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https://www.readbyqxmd.com/read/28340497/p450-inhibitor-ketoconazole-increased-the-intratumor-drug-levels-and-antitumor-activity-of-fenretinide-in-human-neuroblastoma-xenograft-models
#1
Lluis Lopez-Barcons, Barry J Maurer, Min H Kang, C Patrick Reynolds
We previously reported that concurrent ketoconazole, an oral anti-fungal agent and P450 enzyme inhibitor, increased plasma levels of the cytotoxic retinoid, fenretinide (4-HPR) in mice. We have now determined the effects of concurrent ketoconazole on 4-HPR cytotoxic dose-response in four neuroblastoma (NB) cell lines in vitro and on 4-HPR activity against two cell line-derived, subcutaneous NB xenografts (CDX) and three patient-derived NB xenografts (PDX). Cytotoxicity in vitro was assessed by DIMSCAN assay...
March 24, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28335003/identification-of-genetic-variants-affecting-vitamin-d-receptor-binding-and-associations-with-autoimmune-disease
#2
Giuseppe Gallone, Wilfried Haerty, Giulio Disanto, Sreeram V Ramagopalan, Chris P Ponting, Antonio J Berlanga-Taylor
Large numbers of statistically significant associations between sentinel SNPs and case-control status have been replicated by genome-wide association studies. Nevertheless, few underlying molecular mechanisms of complex disease are currently known. We investigated whether variation in binding of a transcription factor, the vitamin D receptor (VDR) whose activating ligand vitamin D has been proposed as a modifiable factor in multiple disorders, could explain any of these associations. VDR modifies gene expression by binding DNA as a heterodimer with the Retinoid X receptor (RXR)...
March 9, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28329611/terap%C3%A3%C2%AAutica-fotodin%C3%A3-mica-com-metil-aminolevulinato-no-tratamento-de-les%C3%A3%C2%B5es-refract%C3%A3-rias-de-micose-fung%C3%A3-ide-resposta-cl%C3%A3-nica-e-histol%C3%A3-gica-mantida-em-dois-doentes
#3
Ana Isabel Teixeira, João Maia E Silva
According to the guidelines proposed by the National Comprehensive Cancer Network, early-stage Mycosis Fungoides (MF) should be treated with skin-directed therapies such as topical steroids or retinoids, topical chemotherapy (carmustin and nitrogen mustard), photochemotherapy, and superficial radiotherapy. Patients with refractory lesions to these therapeutic options are particularly challenging. Photodynamic Therapy (PDT) has been approved to treat cutaneous neoplastic and pre-neoplastic lesions such as superficial basal cell carcinoma, Bowen disease and actinic keratosis...
September 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329545/darier-white-disease
#4
Mitalee P Christman, Evan Reider, Randie H Kim, Nooshin Brinster, Elisa Femia, Miriam Keltz Pomeranz
We present a 58-year-old woman with bipolardisorder and with a longstanding history of yellowbrown,hyperkeratotic papules in a seborrheicdistribution and nail changes. Her father andpaternal grandmother had similar eruptions and alsohad psychiatric disease. Histopathologic examinationshowed acantholysis and dyskeratosis, which wasconsistent with Darier-White disease. Darier-Whitedisease is a rare, hereditary disorder that is inheritedin an autosomal dominant manner and that usuallypresents in adolescence or early adulthood dueto mutations in the SERCA2 calcium pump...
December 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28319634/late-onset-bexarotene-induced-cd4-lymphopenia-in-a-cutaneous-t-cell-lymphoma-patient
#5
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/28318721/-physiology-of-the-visual-retinal-signal-from-phototransduction-to-the-visual-cycle
#6
REVIEW
C Salesse
The retinal photoreceptors (rods and cones) are responsible for light absorption and transduction of the signal, which is transmitted to the other retinal nerve cells and then to the brain. The chromophore of visual pigments of rods and cones is a particular isomer of a vitamin A derivative. Light absorption by this chromophore leads to its isomerization and to a phototransduction cascade, which results in photoreceptor hyperpolarization and cessation of glutamate secretion at their synaptic terminals. Phototransduction of cones and rods differs in their signal amplification and inactivation, which is consistent with their respective functions...
March 17, 2017: Journal Français D'ophtalmologie
https://www.readbyqxmd.com/read/28318351/retinoids-a-journey-from-the-molecular-structures-and-mechanisms-of-action-to-clinical-uses-in-dermatology-and-adverse-effects
#7
Samar Khalil, Tara Bardawil, Carla Stephan, Nadine Darwiche, Ossama Abbas, Abdul Ghani Kibbi, Georges Nemer, Mazen Kurban
Retinoids are a class of compounds derived from vitamin A or have structural and/or functional similarity with vitamin A. They are classified into three generations based on their molecular structures. Inside the body, retinoids bind to several classes of proteins including retinoid-binding proteins and retinoid nuclear receptors. This eventually leads to the activation of specific regulatory regions of DNA - called the retinoic acid response elements - involved in regulating cell growth, differentiation and apoptosis...
March 20, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28314837/risk-reducing-strategies-for-ovarian-cancer-in-brca-mutation-carriers-a-balancing-act
#8
Roi Tschernichovsky, Annekathryn Goodman
OBJECTIVE: The objective of this study was to review the role of bilateral salpingo-oophorectomy in BRCA mutation (mBRCA) carriers and alternative interventions in risk reduction of ovarian cancer (OC). MATERIALS AND METHODS: A systematic review using PubMed, MEDLINE, EMBASE, and the Cochrane library was conducted to identify studies of different strategies to prevent OC in mBRCA carriers, including bilateral salpingo-oophorectomy, prophylactic salpingectomy with delayed oophorectomy, intensive surveillance, and chemoprevention...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28306713/trypanocidal-effect-of-isotretinoin-through-the-inhibition-of-polyamine-and-amino-acid-transporters-in-trypanosoma-cruzi
#9
Chantal Reigada, Edward A Valera-Vera, Melisa Sayé, Andrea E Errasti, Carla C Avila, Mariana R Miranda, Claudio A Pereira
Polyamines are essential compounds to all living organisms and in the specific case of Trypanosoma cruzi, the causative agent of Chagas disease, they are exclusively obtained through transport processes since this parasite is auxotrophic for polyamines. Previous works reported that retinol acetate inhibits Leishmania growth and decreases its intracellular polyamine concentration. The present work describes a combined strategy of drug repositioning by virtual screening followed by in vitro assays to find drugs able to inhibit TcPAT12, the only polyamine transporter described in T...
March 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28301045/beneficial-effect-of-ustekinumab-in-familial-pityriasis-rubra-pilaris-with-a-new-missense-mutation-in-card14
#10
S M Lwin, C-K Hsu, L Liu, H-Y Huang, N J Levell, J A McGrath
Pityriasis rubra pilaris (PRP) represents a group of rare chronic inflammatory skin disorders in which ~1 in 20 affected individuals show autosomal dominant inheritance. In such cases, there may be gain-of-function mutations in CARD14, encoding caspase recruitment domain-containing protein 14 (CARD14) that activates the non-canonical nuclear factor-kappa B (NF-κB) pathway, thereby promoting cutaneous inflammation. Here, we report a mother and son with PRP due to a new missense mutation in CARD14 and describe the beneficial clinical effects of ustekinumab, a monoclonal antibody against interleukins-12 and -23, in both subjects...
March 16, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28298893/bis-retinoid-a2e-induces-an-increase-of-basic-fibroblast-growth-factor-via-inhibition-of-extracellular-signal-regulated-kinases-1-2-pathway-in-retinal-pigment-epithelium-cells-and-facilitates-phagocytosis
#11
Delphine Balmer, Linda Bapst-Wicht, Aswin Pyakurel, Martine Emery, Natacha Nanchen, Christian G Bochet, Raphael Roduit
Age-related macular degeneration (ARMD) is the leading cause of vision loss in developed countries. Hallmarks of the disease are well known; indeed, this pathology is characterized by lipofuscin accumulation, is principally composed of lipid-containing residues of lysosomal digestion. The N-retinyl-N-retinylidene ethanolamine (A2E) retinoid which is thought to be a cytotoxic component for RPE is the best-characterized component of lipofuscin so far. Even if no direct correlation between A2E spatial distribution and lipofuscin fluorescence has been established in aged human RPE, modified forms or metabolites of A2E could be involved in ARMD pathology...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28298266/metabolic-effects-of-inflammation-on-vitamin-a-and-carotenoids-in-humans-and-animal-models
#12
REVIEW
Lewis P Rubin, A Catharine Ross, Charles B Stephensen, Torsten Bohn, Sherry A Tanumihardjo
The association between inflammation and vitamin A (VA) metabolism and status assessment has been documented in multiple studies with animals and humans. The relation between inflammation and carotenoid status is less clear. Nonetheless, it is well known that carotenoids are associated with certain health benefits. Understanding these relations is key to improving health outcomes and mortality risk in infants and young children. Hyporetinolemia, i.e., low serum retinol concentrations, occurs during inflammation, and this can lead to the misdiagnosis of VA deficiency...
March 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28295493/case-of-harlequin-ichthyosis-with-a-favorable-outcome-early-treatment-and-novel-differentially-expressed-alternatively-spliced-transcripts-of-the-atp-binding-cassette-subfamily-a-member-12-gene
#13
Ken Washio, Mayuko Sumi, Kaori Nakata, Atsushi Fukunaga, Keiji Yamana, Tsubasa Koda, Ichiro Morioka, Chikako Nishigori, Kiyofumi Yamanishi
Harlequin ichthyosis (HI) is the most severe form of autosomal recessive congenital ichthyosis, with a high mortality rate. Recent advances in neonatal care and the early administration of retinoids have improved the survival rate of HI. Here, we present a case of HI who was successfully treated with early administration of etretinate and showed good prognosis. Next-generation sequencing identified novel mutations of the ATP-binding cassette subfamily A member 12 gene (ABCA12), c.5884+4_+5delAA and c.7239G>A, which caused skipping of exons 39 and 48, respectively...
March 11, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28286734/identifying-the-receptor-subtype-selectivity-of-retinoid-x-and-retinoic-acid-receptors-via-quantum-mechanics
#14
Motonori Tsuji, Koichi Shudo, Hiroyuki Kagechika
Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands...
March 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28286207/virtual-screening-applications-in-short-chain-dehydrogenase-reductase-research
#15
REVIEW
Katharina R Beck, Teresa Kaserer, Daniela Schuster, Alex Odermatt
Several members of the short-chain dehydrogenase/reductase (SDR) enzyme family play fundamental roles in adrenal and gonadal steroidogenesis as well as in the metabolism of steroids, oxysterols, bile acids, and retinoids in peripheral tissues, thereby controlling the local activation of their cognate receptors. Some of these SDRs are considered as promising therapeutic targets, for example to treat estrogen-/androgen-dependent and corticosteroid-related diseases, whereas others are considered as anti-targets as their inhibition may lead to disturbances of endocrine functions, thereby contributing to the development and progression of diseases...
March 9, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28283894/treatment-of-porokeratosis-a-systematic-review
#16
REVIEW
Till Weidner, Tanja Illing, Diana Miguel, Peter Elsner
BACKGROUND: Porokeratosis (PK) is a rare skin disease of unknown etiology. It consists of a keratinization disorder, which may appear in several clinical forms and can undergo malignant transformation. The histopathological hallmark of PK is the cornoid lamella. While many topical, systemic, and surgical treatment modalities for PK have been described, no randomized controlled trials have been performed yet. Because of a lack of treatment standards for PK, European and international guidelines cannot be created...
March 10, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28283893/tranexamic-acid-in-the-treatment-of-melasma-a-review-of-the-literature
#17
REVIEW
Marina Perper, Ariel Eva Eber, Rachel Fayne, Sebastian Hugo Verne, Robert James Magno, Jessica Cervantes, Mana ALharbi, Ibrahim ALOmair, Abdulkarem Alfuraih, Keyvan Nouri
Melasma is a common acquired pigmentary disorder marked by irregular hyperpigmented macules or patches and most commonly occurs in women of darker skin color. It is a chronic often-relapsing condition that causes negative psychosocial effects in those affected. Current treatments such as hydroquinone, kojic acid, and retinoids, among others, demonstrate variable efficacy and side-effect profiles. We conducted a comprehensive literature review examining the use of tranexamic acid (TA), a well-known anti-fibrinolytic agent, in the treatment of melasma...
March 10, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28275870/synthesis-of-short-retinoidal-amides-related-to-fenretinide-antioxidant-activities-and-differentiation-inducing-ability
#18
Maria Anzaldi, Maurizio Viale, Chiara Macciò, Patrizio Castagnola, Valentina Oliveri, Camillo Rosano, Alessandro Balbi
PURPOSE: By a scaffold shortening strategy, a small series of retinoidal amides fenretinide (4-HPR) analogs have been synthesized from α, β-ionones and tested for their antiproliferative and differentiating activities, and antioxidant effect. METHODS: The antiproliferative activity and triggering of apoptosis of our short retinoids were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 4'-6-diamidino-2-phenylindole staining and microscope evaluation after 3- or 6-day exposure, while their differentiating activity was established by the analysis of the expression of the CD11b marker of differentiation in treated HL60 target cells and by the superoxide production assayed colorimetrically by the nitro blue tetrazolium-reducing activity assay...
March 9, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28274355/topical-treatments-for-acne
#19
Marita Kosmadaki, Andreas Katsambas
Topical drugs have been used successfully to treat acne for decades. This review discusses the use, efficacy, and safety of options available via prescription. Topical antibiotics, dapsone, benzyl peroxide, azelaic acid, and topical retinoids are included. Topical antibiotics should not be used as monotherapy but rather be combined with other agents to avoid resistant Propionibacterium acnes strains. Benzoyl peroxide is effective in preventing bacteria resistance. Topical retinoids address primarily the comedonal but also the inflammatory lesions of acne...
March 2017: Clinics in Dermatology
https://www.readbyqxmd.com/read/28274353/propionibacterium-acnes-and-antimicrobial-resistance-in-acne
#20
Clio Dessinioti, Andreas Katsambas
The human commensal bacterium Propionibacterium acnes (P. acnes) resides in the pilosebaceous duct of the skin. It has been long implicated in the pathogenesis of acne, although its exact role in the development of inflammatory acne lesions and in the formation of the microcomedo in the early stages of acne remains controversial. The worldwide prevalence of antibiotic-resistant P. acnes is increasing, with rates varying in different parts of the world. The reason for the difference in the antibiotic resistance patterns of P...
March 2017: Clinics in Dermatology
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