SKIN CANCERS – RISK FACTORS, PREVENTION AND THERAPY Edited by Caterina AM La Porta Skin Cancers – Risk Factors, Prevention and Therapy Edited by Caterina AM La Porta Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. 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Used under license from Shutterstock.com First published October, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Skin Cancers – Risk Factors, Prevention and Therapy, Edited by Caterina AM La Porta p. cm. ISBN 978-953-307-722-2 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Risk Factors for Skin Cancer 1 Chapter 1 Indoor Tanning: A Bio-Behavioral Risk Factor for Skin Cancer 3 Carolyn J. Heckman and Sharon L. Manne Chapter 2 UV-Induced Immune Suppression that Promotes Skin Cancer Development and Progression 27 Takuma Kato and Linan Wang Chapter 3 Genetic Predisposition to Cutaneous Squamous Cell Carcinoma 53 Yi-Zhen Ng, Jasbani H.S Dayal and Andrew P. South Chapter 4 Melanoma Cell Signalling: Looking Beyond RAS-RAF-MEK 87 Visalini Muthusamy and Terrence J. Piva Chapter 5 Merkel Cell Polyomavirus: A Causal Factor in Merkel Cell Carcinoma 109 Marijke Van Ghelue and Ugo Moens Chapter 6 Macrophage Migration Inhibitory Factor (MIF) Overexpression Accelerates Photocarcinogenesis in the Skin 143 Tadamichi Shimizu Part 2 Skin Cancer Diagnosis 157 Chapter 7 Optical Imaging as Auxiliary Tool in Skin Cancer Diagnosis 159 S. Pratavieira, C. T. Andrade, A. G. Salvio, V.S. Bagnato and C. Kurachi VI Contents Part 3 Prevention and Therapy for Skin Cancer 173 Chapter 8 Cyclooxygenase-2 Overexpression in Non-Melanoma Skin Cancer: Molecular Pathways Involved as Targets for Prevention and Treatment 175 Daniel H. González Maglio, Mariela L. Paz, Eliana M. Cela and Juliana Leoni Chapter 9 Chemoprevention of Skin Cancer by Natural Compounds 197 Gabriela Adriana Filip and Simona Clichici Chapter 10 Photodynamic Therapy in Skin Cancer 221 Simona Clichici and Gabriela Adriana Filip Chapter 11 Topical Administration of Anticancer Drugs for Skin Cancer Treatment 247 Stephânia Fleury Taveira and Renata Fonseca Vianna Lopez Preface Skin cancers are the fastest growing type of cancer in the United States and represent the most commonly diagnosed malignancy, surpassing lung, breast, colorectal and prostate cancer. In Europe, the British Isles have been the highest rates of skin cancer in children and adolescents. The most common types of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In particular BCC of the skin is the most prevalent type of cancer affecting Caucasians. However, the most dangerous type of skin cancer is malignant melanoma. This form of skin cancer can be fatal if it is not treated early but comprises only a small proportion of all skin cancers. This book discusses the most interesting and new aspects related to skin cancer focusing on three main issues: 1) risk factors, including extrinsic factors (i.e., indoor tanning which plays in west society an important social function, or UV and virus) and intrinsic factors (i.e., genetic predisposition, intracellular signaling, inflammation); 2) new diagnostic tools for prevention (i.e. optical imaging); 3) a more clear and scientific explanation of the strategies for prevention and treatment of skin cancer using natural compounds or nano-particle drug delivery and photodynamic therapy. The overall idea of the book is to provide the reader with up to date information on the possible tools to use for prevention, diagnosis and treatment of skin cancer. The impact of indoor tanning is discussed in Chapter 1, which is a quite common practice in USA and Western countries. The chapter contains an interesting historical description and psychological motivations are also discussed. The authors report a robust literature documenting a strong link between indoor tanning and incidence of skin cancer. Policy and regulations are also discussed. The molecular mechanisms triggered by UV radiation are discussed in Chapter 2. In particular, the effect of UV radiation on the immunosystem is discussed in depth. In fact, UV inducing immunosuppression, seems to contribute to the development and progression of skin tumor. The immunosurveillance of tumor is actually an important and crucial aspect as anti-tumor activity. Chapter 3 focuses on cutaneous squamous carcinoma and genetic abnormalities closely associated with it. A number of familial cancer syndromes, recessive dystrophic epidermolysis bullosa appear to be associated with an increased risk of developing X Preface cutaneous squamous carcinoma as well as hereditary skin disorders. The molecular mechanisms involved are not completely understood but an important and interesting aspect seems to be the microenvironment. Chapter 4 focuses on RAS-RAF-MEK pathway in melanoma as chemotherapeutic target. However, an important aspect to further investigate is the toxicity of these drugs. The involvement of Merkel cell polyomavirus in Merkel cell carcinoma is presented in Chapter 5. Interesting perspectives and new development of the research are discussed. For instance, integration sites, route of infection, cell tropism etc. are not clarified yet. Further studies are needed in this filed. Chapter 6 discusses the accelerating effect of over-expression of macrophage migration inhibitor factor (MIF) on photocarcinogenesis in the skin. Chronic exposure to UV irradiation is involved in the early-onset skin carcinogenesis. Many cytokines like as MIF, seem to be related to the induction of UV-induced skin cancer. This chapter points out the pivotal role of inflammation process. Chapter 7 focused on COX-2 as potential target for anti-tumor activity in non melanoma skin cancer. The possible use of pharmacological and natural compounds acting on COX-2 are discussed in view of a chemo-prevention treatment. Several optical modalities are under study to improve cancer diagnosis. Chapter 8 review this aspect, discussing the efficacy of the optical techniques based on its specificity and sensitivity rates. Finally the last three chapters discuss chemoprevention and new therapeutic strategies. Chapter 9 discusses the possible use of natural compounds for chemoprevention in skin cancer and their intracellular mechanisms. Chapter 10 is focused on photodynamic therapy in skin cancer. A critical discussion of the literature is reported. Chapter 11 discusses the use of topical administration of anticancer drugs and, in particular, nanoparticulate drugs to overcome the skin barrier and to improve the efficacy of topical skin cancer therapy. In each chapter there is the state of the art and a critical discussion of the literature with the aim to give to the reader a useful tool for his/her future research. Caterina AM La Porta, PhD Department of Biomolecular Science and Biotechnology, University of Milan, Milan, Italy [...]... Hillhouse and colleagues This booklet focuses on normative influences such as recent fashion trends toward natural skin tones, and also includes material about the 12 Skin Cancers – Risk Factors, Prevention and Therapy history of tanning, UV radiation and its contribution to skin cancer and photo-aging, harm-reduction strategies to reduce or stop indoor tanning including use of sunless tanners, and appearance-enhancing... Skin Cancers – Risk Factors, Prevention and Therapy 7 Conclusion Indoor tanning is common in the Western world and may still be gaining popularity in some countries Indoor tanning is now known to be a definitive risk factor for skin cancers Several studies have demonstrated a dose response relationship between indoor tanning and skin cancer Like tobacco, indoor tanning has been marketed aggressively and. .. Skin Cancers – Risk Factors, Prevention and Therapy Cho, H., Hall, J G., Kosmoski, C., Fox, R L., & Mastin, T (2010) Tanning, skin cancer risk, and prevention: a content analysis of eight popular magazines that target female readers, 1997-2006 Health Commun, 25(1), 1-10 doi: 10.1080/10410230903265938 Choi, K., Lazovich, D., Southwell, B., Forster, J., Rolnick, S J., & Jackson, J (2010) Prevalence and. .. enhancers with minimal sunscreens, further increasing the level of skin cancer risk conferred by tanning 8 Skin Cancers – Risk Factors, Prevention and Therapy The first tanning salon, Tantrific, opened in Arkansas in 1978 (Segrave, 2005) By 1980, there were 1,000 tanning salons in the USA and many individual tanning units in health- and fitness-related establishments (Segrave, 2005) In the early to... (1-9 sessions) For men, measures of sunbed use were not significantly associated with melanoma risk Whereas most cancers strike older individuals, melanoma has become the most common cancer among 25-29 year old women in the USA, and the second most common cancer 6 Skin Cancers – Risk Factors, Prevention and Therapy among 15-29 year old women (Herzog et al., 2007) With regard to studies conducted outside... particularly in Nordic countries A 2001 study of Swedish young adults found that 44% had ever used sunbeds 4 Skin Cancers – Risk Factors, Prevention and Therapy (Branstrom, Ullen, & Brandberg, 2004) One 1993 study of high school students found that about three-quarters (75%) of Norwegian girls and 65% of Norwegian boys had used a sunbed during the past year (Wichstrom, 1994) The prevalence of indoor... inspections of manufacturers, and infrequent FDA inspections of tanning salons 14 Skin Cancers – Risk Factors, Prevention and Therapy The FDA recommends that UV exposure should be restricted to “no more than 0.75 minimal erythemal dose (MED), three times during the first week” of exposure, gradually increasing the exposure thereafter (United States Department of Health and Human Services, 1988; United... that the greater the UV exposure, the greater the risk for melanoma 4 Attitudes toward tanning throughout history 4.1 Pre-industrial revolution Not only has the understanding of UV and skin cancer changed over time, but the societal meaning of skin color also has varied across history and geography Depending on these factors, both darker and lighter skin colors have been associated with social status... reduce indoor tanning is growing, and more rigorous research including more longitudinal trials is needed Interventions for frequent tanners and tanning dependent individuals will likely need to be more intensive and focus on additional emotional and addiction issues beyond appearance and skin cancer risk 6 Policies and regulations Another similarity between tanning and other addictions is that policy... classes worked in factories and lived in polluted, crowded, unsanitary slum areas where tuberculosis and rickets were common (Carter, 2007; Randle, 1997; Stradling, 1999) Pale skin was viewed as unhealthy and even associated with mental illness and alcoholism (Carter, 2007; Randle, 1997; Stradling, 1999) Only the upper classes had the time and money to take beach vacations and engage in outdoor hobbies; . SKIN CANCERS – RISK FACTORS, PREVENTION AND THERAPY Edited by Caterina AM La Porta Skin Cancers – Risk Factors, Prevention and Therapy Edited by. minimal sunscreens, further increasing the level of skin cancer risk conferred by tanning. Skin Cancers – Risk Factors, Prevention and Therapy 8 The first tanning salon, Tantrific, opened. young adults found that 44% had ever used sunbeds Skin Cancers – Risk Factors, Prevention and Therapy 4 (Branstrom, Ullen, & Brandberg, 2004). One 1993 study of high school students