RESUMO
Detection and removal of melanoma, before it has metastasized, dramatically improves prognosis and survival. The purpose of this chapter is to (1) summarize current methods of melanoma detection and (2) review state-of-the-art detection methods and technologies that have the potential to reduce melanoma mortality. Current strategies for the detection of melanoma range from population-based educational campaigns and screening to the use of algorithm-driven imaging technologies and performance of assays that identify markers of transformation. This chapter will begin by describing state-of-the-art methods for educating and increasing awareness of at-risk individuals and for performing comprehensive screening examinations. Standard and advanced photographic methods designed to improve reliability and reproducibility of the clinical examination will also be reviewed. Devices that magnify and/or enhance malignant features of individual melanocytic lesions (and algorithms that are available to interpret the results obtained from these devices) will be compared and contrasted. In vivo confocal microscopy and other cellular-level in vivo technologies will be compared to traditional tissue biopsy, and the role of a noninvasive "optical biopsy" in the clinical setting will be discussed. Finally, cellular and molecular methods that have been applied to the diagnosis of melanoma, such as comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), will be discussed.
Assuntos
Melanoma/diagnóstico , Hibridização Genômica Comparativa , Dermoscopia , Detecção Precoce de Câncer , Humanos , Hibridização in Situ Fluorescente , Microscopia Confocal , Educação de Pacientes como Assunto , AutoexameRESUMO
Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17.
Assuntos
Carcinoma de Células Escamosas/enzimologia , Caspase 7/genética , Queratinas/fisiologia , Lesões Experimentais por Radiação/enzimologia , Neoplasias Cutâneas/enzimologia , Luz Solar/efeitos adversos , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Caspase 7/metabolismo , Células Cultivadas , Epiderme/enzimologia , Epiderme/patologia , Epiderme/efeitos da radiação , Feminino , Técnicas de Inativação de Genes , Queratinócitos/enzimologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteólise , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Carga TumoralRESUMO
61-year-old woman with stage IIIa (T3a N1a M0) left lower leg melanoma with lesions suggestive of in-transit metastases 8 months following wide local excision and femoral nodal dissection. FDG-PET/CT demonstrated 5 FDG-avid in-transit nodal metastases in the distal left leg, confirmed on biopsy. Talimogene laherparepvec (T-VEC) oncolytic immunotherapy consisting of intralesional injections of modified herpes simplex virus-expressing granulocyte-macrophage colony-stimulating factor was completed over 6 months. Subsequent FDG-PET/CT demonstrated reduced or resolved FDG activity in the treated in-transit metastases and a new FDG-avid left thigh in-transit metastasis. FDG-PET/CT can monitor response to T-VEC and potentially other novel viral immunotherapies.
Assuntos
Melanoma/diagnóstico por imagem , Terapia Viral Oncolítica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Feminino , Fluordesoxiglucose F18 , Humanos , Melanoma/terapia , Pessoa de Meia-Idade , Compostos RadiofarmacêuticosRESUMO
Pharmacologic blockade of TNFalpha has been a highly effective approach to treating several immunologically mediated diseases, including rheumatoid arthritis, Crohn's disease, and psoriatic arthritis. 1,2,3 Both etanercept, the recombinant extracellular domain of the tumor necrosis factor receptor 2 (TNFR2), and infliximab, a humanized murine antibody, bind TNFalpha and block its interaction with cell surface receptors. Recently, it has become clear that blockade of TNFalpha action is profoundly immunosuppressive, and may result in reactivation of tuberculosis and histoplasmosis, as well as the emergence of B-cell lymphomas. 4,5,6 In this report, we describe two cases of cutaneous and systemic T-cell lymphoma that progressed rapidly in the setting of TNFalpha blockade. Both cases were characterized by rapid onset, a fulminant clinical course with extensive cutaneous and systemic involvement, and death within months of diagnosis.