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American Journal of Clinical Dermatology
Erschienen in: American Journal of Clinical Dermatology 4/2007

01.08.2007 | Leading Article

The Role of Topical Cyclo-Oxygenase-2 Inhibitors in Skin Cancer

Treatment and Prevention

verfasst von: Dr Huichun Zhan, Haoyi Zheng

Erschienen in: American Journal of Clinical Dermatology | Ausgabe 4/2007

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Abstract

Cyclo-oxygenases (COXs) are rate-limiting enzymes in arachidonic acid metabolism and prostaglandin production. COX-2 is the main UV-responsive COX isoform in human skin and is involved in UV-induced skin inflammation and apoptosis. The topical NSAID diclofenac works as a nonspecific COX inhibitor and is an effective and well tolerated treatment for actinic keratosis, which is a principal precursor of cutaneous squamous cell carcinoma. Oral and topical COX-2 inhibitors have chemopreventive activity against chemically and UV light-induced skin cancer in animal models. The mechanism of action of COX inhibitors in skin tumorigenesis is complex and not completely understood. Clinical trials to evaluate whether topical administration of NSAIDs or specific COX-2 inhibitors can prevent skin cancer in high-risk patients are warranted.
Fußnoten
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Literatur
1.
Johnson TM, Dolan OM, Hamilton TA, et al. Clinical and histologic trends of melanoma. J Am Acad Dermatol May 1998; 38 (5 Pt 1): 681–6PubMedCrossRef
2.
Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Engl J Med 2001 Mar 29; 344 (13): 975–83PubMedCrossRef
3.
Karagas MR, Stukel TA, Greenberg ER, et al. Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer: Skin Cancer Prevention Study Group. JAMA 1992 Jun 24; 267 (24): 3305–10PubMedCrossRef
4.
Marcil I, Stern RS. Risk of developing a subsequent nonmelanoma skin cancer in patients with a history of nonmelanoma skin cancer: a critical review of the literature and meta-analysis. Arch Dermatol Dec 2000; 136 (12): 1524–30PubMedCrossRef
5.
Frankel DH, Hanusa BH, Zitelli JA. 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 1992 May; 26 (5 Pt 1): 720–6PubMedCrossRef
6.
Tsai KY, Tsao H. The genetics of skin cancer. Am J Med Genet C Semin Med Genet 2004 Nov 15; 131C (1): 82–92PubMedCrossRef
7.
Dodson JM, DeSpain J, Hewett JE, et al. Malignant potential of actinic keratoses and the controversy over treatment: a patient-oriented perspective. Arch Dermatol 1991 Jul; 127 (7): 1029–31PubMedCrossRef
8.
Czarnecki D, Meehan CJ, Bruce F, et al. The majority of cutaneous squamous cell carcinomas arise in actinic keratoses. J Cutan Med Surg 2002 May-Jun; 6 (3): 207–9PubMedCrossRef
9.
Jeffes 3rd EW, Tang EH. Actinic keratosis: current treatment options. Am J Clin Dermatol 2000 MayJun; 1 (3): 167–79PubMedCrossRef
10.
11.
Brash DE, Ziegler A, Jonason AS, et al. Sunlight and sunburn in human skin cancer: p53, apoptosis, and tumor promotion. J Investig Dermatol Symp Proc 1996 Apr; 1 (2): 136–42PubMed
12.
Nickoloff BJ, Qin JZ, Chaturvedi V, et al. Life and death signaling pathways contributing to skin cancer. J Investig Dermatol Symp Proc 2002 Dec; 7 (1): 27–35PubMedCrossRef
13.
Berhane T, Halliday GM, Cooke B, et al. Inflammation is associated with progression of actinic keratoses to squamous cell carcinomas in humans. Br J Dermatol 2002 May; 146 (5): 810–5PubMedCrossRef
14.
Nakagawa K, Yamamura K, Maeda S, et al. Bcl-2 expression in epidermal keratinocytic diseases. Cancer 1994 Sep 15; 74 (6): 1720–4PubMedCrossRef
15.
Mann JR, Backlund MG, DuBois RN. Mechanisms of disease: inflammatory mediators and cancer prevention. Nat Clin Pract Oncol 2005 Apr; 2 (4): 202–10PubMedCrossRef
16.
17.
Lee JL, Mukhtar H, Bickers DR, et al. Cyclooxygenases in the skin: pharmacological and toxicological implications. Toxicol Appl Pharmacol 2003 Nov 1; 192 (3): 294–306PubMedCrossRef
18.
Smith WL, Garavito RM, DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 1996 Dec 27; 271 (52): 33157–60PubMedCrossRef
19.
Leong J, Hughes-Fulford M, Rakhlin N, et al. Cyclooxygenases in human and mouse skin and cultured human keratinocytes: association of COX-2 expression with human keratinocyte differentiation. Exp Cell Res 1996 Apr 10; 224 (1): 79–87PubMedCrossRef
20.
Muller-Decker K, Reinerth G, Krieg P, et al. Prostaglandin-H-synthase isozyme expression in normal and neoplastic human skin. Int J Cancer 1999 Aug 27; 82 (5): 648–56PubMedCrossRef
21.
Buckman SY, Gresham A, Hale P, et al. COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer. Carcinogenesis 1998 May; 19 (5): 723–9PubMedCrossRef
22.
Isoherranen K, Punnonen K, Jansen C, et al. Ultraviolet irradiation induces cyclooxygenase-2 expression in keratinocytes. Br J Dermatol 1999 Jun; 140 (6): 1017–22PubMedCrossRef
23.
Gresham A, Masferrer J, Chen X, et al. Increased synthesis of high-molecular-weight cPLA2 mediates early UV-induced PGE2 in human skin. Am J Physiol 1996 Apr; 270 (4 Pt 1): C1037–50PubMed
24.
Wilgus TA, Parrett ML, Ross MS, et al. Inhibition of ultraviolet light B-induced cutaneous inflammation by a specific cyclooxygenase-2 inhibitor. Adv Exp Med Biol 2002; 507: 85–92PubMedCrossRef
25.
Wilgus TA, Ross MS, Parrett ML, et al.Topical application of a selective cyclooxygenase inhibitor suppresses UVB mediated cutaneous inflammation. Prostaglandins Other Lipid Mediat 2000 Oct; 62(4) 367–8PubMedCrossRef
26.
Pruthi RS, Derksen E, Gaston K. Cyclooxygenase-2 as a potential target in the prevention and treatment of genitourinary tumors: a review. J Urol 2003 Jun; 169 (6): 2352–9PubMedCrossRef
27.
Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996 Nov 29; 87 (5): 803–9PubMedCrossRef
28.
Liu CH, Chang SH, Narko K, et al. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice.J Biol Chem 2001 May 25; 276 (21): 18563–9PubMedCrossRef
29.
Athar M, An KP, Morel KD, et al. Ultraviolet B (UVB)-induced cox-2 expression in murine skin: an immunohistochemical study. Biochem Biophys Res Commun 2001 Feb 2; 280 (4): 1042–7PubMedCrossRef
30.
Muller-Decker K, Neufang G, Berger I, et al. Transgenic cyclooxygenase-2 over-expression sensitizes mouse skin for carcinogenesis. Proc Natl Acad Sci USA 2002 Sep 17; 99 (19): 12483–8PubMedCrossRef
31.
An KP, Athar M, Tang X, et al. Cyclooxygenase-2 expression in murine and human nonmelanoma skin cancers: implications for therapeutic approaches.Photochem Photobiol 2002 Jul; 76 (1): 73–80PubMedCrossRef
32.
Tiano HF, Loftin CD, Akunda J, et al. Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. Cancer Res 2002 Jun 15; 62 (12): 3395–401PubMed
33.
Neufang G, Furstenberger G, Heidt M, et al. Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin. Proc Natl Acad Sci U S A 2001 Jun 19; 98 (13): 7629–34PubMedCrossRef
34.
Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 1995 Nov 3; 83 (3): 493–501PubMedCrossRef
35.
Liu XH, Yao S, Kirschenbaum. NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells. Cancer Res 1998 Oct 1; 58 (19): 4245–9PubMed
36.
Sheng H, Shao J, Morrow JD, et al. Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 1998 Jan 15; 58 (2): 362–6PubMed
37.
Arico S, Pattingre S, Bauvy C, et al. Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line. J Biol Chem 2002 Aug 2; 277 (31): 27613–21PubMedCrossRef
38.
Friedman ES, La Natra N, Stiller MJ. NSAIDs in dermatologic therapy: review and preview. J Cutan Med Surg 2002 Sep-Oct; 6 (5): 449–59PubMedCrossRef
39.
Black AK, Greaves MW, Hensby CN. The anti-inflammatory and pharmacological effects of topically applied flurbiprofen human skin 24 hours after ultraviolet B irradiation. Prostaglandins Med 1980;5(5) 405–13PubMedCrossRef
40.
Snyder DS, Eaglstein WH. Topical indomethacin and sunburn. Br J Dermatol 1974 Jan; 90(1) 91–3PubMedCrossRef
41.
Butler GJ, Neale R, Green AC, et al. Nonsteroidal anti-inflammatory drugs and the risk of actinic keratoses and squamous cell cancers of the skin. J Am Acad Dermatol 2005 Dec; 53 (6): 966–72PubMedCrossRef
42.
Gupta AK, Cooper EA, Feldman SR, et al. A survey of office visits for actinic keratosis as reported by NAMCS, 1990-1999: National Ambulatory Medical Care Survey. Cutis 2002 Aug; 70 (2 Suppl.): 8–13PubMed
43.
Riendeau D, Percival MD, Brideau C, et al. Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2. J Pharmacol Exp Ther 2001 Feb; 296 (2): 558–66PubMed
44.
Rivers JK, McLean DI. 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 1997 Oct; 133 (10): 1239–42PubMedCrossRef
45.
Nelson C, Rigel D, Smith S, et al. Phase IV, open-label assessment of the treatment of actinic keratosis with 3.0% diclofenac sodium topical gel (Solaraze). J Drugs Dermatol 2004 Jul-Aug; 3 (4): 401–7PubMed
46.
Wolf Jr JE, Taylor JR, Tschen E, et al. Topical 3.0% diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses. Int J Dermatol 2001 Nov; 40 (11): 709–13PubMedCrossRef
47.
Rivers JK, Arlette J, Shear N, et al. Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel. Br J Dermatol 2002 Jan; 146 (1): 94–100PubMedCrossRef
48.
Gebauer K, Brown P, Varigos G. Topical diclofenac in hyaluronan gel for the treatment of solar keratoses. Australas J Dermatol 2003 Feb; 44 (1): 40–3PubMedCrossRef
49.
Cao Y, Prescott SM. Many actions of cyclooxygenase-2 in cellular dynamics and in cancer. J Cell Physiol 2002 Mar; 190 (3): 279–86PubMedCrossRef
50.
Muller-Decker K, Kopp-Schneider A, Marks F, et al. Localization of prostaglandin H synthase isoenzymes in murine epidermal tumors: suppression of skin tumor promotion by inhibition of prostaglandin H synthase-2. Mol Carcinog 1998 Sep; 23 (1): 36–44PubMedCrossRef
51.
Pentland AP, Schoggins JW, Scott GA, et al. Reduction of UV-induced skin tumors in hairless mice by selective COX-2 inhibition. Carcinogenesis 1999 Oct; 20 (10): 1939–44PubMedCrossRef
52.
Fischer SM, Lo HH, Gordon GB, et al. Chemopreventive activity of celecoxib, a specific cyclooxygenase-2 inhibitor, and indomethacin against ultraviolet light-induced skin carcinogenesis. Mol Carcinog 1999 Aug; 25 (4): 231–40PubMedCrossRef
53.
Orengo IF, Gerguis J, Phillips R, et al. Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer: a study in the hairless mouse model. Arch Dermatol 2002 Jun; 138 (6): 751–5PubMedCrossRef
54.
Wilgus TA, Koki AT, Zweifel BS, et al. Chemotherapeutic efficacy of topical celecoxib in a murine model of ultraviolet light B-induced skin cancer. Mol Carcinog 2003Sep; 38 (1): 33–9PubMedCrossRef
55.
Tober KL, Wilgus TA, Kusewitt DF, et al. Importance of the EP(1) receptor in cutaneous UVB-induced inflammation and tumor development. J Invest Dermatol 2006 Jan; 126 (1): 205–11PubMedCrossRef
56.
57.
Yener G, Gonullu U, Uner. Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of celecoxib through human skin. Pharmazie 2003 May; 58 (5): 330–3PubMed
58.
Subramanian N, Ghosal SK, Moulik SP. Enhanced in vitro percutaneous absorption and in vivo anti-inflammatory effect of a selective cyclooxygenase inhibitor using microemulsion. Drug Dev Ind Pharm 2005 May; 31 (4-5): 405–16PubMedCrossRef
59.
Denkert C, Kobel M, Berger S, et al. Expression of cyclooxygenase 2 in human malignant melanoma. Cancer Res 2001 Jan 1; 61 (1): 303–8PubMed
60.
Kuzbicki L, Sarnecka A, Chwirot BW. Expression of cyclooxygenase-2 in benign naevi and during human cutaneous melanoma progression. Melanoma Res 2006 Feb; 16 (1): 29–36PubMedCrossRef
61.
Gogas H, Polyzos A, Stavrinidis I, et al. Temozolomide in combination with celecoxib in patients with advanced melanoma: a phase II study of the Hellenic Cooperative Oncology Group. Ann Oncol 2006 Dec; 17 (12): 1835–41PubMedCrossRef
62.
Spieth K, Kaufmann R, Gille J. Metronomic oral low-dose treosulfan chemotherapy combined with cyclooxygenase-2 inhibitor in pretreated advanced melanoma: a pilot study. Cancer Chemother Pharmacol 2003 Nov; 52 (5): 377–82PubMedCrossRef
63.
Lejeune FJ, Monnier Y, Ruegg C. Complete and long-lasting regression of disseminated multiple skin melanoma metastases under treatment with cyclooxygenase-2 inhibitor. Melanoma Res 2006 Jun; 16 (3): 263–5
64.
Bresalier RS, Sandler RS, Quan H, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005 Mar 17]; 352 (11): 1092–1PubMedCrossRef
65.
Solomon SD, McMurray JJ, Pfeffer MA, et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005 Mar 17; 352 (11): 1071–80PubMedCrossRef
66.
Nussmeier NA, Whelton AA, Brown MT, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 2005 Mar 17; 352 (11): 1081–91PubMedCrossRef
67.
Jarvis B, Figgitt DP. Topical 3% diclofenac in 2.5% hyaluronic acid gel: a review of its use in patients with actinic keratoses. Am J Clin Dermatol 2003; 4 (3): 203–13PubMedCrossRef
Metadaten
Titel
The Role of Topical Cyclo-Oxygenase-2 Inhibitors in Skin Cancer
Treatment and Prevention
verfasst von
Dr Huichun Zhan
Haoyi Zheng
Publikationsdatum
01.08.2007
Verlag
Springer International Publishing
Erschienen in
American Journal of Clinical Dermatology / Ausgabe 4/2007
Print ISSN: 1175-0561
Elektronische ISSN: 1179-1888
DOI
https://doi.org/10.2165/00128071-200708040-00002

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