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https://www.readbyqxmd.com/read/28535439/critical-focus-on-mechanisms-of-resistance-and-toxicity-of-m-tor-inhibitors-in-pancreatic-neuroendocrine-tumors
#1
REVIEW
L Antonuzzo, M Del Re, V Barucca, F Spada, G Meoni, G Restante, R Danesi, F Di Costanzo, N Fazio
Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms representing less than 2% of all pancreatic malignancies. The PI3K-AKT-mTOR pathway is often deregulated in pNETs and seems to play a key role in tumorigenesis. Everolimus, an inhibitor of the mTOR pathway, has demonstrated efficacy in the treatment of pNETs. Nevertheless de novo or acquired drug resistance is responsible for disease progression and represents a major obstacle to overcome by clinicians. Blocking the PI3K/AKT/mTOR pathway may cover the supposed main mechanisms of resistance to everolimus...
May 11, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28535181/everolimus-with-paclitaxel-and-carboplatin-as-first-line-treatment-for-metastatic-large-cell-neuroendocrine-lung-carcinoma-a-multicenter-phase-ii-trial
#2
P Christopoulos, W Engel-Riedel, C Grohé, C Kropf-Sanchen, J von Pawel, S Gütz, J Kollmeier, W Eberhardt, D Ukena, V Baum, I Nimmrich, C Sieder, P A Schnabel, M Serke, M Thomas
Background: Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare disease with poor prognosis and limited treatment options. Neuroendocrine tumors frequently show overactivation of the mTOR pathway. Based on the good activity of the mTOR inhibitor everolimus in different types of neuroendocrine tumors and the results of a previous phase I trial we evaluated the efficacy and safety of everolimus in combination with carboplatin and paclitaxel as upfront treatment for patients with advanced LCNEC...
May 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28531203/potential-health-gains-for-patients-with-metastatic-renal-cell-carcinoma-in-daily-clinical-practice-a-real-world-cost-effectiveness-analysis-of-sequential-first-and-second-line-treatments
#3
S De Groot, H M Blommestein, W K Redekop, S Sleijfer, L A L M Kiemeney, E Oosterwijk, C A Uyl-de Groot
INTRODUCTION: Randomised controlled trials have shown that targeted therapies like sunitinib are effective in metastatic renal cell carcinoma (mRCC). Little is known about the current use of these therapies, and their associated costs and effects in daily clinical practice. We estimated the real-world cost-effectiveness of different treatment strategies comprising one or more sequentially administered drugs. METHODS: Analyses were performed using patient-level data from a Dutch population-based registry including patients diagnosed with primary mRCC from January 2008 to December 2010 (i...
2017: PloS One
https://www.readbyqxmd.com/read/28523933/the-pazoreal-noninterventional-study-to-assess-effectiveness-and-safety-of-pazopanib-and-everolimus-in-the-changing-metastatic-renal-cell-carcinoma-treatment-landscape
#4
Peter J Goebell, Christian Doehn, Carsten Grüllich, Viktor Grünwald, Thomas Steiner, Rainer Ehneß, Manfred Welslau
VEGFR and mTOR inhibitors are broadly used in metastatic renal cell carcinoma (mRCC) therapy, and sequential first-line pazopanib (VEGFR inhibitor) and second-line everolimus (mTOR inhibitor) is a standard treatment option. Nivolumab and lenvatinib/everolimus combination was recently approved in Europe for use in mRCC after previous therapy. Prospective routine data on sequential therapy including nivolumab and/or lenvatinib are missing. This is a prospective, noninterventional study, which evaluates the effectiveness, tolerability, safety and quality of life following 450 patients with mRCC starting either on pazopanib as first-line therapy or third-line everolimus plus/minus lenvatinib following nivolumab...
May 19, 2017: Future Oncology
https://www.readbyqxmd.com/read/28516156/single-arm-phase-i-ii-study-of-everolimus-and-intravesical-gemcitabine-in-patients-with-primary-or-secondary-carcinoma-in-situ-of-the-bladder-who-failed-bacillus-calmette-guerin-nct01259063
#5
Guido Dalbagni, Nicole Benfante, Daniel D Sjoberg, Bernard H Bochner, S Machele Donat, Harry W Herr, Asia S Mc Coy, Alicia J Fahrner, Caitlyn Retinger, Jonathan E Rosenberg, Dean F Bajorin
Background: Standard treatment for BCG-refractory urothelial cancer is radical cystectomy. Identification of active agents is clearly warranted. Objective: To determine a safe dose of oral everolimus in combination with standard intravesical gemcitabine and to evaluate the efficacy of this combination. Methods: Patients with carcinoma in situ refractory to intravesical bacillus Calmette-Guérin and refusing cystectomy were eligible. Patients in the phase I part of the trial received one of three dose levels of oral everolimus...
April 27, 2017: Bladder Cancer
https://www.readbyqxmd.com/read/28516155/phase-i-clinical-trial-of-everolimus-combined-with-trimodality-therapy-in-patients-with-muscle-invasive-bladder-cancer
#6
Bassel G Bachir, Luis Souhami, Jose João Mansure, Fabio Cury, Marie Vanhuyse, Fadi Brimo, Armen G Aprikian, Simon Tanguay, Jeremy Sturgeon, Wassim Kassouf
Background: Local control following trimodality therapy (TMT) for muscle-invasive bladder cancer (MIBC) requires further optimization. Objective: Evaluating the biologic endpoint, feasibility, and toxicity of integrating everolimus to TMT in patients with MIBC. Methods: This was a phase I trial in patients with MIBC who were not surgical candidates or who refused cystectomy. Following maximal transurethral tumor resection, patients were treated by radiotherapy (50 Gy/20 fractions), gemcitabine (100 mg/m2/weekly) and escalating doses of everolimus (2...
April 27, 2017: Bladder Cancer
https://www.readbyqxmd.com/read/28515249/incorporating-new-systemic-therapies-in-kidney-cancer-treatment
#7
Eric Jonasch
In 2017, pazopanib and sunitinib remain the mainstays of frontline therapy for advanced renal cell carcinoma. Independent review of frontline cabozantinib therapy may alter standard of care for patients at intermediate and poor risk. Multiple agents show a survival advantage in the second-line setting, including nivolumab, cabozantinib, and combination lenvatinib and everolimus. Selection of subsequent therapy will depend on patient disease status, comorbidities, and resource availability.
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28513992/immunoregulatory-protein-b7-h3-promotes-growth-and-decreases-sensitivity-to-therapy-in-metastatic-melanoma-cells
#8
Karine Flem-Karlsen, Christina Tekle, Yvonne Andersson, Kjersti Flatmark, Øystein Fodstad, Caroline E Nunes-Xavier
B7-H3 (CD276) belongs to the B7-family of immunoregulatory proteins, and has been implicated in cancer progression and metastasis. In this study, we found that metastatic melanoma cells with knockdown expression of B7-H3 showed modest decrease in proliferation and glycolytic capacity, and were more sensitive to dacarbazine (DTIC) chemotherapy and small-molecule inhibitors targeting MAP kinase (MAPK)- and AKT/mTOR-pathways: vemurafenib (PLX4032; BRAF inhibitor), binimetinib (MEK-162; MEK inhibitor), everolimus (RAD001; mTOR inhibitor) and triciribidine (API-2; AKT inhibitor)...
May 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28512069/optical-coherence-tomography-findings-insights-from-the-randomised-multicentre-trial-investigating-angiographic-outcomes-of-hybrid-sirolimus-eluting-stents-with-biodegradable-polymer-compared-with-everolimus-eluting-stents-with-durable-polymer-in-chronic-total
#9
Koen Teeuwen, Eva M Spoormans, Johan Bennett, Christophe Dubois, Walter Desmet, Giovanni J Ughi, Ann Belmans, Johannes C Kelder, Jan G P Tijssen, Pierfrancesco Agostoni, Maarten J Suttorp, Tom Adriaenssens
AIMS: The PRISON IV trial investigated the next-generation sirolimus-eluting stent (SES) with ultra-thin struts and biodegradable polymer against the second-generation everolimus-eluting stent (EES) with thin struts and durable polymer in patients with successfully recanalised chronic total occlusions (CTO). In this study, we examined the secondary optical coherence tomography endpoints. METHODS AND RESULTS: The main PRISON IV trial randomised 330 patients to either SES or EES...
May 18, 2017: EuroIntervention
https://www.readbyqxmd.com/read/28511812/acute-management-of-symptomatic-subependymal-giant-cell-astrocytoma-with-everolimus
#10
Monica S Arroyo, Darcy A Krueger, Eileen Broomall, Charles B Stevenson, David N Franz
BACKGROUND: Subependymal giant cell astrocytomas (SEGA) are slow-growing tumors, which can cause obstructive hydrocephalus in patients with tuberous sclerosis complex (TSC). These tumors require routine surveillance with magnetic resonance imaging. Current consensus guidelines recommend treatment of asymptomatic SEGAs with an mechanistic target of rapamycin (mTOR) inhibitor because these medications have demonstrated efficacy and safety in multiple prospective clinical trials. For symptomatic SEGAs, standard therapy typically involves surgical resection of the tumor to relieve mass effect and resolve hydrocephalus...
April 18, 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28511172/donor-specific-anti-human-leukocyte-antigens-antibodies-acute-rejection-renal-function-and-histology-in-kidney-transplant-recipients-receiving-tacrolimus-and-everolimus
#11
Alexandra Ferreira, Claudia Felipe, Marina Cristelli, Laila Viana, Geovana Basso, Suelen Stopa, Juliana Mansur, Mayara Ivani, Adrieli Bessa, Priscila Ruppel, Wilson Aguiar, Erika Campos, Maria Gerbase-DeLima, Henrique Proença, Helio Tedesco-Silva, José Medina-Pestana
BACKGROUND: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). METHODS: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101)...
May 17, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28508247/in-human-cell-cultures-everolimus-is-inferior-to-tacrolimus-in-inhibiting-cellular-alloimmunity-but-equally-effective-as-regards-humoral-alloimmunity
#12
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Georgia Antoniadi, Nikolaos Antoniadis, Vassilios Liakopoulos, Ioannis Stefanidis
PURPOSE: Acute cellular rejection is the major cause of immune-mediated graft failure early in the course of kidney transplantation, whereas chronic antibody-mediated rejection is a major contributor to graft loss in the late post-transplant phase. Based mainly on the results of short-term studies, the calcineurin inhibitor tacrolimus prevails over the mammalian target of rapamycin (mTOR) inhibitors. However, the toxicity profile of the two drug categories differs, making the interchange between them appealing...
May 15, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28507917/systemic-meta-analysis-assessing-the-short-term-applicability-of-early-conversion-to-mammalian-target-of-rapamycin-inhibitors-in-kidney-transplant
#13
Jayant Kumar, Isabella Reccia, Tomokazu Kusano, Bridson M Julie, Ajay Sharma, Ahmed Halawa
AIM: To consolidate the present evidence of effectiveness in renal functioning and graft survival following early introduction of mammalian target of rapamycin (mTOR) inhibitors with or without calcineurin inhibitors (CNIs) in renal transplant recipients. METHODS: We analysed the current literature following PROSPERO approval describing the role of immunosuppressive agent, mTOR inhibitors as an alternative to CNI within six months of renal transplant by searching the PubMed, EMBASE, Cochrane, Crossref, and Scopus using MeSH terms...
April 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28506751/recent-progress-towards-clinically-relevant-atp-competitive-akt-inhibitors
#14
REVIEW
Bayard R Huck, Igor Mochalkin
The frequency of PI3K/Akt/mTOR (PAM) Pathway mutations in human cancers sparked interest to determine if the pathway is druggable. The modest clinical benefit observed with mTOR rapalogs (temsirolimus and everolimus) provided further motivation to identify additional nodes of pathway inhibition that lead to improved clinical benefit. Akt is a central signaling node of the PAM pathway and could be an ideal target for improved pathway inhibition. Furthermore, inhibitors of Akt may be especially beneficial in tumors with Akt1 mutations...
April 29, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28504837/immunotherapy-for-metastatic-renal-cell-carcinoma
#15
REVIEW
Susanne Unverzagt, Ines Moldenhauer, Monika Nothacker, Dorothea Roßmeißl, Andreas V Hadjinicolaou, Frank Peinemann, Francesco Greco, Barbara Seliger
BACKGROUND: Since the mid-2000s, the field of metastatic renal cell carcinoma (mRCC) has experienced a paradigm shift from non-specific therapy with broad-acting cytokines to specific regimens, which directly target the cancer, the tumour microenvironment, or both.Current guidelines recommend targeted therapies with agents such as sunitinib, pazopanib or temsirolimus (for people with poor prognosis) as the standard of care for first-line treatment of people with mRCC and mention non-specific cytokines as an alternative option for selected patients...
May 15, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28500737/clinical-outcomes-of-overlapping-versus-non-overlapping-everolimus-eluting-absorb-bioresorbable-vascular-scaffolds-an-analysis-from-the-multicentre-prospective-rai-registry-clinicaltrials-gov-identifier-nct02298413
#16
Giuseppe Tarantini, Marco Mojoli, Giulia Masiero, Bernardo Cortese, Bruno Loi, Attilio Varricchio, Gabriele Gabrielli, Alessandro Durante, Giampaolo Pasquetto, Paolo Calabrò, Roberto Gistri, Gabriele Tumminello, Leonardo Misuraca, Francesco Pisano, Alfonso Ielasi, Pietro Mazzarotto, Sebastian Coscarelli, Valerio Lucci, Luciano Moretti, Annamaria Nicolino, Alessandro Colombo, Zoran Olivari, Massimo Fineschi, Davide Piraino, Luigi Piatti, Umberto Canosi, Paola Tellaroli, Donatella Corrado, Chiara Rovera, Giuseppe Steffenino
OBJECTIVES: To compare clinical outcomes of patients treated with overlapping versus non-overlapping Absorb BVS. BACKGROUND: Limited data are available on the clinical impact of stent overlap with the Absorb BVS bioresorbable stent. METHODS: We compared outcomes of patients receiving overlapping or non-overlapping Absorb BVS in the multicenter prospective RAI Registry. RESULTS: Out of 1,505 consecutive patients treated with Absorb BVS, 1,384 were eligible for this analysis...
May 13, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28500289/stapled-big3-helical-peptide-erap-potentiates-anti-tumour-activity-for-breast-cancer-therapeutics
#17
Tetsuro Yoshimaru, Keisuke Aihara, Masato Komatsu, Yosuke Matsushita, Yasumasa Okazaki, Shinya Toyokuni, Junko Honda, Mitsunori Sasa, Yasuo Miyoshi, Akira Otaka, Toyomasa Katagiri
Estradiol (E2) and the oestrogen receptor-alpha (ERα) signalling pathway play pivotal roles in the proliferative activity of breast cancer cells. Recent findings show that the brefeldin A-inhibited guanine nucleotide-exchange protein 3-prohibitin 2 (BIG3-PHB2) complex plays a crucial role in E2/ERα signalling modulation in breast cancer cells. Moreover, specific inhibition of the BIG3-PHB2 interaction using the ERα activity-regulator synthetic peptide (ERAP: 165-177 amino acids), derived from α-helical BIG3 sequence, resulted in a significant anti-tumour effect...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28498849/percutaneous-coronary-intervention-with-second-generation-drug-eluting-stent-versus-bare-metal-stent-systematic-review-and-cost-benefit-analysis
#18
Thomas G Poder, Jihane Erraji, Lucien P Coulibaly, Kouamé Koffi
BACKGROUND: Drug-eluting stents (DESs) were considered as ground-breaking technology promising to eradicate restenosis and the necessity to perform multiple revascularization procedures subsequent to percutaneous coronary intervention. Soon after DESs were released on the market, however, there were reports of a potential increase in mortality and of early or late thrombosis. In addition, DESs are far more expensive than bare-metal stents (BMSs), which has led to their limited use in many countries...
2017: PloS One
https://www.readbyqxmd.com/read/28495897/geographical-difference-of-the-interaction-of-sex-with-treatment-strategy-in-patients-with-multivessel-disease-and-left-main-disease-a-meta-analysis-from-syntax-synergy-between-pci-with-taxus-and-cardiac-surgery-precombat-bypass-surgery-versus-angioplasty-using
#19
Yohei Sotomi, Yoshinobu Onuma, Rafael Cavalcante, Jung-Min Ahn, Cheol Whan Lee, David van Klaveren, Robbert J de Winter, Joanna J Wykrzykowska, Vasim Farooq, Marie-Claude Morice, Ewout W Steyerberg, Seung-Jung Park, Patrick W Serruys
BACKGROUND: The impact of sex on clinical outcomes of percutaneous coronary intervention and coronary artery bypass graft for patients with multivessel coronary disease and unprotected left main disease could be dissimilar between Western and Asian populations. METHODS AND RESULTS: To assess clinical outcomes after percutaneous coronary intervention or coronary artery bypass graft in women and men with multivessel coronary disease and unprotected left main disease, a pooled analysis (n=3280) was performed using the patient-level data from 3 large randomized trials: SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and BEST (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) trials...
May 2017: Circulation. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28495808/comprehensive-genomic-profiling-of-esthesioneuroblastoma-reveals-additional-treatment-options
#20
Laurie M Gay, Sungeun Kim, Kyle Fedorchak, Madappa Kundranda, Yazmin Odia, Chaitali Nangia, James Battiste, Gerardo Colon-Otero, Steven Powell, Jeffery Russell, Julia A Elvin, Jo-Anne Vergilio, James Suh, Siraj M Ali, Philip J Stephens, Vincent A Miller, Jeffrey S Ross
BACKGROUND: Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit. MATERIALS AND METHODS: We queried whether comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover genomic alterations (GA) that could identify potential targeted therapies for these patients...
May 11, 2017: Oncologist
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