Este documento resume la biología del cáncer, incluyendo la carcinogénesis, las metástasis y los marcadores tumorales. Explica que el cáncer es el resultado de cambios genéticos y epigenéticos que alteran los procesos celulares como la proliferación, diferenciación y apoptosis. Describe las etapas de la metástasis, desde la invasión de la membrana basal hasta la colonización de otros órganos. Finalmente, define los marcadores tumorales como sustancias que pueden indicar la presencia de c
1. Biología y Marcadores Tumorales Dr. GONZALO MENDOZA DEL SOLAR Ch. Cirujano Oncólogo RNE 9752 Oncólogo Clínico RNE 9399 FACULTAD DE MEDICINA CIRUGIA I
30. Iniciación tumoral y metástasis N Engl J Med: Volume 359:2814-2823 Number 26.- december 25 2008
31. Genes, funciones y participación celular en metástasis órgano específicas
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33. TEORIA DE LOS DOS MODELOS N Engl J Med: Volume 360:297-299 Number 3.- enero 15, 2009
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35. Sistema inmunológico y muerte de células cancerosas N Engl J Med: Volume 354:2503-2504 Number 23.- junio 08 2006
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41. Marcador Tumoral Ideal Especificidad 100% verdaderos neg: 100% falsos positivos: 0% Sensibilidad 100% verdaderos-pos 100% falsos negativos 0% Cut off Población sana Pacientes con Ca
42. Marcador Tumoral Real sensibilidad 100% especificidad ~ 60% especificidad 100% sensibilidad ~ 50% Cut off Población sana y con enferm. benignas Pacientes con Cáncer Concentración
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44. Cronología del Desarrollo Conceptual de M.T. (I) Fosfatasa Ácida prostática Isoemzymas Gutman el al. 1933 Hormona Adreno-corticiotrópica Hormonas Cushing 1932 HGC Hormonas Zondek 1930 Producción hor-monal ectópica Hormonas ectópicas Brown 1928 En orina de Mieloma Proteína específica Bence-Jones 1846 OBSERVACION CONCEPTO INVESTIGADOR AÑO
45. Cronología del Desarrollo Conceptual de M. T. (II) APS Moléculas Inmunológicas Richard Ablin 1970 p53, K-ras, Her Oncogenes Huebner & Todaro 1969 ACE (CEA) Antígenos Oncofetales Gold y Freedman 1965 Alfa fetoproteína Antígenos Oncofetales Abelev 1963 Cromosoma Filadelfia Aberraciones Cromosómicas Newell 1960 OBSERVACION CONCEPTO INVESTIGADOR AÑO
46. Cronología del Desarrollo Conceptual de M. T. (III) NSE Oligosacarido Marangos 1985 Ca 19.9 Antígeno Carbohidratado 1982 Ca 125 Glicoproteinas Bast R.C. 1981 Anticuerpos Monoclonales Milstein & Kohler 1975 OBSERVACION CONCEPTO INVESTIGADOR AÑO
47. Desarrollo de Métodos Inmunológicos FIA / CLIA componentes estables incubaciones largas automatización RIA la base ELISA componentes más estables semiautomatización ECL Reactivos más estables incubaciones cortas alta sensibilidad amplio rango de medición FIA= Fluoro-luminiscencia; ECL= Electro-quimio-luminiscencia
71. Marcadores en tumores germinales Hayes DF, et al: Tumor marker utility grading system: A framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst 88:1456-1466, 1996
Cyclin D1 and the Development of Breast Cancer. Cyclin D1 has a unique role in regulating the cell cycle in alveolar epithelial cells of the breast (Panel A). It is a possible therapeutic target because it is overexpressed in breast cancer, especially estrogen-receptor–positive breast cancers. Trastuzumab, the clinically useful monoclonal antibody against NEU, may indirectly inhibit cyclin D1 through the RAS pathway. In mice, the actions of the Neu and Ras oncogenes in the breast depend on cyclin D1, as suggested in Panel B. Mammary cancer induced in mice by overexpression of the Neu and Ras oncogenes depends on cyclin D1, whereas the Myc and Wnt1 oncogenes can act independently of cyclin D1.
Activity of mammalian Cdkcyclin complexes through the course of the cell cycle in G 0 cells induced to divide by treatment with growth factors. The width of the colored bands is approximately proportional to the protein kinase activity of the indicated complexes. Cyclin D refers to all three D-type cyclins
Activity of mammalian Cdkcyclin complexes through the course of the cell cycle in G 0 cells induced to divide by treatment with growth factors. The width of the colored bands is approximately proportional to the protein kinase activity of the indicated complexes. Cyclin D refers to all three D-type cyclins
Focal-adhesion kinase (FAK) acts to integrate signals from extracellular cues, such as growth-factor receptors and integrins, and from the upstream SRC-family kinases, to control and coordinate adhesion dynamics/cell migration with survival signalling. SRC binds to growth-factor receptors and FAK to integrins (although, this has not been shown in vivo ), and they bind to each other. SRC binding to growth-factor receptors is widely believed to be important, as is FAK signalling from integrins, regardless of whether the interaction between FAK and these transmembrane receptors is direct
Cancer cells that die after treatment with cytotoxic agents can be processed by dendritic cells for presentation to CD4+CD8+ T cells. Some drugs initiate a program of targeting and killing cells that amplifies this process. Dying cells then express molecules that serve as danger signals (yellow box) that activate dendritic cells to present cancer antigens in an inflammatory context. In response, dendritic cells up-regulate costimulatory molecules and secrete cytokines such as interleukin-12. Immunotherapies that target dendritic cells (blue box) may induce an effective immune response even if danger signals are not expressed by dying tumor cells. Additional immunotherapies directed at T cells (red box) may also promote antitumor immunity.