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https://www.readbyqxmd.com/read/29156677/overcoming-resistance-to-single-agent-therapy-for-oncogenic-braf-gene-fusions-via-combinatorial-targeting-of-mapk-and-pi3k-mtor-signaling-pathways
#1
Payal Jain, Amanda Silva, Harry J Han, Shih-Shan Lang, Yuankun Zhu, Katie Boucher, Tiffany E Smith, Aesha Vakil, Patrick Diviney, Namrata Choudhari, Pichai Raman, Christine M Busch, Tim Delaney, Xiaodong Yang, Aleksandra K Olow, Sabine Mueller, Daphne Haas-Kogan, Elizabeth Fox, Phillip B Storm, Adam C Resnick, Angela J Waanders
Pediatric low-grade gliomas (PLGGs) are frequently associated with activating BRAF gene fusions, such as KIAA1549-BRAF, that aberrantly drive the mitogen activated protein kinase (MAPK) pathway. Although RAF inhibitors (RAFi) have been proven effective in BRAF-V600E mutant tumors, we have previously shown how the KIAA1549-BRAF fusion can be paradoxically activated by RAFi. While newer classes of RAFi, such as PLX8394, have now been shown to inhibit MAPK activation by KIAA1549-BRAF, we sought to identify alternative MAPK pathway targeting strategies using clinically relevant MEK inhibitors (MEKi), along with potential escape mechanisms of acquired resistance to single-agent MAPK pathway therapies...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151264/renal-protection-strategies-after-heart-transplantation
#2
REVIEW
Daniel Reichart, Hermann Reichenspurner, Markus Johannes Barten
Renal dysfunction caused by calcineurin inhibitor (CNI) nephrotoxicity occurs often and contributes significantly to late mortality after heart transplantation (HTx). Over the last decades, this has prompted many clinical studies in an effort to develop kidney-protecting immunosuppressive strategies including delayed CNI start, minimization, withdrawal or even de-novo CNI avoidance. In the past, these strategies often failed due to the lack of efficacy. Since 2009, novel CNI-reducing strategies are under investigation...
November 19, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29150493/very-late-pathological-responses-to-cobalt-chromium-everolimus-eluting-stainless-steel-sirolimus-eluting-and-cobalt-chromium-bare-metal-stents-in-humans
#3
Hiroyoshi Mori, Dheeraj R Atmakuri, Sho Torii, Ryan Braumann, Samantha Smith, Hiroyuki Jinnouchi, Anuj Gupta, Emanuel Harari, Melsi Shkullaku, Robert Kutys, David Fowler, Maria Romero, Renu Virmani, Aloke V Finn
BACKGROUND: The "very late" clinical outcomes for durable polymer drug-eluting stents and bare metal stents (BMSs) have been shown to be dissimilar in clinical studies. Conceptually, the long-term vascular compatibility of BMSs is still regarded to be superior to drug-eluting stents; however, no pathologic study to date has specifically addressed this issue. We evaluated the very late (≥1 year) pathologic responses to durable polymer drug-eluting stents (cobalt-chromium [CoCr] everolimus-eluting stents [EESs] and stainless steel sirolimus-eluting stents [SS-SESs]) versus BMSs (CoCr-BMSs)...
November 17, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29148244/real-life-experience-with-bioresorbable-polymer-everolimus-eluting-stents-is-this-an-answer-in-search-of-a-question
#4
EDITORIAL
Youssef Rahban, Carey Kimmelstiel
Stent thrombosis and clinically driven restenosis are rare in the era of newer generation DES. The Synergy bioresorbable polymer DES appears to be comparable to other durable polymer and other bioabsorbable polymer DES in terms of safety and efficacy at 1-year post implantation. Further long-term study is needed to determine the specific role of the Synergy stent and other DES with bioabsorbable polymers.
November 15, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/29147473/bioresorbable-vascular-scaffold-versus-metallic-stent-in-percutaneous-coronary-intervention-results-of-the-aida-trial
#5
Syed Raza Shah, Mazia Fatima, Amin Muhammad Dharani, Waqas Shahnawaz, Syed Arbab Shah
Drug-eluting stents have significantly improved the long-term outcomes of percutaneous coronary intervention (PCI) by decreasing the excessive growth of neointima. However, conventional stents have some limitations. PCI with a bioresorbable vascular scaffold (BVS) has emerged as an alternative since the presence of the prosthesis in the coronary artery is transient. A US Food and Drug Administration advisory panel of experts recommended approval of BVS based on the analysis of its risks and rewards in July 2016...
2017: Journal of Community Hospital Internal Medicine Perspectives
https://www.readbyqxmd.com/read/29146893/von-hippel-lindau-disease-with-multi-organ-involvement-a-case-report-and-8-year-clinical-course-with-follow-up
#6
Ali Yaghobi Joybari, Payam Azadeh
BACKGROUND Von Hippel-Lindau (VHL) disease is a rare autosomal dominant syndrome manifested by a spectrum of benign and malignant tumors.  CASE REPORT The patient presented here was a 31-year-old female with unremarkable family history who presented initially complaining of intermittent abdominal pain. Abdominal CT scan revealed an inhomogeneous solid mass (13×9×7 cm) originating from the tail of the pancreas with splenic and gastric invasion as well as several pancreatic cysts. A nucleotide scan showed left adrenal involvement...
November 17, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/29146887/targeted-therapy-of-gastroenteropancreatic-neuroendocrine-tumours-preclinical-strategies-and-future-targets
#7
Elke Tatjana Aristizabal Prada, Christoph J Auernhammer
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mTOR-inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression free survival due to tumor resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP-system are needed. This paper reviews preclinical research models and signaling pathways in NETs of the GEP-system...
November 16, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29146671/predictors-and-long-term-clinical-outcome-of-longitudinal-stent-deformation-insights-from-pooled-analysis-of-korean-multicenter-drug-eluting-stent-cohort
#8
Tae-Min Rhee, Kyung Woo Park, Joo Myung Lee, Michael S Lee, Ki-Hyun Jeon, Hyun-Jae Kang, Bon-Kwon Koo, Jay Young Rhew, Kwang Soo Cha, Jang-Ho Bae, Kyoo-Rok Han, Si-Hoon Park, Woo-Jung Park, Seung-Woon Rha, Seok-Kyu Oh, Hyuck Moon Kwon, Ki-Bae Seung, Taehoon Ahn, Sang-Hyun Kim, Hyo-Soo Kim
BACKGROUND: There are limited data on the frequency of and factors associated with quantitative coronary angiography (QCA)-defined longitudinal stent deformation (LSD) in various contemporary drug-eluting stents platforms. This study sought to evaluate the predictors of LSD and its long-term clinical implication. METHODS AND RESULTS: A patient-level pooled analysis was performed with 7350 lesions in 5871 patients treated with platinum-chromium-based everolimus-eluting stent (Promus Element), cobalt-chromium-based everolimus-eluting stent (Promus/Xience V), or cobalt-chromium-based zotarolimus-eluting stent (Endeavor Resolute)...
November 2017: Circulation. Cardiovascular Interventions
https://www.readbyqxmd.com/read/29146618/management-of-adverse-events-associated-with-cabozantinib-therapy-in-renal-cell-carcinoma
#9
REVIEW
Manuela Schmidinger, Romano Danesi
Cabozantinib was recently approved for the treatment of advanced renal cell carcinoma (RCC) after treatment with vascular endothelial growth factor (VEGF)-targeted therapy. Cabozantinib is a multikinase inhibitor targeting VEGF receptor (VEGFR) 2, mesenchymal-epithelial transition receptor, and "anexelekto" receptor tyrosine kinase. A 60-mg daily dose led to improved overall survival and progression-free survival (PFS) versus everolimus in advanced RCC patients as a second- or later-line treatment in the METEOR trial...
November 16, 2017: Oncologist
https://www.readbyqxmd.com/read/29143892/update-in-the-therapy-of-advanced-neuroendocrine-tumors
#10
REVIEW
Inbal Uri, Shani Avniel-Polak, David J Gross, Simona Grozinsky-Glasberg
Neuroendocrine tumors (NETs) are rare neoplasms, with an estimated annual incidence of ~ 6.9/100,000. NETs arise throughout the body from cells of the diffuse endocrine system. More than half originate from endocrine cells of the gastrointestinal tract and the pancreas, thus being referred to as gastroenteropancreatic NETs (GEP-NETs). The only treatment that offers a cure is surgery; however, most patients are diagnosed with metastatic disease, and curative surgery is usually not an option. These patients can be offered long-term systemic treatment, for both symptomatic relief and tumor growth suppression...
November 16, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29137819/vascular-response-and-healing-profile-of-everolimus-eluting-bioresorbable-vascular-scaffolds-for-percutaneous-treatment-of-chronic-total-coronary-occlusions-a-one-year-optical-coherence-tomography-analysis-from-the-ghost-cto-registry
#11
Alessio La Manna, Eligio Miccichè, Guido D'Agosta, Gabriel Tensol Rodrigues Pereira, Guilherme Ferragut Attizzani, Piera Capranzano, Davide Capodanno, Corrado Tamburino
BACKGROUND: Bioresorbable vascular scaffolds (BVS) have been heralded with potential benefits that are especially desired in long lesions, including chronic total occlusions (CTOs). Procedural feasibility and mid-term outcomes of BVS in CTOs have been reported. However, there is still a paucity of data regarding the vascular and healing response to BVS in CTOs evaluated by optical coherence tomography (OCT). METHODS: This study included prospectively 21 patients who had a CTO lesion treated with a BVS...
November 8, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/29137418/a-randomized-phase-ii-study-of-aromatase-inhibitors-plus-metformin-in-pre-treated-postmenopausal-patients-with-hormone-receptor-positive-metastatic-breast-cancer
#12
Yannan Zhao, Chengcheng Gong, Zhonghua Wang, Jian Zhang, Leiping Wang, Sheng Zhang, Jun Cao, Zhonghua Tao, Ting Li, Biyun Wang, Xichun Hu
Background: Everolimus significantly improves progression-free survival (PFS) and has been approved to use in aromatase inhibitor pretreated patients with hormone receptor positive advanced breast cancer. Metformin has been shown to inhibit mTOR pathway, with more favorable safety profile, leading to this hypothesis-generating trial to assess whether metformin enhances the efficacy of aromatase inhibitors. Methods: 60 postmenopausal women with hormone receptor positive locally advanced or metastatic breast cancer were randomly assigned 1:1 to aromatase inhibitor (exemestane 25mg/d or letrozole 2...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137365/longitudinal-serum-metabolomics-evaluation-of-trastuzumab-and-everolimus-combination-as-pre-operative-treatment-for-her-2-positive-breast-cancer-patients
#13
Elodie Jobard, Olivier Trédan, Thomas Bachelot, Arnaud M Vigneron, Céline Mahier Aït-Oukhatar, Monica Arnedos, Maria Rios, Jacques Bonneterre, Véronique Diéras, Marta Jimenez, Jean-Louis Merlin, Mario Campone, Bénédicte Elena-Herrmann
The mammalian target of rapamycin complex 1 (mTORC1) is an attractive target for HER-2 positive breast cancer therapy because of its key role in protein translation regulation, cell growth and metabolism. We present here a metabolomic investigation exploring the impact of mTOR inhibition on serum metabolic profiles from patients with non-metastatic breast cancer overexpressing HER-2. Baseline, treatment-related and post-treatment serum samples were analyzed for 79 patients participating in the French clinical trial RADHER, in which randomized patients with HER-2 positive breast cancer received either trastuzumab alone (arm T) or a trastuzumab and everolimus combination (arm T+E)...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131799/multi-slice-computed-tomography-assessment-of-everolimus-eluting-absorb-bioresorbable-scaffold-in-comparison-with-metallic-drug-eluting-stents-from-the-absorb-japan-randomized-trial
#14
Kengo Tanabe, Jeffrey J Popma, Ken Kozuma, Shigeru Saito, Toshiya Muramatsu, Sunao Nakamura, Atsuo Namiki, Yoshihiro Morino, Nobuhisa Hagiwara, Masaaki Uematsu, Tomohiro Kawasaki, Kenshi Fujii, Patrick W Serruys, Yoshinobu Onuma, Shihwa Ying, Hajime Kusano, Gregg W Stone, Takeshi Kimura
AIMS: Blooming artifacts limit accurate coronary assessment by multi-slice computed tomography (MSCT) in metallic stents. We sought to investigate whether bioresorbable vascular scaffold (BVS) could be better assessed by MSCT. Methods and Results: Among 400 patients in the randomized ABSORB Japan trial, a pre-specified MSCT sub-study was performed in 98 patients (103 lesions) in the BVS arm and 49 patients (49 lesions) in the cobalt chromium everolimus-eluting stent (CoCr-EES) arm at 13-month prior to follow-up angiography...
November 14, 2017: EuroIntervention
https://www.readbyqxmd.com/read/29129253/rationale-of-a-novel-study-design-for-the-bioflow-v-study-a-prospective-randomized-multicenter-study-to-assess-the-safety-and-efficacy-of-the-orsiro-sirolimus-eluting-coronary-stent-system-using-a-bayesian-approach
#15
Gheorghe Doros, Joseph M Massaro, David E Kandzari, Ron Waksman, Jacques J Koolen, Donald E Cutlip, Laura Mauri
BACKGROUND: Traditional study design submitted to the Food and Drug Administration to test newer drug-eluting stents (DES) for marketing approval is the prospective randomized controlled trial. However, several DES have extensive clinical data from trials conducted outside the United States that have led to utilization of a novel design using the Bayesian approach. This design was proposed for testing DES with bioresorbable polymer compared with DES most commonly in use today that use durable polymers for drug elution...
November 2017: American Heart Journal
https://www.readbyqxmd.com/read/29126357/successful-treatment-of-high-grade-pancreatic-neuroendocrine-neoplasms-with-everolimus
#16
Cansu G Genç, Heinz-Josef Klümpen, Timm Denecke, Bertram Wiedenmann, Marianne Pavel
No abstract text is available yet for this article.
November 10, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29126203/a-randomized-phase-ii-study-of-everolimus-in-combination-with-chemoradiation-in-newly-diagnosed-glioblastoma-results-of-nrg-oncology-rtog-0913
#17
Prakash Chinnaiyan, Minhee Won, Patrick Y Wen, Amyn M Rojiani, Maria Werner-Wasik, Helen A Shih, Lynn S Ashby, Hsiang-Hsuan Michael Yu, Volker W Stieber, Shawn C Malone, John B Fiveash, Nimish A Mohile, Manmeet S Ahluwalia, Merideth M Wendland, Philip J Stella, Andrew Y Kee, Minesh P Mehta
Background: This Phase II study was designed to determine the efficacy of the mTOR inhibitor everolimus administered daily with conventional radiation therapy and chemotherapy in patients with newly diagnosed glioblastoma. Methods: Patients were randomized to radiation therapy with concurrent and adjuvant temozolomide with or without daily everolimus (10 mg). The primary endpoint was progression-free survival (PFS) and the secondary endpoints were overall survival (OS) and treatment-related toxicities...
November 6, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29123595/community-pharmacist-led-telephone-follow-up-enabled-close-management-of-everolimus-induced-adverse-events-in-an-outpatient-with-metastatic-breast-cancer
#18
Satoshi Yokoyama, Satoko Yajima, Chihiro Sakai, Shuji Yamashita, Yoshihiro Noguchi, Yoko Ino, Kazuhiro Iguchi, Hitomi Teramachi
No abstract text is available yet for this article.
November 2017: Canadian Pharmacists Journal: CPJ, Revue des Pharmaciens du Canada: RPC
https://www.readbyqxmd.com/read/29121714/everolimus-plus-ku0063794-regimen-promotes-anticancer-effects-against-hepatocellular-carcinoma-cells-through-the-paradoxical-inhibition-of-autophagy
#19
Sang Chul Lee, Kee-Hwan Kim, Ok-Hee Kim, Sang Kuon Lee, Ha-Eun Hong, Byung Jo Choi, Wonjun Jeong, Say-June Kim
Purpose: Everolimus only inhibits mammalian target of rapamycin complex 1 (mTORC1), whereas Ku0063794 inhibits both mTORC1 and mTORC2. Although they have similar anticancer effects, their combination has a synergistic effect against hepatocellular carcinoma (HCC) cells. We aimed to determine the mechanism underlying the synergistic effects of everolimus and Ku0063794 associated with autophagy in HCC cells. Materials and Methods: We compared the effects of everolimus and Ku0063794, individually or in combination, on both the in vitro and in vivo models of HCCs...
November 9, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29119080/metastatic-breast-cancer-endocrine-therapy-landscape-reshaped
#20
REVIEW
Mohamad Adham Salkeni, Samantha June Hall
Endocrine therapy (ET) of hormone receptor (HR)-positive and human epidermal growth factor receptor 2-(HER2)-negative metastatic breast cancer (MBC) historically focused on estrogen deprivation and antagonism. The identification of several intracellular pathways promoting resistance to antiestrogen therapy led to the introduction of novel endocrine drug combinations that reformed treatment schema and expanded therapeutic options. There is no doubt that efforts to overcome or delay resistance to ET are fruiting, particularly with the introduction of cyclin-dependent kinase 4/6 inhibitors such as palbociclib and ribociclib, and mechanistic target of rapamycin inhibitors such as everolimus...
October 2017: Avicenna Journal of Medicine
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