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Toxic epidermal

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https://www.readbyqxmd.com/read/29027197/the-risk-of-stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-in-new-users-of-antiepileptic-drugs
#1
Noel Frey, Michael Bodmer, Andreas Bircher, Stephan Rüegg, Susan S Jick, Christoph R Meier, Julia Spoendlin
OBJECTIVE: Older antiepileptic drugs (AEDs) are known to cause Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, evidence for newer AED is sparse. We quantified risks of SJS/TEN in association with use of all AEDs in the United Kingdom. METHODS: In a matched case-control study of 480 previously validated SJS/TEN cases (1995-2013) we used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and calculated absolute risks of SJS/TEN within separate cohorts of new users of 28 AEDs...
October 13, 2017: Epilepsia
https://www.readbyqxmd.com/read/29026345/tolerated-drugs-in-subjects-with-severe-cutaneous-adverse-reactions-scars-induced-by-anticonvulsants-and-review-of-the-literature
#2
REVIEW
Fabrizio De Luca, Laura Michelina Losappio, Corrado Mirone, Jan Walter Schroeder, Antonella Citterio, Maria Gloria Aversano, Joseph Scibilia, Elide Anna Pastorello
BACKGROUND: Anticonvulsant hypersensitivity syndrome represents a rare but potentially fatal kind of adverse drug reaction. This clinical picture often hampers the flexibility with which alternative anticonvulsants or even other classes of drugs are prescribed in these patients, negatively affecting the efficacy of treatment and the course of the disease. The aim of this study was to analyse a group of six patients with severe cutaneous drug reactions induced by anticonvulsants and to report which alternative antiepileptic drugs and which drugs of other classes were tolerated...
2017: Clinical and Molecular Allergy: CMA
https://www.readbyqxmd.com/read/28987609/structure-based-design-and-synthesis-of-2-4-diaminopyrimidines-as-egfr-l858r-t790m-selective-inhibitors-for-nsclc
#3
Lingfeng Chen, Weitao Fu, Chen Feng, Rong Qu, Linjiang Tong, Lulu Zheng, Bo Fang, Yinda Qiu, Jie Hu, Yuepiao Cai, Jianpeng Feng, Hua Xie, Jian Ding, Zhiguo Liu, Guang Liang
Mutated epidermal growth factor receptor (EGFR) is a major driver of non-small cell lung cancer (NSCLC). The EGFR(T790M) secondary mutation has become a leading cause of clinically-acquired resistance to gefitinib and erlotinib. Herein, we present a structure-based design approach to increase the potency and selectivity of the previously reported reversible EGFR inhibitor 7, at the kinase and cellular levels. Three-step structure-activity relationship exploration led to promising compounds 19e and 19h with unique chemical structure and binding mode from the other third-generation tyrosine kinase inhibitors...
September 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28977984/driving-better-and-safer-her2-specific-cars-for-cancer-therapy
#4
Xianqiang Liu, Nan Zhang, Huan Shi
Given the clinical efficacy of chimeric antigen receptor (CAR)-based therapy in hematological malignancies, CAR T-cell therapy for a number of solid tumors has been actively investigated. Human epidermal growth factor receptor 2 (HER2) is a well-established therapeutic target in breast, as well as other types of cancer. However, HER2 CAR T cells pose a risk of lethal toxicity including cytokine release syndrome from "on-target, off-tumor" recognition of HER2. In this review, we summarize the development of conventional HER2 CAR technology, the alternative selection of CAR hosts, the novel HER2 CAR designs, clinical studies and toxicity...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969789/osmyb45-plays-an-important-role-in-rice-resistance-to-cadmium-stress
#5
Shubao Hu, Yao Yu, Qiuhong Chen, Guangmao Mu, Zhenguo Shen, Luqing Zheng
Cadmium (Cd) is one of the most toxic heavy metal elements in nature, and it causes serious damage to plant cells. Here, we report that a transcription factor OsMYB45 is involved in Cd stress response in rice. OsMYB45 is highly expressed in rice leaves, husks, stamens, pistils, and lateral roots, and its expression is induced by Cd stress. OsMYB45 fused to green fluorescent protein localized to the cell nucleus in onion epidermal cells. Mutation of OsMYB45 resulted in hypersensitivity to Cd treatment, and the concentration of H2O2 in the leaves of mutant nearly doubled, while catalase (CAT) activity was halved compared with the wild-type...
November 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28969097/clinical-strategies-for-acquired-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-resistance-in-non-small-cell-lung-cancer-patients
#6
REVIEW
Lijun Dong, Dan Lei, Haijun Zhang
Epidermal growth factor receptor (EGFR) mutations (EGFRm(+)) occur in 10-35% of non-small-cell lung cancer (NSCLC) cases and confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR TKIs are standard treatments for NSCLC patients harboring EGFR exon 19 deletions or exon 21 L858R point mutations. Despite initial benefit, most patients develop drug resistance, posing a challenge to oncologists. The secondary T790M point mutation in EGFR exon 20 contributes to approximately 60% of resistance cases. Optimum strategies for overcoming acquired EGFR TKI resistance are not clearly defined, although current common practice is to switch to platinum-based chemotherapy following resistance onset...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966961/role-of-systemic-antibiotics-in-preventing-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-induced-skin-toxicities
#7
REVIEW
Philomena Charlotte Dsouza, Shiyam Kumar
The epidermal growth factor receptor (EGFR) is actively involved in the growth of multiple tumor types and has been found as an effective treatment target in various solid cancers, for example, lung cancer and head and neck cancer. Of effective drugs which target and inhibit EGFR functions, tyrosine kinase inhibitors have shown promising results, albeit at a cost of side effects, skin toxicity being the most common. This article provides an evidence-based strategy to oncology nurse practitioners in dealing with such toxicity...
October 2017: Asia-Pacific Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28965727/proteome-wide-map-of-targets-of-t790m-egfr-directed-covalent-inhibitors
#8
Sherry Niessen, Melissa M Dix, Sabrina Barbas, Zachary E Potter, Shuyan Lu, Oleg Brodsky, Simon Planken, Douglas Behenna, Chau Almaden, Ketan S Gajiwala, Kevin Ryan, RoseAnn Ferre, Michael R Lazear, Matthew M Hayward, John C Kath, Benjamin F Cravatt
Patients with non-small cell lung cancers that have kinase-activating epidermal growth factor receptor (EGFR) mutations are highly responsive to first- and second-generation EGFR inhibitors. However, these patients often relapse due to a secondary, drug-resistant mutation in EGFR whereby the gatekeeper threonine is converted to methionine (T790M). Several third-generation EGFR inhibitors have been developed that irreversibly inactivate T790M-EGFR while sparing wild-type EGFR, thus reducing epithelium-based toxicities...
September 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28964539/gefitinib-for-patients-with-incurable-cutaneous-squamous-cell-carcinoma-a-single-arm-phase-ii-clinical-trial
#9
William N William, Lei Feng, Renata Ferrarotto, Lawrence Ginsberg, Merrill Kies, Scott Lippman, Bonnie Glisson, Edward S Kim
BACKGROUND: Preclinical data demonstrate a key role for the epidermal growth factor receptor (EGFR) in the carcinogenesis of cutaneous squamous cell carcinomas (CSCCs). There are, however, limited data on the efficacy of EGFR inhibitors in incurable, recurrent, and/or metastatic CSCC. OBJECTIVE: To determine the response rate to gefitinib in patients with CSCC not amenable to curative therapy including surgery or radiation. METHODS: This was a single-arm phase II study...
September 27, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28963996/is-acetaminophen-associated-with-a-risk-of-stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-analysis-of-the-french-pharmacovigilance-database
#10
Bénédicte Lebrun-Vignes, Claire Guy, Marie-Josèphe Jean-Pastor, Valérie Gras-Champel, Marie Zenut
AIM: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare but severe mostly drug-induced cutaneous reactions. Acetaminophen is an over the counter drug worldwide used to treat pain and reduce fever. In 2013, the FDA informed the public that acetaminophen was associated with a rare risk of SJS/TEN. The aim of this retrospective study is to analyse reports of acetaminophen as a possible suspect in the development of SJS/TEN from the French Pharmacovigilance Database (FPDB)...
September 30, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28961832/gemcitabine-combined-with-the-monoclonal-antibody-nimotuzumab-is-an-active-first-line-regimen-in-kras-wildtype-patients-with-locally-advanced-or-metastatic-pancreatic-cancer-a-multicenter-randomized-phase-iib-study
#11
B Schultheis, D Reuter, M P Ebert, J Siveke, A Kerkhoff, W E Berdel, R Hofheinz, D M Behringer, W E Schmidt, E Goker, S De Dosso, M Kneba, S Yalcin, F Overkamp, F Schlegel, M Dommach, R Rohrberg, T Steinmetz, M Bulitta, D Strumberg
Background: This randomized study was designed to investigate the superiority of gemcitabine (gem) plus nimotuzumab (nimo), an anti-epidermal growth factor receptor monoclonal antibody, compared with gem plus placebo as first-line therapy in patients with advanced pancreatic cancer. Patients and methods: Patients with previously untreated, unresectable, locally advanced or metastatic pancreatic cancer were randomly assigned to receive gem: 1000 mg/m2, 30-min i...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28961023/in-vitro-and-in-vivo-antitumor-effect-of-gefitinib-nanoparticles-on-human-lung-cancer
#12
Xiao Ling Ni, Long Xia Chen, Heng Zhang, Bo Yang, Shan Xu, Min Wu, Jing Liu, Ling Lin Yang, Yue Chen, Shao Zhi Fu, Jing Bo Wu
Gefitinib (GEF) is the first epidermal growth factor receptor (EGFR)-targeting agent launched as an anticancer drug. It is an accepted opinion that modifying GEF strong hydrophobicity and poor bioavailability would not only enhance its antitumor effects, but also reduce its side effects. In this study, GEF-loadedpoly(ε-caprolactone)-poly(ethyleneglycol)-poly(ε-caprolactone) (PCEC) -bearing nanoparticles (GEF-NPs) were prepared by a solid dispersion method and characterized. The particle sizes increased with the increase in GEF/PCEC mass ratio in feed...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28959653/p-benzoquinone-initiates-non-invasive-urothelial-cancer-through-aberrant-tyrosine-phosphorylation-of-egfr-map-kinase-activation-and-cell-cycle-deregulation-prevention-by-vitamin-c
#13
Shinjini Ganguly, Ayan Chandra, Dhruba J Chattopadhyay, Indu B Chatterjee
According to WHO classification system, non-invasive urothelial carcinoma represents urothelial carcinoma in situ (CIS) and dysplasia. Dysplastic urothelium often progresses to CIS that further advances to urothelial carcinoma (UC). The strongest risk factor for UC is cigarette smoking. However, the pathogenesis of cigarette smoke (CS)-induced UC is poorly understood. Earlier we had shown that p-benzoquinone (p-BQ), a major toxic quinone derived from p-benzosemiquinone of CS in vivo, is a causative factor for various CS-induced diseases...
2017: Toxicology Reports
https://www.readbyqxmd.com/read/28958837/investigation-of-dermal-toxicity-of-ionic-liquids-in-monolayer-cultured-skin-cells-and-3d-reconstructed-human-skin-models
#14
Jee-Hyun Hwang, Hyeonji Park, Dal Woong Choi, Ki Taek Nam, Kyung-Min Lim
Ionic liquids have gained increasing attention in the chemical industry as potential green substitutes for traditional solvents. However, little is known about toxicity of ionic liquids on the skin, a major exposure portal to toxic substances. Here, we evaluated dermal toxicity of ionic liquids using human keratinocyte and fibroblast cell line, 3D reconstructed human epidermis, and full-thickness model to investigate underlying mechanisms. Cytotoxicity of ionic liquids was evaluated for representative anions, [TFSI], [PF6], [BF4], and [DCA], as well as for cations, [EMIM], [BMPY], [TBA] and [Zn], in human keratinocyte cell line, HaCaT, and human dermal fibroblasts...
September 25, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28949055/allopurinol-suppresses-expression-of-the-regulatory-t-cell-migration-factors-tarc-ccl17-and-mdc-ccl22-in-hacat-keratinocytes-via-restriction-of-nuclear-factor-%C3%AE%C2%BAb-activation
#15
Makoto Osabe, Toshiyuki Tajika, Masahiro Tohkin
Recent studies have shown that sparse distribution of regulatory T cells (Tregs) in the skin might be involved in the onset of severe cutaneous adverse drug reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Treg migration toward epithelial cells is regulated by certain chemokines, including TARC/CCL17 and MDC/CCL22. In this study, we analyzed the effect of allopurinol (APN), a drug known to cause severe adverse reactions, on the expression of factors affecting Treg migration and the mechanisms involved...
September 26, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28948807/fatal-progression-of-multifocal-infection-of-aspergillus-sp-and-multi-resistant-pseudomonas-aeruginosa-in-a-patient-with-toxic-epidermal-necrolysis-and-renal-cancer
#16
B Lipový, H Řihová, M Hanslianová, Z Chaloupková, M Hromaníková, Z Pavlovský, T Kempný, I Suchánek, P Brychta
Toxic epidermal necrolysis is an autoimmune disease expressed predominantly on the skin and mucous membranes. It is a serious bullous disease manifesting itself by induction of apoptosis in the dermo-epidermal junction. In most cases,it is attributable to the use of some drug. The basic approach to stopping progression of the disease is immunosuppression. Unfortunately, patients with such extensive loss of epidermis and defective mucosa are confronted by a variety of opportunistic, potentially pathogenic microorganisms...
2017: Epidemiologie, Mikrobiologie, Imunologie
https://www.readbyqxmd.com/read/28945850/first-line-icotinib-versus-cisplatin-pemetrexed-plus-pemetrexed-maintenance-therapy-for-patients-with-advanced-egfr-mutation-positive-lung-adenocarcinoma-convince-a-phase-3-open-label-randomized-study
#17
Y K Shi, L Wang, B H Han, W Li, P Yu, Y P Liu, C M Ding, X Song, Z Y Ma, X L Ren, J F Feng, H L Zhang, G Y Chen, X H Han, N Wu, C Yao, Y Song, S C Zhang, W Song, X Q Liu, S J Zhao, Y C Lin, X Q Ye, K Li, Y Q Shu, L M Ding, F L Tan, Y Sun
Background: Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. Patients and methods: Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28941473/new-evidence-supporting-cyclosporine-efficacy-in-epidermal%C3%A2-necrolysis
#18
REVIEW
Jean-Claude Roujeau, Maja Mockenhaupt, Jean-Claude Guillaume, Jean Revuz
Sixty years after its original description by Sir Alan Lyell, epidermal necrolysis (from Stevens-Johnson syndrome to toxic epidermal necrolysis) seems finally amenable to a specific treatment in addition to essential symptomatic measures in specialized settings. A recently published systematic review and an article by Gonzales-Herrada et al. strongly suggest that cyclosporine is effective in reducing the risk of death.
October 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28940568/serum-il-17-in-patients-with-erythema-multiforme-or-stevens-johnson-syndrome-toxic-epidermal-necrolysis-drug-reaction-and-correlation-with-disease-severity
#19
H Morsy, E A Taha, D A Nigm, R Shahin, E M K Youssef
BACKGROUND: There is strong evidence that drug-induced cutaneous eruptions have an immunological component. Interleukin (IL)-17, a proinflammatory cytokine that is predominantly produced by T helper 17 cells, has been linked to various autoimmune and inflammatory diseases. AIM: To measure serum IL-17 levels in patients with cutaneous drug reactions [erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)] in order to study the associations between IL-17 and disease severity...
September 20, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28938010/epidermal-growth-factor-receptor-targeted-sonoporation-with-microbubbles-enhances-therapeutic-efficacy-in-a-squamous-cell-carcinoma-model
#20
Fumika Hirabayashi, Kenjiro Iwanaga, Toshinori Okinaga, Osamu Takahashi, Wataru Ariyoshi, Ryo Suzuki, Mutsumi Sugii, Kazuo Maruyama, Kazuhiro Tominaga, Tatsuji Nishihara
Sonoporation is a drug and gene delivery system using ultrasonication that allows the intracellular delivery of foreign molecules that cannot enter cells under normal conditions. We previously reported that sonoporation with microbubbles (MBs) could achieve effective intracellular drug delivery to human gingival squamous carcinoma Ca9-22 cells. In this study, we developed anti-epidermal growth factor receptor (EGFR) antibody-conjugated MBs (EGFR-MBs) and evaluated their capacity to enhance anti-cancer drug toxicity in vitro and in vivo...
2017: PloS One
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