Basal cell carcinoma chemoprevention with nonsteroidal anti-inflammatory drugs in genetically predisposed PTCH1+/- humans and mice
Jean Y. Tang,Michelle Aszterbaum,Mohammad Athar,Franco Barsanti,Carol Cappola,Nini Estevez,Jennifer Hebert,Jimmy Hwang,Yefim Khaimskiy,Arianna Kim,Ying Lu,Po-Lin So,Xiuwei Tang,Michael Kohn,Charles E. McCulloch,Levy Kopelovich,David R. Bickers,Ervin H. Epstein +17 more
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TLDR
Oral celecoxib treatment inhibited BCC carcinogenesis in PTCH1+/− mice and had a significant anti-BCC effect in humans with less severe disease.Abstract:
In vitro and epidemiologic studies favor the efficacy of nonsteroidal anti-inflammatory drugs (NSAID) in preventing skin squamous photocarcinogenesis, but there has been relatively little study of their efficacy in preventing the more common skin basal cell carcinoma (BCC) carcinogenesis. We first compared the relative anti-BCC effects of genetic deletion and NSAID pharmacologic inhibition of cyclooxygenase (COX) enzymes in the skin of Ptch1(+/-) mice. We then assessed the effects of celecoxib on the development of BCCs in a 3-year, double-blinded, randomized clinical trial in 60 (PTCH1(+/-)) patients with the basal cell nevus syndrome. In Ptch1(+/-) mice, genetic deletion of COX1 or COX2 robustly decreased (75%; P < 0.05) microscopic BCC tumor burden, but pharmacologic inhibition with celecoxib reduced microscopic BCCs less efficaciously (35%; P < 0.05). In the human trial, we detected a trend for oral celecoxib reducing BCC burden in all subjects (P = 0.069). Considering only the 60% of patients with less severe disease (<15 BCCs at study entry), celecoxib significantly reduced BCC number and burden: subjects receiving placebo had a 50% increase in BCC burden per year, whereas subjects in the celecoxib group had a 20% increase (P(difference) = 0.024). Oral celecoxib treatment inhibited BCC carcinogenesis in PTCH1(+/-) mice and had a significant anti-BCC effect in humans with less severe disease.read more
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Guidelines of care for the management of cutaneous squamous cell carcinoma
Murad Alam,April W. Armstrong,Christian L. Baum,Jeremy S. Bordeaux,Marc D. Brown,Klaus J. Busam,Daniel B. Eisen,Vivek Iyengar,Clifford W. Lober,David J. Margolis,Jane L. Messina,Alexander R. Miller,Stanley J. Miller,Eliot N. Mostow,Christen M. Mowad,Kishwer S. Nehal,Kristi Schmitt-Burr,Aleksandar Sekulic,Paul A. Storrs,Joyce M.C. Teng,Siegrid S. Yu,Conway C. Huang,Kevin Boyer,Wendy Smith Begolka,Christopher K. Bichakjian,John Y.S. Kim,Jeffrey H. Kozlow,Bharat B. Mittal,Jeffrey S. Moyer,Thomas Olenecki,Phillip Rodgers +30 more
TL;DR: The primary focus of these recommendations is on evaluation and management of primary cSCC and localized disease, but where relevant, applicability to recurrent cS CC is noted, as is general information on the management of patients with metastatic disease.
Journal ArticleDOI
Guidelines of care for the management of basal cell carcinoma.
Christian L. Baum,Jeremy S. Bordeaux,Marc Brown,Klaus Busam,Daniel B. Eisen,Vivek Iyengar,Clifford W. Lober,David J. Margolis,Jane Messina,Alexander R. Miller,Stanley J. Miller,Eliot N. Mostow,Christen Mowad,Kishwer S. Nehal,Kristi Schmitt-Burr,Aleksandar Sekulic,Paul A. Storrs,Joyce M.C. Teng,Siegrid Yu,Conway C. Huang,Kevin Boyer,Wendy Smith Begolka,Murad Alam,John Y.S. Kim,Jeffrey H. Kozlow,Bharat B. Mittal,Jeffrey S. Moyer,Thomas Olencki,Phillip Rodgers +28 more
TL;DR: Recommendations for the management of patients with BCC and recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy are provided.
Journal ArticleDOI
Chemoprevention of Nonmelanoma Skin Cancer With Celecoxib: A Randomized, Double-Blind, Placebo-Controlled Trial
Craig A. Elmets,Craig A. Elmets,Jaye L. Viner,Jaye L. Viner,Alice P. Pentland,Wendy Cantrell,Hui Yi Lin,Hui Yi Lin,Howard H. Bailey,Sewon Kang,Sewon Kang,Kenneth G. Linden,Michael J. Heffernan,Michael J. Heffernan,Madeleine Duvic,Ellen Richmond,Boni E. Elewski,Asad Umar,Walter C. Bell,Gary Gordon +19 more
TL;DR: Celecoxib may be effective for prevention of SCCs and BCCs in individuals who have extensive actinic damage and are at high risk for development of nonmelanoma skin cancers.
Journal ArticleDOI
Epidemiologia do carcinoma basocelular
TL;DR: The authors present a review of the epidemiology of basal cell carcinoma, finding that between 30% and 75% of the sporadic cases are associated with patched hedgehog gene mutation, but other genetic changes are also described.
Journal ArticleDOI
Sonic Hedgehog Signaling in Basal Cell Nevus Syndrome
TL;DR: Information related to the pathogenesis of this neoplasm is summarized, pathways that crosstalk with Shh signaling are discussed, and the importance of the primary cilium is discussed, as well as the role of transcription factors Glis and GAPD in cell proliferation and tumor growth.
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