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Pasireotide

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https://www.readbyqxmd.com/read/28597198/long-term-treatment-of-cushing-s-disease-with-pasireotide-5-year-results-from-an-open-label-extension-study-of-a-phase-iii-trial
#1
S Petersenn, L R Salgado, J Schopohl, L Portocarrero-Ortiz, G Arnaldi, A Lacroix, C Scaroni, S Ravichandran, A Kandra, B M K Biller
BACKGROUND: Treating hypercortisolism in patients with Cushing's disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. METHODS: In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing's disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein...
June 9, 2017: Endocrine
https://www.readbyqxmd.com/read/28592706/efficacy-and-safety-of-long-acting-pasireotide-in-japanese-patients-with-acromegaly-or-pituitary-gigantism-results-from-a-multicenter-open-label-randomized-phase-2-study
#2
Shigeyuki Tahara, Mami Murakami, Tomomi Kaneko, Akira Shimatsu
A multicenter, open-label, phase 2 study was conducted to investigate the efficacy and safety of long-acting pasireotide formulation in Japanese patients with acromegaly or pituitary gigantism. Medically naïve or inadequately controlled patients (on somatostatin analogues or dopamine agonists) were included. Primary end point was the proportion of all patients who achieved biochemical control (mean growth hormone [GH] levels<2.5μg/L and normalized insulin-like growth factor-1 [IGF-1]) at month 3. Thirty-three patients (acromegaly, n=32; pituitary gigantism, n=1) were enrolled and randomized 1:1:1 to receive open-label pasireotide 20mg, 40mg, or 60mg...
June 8, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28579289/effects-of-anti-somatostatin-agents-on-glucose-metabolism
#3
REVIEW
B Vergès
The anti-somatostatin agents used to treat acromegaly, Cushing's disease and neuroendocrine tumours also have hyperglycaemic effects. This is particularly true for pasireotide. Hyperglycaemic events are seen in 57-73% of patients with Cushing's treated with pasireotide, with a need to initiate antidiabetic treatment in about 50% of these patients. In acromegaly, treatment with pasireotide induces hyperglycaemia in 29-61% of patients. Pasireotide-induced hyperglycemia occurs early, within the first 3 months of treatment, due to a decrease in insulin secretion secondary to a fall in secretion of GLP-1 and GIP, and potentially also due to a direct inhibitory effect of pasireotide on beta cells...
June 1, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28567297/pasireotide-in-an-insulin-requiring-diabetic-acromegalic-patient-without-worsening-of-hyperglycemia
#4
Murray B Gordon, Kellie L Spiller
Long-acting pasireotide is an effective treatment option for acromegaly, but it is associated with hyperglycemia, which could impact its use in patients with diabetes. We present a case of a 53-year-old man with acromegaly and type 2 diabetes mellitus (glycated hemoglobin (HbA1c): 7.5%), who refused surgery to remove a pituitary macroadenoma and enrolled in a Phase 3 clinical trial comparing long-acting pasireotide and long-acting octreotide in acromegalic patients. The patient initially received octreotide, but insulin-like growth factor 1 (IGF-1) levels remained elevated after 12 months (383...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28543567/tgr5-contributes-to-hepatic-cystogenesis-in-rodents-with-polycystic-liver-diseases-via-camp-g%C3%AE-s-signaling
#5
Tatyana V Masyuk, Anatoliy I Masyuk, Maria Lorenzo Pisarello, Brynn N Howard, Bing Q Huang, Pui-Yuen Lee, Xavier Fung, Eduard Sergienko, Robert J Ardesky, Thomas Dy Chung, Anthony B Pinkerton, Nicholas F LaRusso
Hepatic cystogenesis in Polycystic Liver Disease (PLD) is associated with increased levels of cAMP in cholangiocytes lining liver cysts. TGR5, a G protein-coupled bile acid receptor, is linked to cAMP and expressed in cholangiocytes. Therefore, we hypothesized that TGR5 might contribute to disease progression. We examined expression of TGR5 and Gα proteins in cultured cholangiocytes and in livers of animal models and humans with PLD. In vitro, we assessed cholangiocyte proliferation, cAMP levels, and cyst growth in response to: (i) TGR5 agonists [taurolithocholic acid (TLCA), oleanolic acid (OA) and two synthetic compounds]; (ii) a novel TGR5 antagonist (SBI-115); and (iii) a combination of SBI-115 and pasireotide, a somatostatin receptor (SSTR) analog...
May 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28542433/beneficial-effect-of-combined-treatment-with-octreotide-and-pasireotide-in-pck-rats-an-orthologous-model-of-human-autosomal-recessive-polycystic-kidney-disease
#6
Masanori Kugita, Kazuhiro Nishii, Tamio Yamaguchi, Atsushi Suzuki, Yukio Yuzawa, Shigeo Horie, Eiji Higashihara, Shizuko Nagao
Increased intracellular cyclic AMP (cAMP) in renal tubular epithelia accelerates the progression of polycystic kidney disease (PKD). Thus, decreasing cAMP levels by an adenylyl cyclase inhibitory G protein activator is considered to be an effective approach in ameliorating PKD. In fact, pasireotide (PAS) was effective in reducing disease progression in animal models of PKD. However, hyperglycemia caused by the administration of PAS is an adverse effect in its clinical use. Whereas, co-administration of octreotide (OCT) with PAS did not increase serum glucose in normal rats...
2017: PloS One
https://www.readbyqxmd.com/read/28500831/somatotropinomas-inadequately-controlled-with-octreotide-may-over-respond-to-pasireotide-the-importance-of-dose-adjustment-to-achieve-long-term-biochemical-control
#7
Ilan Shimon, Wolfgang Saeger, Luiz Eduardo Wildemberg, Monica R Gadelha
OBJECTIVE: To present two female patients with acromegaly inadequately controlled with long-acting octreotide who were subsequently treated with the multireceptor-targeted somatostatin analogue pasireotide that over-suppressed IGF-1 levels. METHODS: We report two patients who failed surgery and received long-acting octreotide 20-30 mg/month as part of two double-blind, Phase III clinical trials. After 6-12 months of octreotide treatment, both patients remained inadequately controlled and were switched to long-acting pasireotide 40 mg/month as part of a crossover extension phase...
January 2017: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28458898/efficacy-of-pasireotide-in-controlling-severe-hypercortisolism-until-cardiac-transplantation
#8
Roberto Attanasio, Liana Cortesi, Daniela Gianola, Claudia Vettori, Fulvio Sileo, Roberto Trevisan
SUMMARY: Cushing's syndrome is associated with increased morbidity and mortality. Although surgery is the first-line treatment, drugs can still play a role as an ancillary treatment to be employed while waiting for surgery, after unsuccessful operation or in patients unsuitable for surgery. We were asked to evaluate a 32-year-old male waiting for cardiac transplantation. Idiopathic hypokinetic cardiomyopathy had been diagnosed since 6 years. He was on treatment with multiple drugs, had a pacemaker, an implantable cardioverter and an external device for the support of systolic function...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28454119/anti-proliferative-and-anti-secretory-effects-of-everolimus-on-human-pancreatic-neuroendocrine-tumors-primary-cultures-is-there-any-benefit-from-combination-with-somatostatin-analogs
#9
Amira Mohamed, David Romano, Alexandru Saveanu, Catherine Roche, Manuela Albertelli, Federica Barbieri, Thierry Brue, Patricia Niccoli, Jean-Robert Delpero, Stephane Garcia, Diego Ferone, Tullio Florio, Vincent Moutardier, Flora Poizat, Anne Barlier, Corinne Gerard
Therapeutic management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is challenging. The mammalian target of rapamycin (mTOR) inhibitor everolimus recently obtained approval from the Food and Drug Administration for the treatment of patients with advanced pancreatic neuroendocrine tumors (pNETs). Despite its promising antitumor efficacy observed in cell lines, clinical benefit for patients is unsatisfactory. The limited therapeutic potential of everolimus in cancer cells has been attributed to Akt activation due to feedback loops relief following mTOR inhibition...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386722/does-pasireotide-directly-modulate-skeletal-muscle-metabolism
#10
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
#11
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
#12
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. Patients and methods: Patients were randomized 1 : 1 to receive a combination of everolimus (10 mg/day, orally) and pasireotide long-acting release (60 mg/28 days, intramuscularly) or everolimus alone (10 mg/day, orally); stratified by prior SSA use, and baseline serum chromogranin A and neuron-specific enolase...
June 1, 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
#13
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 antisecretory effect of OCT and PAS in primary cultures of growth hormone (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 cultures...
June 1, 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
#14
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
#15
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
#16
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
#17
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...
June 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28191290/loss-of-efficacy-of-pasireotide-after-its-re-administration-is-there-a-reason-why
#18
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
#19
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
#20
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
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