Tópicos em Biologia Tumoral: Biologia da Transformação

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

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. p. 864
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, p. 7
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, p. 13
WEGROWSKI, Y., MAQUART, F.X. Chondroitin sulfate proteoglycans in tumor progression. Advances in Pharmacology, v. 53, p. 297-321, 2006.