity and mortality. Surgery is the treatment of choice, but is not always successful. Alternatives include radiotherapy, adrenal surgery, and pharmaceutical therapy. The latter is increasingly gaining momentum due to the recent development of compounds that reduce hypercortisolaemia or its symptoms, acting through different mechanisms. Areas covered: In this article, the authors provide a complete overview of the treatment options for Cushing´s disease, including adrenal-directed, tumor-targeted, and peripheral therapies that are currently used or in development, and discuss their potential advantages and limitations...
January 2017: Expert Opinion on Investigational Drugs
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