The Oncologist-2004-Perlis-182-7

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Unformatted text preview: .edu Received February 13, 2003; accepted for publication August 27, 2003. ©AlphaMed Press 1083-7159/2003/$12.00/0 The Oncologist 2004;9:182-187 www.TheOncologist.com 183 have been experienced with interleukin-2 therapy. In light of the rising incidence and high mortality rate in advanced disease, several countries now recognize melanoma as a top public health priority. This article reviews selected recent advances in the understanding of melanoma biology that involve the initiation, progression, and programmed cell death processes. UV LIGHT AND MELANOMA UV light has been implicated in the genesis of several forms of cutaneous malignancies: squamous cell carcinoma, basal cell carcinoma, and melanoma. Epidemiological studies reveal a strong association between melanoma formation and sunlight exposure. Whereas squamous and basal cell carcinomas appear to be linked to total lifetime sun exposure, melanoma development is most closely associated with intense, intermittent exposure [5-9]. A history of sunburn is often used as a surrogate measure for intense intermittent exposure. The odds ratios for increased risk of melanoma due to sunburns in adult life, adolescence, and in childhood were 1.91, 1.73, and 1.95, respectively. In addition, the locations of melanomas suggest causation by intermittent sun exposure. Melanomas occur relatively less frequently in areas that are continuously exposed to sunlight, like the face, hands, and arms, and more frequently in sun-protected areas receiving intermittent exposure, like the trunk in men and the backs of legs in women [8]. Experimental studies support the epidemiologic evidence implicating sun exposure in causing melanoma. Intense intermittent exposure apparently does not give melanocytes time to synthesize melanin to protect themselves from UV irradiation. This irradiation leads to DNA mutations. Although UV-A light is more abundant in sunlight than UV-B light, the latter is responsible for several types of DNA lesions; it induces cyclobutane-pyrimidine dimers and pyrimidine-pyrimidone photoproducts [10-11]. DNA mutations result from incorrect repair of these lesions [11]. Prolonged sun exposure allows melanocytes to increase melanin production. UV-B light can stimulate the transfer of melanin to form protective caps above the nuclei of suprabasal keratinocytes. During intense intermittent exposure, however, cells receive large doses of UV radiation without protection from increased melanin synthesis. In addition, melanocytes contain several prosurvival or antiapoptotic proteins. These may inhibit cell death following intense UV exposure [12-14]. Therefore, melanocytes can receive intense mutagenic UV light and survive. If they are stimulated by growth factors, chances for transformation increase [15]. UV-B irradiation may also stimulate melanoma genesis by modulating growth factors, inhibiting the endogenous antioxidant system, or inhibiting cell-mediated immunity. Recent Advances in Melanoma Biology Animal experimental systems support a role for UV light in melanoma causation. For ex...
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