RESUMEN
CONTEXT: The rapidly developing fields of melanoma research are revolutionizing the current concepts on melanoma etiology and pathogenesis and are introducing newer diagnostic techniques and potential therapeutic approaches. OBJECTIVES: To present the most current concepts on the etiology and pathogenesis of melanoma and to introduce the recent diagnostic techniques and the potential therapeutic approaches. METHODS: Data sources were reports on melanoma published in the English language literature and observations made using specimens available at Harvard University, Johns Hopkins Medical Center, Albany Medical College, Loyola University Medical Center, and University of Tennessee Health Science Center. RESULTS: Studies on melanoma containing chromosomal or genetic evaluation were selected for further analysis. Current clinical and pathologic categories with the reported genetic abnormalities were related to the latest information on pigment biology. The data extracted were used to develop a conceptual framework on the pathogenesis of melanoma; the generated model was then evaluated and used to suggest potential therapeutic approaches. CONCLUSIONS: (1) Melanoma is not genetically homogeneous, and the existing differences between the pathologic categories, particularly in areas such as type of growth phase (radial vs vertical growth), total vertical dimension, ulceration of primary tumor, and metastatic process, have profound prognostic and therapeutic implications. (2) Chromosomal aberrations and gene mutations are found in sporadic and familial melanomas; among the most important are those affecting the 9p21, which contains the p16 locus, a site known to be critical for normal progression of the cell cycle. Aberrant p16 expression is associated with more aggressive behavior. (3) Melanoma cells possess a remarkable repertoire of biosynthetic capacities represented by the production of hormones, growth factors, and their receptors that may sustain and accelerate tumor development and progression. For example, expression of the tumoral products alpha-melanocyte-stimulating hormone and adrenocorticotropic hormone is regulated in vitro by ultraviolet light, a known carcinogen. (4) Melanomas differ from other tumors in their intrinsic capability to express melanogenic enzymes with the corresponding structural proteins to actually synthesize melanin. Melanogenesis-related proteins are rapidly entering the clinical arena, being used not only as diagnostic markers, but also as potential targets for melanoma therapy.
Asunto(s)
Melanoma , Aberraciones Cromosómicas , Trastornos de los Cromosomas , Susceptibilidad a Enfermedades , Femenino , Predisposición Genética a la Enfermedad , Sustancias de Crecimiento/fisiología , Humanos , Inmunoterapia , Masculino , Melaninas/biosíntesis , Melanoma/diagnóstico , Melanoma/etiología , Melanoma/patología , Melanoma/terapia , Metástasis de la NeoplasiaRESUMEN
Contemporary 14-valent pneumococcal polysaccharide vaccine was first licensed in 1977 in the United States, where about four million doses of vaccine have been distributed to date. The vaccine induces excellent antibody responses in elderly persons as well as in young adults. The antigen content of the vaccine is 50 microgram of each serotype of polysaccharide per dose, and lower titers of antibody are induced when the dose is reduced to 25 or 12.5 microgram of antigen. Adverse reactions are usually mild and consist principally of local erythema and induration at the injection site, with mild fever in a small proportion of subjects. Antibody persists well for at least four years, and it is expected that immunity will last for at least 5 years after vaccination. Local and systemic reactions to the vaccine may be greater when a second dose of vaccine is administered within three years after the initial dose, and this reactivity appears to be due to a Arthus-like response that results from local formation of antigen-antibody complexes. Pneumococcal and influenza vaccines can be injected simultaneously into separate sites without impairment of antibody responses to either vaccine; this feature should facilitate administration of these two vaccines.