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Bexarotene

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https://www.readbyqxmd.com/read/28872641/polyunsaturated-fatty-acid-deficiency-during-neurodevelopment-in-mice-models-the-prodromal-state-of-schizophrenia-through-epigenetic-changes-in-nuclear-receptor-genes
#1
M Maekawa, A Watanabe, Y Iwayama, T Kimura, K Hamazaki, S Balan, H Ohba, Y Hisano, Y Nozaki, T Ohnishi, M Toyoshima, C Shimamoto, K Iwamoto, M Bundo, N Osumi, E Takahashi, A Takashima, T Yoshikawa
The risk of schizophrenia is increased in offspring whose mothers experience malnutrition during pregnancy. Polyunsaturated fatty acids (PUFAs) are dietary components that are crucial for the structural and functional integrity of neural cells, and PUFA deficiency has been shown to be a risk factor for schizophrenia. Here, we show that gestational and early postnatal dietary deprivation of two PUFAs-arachidonic acid (AA) and docosahexaenoic acid (DHA)-elicited schizophrenia-like phenotypes in mouse offspring at adulthood...
September 5, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28805086/brentuximab-vedotin-therapy-for-cd30-positive-cutaneous-t-cell-lymphoma-a-targeted-approach-to-management
#2
Julia J Scarisbrick
CD30-positive primary cutaneous T-cell lymphoma (CTCL) includes mycosis fungoides, anaplastic large-cell lymphoma and lymphomatoid papulosis type A. Brentuximab vedotin (BV) consists of an antibody targeting CD30 with a protease-cleavable linker to vedotin. CD30 binding allows internalization of BV inducing cell-cycle arrest and apoptosis. Response rates >75% with manageable adverse effects in refractory Hodgkin lymphoma and systemic anaplastic large-cell lymphoma led to accelerated approval for both. Phase II studies in CD30-expressing CTCL followed and showed similar efficacy, which was ratified in a Phase III trial of BV versus physician's choice (methotrexate or bexarotene) showing significant improved responses without increase in severe adverse effects although peripheral neuropathy is frequent...
August 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/28804273/influence-of-the-number-of-axial-bexarotene-ligands-on-the-cytotoxicity-of-pt-iv-analogs-of-oxaliplatin
#3
Yulia N Nosova, Ilia V Zenin, Varvara P Maximova, Ekaterina M Zhidkova, Kirill I Kirsanov, Ekaterina A Lesovaya, Anna A Lobas, Mikhail V Gorshkov, Olga N Kovaleva, Elena R Milaeva, Markus Galanski, Bernhard K Keppler, Alexey A Nazarov
We present the synthesis and cytotoxic potencies of new Pt(IV) complexes with bexarotene, an anticancer drug that induces cell differentiation and apoptosis via selective activation of retinoid X receptors. In these complexes bexarotene is positioned as an axial ligand. The complex of one bexarotene ligand attached to Pt(IV) oxaliplatin moiety was potent whereas its counterpart carrying two bexarotene ligands was inactive.
2017: Bioinorganic Chemistry and Applications
https://www.readbyqxmd.com/read/28770285/-treatment-of-mycosis-fungoides-and-s%C3%A3-zary-syndrome
#4
REVIEW
J P Nicolay, C Assaf
Adequate therapeutic management of cutaneous T-cell lymphoma (CTCL) requires the identification of the exact CTCL stage and entity within the current WHO classification. There is no curative therapy for CTCL yet, so that treatment currently aims at improving symptoms and quality of life as well as reducing relapse rates. The treatment has to be stage-adapted. Therapeutic options comprise skin-directed as well as systemic treatment. In early stages, phototherapy and local steroids are the first-line therapeutic options...
August 2, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28753292/synthesis-of-11-c-labeled-rxr-partial-agonist-1-3-5-5-8-8-pentamethyl-5-6-7-8-tetrahydronaphthalen-2-yl-amino-benzotriazole-5-carboxylic-acid-cbt-pmn-by-direct-11-c-carbon-dioxide-fixation-via-organolithiation-of-trialkyltin-precursor-and-pet-imaging-thereof
#5
Osamu Shibahara, Masaki Watanabe, Shoya Yamada, Masaru Akehi, Takanori Sasaki, Akiya Akahoshi, Takahisa Hanada, Hiroyuki Hirano, Shunsuke Nakatani, Hiromi Nishioka, Yasuo Takeuchi, Hiroki Kakuta
The retinoid X receptor (RXR) partial agonist 1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (1; CBt-PMN, Emax = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimer's and Parkinson's diseases based on reports that RXR-full agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) shows therapeutic effects on these disease in rodent models. Here, we synthesized carbon-11-labeled ([(11)C]1) as a tracer for positron emission tomography (PET) and used it in a PET imaging study to examine the brain uptake and biodistribution of 1...
August 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28748653/oral-bexarotene-for-post-transplant-cutaneous-t-cell-lymphoma
#6
Daniel J Lewis, Simo Huang, Madeleine Duvic
Organ transplant recipients receiving immunosuppression have an increased risk of developing post-transplant lymphoproliferative diseases (PTLDs). Traditionally, PTLDs refer to Epstein-Barr virus (EBV)-induced B-cell lymphoma. However, post-transplant T-cell lymphoma may also occur and tends to have a poorer response to reduced immunosuppressive therapy. As such, additional therapy is often needed for post-transplant T-cell lymphoma, including post-transplant cutaneous T-cell lymphoma (PT-CTCL). We present only the third case of PT-CTCL occurring after liver transplantation...
July 26, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28689412/bexarotene-does-not-clear-amyloid-beta-plaques-but-delays-fibril-growth-molecular-mechanisms
#7
Pham Dinh Quoc Huy, Nguyen Quoc Thai, Zuzana Bednarikova, Le Huu Phuc, Huynh Quang Linh, Zuzana Gazova, Mai Suan Li
In 2012, it was reported that anticancer drug bexarotene reduced amyloid plaque and improved mental functioning in a small sample of mice engineered to exhibit Alzheimer's like symptoms. It has been suggested that bexarotene stimulates expression of apolipoprotein E (ApoE) leading to intracellular clearance of amyloid beta (Aβ). However, the effect of bexarotene on clearance of plaques has not been seen in some mouse models. Two interesting questions include whether bexarotene can destroy Aβ fibrils via direct interaction with them and how this compound impacts the lag phase in the fibril growth process...
July 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28687611/vitamin-a-regulates-akt-signaling-through-the-phospholipid-fatty-acid-composition
#8
Helmut Pein, Solveigh C Koeberle, Maria Voelkel, Freya Schneider, Antonietta Rossi, Maria Thürmer, Konstantin Loeser, Lidia Sautebin, Helen Morrison, Oliver Werz, Andreas Koeberle
Protein kinases, including the serine/threonine kinase Akt, mediate manifold bioactivities of vitamin A, although the mechanisms behind the sustained kinase activation are diffuse. To investigate the role of cellular lipids as targetable factors in Akt signaling, we combined mass spectrometry-based lipidomics with immunologic detection of Akt (Ser473) phosphorylation. A screening campaign revealed retinol (vitamin A alcohol) and all-trans retinoic acid (vitamin A acid) (RA) as hits that time-dependently (≥24 h) deplete phosphatidylcholine-bound polyunsaturated fatty acids (PUFA-PCs) from NIH-3T3 mouse fibroblasts while inducing Akt activation (EC50 ≈ 0...
July 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28648516/-mycosis-fungoides-in-a-heart-transplant-recipient
#9
Q Bodard, N Litrowski, D Carre, M Midhat, P Chenal, P Bravard
BACKGROUND: Skin cancer occurs frequently in organ transplant patients as a result of induced immunosuppression. Most cases involve carcinomas or B-cell lymphomas induced by the Epstein Barr virus (EBV). Cutaneous T-cell lymphomas remain rare. We report a case of cutaneous T-cell lymphoma of the mycosis fungoides type in a heart transplant recipient. PATIENTS AND METHODS: A 68-year-old man who had received a heart transplant 21years earlier and was being treated with tacrolimus, mycophenolate mofetil and prednisolone had been presenting a psoriasiform rash on his trunk, limbs and head for 4years...
June 22, 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/28641286/effect-of-bexarotene-on-platelet-activation-and-apoptosis
#10
Hang Cao, Rosi Bissinger, Anja T Umbach, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The retinoid X receptor (RXRs) stimulator Bexarotene ((4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl] benzoic acid) is used for the treatment of several malignancies. Bexarotene is at least in part effective by stimulation of apoptosis of tumor cells. Moreover, Bexarotene triggers eryptosis, the suicidal death of erythrocytes. Similar to erythrocytes, blood platelets lack nuclei but are nevertheless able to enter an apoptosis-like phenotype, characterized by caspase activation, cell shrinkage and cell membrane scrambling with phospha-tidylserine translocation to the cell surface...
2017: Cellular Physiology and Biochemistry
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
#11
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...
August 5, 2017: Lancet
https://www.readbyqxmd.com/read/28540091/a-severe-case-of-lymphomatoid-papulosis-type-e-successfully-treated-with-interferon-alfa-2a
#12
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
#13
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
#14
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 24h after birth) (n=20) were used to generate a "controlled cortical impact" (CCI) model and harvest primary cortex neurons, respectively. The HT22 cell line and the BV2 cell line were cultured under "normal" or "oxygen/glucose-deprived" (OGD) conditions...
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
#15
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
#16
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...
August 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
#17
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
#18
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
#19
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
#20
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
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