Article information
Abstract
Actinic keratoses (AK) represent the most common carcinoma in situ of the skin and show continuously increasing incidences worldwide. Clinically, AK occur as multiple lesions in sun-exposed areas, which has been referred to as field cancerization. Novel treatment modalities for actinic field cancerization include 3% diclofenac in 2.5% hyaluronic acid (HA). Recent investigations have gained insights in the mode of action of diclofenac in HA, showing that the induction of apoptosis is the major mode of action of this treatment.
Herein, we give an overview about actinic keratosis focusing on treatment with the COX-2 inhibitor diclofenac 3% gel and summarize current concepts of its antineoplastic mode of action.
Key words:
actinic keratoses
carcinoma in situ
diclofenac
hyaluronic acid
apoptosis
COX-2
Resumen
Las queratosis actínicas representan el carcinoma intraepidérmico más frecuente de la piel y muestran un incremento continuo de la incidencia mundialmente. Clínicamente, las queratosis actínicas aparecen de forma múltiple en áreas fotoexpuestas, lo que se conoce como campo de cancerización. Las nuevas opciones para el tratamiento del campo de cancerización actínico incluyen diclofenaco al 3% en ácido hialurónico al 2,5%. Investigaciones recientes han revelado el principal mecanismo de acción de diclofenaco, que consiste en la inducción de la apoptosis.
En este artículo aportaremos una visión de conjunto sobre las queratosis actínicas, centrándonos en el tratamiento con un inhibidor de la enzima COX-2, diclofenaco al 3%, y resumiremos los conceptos actuales sobre su mecanismo de acción antineoplásico.
Palabras clave:
queratosis actínicas
carcinoma intraepidérmico
diclofenaco
ácido hialurónico
apoptosis
COX-2
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References
[1.]
A.A. Memon, J.A. Tomenson, J. Bothwell, P.S. Friedmann.
Prevalence of solar damage and actinic keratosis in a Merseyside population.
Br J Dermatol, 142 (2000), pp. 1154-1159
[2.]
S.J. Salasche.
Epidemiology of actinic keratoses and squamous cell carcinoma.
J Am Acad Dermatol, 42 (2000), pp. 4-7
[3.]
C. Frost, G. Williams, A. Green.
High incidence and regression rates of solar keratoses in a queensland community.
J Invest Dermatol, 115 (2000), pp. 273-277
[4.]
M. Trakatelli, C. Ulrich, V. del Marmol, S. Euvrard, E. Stockfleth, D. Abeni.
Epidemiology of nonmelanoma skin cancer (NMSC) in Europe: accurate and comparable data are needed for effective public health monitoring and interventions.
Br J Dermatol, 156 (2007), pp. 1-7
[5.]
E. Stockfleth, C. Ulrich, T. Meyer, E. Christophers.
Epithelial malignancies in organ transplant patients: clinical presentation and new methods of treatment.
Recent Results Cancer Res, 160 (2002), pp. 251-258
[6.]
C. Ulrich, E. Christophers, W. Sterry, T. Meyer, E. Stockfleth.
Skin diseases in organ transplant patients.
Hautarzt, 53 (2002), pp. 524-533
[7.]
A.B. Ackerman.
Solar keratosis is squamous cell carcinoma.
Arch Dermatol, 139 (2003), pp. 1216-1217
[8.]
M.R. Heaphy Jr, A.B. Ackerman.
The nature of solar keratosis: a critical review in historical perspective.
J Am Acad Dermatol, 43 (2000), pp. 138-150
[9.]
J. Röwert-Huber, M.J. Patel, T. Forschner, C. Ulrich, J. Eberle, H. Kerl, et al.
Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification.
Br J Dermatol, 156 (2007), pp. 8-12
[10.]
W.S. Park, H.K. Lee, J.Y. Lee, N.J. Yoo, C.S. Kim, S.H. Kim.
P53 mutations in solar keratosis.
Hum Pathol, 27 (1996), pp. 1180-1184
[11.]
Y. Kushida, H. Miki, M. Ohmori.
Loss of herterozygosity in actinic keratosis, squamous cell carcinoma and sun-exposed normal appearing skin: difference between Japanese and Caucasians.
Cancer, 140 (1999), pp. 169-175
[12.]
M.A. Nelson, J.G. Einspahr, D.S. Alberts, C.A. Balfour, J.A. Wymer, K.L. Welch, et al.
Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers.
Cancer Lett, 85 (1994), pp. 23-29
[13.]
T.Y. Chuang, L.A. Heinrich, M.D. Schultz, G.T. Reizner, R.C. Kumm, D.J. Cripps.
PUVA and skin cancer. A historical cohort study on 492 patients.
J Am Acad Dermatol, 26 (1992), pp. 173-177
[14.]
S. Jackson, A. Storey.
E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage.
Oncogene, 19 (2000), pp. 592-598
[15.]
S. Jackson, C. Harwood, M. Thomas, L. Banks, A. Storey.
Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins.
Genes Dev, 14 (2000), pp. 3065-3073
[16.]
K. Hazard, A. Karlsson, K. Andersson, H. Ekberg, J. Dillner, O. Forslund.
Cutaneous human papillomaviruses persist on healthy skin.
J Invest Dermatol, 127 (2007), pp. 116-119
[17.]
I. Nindl, M. Gottschling, E. Stockfleth.
Human papillomaviruses and non-melanoma skin cancer: basic virology and clinical manifestations.
Dis Markers, 23 (2007), pp. 247-259
[18.]
B.J.M. Braakhuis, M.P. Tabor, J.A. Kummer, C.R. Leemans, R.H. Brakenhoff.
A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications.
Cancer Res, 63 (2003), pp. 1727-1730
[19.]
L.F. Fecker, E. Stockfleth, I. Nindl, C. Ulrich, T. Forschner, J. Eberle.
The role of apoptosis in therapy and prophylaxis of epithelial tumours by nonsteroidal anti-inflammatory drugs (NSAIDs).
Br J Dermatol, 156 (2007), pp. 25-33
[20.]
J. Eberle, L.F. Fecker, T. Forschner, C. Ulrich, J. Röwert-Huber, E. Stockfleth.
Apoptosis pathways as promising targets for skin cancer therapy.
Br J Dermatol, 156 (2007), pp. 18-24
[21.]
J.R. Vane, R.M. Botting.
New insights into the mode of action of anti-inflammatory drugs.
Inflamm Res, 44 (1995), pp. 1-10
[22.]
D. Wang, R.N. DuBois.
Prostaglandins and cancer.
Gut, 55 (2006), pp. 115-122
[23.]
R.N. DuBois, S.B. Abrahamson, L. Crofford, R.A. Gupta, L.S. Simon, L.B. Van De Putte, et al.
Cyclooxygenase in biology and disease.
FASEB J, 12 (1998), pp. 1063-1073
[24.]
W.L. Smith, D.L. DeWitt, R.M. Garavito.
Cyclooxygenases: structural, cellular and molecular biology.
Ann Rev Biochem, 69 (2000), pp. 145-182
[25.]
W. Yu, N.R. Murray, C. Weems, L. Chen, H. Guo, R. Ethridge, et al.
Role of Cyclooxygenase 2 in protein kinase C beta IImediated colon carcinogenesis.
J Biol Chem, 278 (2003), pp. 11167-11174
[26.]
K. Muller-Decker.
Cyclooxegenases in the skin.
J Dtsch Dermatol Ges, 2 (2004), pp. 668-675
[27.]
T. Nijsten, C.G. Colpaert, P.B. Vermeulen, A.L. Harris, E. Van Marck, J. Lambert.
Cyclooxegenase-2 expression and angiogenesis in squamous cell carcinoma of the skin and its precursors: a paired immunohistochemical of 35 cases.
Br J Dermatol, 151 (2004), pp. 837-845
[28.]
J.I. Johnsen, M. Lindskog, F. Ponthan, I. Pettersen, L. Elfman, A. Orrego, et al.
Cyclooxygenase-2 is expressed in neuroblastoma, and nonsteroidal anti-inflammatory drugs induce apoptosis and inhibit tumor growth in-vivo.
Cancer Res, 64 (2004), pp. 7210-7215
[29.]
J.I. Johnsen, M. Lindskog, F. Ponthan, I. Pettersen, L. Elfman, A. Orrego, et al.
NSAIDs in neuroblastoma therapy.
Cancer Lett, 228 (2005), pp. 195-2001
[30.]
M.P. Seed, J.R. Brown, C.N. Freemantle, J.L. Papworth, P.R. Colville-Nash, D. Willis, et al.
The inhibition of colon-26 adenocarcinoma development and angiogenesis by topical diclofenac in 2.5% hyaluran.
Cancer Res, 57 (1997), pp. 1625-1629
[31.]
C. Wang, M. Tammi, R. Tammi.
Distribution of hyaluran and its CD 44 receptor in the epithelia of human skin appendages.
Histochemistry, 98 (1992), pp. 105-112
[32.]
R.K. Jain.
Tumor angiogenesis and accessibility: role of vascular endothelial growth factor.
Semin Oncol, 29 (2002), pp. 3-9
[33.]
O. Gallo, A. Franchi, L. Magnelli, I. Sardi, A. Vannacci, V. Boddi, et al.
Cyclooxygenase pathway correlates with VEGF expression in head and neck cancer. Implications for tumour angiogenesis and metastasis.
Neoplasia, 3 (2001), pp. 53-61
[34.]
J.K. Rivers, J. Arlette, N. Shear, L. Guenther, W. Carey, Y. Poulin.
Topical treatment of actinic keratoses with 3.0% diclofenac in 2,5% hyaluronan gel.
Br J Dermatol, 146 (2002), pp. 94-100
[35.]
K. Gebauer, P. Brown, G. Varigos.
Topical diclofenac in hyaluronan gel for the treatment of solar keratoses.
Austr J Dermatol, 44 (2003), pp. 40-45
[36.]
J.E. Wolf Jr, J.R. Taylor, E. Tschen, S. Kang.
Topical 3,0% diclofenac in 2,5% hyaluronan gel in the treatment of actinic keratoses.
Int J Dermatol, 40 (2001), pp. 709-713
[37.]
C. Ulrich, M. Hackethal, M. Ulrich, A. Howorka, T. Forschner, W. Sterry, et al.
Treatment of multiple actinic keratosis with topical diclofenac 3% gel (Solaraze™) in organ transplant recipients: a series of 6 cases.
Br J Dermatol, 156 (2007), pp. 40-42
[38.]
C. Ulrich, T. Forschner, M. Ulrich, E. Stockfleth, W. Sterry, C. Termeer.
Management of actinic cheilitis using diclofenac 3% gel: a report of six cases.
Br J Dermatol, 156 (2007), pp. 43-46
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