Skin Cancer Prevention

  • Maria Lluria-PrevattEmail author
  • Sally E. Dickinson
  • David S. Alberts


Skin cancer is the most common form of cancer, accounting for 40–50% of all cancers diagnosed in the United States (Sample and He, Photodermatol Photoimmunol Photomed 34:13–24, 2017) and the incidence continues to increase worldwide. In 2012, the estimated occurrence for nonmelanoma skin cancers (NMSC) was 5.4 million cases among 3.3 million people and the American Cancer Society estimates that 99,550 cases of other skin cancer, primarily melanoma, will occur in 2018 leading to 9320 deaths from melanoma (2018). While the incidence of the majority of cancers is currently declining, the epidemic of skin cancer continues (Lazovich et al., Cancer Epidemiol Biomark Prev 21:1893–1901, 2012). With the continuing rise in incidence, there is an extensive impact of morbidity and health care costs. The estimated annual health care cost for treating skin cancer exceeds $8.1 billion demonstrating a 126% rise in cost from 2006 to 2011 while other cancers increased by 25.1% (Jemal et al., J Am Acad Dermatol 65:S17–25.e11–13, 2011; Guy et al., Am J Prev Med 48:183–187, 2015).


Signaling pathways Chemoprevention Skin cancer Topical drug formulations Enhanced program cell death Ultraviolet light-induced DNA damage Melanoma Nonmelanoma skin cancer Skin types I and II Karyometric analysis of sun damage 


  1. Abe Y, Matsumoto S, Kito K, Ueda N (2000) Cloning and expression of a novel MAPKK-like protein kinase, lymphokine-activated killer T-cell-originated protein kinase, specifically expressed in the testis and activated lymphoid cells. J Biol Chem 275(28):21525–21531PubMedCrossRefPubMedCentralGoogle Scholar
  2. Abe Y, Takeuchi T, Kagawa-Miki L, Ueda N, Shigemoto K, Yasukawa M, Kito K (2007) A mitotic kinase TOPK enhances Cdk1/cyclin B1-dependent phosphorylation of PRC1 and promotes cytokinesis. J Mol Biol 370(2):231–245PubMedCrossRefPubMedCentralGoogle Scholar
  3. Adhami VM, Aziz MH, Mukhtar H, Ahmad N (2003) Activation of prodeath Bcl-2 family proteins and mitochondrial apoptosis pathway by sanguinarine in immortalized human HaCaT keratinocytes. Clin Cancer Res 9(8):3176–3182PubMedPubMedCentralGoogle Scholar
  4. Afaq F, Adhami VM, Mukhtar H (2005) Photochemoprevention of ultraviolet B signaling and photocarcinogenesis. Mutat Res 571(1–2):153–173PubMedCrossRefPubMedCentralGoogle Scholar
  5. Agarwala SS, di Pietro A, Flaherty KT, Garbe C, Grob JJ, Kashani-Sabet M, Kirkwood JM, Leachman S, Messina J, O’Day S, Ribas A, Sondak V (2010) Meeting report from the Third Global Workshop on Melanoma. Pigment Cell Melanoma Res 23(5):e1–e7PubMedCrossRefPubMedCentralGoogle Scholar
  6. Ahsan H, Reagan-Shaw S, Eggert DM, Tan TC, Afaq F, Mukhtar H, Ahmad N (2007) Protective effect of sanguinarine on ultraviolet B-mediated damages in SKH-1 hairless mouse skin: implications for prevention of skin cancer. Photochem Photobiol 83(4):986–993PubMedCrossRefPubMedCentralGoogle Scholar
  7. Albanell J, Rojo F, Averbuch S, Feyereislova A, Mascaro JM, Herbst R, LoRusso P, Rischin D, Sauleda S, Gee J, Nicholson RI, Baselga J (2002) Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. J Clin Oncol 20(1):110–124PubMedCrossRefPubMedCentralGoogle Scholar
  8. Alberts DS, Dorr RT, Einspahr JG, Aickin M, Saboda K, Xu MJ, Peng YM, Goldman R, Foote JA, Warneke JA, Salasche S, Roe DJ, Bowden GT (2000) Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine. Cancer Epidemiol Biomark Prev 9(12):1281–1286Google Scholar
  9. Alberts D, Ranger-Moore J, Einspahr J, Saboda K, Bozzo P, Liu Y, Xu XC, Lotan R, Warneke J, Salasche S, Stratton S, Levine N, Goldman R, Islas M, Duckett L, Thompson D, Bartels P, Foote J (2004) Safety and efficacy of dose-intensive oral vitamin A in subjects with sun-damaged skin.[Erratum appears in Clin Cancer Res. 2004 Aug 15;10(16):5640]. Clin Cancer Res 10(6):1875–1880PubMedCrossRefPubMedCentralGoogle Scholar
  10. Almahroos M, Kurban AK (2004) Ultraviolet carcinogenesis in nonmelanoma skin cancer. Part I: incidence rates in relation to geographic locations and in migrant populations. Skinmed 3(1):29–35; quiz 35-26PubMedCrossRefPubMedCentralGoogle Scholar
  11. Altieri DC (2001) The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med 7(12):542–547PubMedCrossRefPubMedCentralGoogle Scholar
  12. Altieri DC (2003) Validating survivin as a cancer therapeutic target. Nat Rev Cancer 3(1):46–54PubMedCrossRefPubMedCentralGoogle Scholar
  13. Altieri DC, Marchisio PC (1999) Survivin apoptosis: an interloper between cell death and cell proliferation in cancer. Lab Investig 79(11):1327–1333PubMedPubMedCentralGoogle Scholar
  14. An KP, Athar M, Tang X, Katiyar SK, Russo J, Beech J, Aszterbaum M, Kopelovich L, Epstein EH Jr, Mukhtar H, Bickers DR (2002) Cyclooxygenase-2 expression in murine and human nonmelanoma skin cancers: implications for therapeutic approaches. Photochem Photobiol 76(1):73–80PubMedCrossRefPubMedCentralGoogle Scholar
  15. Angel P, Hattori K, Smeal T, Karin M (1988) The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell 55(5):875–885PubMedCrossRefPubMedCentralGoogle Scholar
  16. Ascenso A, Pedrosa T, Pinho S, Pinho F, de Oliveira JM, Cabral Marques H, Oliveira H, Simoes S, Santos C (2016) The effect of lycopene preexposure on UV-B-irradiated human keratinocytes. Oxidative Med Cell Longev 2016:8214631CrossRefGoogle Scholar
  17. Asgari MM, Brasky TM, White E (2012) Association of vitamin A and carotenoid intake with melanoma risk in a large prospective cohort. J Investig Dermatol 132(6):1573–1582PubMedCrossRefPubMedCentralGoogle Scholar
  18. Aszterbaum M, Rothman A (1998) Identification of mutation in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome. J Invest Dermatol 110(6):885–888PubMedCrossRefPubMedCentralGoogle Scholar
  19. Auger KR, Serunian LA, Soltoff SP, Libby P, Cantley LC (1989) PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells. Cell 57(1):167–175PubMedCrossRefPubMedCentralGoogle Scholar
  20. Ayllon V, O’Connor R (2007) PBK/TOPK promotes tumour cell proliferation through p38 MAPK activity and regulation of the DNA damage response. Oncogene 26(24):3451–3461PubMedCrossRefPubMedCentralGoogle Scholar
  21. Aziz MH, Kumar R, Ahmad N (2003) Cancer chemoprevention by resveratrol: in vitro and in vivo studies and the underlying mechanisms (review). Int J Oncol 23(1):17–28PubMedPubMedCentralGoogle Scholar
  22. Aziz MH, Reagan-Shaw S, Wu J, Longley BJ, Ahmad N (2005) Chemoprevention of skin cancer by grape constituent resveratrol: relevance to human disease?.[Erratum appears in FASEB J. 2005 Jul;19(9):1 p following 1195]. FASEB J 19(9):1193–1195PubMedCrossRefPubMedCentralGoogle Scholar
  23. Bachelor MA, Bowden GT (2004a) Ultraviolet A-induced modulation of Bcl-XL by p38 MAPK in human keratinocytes: post-transcriptional regulation through the 3′-untranslated region. J Biol Chem 279(41):42658–42668PubMedCrossRefPubMedCentralGoogle Scholar
  24. Bachelor MA, Bowden GT (2004b) UVA-mediated activation of signaling pathways involved in skin tumor promotion and progression. Semin Cancer Biol 14(2):131–138PubMedCrossRefPubMedCentralGoogle Scholar
  25. Bachelor MA, Cooper SJ, Sikorski ET, Bowden GT (2005) Inhibition of p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase decreases UVB-induced activator protein-1 and cyclooxygenase-2 in a SKH-1 hairless mouse model. Mol Cancer Res 3(2):90–99PubMedCrossRefPubMedCentralGoogle Scholar
  26. Bair WB 3rd, Hart N, Einspahr J, Liu G, Dong Z, Alberts D, Bowden GT (2002) Inhibitory effects of sodium salicylate and acetylsalicylic acid on UVB-induced mouse skin carcinogenesis. Cancer Epidemiol Biomark Prev 11(12):1645–1652Google Scholar
  27. Baldi A, Santini D, Battista T, Dragonetti E, Ferranti G, Petitti T, Groeger AM, Angelini A, Rossiello R, Baldi F, Natali PG, Paggi MG (2001) Expression of AP-2 transcription factor and of its downstream target genes c-kit, E-cadherin and p21 in human cutaneous melanoma. J Cell Biochem 83(3):364–372PubMedCrossRefPubMedCentralGoogle Scholar
  28. Bartels PH, Ranger-Moore J, Stratton MS, Bozzo P, Einspahr J, Liu Y, Thompson D, Alberts DS (2002) Statistical analysis of chemopreventive efficacy of vitamin A in sun-exposed, normal skin. Anal Quant Cytol Histol 24(4):185–197PubMedPubMedCentralGoogle Scholar
  29. Barthelman M, Bair WB 3rd, Stickland KK, Chen W, Timmermann BN, Valcic S, Dong Z, Bowden GT (1998a) (-)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity. Carcinogenesis 19(12):2201–2204PubMedCrossRefPubMedCentralGoogle Scholar
  30. Barthelman M, Chen W, Gensler HL, Huang C, Dong Z, Bowden GT (1998b) Inhibitory effects of perillyl alcohol on UVB-induced murine skin cancer and AP-1 transactivation. Cancer Res 58(4):711–716PubMedPubMedCentralGoogle Scholar
  31. Barton JK, Gossage KW, Xu W, Ranger-Moore JR, Saboda K, Brooks CA, Duckett LD, Salasche SJ, Warneke JA, Alberts DS (2003) Investigating sun-damaged skin and actinic keratosis with optical coherence tomography: a pilot study. Technol Cancer Res Treat 2(6):525–535PubMedCrossRefPubMedCentralGoogle Scholar
  32. Basset-Seguin N, Escot C, Blanchard JM, Kerai C, Verrier B, Mion H, Guilhou JJ (1990) High levels of c-fos proto-oncogene expression in normal human adult skin. J Invest Dermatol 94(4):418–422PubMedCrossRefPubMedCentralGoogle Scholar
  33. Bastiaens MT, ter Huurne JA, Kielich C, Gruis NA, Westendorp RG, Vermeer BJ, Bavinck JN (2001) Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair. Am J Hum Genet 68(4):884–894PubMedPubMedCentralCrossRefGoogle Scholar
  34. Bedogni B, O’Neill MS, Welford SM, Bouley DM, Giaccia AJ, Denko NC, Powell MB (2004) Topical treatment with inhibitors of the phosphatidylinositol 3′-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways reduces melanoma development in severe combined immunodeficient mice. Cancer Res 64(7):2552–2560PubMedCrossRefPubMedCentralGoogle Scholar
  35. Bedogni B, Welford SM, Kwan AC, Ranger-Moore J, Saboda K, Powell MB (2006) Inhibition of phosphatidylinositol-3-kinase and mitogen-activated protein kinase kinase 1/2 prevents melanoma development and promotes melanoma regression in the transgenic TPRas mouse model. Mol Cancer Ther 5(12):3071–3077PubMedCrossRefPubMedCentralGoogle Scholar
  36. Bennett BL, Sasaki DT, Murray BW, O’Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM, Anderson DW (2001) SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci U S A 98(24):13681–13686PubMedPubMedCentralCrossRefGoogle Scholar
  37. Berman B, Ricotti CA Jr, Cazzaniga A, Davis SC (2004) Determination of the area of skin capable of being covered by the application of 250 mg of 5% imiquimod cream. Dermatol Surg 30(5):784–786PubMedPubMedCentralGoogle Scholar
  38. Berton TR, Mitchell DL, Fischer SM, Locniskar MF (1997) Epidermal proliferation but not quantity of DNA photodamage is correlated with UV-induced mouse skin carcinogenesis. J Investig Dermatol 109(3):340–347PubMedCrossRefPubMedCentralGoogle Scholar
  39. Bibbo M, Bartels PH, Galera-Davidson H, Dytch HE, Wied GL (1986) Markers for malignancy in the nuclear texture of histologically normal tissue from patients with thyroid tumors. Anal Quant Cytol Histol 8(2):168–176PubMedPubMedCentralGoogle Scholar
  40. Bibbo M, Michelassi F, Bartels PH, Dytch H, Bania C, Lerma E, Montag AG (1990) Karyometric marker features in normal-appearing glands adjacent to human colonic adenocarcinoma. Cancer Res 50(1):147–151PubMedPubMedCentralGoogle Scholar
  41. Birt DF, Mitchell D, Gold B, Pour P, Pinch HC (1997) Inhibition of ultraviolet light induced skin carcinogenesis in SKH-1 mice by apigenin, a plant flavonoid. Anticancer Res 17(1a):85–91PubMedPubMedCentralGoogle Scholar
  42. Bishop DT, Demenais F, Goldstein AM, Bergman W, Bishop JN, Bressac-de Paillerets B, Chompret A, Ghiorzo P, Gruis N, Hansson J, Harland M, Hayward N, Holland EA, Mann GJ, Mantelli M, Nancarrow D, Platz A, Tucker MA, Melanoma Genetics C (2002) Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst 94(12):894–903PubMedCrossRefPubMedCentralGoogle Scholar
  43. Bjornhagen V, Bonfoco E, Brahme EM, Lindholm J, Auer G (1994) Morphometric, DNA, and proliferating cell nuclear antigen measurements in benign melanocytic lesions and cutaneous malignant melanoma. Am J Dermatopathol 16(6):615–623PubMedCrossRefPubMedCentralGoogle Scholar
  44. Bode AM, Dong Z (2004) Targeting signal transduction pathways by chemopreventive agents. Muta Res 555(1-2):33–51PubMedCrossRefPubMedCentralGoogle Scholar
  45. Bode AM, Dong Z (2011) The two faces of capsaicin. Cancer Res 71(8):2809–2814PubMedCrossRefPubMedCentralGoogle Scholar
  46. Bordbar A, Dias D, Cabral A, Beck S, Boon ME (2007) Assessment of cell proliferation in benign, premalignant and malignant skin lesions. Appl Immunohistochem Mol Morphol 15(2):229–235PubMedCrossRefPubMedCentralGoogle Scholar
  47. Borland R, Marks R, Noy S (1992) Public knowledge about characteristics of moles and melanomas. Aust J Public Health 16(4):370–375PubMedCrossRefPubMedCentralGoogle Scholar
  48. Bowden GT (2004) Prevention of non-melanoma skin cancer by targeting ultraviolet-B-light signalling. Nat Rev Cancer 4(1):23–35PubMedCrossRefPubMedCentralGoogle Scholar
  49. Box NF, Wyeth JR, O’Gorman LE, Martin NG, Sturm RA (1997) Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair. Hum Mol Genet 6(11):1891–1897PubMedCrossRefPubMedCentralGoogle Scholar
  50. Bozzo PD, Vaught LC, Alberts DS, Thompson D, Bartels PH (1998) Nuclear morphometry in solar keratosis. Anal Quant Cytol Histol 20(1):21–28PubMedPubMedCentralGoogle Scholar
  51. Bozzo P, Alberts DS, Vaught L, da Silva VD, Thompson D, Warnecke J, Miller RC, Einspahr J, Bartels PH (2001) Measurement of chemopreventive efficacy in skin biopsies. Anal Quant Cytol Histol 23(4):300–312PubMedPubMedCentralGoogle Scholar
  52. Brash DE, Rudolph JA, Simon JA, Lin A, McKenna GJ, Baden HP, Halperin AJ, Ponten J (1991) A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci U S A 88(22):10124–10128PubMedPubMedCentralCrossRefGoogle Scholar
  53. Bregman MD, Meyskens FL Jr (1986) Difluoromethylornithine enhances inhibition of melanoma cell growth in soft agar by dexamethasone, clone A interferon and retinoic acid. Int J Cancer 37(1):101–107PubMedCrossRefPubMedCentralGoogle Scholar
  54. Broome Powell M, Gause PR, Hyman P, Gregus J, Lluria-Prevatt M, Nagle R, Bowden GT (1999) Induction of melanoma in TPras transgenic mice. Carcinogenesis 20(9):1747–1753PubMedCrossRefPubMedCentralGoogle Scholar
  55. Brunssen A, Waldmann A, Eisemann N, Katalinic A (2016) Impact of skin cancer screening and secondary prevention campaigns on skin cancer incidence and mortality: a systematic review. J Am Acad Dermatol 76(1):129–139.e110PubMedCrossRefPubMedCentralGoogle Scholar
  56. Buchwald H (1992) Cholesterol inhibition, cancer, and chemotherapy. Lancet 339(8802):1154–1156PubMedCrossRefPubMedCentralGoogle Scholar
  57. Buckman SY, Gresham A, Hale P, Hruza G, Anast J, Masferrer J, Pentland AP (1998) COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer. Carcinogenesis 19(5):723–729PubMedCrossRefPubMedCentralGoogle Scholar
  58. Budden T, Davey RJ, Vilain RE, Ashton KA, Braye SG, Beveridge NJ, Bowden NA (2016) Repair of UVB-induced DNA damage is reduced in melanoma due to low XPC and global genome repair. Oncotarget 7(38):60940–60953PubMedPubMedCentralCrossRefGoogle Scholar
  59. Burren R, Scaletta C, Frenk E, Panizzon RG, Applegate LA (1998) Sunlight and carcinogenesis: expression of p53 and pyrimidine dimers in human skin following UVA I, UVA I + II and solar simulating radiations. Int J Cancer 76(2):201–206PubMedCrossRefPubMedCentralGoogle Scholar
  60. Bush JA, Cheung KJ Jr, Li G (2001) Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53. Exp Cell Res 271(2):305–314PubMedCrossRefPubMedCentralGoogle Scholar
  61. Callen J (2000) Statement on actinic keratosis. J Am Acad Dermatol 42(1Part 2):1CrossRefGoogle Scholar
  62. CDC (2012) Sunburn and sun protective behaviors among adults aged 19-29 years-Unites States, 2000-2010. MMWR Morb Mortal Wkly Rep 61:317–322Google Scholar
  63. Challacombe JM, Suhrbier A, Parsons PG, Jones B, Hampson P, Kavanagh D, Rainger GE, Morris M, Lord JM, Le TT, Hoang-Le D, Ogbourne SM (2006) Neutrophils are a key component of the antitumor efficacy of topical chemotherapy with ingenol-3-angelate. J Immunol 177(11):8123–8132PubMedCrossRefPubMedCentralGoogle Scholar
  64. Chen W, Bowden GT (1999) Activation of p38 MAP kinase and ERK are required for ultraviolet-B induced c-fos gene expression in human keratinocytes. Oncogene 18(52):7469–7476PubMedCrossRefPubMedCentralGoogle Scholar
  65. Chen W, Bowden GT (2000) Role of p38 mitogen-activated protein kinases in ultraviolet-B irradiation-induced activator protein 1 activation in human keratinocytes. Mol Carcinog 28(4):196–202PubMedCrossRefPubMedCentralGoogle Scholar
  66. Chen W, Borchers AH, Dong Z, Powell MB, Bowden GT (1998) UVB irradiation-induced activator protein-1 activation correlates with increased c-fos gene expression in a human keratinocyte cell line. J Biol Chem 273(48):32176–32181PubMedCrossRefPubMedCentralGoogle Scholar
  67. Chen N, Nomura M, She QB, Ma WY, Bode AM, Wang L, Flavell RA, Dong Z (2001a) Suppression of skin tumorigenesis in c-Jun NH(2)-terminal kinase-2-deficient mice. Cancer Res 61(10):3908–3912PubMedPubMedCentralGoogle Scholar
  68. Chen W, Tang Q, Gonzales MS, Bowden GT (2001b) Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes. Oncogene 20(29):3921–3926PubMedCrossRefPubMedCentralGoogle Scholar
  69. Chen TC, Lee SA, Hong TM, Shih JY, Lai JM, Chiou HY, Yang SC, Chan CH, Kao CY, Yang PC, Huang CY (2009) From midbody protein-protein interaction network construction to novel regulators in cytokinesis. J Proteome Res 8(11):4943–4953PubMedCrossRefPubMedCentralGoogle Scholar
  70. Chin L, Garraway LA, Fisher DE (2006) Malignant melanoma: genetics and therapeutics in the genomic era. Genes Dev 20(16):2149–2182PubMedCrossRefPubMedCentralGoogle Scholar
  71. Choi K, Lazovich D, Southwell BG, Forster J, Rolnick S, Jackson J (2010) Prevalence and characteristics of indoor tanning use among men and women in the United States. Arch Dermatol 146(12):1356–1361PubMedCrossRefPubMedCentralGoogle Scholar
  72. Chun KS, Kundu J, Kundu JK, Surh YJ (2014) Targeting Nrf2-Keap1 signaling for chemoprevention of skin carcinogenesis with bioactive phytochemicals. Toxicol Lett 229(1):73–84PubMedCrossRefPubMedCentralGoogle Scholar
  73. Clark LC, Combs GF et al (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. National Prevention of Cancer Study Group. JAMA 276:1957–1963PubMedCrossRefPubMedCentralGoogle Scholar
  74. Cohen C, Zavala-Pompa A, Sequeira JH, Shoji M, Sexton DG, Cotsonis G, Cerimele F, Govindarajan B, Macaron N, Arbiser JL (2002) Mitogen-activated protein kinase activation is an early event in melanoma progression. Clin Cancer Res 8(12):3728–3733Google Scholar
  75. Coso OA, Chiariello M, Kalinec G, Kyriakis JM, Woodgett J, Gutkind JS (1995) Transforming G protein-coupled receptors potently activate JNK (SAPK). Evidence for a divergence from the tyrosine kinase signaling pathway. J Biol Chem 270(10):5620–5624PubMedCrossRefPubMedCentralGoogle Scholar
  76. Craythorne E, Al-Niami F (2017) Skin cancer. Medicine 45(7):431–434CrossRefGoogle Scholar
  77. Crowell PL (1999) Prevention and therapy of cancer by dietary monoterpenes. J Nutr 129(3):775s–778sPubMedCrossRefPubMedCentralGoogle Scholar
  78. Cummins DL, Cummins JM, Pantle H, Silverman MA, Leonard AL, Chanmugam A (2006) Cutaneous malignant melanoma. Mayo Clin Proc 81(4):500–507PubMedCrossRefPubMedCentralGoogle Scholar
  79. Curran T, Franza BR Jr (1988) Fos and Jun: the AP-1 connection. Cell 55(3):395–397PubMedCrossRefPubMedCentralGoogle Scholar
  80. CWG, I. A. R (2006) The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: a systematic review. Int J Cancer 120:1116–1122Google Scholar
  81. Dahle J, Brunborg G, Svendsrud DH, Stokke T, Kvam E (2008) Overexpression of human OGG1 in mammalian cells decreases ultraviolet A induced mutagenesis. Cancer Lett 267(1):18–25PubMedCrossRefPubMedCentralGoogle Scholar
  82. Davies MA, Stemke-Hale K, Tellez C, Calderone TL, Deng W, Prieto VG, Lazar AJ, Gershenwald JE, Mills GB (2008) A novel AKT3 mutation in melanoma tumours and cell lines. Br J Cancer 99(8):1265–1268PubMedPubMedCentralCrossRefGoogle Scholar
  83. De Fabo EC, Noonan FP, Fears T, Merlino G (2004) Ultraviolet B but not ultraviolet A radiation initiates melanoma. Cancer Res 64(18):6372–6376PubMedCrossRefPubMedCentralGoogle Scholar
  84. de Gruijl FR (2000) Photocarcinogenesis: UVA vs UVB. Methods Enzymol 319:359–366PubMedCrossRefPubMedCentralGoogle Scholar
  85. Del Rosso JQ (2003) New and emerging topical approaches for actinic keratoses. Cutis 72(4):273–276, 279PubMedPubMedCentralGoogle Scholar
  86. Dellavalle RP, Nicholas MK, Schilling LM (2003) Melanoma chemoprevention: a role for statins or fibrates? Am J Ther 10(3):203–210PubMedCrossRefPubMedCentralGoogle Scholar
  87. Demetriou SK, Ona-Vu K, Teichert AE, Cleaver JE, Bikle DD, Oh DH (2012) Vitamin D receptor mediates DNA repair and is UV inducible in intact epidermis but not in cultured keratinocytes. J Investig Dermatol 132(8):2097–2100PubMedCrossRefPubMedCentralGoogle Scholar
  88. Denkert C, Kobel M, Berger S, Siegert A, Leclere A, Trefzer U, Hauptmann S (2001) Expression of cyclooxygenase 2 in human malignant melanoma. Cancer Res 61(1):303–308PubMedPubMedCentralGoogle Scholar
  89. Derijard B, Hibi M, Wu IH, Barrett T, Su B, Deng T, Karin M, Davis RJ (1994) JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76(6):1025–1037PubMedCrossRefPubMedCentralGoogle Scholar
  90. Dickinson SE, Melton TF, Olson ER, Zhang J, Saboda K, Bowden GT (2009) Inhibition of activator protein-1 by sulforaphane involves interaction with cysteine in the cFos DNA-binding domain: implications for chemoprevention of UVB-induced skin cancer. Cancer Res 69(17):7103–7110PubMedPubMedCentralCrossRefGoogle Scholar
  91. Dickinson SE, Olson ER, Zhang J, Cooper SJ, Melton T, Criswell PJ, Casanova A, Dong Z, Hu C, Saboda K, Jacobs ET, Alberts DS, Bowden GT (2011) p38 MAP kinase plays a functional role in UVB-induced mouse skin carcinogenesis. Mol Carcinog 50(6):469–478PubMedPubMedCentralCrossRefGoogle Scholar
  92. Diepgen TL, Mahler V (2002) The epidemiology of skin cancer. Br J Dermatol 146(Suppl 61):1–6PubMedCrossRefPubMedCentralGoogle Scholar
  93. Dinehart SM (2000) The treatment of actinic keratoses. J Am Acad Dermatol 42(1 Pt 2):25–28PubMedCrossRefPubMedCentralGoogle Scholar
  94. Dinehart SM, Nelson-Adesokan P, Cockerell C, Russell S, Brown R (1997) Metastatic cutaneous squamous cell carcinoma derived from actinic keratosis. Cancer 79(5):920–923PubMedCrossRefPubMedCentralGoogle Scholar
  95. Dinkova-Kostova AT, Jenkins SN, Fahey JW, Ye L, Wehage SL, Liby KT, Stephenson KK, Wade KL, Talalay P (2006) Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts. Cancer Lett 240(2):243–252CrossRefGoogle Scholar
  96. Dissanayake NS, Greenoak GE, Mason RS (1993) Effects of ultraviolet irradiation on human skin-derived epidermal cells in vitro. J Cell Physiol 157(1):119–127PubMedCrossRefPubMedCentralGoogle Scholar
  97. Domann FE, Levy JP, Birrer MJ, Bowden GT (1994) Stable expression of a c-JUN deletion mutant in two malignant mouse epidermal cell lines blocks tumor formation in nude mice. Cell Growth Differ 5(1):9–16PubMedPubMedCentralGoogle Scholar
  98. Dong Z, Birrer MJ, Watts RG, Matrisian LM, Colburn NH (1994) Blocking of tumor promoter-induced AP-1 activity inhibits induced transformation in JB6 mouse epidermal cells. Proc Natl Acad Sci U S A 91(2):609–613PubMedPubMedCentralCrossRefGoogle Scholar
  99. Dong Z, Huang C, Ma WY, Malewicz B, Baumann WJ, Kiss Z (1998) Increased synthesis of phosphocholine is required for UV-induced AP-1 activation. Oncogene 17(14):1845–1853PubMedCrossRefPubMedCentralGoogle Scholar
  100. Dorr RT, Dvorakova K et al (2000) Increased eumelanin expression and tanning is induced by a superpotent melanotropin [Nle4 D Phe7] alpha MSH in humans. Photochem Photobiol 72(4):526–532PubMedCrossRefPubMedCentralGoogle Scholar
  101. Dorr RT, Ertl G, Levine N, Brooks C, Bangert JL, Powell MB, Humphrey S, Alberts DS (2004) Effects of a superpotent melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers. Arch Dermatol 140(7):827–835CrossRefGoogle Scholar
  102. Downes CP, Carter AN (1991) Phosphoinositide 3-kinase: a new effector in signal transduction? Cell Signal 3(6):501–513PubMedCrossRefPubMedCentralGoogle Scholar
  103. Dracopoli NC, Bruns GA, Brodeur GM, Landes GM, Matise TC, Seldin MF, Vance JM, Weith A (1994) Report and abstracts of the First International Workshop on Human Chromosome 1 Mapping 1994. Bethesda, Maryland, March 25-27, 1994. Cytogen Cell Genet 67(3):144–165CrossRefGoogle Scholar
  104. Drane P, Compe E, Catez P, Chymkowitch P, Egly JM (2004) Selective regulation of vitamin D receptor-responsive genes by TFIIH. Mol Cell 16(2):187–197PubMedCrossRefPubMedCentralGoogle Scholar
  105. Dutton-Regester K, Hayward NK (2012) Reviewing the somatic genetics of melanoma: from current to future analytical approaches. Pigment Cell Melanoma Res 25(2):144–154PubMedCrossRefPubMedCentralGoogle Scholar
  106. Dvorakova K, Dorr RT, Valcic S, Timmermann B, Alberts DS (1999) Pharmacokinetics of the green tea derivative, EGCG, by the topical route of administration in mouse and human skin. Cancer Chemother Pharmacol 43(4):331–335PubMedCrossRefPubMedCentralGoogle Scholar
  107. Einspahr J, Alberts DS, Aickin M, Welch K, Bozzo P, Levine N, Grogan T (1996) Evaluation of proliferating cell nuclear antigen as a surrogate end point biomarker in actinic keratosis and adjacent, normal-appearing, and non-sun-exposed human skin samples. Cancer Epidemiol Biomark Prev 5(5):343–348Google Scholar
  108. Einspahr JG, Alberts DS, Gapstur SM, Bostick RM, Emerson SS, Gerner EW (1997) Surrogate end-point biomarkers as measures of colon cancer risk and their use in cancer chemoprevention trials. Cancer Epidemiol Biomark Prev 6(1):37–48Google Scholar
  109. Einspahr JG, Alberts DS, Warneke JA, Bozzo P, Basye J, Grogan TM, Nelson MA, Bowden GT (1999) Relationship of p53 mutations to epidermal cell proliferation and apoptosis in human UV-induced skin carcinogenesis. Neoplasia 1(5):468–475PubMedPubMedCentralCrossRefGoogle Scholar
  110. Einspahr JG, Nelson MA, Saboda K, Warneke J, Bowden GT, Alberts DS (2002) Modulation of biologic endpoints by topical difluoromethylornithine (DFMO), in subjects at high-risk for nonmelanoma skin cancer. Clin Cancer Res 8(1):149–155PubMedPubMedCentralGoogle Scholar
  111. Einspahr JG, Bowden GT, Alberts DS (2003) Skin cancer chemoprevention: strategies to save our skin. Recent Results Cancer Res 163:151–164; discussion 264-156PubMedCrossRefPubMedCentralGoogle Scholar
  112. Einspahr JG, Xu MJ, Warneke J, Saboda K, Ranger-Moore J, Bozzo P, Duckett L, Goldman R, Lin P, Buckmeier J, Alberts DS (2006) Reproducibility and expression of skin biomarkers in sun-damaged skin and actinic keratoses. Cancer Epidemiol Biomark Prev 15(10):1841–1848CrossRefGoogle Scholar
  113. Einspahr JG, Calvert V, Alberts DS, Curiel-Lewandrowski C, Warneke J, Krouse R, Stratton SP, Liotta L, Longo C, Pellacani G, Prasad A, Sagerman P, Bermudez Y, Deng J, Bowden GT, Petricoin EF 3rd (2012) Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma. Cancer Prev Res (Phila) 5(3):403–413CrossRefGoogle Scholar
  114. Elder DE (2010) Dysplastic naevi: an update. Histopathology 56(1):112–120PubMedCrossRefPubMedCentralGoogle Scholar
  115. Elmets CA, Viner JL, Pentland AP, Cantrell W, Lin HY, Bailey H, Kang S, Linden KG, Heffernan M, Duvic M, Richmond E, Elewski BE, Umar A, Bell W, Gordon GB (2010) Chemoprevention of nonmelanoma skin cancer with celecoxib: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst 102(24):1835–1844PubMedPubMedCentralCrossRefGoogle Scholar
  116. English DR, Armstrong BK, Kricker A, Winter MG, Heenan PJ, Randell PL (1998) Demographic characteristics, pigmentary and cutaneous risk factors for squamous cell carcinoma of the skin: a case-control study. Int J Cancer 76(5):628–634PubMedCrossRefPubMedCentralGoogle Scholar
  117. Erlendsson AM (2017) Exploring the use of ingenol mebutate to prevent non-melanoma skin cancer. Dan Med J 64(11)Google Scholar
  118. Facchin S, Ruzzene M, Peggion C, Sartori G, Carignani G, Marin O, Brustolon F, Lopreiato R, Pinna LA (2007) Phosphorylation and activation of the atypical kinase p53-related protein kinase (PRPK) by Akt/PKB. Cell Mol Life Sci 64(19–20):2680–2689PubMedCrossRefPubMedCentralGoogle Scholar
  119. Farber MJ, Heilman ER, Friedman RJ (2012) Dysplastic nevi. Dermatol Clin 30(3):389–404PubMedCrossRefPubMedCentralGoogle Scholar
  120. Fazekas Z, Gao D, Saladi RN, Lu Y, Lebwohl M, Wei H (2003) Protective effects of lycopene against ultraviolet B-induced photodamage. Nutr Cancer 47(2):181–187PubMedCrossRefPubMedCentralGoogle Scholar
  121. Fercher AF, Mengedoht K, Werner W (1988) Eye-length measurement by interferometry with partially coherent light. Opt Lett 13(3):186–188PubMedCrossRefPubMedCentralGoogle Scholar
  122. Fernandes NV, Guntipalli PK, Mo H (2010) d-delta-Tocotrienol-mediated cell cycle arrest and apoptosis in human melanoma cells. Anticancer Res 30(12):4937–4944PubMedPubMedCentralGoogle Scholar
  123. Fischer SM, Lo HH, Gordon GB, Seibert K, Kelloff G, Lubet RA, Conti CJ (1999) Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis. Mol Carcinog 25(4):231–240PubMedCrossRefPubMedCentralGoogle Scholar
  124. Fisher GJ, Voorhees JJ (1998) Molecular mechanisms of photoaging and its prevention by retinoic acid: ultraviolet irradiation induces MAP kinase signal transduction cascades that induce Ap-1-regulated matrix metalloproteinases that degrade human skin in vivo. J Investig Dermatol Symp Proc 3(1):61–68PubMedPubMedCentralGoogle Scholar
  125. Fisher C, Byers MR, Iadarola MJ, Powers EA (1991) Patterns of epithelial expression of Fos protein suggest important role in the transition from viable to cornified cell during keratinization. Development 111(2):253–258PubMedPubMedCentralGoogle Scholar
  126. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90(18):1371–1388PubMedPubMedCentralCrossRefGoogle Scholar
  127. Fitzgerald LM, Fryer JL, Dwyer T, Humphrey SM (2006) Effect of MELANOTAN, [Nle(4), D-Phe(7)]-alpha-MSH, on melanin synthesis in humans with MC1R variant alleles. Peptides 27(2):388–394PubMedCrossRefPubMedCentralGoogle Scholar
  128. Flach J, Antoni I, Villemin P, Bentzen CL, Niesor EJ (2000) The mevalonate/isoprenoid pathway inhibitor apomine (SR-45023A) is antiproliferative and induces apoptosis similar to farnesol. Biochem Biophys Res Commun 270(1):240–246PubMedCrossRefPubMedCentralGoogle Scholar
  129. Foote JA, Harris RB, Giuliano AR, Roe DJ, Moon TE, Cartmel B, Alberts DS (2001) Predictors for cutaneous basal- and squamous-cell carcinoma among actinically damaged adults. Int J Cancer 95(1):7–11PubMedPubMedCentralCrossRefGoogle Scholar
  130. Frankel DH, Hanusa BH, Zitelli JA (1992) New primary nonmelanoma skin cancer in patients with a history of squamous cell carcinoma of the skin. Implications and recommendations for follow-up. J Am Acad Dermatol 26(5 Pt 1):720–726PubMedCrossRefPubMedCentralGoogle Scholar
  131. Fransen M, Karahalios A, Sharma N, English DR, Giles GG, Sinclair RD (2012) Non-melanoma skin cancer in Australia. Med J Aust 197(10):565–568PubMedCrossRefPubMedCentralGoogle Scholar
  132. Fry DW, Kraker AJ, McMichael A, Ambroso LA, Nelson JM, Leopold WR, Connors RW, Bridges AJ (1994) A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. Science 265(5175):1093–1095PubMedCrossRefPubMedCentralGoogle Scholar
  133. Funasaka Y, Boulton T, Cobb M, Yarden Y, Fan B, Lyman SD, Williams DE, Anderson DM, Zakut R, Mishima Y et al (1992) c-Kit-kinase induces a cascade of protein tyrosine phosphorylation in normal human melanocytes in response to mast cell growth factor and stimulates mitogen-activated protein kinase but is down-regulated in melanomas. Mol Biol Cell 3(2):197–209PubMedPubMedCentralCrossRefGoogle Scholar
  134. Gallagher TF, Seibel GL, Kassis S, Laydon JT, Blumenthal MJ, Lee JC, Lee D, Boehm JC, Fier-Thompson SM, Abt JW, Soreson ME, Smietana JM, Hall RF, Garigipati RS, Bender PE, Erhard KF, Krog AJ, Hofmann GA, Sheldrake PL, McDonnell PC, Kumar S, Young PR, Adams JL (1997) Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase. Bioorg Med Chem 5(1):49–64PubMedCrossRefPubMedCentralGoogle Scholar
  135. Gao G, Zhang T, Wang Q, Reddy K, Chen H, Yao K, Wang K, Roh E, Zykova T, Ma W, Ryu J, Curiel-Lewandrowski C, Alberts D, Dickinson SE, Bode AM, Xing Y, Dong Z (2017) ADA-07 suppresses solar ultraviolet-induced skin carcinogenesis by directly inhibiting TOPK. Mol Cancer Ther 16(9):1843–1854PubMedPubMedCentralCrossRefGoogle Scholar
  136. Gause PR, Lluria-Prevatt M, Keith WN, Balmain A, Linardopolous S, Warneke J, Powell MB (1997) Chromosomal and genetic alterations of 7,12-dimethylbenz[a]anthracene-induced melanoma from TP-ras transgenic mice. Mol Carcinog 20(1):78–87PubMedCrossRefPubMedCentralGoogle Scholar
  137. Gazit A, Chen J, App H, McMahon G, Hirth P, Chen I, Levitzki A (1996) Tyrphostins IV--highly potent inhibitors of EGF receptor kinase. Structure-activity relationship study of 4-anilidoquinazolines. Bioorg Med Chem 4(8):1203–1207PubMedCrossRefPubMedCentralGoogle Scholar
  138. Geilen CC, Wieprecht M, Orfanos CE (1996) The mitogen-activated protein kinases system (MAP kinase cascade): its role in skin signal transduction. A review. J Dermatol Sci 12(3):255–262PubMedCrossRefPubMedCentralGoogle Scholar
  139. Geller AC, Colditz G, Oliveria S, Emmons K, Jorgensen C, Aweh GN, Frazier AL (2002) Use of sunscreen, sunburning rates, and tanning bed use among more than 10 000 US children and adolescents. Pediatrics 109(6):1009–1014PubMedCrossRefPubMedCentralGoogle Scholar
  140. Gensler HL (1991) Prevention by alpha-difluoromethylornithine of skin carcinogenesis and immunosuppression induced by ultraviolet irradiation. J Cancer Res Clin Oncol 117(4):345–350PubMedCrossRefPubMedCentralGoogle Scholar
  141. Gerber B, Mathys P, Moser M, Bressoud D, Braun-Fahrlander C (2002) Ultraviolet emission spectra of sunbeds. Photochem Photobiol 76(6):664–668PubMedCrossRefPubMedCentralGoogle Scholar
  142. Ghosh S, Xie WQ, Quest AF, Mabrouk GM, Strum JC, Bell RM (1994) The cysteine-rich region of raf-1 kinase contains zinc, translocates to liposomes, and is adjacent to a segment that binds GTP-ras. J Biol Chem 269(13):10000–10007PubMedPubMedCentralGoogle Scholar
  143. Gianpaolo-Ostravage C, Bankston D (2001) Anti-tumor efficacy of the orally active Raf kinase inhibitor BAY 43–9006 in human tumor xenograft models. Proc Am Assoc Cancer ResGoogle Scholar
  144. Gilchrest BA, Eller MS, Geller AC, Yaar M (1999) The pathogenesis of melanoma induced by ultraviolet radiation. N Engl J Med 340(17):1341–1348PubMedCrossRefPubMedCentralGoogle Scholar
  145. Gillardon F, Eschenfelder C, Uhlmann E, Hartschuh W, Zimmermann M (1994) Differential regulation of c-fos, fosB, c-jun, junB, bcl-2 and bax expression in rat skin following single or chronic ultraviolet irradiation and in vivo modulation by antisense oligodeoxynucleotide superfusion. Oncogene 9(11):3219–3225PubMedPubMedCentralGoogle Scholar
  146. Gills JJ, Jeffery EH, Matusheski NV, Moon RC, Lantvit DD, Pezzuto JM (2006) Sulforaphane prevents mouse skin tumorigenesis during the stage of promotion. Cancer Lett 236(1):72–79PubMedCrossRefPubMedCentralGoogle Scholar
  147. Glazer ES, Bartels PH, Prasad AR, Yozwiak ML, Bartels HG, Einspahr JG, Alberts DS, Krouse RS (2011) Nuclear morphometry identifies a distinct aggressive cellular phenotype in cutaneous squamous cell carcinoma. Cancer Prev Res (Phila) 4(11):1770–1777CrossRefGoogle Scholar
  148. Glogau RG (2000) The risk of progression to invasive disease. J Am Acad Dermatol 42(1 Pt 2):23–24PubMedCrossRefPubMedCentralGoogle Scholar
  149. Goldstein AM, Tucker MA (2001) Genetic epidemiology of cutaneous melanoma: a global perspective. Arch Dermatol 137(11):1493–1496PubMedCrossRefPubMedCentralGoogle Scholar
  150. Gonzales M, Bowden GT (2002) Nordihydroguaiaretic acid-mediated inhibition of ultraviolet B-induced activator protein-1 activation in human keratinocytes. Mol Carcinog 34(2):102–111PubMedCrossRefPubMedCentralGoogle Scholar
  151. Gordon-Thomson C, Gupta R, Tongkao-on W, Ryan A, Halliday GM, Mason RS (2012) 1alpha,25 dihydroxyvitamin D3 enhances cellular defences against UV-induced oxidative and other forms of DNA damage in skin. Photochem Photobiol Sci 11(12):1837–1847PubMedPubMedCentralCrossRefGoogle Scholar
  152. Gould MN, Moore CJ, Zhang R, Wang B, Kennan WS, Haag JD (1994) Limonene chemoprevention of mammary carcinoma induction following direct in situ transfer of v-Ha-ras. Cancer Res 54(13):3540–3543PubMedPubMedCentralGoogle Scholar
  153. Goulet AC, Einsphar JG, Alberts DS, Beas A, Burk C, Bhattacharyya A, Bangert J, Harmon JM, Fujiwara H, Koki A, Nelson MA (2003) Analysis of cyclooxygenase 2 (COX-2) expression during malignant melanoma progression. Cancer Biol Ther 2(6):713–718PubMedCrossRefPubMedCentralGoogle Scholar
  154. Greenberg ER, Baron JA et al (1990) A clinical trial of beta carotene to prevent basal cell and squamous cell cancers of the skin. N. Eng J Med 323:789–795CrossRefGoogle Scholar
  155. Greene MH (1997) Genetics of cutaneous melanoma and nevi. Mayo Clin Proc 72(5):467–474PubMedCrossRefPubMedCentralGoogle Scholar
  156. Greene MH, Clark WH Jr, Tucker MA, Elder DE, Kraemer KH, Guerry DT, Witmer WK, Thompson J, Matozzo I, Fraser MC (1985a) Acquired precursors of cutaneous malignant melanoma. The familial dysplastic nevus syndrome. N Engl J Med 312(2):91–97PubMedCrossRefPubMedCentralGoogle Scholar
  157. Greene MH, Clark WH Jr, Tucker MA, Kraemer KH, Elder DE, Fraser MC (1985b) High risk of malignant melanoma in melanoma-prone families with dysplastic nevi. Ann Intern Med 102(4):458–465PubMedCrossRefPubMedCentralGoogle Scholar
  158. Grimes PE, Hamzavi I, Lebwohl M, Ortonne JP, Lim HW (2013) The efficacy of afamelanotide and narrowband UV-B phototherapy for repigmentation of vitiligo. JAMA Dermatol 149(1):68–73PubMedCrossRefGoogle Scholar
  159. Grossman D, Kim PJ, Schechner JS, Altieri DC (2001) Inhibition of melanoma tumor growth in vivo by survivin targeting. Proc Natl Acad Sci U S A 98(2):635–640PubMedPubMedCentralCrossRefGoogle Scholar
  160. Gudas LJ (1994) Retinoids and vertebrate development. J Biol Chem 269(22):15399–15402PubMedPubMedCentralGoogle Scholar
  161. Gupta A, Myrdal PB (2004) Development of a perillyl alcohol topical cream formulation. Int J Pharm 269(2):373–383PubMedCrossRefPubMedCentralGoogle Scholar
  162. Gupta AK, Cherman AM, Tyring SK (2004) Viral and nonviral uses of imiquimod: a review. J Cutan Med Surg 8(5):338–352PubMedCrossRefGoogle Scholar
  163. Guy GP Jr, Machlin SR, Ekwueme DU, Yabroff KR (2015) Prevalence and costs of skin cancer treatment in the U.S., 2002-2006 and 2007-2011. Am J Prev Med 48(2):183–187PubMedCrossRefGoogle Scholar
  164. Haag JD, Gould MN (1994) Mammary carcinoma regression induced by perillyl alcohol, a hydroxylated analog of limonene. Cancer Chemother Pharmacol 34(6):477–483PubMedCrossRefGoogle Scholar
  165. Haake AR, Polakowska RR (1993) Cell death by apoptosis in epidermal biology. J Invest Dermatol 101(2):107–112PubMedCrossRefPubMedCentralGoogle Scholar
  166. Hacker E, Irwin N, Muller HK, Powell MB, Kay G, Hayward N, Walker G (2005) Neonatal ultraviolet radiation exposure is critical for malignant melanoma induction in pigmented Tpras transgenic mice. J Invest Dermatol 125(5):1074–1077PubMedCrossRefGoogle Scholar
  167. Hacker E, Muller HK, Irwin N, Gabrielli B, Lincoln D, Pavey S, Powell MB, Malumbres M, Barbacid M, Hayward N, Walker G (2006) Spontaneous and UV radiation-induced multiple metastatic melanomas in Cdk4R24C/R24C/TPras mice. Cancer Res 66(6):2946–2952PubMedCrossRefPubMedCentralGoogle Scholar
  168. Hadley ME, Dorr RT (2006) Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization. Peptides 27(4):921–930PubMedCrossRefPubMedCentralGoogle Scholar
  169. Halaban R, Fan B, Ahn J, Funasaka Y, Gitay-Goren H, Neufeld G (1992) Growth factors, receptor kinases, and protein tyrosine phosphatases in normal and malignant melanocytes. J Immunother 12(3):154–161PubMedCrossRefPubMedCentralGoogle Scholar
  170. Halachmi S, Gilchrest BA (2001) Update on genetic events in the pathogenesis of melanoma. Curr Opin Oncol 13(2):129–136PubMedCrossRefPubMedCentralGoogle Scholar
  171. Hall PA, Levison DA, Woods AL, Yu CC, Kellock DB, Watkins JA, Barnes DM, Gillett CE, Camplejohn R, Dover R et al (1990) Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol 162(4):285–294PubMedCrossRefPubMedCentralGoogle Scholar
  172. Haluska FG, Hodi FS (1998) Molecular genetics of familial cutaneous melanoma. J Clin Oncol 16(2):670–682PubMedCrossRefPubMedCentralGoogle Scholar
  173. Hampson P, Kavanagh D, Smith E, Wang K, Lord JM, Ed Rainger G (2008) The anti-tumor agent, ingenol-3-angelate (PEP005), promotes the recruitment of cytotoxic neutrophils by activation of vascular endothelial cells in a PKC-delta dependent manner. Cancer Immunol Immunother 57(8):1241–1251PubMedCrossRefGoogle Scholar
  174. Han Z, Boyle DL, Chang L, Bennett B, Karin M, Yang L, Manning AM, Firestein GS (2001) c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 108(1):73–81PubMedPubMedCentralCrossRefGoogle Scholar
  175. Handler MZ, Bloom BS, Goldberg DJ (2017) Clinical and histologic evaluation of ingenol mebutate 0.015% gel for the cosmetic improvement of photoaged skin. Dermatol Surg 44(1):61–67CrossRefGoogle Scholar
  176. Hanke CW, Berman B, Swanson N, Pariser DM, Weiss JS, Bukhalo M, Skov T, Villumsen J, Siegel D (2017) Safety and efficacy of escalating doses of ingenol mebutate for field treatment of actinic keratosis on the full face, full balding scalp, or chest. J Drugs Dermatol 16(5):438–444PubMedGoogle Scholar
  177. Harris RB, Griffith K, Moon TE (2001a) Trends in the incidence of nonmelanoma skin cancers in southeastern Arizona, 1985-1996. J Am Acad Dermatol 45(4):528–536PubMedCrossRefGoogle Scholar
  178. Harris RE, Beebe-Donk J, Namboodiri KK (2001b) Inverse association of non-steroidal anti-inflammatory drugs and malignant melanoma among women. Oncol Rep 8(3):655–657PubMedGoogle Scholar
  179. He F, Yan Q, Fan L, Liu Y, Cui J, Wang J, Wang L, Wang Y, Wang Z, Guo Y, Huang G (2010) PBK/TOPK in the differential diagnosis of cholangiocarcinoma from hepatocellular carcinoma and its involvement in prognosis of human cholangiocarcinoma. Hum Pathol 41(3):415–424PubMedCrossRefGoogle Scholar
  180. Healy E, Flannagan N, Ray A, Todd C, Jackson IJ, Matthews JN, Birch-Machin MA, Rees JL (2000) Melanocortin-1-receptor gene and sun sensitivity in individuals without red hair. Lancet 355(9209):1072–1073PubMedCrossRefPubMedCentralGoogle Scholar
  181. Herbert JL, Khugyani F et al (2001) Chemoprevention of basal cell carcinoma in the ptc1 +/- mouse-green and black tea. Skin Pharmacol Appl Skin Physiol 14(6):358–362CrossRefGoogle Scholar
  182. Herlyn M, Satyamoorthy K (1996) Activated ras. Yet another player in melanoma? Am J Pathol 149(3):739–744PubMedPubMedCentralGoogle Scholar
  183. Hery C, Tryggvadottir L, Sigurdsson T, Olafsdottir E, Sigurgeirsson B, Jonasson JG, Olafsson JH, Boniol M, Byrnes GB, Dore JF, Autier P (2010) A melanoma epidemic in Iceland: possible influence of sunbed use. Am J Epidemiol 172(7):762–767PubMedCrossRefPubMedCentralGoogle Scholar
  184. Hill CS, Treisman R (1995) Transcriptional regulation by extracellular signals: mechanisms and specificity. Cell 80(2):199–211PubMedCrossRefPubMedCentralGoogle Scholar
  185. Hohl RJ, Lewis K (1995) Differential effects of monoterpenes and lovastatin on RAS processing. J Biol Chem 270(29):17508–17512PubMedCrossRefPubMedCentralGoogle Scholar
  186. Hu F, Gartenhaus RB, Eichberg D, Liu Z, Fang HB, Rapoport AP (2010) PBK/TOPK interacts with the DBD domain of tumor suppressor p53 and modulates expression of transcriptional targets including p21. Oncogene 29(40):5464–5474PubMedCrossRefPubMedCentralGoogle Scholar
  187. Huang C, Ma W, Ding M, Bowden GT, Dong Z (1997a) Direct evidence for an important role of sphingomyelinase in ultraviolet-induced activation of c-Jun N-terminal kinase. J Biol Chem 272(44):27753–27757PubMedCrossRefPubMedCentralGoogle Scholar
  188. Huang C, Ma WY, Hecht SS, Dong Z (1997b) Inositol hexaphosphate inhibits cell transformation and activator protein 1 activation by targeting phosphatidylinositol-3′ kinase. Cancer Res 57(14):2873–2878PubMedPubMedCentralGoogle Scholar
  189. Huang C, Ma WY, Ryan CA, Dong Z (1997c) Proteinase inhibitors I and II from potatoes specifically block UV-induced activator protein-1 activation through a pathway that is independent of extracellular signal-regulated kinases, c-Jun N-terminal kinases, and P38 kinase. Proc Natl Acad Sci U S A 94(22):11957–11962PubMedPubMedCentralCrossRefGoogle Scholar
  190. Huang C, Li J, Chen N, Ma W, Bowden GT, Dong Z (2000) Inhibition of atypical PKC blocks ultraviolet-induced AP-1 activation by specifically inhibiting ERKs activation. Mol Carcinog 27(2):65–75PubMedCrossRefPubMedCentralGoogle Scholar
  191. Hunter T (1997) Oncoprotein networks. Cell 88(3):333–346PubMedCrossRefPubMedCentralGoogle Scholar
  192. Hussussian CJ, Struewing JP, Goldstein AM, Higgins PA, Ally DS, Sheahan MD, Clark WH Jr, Tucker MA, Dracopoli NC (1994) Germline p16 mutations in familial melanoma. Nat Genet 8(1):15–21PubMedCrossRefPubMedCentralGoogle Scholar
  193. Hwang MK, Bode AM, Byun S, Song NR, Lee HJ, Lee KW, Dong Z (2010) Cocarcinogenic effect of capsaicin involves activation of EGFR signaling but not TRPV1. Cancer Res 70(17):6859–6869PubMedCrossRefPubMedCentralGoogle Scholar
  194. Ibuki Y, Allanson M, Dixon KM, Reeve VE (2007) Radiation sources providing increased UVA/UVB ratios attenuate the apoptotic effects of the UVB waveband UVA-dose-dependently in hairless mouse skin. J Invest Dermatol 127(9):2236–2244PubMedCrossRefPubMedCentralGoogle Scholar
  195. International Medical News Group (2002). Nonmelanoma skin cancer new solutions to treatments. Suppl Skin Allergy NewsGoogle Scholar
  196. Iotzova-Weiss G, Freiberger SN, Johansen P, Kamarachev J, Guenova E, Dziunycz PJ, Roux GA, Neu J, Hofbauer GFL (2017) TLR4 as a negative regulator of keratinocyte proliferation. PLoS One 12(10):e0185668PubMedPubMedCentralCrossRefGoogle Scholar
  197. Irinopoulou T, Rigaut JP, Benson MC (1993) Toward objective prognostic grading of prostatic carcinoma using image analysis. Anal Quant Cytol Histol 15(5):341–344PubMedPubMedCentralGoogle Scholar
  198. Ishibashi M, Arai M, Tanaka S, Onda K, Hirano T (2012) Antiproliferative and apoptosis-inducing effects of lipophilic vitamins on human melanoma A375 cells in vitro. Biol Pharm Bull 35(1):10–17PubMedCrossRefPubMedCentralGoogle Scholar
  199. Ja B, Li G (2003) The role of Bcl-2 family members in the progression of cutaneous melanoma. Clin Exp Metastasis 20(6):531–539CrossRefGoogle Scholar
  200. Jain N, Rademaker A, Robinson JK (2012) Implementation of the federal excise tax on indoor tanning services in Illinois. Arch Dermatol 148(1):122–124PubMedCrossRefPubMedCentralGoogle Scholar
  201. Janda J, Burkett NB, Blohm-Mangone K, Huang V, Curiel-Lewandrowski C, Alberts DS, Petricoin EF 3rd, Calvert VS, Einspahr J, Dong Z, Bode AM, Wondrak GT, Dickinson SE (2016) Resatorvid-based pharmacological antagonism of cutaneous TLR4 blocks UV-induced NF-kappaB and AP-1 signaling in keratinocytes and mouse skin. Photochem Photobiol 92(6):816–825PubMedPubMedCentralCrossRefGoogle Scholar
  202. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275(5297):218–220CrossRefGoogle Scholar
  203. Jansen B, Wacheck V, Heere-Ress E, Schlagbauer-Wadl H, Hoeller C, Lucas T, Hoermann M, Hollenstein U, Wolff K, Pehamberger H (2000) Chemosensitisation of malignant melanoma by BCL2 antisense therapy. Lancet 356(9243):1728–1733PubMedCrossRefPubMedCentralGoogle Scholar
  204. Jemal A, Saraiya M, Patel P, Cherala SS, Barnholtz-Sloan J, Kim J, Wiggins CL, Wingo PA (2011) Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992-2006. J Am Acad Dermatol 65(5 Suppl 1):S17–25.e11-13PubMedPubMedCentralGoogle Scholar
  205. John PR, Ramsay M (2002) Four novel variants in MC1R in red-haired South African individuals of European descent: S83P, Y152X, A171D, P256S. Hum Mutat 19(4):461–462PubMedCrossRefPubMedCentralGoogle Scholar
  206. Juge N, Mithen RF, Traka M (2007) Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci 64(9):1105–1127PubMedCrossRefPubMedCentralGoogle Scholar
  207. Kabuyama Y, Hamaya M, Homma Y (1998) Wavelength specific activation of PI 3-kinase by UVB irradiation. FEBS Lett 441(2):297–301PubMedCrossRefPubMedCentralGoogle Scholar
  208. Kallunki T, Su B, Tsigelny I, Sluss HK, Derijard B, Moore G, Davis R, Karin M (1994) JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation. Genes Dev 8(24):2996–3007PubMedCrossRefPubMedCentralGoogle Scholar
  209. Kamb A, Shattuck-Eidens D, Eeles R, Liu Q, Gruis NA, Ding W, Hussey C, Tran T, Miki Y, Weaver-Feldhaus J et al (1994) Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet 8(1):23–26PubMedCrossRefPubMedCentralGoogle Scholar
  210. Kapadia GJ, Azuine MA, Tokuda H, Takasaki M, Mukainaka T, Konoshima T, Nishino H (2002) Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis. Pharmacol Res 45(6):499–505PubMedCrossRefPubMedCentralGoogle Scholar
  211. Kedei N, Lundberg DJ, Toth A, Welburn P, Garfield SH, Blumberg PM (2004) Characterization of the interaction of ingenol 3-angelate with protein kinase C. Cancer Res 64(9):3243–3255PubMedCrossRefPubMedCentralGoogle Scholar
  212. Kennedy C, ter Huurne J, Berkhout M, Gruis N, Bastiaens M, Bergman W, Willemze R, Bavinck JN (2001) Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color. J Invest Dermatol 117(2):294–300PubMedCrossRefPubMedCentralGoogle Scholar
  213. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26(4):239–257PubMedPubMedCentralCrossRefGoogle Scholar
  214. Khan AQ, Travers JB, Kemp MG (2018) Roles of UVA radiation and DNA damage responses in melanoma pathogenesis. Environ Mol Mutagen 21:21Google Scholar
  215. Kim DJ, Li Y, Reddy K, Lee MH, Kim MO, Cho YY, Lee SY, Kim JE, Bode AM, Dong Z (2012) Novel TOPK inhibitor HI-TOPK-032 effectively suppresses colon cancer growth. Cancer Res 72(12):3060–3068PubMedCrossRefPubMedCentralGoogle Scholar
  216. Koh HK, Geller AC, Miller DR, Grossbart TA, Lew RA (1996) Prevention and early detection strategies for melanoma and skin cancer. Current status. Arch Dermatol 132(4):436–443PubMedCrossRefPubMedCentralGoogle Scholar
  217. Kolch W, Heidecker G, Kochs G, Hummel R, Vahidi H, Mischak H, Finkenzeller G, Marme D, Rapp UR (1993) Protein kinase C alpha activates RAF-1 by direct phosphorylation. Nature 364(6434):249–252PubMedCrossRefPubMedCentralGoogle Scholar
  218. Konig H, Ponta H, Rahmsdorf HJ, Herrlich P (1992) Interference between pathway-specific transcription factors: glucocorticoids antagonize phorbol ester-induced AP-1 activity without altering AP-1 site occupation in vivo. EMBO J 11(6):2241–2246PubMedPubMedCentralCrossRefGoogle Scholar
  219. Kopp P (1998) Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the ‘French paradox’? Eur J Endocrinol 138(6):619–620PubMedCrossRefPubMedCentralGoogle Scholar
  220. Kuehl PJ, Angersbach BS, Stratton SP, Myrdal PB (2006) Development of an HPLC method for the analysis of Apomine in a topical cream formulation. J Pharm Biomed Anal 40(4):975–980PubMedCrossRefPubMedCentralGoogle Scholar
  221. Kuo WT, Lee TC, Yu LC (2016) Eritoran suppresses colon cancer by altering a functional balance in toll-like receptors that bind lipopolysaccharide. Cancer Res 76(16):4684–4695PubMedCrossRefPubMedCentralGoogle Scholar
  222. Lahti JM, Xiang J, Kidd VJ (1995) The PITSLRE protein kinase family. Prog Cell Cycle Res 1:329–338PubMedCrossRefPubMedCentralGoogle Scholar
  223. Lambert JD, Meyers RO, Timmermann BN, Dorr RT (2001) tetra-O-methylnordihydroguaiaretic acid inhibits melanoma in vivo. Cancer Lett 171(1):47–56PubMedCrossRefPubMedCentralGoogle Scholar
  224. Larsen HK, Banzhaf CA, Thomsen SF, Gormsen M, Schopf RE, Haedersdal M (2017) An exploratory, prospective, open-label trial of ingenol mebutate gel 0.05% for the treatment of external anogenital warts. J Eur Acad Dermatol VenereolGoogle Scholar
  225. Lazovich D, Vogel RI, Berwick M, Weinstock MA, Anderson KE, Warshaw EM (2010) Indoor tanning and risk of melanoma: a case-control study in a highly exposed population. Cancer Epidemiol Biomark Prev 19(6):1557–1568CrossRefGoogle Scholar
  226. Lazovich D, Choi K, Vogel RI (2012) Time to get serious about skin cancer prevention. Cancer Epidemiol Biomark Prev 21(11):1893–1901CrossRefGoogle Scholar
  227. Le Clair MZ, Cockburn MG (2016) Tanning bed use and melanoma: establishing risk and improving prevention interventions. Preven Med Reports 3:139–144CrossRefGoogle Scholar
  228. Lear W, Dahlke E, Murray CA (2007) Basal cell carcinoma: review of epidemiology, pathogenesis, and associated risk factors. J Cutan Med Surg 11(1):19–30PubMedCrossRefPubMedCentralGoogle Scholar
  229. Lee W, Haslinger A, Karin M, Tjian R (1987) Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40. Nature 325(6102):368–372PubMedCrossRefPubMedCentralGoogle Scholar
  230. Lee JC, Griswold DE, Votta B, Hanna N (1988) Inhibition of monocyte IL-1 production by the anti-inflammatory compound, SK&F 86002. Int J Immunopharmacol 10(7):835–843PubMedCrossRefPubMedCentralGoogle Scholar
  231. Lee JC, Badger AM, Griswold DE, Dunnington D, Truneh A, Votta B, White JR, Young PR, Bender PE (1993) Bicyclic imidazoles as a novel class of cytokine biosynthesis inhibitors. Ann N Y Acad Sci 696:149–170PubMedCrossRefPubMedCentralGoogle Scholar
  232. Lee SK, Song L, Mata-Greenwood E, Kelloff GJ, Steele VE, Pezzuto JM (1999) Modulation of in vitro biomarkers of the carcinogenic process by chemopreventive agents. Anticancer Res 19(1a):35–44PubMedPubMedCentralGoogle Scholar
  233. Lee JC, Kumar S, Griswold DE, Underwood DC, Votta BJ, Adams JL (2000) Inhibition of p38 MAP kinase as a therapeutic strategy. Immunopharmacology 47(2–3):185–201PubMedCrossRefPubMedCentralGoogle Scholar
  234. Levine N, Dorr RT, Ertl GA, Brooks C, Alberts DS (1999) Effects of a potent synthetic melanotropin NI4-D-Phe2 MSH(Melanotan 1) on tanning: a dose range study. J Dermatolog Treat 10:127–132CrossRefGoogle Scholar
  235. Li G, Herlyn M (2000) Dynamics of intercellular communication during melanoma development. Mol Med Today 6(4):163–169PubMedCrossRefPubMedCentralGoogle Scholar
  236. Li G, Mitchell DL, Ho VC, Reed JC, Tron VA (1996) Decreased DNA repair but normal apoptosis in ultraviolet-irradiated skin of p53-transgenic mice. Am J Pathol 148(4):1113–1123PubMedPubMedCentralGoogle Scholar
  237. Li G, Satyamoorthy K, Herlyn M (2002) Dynamics of cell interactions and communications during melanoma development. Crit Rev Oral Biol Med 13(1):62–70PubMedCrossRefPubMedCentralGoogle Scholar
  238. Li X, Wu X, Chen Q (2014) Statin use is not associated with reduced risk of skin cancer: a meta-analysis. Br J Cancer 110:802–807PubMedCrossRefPubMedCentralGoogle Scholar
  239. Liaw GJ, Steingrimsson E, Pignoni F, Courey AJ, Lengyel JA (1993) Characterization of downstream elements in a Raf-1 pathway. Proc Natl Acad Sci U S A 90(3):858–862PubMedPubMedCentralCrossRefGoogle Scholar
  240. Liggett WH Jr, Sidransky D (1998) Role of the p16 tumor suppressor gene in cancer. J Clin Oncol 16(3):1197–1206PubMedCrossRefPubMedCentralGoogle Scholar
  241. Linos E, Swetter SM, Cockburn MG, Colditz GA, Clarke CA (2009) Increasing burden of melanoma in the United States. J Investig Dermatol 129(7):1666–1674PubMedCrossRefPubMedCentralGoogle Scholar
  242. Lippman SM, Brown PH (1999) Tamoxifen prevention of breast cancer: an instance of the fingerpost. J Natl Cancer Inst 91(21):1809–1819PubMedCrossRefPubMedCentralGoogle Scholar
  243. Lippman SM, Hong WK (2002) Cancer prevention by delay. Commentary re: J. A. O’Shaughnessy et al., Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. Clin. Cancer Res., 8: 314-346, 2002. Clin Cancer Res 8(2):305–313PubMedPubMedCentralGoogle Scholar
  244. Lluria-Prevatt M, Morreale J, Gregus J, Alberts DS, Kaper F, Giaccia A, Powell MB (2002) Effects of perillyl alcohol on melanoma in the TPras mouse model. Cancer Epidemiol Biomark Prev 11(6):573–579Google Scholar
  245. Lober BA, Fenske NA (2004) Optimum treatment strategies for actinic keratosis (intraepidermal squamous cell carcinoma). Am J Clin Dermatol 5(6):395–401PubMedCrossRefPubMedCentralGoogle Scholar
  246. Lorusso PM (2003) Phase I studies of ZD1839 in patients with common solid tumors. Semin Oncol 30(1 Suppl 1):21–29PubMedCrossRefPubMedCentralGoogle Scholar
  247. Lu YP, Lou YR, Lin Y, Shih WJ, Huang MT, Yang CS, Conney AH (2001) Inhibitory effects of orally administered green tea, black tea, and caffeine on skin carcinogenesis in mice previously treated with ultraviolet B light (high-risk mice): relationship to decreased tissue fat. Cancer Res 61(13):5002–5009PubMedPubMedCentralGoogle Scholar
  248. Lucas RM, McMichael AJ, Armstrong BK, Smith WT (2008) Estimating the global disease burden due to ultraviolet radiation exposure. Int J Epidemiol 37(3):654–667PubMedCrossRefPubMedCentralGoogle Scholar
  249. Luo C, Sheng J, Hu M (2013) Loss of ARF sensitizes transgenic BRAF V600E mice to UV-induced melanoma via suppression of XPC. Cancer Res 73:4337–4348PubMedPubMedCentralCrossRefGoogle Scholar
  250. Luo H, Umebayashi M, Doi K, Morisaki T, Shirasawa S, Tsunoda T (2016) Resveratrol overcomes cellular resistance to Vemurafenib through dephosphorylation of AKT in BRAF-mutated melanoma cells. Anticancerr Res 36:3585–3589Google Scholar
  251. Lyons JF, Wilhelm S, Hibner B, Bollag G (2001) Discovery of a novel Raf kinase inhibitor. Endocr Relat Cancer 8(3):219–225PubMedCrossRefPubMedCentralGoogle Scholar
  252. MacAulay C, Lam S, Payne PW, LeRiche JC, Palcic B (1995) Malignancy-associated changes in bronchial epithelial cells in biopsy specimens. Anal Quant Cytol Histol 17(1):55–61PubMedPubMedCentralGoogle Scholar
  253. Madan V, Bisset D, Harris P, Howard S, Beck MH (2006) Phaeohyphomycosis caused by Exophiala salmonis. Br J Dermatol 155(5):1082–1084PubMedCrossRefPubMedCentralGoogle Scholar
  254. Maden V, Leah JT, Szeimies RM (2010) Non-melanoma skin cancer. Lancet 375:673–685CrossRefGoogle Scholar
  255. Mandel ID (1988) Chemotherapeutic agents for controlling plaque and gingivitis. J Clin Periodontol 15(8):488–498PubMedCrossRefPubMedCentralGoogle Scholar
  256. Mangelsdorf D, Unesonso K et al (1994) The retinoid receptors. In: Sporn MB, Roberts AB, Goodman DS (eds) The retinoids. Raven Press, New York, pp 319–349Google Scholar
  257. Manson JE, Rexrode KM, Garland FC, Garland CF, Weinstock MA (2000) The case for a comprehensive national campaign to prevent melanoma and associated mortality. Epidemiology 11(6):728–734PubMedCrossRefPubMedCentralGoogle Scholar
  258. Marks R (1999) Two decades of the public health approach to skin cancer control in Australia: why, how and where are we now? Australas J Dermatol 40(1):1–5PubMedCrossRefPubMedCentralGoogle Scholar
  259. Marras S, Faa G, Dettori T, Congiu L, Vanni R (1999) Chromosomal changes in dysplastic nevi. Cancer Genet Cytogenet 113(2):177–179PubMedCrossRefPubMedCentralGoogle Scholar
  260. Marshall CJ (1995) Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80(2):179–185PubMedCrossRefPubMedCentralGoogle Scholar
  261. Martin G, Swanson N (2013) Clinical findings using ingenol mebutate gel to treat actinic keratoses. J Am Acad Dermatol 68(1 Suppl 1):S39–S48PubMedCrossRefPubMedCentralGoogle Scholar
  262. Matsumoto S, Abe Y, Fujibuchi T, Takeuchi T, Kito K, Ueda N, Shigemoto K, Gyo K (2004) Characterization of a MAPKK-like protein kinase TOPK. Biochem Biophys Res Commun 325(3):997–1004PubMedCrossRefPubMedCentralGoogle Scholar
  263. Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H (1996) Characterization of p53 gene mutations in basal-cell carcinomas: comparison between sun-exposed and less-exposed skin areas. Int J Cancer 65(6):778–780PubMedCrossRefPubMedCentralGoogle Scholar
  264. McEwan LE, Smith JG (1997) Topical diclofenac/hyaluronic acid gel in the treatment of solar keratoses. Australas J Dermatol 38(4):187–189PubMedCrossRefPubMedCentralGoogle Scholar
  265. Melamed RD, Aydin IT, Rajan GS, Phelps R, Silvers DN, Emmett KJ, Brunner G, Rabadan R, Celebi JT (2017) Genomic characterization of dysplastic nevi unveils implications for diagnosis of melanoma. J Investig Dermatol 137(4):905–909PubMedCrossRefPubMedCentralGoogle Scholar
  266. Meyskens FL Jr (1988) Thinking about cancer causality and chemoprevention. J Natl Cancer Inst 80(16):1278–1281PubMedCrossRefPubMedCentralGoogle Scholar
  267. Meyskens FL Jr, Farmer PJ, Anton-Culver H (2004) Etiologic pathogenesis of melanoma: a unifying hypothesis for the missing attributable risk. Clin Cancer Res 10(8):2581–2583PubMedCrossRefPubMedCentralGoogle Scholar
  268. Meyskens FL, Kingsley EM, Glattke T, Loescher L, Booth A (1986) A phase II study of alpha-difluoromethylornithine (DFMO) for the treatment of metastatic melanoma. Investig New Drugs 4(3):257–262CrossRefGoogle Scholar
  269. Mills JJ, Chari RS, Boyer IJ, Gould MN, Jirtle RL (1995) Induction of apoptosis in liver tumors by the monoterpene perillyl alcohol. Cancer Res 55(5):979–983PubMedPubMedCentralGoogle Scholar
  270. Mitscher LA, Park YH, Clark D, Clark GW 3rd, Hammesfahr PD, Wu WN, Beal JL (1978) Antimicrobial agents from higher plants. An investigation of Hunnemannia fumariaefolia pseudoalcoholates of sanguinarine and chelerythrine. Lloydia 41(2):145–150PubMedPubMedCentralGoogle Scholar
  271. Montagnani Marelli M, Marzagalli M, Moretti RM, Beretta G, Casati L, Comitato R, Gravina GL, Festuccia C, Limonta P (2016) Vitamin E delta-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells. Sci Rep 6:30502PubMedPubMedCentralCrossRefGoogle Scholar
  272. Montes de Oca MK, Pearlman RL, McClees SF, Strickland R, Afaq F (2017) Phytochemicals for the Prevention of Photocarcinogenesis. Photochem Photobiol 93(4):956–974PubMedPubMedCentralCrossRefGoogle Scholar
  273. Moon TE, Levine N et al (1997) Effect of retinol in preventing squamous cell skin cancer in moderate risk subjects: a randomized, double blind, controlled trial, Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev 6(11):949–956PubMedPubMedCentralGoogle Scholar
  274. Morse MA, Stoner GD (1993) Cancer chemoprevention: principles and prospects. Carcinogenesis 14(9):1737–1746PubMedCrossRefPubMedCentralGoogle Scholar
  275. Nakazawa H, English D, Randell PL, Nakazawa K, Martel N, Armstrong BK, Yamasaki H (1994) UV and skin cancer: specific p53 gene mutation in normal skin as a biologically relevant exposure measurement. Proc Natl Acad Sci U S A 91(1):360–364PubMedPubMedCentralCrossRefGoogle Scholar
  276. Narayanan DL, Saladi RN, Fox JL (2010) Ultraviolet radiation and skin cancer. Int J Dermatol 49(9):978–986PubMedCrossRefPubMedCentralGoogle Scholar
  277. Nelson MA, Einspahr JG, Alberts DS, Balfour CA, Wymer JA, Welch KL, Salasche SJ, Bangert JL, Grogan TM, Bozzo PO (1994) Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers. Cancer Lett 85(1):23–29PubMedCrossRefPubMedCentralGoogle Scholar
  278. Nelson MA, Ariza ME, Yang JM, Thompson FH, Taetle R, Trent JM, Wymer J, Massey-Brown K, Broome-Powell M, Easton J, Lahti JM, Kidd VJ (1999) Abnormalities in the p34cdc2-related PITSLRE protein kinase gene complex (CDC2L) on chromosome band 1p36 in melanoma. Cancer Gen Cytogen 108(2):91–99CrossRefGoogle Scholar
  279. Niesor EJ, Flach J (1999) Synthetic Farnesoid X Receptor (FXR) agonists: a new class of cholesterol synthesis inhibitors and antiproliferative drugs. Drugs Future 24:431–438CrossRefGoogle Scholar
  280. Nomura M, Ma WY, Huang C, Yang CS, Bowden GT, Miyamoto K, Dong Z (2000) Inhibition of ultraviolet B-induced AP-1 activation by theaflavins from black tea. Mol Carcinog 28(3):148–155PubMedCrossRefPubMedCentralGoogle Scholar
  281. Nomura M, Kaji A, He Z, Ma WY, Miyamoto K, Yang CS, Dong Z (2001a) Inhibitory mechanisms of tea polyphenols on the ultraviolet B-activated phosphatidylinositol 3-kinase-dependent pathway. J Biol Chem 276(49):46624–46631PubMedCrossRefPubMedCentralGoogle Scholar
  282. Nomura M, Kaji A, Ma WY, Zhong S, Liu G, Bowden GT, Miyamoto KI, Dong Z (2001b) Mitogen- and stress-activated protein kinase 1 mediates activation of Akt by ultraviolet B irradiation. J Biol Chem 276(27):25558–25567PubMedCrossRefPubMedCentralGoogle Scholar
  283. Noonan FP, Recio JA, Takayama H, Duray P, Anver MR, Rush WL, De Fabo EC, Merlino G (2001) Neonatal sunburn and melanoma in mice. Nature 413(6853):271–272PubMedCrossRefPubMedCentralGoogle Scholar
  284. Ogbourne SM, Suhrbier A, Jones B, Cozzi SJ, Boyle GM, Morris M, McAlpine D, Johns J, Scott TM, Sutherland KP, Gardner JM, Le TT, Lenarczyk A, Aylward JH, Parsons PG (2004) Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death. Cancer Res 64(8):2833–2839PubMedCrossRefPubMedCentralGoogle Scholar
  285. Oh SM, Zhu F, Cho YY, Lee KW, Kang BS, Kim HG, Zykova T, Bode AM, Dong Z (2007) T-lymphokine-activated killer cell-originated protein kinase functions as a positive regulator of c-Jun-NH2-kinase 1 signaling and H-Ras-induced cell transformation. Cancer Res 67(11):5186–5194PubMedCrossRefPubMedCentralGoogle Scholar
  286. Omholt K, Krockel D, Ringborg U, Hansson J (2006) Mutations of PIK3CA are rare in cutaneous melanoma. Melanoma Res 16(2):197–200PubMedCrossRefPubMedCentralGoogle Scholar
  287. Orengo IF, Gerguis J, Phillips R, Guevara A, Lewis AT, Black HS (2002) Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer: a study in the hairless mouse model. Arch Dermatol 138(6):751–755PubMedCrossRefGoogle Scholar
  288. Ortega Del Olmo R, Salido-Vallejo R (2017) Ingenol mebutate for the treatment of actinic keratosis: effectiveness and safety in 246 patients treated in real-life clinical practice. J Dermatolog Treat 29(4):393–399PubMedCrossRefPubMedCentralGoogle Scholar
  289. Ortonne JP (2002) Photobiology and genetics of malignant melanoma. Br J Dermatol 146(Suppl 61):11–16PubMedCrossRefPubMedCentralGoogle Scholar
  290. O’Shaughnessy JA, Kelloff GJ, Gordon GB, Dannenberg AJ, Hong WK, Fabian CJ, Sigman CC, Bertagnolli MM, Stratton SP, Lam S, Nelson WG, Meyskens FL, Alberts DS, Follen M, Rustgi AK, Papadimitrakopoulou V, Scardino PT, Gazdar AF, Wattenberg LW, Sporn MB, Sakr WA, Lippman SM, Von Hoff DD (2002) Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. Clin Cancer Res 8(2):314–346PubMedPubMedCentralGoogle Scholar
  291. Oyagbemi AA, Saba AB, Azeez OI (2010) Capsaicin: novel chemopreventive molecule and its underlying molecular mechanisms of action. Indian J Cancer 47(1):53–58PubMedCrossRefPubMedCentralGoogle Scholar
  292. Pacifico A, Goldberg LH, Peris K, Chimenti S, Leone G, Ananthaswamy HN (2008) Loss of CDKN2A and p14ARF expression occurs frequently in human nonmelanoma skin cancers.[Erratum appears in Br J Dermatol. 2008 Mar;158(3):657]. Br J Dermatol 158(2):291–297PubMedCrossRefGoogle Scholar
  293. Pagoto SL, Baker K, Griffith J, Oleski JL, Palumbo A, Walkosz BJ, Hillhouse J, Henry KL, Buller DB (2016) Engaging moms on teen indoor tanning through social media: protocol of a randomized controlled trial. JMIR Res Prot 5(4):e228CrossRefGoogle Scholar
  294. Pal HC, Baxter RD, Hunt KM, Agarwal J, Elmets CA, Athar M, Afaq F (2015) Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. Oncotarget 6(29):28296–28311PubMedPubMedCentralCrossRefGoogle Scholar
  295. Pal HC, Diamond AC, Strickland LR, Kappes JC, Katiyar SK, Elmets CA, Athar M, Afaq F (2016) Fisetin, a dietary flavonoid, augments the anti-invasive and anti-metastatic potential of sorafenib in melanoma. Oncotarget 7(2):1227–1241PubMedCrossRefGoogle Scholar
  296. Palmer JS, Duffy DL, Box NF, Aitken JF, O’Gorman LE, Green AC, Hayward NK, Martin NG, Sturm RA (2000) Melanocortin-1 receptor polymorphisms and risk of melanoma: is the association explained solely by pigmentation phenotype? Am J Hum Genet 66(1):176–186PubMedCrossRefGoogle Scholar
  297. Park JH, Nishidate T, Nakamura Y, Katagiri T (2010) Critical roles of T-LAK cell-originated protein kinase in cytokinesis. Cancer Sci 101(2):403–411PubMedCrossRefGoogle Scholar
  298. Pena JC, Rudin CM, Thompson CB (1998) A Bcl-xL transgene promotes malignant conversion of chemically initiated skin papillomas. Cancer Res 58(10):2111–2116PubMedPubMedCentralGoogle Scholar
  299. Pentland AP, Schoggins JW, Scott GA, Khan KN, Han R (1999) Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis 20(10):1939–1944PubMedCrossRefPubMedCentralGoogle Scholar
  300. Peyssonnaux C, Eychene A (2001) The Raf/MEK/ERK pathway: new concepts of activation. Biol Cell 93(1–2):53–62PubMedCrossRefPubMedCentralGoogle Scholar
  301. Piepkorn M (2000) The expression of p16(INK4a), the product of a tumor suppressor gene for melanoma, is upregulated in human melanocytes by UVB irradiation. J Am Acad Dermatol 42(5 Pt 1):741–745PubMedCrossRefPubMedCentralGoogle Scholar
  302. Pierceall WE, Goldberg LH, Tainsky MA, Mukhopadhyay T, Ananthaswamy HN (1991) Ras gene mutation and amplification in human nonmelanoma skin cancers. Mol Carcinog 4(3):196–202PubMedCrossRefGoogle Scholar
  303. Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J, Salem G, Pohida T, Heenan P, Duray P, Kallioniemi O, Hayward NK, Trent JM, Meltzer PS (2003) High frequency of BRAF mutations in nevi. Nat Genet 33(1):19–20PubMedCrossRefGoogle Scholar
  304. Ponti G, Manfredini M, Greco S, Pellacani G, Depenni R, Tomasi A, Maccaferri M, Cascinu S (2017) BRAF, NRAS and C-KIT Advanced Melanoma: Clinico-pathological Features, Targeted-Therapy Strategies and Survival. Anticancer Res 37(12):7043–7048PubMedGoogle Scholar
  305. Porter RS (2011) The Merck manual of diagnosis and therapy. Merck Sharp & Dohme Corp, West Point, PAGoogle Scholar
  306. Pourpak A, Dorr R (2005) Anti-melanoma activity of the bisphosphonate ester APOMINE is independent of Ras Farnesylation and apoptotic cell death in human melanoma cell lines. Am Assoc Cancer ResGoogle Scholar
  307. Powell M, Alberts D (2002) Preclinical and clinical activity of Apomine, a novel bisphosphonate ester in the prevention and treatment of melanoma. Proc Am Assoc Cancer ResGoogle Scholar
  308. Powis G, Berggren M, Gallegos A, Frew T, Hill S, Kozikowski A, Bonjouklian R, Zalkow L, Abraham R, Ashendel C et al (1995) Advances with phospholipid signalling as a target for anticancer drug development. Acta Biochim Pol 42(4):395–403PubMedGoogle Scholar
  309. Quinn AG, Sikkink S, Rees JL (1994) Basal cell carcinomas and squamous cell carcinomas of human skin show distinct patterns of chromosome loss. Cancer Res 54(17):4756–4759PubMedPubMedCentralGoogle Scholar
  310. Rallis E, Liakopoulou A, Christodoulopoulos C (2017) Ingenol mebutate for the treatment of intraepidermal squamous cell carcinoma. J Clin Aesthet Dermatol 10(7):12–13PubMedPubMedCentralGoogle Scholar
  311. Ramirez CC, Ma F, Federman DG, Kirsner RS (2005) Use of cyclooxygenase inhibitors and risk of melanoma in high-risk patients. Dermatol Surg 31(7 Pt 1):748–752PubMedCrossRefPubMedCentralGoogle Scholar
  312. Ranger-Moore J, Alberts DS, Montironi R, Garcia F, Davis J, Frank D, Brewer M, Mariuzzi GM, Bartels HG, Bartels PH (2005) Karyometry in the early detection and chemoprevention of intraepithelial lesions. Eur J Cancer 41(13):1875–1888PubMedCrossRefPubMedCentralGoogle Scholar
  313. Reagan-Shaw S, Afaq F, Aziz MH, Ahmad N (2004) Modulations of critical cell cycle regulatory events during chemoprevention of ultraviolet B-mediated responses by resveratrol in SKH-1 hairless mouse skin. Oncogene 23(30):5151–5160PubMedCrossRefPubMedCentralGoogle Scholar
  314. Reagan-Shaw S, Breur J, Ahmad N (2006) Enhancement of UVB radiation-mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes. Mol Cancer Ther 5(2):418–429PubMedCrossRefPubMedCentralGoogle Scholar
  315. Reed JA, Loganzo F Jr, Shea CR, Walker GJ, Flores JF, Glendening JM, Bogdany JK, Shiel MJ, Haluska FG, Fountain JW et al (1995) Loss of expression of the p16/cyclin-dependent kinase inhibitor 2 tumor suppressor gene in melanocytic lesions correlates with invasive stage of tumor progression. Cancer Res 55(13):2713–2718PubMedPubMedCentralGoogle Scholar
  316. Rehman I, Takata M, Wu YY, Rees JL (1996) Genetic change in actinic keratoses. Oncogene 12(12):2483–2490PubMedPubMedCentralGoogle Scholar
  317. Report SG (2014) The Surgeon General’s call to action to prevent skin cancer. Services USDoHaH. Reports for the Surgeon General. Office of the Surgeon General, Washington DCGoogle Scholar
  318. Richmond A, Fine R, Murray D, Lawson DH, Priest JH (1986) Growth factor and cytogenetic abnormalities in cultured nevi and malignant melanomas. J Invest Dermatol 86(3):295–302PubMedCrossRefPubMedCentralGoogle Scholar
  319. Rigel DS (2010) Epidemiology of melanoma. Sem Cutan Med Surg 29(4):204–209CrossRefGoogle Scholar
  320. Rivers JK, McLean DI (1997) An open study to assess the efficacy and safety of topical 3% diclofenac in a 2.5% hyaluronic acid gel for the treatment of actinic keratoses. Arch Dermatol 133(10):1239–1242PubMedCrossRefPubMedCentralGoogle Scholar
  321. Rivers JK, Arlette J, Shear N, Guenther L, Carey W, Poulin Y (2002) Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel. Br J Dermatol 146(1):94–100PubMedCrossRefPubMedCentralGoogle Scholar
  322. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J (1999) Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 341(6):410–418PubMedCrossRefPubMedCentralGoogle Scholar
  323. Runger TM (1999) Role of UVA in the pathogenesis of melanoma and non-melanoma skin cancer. A short review. Photodermatol Photoimmunol Photomed 15(6):212–216PubMedCrossRefPubMedCentralGoogle Scholar
  324. Runger TM (2007) How different wavelengths of the ultraviolet spectrum contribute to skin carcinogenesis: the role of cellular damage responses. J Invest Dermatol 127(9):2103–2105PubMedCrossRefPubMedCentralGoogle Scholar
  325. Runger TM, Kappes UP (2008) Mechanisms of mutation formation with long-wave ultraviolet light (UVA). Photodermatol Photoimmunol Photomed 24(1):2–10PubMedCrossRefPubMedCentralGoogle Scholar
  326. Russo I, Caroppo F, Alaibac M (2015) Vitamins and melanoma. Cancers 7(3):1371–1387PubMedPubMedCentralCrossRefGoogle Scholar
  327. Ryseck RP, Hirai SI, Yaniv M, Bravo R (1988) Transcriptional activation of c-jun during the G0/G1 transition in mouse fibroblasts. Nature 334(6182):535–537PubMedCrossRefPubMedCentralGoogle Scholar
  328. Salasche SJ (2000) Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol 42(1 Pt 2):4–7PubMedCrossRefPubMedCentralGoogle Scholar
  329. Sample A, He YY (2017) Mechanisms and prevention of UV-induced melanoma. Photodermatol Photoimmunol Photomed 34(1):13–24PubMedPubMedCentralCrossRefGoogle Scholar
  330. Samuels ML, Weber MJ, Bishop JM, McMahon M (1993) Conditional transformation of cells and rapid activation of the mitogen-activated protein kinase cascade by an estradiol-dependent human raf-1 protein kinase. Mol Cell Biol 13(10):6241–6252PubMedPubMedCentralCrossRefGoogle Scholar
  331. Setlow RB, Grist E, Thompson K, Woodhead AD (1993) Wavelengths effective in induction of malignant melanoma. Proc Natl Acad Sci U S A 90(14):6666–6670PubMedPubMedCentralCrossRefGoogle Scholar
  332. Shah M, Stebbins JL, Dewing A, Qi J, Pellecchia M, Ronai ZA (2009) Inhibition of Siah2 ubiquitin ligase by vitamin K3 (menadione) attenuates hypoxia and MAPK signaling and blocks melanoma tumorigenesis. Pigment Cell Melanoma Res 22(6):799–808PubMedPubMedCentralCrossRefGoogle Scholar
  333. Shamma M, Guinaudeau H (1986) Aporphinoid alkaloids. Nat Prod Rep 3(4):345–351PubMedCrossRefPubMedCentralGoogle Scholar
  334. Sherman A, Koss L (1983) Morphometry of benign urothelial cells in the presence of cancer. Anal Quant Cytol Histol 5:221Google Scholar
  335. Sherwani MA, Tufail S, Muzaffar AF, Yusuf N (2018) The skin microbiome and immune system: Potential target for chemoprevention? Photodermatol Photoimmunol Photomed 34(1):25–34PubMedCrossRefPubMedCentralGoogle Scholar
  336. Shibata A, Nakagawa K, Yamanoi H, Tsuduki T, Sookwong P, Higuchi O, Kimura F, Miyazawa T (2010) Sulforaphane suppresses ultraviolet B-induced inflammation in HaCaT keratinocytes and HR-1 hairless mice. J Nutr Biochem 21(8):702–709PubMedCrossRefPubMedCentralGoogle Scholar
  337. Silvers AL, Bowden GT (2002) UVA irradiation-induced activation of activator protein-1 is correlated with induced expression of AP-1 family members in the human keratinocyte cell line HaCaT. Photochem Photobiol 75(3):302–310PubMedCrossRefPubMedCentralGoogle Scholar
  338. Silvers AL, Bachelor MA, Bowden GT (2003) The role of JNK and p38 MAPK activities in UVA-induced signaling pathways leading to AP-1 activation and c-Fos expression. Neoplasia 5(4):319–329PubMedPubMedCentralCrossRefGoogle Scholar
  339. Simons-Evelyn M, Bailey-Dell K, Toretsky JA, Ross DD, Fenton R, Kalvakolanu D, Rapoport AP (2001) PBK/TOPK is a novel mitotic kinase which is upregulated in Burkitt’s lymphoma and other highly proliferative malignant cells. Blood Cells Mol Dis 27(5):825–829PubMedCrossRefPubMedCentralGoogle Scholar
  340. Skin Cancer Foundation (2015) Skin cancer facts & statisticsGoogle Scholar
  341. Sober AJ, Burstein JM (1995) Precursors to skin cancer. Cancer 75(2 Suppl):645–650PubMedCrossRefPubMedCentralGoogle Scholar
  342. Soufir N, Avril MF, Chompret A, Demenais F, Bombled J, Spatz A, Stoppa-Lyonnet D, Benard J, Paillerets B B-d (1999a) Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group.[Erratum appears in Hum Mol Genet 1998 May;7(5):941]. Hum Mol Genet 7(2):209–216CrossRefGoogle Scholar
  343. Soufir N, Moles JP, Vilmer C, Moch C, Verola O, Rivet J, Tesniere A, Dubertret L, Basset-Seguin N (1999b) P16 UV mutations in human skin epithelial tumors. Oncogene 18(39):5477–5481PubMedCrossRefPubMedCentralGoogle Scholar
  344. Soufir N, Daya-Grosjean L, de La Salmoniere P, Moles JP, Dubertret L, Sarasin A, Basset-Seguin N (2000) Association between INK4a-ARF and p53 mutations in skin carcinomas of xeroderma pigmentosum patients. J Natl Cancer Inst 92(22):1841–1847PubMedCrossRefPubMedCentralGoogle Scholar
  345. Spencer JM, Kahn SM, Jiang W, DeLeo VA, Weinstein IB (1995) Activated ras genes occur in human actinic keratoses, premalignant precursors to squamous cell carcinomas. Arch Dermatol 131(7):796–800PubMedCrossRefPubMedCentralGoogle Scholar
  346. Spencer JM, Hazan C, Hsiung SH, Robins P (2005) Therapeutic decision making in the therapy of actinic keratoses. J Drugs Dermatol 4(3):296–301PubMedPubMedCentralGoogle Scholar
  347. Sporn MB, Suh N (2000) Chemoprevention of cancer. Carcinogenesis 21(3):525–530PubMedCrossRefPubMedCentralGoogle Scholar
  348. Stahlhut M, Bertelsen M, Hoyer-Hansen M, Svendsen N, Eriksson AH, Lord JM, Scheel-Toellner D, Young SP, Zibert JR (2012) Ingenol mebutate: induced cell death patterns in normal and cancer epithelial cells. J Drugs Dermatol 11(10):1181–1192PubMedPubMedCentralGoogle Scholar
  349. Stam-Posthuma JJ, Vink J, le Cessie S, Bruijn JA, Bergman W, Pavel S (1998) Effect of topical tretinoin under occlusion on atypical naevi. Melanoma Res 8(6):539–548PubMedCrossRefPubMedCentralGoogle Scholar
  350. Stam-Posthuma JJ, van Duinen C, Scheffer E, Vink J, Bergman W (2001) Multiple primary melanomas. J Am Acad Dermatol 44(1):22–27PubMedCrossRefPubMedCentralGoogle Scholar
  351. Stayrook KR, McKinzie JH, Barbhaiya LH, Crowell PL (1998) Effects of the antitumor agent perillyl alcohol on H-Ras vs. K-Ras farnesylation and signal transduction in pancreatic cells. Anticancer Res 18(2a):823–828PubMedPubMedCentralGoogle Scholar
  352. Stein B, Angel P, van Dam H, Ponta H, Herrlich P, van der Eb A, Rahmsdorf HJ (1992) Ultraviolet-radiation induced c-jun gene transcription: two AP-1 like binding sites mediate the response. Photochem Photobiol 55(3):409–415PubMedCrossRefPubMedCentralGoogle Scholar
  353. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B, Godio L, Patterson S, Rodriguez-Bigas MA, Jester SL, King KL, Schumacher M, Abbruzzese J, DuBois RN, Hittelman WN, Zimmerman S, Sherman JW, Kelloff G (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342(26):1946–1952PubMedCrossRefPubMedCentralGoogle Scholar
  354. Stolz W, Vogt T, Landthaler M, Hempfer S, Bingler P, Abmayr W (1994) Differentiation between malignant melanomas and benign melanocytic nevi by computerized DNA cytometry of imprint specimens. J Cutan Pathol 21(1):7–15PubMedCrossRefPubMedCentralGoogle Scholar
  355. Stratton SP (2001) Prevention of non-melanoma skin cancer. Curr Oncol Rep 3(4):295–300PubMedCrossRefPubMedCentralGoogle Scholar
  356. Stratton SP, Dorr RT, Alberts DS (2000) The state-of-the-art in chemoprevention of skin cancer. Eur J Cancer 36(10):1292–1297PubMedCrossRefPubMedCentralGoogle Scholar
  357. Stratton SP, Alberts DS, Einspahr JG, Sagerman PM, Warneke JA, Curiel-Lewandrowski C, Myrdal PB, Karlage KL, Nickoloff BJ, Brooks C, Saboda K, Yozwiak ML, Krutzsch MF, Hu C, Lluria-Prevatt M, Dong Z, Bowden GT, Bartels PH (2010) A phase 2a study of topical perillyl alcohol cream for chemoprevention of skin cancer. Cancer Prev Res (Phila) 3(2):160–169CrossRefGoogle Scholar
  358. Straume O, Akslen LA (1997) Alterations and prognostic significance of p16 and p53 protein expression in subgroups of cutaneous melanoma. Int J Cancer 74(5):535–539PubMedCrossRefPubMedCentralGoogle Scholar
  359. Strumberg D, Schuehly W, Moeller J, Hedler D, Hilger R, Stellberg W, Richly H, Heinig R, Ahr G, Wensing G, Kuhlmann J, Scheulen M, Seeber S (2001) Phase I clinical, pharmacokinetic and pharmacodynamic study of the Raf kinase inhibitor BAY 49–9006 in patients with locally advanced or metastatic cancer. Proc Am Assoc Cancer Res 330Google Scholar
  360. Sun AY, Simonyi A, Sun GY (2002) The "French Paradox" and beyond: neuroprotective effects of polyphenols. Free Radic Biol Med 32(4):314–318PubMedCrossRefPubMedCentralGoogle Scholar
  361. Susnik B, Worth A, LeRiche J, Palcic B (1995) Malignancy-associated changes in the breast. Changes in chromatin distribution in epithelial cells in normal-appearing tissue adjacent to carcinoma. Anal Quant Cytol Histol 17(1):62–68PubMedPubMedCentralGoogle Scholar
  362. Swerdlow AJ, Weinstock MA (1998) Do tanning lamps cause melanoma? An epidemiologic assessment. J Am Acad Dermatol 38(1):89–98PubMedCrossRefPubMedCentralGoogle Scholar
  363. Tada A, Pereira E, Beitner-Johnson D, Kavanagh R, Abdel-Malek ZA (2002) Mitogen- and ultraviolet-B-induced signaling pathways in normal human melanocytes. J Invest Dermatol 118(2):316–322PubMedCrossRefPubMedCentralGoogle Scholar
  364. Takigawa M, Enormoto M (1990) Tumor angiogenesis and polyamines: alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, inhibits B16 melanoma-induced angiogenesis in vivo and the proliferation of vascular endothelial cells in vitro. Cancer Res 50(13):4131–4138PubMedPubMedCentralGoogle Scholar
  365. Talalay P, Fahey JW, Healy ZR, Wehage SL, Benedict AL, Min C, Dinkova-Kostova AT (2007) Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiation. Proc Natl Acad Sci U S A 104(44):17500–17505PubMedPubMedCentralCrossRefGoogle Scholar
  366. Tang Q, Gonzales M, Inoue H, Bowden GT (2001) Roles of Akt and glycogen synthase kinase 3beta in the ultraviolet B induction of cyclooxygenase-2 transcription in human keratinocytes. Cancer Res 61(11):4329–4332PubMedPubMedCentralGoogle Scholar
  367. Tangrea JA, Edwards BK et al (1992) Long term therapy with low dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. J Natl Cancer Inst 84:328–332PubMedCrossRefPubMedCentralGoogle Scholar
  368. The International Agency for Research on Cancer Working Group on Artificial Ultraviolet (UV) Light and Skin Cancer (2007) The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: A systematic review. Int J Cancer 120(5):1116–1122Google Scholar
  369. Thomas T, Bozzo P (2006) Biomarkers of angiogenesis in progression from dysplastic nevi to malignant melanoma. Society of Investigative Dermatology, PhiladelphiaGoogle Scholar
  370. Thompson FH, Emerson J, Olson S, Weinstein R, Leavitt SA, Leong SP, Emerson S, Trent JM, Nelson MA, Salmon SE et al (1995) Cytogenetics of 158 patients with regional or disseminated melanoma. Subset analysis of near-diploid and simple karyotypes. Cancer Genet Cytogenet 83(2):93–104PubMedCrossRefPubMedCentralGoogle Scholar
  371. Tsao H (2001) Genetics of nonmelanoma skin cancer. Arch Dermatol 137(11):1486–1492PubMedPubMedCentralGoogle Scholar
  372. Tsao H, Mihm M, Sheehan C (2003) PTEN expression in normal skin, acquired melanocytic nevi, and cutaneous melanoma. J Am Acad Dermatol 49(5):865–872PubMedCrossRefPubMedCentralGoogle Scholar
  373. Uhlman M (2002) Teens take risks for tans: sunscreen often goes by the wayside, a study shows. FDA is evaluating labeling. Philadelphia Inquirer, Philadelphia, PA, p A08Google Scholar
  374. Valverde P, Healy E, Sikkink S, Haldane F, Thody AJ, Carothers A, Jackson IJ, Rees JL (1996) The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma. Hum Mol Genet 5(10):1663–1666PubMedCrossRefPubMedCentralGoogle Scholar
  375. Vavreckova C, Ulrichova J, Hajduch M, Grambal F, Weigl E, Simanek V (1994) Effect of quaternary benzo[c]phenanthridine alkaloids sanguinarine, chelerythrine and fagaronine on some mammalian cells. Acta Univ Palacki Olomuc Fac Med 138:7–10PubMedPubMedCentralGoogle Scholar
  376. Veierod MB, Weiderpass E, Thorn M, Hansson J, Lund E, Armstrong B, Adami HO (2003) A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Cancer Inst 95(20):1530–1538PubMedCrossRefPubMedCentralGoogle Scholar
  377. Viros A, Sanchez-Laorden B, Pedersen M, Furney SJ, Rae J, Hogan K, Ejiama S, Girotti MR, Cook M, Dhomen N, Marais R (2014) Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53. Nature 511(7510):478–482PubMedPubMedCentralCrossRefGoogle Scholar
  378. Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2(7):489–501PubMedCrossRefPubMedCentralGoogle Scholar
  379. Volkov A, Dobbinson S, Wakefield M, Slevin T (2013) Seven-year trends in sun protection and sunburn among Australian adolescents and adults. Aust N Z J Public Health 37(1):63–69PubMedCrossRefPubMedCentralGoogle Scholar
  380. Wakeling AE (2002) Epidermal growth factor receptor tyrosine kinase inhibitors. Curr Opin Pharmacol 2(4):382–387PubMedCrossRefPubMedCentralGoogle Scholar
  381. Wales MM, Biel MA, el Deiry W, Nelkin BD, Issa JP, Cavenee WK, Kuerbitz SJ, Baylin SB (1995) p53 activates expression of HIC-1, a new candidate tumour suppressor gene on 17p13.3. Nat Med 1(6):570–577PubMedCrossRefPubMedCentralGoogle Scholar
  382. Wan YS, Wang ZQ, Shao Y, Voorhees JJ, Fisher GJ (2001a) Ultraviolet irradiation activates PI 3-kinase/AKT survival pathway via EGF receptors in human skin in vivo. Int J Oncol 18(3):461–466PubMedPubMedCentralGoogle Scholar
  383. Wan YS, Wang ZQ, Voorhees J, Fisher G (2001b) EGF receptor crosstalks with cytokine receptors leading to the activation of c-Jun kinase in response to UV irradiation in human keratinocytes. Cell Signal 13(2):139–144PubMedCrossRefPubMedCentralGoogle Scholar
  384. Wang SQ, Setlow R, Berwick M, Polsky D, Marghoob AA, Kopf AW, Bart RS (2001) Ultraviolet A and melanoma: a review. J Am Acad Dermatol 44(5):837–846PubMedCrossRefPubMedCentralGoogle Scholar
  385. Warne PH, Viciana PR, Downward J (1993) Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro. Nature 364(6435):352–355PubMedCrossRefPubMedCentralGoogle Scholar
  386. Watson M, Shoemaker M, Baker K (2017) Indoor tanning initiation among tanners in the United States. JAMA Dermatol 53(5):470–472CrossRefGoogle Scholar
  387. Weinzweig J, Tattini C, Lynch S, Zienowicz R, Weinzweig N, Spangenberger A, Edstrom L (2003) Investigation of the growth and metastasis of malignant melanoma in a murine model: the role of supplemental vitamin A. Plast Reconstr Surg 112(1):152–158; discussion 159-161PubMedCrossRefPubMedCentralGoogle Scholar
  388. Wellbrock C, Ogilvie L, Hedley D, Karasarides M, Martin J, Niculescu-Duvaz D, Springer CJ, Marais R (2004) V599EB-RAF is an oncogene in melanocytes. Cancer Res 64(7):2338–2342PubMedCrossRefPubMedCentralGoogle Scholar
  389. Welzel J (2001) Optical coherence tomography in dermatology: a review. Skin Res Technol 7(1):1–9PubMedCrossRefPubMedCentralGoogle Scholar
  390. Weng H, Deng Y, Xie Y, Liu H, Gong F (2013) Expression and significance of HMGB1, TLR4 and NF-kappaB p65 in human epidermal tumors. BMC Cancer 13:311PubMedPubMedCentralCrossRefGoogle Scholar
  391. Weyn B, Jacob W, da Silva VD, Montironi R, Hamilton PW, Thompson D, Bartels HG, Van Daele A, Dillon K, Bartels PH (2000) Data representation and reduction for chromatin texture in nuclei from premalignant prostatic, esophageal, and colonic lesions. Cytometry 41(2):133–138PubMedCrossRefPubMedCentralGoogle Scholar
  392. Whitman M, Downes CP, Keeler M, Keller T, Cantley L (1988) Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature 332(6165):644–646PubMedCrossRefPubMedCentralGoogle Scholar
  393. Wied GL, Bartels PH, Bibbo M, Sychra JJ (1980) Cytomorphometric markers for uterine cancer in intermediate cells. Anal Quant Cytol 2(4):257–263PubMedPubMedCentralGoogle Scholar
  394. Wikonkal NM, Brash DE (1999) Ultraviolet radiation induced signature mutations in photocarcinogenesis. J Investig Dermatol Symp Proc 4(1):6–10PubMedCrossRefPubMedCentralGoogle Scholar
  395. Wilgus TA, Ross MS, Parrett ML, Oberyszyn TM (2000) Topical application of a selective cyclooxygenase inhibitor suppresses UVB mediated cutaneous inflammation. Prostaglandins Other Lipid Mediat 62(4):367–384PubMedCrossRefPubMedCentralGoogle Scholar
  396. Wilgus TA, Breza TS Jr, Tober KL, Oberyszyn TM (2004) Treatment with 5-fluorouracil and celecoxib displays synergistic regression of ultraviolet light B-induced skin tumors. J Invest Dermatol 122(6):1488–1494PubMedCrossRefPubMedCentralGoogle Scholar
  397. Wolf JE Jr, Taylor JR, Tschen E, Kang S (2001) Topical 3.0% diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses. Int J Dermatol 40(11):709–713PubMedCrossRefPubMedCentralGoogle Scholar
  398. Wondrak GT, Jacobson MK, Jacobson EL (2005) Identification of quenchers of photoexcited States as novel agents for skin photoprotection. J Pharmacol Exp Ther 312(2):482–491CrossRefGoogle Scholar
  399. Wood WR, Seftor EA, Lotan D, Nakajima M, Misiorowski RL, Seftor RE, Lotan R, Hendrix MJ (1990) Retinoic acid inhibits human melanoma tumor cell invasion. Anticancer Res 10(2A):423–432PubMedPubMedCentralGoogle Scholar
  400. Wright TI, Spencer JM, Flowers FP (2006) Chemoprevention of nonmelanoma skin cancer. J Am Acad Dermatol 54(6):933–946; quiz 947-950PubMedCrossRefPubMedCentralGoogle Scholar
  401. Wu DC, Guiha I, Goldman MP (2017) A prospective pilot clinical trial to evaluate the efficacy and safety of topical therapy with ingenol mebutate gel 0.015% for actinic keratosis on an expanded area of the chest. J Clin Aesthet Dermatol 10(8):31–36PubMedPubMedCentralGoogle Scholar
  402. Xu XC, Clifford JL et al (1994) Detection of nuclear retinoic acid receptor mRNA in histological tissue sections using nonradioactive in sit hybridization histochemistry. Diagn Mol Pathol 3(2):122–131PubMedCrossRefPubMedCentralGoogle Scholar
  403. Xu C, Huang MT, Shen G, Yuan X, Lin W, Khor TO, Conney AH, Kong AN (2006) Inhibition of 7,12-dimethylbenz(a)anthracene-induced skin tumorigenesis in C57BL/6 mice by sulforaphane is mediated by nuclear factor E2-related factor 2. Cancer Res 66(16):8293–8296CrossRefGoogle Scholar
  404. Yasuda H, Kobayashi H, Ohkawara A, Kuzumaki N (1989) Differential expression of ras oncogene products among the types of human melanomas and melanocytic nevi. J Investig Dermatol 93(1):54–59PubMedCrossRefPubMedCentralGoogle Scholar
  405. Youl PH, Youlden DR, Baade PD (2013) Changes in the site distribution of common melanoma subtypes in Queensland, Australia over time: implications for public health campaigns. Br J Dermatol 168(1):136–144PubMedCrossRefPubMedCentralGoogle Scholar
  406. Zaravinos A, Kanellou P, Spandidos DA (2010) Viral DNA detection and RAS mutations in actinic keratosis and nonmelanoma skin cancers. Br J Dermatol 162(2):325–331PubMedCrossRefPubMedCentralGoogle Scholar
  407. Zhang J, Bowden GT (2012) Activation of p38 MAP kinase and JNK pathways by UVA irradiation. Photochem Photobiol Sci 11(1):54–61PubMedCrossRefPubMedCentralGoogle Scholar
  408. Zhang H, Rosdahl I (2006) Bcl-xL and bcl-2 proteins in melanoma progression and UVB-induced apoptosis. Int J Oncol 28(3):661–666PubMedPubMedCentralGoogle Scholar
  409. Zhang Y, Zhong S, Dong Z, Chen N, Bode AM, Ma W, Dong Z (2001) UVA induces Ser381 phosphorylation of p90RSK/MAPKAP-K1 via ERK and JNK pathways. J Biol Chem 276(18):14572–14580PubMedCrossRefPubMedCentralGoogle Scholar
  410. Zhang YP, Chu RX, Liu H (2014) Vitamin A intake and risk of melanoma: a meta-analysis. PLoS One 9(7):e102527PubMedPubMedCentralCrossRefGoogle Scholar
  411. Zhu M, Bowden GT (2004) Molecular mechanism(s) for UV-B irradiation-induced glutathione depletion in cultured human keratinocytes. Photochem Photobiol 80(2):191–196PubMedCrossRefPubMedCentralGoogle Scholar
  412. Zhu M, Zhang Y, Bowden GT (2006) Involvement of mitogen-activated protein kinases and protein kinase C in regulation of antioxidant response element activity in human keratinocytes. Cancer Lett 244(2):220–228PubMedCrossRefGoogle Scholar
  413. Zhu F, Zykova TA, Kang BS, Wang Z, Ebeling MC, Abe Y, Ma WY, Bode AM, Dong Z (2007) Bidirectional signals transduced by TOPK-ERK interaction increase tumorigenesis of HCT116 colorectal cancer cells. Gastroenterology 133(1):219–231PubMedCrossRefPubMedCentralGoogle Scholar
  414. Ziegler A, Leffell DJ, Kunala S, Sharma HW, Gailani M, Simon JA, Halperin AJ, Baden HP, Shapiro PE, Bale AE et al (1993) Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers. Proc Natl Acad Sci U S A 90(9):4216–4220PubMedPubMedCentralCrossRefGoogle Scholar
  415. Zuo L, Weger J, Yang Q, Goldstein AM, Tucker MA, Walker GJ, Hayward N, Dracopoli NC (1996) Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet 12(1):97–99PubMedCrossRefGoogle Scholar
  416. Zykova TA, Zhu F, Lu C, Higgins L, Tatsumi Y, Abe Y, Bode AM, Dong Z (2006) Lymphokine-activated killer T-cell-originated protein kinase phosphorylation of histone H2AX prevents arsenite-induced apoptosis in RPMI7951 melanoma cells. Clin Cancer Res 12(23):6884–6893PubMedPubMedCentralCrossRefGoogle Scholar
  417. Zykova TA, Zhu F, Vakorina TI, Zhang J, Higgins LA, Urusova DV, Bode AM, Dong Z (2010) T-LAK cell-originated protein kinase (TOPK) phosphorylation of Prx1 at Ser-32 prevents UVB-induced apoptosis in RPMI7951 melanoma cells through the regulation of Prx1 peroxidase activity. J Biol Chem 285(38):29138–29146PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Maria Lluria-Prevatt
    • 1
    Email author
  • Sally E. Dickinson
    • 1
  • David S. Alberts
    • 2
  1. 1.College of MedicineUniversity of ArizonaTucsonUSA
  2. 2.College of MedicineUniversity of Arizona Cancer CenterTucsonUSA

Personalised recommendations