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Bexarotene

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https://www.readbyqxmd.com/read/28600132/brentuximab-vedotin-or-physician-s-choice-in-cd30-positive-cutaneous-t-cell-lymphoma-alcanza-an-international-open-label-randomised-phase-3-multicentre-trial
#1
H Miles Prince, Youn H Kim, Steven M Horwitz, Reinhard Dummer, Julia Scarisbrick, Pietro Quaglino, Pier Luigi Zinzani, Pascal Wolter, Jose A Sanches, Pablo L Ortiz-Romero, Oleg E Akilov, Larisa Geskin, Judith Trotman, Kerry Taylor, Stephane Dalle, Michael Weichenthal, Jan Walewski, David Fisher, Brigitte Dréno, Rudolf Stadler, Tatyana Feldman, Timothy M Kuzel, Yinghui Wang, Maria Corinna Palanca-Wessels, Erin Zagadailov, William L Trepicchio, Wenwen Zhang, Hui-Min Lin, Yi Liu, Dirk Huebner, Meredith Little, Sean Whittaker, Madeleine Duvic
BACKGROUND: Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. METHODS: In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated...
June 6, 2017: Lancet
https://www.readbyqxmd.com/read/28540091/a-severe-case-of-lymphomatoid-papulosis-type-e-successfully-treated-with-interferon-alfa-2a
#2
Aslı Bilgiç Temel, Betül Unal, Hatice Erdi Şanlı, Şeniz Duygulu, Soner Uzun
Lymphomatoid papulosis (LyP) is a benign papulonodular skin eruption with histologic features of malignant lymphoma. A new variant of LyP which was termed "type E" was recently described with similar clinical and histological features to angiocentric and angiodestructive T-cell lymphoma. LyP type E is characterized with recurrent papulonodular lesions which rapidly turn into hemorrhagic necrotic ulcers and spontaneous regression by leaving a scar. None of the available treatment modalities affects the natural course of LyP...
2017: Case Reports in Dermatological Medicine
https://www.readbyqxmd.com/read/28512419/successful-treatment-of-primary-cutaneous-peripheral-t-cell-lymphoma-presenting-acquired-ichthyosis-with-oral-bexarotene-monotherapy
#3
Kayo Tanita, Taku Fujimura, Yota Sato, Takanori Hidaka, Sadanori Furudate, Yumi Kambayashi, Akira Tsukada, Akira Hashimoto, Setsuya Aiba
Acquired ichthyosis (AI) is a reactive cutaneous manifestation that can be associated with malignant hematological disease, including cutaneous T-cell lymphoma (CTCL). Since it is difficult to distinguish AI from ichthyosiform mycosis fungoides, to select the treatment for CTCL with ichthyosis-like appearance and to evaluate its efficacy is sometimes challenging. In this report, we describe a case of primary cutaneous peripheral T-cell lymphoma not otherwise specified presenting AI successfully treated with oral bexarotene...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28483659/the-long-non-coding-rna-neat1-is-an-important-mediator-of-the-therapeutic-effect-of-bexarotene-on-traumatic-brain-injury-in-mice
#4
Jianjun Zhong, Li Jiang, Zhijian Huang, Hongrong Zhang, Chongjie Cheng, Han Liu, Junchi He, Jingchuan Wu, Rami Darwazeh, Yue Wu, Xiaochuan Sun
OBJECTIVE: Bexarotene treatments exert neuroprotective effects on mice following traumatic brain injury (TBI). The present study aims to investigate the potential roles of the long noncoding RNA Neat1 in the neuroprotective effects of bexarotene. MATERIALS AND METHODS: Adult male C57BL/6J mice (n=80) and newborn mice (within 24 h after birth) (n=20) were used to generate a "controlled cortical impact" (CCI) model and harvest primary cortex neurons, respectively...
May 5, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28469839/gene-expression-profiling-discerns-molecular-pathways-elicited-by-ligand-signaling-to-enhance-the-specification-of-embryonic-stem-cells-into-skeletal-muscle-lineage
#5
REVIEW
Katherine Dixon, Jihong Chen, Qiao Li
Regulation of lineage specification and differentiation in embryonic stem (ES) cells can be achieved through the activation of endogenous signaling, an avenue for potential application in regenerative medicine. During vertebrate development, retinoic acid (RA) plays an important role in body axis elongation and mesoderm segmentation in that graded exposure to RA provides cells with positional identity and directs commitment to specific tissue lineages. Nevertheless, bexarotene, a clinically approved rexinoid, enhances the specification and differentiation of ES cells into skeletal myocytes more effectively than RA...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28378336/review-of-treatment-for-alopecia-totalis-and-alopecia-universalis
#6
REVIEW
Sama Kassira, Dorota Z Korta, Lance W Chapman, Francis Dann
Alopecia areata (AA) is an autoimmune disease directed at the hair follicle. Although usually limited to patchy hair loss over the scalp (focalis), AA can present as total loss of scalp hair (totalis; AT) or as total loss of both scalp and body hair (universalis; AU). Management of AT and AU can be challenging, and although multiple treatment modalities have been explored, no therapy is currently FDA-approved. This review focuses on the evidence for current treatment options for AT and AU. The PubMed database was searched from January 1, 2000, to September 1, 2016, for clinical trials, retrospective studies, and case reports of treatments for AT and AU...
April 5, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28356009/ecpirm-a-potential-therapeutic-agent-for-cutaneous-t-cell-lymphoma-inhibits-cell-proliferation-and-promotes-apoptosis-via-a-jak-stat-pathway-the-biological-effect-of-ecpirm-in-ctcl-cell
#7
Hua Yang, Pengcheng Ma, Yuping Cao, Mengli Zhang, Lingjun Li, Jun Wei, Lei Tao, Kun Qian
BACKGROUND: Retinoids are important agents for treatment of cutaneous T-cell lymphomas (CTCL). But side effects and drug resistance caused by activation of RAR/RXR limited their clinical application. So it is urgent to develop new agents fight against CTCL. ECPIRM, a 13-cis retinoic acid derivative, was reported that it inhibited proliferation and induced apoptosis of SCL-1 cells. OBJECTIVE: To evaluated the biological activities and mechanisms of ECPIEM. METHODS: Effect of ECPIRM on cell proliferation was determined by MTT assay and Trypan blue exclusion assay while FACS analysis was used to detect changes of cell cycle and apoptosis in HUT78 cells...
March 27, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28329468/cutaneous-t-cell-lymphoma-associated-leser-tr%C3%A3-lat-sign-report-and-world-literature-review
#8
Saisindhu Narala, Philip R Cohen
BACKGROUND: The sign of Leser-Trélat is characterizedby the sudden appearance of seborrheic keratosesassociated with an underlying malignancy. OBJECTIVES: An elderly man who developed multiple new-onsetseborrheic keratoses temporally associated witha diagnosis of mycosis fungoides is described andlymphoma-associated Leser-Trélat sign is reviewed. METHODS: Pubmed was used to search the followingterms: cutaneous T-cell lymphoma, Leser-Trélat,leukemia, lymphoma, mycosis fungoides, and Sézarysyndrome...
January 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28319634/late-onset-bexarotene-induced-cd4-lymphopenia-in-a-cutaneous-t-cell-lymphoma-patient
#9
Karin Eshagh, Laura S Romero, Jessica K So, Xianfeng Frank Zhao
Various infections, autoimmune diseases, medications, and total-body irradiation are known factors associated with CD4 lymphopenia, defined as a CD4 T-cell count below 300 cells/mL or less than 20% of total lymphocytes. We report a rare case of a patient with cutaneous T-cell lymphoma (CTCL) who developed profound CD4 lymphopenia in the setting of long-term bexarotene therapy. Bexarotene is a third-generation retinoid that inhibits epithelial cell proliferation and is approved for treatment of advanced CTCL (stages IIB-IVB) in adult patients who have failed at least 1 prior systemic therapy...
February 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28251414/molecular-dynamics-simulations-and-molecular-flooding-studies-of-the-retinoid-x-receptor-ligand-binding-domain
#10
Geoffrey M Gray, Ning Ma, Carl E Wagner, Arjan van der Vaart
Bexarotene is an FDA approved retinoid X-receptor (RXR) agonist for the treatment of cutaneous T-cell lymphoma, and its use in other cancers and Alzheimer's disease is being investigated. The drug causes serious side effects, which might be reduced by chemical modifications of the molecule. To rationalize known agonists and to help identify sites for potential substitutions we present molecular simulations in which the RXR ligand-binding domain was flooded with a large number of drug-like molecules, and molecular dynamics simulations of a series of bexarotene-like ligands bound to the RXR ligand-binding domain...
March 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28205585/neuronally-directed-effects-of-rxr-activation-in-a-mouse-model-of-alzheimer-s-disease
#11
M M Mariani, T Malm, R Lamb, T R Jay, L Neilson, B Casali, L Medarametla, G E Landreth
Alzheimer's disease (AD) is characterized by extensive neuron loss that accompanies profound impairments in memory and cognition. We examined the neuronally directed effects of the retinoid X receptor agonist bexarotene in an aggressive model of AD. We report that a two week treatment of 3.5 month old 5XFAD mice with bexarotene resulted in the clearance of intraneuronal amyloid deposits. Importantly, neuronal loss was attenuated by 44% in the subiculum in mice 4 months of age and 18% in layer V of the cortex in mice 8 months of age...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28169169/drugbank-screening-revealed-alitretinoin-and-bexarotene-as-liver-x-receptor-modulators
#12
Pascal Heitel, Janosch Achenbach, Daniel Moser, Ewgenij Proschak, Daniel Merk
In silico screening of DrugBank database to detect liver X receptor (LXR) agonism of marketed drugs using a self-organizing map and successive LXR-Gal4 hybrid reporter gene assay evaluation in vitro discovered alitretinoin and bexarotene as partial liver X receptor agonists. Dose-response curves demonstrated that plasma concentrations observed in clinical trials are sufficient for LXR activation and thus could account for LXR-mediated side-effects such as hypercholesterolemia and hyperlipidemia. The discovered drugs are the first reported dual LXR/RXR agonists and can serve as lead structures for LXR and dual LXR/RXR modulator development...
January 25, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28167509/results-from-a-phase-i-ii-open-label-dose-finding-study-of-pralatrexate-and-oral-bexarotene-in-patients-with-relapsed-refractory-cutaneous-t-cell-lymphoma
#13
Madeleine Duvic, Youn H Kim, Pier Luigi Zinzani, Steven M Horwitz
Pralatrexate is a folic acid analogue metabolic inhibitor similar to methotrexate, which has shown tolerability and efficacy with an overall response rate of 45% in a phase I dose deescalation study of patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL). The object of this phase I/II open-label, multicenter clinical trial was to determine the MTD and recommended dose of pralatrexate plus oral bexarotene in 34 patients with relapsed/refractory CTCL who had failed prior systemic therapies. Pralatrexate was administered by intravenous push at 15 mg/m(2) given weekly 3 weeks out of 4 weeks with daily oral bexarotene (150 or 300 mg/m(2)), levothyroxine, atorvastatin, folate, and with B12 every 2 months...
February 6, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28119332/brentuximab-beats-standard-therapies-for-ctcl
#14
(no author information available yet)
Compared with a physician's choice of either methotrexate or bexarotene, the CD30-directed antibody-drug conjugate brentuximab vedotin led to significantly superior clinical responses in patients with cutaneous T-cell lymphomas, according to the results of the international phase III ALCANZA trial.
January 24, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28099842/brown-adipogenic-reprogramming-induced-by-a-small-molecule
#15
Baoming Nie, Tao Nie, Xiaoyan Hui, Ping Gu, Liufeng Mao, Kuai Li, Ran Yuan, Jiashun Zheng, Haixia Wang, Ke Li, Shibing Tang, Yu Zhang, Tao Xu, Aimin Xu, Donghai Wu, Sheng Ding
Brown adipose tissue (BAT) has attracted considerable research interest because of its therapeutic potential to treat obesity and associated metabolic diseases. Augmentation of brown fat mass and/or its function may represent an attractive strategy to enhance energy expenditure. Using high-throughput phenotypic screening to induce brown adipocyte reprogramming in committed myoblasts, we identified a retinoid X receptor (RXR) agonist, bexarotene (Bex), that efficiently converted myoblasts into brown adipocyte-like cells...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28088372/nanoformulation-of-dual-bexarotene-tailed-phospholipid-conjugate-with-high-drug-loading
#16
Ruiyu He, Yawei Du, Longbing Ling, Muhammad Ismail, Yongpeng Hou, Chen Yao, Xinsong Li
Bexarotene (Bex), a synthetic retinoid X receptor-selective activator, has been proved to be an efficacious chemotherapeutic agent. But, its clinical application is limited due to the poor solubility. In this report, dual bexarotene-tailed phospholipid (DBTP) conjugate based nanovesicles were prepared in order to develop new nanoformulation. DBTP conjugate was first synthesized by conjugating two Bex molecules with glycerophosphorylcholine (GPC) through facial esterification. The amphiphilic DBTP nanovesicles were prepared without any additive by reverse-phase evaporation method...
March 30, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27978471/simple-and-sensitive-hplc-uv-method-for-determination-of-bexarotene-in-rat-plasma
#17
Jong Bong Lee, Atheer Zgair, Tae Hwan Kim, Min Gi Kim, Sun Dong Yoo, Peter M Fischer, Pavel Gershkovich
Bexarotene is currently marketed for treatment of cutaneous T-cell lymphoma and there has been growing interest in its therapeutic effectiveness for other cancers. Neuroprotective effects of bexarotene have also been reported. In this study, a simple, sensitive and cost-efficient bioanalytical method for determination of bexarotene in rat plasma was developed and fully validated. The method utilises protein precipitation with acetonitrile and liquid-liquid extraction with n-hexane-ethyl acetate (10:1, v/v)...
January 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27865806/ikaros-exploiting-and-targeting-the-hematopoietic-stem-cell-niche-in%C3%A2-b-progenitor-acute-lymphoblastic-leukemia
#18
REVIEW
Michelle L Churchman, Charles G Mullighan
Genetic alterations of IKZF1 encoding the lymphoid transcription factor IKAROS are a hallmark of high-risk B-progenitor acute lymphoblastic leukemia (ALL), such as BCR-ABL1-positive (Ph+) and Ph-like ALL, and are associated with poor outcome even in the era of contemporary chemotherapy incorporating tyrosine kinase inhibitors. Recent experimental mouse modeling of B-progenitor ALL has shown that IKZF1 alterations have multiple effects, including arresting differentiation, skewing lineage of leukemia from myeloid to lymphoid, and, in Ph+ leukemia, conferring resistance to tyrosine kinase inhibitor (TKI) therapy without abrogating ABL1 inhibition...
February 2017: Experimental Hematology
https://www.readbyqxmd.com/read/27842487/possible-molecular-interactions-of-bexarotene-a-retinoid-drug-and-alzheimer-s-a%C3%AE-peptide-a-docking-study
#19
Zeenat Mirza, Mohd Amin Beg
BACKGROUND: Alzheimer's disease (AD) pathogenesis is primarily hallmarked by the production and accumulation of amyloid beta (Aβ) peptide. Along with the understanding of the neurodegenerative disease progression and its pathophysiological mechanisms, development of anti-Aβ targeted effective therapeutics is essential for AD management. Numerous therapeutic approaches targeting the production, toxicity and removal of Aβ are being attempted worldwide. Prime need is to design inhibitors which can slow down the Aβ aggregation process in a physiological environment...
2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/27833522/histamine-h3-receptors-and-its-antagonism-as-a-novel-mechanism-for-antipsychotic-effect-a-current-preclinical-clinical-perspective
#20
REVIEW
Danish Mahmood
Histamine H3 receptors are present as autoreceptors on histaminergic neurons and as heteroreceptors on nonhistaminergic neurones. They control the release and synthesis of histamine and several other key neurotransmitters in the brain. H3 antagonism may be a novel approach to develop a new class of antipsychotic medications given the gathering evidence reporting therapeutic efficacy in several central nervous system disorders. Several medications such as cariprazine, lurasidone, LY214002, bexarotene, rasagiline, raloxifene, BL-1020 and ITI-070 are being developed to treat the negative symptoms and cognitive impairments of schizophrenia...
October 2016: International Journal of Health Sciences
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