• 1
    Yamauchi PS, Rizk D, Lowe NJ. Reti-noid therapy for psoriasis. Dermatol Clin 2004, 22: 467476.
  • 2
    Kunynetz RA. A review of systemic re-tinoid therapy for acne and related conditions. Skin Therapy Lett 2004; 9: 14.
  • 3
    Thielitz A, Krautheim A, Gollnick H. Update in retinoid therapy of acne. Dermatol Ther 2006; 9: 272279.
  • 4
    Penniston KL, Tanumihardjo SA. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr 2006; 83: 191201.
  • 5
    Geiger JM, Baudin M, Saurat JH. Tera-togenic risk with etretinate and acitre-tin treatment. Dermatology 1994; 189: 109116.
  • 6
    Wolbach SB, Howe PR. Tissue changes following deprivation of fat-soluble vitamin A. J Exp Med 1925; 47: 753777.
  • 7
    Frey JR, Schoch MA. Therapeutische Versuche bei Psoriasis mit Vitamin A, zugleich ein Beitrag zur A-Hypervita-minose. Dermatologica 1952; 104: 80.
  • 8
    Wiegand UW, Chou RC. Pharmacoki-netics of acitretin and etretinate. J Am Acad Dermatol 1998; 39: S25S33.
  • 9
    Millikan LE. Adapalene: an update on newer comparative studies between the various retinoids. Int J Dermatol 2000; 39: 784788.
  • 10
    Kakita L. Tazarotene versus tretinoin or adapalene in the treatment of acne vul-garis. J Am Acad Dermatol 2000; 43: S51S54.
  • 11
    Farol LT, Hymes KB. Bexarotene: a clinical review. Expert Rev Anticancer Ther 2004; 4: 180188.
  • 12
    Smit JV, Franssen ME, De Jong EM, Lambert J, Roseeuw DI, De Weert J, Yocum RC, Stevens VJ, Van De Kerk-hof PC. A phase II multicenter clinical trial of systemic bexarotene in psoriasis. J Am Acad Dermatol 2004; 51: 24956.
  • 13
    Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J 1996; 10: 940954.
  • 14
    Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 1992; 68: 397406.
  • 15
    Levin AA, Sturzenbecker LJ, Kazmer S, Bosakowski T, Huselton C, Allenby G, Speck J, Kratzeisen C, Rosenberger M, Lovey A, Grippo JF. 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRα. Nature 1992; 355: 359361.
  • 16
    Mangelsdorf DJ, Borgmeyer U, Hey-man RA, Zhou JY, Ong ES, Oro AE, Kakizuka A, Evans RM. Characterization of three RXR genes that mediate the action of 9-cis-retinoic acid. Genes Dev 1992; 6: 329344.
  • 17
    Allenby G, Bocquel M-T, Saunders M, Kazmer S, Speck J, Rosenberger M, Lovey A, Kastner P, Grippo JF, Cham-bon P, Levin AA. Retinoic acid receptors and retinoic X receptors: interactions with endogenous retinoic acids. Proc Natl Acad Sci USA 1993; 90: 3034.
  • 18
    Fogh K, Voorhees JJ, Aström A. Expression, purification and binding pro-perties of human cellular retinoic acid-binding protein type I and type II. Arch Biochem Biophys 1993; 300: 751755.
  • 19
    Mollard R, Viville S, Ward SJ, Decimo D, Chambon P, Dolle P. Tissue-specific expression of retinoic acid receptor iso-form transcripts in the mouse embryo. Mech Dev 2000; 94: 223232.
  • 20
    Giguere V. Retinoic acid receptors and cellular retinoid binding proteins: complex interplay in retinoid signaling. En-doc Rev 1994; 15: 6179.
  • 21
    Fisher GJ, Talwar HS, Xiao JH, Datta SC, Reddy AP, Gaub MP, Rochette-Egly C, Chambon P, Voorhees JJ. Immunological identification and functional quantification of retinoic and retinoid X receptor protein in human skin. J Biol Chem 1994; 269: 2062920635.
  • 22
    Xiao JH, Durand B, Chambon P, Voor-hees JJ. Endogenous retinoic acid receptor (RAR) – retinoid X-receptor (RXR) heterodimers are the major functional forms regulating retinoid-responsive elements in adult human kera-tinocytes. Binding of ligands to RAR only is sufficient for RAR-RXR hetero-dimers to confer ligand-dependent activation of hRAR beta 2/RARE (DR5). J Biol Chem 1995; 270: 30013011.
  • 23
    Moras D, Gronemeyer H. The nuclear receptor ligand-binding domain: structure and function. Curr Opin Cell Biol 1998; 10: 384391.
  • 24
    Balmer JE, Blomhoff R. Gene expression regulation by retinoic acid. J Lipid Res 2002; 43: 17731808.
  • 25
    Chawla A, Repa J, Evans RM, Man-gelsdorf DJ. Nuclear receptors and lipid physiology: opening the X-files. Science 2001; 294: 18661870.
  • 26
    McKenna NJ, Lanz RB, O’Malley BW. Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev 1999; 20: 321344.
  • 27
    Dilworth FJ, Chambon P. Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription. Oncogene 2001; 20: 30473054.
  • 28
    Gaub MP, Lutz Y, Ghyselinck NB, Scheuer I, Pfister V, Chambon P, Ro-chette-Egly C. Nuclear detection of cellular retinoic acid binding proteins I and II with new antibodies. J Histo-chem Cytochem 1998; 46: 11031111.
  • 29
    Ong DE. Cellular transport and metabolism of vitamin A: roles of the cellu-lar retinoid-binding proteins. Nutr Rev 1994; 52: S24S31.
  • 30
    Li E, Norris AW. Structure/function of cytoplasmic vitamin A-binding proteins. Ann Rev Nutr 1996; 16: 205234.
  • 31
    Noy N. Retinoid-binding proteins: mediators of retinoid action. Biochem J 2000; 348: 481495.
  • 32
    Lampron C, Rochette-Egly C, Gorry P, Dolle P, Mark M, Lufkin T, LeMeur M, Chambon P. Mice deficient in cellular retinoic acid binding protein II (CRABP II) or in both CRABP I and CRABP II are essentially normal. Development 1995; 121: 539548.
  • 33
    Olson JA. Provitamin A function of ca-rotenoids: the conversion of beta-carotene into vitamin A. J Nutr 1989; 119: 105108.
  • 34
    Blomhoff R, Green MH, Green JB, Berg T, Norum KR. Vitamin A metabolism: new perspectives on absorption, transport, and storage. Physiol Rev 1991; 71: 95190.
  • 35
    Kakkad BP, Ong DE. Reduction of re-tinaldehyde bound to cellular retinol-binding protein (type II) by microso-mes from rat small intestine. J Biol Chem 1988; 263: 1291612919.
  • 36
    Blomhoff R, Green MH, Berg T, Norum KR. Transport and storage of Vitamin A. Science 1990; 250: 399404.
  • 37
    Harrison EH, Hussain MM. Mechanisms involved in the intestinal digestion and absorption of dietary vitamin A. J Nutr 2001, 131: 14051408.
  • 38
    Blomhoff R. Transport and metabolism of vitamin A. Nutr Rev 1994; 52: S1323.
  • 39
    Blaner WS, Olson JA. Retinol and reti-noic acid metabolism. In The Reti-noids: Biology, Chemistry, and Medicine, 2nd edn. (SpornMB, RobertsAB, GoodmanDS. eds.). New York : Raven Press, 1994; 283318.
  • 40
    Ong DE. Cellular transport and metabolism of vitamin A: roles of the cellular retinoid-binding proteins. Nutr Rev 1994; 52: S24S31.
  • 41
    Vogel S, Gamble MV, Blaner WS. Biosynthesis, absorption, metabolism and transport of retinoids. In Retinoids: The Biochemical and Molecular Basis of Vitamin A and Retinoid Action (NauH, BlanerWS, eds), Vol.139. Berlin : Springer-Verlag, 1999; 3196.
  • 42
    Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, Wiita P, Bok D, Sun H. A Membrane Receptor for Reti-nol Binding Protein Mediates Cellular Uptake of Vitamin A. Science 2007; 315: 820825.
  • 43
    Napoli JL. Retinoic acid: its biosynthesis and metabolism. Prog Nucl Acid Res Mol Biol 1999; 6: 139188.
  • 44
    Noy N, Blaner WS. Interactions of reti-nol with binding proteins: studies with rat cellular retinol-binding protein and with rat retinol-binding protein. Biochemistry 1991; 30: 63806386.
  • 45
    White JA, Guo YD, Baetz K, Beckett-Jones B, Bonasoro J, Hsu KE, Dilworth FJ, Jones G, Petkovich M. M. Identification of the retinoic acid-inducible all-trans-retinoic acid 4-hydroxylase. J Biol Chem 1996; 271: 2992219927.
  • 46
    Fiorella PD, Napoli JL. Microsomal reti-noic acid metabolism. Effects of cellular retinoic acid-binding protein (Type 1) and C18-hydroxylation as an initial step. J Biol Chem 1994; 269: 1053810544.
  • 47
    Marill J, Capron CC, Idres N, Chabot GG. Human cytochrome P450s involved in the metabolism of 9-cis- and 13-cis-retinoic acids. Biochem Pharmacol 2002; 63: 933943.
  • 48
    White JA, Beckett-Jones B, Guo YD, Dilworth FJ, Bonasoro J, Jones G, Pet-kovich M. cDNA cloning of human re-tinoic acid-metabolizing enzyme (hP450RAI) identifies a novel family of cytochromes P450. J Biol Chem 1997; 272: 1853818541.
  • 49
    Ray WJ, Baion G, Yao M, Gottlieb DI. Cyp26, a novel mammalian cyto-chrome P450, is induced by retinoic acid and defines a new family. J Biol Chem 1997; 272: 1870218708.
  • 50
    Yamamoto Y, Zolfaghari R, Ross C. Regulation of CYP26 (cytochrome P450RAI) mRNA expression and reti-noic acid metabolism by retinoids and dietary vitamin A in liver of mice and rats. FASEB J 2000; 14: 21192127.
  • 51
    White JA, Ramshaw H, Taimi M, Stangle W, Zhang A, Everingham S, Creighton S, Tam SP, Jones G, Petko-vich M. Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism. Proc Natl Acad Sci USA 2000; 97: 64036408.
  • 52
    Nelson DR. A second CYP26 P450 in humans and zebrafish: CYP26B1. Arch Biochem Biophys 1999; 371: 345347.
  • 53
    MacLean G, Abu-Abed S, Dolle P, Ta-hayato A, Chambon P, Petkovich M. Cloning of a novel retinoic-acid metabolizing cytochrome P450, Cyp26B1, and comparative expression analysis with Cyp26A1 during early murine development. Mech Dev 2001; 107: 195201.
  • 54
    Zhu Z, Hotchkiss SA, Boobis AR, Edwards RJ. Expression of P450 enzymes in rat whole skin and cultured epider-mal keratinocytes. Biochem Biophys Res Commun 2002; 297: 6570.
  • 55
    Heise R, Mey J, Neis MM, Marquardt Y, Joussen S, Ott H, Wiederholt T, Kurschat P, Megahed M, Bickers DR, Merk HF, Baron JM. Skin Retinoid Concentrations Are Modulated by CYP26AI Expression Restricted to Basal Keratinocytes in Normal Human Skin and Differentiated 3D Skin Models. J Invest Dermatol 2006; 126: 24732480.
  • 56
    Duell EA, Astrom A, Griffiths CE, Chambon P, Voorhees JJ. Human skin levels of retinoic acid and cytochrome P-450-derived 4-hydroxyretinoic acid after topical application of retinoic acid in vivo compared to concentrations required to stimulate retinoic acid receptor-mediated transcription in vitro. J Clin Invest 1992; 90: 12691274.
  • 57
    Smith G, Wolf CR, Deeni YY, Dawe RS, Evans AT, Comrie MM, Ferguson J, Ibbotson SH. Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases. The Lancet 2003; 361: 13361343.
  • 58
    Rylander T, Neve EP, Ingelman-Sund-berg M, Oscarson M. Identification and tissue distribution of the novel human cytochrome P4502S1 (CYP2S1). Biochem Biophys Res Commun 2001; 281: 529535.
  • 59
    Buck J, Myc A, Garbe G, Cathomas G. Differences in the action and metabolism between retinol and retinoic acid in B lymphocytes. J Cell Biol 1991; 115: 851859.
  • 60
    Randolph RK, Simon M. Metabolism of all-trans-retinoic acid by cultured human epidermal keratinocytes. J Lipid Res 1997; 38: 13741383.
  • 61
    Zachman RD, Dunagin PE Jr, Olson JA. Formation and enterohepatic circulation of metabolites of retinol and reti-noic acid in bile duct-cannulated rats. J Lipid Res 1966; 7: 39.
  • 62
    Formelli F, Barua AB, Olson JA. Bioac-tivities of N-(4-hydroxyphenyl) retina-mide and retinoyl beta-glucuronide. FASEB J 1996; 10: 10141024.
  • 63
    Petkovich PM. Retinoic acid metabolism. J Am Acad Dermatol 2001; 45: S136S142.
  • 64
    Van Wauwe JP, Coene MC, Goossens J, Van Nijen G, Cools W, Lauwers W. Ketoconazole inhibits the in vitro and in vivo metabolism of all-trans- retinoic acid. J Pharmacol Exp Ther 1988; 245: 718722.
  • 65
    Van Wauwe J, Coene MC, Goossens J, Cools W, Mombaliu J. Effects of cyto-chrome P-450 inhibition on the in vivo metabolism of all-trans-retinoic acid in rats. J Pharmacol Exp Ther 1990; 252: 365369.
  • 66
    Van Wauwe J, Van Nyen G, Coene MC, Stoppie P, Cools W, Goosens J, Borghgraef P, Janssen PA. Liarozole, an inhibitor of retinoic acid metabolism, exerts retinoid-mimetic effects in vivo. J Pharmacol Exp Ther 1992; 261: 773778.
  • 67
    Kang S, Duell E, Kim K, Voorhees JJ. Liarozole inhibits human epidermal re-tinoic acid 4-hydroxylase activity and differentially augments human skin responses to retinoic acid and retinol in vivo. J Invest Dermatol 1996; 107: 183187.
  • 68
    Huynh CK, Brodie AM, Njar VC. Inhibitory effects of retinoic acid metabolism blocking agents (RAMBAs) on the growth of human prostate cancer cells and LNCaP prostate tumour xeno-grafts in SCID mice. Br J Cancer 2006; 94: 513523.
  • 69
    Vanden Bossche H, Willemsens G, Janssen PAJ. Cytochrome P450- dependent metabolism of retinoic acid in rat skin microsomes: inhibition by ke-toconazole. Skin Pharmacol 1988; 1: 176185.
  • 70
    De Coster R, Wouters W, Van Ginckel R, End D, Krekels M, Coene MC, Bo-wden C. Experimental studies with li-arozole (R75251): an antitumoral agent which inhibits retinoic acid breakdown. J Steroid Biochem Mol Biol 1992; 43: 197201.
  • 71
    Bryson HM, Wagstaff AJ. Liarozole. Drugs Aging 1996; 9: 478484.
  • 72
    Stoppie P, Borgers M, Borghgraef P, Dil-len L, Goossens J, Sanz G, Szel H, Van Hove C, Van Nyen G, Nobels G, Van-den Bossche H, Venet M, Willemsen G, Van Wauwe J. R115866 inhibits all-trans-retinoic acid metabolism and exerts retinoidal effects in rodents. J Pharmacol Exp Ther 2000; 293: 304312.
  • 73
    Rambazole™ (R115866) Investigational Drug Brochure; version 3.0.; Oct. 2005. Data on file at Barrier Therapeutics.
  • 74
    Stoppie P, Van Wauwe J, Wouters L, Borgers M. Rambazole™, a potent inhibitor of all-trans-retinoic acid metabolism, applied topically to mouse tail skin exerts retinoid mimetic activity. J Invest Dermatol 2004; 122: A70 (#420).
  • 75
    Cools M, Stoppie P, Cauwenbergh G, Vanhoutte F, Vandeplassche L. Tolerability, safety and pharmacokinetics of single and multiple oral dosages of R115866 (Rambazole™) in healthy volunteers. Presented at Eur Acad Der-matol & Venereol 2006, Rhodos, P035.22.
  • 76
    Verfaille CJ, Thissen CACB, Boven-schen HJ, Mertens J, Steijlen PM, Van De Kerkhof PCM. Oral R115866 in the treatment of moderate to severe plaque-type psoriasis. JEADV 2007, in press.
  • 77
    Dockx P, Decree J, Degreef H. Inhibition of the metabolism of endogenous retinoic acid as treatment for severe psoriasis: an open study with oral liaro-zole. Br J Dermatol 1995; 133: 426432.
  • 78
    Berth-Jones J, Todd G, Hutchinson P, Thestrup-Pedersen K, Vanhoutte FP. Treatment of psoriasis with oral liaro-zole: a dose-ranging study. Br J Derma-tol 2000; 143: 11701176.
  • 79
    Bhushan M, Burden AD, McElhone K, James R, Vanhoutte FP, Griffiths CEM. Oral liarozole in the treatment of palmoplantar pustular psoriasis: a randomized, double-blind, placebo-controlled study. Br J Dermatol 2001; 145: 54653.
  • 80
    Vandeplassche G, Beger B, Staszak J, Petit L, Blockhuys S. Long-term safety of oral liarozole, a new retinoic acid metabolism blocking agent. J Eur Acad Dermatol Venereol 2005; 19 (Suppl. 2): FC13.14.
  • 81
    Vandeplassche G, Verfaille CJ, Beger B, Wouters L, Snoeck E, Cauwenbergh G. Safety of oral liarozole in subjects with ichthyosis or psoriasis. J Eur Acad Der-matol Venereol 2004; 18 (Suppl. 2): 395396.
  • 82
    Lucker GPH, Heremans AMC, Boeg-heim PJ, Van De Kerkhof PCM, Steijlen PM. Oral treatment of ichthyosis by the cytochrome P-450 inhibitor liaro-zole. Br J Dermatol 1997; 136: 7175.
  • 83
    Verfaille CJ, Vanhoutte FP, Blanchet-Bardon C, Van Steensel MA, Steijlen PM. Oral liarozole vs. acitretin in the treatment of ichthyosis: a phase II/III multicentre, double-blind, randomized, active-controlled study. Br J Der-matol 2007; 156: 965973.
  • 84
    Lucker G, Verfaille CJ, Heremans A, Vanhoutte FP, Boegheim JP, Steijlen PM. Topical liarozole in ichthyosis: a double-blind, left-right comparative study followed by a long-term open maintenance study. Br J Dermatol 2005; 152: 566569.
  • 85
    Vahlquist C, Selinus I, Vessby B. Serum lipids changes during acitretin (etretin) treatment of psoriasis and palmo-plan-tar pustulosis. Acta Derm Venereol 1988; 6: 300305.
  • 86
    Piskin S, Gurkok F, Ekuklu G, Senol M. Serum lipids in psoriasis. Yonsei Med J 2003; 44: 2426.
  • 87
    Mallbris L, Granath F, Hamsten A, Ståhle M. Psoriasis is associated with lipid abnormalities at the onset of skin disease. J Am Acad Dermatol 2006; 54: 614620.
  • 88
    Bovenschen HJ, Otero ME, Langew-outers AM, Van Vlijmen-Willems IMJJ, Van Rens DWA, Seyger MMB, Van De Kerkhof PCM. Oral retinoic acid metabolism blocking agent ramba-zole for plaque psoriasis: an immunohi-stochemical study. Br J Dermatol 2007; 156: 263270.
  • 89
    Cools M, Pavez-Lorie E, Borgers M, Cauwenbergh G, Vandeplassche L, Wouters L, Torma H, Vahlquist A. Effect of topical R115866 (Rambazo-le™) gel on the expression of biomar-kers in the skin of healthy volunteers. J Invest Dermatol 2006; 126: S40 (#240).
  • 90
    Verfaille CJ, Coel M, Boersma IH, Mertens J, Borgers M, Roseeuw. Oral R115866 in the treatment of moderate to severe facial acne vulgaris: an exploratory study. Br J Dermatol 2007; 157: 122126.