Programa de Pós-Graduação Stricto Sensu em Patologia Ambiental e Experimental

Tópicos em Biologia Tumoral: Biologia da Transformação

Ementa

Abordagem de elementos relevantes da biologia tumoral, dentro de um enfoque celular e molecular, destacando-se: conceito, classificação, diferenças entre neoplasias benignas e malignas. Circuitaria molecular no câncer: ciclo celular, proliferação e diferenciação celular. Imuno-histoquímica: princípios e aplicações. Tumores transplantáveis. Genética molecular do câncer: instabilidade cromossômica e mutações, oncogenes, genes supressores de tumores. Microambiente tumoral; estroma e invasão. Vasculogênese tumoral (contexto molecular, padrões de organização, marcadores e quantificação). Marcadores prognósticos em oncologia. Inflamação, imunidade e imunoterapia no câncer: aspectos críticos.

Bibliografia

Aspectos gerais
GREAVES, M. Darwinian medicine: a case for cancer. Nature Reviews/ Cancer, v. 7, p. 213-221, 2007.
HANAHAN, D.; WEINBERG, R.A. The hallmarks of câncer. Cell, v. 100, p. 57-70, 2000.
HANAHAN, D.; WEINBERG, R.A. The hallmarks of cancer. The new generation. Cell, v. 100: 57-70, 2011.
LOEB, L.A.; LOEB, K.R.; ANDERSON, J.P. Multiple mutations and câncer. Proceedings of the National Academy of Sciences, v. 100, p. 776-781, 2003.
WEINBERG, R.A. A biologia do câncer. Porto Alegre: Artmed, 2008. 864p.
Angiogênese neoplásica
CASTERMANS, K.; GRIFFIOEN, A.W. Tumor blood vessels, a difficult hurdle for infiltrating leukocytes. Biochimica et Biophysica, v. 1776, p. 160-174, 2007.
FOX, S.B.; HARRIS, A.L. Histological quantitation of tumour angiogenesis. APMIS, v. 112, p. 413-430, 2004.
HOFF, P.M.; MACHADO, K.K. Role of angiogenesis in the pathogenesis of cancer. Cancer Treatments Reviews, v. 38, p. 825-833, 2012.
RIBATTI, D., NICO, B.; CRIVELLATO, E.; VACCA, A. The structure of the vascular network of tumors. Cancer Letters, 2006.
SCAVELLI, C.; WEBER, E.; AGLIANO, M.; CIRULLI, T.; NICO, B.; VACCA, A.; RIBATTI, D. Lymphatics at the crossroads of angiogenesis and lymphangiogenesis. Journal of Anatomy, v. 204, p. 433-449, 2004.
Metástase
FOKAS, E.; ENGENHART-CABILLIC, R.; DANIILIDIS, K.; ROSE, F.; NA, HX. Metastasis:the seed and soil theory gains identity. Cancer Metastasis Reviews, v. 26, p. 705-715, 2007.
FREIREICH, E.J.; KURZROCK, R.; ESTROV, Z. Metastasis- an alternative hypothesis. Cancer, v. 103, p. 1537-1539, 2005.
GUARINO, M. Epithelial-mesenchymal transition and tumour invasion. International Journal of Biochemistry Cell Biology, v. 39, p. 2153-60, 2007.
KLEIN, C.A. The metastatic cascade. Science, v. 321, p. 1785-1787, 2008.
PSAILA, B.; LYDEN, D. The metastatic niche: adapting the foreign soil. Nature Cancer Reviews, v. 9, p. 285-293, 2009.
SCHEEL, C.; ONDER, T.; KAMOUB, A.; WEINBERG, RA. Adaptation versus selction: the origins of metastatic behavior. Cancer Research, v. 87, p. 11476-11480, 2007.
SHIBUE, T.; WEINBERG, R.A. Metastatic colonization: settlement, adaptation and propagation of tumor cells in a foreign tissue environment. Seminars in Cancer Biology, v. 21, p. 99-106, 2011.
SLEEMAN, J.P.; CHRISTOFORI, G.; FODDE, R.; COLLARD, JG.; BERX, G.; DECRAENE, C.; RUEGG, C. Concepts of metastasis in flux: the stromal progression model,  Seminars in Cancer Biology , v. 22, p. 174-186, 2012.
TALMADGE, J.E. Clonal selection of metastasis within the life history of a tumor. Cancer Research, v. 67, p. 11471-11475, 2007.
Cancer stem cells
BOROVSKI, T.; MELO, F.S.; VERMEULEN, L.; MEDEMA, J.P. Cancer stem cell niche: the place to be. Cancer Research, v. 7, p. 634-639, 2011.
MALANCHI, I.; HUELSKEN, J. Cancer stem cells: never Wnt away from the niche. Current Opinion in Oncology, v. 21, p. 41-46, 2008.
SAMPIERI, K.; FODDE, R. Cancer stem cells and metastasis. Seminars in Cancer Biology, v. 22, p. 187-193, 2012.
YI, S.; HAO, Y.; NAN, K.; FAN, T. Cancer stem cell niche: a target for novel cancer therapeutics. Cancer Treatments Reviews, v. 39, p. 290-296, 2013.
Microambiente tumoral
CHEN, J.L.; QIN, Z. Multifaceted tumor stromal fibroblasts. Cancer Microenvironment, 2012.
PIETRAS, K.; OSTMAN, A. Hallmarks of cancer: interactions with the tumor stroma. Experimental Cell Research, v. 316, p. 1324-1331, 2010.
REDDY, B.Y..; LIM, P.K..; SILVERIO, K.; PATEL, A,S.; WON, B.W.; RAMESHWAR, P. The microenvironment effect in the progression, metastasis and dormancy of breast cancer: a model system within bone marrow. International Journal of Breast Cancer, 2012, 7p.
UHR, J.W.; PANTEL, K. Controversies in clinical cancer dormancy. Proceedings of the National Academy of Sciences, v. 108, p. 12396-1240, 2011.
WITZ, I.P. Ying-yang activities and vicious cycles in the tumor microenvironment. Cancer Research, v. 88, p. 9-13, 2008.
Inflamação e câncer
CHEN, J.J.W.; LIN, Y.C.; YAO, P.L.; YUAN, A.; CHEN, H.Y.; SHUN, C.T.; TSAI, M.F.; CHEN, C.H.; YANG, P.C. Tumor-associated macrophages: the double-edged sword in cancer progression. Journal of Clinical Oncology, v. 23, p. 953-964, 2005.
LEWIS, C.; MURDOCH, C. Macrophage responses to hypoxia-implications for tumor progression and anti-cancer therapies. American Journal of Pathology, v. 167: 627-635, 2005.
RUEGG, C. Leukocytes, inflammation, and angiogenesis in cancer: fatal attractions. Journal of Leukocyte Biology, v. 80, p.1-3, 2006.
TALMADEE, J.E.; DONKOR, M.; SCHOLAR, E. Inflammatory cell infiltration of tumors: Jekyll or Hyde. Cancer Metastasis Reviews, v. 26, p. 373-400,2007.
ZUMSTEG, A.; CHRISTOFORI, G. Corrupt policemen: inflammatory cells promote tumor angiogenesis. Current Opinion in Oncology, v. 21, p. 60-70, 2008.
Imuno-histoquímica
LEONG, T.Y.M.; LEONG, A.S.Y. How does antigen retrieval work? Advances in Anatomic Pathology, v. 14: 129-131, 2007.
RAMOS-VARA, J.A. Technical aspects of immunohistochemistry. Veterinary Pathology, v. 42, p. 405-426, 2005.
YAZIJI, H.; BARRY, T. Diagnostic immunohistochemistry:what can go wrong? Advances in Anatomic Pathology, v. 13, p. 238-246, 2006.
Metabolismo tumoral
CANAPLE, L.; KAKIZAWA, T.; LAUDET, V. The days and nights of cancer cells. Cancer Research, v. 63, p. 7245-7552, 2003.
DENKO, N.C. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nature Reviews/Cancer, v. 8, p. 705-713, 2008.
GATENBY, R.A.; GILLIES, R.J. Why do cancer have a high aerobic glycolysis?, Nature Reviews/Cancer, v. 4, p. 891-899, 2004.
KROEMER, G.; POUYSSEGUR, J. Tumor cell metabolism: cancer´s Achilles´heel. Cancer Cell, v. 13, p. 472-482, 2008.
MUCAJ, V.; SHAY, J.E.S.; SIMON, M.C. Effects of hypoxia and HIFS on cancer metabolism. International Journal of Hematology, v. 95, p. 464-470, 2012.
MURPHY, M.E. Regulation of cell death in oncogenesis. Cancer Research, v. 65, p. 8069-8071, 2005.
TAFANI, M.; PUCCI, B.; RUSSO, A.; SCHITO, L.; PELLEGRINI, L.; PERRONE, G.A.; VILLANOVA, L.; SALVATORI, L.; RAVENNA, L.; PETRANGELI, E.; RUSSO, M.A. Modulators of HIF1 and NFkB in cancer treatment: is it a rational approach for controlling malignant progression? Frontiers in Pharmacology, v. 4, 2013, 13 p.
WEGROWSKI, Y., MAQUART, F.X. Chondroitin sulfate proteoglycans in tumor progression. Advances in Pharmacology, v. 53, p.297-321, 2006.