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RXRs are important in controlling apoptosis 9-cis-retinoic acid (Pan-Retin), which is currently approved by the FDA for the treatment of Kaposi s sarcoma, binds the RXR , , and receptors Its use in acne and photoaging has not yet been studied Targretin gel is another RXR selective retinoid Targretin selectively binds all three RXRs, , , and , and is now being reviewed in trials for psoriasis It can repress AP-1 function, though not as well as retinoids such as retinoic acid or 9-cis-retinoic acid (Personal communication Reid Bissonnette, PhD Nuclear Receptor Discovery Department of Ligand Pharmacuticals) The use of RXR ligands in cancer treatments implies that these drugs may have utility in preventing some of the benign neoplasms seen in aging skin; however, this has not yet been studied
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CHAPTER 30 RETINOIDS
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Retinoids are among one of the most often used classes of agents in the dermatologic armamentarium Many years of research have led to an ever-widening scope of uses for these products The promotion of exfoliation, dermal collagen synthesis, and angiogenesis from topical retinoids suggests an important role for these products in the attempt to curtail the cutaneous effects of photoaging
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1 Fisher GJ, Datta SC, Talwar HS, et al Molecular basis of sun-induced premature skin ageing and retinoid antagonism Nature 1996;379:335 2 Kligman L, Kligman AM Photoaging Retinoids, alpha hydroxy acids, and antioxidants In: Gabard B, Elsner P, Surber C, Treffel P, eds Dermatopharmacology of Topical Preparations, New York, NY: Springer; 2000:383
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3 Kligman AM, Grove GL, Hirose R, et al Topical tretinoin for photoaged skin J Am Acad Dermatol 1986;15:836 4 Karrer P, Morf R, Schopp K Zur kenntnis des vitamin-a aus fischtranin Helv Chim Acta 1931;14:1036 5 Kligman AM The growing importance of topical retinoids in clinical dermatology: a retrospective and prospective analysis J Am Acad Dermatol 1998;39:S2 6 Chandraratna RA Tazarotene first of a new generation of receptor-selective retinoids Br J Dermatol 1996;135:18 7 Millikan LE Adapalene: an update on newer comparative studies between the various retinoids Int J Dermatol 2000; 39:784 8 Weiss JS Current options for topical treatment of acne vulgaris Pediatr Dermatol 1997;14:480 9 Chytil F, Ong D Cellular retinoid-binding proteins In: Sporn MB, Roberts A, Goodman D, eds The Retinoids Vol 2 Orlando, FL: Academic Press; 1984: 89 123 10 Giguere V, Ong ES, Segui P, et al Identification of a receptor for the morphogen retinoic acid Nature 1987;330: 624 11 Petkovich M, Brand NJ, Krust A, et al A human retinoic acid receptor which belongs to the family of nuclear receptors Nature 1987;330:444 12 Pfahl M The molecular mechanism of retinoid action Retinoids today and tomorrow Retinoids Dermatol 1996;44:2 13 Petkovich M Regulation of gene expression by vitamin A: the role of nuclear retinoic acid receptors Annu Rev Nutr 1992;12:443 14 Chambon P A decade of molecular biology of retinoic acid receptors FASEB J 1996;10:940 15 Nagpal S, Chandraratna RA Recent developments in receptor-selective retinoids Curr Pharm Des 2000;6:919 16 Lippman S, Lotan R Advances in the development of retinoids as chemopreventive agents J Nutr 2000;130:S479 17 Fisher GJ, Wang ZQ, Datta SC, et al Pathophysiology of premature skin aging induced by ultraviolet light N Engl J Med 1997;337:1419 18 Fisher GJ, Datta S, Wang Z, et al cJun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by alltrans retinoic acid J Clin Invest 2000; 106:663 19 Fisher GJ, Talwar HS, Lin J, et al Molecular mechanisms of photoaging in human skin in vivo and their prevention by all-trans retinoic acid Photochem Photobiol 1999;69:154 20 Weiss JS, Ellis CN, Headington JT, et al Topical tretinoin improves photoaged
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30 31
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skin: a double-blind vehicle-controlled study JAMA 1988;259:527 Griffiths CE, Kang S, Ellis CN, et al Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degrees of irritation A double-blind, vehicle-controlled comparison of 01% and 0025% tretinoin creams Arch Dermatol 1995;131:1037 Woodley DT, Zelickson AS, Briggaman RA, et al Treatment of photoaged skin with topical tretinoin increases epidermal-dermal anchoring fibrils A preliminary report JAMA 1990;263:3057 Rosenthal DS, Griffiths CE, Yuspa SH, et al Acute or chronic topical retinoic acid treatment of human skin in vivo alters the expression of epidermal transglutaminase, loricrin, involucrin, filaggrin, and keratins 6 and 13 but not keratins 1, 10, and 14 J Invest Dermatol 1992;98:343 Griffiths CE, Finkel LJ, Tranfaglia MG, et al An in vivo experimental model for effects of topical retinoic acid in human skin Br J Dermatol 1993;129:389 Feng X, Peng ZH, Di W, et al Suprabasal expression of a dominant-negative RXR alpha mutant in transgenic mouse epidermis impairs regulation of gene transcription and basal keratinocyte proliferation by RAR-selective retinoids Genes Dev 1997;11:59 Kang S, Voorhees JJ Photoaging therapy with topical tretinoin: an evidencebased analysis J Am Acad Dermatol 1998;39:S55 Olsen EA, Katz HI, Levine N, et al Sustained improvement in photodamaged skin with reduced tretinoin emollient cream treatment regimen: effect of once-weekly and three-times-weekly applications J Am Acad Dermatol 1997;37:227 Tagami H, Tadaki T, Obata M, et al Functional assessment of the stratum corneum under the influence of oral aromatic retinoid (etretinate) in guineapigs and humans Comparison with topical retinoic acid treatment Br J Dermatol 1992;127:470 Effendy I, Kwangsukstith C, Lee LY, et al Functional changes in human stratum corneum induced by topical glycolic acid: comparison with all-trans retinoic acid Acta Derm Venereol 1995; 75:455 Griffiths CE, Voorhees JJ Human in vivo pharmacology of topical retinoids Arch Dermatol Res 1994;287:53 Buchan P, Eckhoff C, Caron D, et al Repeated topical administration of alltrans-retinoic acid and plasma levels of retinoic acids in humans J Am Acad Dermatol 1994;30:428
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32 Jick SS, Terris BZ, Jick H First trimester topical tretinoin and congenital disorders Lancet 1993;341:1181 33 Levin AA, Sturzenbecker LJ, Kazmer S, et al 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha Nature 1992;355:359 34 Kurlandsky SB, Xiao JH, Duell EA, et al Biological activity of all-trans retinol requires metabolic conversion to alltrans retinoic acid and is mediated through activation of nuclear retinoid receptors in human keratinocytes J Biol Chem 1994;269:32821 35 Kafi R, Kwak HS, Schumacher WE, et al Improvement of naturally aged skin with vitamin A (retinol) Arch Dermatol 2007;143:606 36 Kang S, Duell EA, Fisher GJ, et al Application of retinol to human skin in vivo induces epidermal hyperplasia and cellular retinoid binding proteins characteristic of retinoic acid but without measurable retinoic acid levels or irritation J Invest Dermatol 1995; 105:549 37 Duell EA, Kang S, Voorhees JJ Unoccluded retinol penetrates human skin in vivo more effectively than unoccluded retinyl palmitate or retinoic acid J Invest Dermatol 1997;109:301 38 Shalita A, Weiss JS, Chalker DK, et al A comparison of the efficacy and safety of adapalene gel 01% and tretinoin gel 0025% in the treatment of acne vulgaris: a multicenter trial J Am Acad Dermatol 1996;34:482 39 Chandraratna RA Tazarotene: the first receptor-selective topical retinoid for the treatment of psoriasis J Am Acad Dermatol 1997;37:S12 40 Burke BM, Cunliffe WJ The assessment of acne vulgaris the Leeds technique Br J Dermatol 1984;111:83 41 Verschoore M, Bouclier M, Czernielewski J, et al Topical retinoids Their uses in dermatology Dermatol Clin 1993;11:107 42 Verschoore M, Poncet M, Czernielewski J, et al Adapalene 01% gel has low skin-irritation potential J Am Acad Dermatol 1997;36:S104 43 Sefton J, Kligman AM, Kopper SC, et al Photodamage pilot study: a double-blind, vehicle-controlled study to assess the efficacy and safety of tazarotene 01% gel J Am Acad Dermatol 2000;43:656 44 Leyden J Split-face evaluation of the facial tolerability of tazarotene gel compared with tretinoin gels and adapalene gel Poster presented at the 58th Annual Meeting of the American Academy of Dermatology San Francisco, CA: March 10-15, 2000 45 Kakita L Tazarotene versus tretinoin or adapalene in the treatment of acne vulgaris J Am Acad Dermatol 2000;43:S51
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