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Everolimus

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https://www.readbyqxmd.com/read/28930797/optimizing-the-safety-profile-of-everolimus-by-delayed-initiation-in-de-novo-heart-transplant-recipients-results-of-the-prospective-randomized-study-everheart
#1
Luciano Potena, Carlo Pellegrini, Francesco Grigioni, Cristiano Amarelli, Ugolino Livi, Massimo Maccherini, Gabriella Masciocco, Giuseppe Faggian, Paola Lilla Della Monica, Gino Gerosa, Nicola Marraudino, Marco Corda, Massimo Boffini
BACKGROUND: Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization. METHODS: This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion (PCEs), pleural effusion (PLEs) needing drainage, and renal insufficiency events (estimated glomerular filtration rate [eGFR] ≤30/mL/min/1...
September 19, 2017: Transplantation
https://www.readbyqxmd.com/read/28928860/the-impact-of-cetuximab-plus-akt-or-mtor-inhibitor-in-a-patient-derived-colon-cancer-cell-model-with-wild-type-ras-and-pik3ca-mutation
#2
Ju Sun Kim, Jung Eun Kim, Kyung Kim, Jeeyun Lee, Joon Oh Park, Ho Yeong Lim, Young Suk Park, Won Ki Kang, Seung Tae Kim
Background: Anti-EGFR therapies have been recommended for advanced colorectal cancer (CRC) with wild-type RAS and PIK3CA mutation. However, PIK3CA mutations are a poor prognostic marker and a negative predictor of response to anti-EGFR therapies in RAS wild-type CRC. Therefore, new and advanced treatment strategies are needed for personalized medical treatment of patients with wild-type RAS and PIK3CA mutation. Methods: Patient-derived tumor cells were collected from the ascites of a refractory colon cancer patient with wild-type RAS and PIK3CA mutation...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28927154/resistance-to-the-mtor-inhibitor-everolimus-is-reversed-by-the-downregulation-of-survivin-in-breast-cancer-cells
#3
Ludovica Taglieri, Francesca De Iuliis, Anna Giuffrida, Sabrina Giantulli, Ida Silvestri, Susanna Scarpa
Everolimus (RAD001) is an inhibitor of mammalian target of rapamycin used in combination with exemestane to treat hormone receptor-positive advanced breast cancer. However, not all patients are equally sensitive to RAD001 and certain patients develop resistance. Therefore, the present study analyzed the mechanisms involved in the resistance of breast cancer cells to RAD001 in order to identify a potential tool to overcome it. The effects of RAD001 on the inhibition of cell viability, on the induction of apoptosis and autophagy and on the regulation of survivin, an anti-apoptotic protein, were evaluated in two breast cancer cell lines: BT474 (luminal B) and MCF7 (luminal A)...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923786/final-five-year-clinical-outcomes-in-the-evolve-trial-a-randomized-evaluation-of-a-novel-bioabsorbable-polymer-coated-everolimus-eluting-stent
#4
Ian T Meredith, Stefan Verheye, Christophe Dubois, Joseph Dens, Bruno Farah, Didier Carrié, Simon Walsh, Keith Oldroyd, Olivier Varenne, Seif El-Jack, Raul Moreno, Thomas Christen, Dominic J Allocco
AIMS: Long-term data for bioabsorbable polymer-coated everolimus-eluting stents (BP-EES) are limited. The EVOLVE trial compared the safety and efficacy of 2 dose formulations of SYNERGY BP-EES with permanent polymer-coated PROMUS Element EES (PE). METHODS AND RESULTS: The EVOLVE study was a prospective, multicentre, noninferiority trial that randomised 291 patients with de novo coronary lesions (length: ≤28mm; diameter: ≥2.25 to ≤3.5 mm) to receive PE (n=98), SYNERGY (n=94), or SYNERGY half-dose (n=99)...
September 19, 2017: EuroIntervention
https://www.readbyqxmd.com/read/28923653/effects-of-the-mammalian-target-of-rapamycin-inhibitor-everolimus-on-hepatitis-c-virus-replication-in%C3%A2-vitro-and-in%C3%A2-vivo
#5
A Frey, E-M Ecker, K Piras-Straub, A Walker, T G Hofmann, J Timm, B B Singer, G Gerken, K Herzer
BACKGROUND: The influence of immunosuppressants on hepatitis C virus (HCV) re-infection after liver transplantation, particularly mammalian target of rapamycin inhibitors, remains unclear. The aim of our study was to analyze the influence of everolimus (EVR) on HCV replication activity in the context of underlying molecular mechanisms, with focus on the pro-myelocytic leukemia protein (PML). METHODS: HCV viral load was recorded in 40 patients with post-transplant HCV re-infection before and 8 weeks after introduction of EVR...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923623/mycophenolate-mofetil-withdrawal-with-conversion-to-everolimus-to-treat-bk-virus-infection-in-kidney-transplant-recipients
#6
D Wojciechowski, S Chandran, A Webber, R Hirose, F Vincenti
BACKGROUND: BK virus (BKV) is a significant post-transplant infection. Mammalian target of rapamycin inhibitors (mTORis) reduce BKV large T antigen expression in vitro and are associated with lower rates of BKV infection when used as de novo immunosuppression in clinical studies. METHODS: We performed a prospective, single-center, randomized, open label pilot trial to evaluate the impact of mycophenolate mofetil (MMF) withdrawal with conversion to the mTORi everolimus versus a 50% reduction of the MMF dose for the treatment of BKV infection after kidney transplantation...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923619/ten-year-follow-up-of-pharmacokinetics-guided-very-early-cyclosporine-minimization-synchronized-with-everolimus-initiation-in-de-novo-kidney-transplantation
#7
V Sumethkul, P Tankee, S Worawichawong, S Jirasiritham
BACKGROUND: Minimization of calcineurin inhibitor (CNI) from the 1st week after kidney transplantation (KT) may reduce the risk of CNI nephrotoxicity. METHODS: Ten de novo KT recipients who received full exposure cyclosporine (CsA) and prednisolone as initial therapy were enrolled. Initial CsA minimization was 50% and started at day 7 after KT. This was synchronized with everolimus (EVL) initiation. Target trough level of EVL was 3-8 ng/mL. Pharmacokinetics studies of CsA and EVL were studied at week 4...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28923615/effective-and-safe-reduction-of-conventional-immunosuppressants-using-everolimus-in-maintenance-kidney-transplant-recipients
#8
K Nanmoku, A Kurosawa, T Kubo, T Shinzato, T Shimizu, T Kimura, T Yagisawa
BACKGROUND: Adverse events due to conventional immunosuppressive therapy decrease both graft and patient survival. We aimed to establish a new protocol using everolimus (EVR) to safely minimize conventional immunosuppressants in maintenance kidney transplant recipients. METHODS: A total of 86 consecutive kidney transplant recipients with no complications were maintained with triple-drug combination therapy (conventional group). In case of complications, the administration of very low-dose tacrolimus (C0: 5...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28920492/recommendations-on-managing-lenvatinib-and-everolimus-in-patients-with-advanced-or-metastatic-renal-cell-carcinoma
#9
E Grande, H Glen, J Aller, G Argenziano, M J Lamas, P Ruszniewski, J L Zamorano, K Edmonds, S Sarker, M Staehler, J Larkin
There are several second-line treatment options for patients with renal cell carcinoma after first-line failure of a tyrosine kinase inhibitor, especially with the recent approvals of cabozantinib, nivolumab, and the lenvatinib plus everolimus combination. A lack of reliable biomarkers and an overall lack of prospective head-to-head comparisons make it a challenge to choose a second-line treatment in the clinic. Areas covered: In this review/meta-opinion, we describe the safety profile of the lenvatinib plus everolimus combination in renal cell carcinoma...
September 18, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28913627/everolimus-eluting-bioresorbable-vascular-scaffold-in-daily-clinical-practice-a%C3%A2-single-centre-experience
#10
W S Remkes, R S Hermanides, M W Kennedy, E Fabris, E Kaplan, J P Ottervanger, A W J van 't Hof, E Kedhi
BACKGROUND: Recent evidence has raised concerns regarding the safety of the everolimus-eluting bioresorbable vascular scaffold (E-BVS) (Absorb, Abbott Vascular, Santa Clara, CA, USA). Following these data, the use of this device has diminished in the Netherlands; however, daily practice data are limited. Therefore we studied the incidence of safety and efficacy outcomes with this device in daily clinical practice in a single large tertiary centre in the Netherlands. METHODS: All E‑BVS treated patients were included in this analysis...
September 14, 2017: Netherlands Heart Journal
https://www.readbyqxmd.com/read/28905990/the-mtor-kinase-inhibitor-everolimus-synergistically-enhances-the-anti-tumor-effect-of-the-bruton-s-tyrosine-kinase-btk-inhibitor-pls-123-on-mantle-cell-lymphoma
#11
Jiao Li, Xiaogan Wang, Yan Xie, Zhitao Ying, Weiping Liu, Lingyan Ping, Chen Zhang, Zhengying Pan, Ning Ding, Yuqin Song, Jun Zhu
Mantle cell lymphoma (MCL) is an aggressive and incurable malignant disease. Despite of general chemotherapy, relapse and mortality are common, highlighting the need for the development of novel targeted drugs or combination of therapeutic regimens. Recently, several drugs that target the B-cell receptor (BCR) signaling pathway, especially the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicate that pharmacological inhibition of BCR pathway holds promise in MCL treatment...
September 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28905429/intermittent-everolimus-administration-for-renal-angiomyolipoma-associated-with-tuberous-sclerosis-complex
#12
Takashi Hatano, Hiroyuki Inaba, Katsuhisa Endo, Shin Egawa
OBJECTIVES: To evaluate the effects and utility of intermittent everolimus treatment for renal angiomyolipoma associated with tuberous sclerosis complex. METHODS: We investigated a total of 26 patients with tuberous sclerosis complex who had angiomyolipoma ≥4 cm in diameter. For each patient, we analyzed the reduction in the size of the angiomyolipoma, the change in size after everolimus withdrawal, the size reduction rate on everolimus readministration and adverse events caused by everolimus...
September 14, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28905424/editorial-comment-to-intermittent-everolimus-administration-for-renal-angiomyolipoma-associated-with-tuberous-sclerosis-complex
#13
Suguru Shirotake, Koshiro Nishimoto
No abstract text is available yet for this article.
September 14, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28904441/everolimus-associated-acute-kidney-injury-in-patients-with-metastatic-breast-cancer
#14
A Chandra, N S Rao, K P Malhotra, M Rastogi, R Khurana
Recently, everolimus (Evl) has been introduced in the management of hormone receptor-positive metastatic breast cancer, in combination with aromatase inhibitors. Evl-induced acute kidney injury has hitherto been described in other malignancies, especially renal cell cancer, but only once before in a patient with breast cancer. We describe two cases of Evl-associated nephrotoxicity in patients with breast cancer, one of whom underwent a renal biopsy showing acute tubular necrosis. Both our patients improved after withdrawal of the offending agent and have normal renal functions on follow-up...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28903445/predicting-clinical-benefit-from-everolimus-in-patients-with-advanced-solid-tumors-the-cpct-03-study
#15
Fleur Weeber, Geert A Cirkel, Marlous Hoogstraat, Sander Bins, Christa G M Gadellaa-van Hooijdonk, Salo Ooft, Erik van Werkhoven, Stefan M Willems, Marijn van Stralen, Wouter B Veldhuis, Nicolle J M Besselink, Hugo M Horlings, Neeltje Steeghs, Maja J de Jonge, Marlies H G Langenberg, Lodewyk F A Wessels, Edwin P J G Cuppen, J H Schellens, Stefan Sleijfer, Martijn P Lolkema, Emile E Voest
BACKGROUND: In this study, our aim was to identify molecular aberrations predictive for response to everolimus, an mTOR inhibitor, regardless of tumor type. METHODS: To generate hypotheses about potential markers for sensitivity to mTOR inhibition, drug sensitivity and genomic profiles of 835 cell lines were analyzed. Subsequently, a multicenter study was conducted. Patients with advanced solid tumors lacking standard of care treatment options were included and underwent a pre-treatment tumor biopsy to enable DNA sequencing of 1,977 genes, derive copy number profiles and determine activation status of pS6 and pERK...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903425/pasireotide-is-more-effective-than-octreotide-alone-or-combined-with-everolimus-on-human-meningioma-in-vitro
#16
Thomas Graillon, David Romano, Céline Defilles, Christophe Lisbonis, Alexandru Saveanu, Dominique Figarella-Branger, Pierre-Hugues Roche, Stéphane Fuentes, Olivier Chinot, Henry Dufour, Anne Barlier
Pasireotide is a somatostatin analog (SSA) that targets somatostatin receptor subtype 1 (SST1), SST2, SST3, and SST5 with a high affinity. Pasireotide has a better antisecretory effect in acromegaly, Cushing's disease, and neuroendocrine tumors than octreotide. In this study, we compared the effects of pasireotide to those of octreotide in vitro on meningioma primary cell cultures, both alone and in combination with the mTOR inhibitor everolimus. Significant mRNA expression levels of SST1, SST2, and SST5 were observed in 40...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901501/mtor-inhibition-reduces-growth-and-adhesion-of-hepatocellular-carcinoma-cells-in%C3%A2-vitro
#17
Tobias Engl, Jochen Rutz, Sebastian Maxeiner, Eva Juengel, Frederik Roos, Wael Khoder, Wolf O Bechstein, Karen Nelson, Igor Tsaur, Axel Haferkamp, Roman A Blaheta
Mechanistic target of rapamycin (mTOR) signaling is typically increased in hepatocellular carcinoma (HCC). A panel of HCC cell lines (HepG2, Hep3B and HuH6) was exposed to various concentrations of the mTOR inhibitors, everolimus and temsirolimus, in order to investigate their effects on cell growth, clonal formation, cell cycle progression, and adhesion and chemotactic migration using MTT and clonal cell growth assays, fluorometric detection of cell cycle phases and a Boyden chamber assay. In addition, integrin α and β adhesion receptors were analyzed by flow cytometry and blocking studies using function blocking monoclonal antibodies were conducted to explore functional relevance...
August 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28894595/the-impact-of-the-3-year-absorb-ii-trial-results-on-my-clinical-practice-an-italian-survey
#18
Matteo Serenelli, Simone Biscaglia, Elisabetta Tonet, Arnaldo Poli, Elisa Nicolini, Alfonso Ielasi, Andrea Erriquez, Gianluca Campo
BACKGROUND: To evaluate how the 3-year results from the "A clinical evaluation to compare the safety, efficacy and performance of ABSORB everolimus eluting bioresorbable vascular scaffold (BVS) system against XIENCE everolimus eluting coronary stent system in the treatment of subjects with ischemic heart disease caused by de novo native coronary artery lesions" (ABSORB II) trial have influenced clinical practice among Italian interventional cardiologists. METHODS: We performed a survey among 95 interventional cardiologists sending a brief questionnaire by electronic mail...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28894594/effectiveness-and-safety-of-the-absorb-bioresorbable-vascular-scaffold-for-the-treatment-of-coronary-artery-disease-systematic-review-and-meta-analysis-of-randomized-clinical-trials
#19
Rita Pavasini, Matteo Serenelli, Francesco Gallo, Giulia Bugani, Salvatore Geraci, Paolo Vicinelli, Gianluca Campo
BACKGROUND: In the last years bioresorbable vascular scaffold (BVS) become a new therapeutic option for interventional cardiologists, with the advantage of a scaffold inducing a possible vessel wall restoration. Nevertheless, several trials tried to prove the safety and efficacy profile of scaffolds, but with conflicting results. METHODS: A systematic review and meta-analysis was performed. The search was carried out in PubMed, Google Scholar, Biomed Central and Cochrane Library between January and March 2017...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28893770/serial-5-year-evaluation-of-side-branches-jailed-by-bioresorbable-vascular-scaffolds-using-3-dimensional-optical-coherence-tomography-insights-from-the-absorb-cohort-b-trial-a-clinical-evaluation-of-the-bioabsorbable-everolimus-eluting-coronary-stent-system
#20
Yoshinobu Onuma, Maik J Grundeken, Shimpei Nakatani, Taku Asano, Yohei Sotomi, Nicolas Foin, Jaryl Ng, Takayuki Okamura, Joanna J Wykrzykowska, Robbert J de Winter, Robert-Jan van Geuns, Jacques Koolen, Evald Christiansen, Robert Whitbourn, Dougal McClean, Pieter Smits, Stephan Windecker, John A Ormiston, Patrick W Serruys
BACKGROUND: The long-term fate of Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, CA) struts jailing side branch ostia has not been clarified. We therefore evaluate serially (post-procedure and at 6 months, 1, 2, 3, and 5 years) the appearance and fate of jailed Absorb bioresorbable vascular scaffold struts. METHODS AND RESULTS: We performed 3-dimensional optical coherence tomographic analysis of the ABSORB Cohort B trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) up to 5 years using a novel, validated cut-plane analysis method...
September 2017: Circulation. Cardiovascular Interventions
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