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Thalidomide

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https://www.readbyqxmd.com/read/28439852/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-a-concise-review-with-a-comprehensive-summary-of-therapeutic-interventions-emphasizing-supportive-measures
#1
REVIEW
Jeremy A Schneider, Philip R Cohen
INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two of the most severe dermatologic conditions occurring in the inpatient setting. There is a lack of consensus regarding appropriate management of SJS and TEN. PURPOSE: The scientific literature pertaining to SJS and TEN (subsequently referred to as SJS/TEN) is summarized and assessed. In addition, an interventional approach for the clinician is provided. METHODS: PubMed was searched with the key words: corticosteroids, cyclosporine, etanercept, intravenous immunoglobulin, Stevens-Johnson syndrome, and toxic epidermal necrolysis...
April 24, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28430175/carfilzomib-lenalidomide-dexamethasone-vs-lenalidomide-dexamethasone-in-relapsed-multiple-myeloma-by-previous-treatment
#2
M A Dimopoulos, A K Stewart, T Masszi, I Špička, A Oriol, R Hájek, L Rosiñol, D Siegel, G G Mihaylov, V Goranova-Marinova, P Rajnics, A Suvorov, R Niesvizky, A Jakubowiak, J San-Miguel, H Ludwig, S Ro, S Aggarwal, P Moreau, A Palumbo
Carfilzomib, a proteasome inhibitor, is approved as monotherapy and in combination with dexamethasone or lenalidomide-dexamethasone (Rd) for relapsed or refractory multiple myeloma. The approval of carfilzomib-lenalidomide-dexamethasone (KRd) was based on results from the randomized, phase 3 study ASPIRE (NCT01080391), which showed KRd significantly improved progression-free survival (PFS) vs Rd (median 26.3 vs 17.6 months; hazard ratio (HR)=0.690; P=0.0001). This subgroup analysis of ASPIRE evaluated KRd vs Rd by number of previous lines of therapy and previous exposure to bortezomib, thalidomide or lenalidomide...
April 21, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28429672/the-molecular-mechanisms-of-thalidomide-teratogenicity-and-implications-for-modern-medicine
#3
J Knobloch, D Jungck, A Koch
Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and anti-angiogenic activities are considered in many other refractory diseases...
March 31, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28427509/efficacy-and-safety-of-bortezomib-thalidomide-and-lenalidomide-in-multiple-myeloma-an-overview-of-systematic-reviews-with-meta-analyses
#4
REVIEW
Patricia Melo Aguiar, Tácio de Mendonça Lima, Gisele Wally Braga Colleoni, Sílvia Storpirtis
This overview summarizes evidence for the efficacy and safety of bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma. We searched the Medline, Scopus, and LILACS databases through August 2016, including systematic reviews with meta-analyses of randomized controlled trials assessing the efficacy and/or safety of bortezomib, thalidomide, or lenalidomide in patients with multiple myeloma. Two authors performed study selection, data extraction, and quality assessment using AMSTAR and GRADE instruments...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427176/metronomic-regimen-as-an-effective-treatment-for-aggressive-t-lgl-leukemia-with-central-nervous-system-infiltration-clinical-experience-and-review-of-literature
#5
REVIEW
Yun Liu, Lei Fan, Huihui Zhao, Wei Xu, Jianyong Li
A 71-year-old man was diagnosed with T-Large granular lymphocytic (LGL) leukemia, which usually represents a relatively indolent clinical course. While the clinical manifestation of this patient we report herein was aggressive with lasting fever, splenomegaly and hemophagocytic lymphohistiocytosis (HLH). T-cell immunophenotype was CD3+CD4-CD8-CD5-CD7-TCRαβ+. After comprehensive evaluation, an adjusted chemotherapy regimen CEOP (cyclophosphamide, vincristine, etoposide, prednisone) with etoposide, a potential effective regimen for HLH was administrated to the patient...
February 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422447/lc-ms-ms-and-chiroptical-spectroscopic-analyses-of-multidimensional-metabolic-systems-of-chiral-thalidomide-and-its-derivatives
#6
Yoshiyuki Ogino, Masahito Tanaka, Togo Shimozawa, Toru Asahi
Enantiomeric thalidomide undergoes various kinds of biotransformations including chiral inversion, hydrolysis, and enzymatic oxidation, which results in several metabolites, thereby adding to the complexity in the understanding of the nature of thalidomide. To decipher this complexity, we analyzed the multidimensional metabolic reaction networks of thalidomide and related molecules in vitro. Characteristic patterns in the amount of various metabolites of thalidomide and related molecules generated during a combination of chiral inversion, hydrolysis, and hydroxylation were observed using liquid chromatography-tandem mass spectrometry and chiroptical spectroscopy...
April 19, 2017: Chirality
https://www.readbyqxmd.com/read/28421232/clinical-spectrum-quality-of-life-braf-mutation-status-and-treatment-of-skin-involvement-in-adult-langerhans-cell-histiocytosis
#7
Etienne Crickx, Jean-David Bouaziz, Gwenaël Lorillon, Mathilde de Menthon, Florence Cordoliani, Emmanuell Bugnet, Martine Bagot, Michel Rybojad, Samia Mourah, Abdellatif Tazi
Langerhans cell histiocytosis is a rare histiocytic disorder for which skin involvement and management are poorly described in adults. The aim of this retrospective monocentric study in a national reference centre is to describe the clinical characteristics, quality of life, BRAF mutation status and outcomes of skin involvement in adult patients with Langerhans cell histiocytosis. Twenty-five patients (14 females, mean age 47 years) were included, with a median follow-up of 33 months (range 4-420 months). Patients experienced poor dermatological quality of life despite low body surface involvement...
April 19, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28418273/thalidomide-for-epistaxis-in-patients-with-hereditary-hemorrhagic-telangiectasia-a-preliminary-study
#8
Jia Fang, Xiaomeng Chen, Bijun Zhu, Haibo Ye, Weitian Zhang, Jian Guan, Kaiming Su
To evaluate the effectiveness of thalidomide for epistaxis in hereditary hemorrhagic telangiectasia (HHT), 7 HHT patients with recurrent epistaxis were treated with thalidomide at an initial dose of 50 mg/d, gradually increasing to 100 mg/d if needed. The Epistaxis Severity Score (ESS) was used to evaluate the treatment effects. Patients reported that epistaxis improved 1 to 3 weeks after starting thalidomide. The mean ESS before treatment, at the end of treatment, and 3 months after stopping treatment was 5...
April 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28415757/an-absence-of-platelet-activation-following-thalidomide-treatment-in-vitro-or-in-vivo
#9
Jianlin Qiao, Yulu Wu, Xiaoqing Wu, Yun Liu, Xiaoqian Li, Wen Ju, Kunming Qi, Depeng Li, Elizabeth E Gardiner, Robert K Andrews, Lingyu Zeng, Kailin Xu
Increased risk of thromboembolism and platelet hyperreactivity has been reported in patients receiving thalidomide therapy. Whether thalidomide induces platelet activation directly or through other factors remains unclear. The aim of this study was to evaluate the effect of thalidomide on platelet activation under resting conditions in vitro and in vivo. Isolated human or mouse platelets were treated with different concentrations of thalidomide (10, 50 and 100 μg/ml) for 60 min at 37°C followed by analysis of platelet surface expression of platelet receptors GPIbα, GPVI, αIIbβ3 and P-selectin, and PAC-1 or fibrinogen binding, by flow cytometry and collagen- or ADP-induced platelet aggregation...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409562/chemotherapy-induced-intestinal-inflammatory-responses-are-mediated-by-exosome-secretion-of-double-strand-dna-via-aim2-inflammasome-activation
#10
Qiaoshi Lian, Jun Xu, Shanshan Yan, Min Huang, Honghua Ding, Xiaoyu Sun, Aiwei Bi, Jian Ding, Bing Sun, Meiyu Geng
Chemotherapies are known often to induce severe gastrointestinal tract toxicity but the underlying mechanism remains unclear. This study considers the widely applied cytotoxic agent irinotecan (CPT-11) as a representative agent and demonstrates that treatment induces massive release of double-strand DNA from the intestine that accounts for the dose-limiting intestinal toxicity of the compound. Specifically, "self-DNA" released through exosome secretion enters the cytosol of innate immune cells and activates the AIM2 (absent in melanoma 2) inflammasome...
April 14, 2017: Cell Research
https://www.readbyqxmd.com/read/28402958/thalidomide-combined-with-thanscatheter-artierial-chemoembolzation-for-primary-hepatocellular-carcinoma-a-systematic-review-and-meta-analysis
#11
REVIEW
De-Dong Cao, Hui-Lin Xu, Liang Liu, Yong-Fa Zheng, Si-Fa Gao, Xi-Ming Xu, Wei Ge
OBJECTIVE: Transcatheter arterial chemoembolization (TACE) and thalidomide have been used for treating primary hepatocellular carcinoma(HCC). This study aims to evaluate the clinical efficacy and safety of thalidomide and TACE in primary HCC. METHODS: Randomized controlled trials(RCTs) about efficacy and safety of thalidomide combined with TACE for primary HCC were identified from the Cochrane Library, Pubmed, Embase, CNKI, and Wan Fang until August, 2016. The retrieved trials were reviewed and the data were extracted by two reviewers, independently...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399522/autologous-stem-cell-transplantation-in-multiple-myeloma-in-the-era-of-novel-drug-induction-a-retrospective-single-center-analysis
#12
Gabriela B Thoennissen, Dennis Görlich, Ulrike Bacher, Thomas Aufenberg, Anne-Christin Hüsken, Anna Antonia Hansmeier, Georg Evers, Jan-Henrik Mikesch, Fleur Fritz, Carsten Bokemeyer, Carsten Müller-Tidow, Matthias Stelljes, Rolf M Mesters, Utz Krug, Martin H Kropff, Nils H Thoennissen, Wolfgang E Berdel
Within this retrospective single-center study, we analyzed the survival of 320 multiple myeloma (MM) patients receiving melphalan high-dose chemotherapy (HDCT) and either single (n = 286) or tandem (n = 34) autologous stem cell transplantation (ASCT) from 1996 to 2012. Additionally, the impact of novel induction regimens was assessed. Median follow-up was 67 months, median overall survival (OS) 62 months, median progression-free survival (PFS) 33 months (95% CI 27-39), and treatment-related death (TRD) 3%. Multivariate analysis revealed age ≥60 years (p = 0...
April 12, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28398668/-the-legacy-of-thalidomide-a-multidisciplinary-meeting-held-at-the-university-of-york-united-kingdom-on-september-30-2016
#13
Elizabeth Newbronner, Neil Vargesson, Karl Atkin
BACKGROUND: Between 1957 and 1962 thalidomide was used as a nonaddictive, nonbarbiturate sedative that also was successful in relieving the symptoms of morning sickness in early pregnancy. Infamously, thousands of babies were subsequently born with severe birth defects. The drug is used again, today, to successfully treat leprosy, and tragically, there is a new generation of thalidomide damaged children in Brazil. While the outward damage in babies has been documented, the effects of the damage upon the survivors as they grow up, the lifestyle changes and adaptations required to be made, as well as studies into ageing in survivors, has received little attention and remains understudied...
March 1, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28384657/metronomic-chemotherapy-vs-best-supportive-care-in-progressive-pediatric-solid-malignant-tumors-a-randomized-clinical-trial
#14
Raja Pramanik, Sandeep Agarwala, Yogendra Kumar Gupta, Sanjay Thulkar, Sreenivas Vishnubhatla, Atul Batra, Deepa Dhawan, Sameer Bakhshi
Importance: Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. Objectives: To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy...
April 6, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28379698/chemically-induced-degradation-of-sirtuin-2-sirt2-by-a-proteolysis-targeting-chimera-protac-based-on-sirtuin-rearranging-ligands-sirreals
#15
Matthias Schiedel, Daniel Herp, Sören Hammelmann, Sören Swyter, Attila Lehotzky, Dina Robaa, Judit Oláh, Judit Ovádi, Wolfgang Sippl, Manfred Jung
Here we report the development of a proteolysis targeting chimera (PROTAC) based on the combination of the unique features of the sirtuin rearranging ligands (SirReals) as highly potent and isotype-selective Sirt2 inhibitors with thalidomide, a bona fide cereblon ligand. For the first time, we report the formation of a PROTAC by Cu(I)-catalyzed cycloaddition of a thalidomide-derived azide to an alkynylated inhibitor. This thalidomide-derived azide as well as the highly versatile linking strategy can be readily adapted to alkynylated ligands of other targets...
April 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28377012/mental-disorders-in-people-affected-by-thalidomide
#16
Alexander Niecke, Klaus Peters, Christina Samel, Kristin Forster, Markus Lüngen, Holger Pfaff, Christian Albus
BACKGROUND: More than 50 years after the withdrawal of thalidomide from the market, subsequent orthopedic damages and psychosocial impairments dominate the complaints of thalidomide-affected individuals. The aim of the study was to determine the prevalence of mental disorders in this group. METHODS: A total of 193 thalidomide-affected individuals from North Rhine-Westphalia (mean age 50.5 years, 56.5% women) underwent personal and comprehensive psychodiagnostic testing, which was based on the Structured Clinical Interview for DSM-IV disorders (SCID-I & SCID-II) and self-reporting questionnaires...
March 10, 2017: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/28373917/leflunomide-in-the-treatment-of-a-pseudotumoral-genital-herpes-simplex-virus-infection-in-an-hiv-patient
#17
Marie R Roger, Gregory M Anstead
The patient is a 52-year-old African American man with a past medical history of HIV infection (on antiretroviral therapy, CD4 count 399 cells/µL, and undetectable HIV viral load) and recurrent genital herpes. While on valacyclovir, the patient presented with four tumorous lesions on the perineum and scrotum. A biopsy specimen stained positively with HSV-1 and HSV-2 immunostains and displayed a lymphoplasmacytic infiltrate. The patient received foscarnet and imiquimod for two weeks with minimal improvement...
2017: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/28373701/benefit-of-continuous-treatment-for-responders-with-newly-diagnosed-multiple-myeloma-in-the-randomized-first-trial
#18
N J Bahlis, A Corso, L-O Mugge, Z-X Shen, P Desjardins, A-M Stoppax, O Decaux, T de Revel, M Granell, G Marit, H Nahi, H Demuynck, S-Y Huang, S Basu, T H Guthrie, A Ervin-Haynes, J Marek, G Chen, T Facon
The phase 3, randomized FIRST trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone, and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response...
April 4, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28370149/determination-of-4-1-3-dioxo-1-3-dihydro-2h-isoindol-2-yl-n-4-ethoxyphenyl-methylidene-benzohydrazide-a-novel-anti-inflammatory-agent-in-biological-fluids-by-uplc-ms-ms-assay-development-validation-and-in-vitro-metabolic-stability-study
#19
Muzaffar Iqbal, Mashooq A Bhat, Mohammad Raish, Essam Ezzeldin
A thalidomide analogue, (4-(1,3-dioxo-1,3-dihydro-2H-isoindol- 2-yl)-N'-[(4-ethoxyphenyl) methylidene] benzohydrazide), has been identified as a promising broad spectrum anti-inflammatory agent in previous study. In this study, a sensitive and selective UPLC-MS/MS assay was developed and validated for its determination in rat plasma samples. The chromatographic separation was performed on Aquity BEH C18 column using mobile phase comprising of acetonitrile and 10 mM ammonium acetate in the ratio of 85:15, at flow rate of 0...
March 31, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28365861/tnf-%C3%AE-tnfr1-signaling-is-required-for-the-full-expression-of-acute-and-chronic-itch-in-mice-via-peripheral-and-central-mechanisms
#20
Xiuhua Miao, Ya Huang, Teng-Teng Liu, Ran Guo, Bing Wang, Xue-Long Wang, Li-Hua Chen, Yan Zhou, Ru-Rong Ji, Tong Liu
Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-α antagonist etanercept dose-dependently suppressed acute itch...
April 1, 2017: Neuroscience Bulletin
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