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https://www.readbyqxmd.com/read/28817826/the-safety-and-efficacy-of-the-s1-temozolomide-regimen-in-patients-with-metastatic-neuroendocrine-tumors
#1
Jiuda Zhao, Hong Zhao, Yihebali Chi
<br><br>Purpose Both capecitabine alone and capecitabine in combination with temozolomide have activities against neuroendocrine tumors (NETs). However, the role of S-1 in NETs is still unknown. We performed a study to evaluate the safety and efficacy of the S-1 plus temozolomide (STEM) regimen in patients with locally advanced or metastatic NETs. Methods A retrospective review was conducted in 20 patients with locally advanced or metastatic NETs treated with the STEM regimen. Of the patients, 15 (75...
August 17, 2017: Neuroendocrinology
https://www.readbyqxmd.com/read/28817434/everolimus-is-associated-with-less-weight-gain-than-tacrolimus-2-years-following-liver-transplantation-results-of-a-randomized-multicenter-study
#2
Michael Charlton, Mary Rinella, Dharmesh Patel, Kevin McCague, Julie Heimbach, Kymberly Watt
BACKGROUND: Weight gain early after transplant is a risk factor for posttransplant metabolic syndrome (PTMS), cardiovascular events, and renal insufficiency. The impact of mTOR inhibition on posttransplant weight gain and the development of PTMS components postliver transplantation were examined in a randomized, controlled study. METHODS: Following a run-in period, patients (N = 719) were randomized at 30±5 days posttransplant in a 1:1:1 ratio to 3 treatment groups: (i) everolimus (EVR) + reduced tacrolimus (TAC)(n=245); (ii) TAC control (n=243) or (iii) TAC elimination (n=231)...
August 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28817387/response-of-an-ovarian-granulosa-cell-tumor-with-everolimus-and-exemestane-after-initial-response-to-letrozole
#3
Tarek Assi, Hampig R Kourie, Elie El Rassy, Tania Moussa, Joseph Kattan
Granulosa cell tumors of the ovaries (GCTO), the most common sex cord tumors of the female genitalia, are characterized by a remarkably favorable prognosis but tend to recur even after several years of follow-up. Standard approach to manage these relapsing tumors is almost inexistent and physicians' choice is most commonly based on his/her personal expertise. Recently, the use of hormone therapy in GCTO has induced prolonged response and survival. In this case report, we report the first successful use of everolimus in the combination of exemestane to reverse the resistance to hormonal therapy with letrozole in a 53-year-old woman with GCTO...
September 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28814434/combined-cdk4-6-and-mtor-inhibition-is-synergistic-against-glioblastoma-via-multiple-mechanisms
#4
Inan Olmez, Breanna Brenneman, Aizhen Xiao, Vlad Serbulea, Mouadh Benamar, Ying Zhang, Laryssa Manigat, Tarek Abbas, Jeongwu Lee, Ichiro Nakano, Jakub Godlewski, Agnieszka Bronisz, Roger Abounader, Norbert Leitinger, Benjamin Purow
PURPOSE: Glioblastoma (GBM) is a deadly brain tumor marked by dysregulated signaling and aberrant cell cycle control. Molecular analyses have identified that the CDK4/6-Rb-E2F axis is dysregulated in about 80% of GBMs. Single-agent CDK4/6 inhibitors have failed to provide durable responses in GBM, suggesting a need to combine them with other agents. We investigate the efficacy of the combination of CDK4/6 inhibition and mTOR inhibition against GBM. EXPERIMENTAL DESIGN: Preclinical in vitro and in vivo assays using primary GBM cell lines were performed...
August 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28811655/a-tissue-engineered-blood-vessel-model-of-hutchinson-gilford-progeria-syndrome-using-human-ipsc-derived-smooth-muscle-cells
#5
Leigh Atchison, Haoyue Zhang, Kan Cao, George A Truskey
Hutchison-Gilford Progeria Syndrome (HGPS) is a rare, accelerated aging disorder caused by nuclear accumulation of progerin, an altered form of the Lamin A gene. The primary cause of death is cardiovascular disease at about 14 years. Loss and dysfunction of smooth muscle cells (SMCs) in the vasculature may cause defects associated with HGPS. Due to limitations of 2D cell culture and mouse models, there is a need to develop improved models to discover novel therapeutics. To address this need, we produced a functional three-dimensional model of HGPS that replicates an arteriole-scale tissue engineered blood vessel (TEBV) using induced pluripotent stem cell (iPSC)-derived SMCs from an HGPS patient...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811537/prognostic-significance-and-function-of-mammalian-target-of-rapamycin-in-tongue-squamous-cell-carcinoma
#6
Shau-Hsuan Li, Chih-Yen Chien, Wan-Ting Huang, Sheng-Dean Luo, Yan-Ye Su, Wan-Yu Tien, Ya-Chun Lan, Chang-Han Chen
Despite improvement in preoperative imaging, surgical technique, and adjuvant therapy, the prognosis of patients with tongue squamous cell carcinoma (SCC) is still unsatisfactory. The mammalian target of rapamycin (mTOR) play a key role in the regulation of tumor cell proliferation and survival. However, the significance of mTOR on the prognosis of tongue SCC remains largely undefined. In the present study, immunohistochemistry was performed to evaluate the expression of phosphorylated mTOR (p-mTOR) in 160 surgically resected tongue SCC, and correlated with survival...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807351/cost-effectiveness-of-nivolumab-in-advanced-renal-cell-carcinoma
#7
Michal Sarfaty, Moshe Leshno, Noa Gordon, Assaf Moore, Victoria Neiman, Eli Rosenbaum, Daniel A Goldstein
BACKGROUND: In recent years, new drugs have been introduced for second-line treatment of advanced renal cell carcinoma (RCC). Nivolumab increases overall survival and is associated with less toxicity compared to everolimus in this setting according to the CheckMate 025 study. However, because of the high cost of nivolumab, there is a need to define its value by considering both efficacy and cost. OBJECTIVE: To estimate the cost effectiveness of nivolumab for second-line treatment of advanced RCC from the US payer perspective...
August 11, 2017: European Urology
https://www.readbyqxmd.com/read/28805979/effects-of-mtor-inhibition-on-cardiac-and-adipose-tissue-pathology-and-glucose-metabolism-in-rats-with-metabolic-syndrome
#8
Ayako Uchinaka, Mamoru Yoneda, Yuichiro Yamada, Toyoaki Murohara, Kohzo Nagata
The mammalian target of rapamycin (mTOR) is a regulator of metabolism and is implicated in pathological conditions such as obesity and diabetes. We aimed to investigate the role of mTOR in obesity. A new animal model of metabolic syndrome (MetS), named DahlS.Z-Lepr(fa) /Lepr(fa) (DS/obese) rats was established previously in our laboratory. In this study, we used this model to evaluate the effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism. DS/obese rats were treated with the mTOR inhibitor, everolimus, (0...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28804814/factors-associated-with-cardiovascular-target-organ-damage-in-children-after-renal-transplantation
#9
Bianca Borchert-Mörlins, Daniela Thurn, Bernhard M W Schmidt, Anja K Büscher, Jun Oh, Tanja Kier, Elena Bauer, Sabrina Baig, Nele Kanzelmeyer, Markus J Kemper, Rainer Büscher, Anette Melk
BACKGROUND: Cardiovascular disease is the second-most common cause of death in pediatric renal transplant recipients. The aim of this study was to evaluate subclinical cardiovascular target organ damage defined as the presence of arterio- and atherosclerotic lesions and cardiac remodeling and to analyze contributing risk factors in a large cohort of children after renal transplantation (RT). METHODS: A total of 109 children aged 13.1 ± 3.3 years who had undergone RT at one of three German transplant centers were enrolled in this study...
August 13, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28800359/the-selective-pi3k%C3%AE-inhibitor-byl719-as-a-novel-therapeutic-option-for-neuroendocrine-tumors-results-from-multiple-cell-line-models
#10
Svenja Nölting, Jakob Rentsch, Helma Freitag, Katharina Detjen, Franziska Briest, Markus Möbs, Victoria Weissmann, Britta Siegmund, Christoph J Auernhammer, Elke Tatjana Aristizabal Prada, Michael Lauseker, Ashley Grossman, Samantha Exner, Christian Fischer, Carsten Grötzinger, Jörg Schrader, Patricia Grabowski
BACKGROUND/AIMS: The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. METHODS: Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA...
2017: PloS One
https://www.readbyqxmd.com/read/28799817/discontinuation-of-everolimus-due-to-related-and-unrelated-adverse-events-in-cancer-patients-a-meta-analysis
#11
Sherise C Rogers, Christine A Garcia, Shenhong Wu
A meta-analysis of randomized controlled trials (RCTs) was performed to examine the risk of everolimus discontinuation due to related and unrelated adverse events (AE) in cancer patients. Fifteen RCTs were analyzed that compared everolimus to placebo and reported discontinuation due to AE with everolimus (related and unrelated to everolimus) and placebo (unrelated to everolimus). Incidence of discontinuation with everolimus due to AE and placebo was 12.3% and 4.7% respectively. Relative risk of everolimus discontinuation due to related AE was 2...
August 11, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28799516/antiepileptic-drugs-in-clinical-development-differentiate-or-die
#12
Gaetano Zaccara, D Schmidt
BACKGROUND: Animal models when carefully selected, designed and conducted, are important parts of any translational drug development strategy. However, research of new compounds for patients with drug-resistant epilepsies is still based on animal experiments, mostly in rodents, which are far from being a model of chronic human epilepsy and have failed to differentiate the efficacy of new compounds versus standard drug treatment. Objective The objective was identification and description of compounds in clinical development in 2016...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28799238/everolimus-eluting-bioresorbable-vascular-scaffold-implantation-to-treat-saphenous-vein-graft-disease-single-center-initial-experience
#13
Fabien Picard, Guillaume Marquis-Gravel, Robert Avram, Hung Q Ly, Jean-François Dorval, Serge Doucet, Quentin de Hemptinne, Philippe L L'allier, Jean-François Tanguay
AIMS: Recent studies have shown favorable outcomes with everolimus-eluting bioresorbable vascular scaffold (BVS) in patients with stable coronary artery disease. Data on the use of BVS in saphenous vein graft disease (SVG) is currently lacking. METHODS AND RESULTS: A total of 10 consecutive patients (13 lesions, including 6 in-stent restenosis) who underwent BVS for SVG disease between May 2013 and June 2015 at a tertiary care institution were included. Median follow-up period was 874 (720-926) days...
August 10, 2017: Journal of Interventional Cardiology
https://www.readbyqxmd.com/read/28797401/a-58-year-old-man-with-position-dependent-nocturnal-dyspnea
#14
Anke Schertel, Christian M Horvath, Jacqueline Pichler Hefti, John-David Aubert, Anne-Kathrin Brill
A 58-year-old man with idiopathic pulmonary fibrosis, who had received a right-sided single-lung transplant 2 years earlier, was referred to the sleep clinic for the assessment of nocturnal position-dependent episodes of dyspnea and frequent arousals when lying on his right side. There was no subjective worsening of daytime respiratory symptoms, but he complained of fatigue and unrefreshing sleep. His Epworth Sleepiness Scale score was 12/24. After lung transplantation he had a favorable course while receiving immunosuppression with prednisolone, everolimus, and mycophenolate mofetil...
August 2017: Chest
https://www.readbyqxmd.com/read/28797113/clinical-outcomes-of-biodegradable-polymer-biolimus-eluting-biomatrix-stents-versus-durable-polymer-everolimus-eluting-xience-stents
#15
Da Hyon Lee, Taek Kyu Park, Young Bin Song, Woo Jung Chun, Rak Kyeong Choi, Jin-Ok Jeong, Eul Soon Im, Sang Wook Kim, Joo Myung Lee, Jeong Hoon Yang, Joo-Yong Hahn, Seung-Hyuk Choi, Jin-Ho Choi, Sang Hoon Lee, Hyeon-Cheol Gwon
There are limited data about clinical outcomes of biodegradable polymer biolimus-eluting BioMatrix stents (BP-BES) and durable polymer everolimus-eluting Xience stents (DP-EES) in real world practice. We sought to compare the clinical outcomes of BP-BES and DP-EES in real world cohorts of patients undergoing percutaneous coronary intervention. A prospective multicenter registry enrolled 999 patients treated with BP-BES and 1,000 patients treated with DP-EES. The primary outcome was target lesion failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization...
2017: PloS One
https://www.readbyqxmd.com/read/28796809/a-randomized-multicenter-trial-comparing-the-xience-everolimus-eluting-stent-with-the-cypher-sirolimus-eluting-stent-in-the-treatment-of-female-patients-with-de-novo-coronary-artery-lesions-the-spirit-women-study
#16
Anna Franzone, Serge Zaugg, Raffaele Piccolo, Maria Grazia Modena, Ghada W Mikhail, Josepa Mauri Ferré, Ruth Strasser, Liliana Grinfeld, Dik Heg, Peter Jüni, Stephan Windecker, Marie-Claude Morice
BACKGROUND: The comparative performance of different drug-eluting stents (DES) among female patients has not been assessed in a randomized manner. OBJECTIVES: The SPIRIT Women Clinical Evaluation trial compared the durable polymer everolimus-eluting XIENCE stent (DP-EES) with the durable polymer sirolimus-eluting Cypher stent (DP-SES) in women undergoing percutaneous coronary intervention (PCI). METHODS: A total of 455 female patients with stable CAD were randomly assigned to receive DP-EES (n = 304) or DP-SES (n = 151)...
2017: PloS One
https://www.readbyqxmd.com/read/28796163/hypertension-caused-by-lenvatinib-and-everolimus-in-the-treatment-of-metastatic-renal-cell-carcinoma
#17
REVIEW
Mathias Alrø Fichtner Bendtsen, Daniela Grimm, Johann Bauer, Markus Wehland, Petra Wise, Nils E Magnusson, Manfred Infanger, Marcus Krüger
Multikinase inhibitors (MKI) and mammalian target of rapamycin (mTOR) inhibitors prolong progression-free (PFS) and overall survival (OS) in the treatment of metastatic renal cell carcinoma (mRCC) by reducing angiogenesis and tumor growth. In this regard, the MKI lenvatinib and the mTOR inhibitor everolimus proved effective when applied alone, but more effective when they were administered combined. Recently, both drugs were included in clinical trials, resulting in international clinical guidelines for the treatment of mRCC...
August 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28793923/concurrent-antitumor-and-bone-protective-effects-of-everolimus-in-osteotropic-breast-cancer
#18
Andrew J Browne, Marie L Kubasch, Andy Göbel, Peyman Hadji, David Chen, Martina Rauner, Friedrich Stölzel, Lorenz C Hofbauer, Tilman D Rachner
BACKGROUND: The mammalian target of rapamycin inhibitor everolimus is approved as an antitumor agent in advanced estrogen receptor-positive breast cancer. Surrogate bone marker data from clinical trials suggest effects on bone metabolism, but the mode of action of everolimus in bone biology remains unclear. In this study, we assessed potential bone-protective effects of everolimus in the context of osteotropic tumors. METHODS: The effects of everolimus on cancer cell viability in vitro and on tumor growth in vivo were assessed...
August 9, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28792952/everolimus-long-term-use-in-patients-with-tuberous-sclerosis-complex-four-year-update-of-the-exist-2-study
#19
John J Bissler, J Chris Kingswood, Elzbieta Radzikowska, Bernard A Zonnenberg, Elena Belousova, Michael D Frost, Matthias Sauter, Susanne Brakemeier, Petrus J de Vries, Noah Berkowitz, Maurizio Voi, Severine Peyrard, Klemens Budde
OBJECTIVES: We examined the long-term effects of everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. METHODS: Following favorable results from the double-blind core phase of EXIST-2 (NCT00790400), patients were allowed to receive open-label everolimus (extension phase). Patients initially randomly assigned to everolimus continued on the same dose; those who were receiving placebo crossed over to everolimus 10 mg/day...
2017: PloS One
https://www.readbyqxmd.com/read/28780710/regression-of-neonatal-cardiac-rhabdomyoma-in-two%C3%A2-months-through-low-dose-everolimus-therapy-a-report-of-three-cases
#20
Jeng-Sheng Chang, Ping-Yun Chiou, Shu-Hui Yao, I-Ching Chou, Ching-Yuang Lin
Cardiac rhabdomyoma (CR) is the most common cardiac tumor in newborns. Approximately 75% of cases are associated with tuberous sclerosis complex. Although these tumors usually spontaneously regress after 2 years of age, they can be life-threatening when they obstruct major cardiac inflow or outflow pathways. Everolimus is an inhibitor of the mammalian target of rapamycin, reducing its production of the proteins harmartin and tuberin. Everolimus has demonstrated a remarkable suppression effect in children with tuberous sclerosis complex at doses of 4...
August 5, 2017: Pediatric Cardiology
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