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https://www.readbyqxmd.com/read/28629896/randomized-phase-ii-study-of-preoperative-chemoradiotherapy-panitumumab-followed-by-consolidation-chemotherapy-in-potentially-operable-locally-advanced-stage-iiia-n2-non-small-cell-lung-cancer-nrg-oncology-rtog-0839
#1
Martin J Edelman, Chen Hu, Quynh-Thu Le, Jessica S Donington, Warren D D'Souza, Adam P Dicker, Billy W Loo, Elizabeth M Gore, Gregory M M Videtic, Nathaniel R Evans, Joseph W Leach, Maximilian Diehn, Steven J Feigenberg, Yuhchyau Chen, Rebecca Paulus, Jeffrey D Bradley
INTRODUCTION: Multimodality therapy has curative potential in locally advanced non-small cell lung cancer (LASCLC). Mediastinal nodal sterilization (MNS) after induction chemoradiotherapy (CRT) can serve as an intermediate marker for efficacy. NRG Oncology RTOG 0229 demonstrated the feasibility and efficacy of combining full dose radiation (61.2Gy) with chemotherapy followed by resection and chemotherapy. Based upon that experience and evidence that epidermal growth factor receptor (EGFR) antibodies are radiosensitizing, we explored adding panitumumab to CRT followed by resection and consolidation chemotherapy in LANSCLC with a primary endpoint of MNS...
June 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28629338/a-phase-2-randomized-trial-to-evaluate-the-impact-of-a-supervised-exercise-program-on-cardiotoxicity-at-3%C3%A2-months-in-patients-with-her2-overexpressing-breast-cancer-undergoing-adjuvant-treatment-by-trastuzumab-design-of-the-cardapac-study
#2
Quentin Jacquinot, Nathalie Meneveau, Marion Chatot, Franck Bonnetain, Bruno Degano, Malika Bouhaddi, Gilles Dumoulin, Dewi Vernerey, Xavier Pivot, Fabienne Mougin
BACKGROUND: The overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancer is a poor prognosis. Trastuzumab improves overall survival but is associated with cardiotoxicity, especially a decline in left ventricular ejection fraction (LVEF). In addition, chemotherapy and radiotherapy increase fatigue and pain, decrease physical capacity and health-related quality of life. To date, no study has evaluated the benefits of physical activity on the side effects of treatment in patients with HER2 positive breast cancer...
June 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28627324/preparation-characterization-and-in-vitro-cytotoxicity-of-chitosan-hydrogels-containing-silver-nanoparticles
#3
Bożena Tyliszczak, Anna Drabczyk, Sonia Kudłacik-Kramarczyk, Agnieszka Sobczak-Kupiec
Hydrogels, chitosan as well as silver nanoparticles become in recent years materials characterized by a great interest. In present paper hydrogel based on chitosan and containing mention type of nano-sized particles have been synthesized by means of photopolymerization. Sorption capacity in selected liquids as well as behavior in simulated body fluid (such as Ringer's liquid) have been determined. Particularly attention was paid to the studies on toxicity of the hydrogels in relation to the epidermal cells as well as on their impact on growth of selected strain of bacteria (Escherichia coli)...
June 17, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28626936/a-pilot-study-comparing-histological-and-immunophenotypic-patterns-in-stage-4-skin-graft-versus-host-disease-from-toxic-epidermal-necrolysis
#4
Haley Naik, Stephen Lockwood, Arturo Saavedra
Since the inception of bone marrow transplantation, clinicians have sought to distinguish stage 4 skin graft versus host disease (GVHD) from toxic epidermal necrolysis (TEN).(1-3) In certain contexts, it can be difficult to discern among these two entities, both clinically and histologically. However, the distinction is critical because both diseases can be life-threatening and their respective management and prognosis differ.
June 19, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28625629/a-phase-ib-trial-of-continuous-once-daily-oral-afatinib-plus-sirolimus-in-patients-with-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-cancer-and-or-disease-progression-following-prior-erlotinib-or-gefitinib
#5
Teresa Moran, Ramón Palmero, Mariano Provencio, Amelia Insa, Margarita Majem, Noemí Reguart, Joaquim Bosch-Barrera, Dolores Isla, Enric Carcereny Costa, Chooi Lee, Marta Puig, Sandrine Kraemer, David Schnell, Rafael Rosell
OBJECTIVES: Dysregulation of the downstream PI3K/AKT/mTOR signaling pathway is a proposed mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We investigated safety and antitumor activity of afatinib plus sirolimus as a potential combination to reverse acquired resistance to EGFR-TKIs in a phase IB trial in patients with EGFR mutation-positive non-small-cell lung cancer (EGFR mut NSCLC) and/or disease progression following prior erlotinib/gefitinib...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28618376/association-between-the-hla-b-alleles-and-carbamazepine-induced-sjs-ten-a-meta-analysis
#6
REVIEW
Qianyu Wang, Shusen Sun, Meng Xie, Kun Zhao, Xingang Li, Zhigang Zhao
PURPOSE: From our current understanding, the association between the human leukocyte antigen (HLA), HLA-B*1502, and carbamazepine(CBZ)-induced Stevens-Jonson syndrome and toxic epidermal necrolysis (SJS/TEN) in the Asian population is quite clear. However the relationship between other HLA-B alleles and CBZ-induced severe cutaneous adverse drug reactions (SCADRs) remains unclear. We aimed to identify other non-HLA-B*1502 alleles in patients with CBZ-induced SCADRs through a meta-analysis...
June 3, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28618305/phase-i-study-of-temsirolimus-in-combination-with-cetuximab-in-patients-with-advanced-solid-tumours
#7
A Hollebecque, R Bahleda, L Faivre, J Adam, V Poinsignon, A Paci, C Gomez-Roca, J C Thery, M C Le Deley, A Varga, A Gazzah, E Ileana, M Gharib, E Angevin, K Malekzadeh, C Massard, J C Soria, J P Spano
BACKGROUND: Preclinical studies suggest synergistic antitumour effects of mammalian target of rapamycin (mTOR) inhibitor such as temsirolimus combined with anti-EGFR monoclonal antibody such as cetuximab. METHODS: Temsirolimus (T) and cetuximab (C) were combined and escalated in cohorts of patients with advanced or metastatic solid tumours, respectively from 15 to 25 mg and 150-250 mg/m(2), until the maximum tolerated dose (MTD) was determined. Effort was made in the expansion cohort to enrol patients harbouring a molecular aberration in the human epidermal growth factor receptor (EGFR) and/or phosphoinositide 3-kinase (PI3K) pathways...
June 12, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28611628/overlapping-dress-and-stevens-johnson-syndrome-case-report-and-review-of-the-literature
#8
Aneline Casagranda, Mariano Suppa, Florence Dehavay, Véronique Del Marmol
Drug-induced severe cutaneous adverse reactions (SCARs) include acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), and epidermal necrolysis (Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis). The identification of the causal drug is crucial in order to avoid further exposure, but making the right differential diagnosis of the type of SCAR is equally important since treatment, follow-up, and prognosis of different SCARs are not the same. These syndromes are distinct entities with different clinical, biological, and histological patterns, but sometimes the early distinction between 2 SCARs can be extremely challenging, and overlapping conditions could therefore be taken into consideration, although true overlapping SCARs are very rare when using strict diagnostic criteria (described by the RegiSCAR group)...
May 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28603991/trisubstituted-pyridinylimidazoles-as-potent-inhibitors-of-the-clinically-resistant-l858r-t790m-c797s-egfr-mutant-targeting-of-both-hydrophobic-regions-and-the-phosphate-binding-site
#9
Marcel Günther, Jonas Lategahn, Michael Juchum, Eva Döring, Marina Keul, Julian Engel, Hannah L Tumbrink, Daniel Rauh, Stefan Laufer
Inhibition of the epidermal growth factor receptor represents one of the most promising strategies in the treatment of lung cancer. Acquired resistance compromises the clinical efficacy of EGFR inhibitors during long-term treatment. The recently discovered EGFR-C797S mutation causes resistance against third-generation EGFR inhibitors. Here we present a rational approach based on extending the inhibition profile of a p38 MAP kinase inhibitor toward mutant EGFR inhibition. We used a privileged scaffold with proven cellular potency as well as in vivo efficacy and low toxicity...
June 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28601433/characterization-of-xenobiotic-metabolizing-enzymes-of-a-reconstructed-human-epidermal-model-from-adult-hair-follicles
#10
Daniel Bacqueville, Carine Jacques, Laure Duprat, Emilien L Jamin, Beatrice Guiraud, Elisabeth Perdu, Sandrine Bessou-Touya, Daniel Zalko, Hélène Duplan
In this study, a comprehensive characterization of xenobiotic metabolizing enzymes (XMEs) based on gene expression and enzyme functionality was made in a reconstructed skin epidermal model derived from the outer root sheath (ORS) of hair follicles (ORS-RHE). The ORS-RHE model XME gene profile was consistent with native human skin. Cytochromes P450 (CYPs) consistently reported to be detected in native human skin were also present at the gene level in the ORS-RHE model. The highest Phase I XME gene expression levels were observed for alcohol/aldehyde dehydrogenases and (carboxyl) esterases...
June 7, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28599296/microwave-ablation-combined-with-egfr-tkis-versus-only-egfr-tkis-in-advanced-nsclc-patients-with-egfr-sensitive-mutations
#11
Zhigang Wei, Xin Ye, Xia Yang, Aimin Zheng, Guanghui Huang, Wenhong Li, Jiao Wang, Xiaoying Han, Min Meng, Yang Ni
We conducted this retrospective study to investigate whether microwave ablation (MWA) of primary tumor sites plus epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) could improve survival in advanced non small cell lung cancer (NSCLC) with EGFR mutations. MWA was conducted at the primary tumor sites, followed by EGFR-TKIs in the MWA plus EGFR-TKIs group. EGFR-TKIs were administered until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS) and objective response rate (ORR)...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28592616/multicenter-phase-ii-study-of-panitumumab-in-platinum-pretreated-advanced-head-and-neck-squamous-cell-cancer
#12
Marco Siano, Francesca Molinari, Vittoria Martin, Nicolas Mach, Martin Früh, Stefania Freguia, Irene Corradino, Michele Ghielmini, Milo Frattini, Vittoria Espeli
LESSONS LEARNED: Panitumumab shows activity in terms of disease control rate and preventing disease progression but not for tumor shrinkage in head and neck squamous cell cancer for second-line treatment. Epidermal growth factor receptor (EGFR) copy number gain, a property of tumor cells that theoretically could identify patients more likely to experience disease response, was common among patients having disease control.Our trial, given the lower toxicity with an every-2-week schedule, provides guidance for future trials, for example, in combinations of immune therapies and anti-EGFR-antibodies...
June 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28592615/a-phase-ib-dose-escalation-study-of-the-safety-tolerability-and-pharmacokinetics-of-cobimetinib-and-duligotuzumab-in-patients-with-previously-treated-locally-advanced-or-metastatic-cancers-with-mutant-kras
#13
Christopher H Lieu, Manuel Hidalgo, Jordan D Berlin, Andrew H Ko, Andres Cervantes, Patricia LoRusso, David E Gerber, J Paul Eder, S Gail Eckhardt, Amy V Kapp, Amy Tsuhako, Bruce McCall, Andrea Pirzkall, Anne Uyei, Josep Tabernero
LESSONS LEARNED: Cobimetinib and duligotuzumab were well tolerated as single agents and in combination with other agents.The cobimetinib and duligotuzumab combination was associated with increased toxicity, most notably gastrointestinal, and limited efficacy in the patient population tested. BACKGROUND: KRAS-mutant tumors possess abnormal mitogen-activated protein kinases (MAPK) pathway signaling, leading to dysregulated cell proliferation. Cobimetinib blocks MAPK signaling...
June 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28581470/low-egf-in-myeloablative-allotransplantation-association-with-severe-acute-gvhd-in-bmt-ctn-0402
#14
S G Holtan, L F Newell, C Cutler, M R Verneris, T E DeFor, J Wu, A Howard, M L MacMillan, J H Antin, B R Blazar, D J Weisdorf, A Panoskaltsis-Mortari
Epidermal growth factor (EGF) is a recently described biomarker of acute GvHD (aGvHD). Whether low plasma EGF prior to hematopoietic cell transplantation (HCT) predisposes to the development of aGvHD, or whether EGF levels fall because of severe aGvHD, is unknown. To evaluate this, we tested plasma samples collected at pre-HCT baseline, day +28 and day +100 during the course of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0402. We found that baseline EGF plasma concentrations were three-fold lower in HCT recipients compared to donors (24...
June 5, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28580160/oxcarbazepine-induced-stevens-johnson-syndrome-a-pediatric-case-report
#15
Burçin Beken, Ceren Can, Aysegül Örencik, Nuray Can, Mehtap Yazıcıoğlu
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are two rare but life-threatening diseases characterized by detachment of epidermis, bullous skin lesions and mucous membrane erosions. Anti-epileptic drugs are highly suspected to be the causative agents. Although carbamazepine (CBZ) is the most associated anti-epileptic drug, oxcarbazepine (OXC), which is a monohydrated derivative of CBZ, is proposed to be safer because of the different metabolism of the two drugs. Herein, we report a case of SJS induced by oxcarbazepine...
June 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/28578601/olaparib-for-metastatic-breast-cancer-in-patients-with-a-germline-brca-mutation
#16
Mark Robson, Seock-Ah Im, Elżbieta Senkus, Binghe Xu, Susan M Domchek, Norikazu Masuda, Suzette Delaloge, Wei Li, Nadine Tung, Anne Armstrong, Wenting Wu, Carsten Goessl, Sarah Runswick, Pierfranco Conte
Background Olaparib is an oral poly(adenosine diphosphate-ribose) polymerase inhibitor that has promising antitumor activity in patients with metastatic breast cancer and a germline BRCA mutation. Methods We conducted a randomized, open-label, phase 3 trial in which olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation and human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer who had received no more than two previous chemotherapy regimens for metastatic disease...
June 4, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28576675/buparlisib-plus-fulvestrant-versus-placebo-plus-fulvestrant-in-postmenopausal-hormone-receptor-positive-her2-negative-advanced-breast-cancer-belle-2-a-randomised-double-blind-placebo-controlled-phase-3-trial
#17
José Baselga, Seock-Ah Im, Hiroji Iwata, Javier Cortés, Michele De Laurentiis, Zefei Jiang, Carlos L Arteaga, Walter Jonat, Mark Clemons, Yoshinori Ito, Ahmad Awada, Stephen Chia, Agnieszka Jagiełło-Gruszfeld, Barbara Pistilli, Ling-Ming Tseng, Sara Hurvitz, Norikazu Masuda, Masato Takahashi, Peter Vuylsteke, Soulef Hachemi, Bharani Dharan, Emmanuelle Di Tomaso, Patrick Urban, Cristian Massacesi, Mario Campone
BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) pathway activation is a hallmark of endocrine therapy-resistant, hormone receptor-positive breast cancer. This phase 3 study assessed the efficacy of the pan-PI3K inhibitor buparlisib plus fulvestrant in patients with advanced breast cancer, including an evaluation of the PI3K pathway activation status as a biomarker for clinical benefit. METHODS: The BELLE-2 trial was a randomised, double-blind, placebo-controlled, multicentre study...
May 30, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28576247/burn-center-care-of-patients-with-stevens-johnson-syndrome-and-toxic-epidermal-necrolysis
#18
REVIEW
Robert Cartotto
Stevens-Johnson syndrome and toxic epidermal necrolysis are rare, life-threatening, cutaneous drug reactions. Medications are the most common cause, although an infection may be responsible. A link between genetics and certain medications has been established. Clinical diagnosis should be confirmed with biopsy. When the area of epidermal detachment approaches 30%, burn center care is advisable. An ophthalmologist should be consulted to optimize ocular care. Pharmacologic interruption has been sought but there is little consensus on the most appropriate agent and no high-quality studies have been conducted to demonstrate if any of these agents lead to improved survival...
July 2017: Clinics in Plastic Surgery
https://www.readbyqxmd.com/read/28576031/fabrication-of-a-three-dimensional-spongy-scaffold-using-human-wharton-s-jelly-derived-extra-cellular-matrix-for-wound-healing
#19
Bahareh Beiki, Bahman Zeynali, Ehsan Seyedjafari
The Wharton's jelly (WJ) contains significant amounts of extracellular matrix (ECM) components and rich source of endogenous growth factors. In this study, we designed a new biomimetic spongy scaffold from decellularized WJ-derived ECM and used it as a skin substitute. Histological analysis and biochemical assays showed that bio-active molecules preserved in the fabricated scaffolds and that the scaffolds have highly interconnected porous structure. Cytotoxicity and mechanical evaluation of the scaffold indicated that it is non-toxic and has appropriate mechanical properties...
September 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28571578/immunotherapy-in-head-and-neck-cancer-aiming-at-extreme-precision
#20
Petr Szturz, Jan B Vermorken
BACKGROUND: Locoregionally advanced, recurrent, and metastatic squamous cell carcinomas of the head and neck (SCCHN) remain difficult to treat disease entities, in which systemic treatment often forms an integral part of their management. Immunotherapy is based on functional restoration of the host immune system, helping to counteract various tumour evasion strategies. Broadly, immunotherapeutic approaches encompass tumour-specific antibodies, cancer vaccines, cytokines, adoptive T-cell transfer, and immune-modulating agents...
June 2, 2017: BMC Medicine
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