The Oncologist-2004-Perlis-182-7

B histologic section hematoxylin and eosin stained

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Unformatted text preview: k). B) Histologic section (hematoxylin and eosin stained, magnification 200×) of a lentiginous form of malignant melanoma in a human skin graft on a SCID mouse. The graft had received a total of seven injections of bFGF/Ad5 and 26 UV-B irradiations. Note the hyperplastic atypical melanocytic cells (arrows) in the epidermis in a dense lentiginous growth pattern. Photographs courtesy of Carolla Berking. Figure 2. Altered cadherin expression during melanoma progression. The progression of melanoma along with its accompanying change in cadherin expression is illustrated. A) Keratinocytes and melanocytes both express E-cadherin. Through E-cadherin expression, keratinocytes dictate melanocyte behavior. B) While keratinocytes continue to express E-cadherin, early melanomas begin to lose expression of E-cadherin and escape keratinocyte control. C) More advanced melanomas begin to express N-cadherin and may interact with other cells that express N-cadherin, like fibroblasts and endothelial cells. Perlis, Herlyn predominantly target tumor-infiltrating endothelial cells. In melanoma, we expect dual targeting for normal and malignant cells. CONCLUSION Recent advances in the understanding of the biology of melanoma promise to provide not just keys to further knowledge per se, but also clues to novel and more effective therapies. Models employing UV-B light to induce melanoma in human skin promise to lead to significant advancements in prevention. Scientists can now better dissect the specific mechanisms of UV-B-radiation-induced melanoma genesis as well as observe key steps in tumor initiation and progression. Findings from studies of the B-raf gene illustrate that broad screening approaches have a value for identifying new targets for therapy by developing spe- 186 cific inhibitors. Better knowledge of the intricate cellular interactions in melanoma provides us with new clues to developing novel therapies to reestablish control of malignant cells by keratinocytes. We may even develop strategies in which small molecules mimic keratinocytes and maintain lasting control. Models can be used to test the efficacy of sunscreens or anticipate the effects of ozone depletion on melanoma rates. Models confirm the importance of public health initiatives encouraging the use of sunblocks. Insights into the roles of E- and N-cadherins should prove similarly valuable. These cell adhesion molecules may serve both as prognostic markers for disease behavior and sites for possible therapeutic interventions. Increased knowledge about apoptotic pathways should also offer hope for new and effective treatments. R EFERENCES 1 Hall HI, Miller DR, Rogers JD et al. Update on the incidence and mortality from melanoma in the United States. J Am Acad Dermatol 1999;40:35-42. 12 Klein-Parker HA, Warshawski L, Tron VA. Melanocytes in human skin express bcl-2 protein. J Cutan Pathol 1994;21:297301. 2 Greenlee RT, Hill-Harmon MB, Murray T et al. Cancer statistics, 2001. CA Cancer J Clin 2001;51:15-36. 1...
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This document was uploaded on 03/06/2014.

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