BIBLIOGRAFIA

191

(1) Abeloff, M.D., Armitage, J.O., Lichter, A.S. & Niederhuber, J.E. (2000). Clinical Oncology. Second edition. Churchill Livingstone. Edinburgh.

(2) Hanahan, D. & Weinberg, R.A. (2000). The Hallmarks of Cancer. Cell. 100, 57-70. (3) Bertram, J.S. (2001). The Molecular Biology of Cancer. Mol Aspect Med. 21, 167-

223. (4) Spencer, S.L., Berryman, M.J., Garcia, J.A. & Abbott, D. (2004). An ordinary

differencial equation model for the multistep transformation to cancer. J Theor Biol. 231, 515-524.

(5) Gilligan, T.D., Steele, G.S., Zietman, A.L. & Kantoff, P.W. (2003). Bladder

Cancer. In Kufe, D.W., Pollock, R.E., Weichselbaum, R.R., Bast Jr., R.C., Gansler, T.S., Holland, J.F. & Frei, E., Cancer Medicine. Sixth edition. B.C. Decker Inc. Hamilton.

(6) Cooper, G.G. (2000). The Cell – A Molecular Approach. Second Edition. ASM Press.

Washington, D.C.

(7) DeVita, V.T., Hellman, S. & Rosenberg, S.A. (2000). Cancer Principles & Practice of Oncology. Sixth edition. Lippincott. Philadelphia.

(8) Lodish, H., Berk, A., Zipursky, S.L., Matsudaisra, P., Baltimore, D. & Darnell, J.

(2000). Molecular Cell Biology. Fourth edition. W. H. Freeman and Company. New York.

(9) Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J. & Thun, M.J. (2007) Cancer

Statistics, 2007. CA Cancer J Clin. 57, 43-66. (10) Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., Smigal, C. & Thun, M.J.

(2006) Cancer Statistics, 2006. CA Cancer J Clin. 56, 106-130. (11) Instituto Nacional de Estatística. Óbitos por causa de morte, segundo a idade e o

sexo (Portugal 2006). Disponível em: http://www.ine.pt (12) Pinheiro, P.S., Tyczynski, J.E., Bray, F., Amado, J., Matos, E. & Parkin, D.M.

(2003). Cancer incidence and mortality in Portugal. Eur J Cancer. 39, 2507-2520. (13) Algaba, F. & Trias, I. (2000). Morfobiología de las neoplasias superficiales de la

vejiga urinaria. In Vicent, J., Chechile, G. & Salvador, J., Tumores vesicales superficiales. Edita Acción Médica, SA. Madrid.

(14) Young, B. & Heath, J.W. (2000). Wheater’s Functional Histology – A Text and

Colour Atlas. Fourth edition. Churchill Livingstone. Edinburgh. (15) Junqueira, L.C. & Carneiro, J. (2004). Histologia Básica. Décima edição.

Guanabara Koogan. Rio de Janeiro.

BIBLIOGRAFIA 192

(16) Wu, X. (2005). Urothelial Tumorigenesis: a tale of divergent pathways. Nat Rev Cancer. 5, 713-725.

(17) Johansson, S.L. & Coihen, S.M. (1997). Epidemiology and Ethiology of Bladder

Cancer. Semin Surg Oncol. 13,291-298. (18) Redman, B.G., Kawachi, M. & Hurwitz, M. (2005). Urothelial and Kidney Cancer.

In Pazdur, R., Coia, L.R., Hoskins, W.J. & Wagman, L.D., Cancer Management – A Multidisciplinary Approach. Ninth edition. CMP Healthcare Media. New York.

(19) Reuter, V.E. (2006). The Pathology of Bladder Cancer. Urology. 67(3A), 11-18. (20) Koss, L.G. (1992). Bladder cancer from a perspective of 40 years. J Cell Biochem

Suppl. 161, 23-29. (21) Spiess, P.E. & Czerniak, B. (2006). Dual-track Pathway in Bladder Carcinogenesis.

Arch Pathol Lab Med. 130, 844-852. (22) Knowles, M.A. (2005). Molecular subtypes of bladder cancer: Jekyll and Hyde or

chalk and cheese? Carcinogenesis. 27(3), 361-373. (23) Williams, S.G. & Stein J.P. (2004). Molecular Pathways in Bladder Cancer. Urol

Research. 32(6), 373-385. (24) Kausch, I. & Böhle, A. (2002). Molecular Aspects of Bladder Cancer III. Prognostic

Markers of Bladder Cancer. Eur Urol. 41, 15-29. (25) Baffa, R., Letko, J., McClung, C., Lenoir, J., Vecchione, A. & Gomella, L.G.

(2006). Molecular genetics of bladder cancer: targets for diagnosis and therapy. J Exp Clin Cancer Res. 25(2), 145-160.

(26) Orntoft, T.F., Zieger, K. & Dyrskjot, L. (2006). Recent developments in molecular

profiling of bladder cancer. Curr Opin Urol. 16(5), 377-381. (27) Lianes, P. (2000). Biologia molecular del cáncer de vejiga. In Vicent, J., Chechile,

G. & Salvador, J., Tumores vesicales superficiales. Edita Acción Médica, SA. Madrid.

(28) Santos, L. (2003). Aspectos Moleculares na Progressão do Carcinoma Urotelial da

Bexiga. Tese de Doutoramento. Faculdade de Medicina da Universidade do Porto. (29) Jerónimo, C., Henrique, R., Medeiros, R., Santos, L., Silva, C., Bento, M.J.,

Oliveira, J., Carvalho, R. & Lopes, C. (1999). Expression of p53, bcl-2, nm-23, CD44s, CD44V6 and BL2-10 D1 and their relation to histologic grade and stage in transitional-cell carcinoma. J Urol Pathol. 10, 189-205.

(30) Santos, L., Amaro, T., Costa, C., Pereira, S., Bento, M.J., Lopes, P., Oliveira, J.,

Criado, B. & Lopes, C. (2003). Ki-67 index enhances the prognostic accuracy of the

BIBLIOGRAFIA

193

urothelial superficial bladder carcinoma risk group classification. Int J Cancer. 105(2), 267-272.

(31) Santos, L.L., Amaro, T., Pereira, S.A., Lameiras, C.R., Lopes, P., Bento, M.J.,

Oliveira, J., Criado, B. & Lopes, C.S. (2003). Expression of cell-cycle regulatory proteins and their prognostic value in superficial low-grade urothelial cell carcinoma of the bladder. Eur J Surg Oncol. 29(1), 74-80.

(32) Miyao, N., Tsai, Y.C., Lerner, S.P., Olumi, A.F., Spruck, C.H., Gonzalez-Zulueta,

M., Nichols, P.W., Skinner, D.G. & Jones PA. (1993). Role of chromosome 9 in human bladder cancer. Cancer Res. 53, 4066-4070.

(33) Orlow, I., Lianes, P., Lacombe, L., Dalbagni, G., Reuter, V.E. & Cordon-Cardo,

C. (1994). Chromosome 9 allelic loss and microsatellite alterations in human bladder cancer. Cancer Res. 54, 2848-2851.

(34) Fadl-Elmula, I., Gorunova, L., Mandahl, N., Elfving, P., Lundgren, R., Mitelman,

F. & Heim, S. (2000) Karyotypic characterization of urinary bladder transitional cell carcinomas. Genes Chrom Cancer. 29, 256-265.

(35) Stoehr, R., Zietz, S., Burger, M., Filbeck, T., Denzinger, S., Obermann, E.C.,

Hammerschmied, C., Wieland, W.F., Knuechel, R. & Hartmann, A. (2005) Deletions of chromosomes 9 and 8p in histologically normal urothelium of patients with bladder cancer. Eur Urol. 47, 58-63.

(36) Lindgren, D., Liedberg, F., Andersson, A., Chebil, G., Gudjonsson, S., Borg, A.,

Mansson, W., Fioretos, T. & Hoglund M. (2006). Molecular characterization of early bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q. Oncogene. 25(18), 2685-2696.

(37) Tsai, Y.C., Nichols, P.W., Hit, A.L., Williams, Z., Skinner, D. & Jones, P.A.

(1990). Allelic losses of chromosomes 9, 11 and 17 in human bladder cancer. Cancer Res. 50, 44-47.

(38) Sandberg, A.A., & Berger, C.S. (1994). Review of chromosome studies in urological

tumors. II. Cytogenetics and molecular genetics of bladder cancer. J Urol. 151, 545-560.

(39) Habuchi, T., Devlin, J., Elder, P.A. & Knowles, M.A. (1995). Detailed deletion

mapping of chromosome 9q in bladder cancer : evidence for two tumour supressor loci. Oncogene. 11, 1671-1674.

(40) Czerniak, B., Chaturvedi, V., Li, L., Hodges, S., Johnston, D., Roy, J.Y., Luthra,

R., Logothetis, C., Von Eschenbach, A.C., Grossman, H.B., Benedict, W.F. & Batsakis, J.G. (1999). Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasia: implications for a genetic model of multistep urothelial carcinogenesis and early detection of urinary bladder cancer. Oncogene. 18, 1185-1196.

BIBLIOGRAFIA 194

(41) Presti, J.C., Reuter, V.E., Galan, T., Fair, W.R., & Cordon-Cardo, C. (1991). Molecular genetic alterations in superficial and locally advanced human bladder cancer. Cancer Res. 51, 5405-5409.

(42) Fearon, E.R., Feinberg, A.P., Hamilton, S.H. & Vogelstein, B. (1985). Loss of

genes on the short arm of chromosome 11 in bladder cancer. Nature. 318, 377-380. (43) Shaw, M.E. & Knowles, M.A. (1995). Deletion mapping of chromosome 11 in

carcinoma of the bladder. Genes Chrom Cancer. 13, 1-8. (44) Dalbagni, G., Presti, J., Reiter, V.E., Fair, W.R. & Cordón-Cardó, C. (1993).

Genetic alterations in bladder cancer. Lancet. 342, 469-471. (45) Cairns, P., Shaw, M.E. & Knowles, M.A. (1993). Initiation of bladder cancer may

involve deletion of a tumour-supressor gene on chromosome 9. Oncogene. 8, 1083-1085.

(46) Kowles, M.A. & Willamson, M. (1993). Mutations of H-ras is infrequent in bladder

cancer: Confirmation by single-strand confirmation polymorphism and direct sequencing. Cancer Res. 53, 133-139.

(47) Czerniak, B., Deich, D., Simmons, H., Etkind, P., Herz, F. & Koss, L.G. (1990).

H-ras gene codon 12 mutation and DNA ploidy in urinary bladder carcinoma. Br J Cancer. 62, 762-763.

(48) Fontana, D., Bellina, M., Scoffone, C., Cagnazzi, E., Cappia, S., Cavallo, F. &

Russo, R. (1996). Evaluation of c-ras oncogene product (p21) in superficial bladder cancer. Eur Urol. 29, 470-476.

(49) Zhang, Z.T., Pak, J., Huang, H.Y., Shapiro, E., Sun, T.T., Pellicer, A., & Wu,

X.R. (2001). Role of H-ras activation in superficial papillary pathway of urothelial tumor formation. Oncogene. 20, 1973-1980.

(50) Billerey, C., Chopin, D., Aubriot-Lorton, M.H., Ric ol, D., Gil Diez de Medina, S.,

Van Rhijn, B., Bralet, M.P., Lefrere-Belda, M.A., Lahaye, J.B., Abbou, C.C., Bonaventure, J., Zafrani, E.S., van der Kwast, T., Thiery, J.P. & Radvanyi, F. (2001). Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol. 158, 1955-1999.

(51) van Rhijn, B.W., Lurkin, I., Radvanyi, F., Kirkels, W.J., van der Kwast, T.H. &

Zwarthoff, E.C. (2001). The fibroblast growth factor receptor 3 (FGFR3) mutation is a strong indicator of superficial bladder cancer with low recurrence rate. Cancer Res. 61, 1265-1268.

(52) van Rhijn, B.W., van der Kwast, T.H., Vis, A.N., Kirkels, W.J., Boeve, E.R.,

Jobsis, A.C. & Zwarthoff, E.C. (2004). FGFR3 and p53 characterize alternative genetic pathways in the pathogenesis of urothelial cell carcinoma. Cancer Res. 64, 1911-1914.

BIBLIOGRAFIA

195

(53) van Rhijn, B.W., Montironi, R., Zwarthoff, E.C., Jobsis, A.C. & van der Kwast, T.H. (2002). Frequent FGFR3 mutations in urothelial papilloma. J Pathol. 198, 245-251.

(54) Jebar, A.H., Hurst, C.D., Tomlinson, D.C., Johnston, C., Taylor, C.F. & Knowles,

M.A. (2005). FGFR3 and Ras gene mutations are mutually exclusive genetic events in urothelial cell carcinoma. Oncogene. 24, 5218-5225.

(55) Reznikoff, C.A., Belair, C.D., Yeager, T.R., Savelieva, E., Blelloch, R.H.,

Puthenveettil, J.A. & Cuthill, S. (1996). A molecular genetic model of human bladder cancer pathogenesis. Semin Oncol. 23, 571-584.

(56) Grossman, H.B., Liebert, M., Antelo, M., Dinney, C.P., Hu, S.X., Palmer, J.L. &

Benedict, W.F. (1998). p53 and RB expression predict progression in T1 bladder cancer. Clin Cancer Res. 4, 829-834.

(57) Jung, I. & Messing, E. (2000). Molecular Mechanisms and Pathways in Bladder

Cancer Development and Progression. Cancer Control. 7(4), 325-334. (58) Hartmann, A., Schlake, G., Zaak, D., Hungerhuber, E., Hofstetter, A.,

Hofstaedter, F. & Knuechel R. (2002). Occurrence of chromosome 9 and p53 alterations in multifocal dysplasia and carcinoma in situ of human urinary bladder. Cancer Res. 62, 809-818.

(59) Shariat, S.F., Tokunaga, H., Zhou, J., Kim, J., Ayala, G.E., Benedict, W.F. &

Lerner, S.P. (2004). p53, p21, pRb and p16 expression predict clinical outcome in cystectomy with bladder cancer. J Clin Oncol. 22, 1014-1024.

(60) Hernando, E., Nahle, Z., Juan, G., Diaz-Rodriguez, E., Alaminos, M., Hemann,

M., Michel, L., Mittal, V., Gerald, W., Benezra, R., Lowe, S.W. & Cordon-Cardo, C. (2004). Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control. Nature. 430, 797-802.

(61) Knowles, M.A. (1998). Molecular genetics of bladder cancer: Pathways of

development and progression. Cancer surveys. 31, 49-69. (62) Cordon-Cardo, C., Zhang, Z.F., Dalbagni, G., Drobnjak, M., Charytonowicz, E.,

Hu, S.X., Xu, H.J., Reuter, V.E. & Benedict, W.F. (1997). Cooperative effects of p53 and pRB alterations in primary superficial bladder tumors. Cancer Res. 57, 1217-1221.

(63) Chatterjee, S.J., Datar, R., Youssefzadeh, D., George, B., Goebell, P.J., Stein,

J.P., Young, L., Shi, S.R., Gee, C., Groshen, S., Skinner, D.G. & Cote R.J. (2004). Combined effects of p53, p21 and pRb expression in the progression of bladder transitional cell carcinoma. J Clin Oncol. 22, 1007-1013.

(64) Folkman, J. & Klagsbrun, M. (1987). Vascular physiology. A family of angiogenic

peptides. Nature. 329, 671-672.

BIBLIOGRAFIA 196

(65) Bochner, B.H., Cote, R.J., Weidner, N., Groshen, S., Chen, S.C., Skinner, D.G. & Nichols, P.W. (1995). Angiogenesis in bladder cancer: relationship between microvessel density and tumor prognosis. J Natl Cancer Inst. 87, 1603-1612.

(66) Chaudhary, R., Bromley, M., Clarke, N.W., Betts, C.D., Barnard, R.J., Ryder,

W.D. & Kumar, S. (1999). Prognostic relevance of micro-vessel density in cancer of the urinary bladder. Anticancer Res. 19, 3479-3484.

(67) Grossfeld, G.D., Ginsberg, D.A., Stein, J.P., Bochner, B.H., Esrig, D., Groshen, S.

& Dunn, M. (1997). Thrombospondin-1 expression in bladder cancer: association with p53 alterations, tumor angiogenesis, and tumor progression. J Natl Cancer Inst. 89, 219-227.

(68) Campbell, S.C., Volpert, O.V., Ivanovich, M. & Bouck, N.P. (1998). Molecular

Mediators of Angiogenesis in Bladder Cancer. Cancer Res. 58, 1298-1304. (69) Liebert, M., Gebhardt, D., Wood, C., Chen, I.L., Ellard, J., Amancio, D. &

Grossman, H.B. (1999). Urothelial differentiation and bladder cancer. Adv Exp Med Biol. 462, 437-448.

(70) Bringuier, P.P., Umbas, R., Schaafsma, H.E., Karthaus, F.M., Debruyne, F.M.J.

& Schalken, J.A. (1993). Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res. 53, 3421-3425.

(71) Fujisawa, M., Miyazaki, J., Takechi, Y., Arakawa, S. & Kamidono, S. (1996). The

significance of E-cadherin in transitional-cell carcinoma of the human urinary bladder. World J Urol. 14, 12-15.

(72) Lipponen, P.K. & Eskelinen, M.J. (1995). Reduced expression of E-cadherin is

related to invasive disease and frequent recurrence in bladder cancer. J Cancer Res Clin Oncol. 121, 303-308.

(73) Garcia del Muro, X., Torregrosa, A., Munoz, J., Castellsague, X., Condom, E.,

Vigues, F., Arance, A., Fabra, A. & Germa, J.R. (2000). Prognostic value of the expression of E-cadherin and β-catenin in bladder cancer. Eur J Cancer. 36, 357-362.

(74) Serdar, A., Turhan, C., Soner, G., Cem, S.N., Bayram, K., Damla, B.E. & Erbil E .

(2005). The prognostic importance of e-cadherin and p53 gene expression in transitional bladder carcinoma patients. Int Urol Nephrol. 37(3), 485-492.

(75) Lascombe I., Clairotte, A., Fauconnet, S., Bernardini, S., Wallerand, H.,

Kantelip, B. & Bittard, H. (2006). N-cadherin as a novel prognostic marker of progression in superficial urothelial tumors. Clin Cancer Res. 12(9), 2780-2787.

(76) Polette, M., Nawrocki-Raby, B., Gilles, C. & Clavel, C. (2004). Tumour invasion

and matrix metalloproteinases. Crit Rev Oncol Hematol. 49(3), 179-186. (77) Kanayama, H. (2001). Matrix metttalloproteinases and bladder cancer. J Med Invest.

BIBLIOGRAFIA

197

48, 31-43. (78) Santos, L., Amaro, T., Pereira, S., Bento, M.J., Lopes, P., Koch, A., Criado, B. &

Lopes, C.S. (2001). Alterações Moleculares do Carcinoma Papilar e Transicional da Bexiga. Uro. 6(1), 11-16.

(79) Leppert, J. T., Shvarts, O., Kawaoka, K., Lieberman, R., Belldegrun, A.S. &

Pantuck, A.J. (2006). Prevention of Bladder Cancer: A Review. Eur Urol. 49, 226-234.

(80) Matsumoto, K., Irie, A., Satoh, T., Kuruma, H., Arakawa, T. & Baba, S. (2005).

Occupational Bladder Cancer: from cohort study to biologic molecular marker. Med Sci Monit. 11(10), 311-315.

(81) Kirkali, Z., Chan, T., Manoharan, M., Algaba, F., Busch, C., Cheng, L.,

Kiemeney, L., Kriegmair, M., Montironi, R., Murphy, W., Sesterhenn, I.A., Tachibana, M. & Weider, J. (2005). Bladder Cancer: Epidemiology, Staging and Grading, and Diagnosis. Urology. 66(6A), 4-34.

(82) Jankovic, S. & Radosavljevic, V. (2007). Risk factors for bladder cancer. Tumori.

93(1), 4-12. (83) Augustine, A., Hebert, J.R., Kabat, G.C. & Wynder, E. (1998). Bladder Cancer in

relation to Cigarette smoking. Cancer Res. 48, 4405-1998. (84) Thompson, I.M., Peek, M. & Rodriguez, F.R. (1987). The impact of cigarette

smoking on stage, grade and number of recurrences of transitional cell carcinoma of the bladder. J Urol. 137(3), 401-403.

(85) Wallerand, H., Bakkar, A.A., de Medina, S.G., Pairon, J.C., Yang, Y.C., Vordos,

D., Bittard, H., Fauconnet, S., Kouyoumdjian, J.C., Jaurand, M.C., Zhang, Z.F., Radvanyi, F., Thiery, J.P. & Chopin, D.K. (2005). Mutations in TP53, but not FGFR3, in urothelial cell carcinoma of the bladder are influenced by smoking: contribution of exogenous versus endogenous carcinogens. Carcinogenesis. 26(1), 177-184.

(86) Kadlubar, F.F. & Badawi, A.F. (1995). Genetic Susceptibility and Carcinogen –

DNA Adduct Formation in Human Urinary Bladder Carcinogenesis. Toxicol Lett. 82, 627-632.

(87) Risch, A., Wallace, D.M., Bathers, S. & Sim, E. (1995). Slow N-acetylation

Genotype is a susceptibility factor in Occupational and Smoking related Bladder Cancer. Hum Mol Gen. 4, 231-236.

(88) Yu, M.C., Skipper, P.L., Taghizadeh, K., Tannenbaum, S.R., Chan, K.K.,

Henderson, B.E. & Ross R.K. (1994). Acetylator phenotype, aminobiphenyl-hrmoglobin adduct levels, and bladder cancer risk in white, black, and Asian men in Los Angeles, California. J Natl Cancer Inst. 86, 712-716.

BIBLIOGRAFIA 198

(89) Vineis, P. & Simonato L. (1991). Proportion of lung and bladder cancers in males resulting from occupation: a systematic approach. Argh Environ Health. 46, 6-15.

(90) Bosetti C, Pira E & Vecchia CL. (2005). Bladder cancer risk in painters: a review of

the epidemiological evidence, 1989-2004. Cancer Causes Control. 16(9), 997-1008. (91) Kroft, H.S. & Oyasu, R. (1994). Biology of Disease - Urinary Bladder Cancer:

Mechanisms of Development and Progression. Lab Invest. 71(2), 158-174. (92) Carreon, T., Lemasters, G.K., Ruder, A.M. & Schulte, P.A. (2006). The genetic

and environmental factors involved in benzidine metabolism and bladder carcinogenesis in exposed workers. Front Biosci. 11, 2889-2902.

(93) Carreon, T., Ruder, A.M., Schulte, P.A., Hayes, R.B., Rothman, N., Waters, M.,

Grant, D.J., Boissy, R., Bell, D.A., Kadlubar, F.F., Hemstreet, G.P.3rd, Yin, S. & LeMasters, G.K. (2006). NAT2 slow acetylation and bladder cancer in workers exposed to benzidine. Int J Cancer. 118(1), 161-168.

(94) Practical Science. Parasitology – Schistosoma haematobium.

Available at: http://www.practicalscience.com/schistosoma.html

(95) Lopes, C. (1984). Cancerização vesical e Schistosomíase. Tese de Doutoramento. Faculdade de Medicina da Universidade do Porto.

(96) Badawi, A.F. (1996). Molecular and genetic in schistosomiasis-associated human

bladder cancer: role and oncogenes and tumor supressor genes. Cancer Lett. 105, 123-138.

(97) Vaidyanathan, S., Soni1, B.M., Oo, T., Hughes, P.L., Singh, G., Watt, J.W.H. &

Sett, P. (2003). Bladder stones – red herring for resurgence of spasticity in a spinal cord injury patient with implantation of Medtronic Synchromed pump for intrathecal delivery of baclofen – a case report. BMC Urology. 3, 3-9.

(98) Stonehill, W.H., Dmochowski, R.R., Patterson, A.L. & Cox, C.E. (1996). Risk

factors for bladder tumors in spinal cord injury patients. J Urol. 155, 1248-1250. (99) Travis, L.B., Curtis, R.E., Glimelius, B., Holowaty, E.J., Van Leeuwen, F.E.,

Lynch, C.F., Hagenbeek, A., Stovall, M., Banks, P.M., Adami, J., et al. (1995). Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin’s lymphoma. J Natl Cancer Inst. 87, 524-530.

(100) Fernandes, E.T., Manivel, J.C., Reddy, P.K. & Ercole, C.J. (1996).

Cyclophosphamide associated bladder cancer: a highly aggressive disease. Analysis of 12 cases. J Urol. 156, 1931-1933.

(101) Cohen, S.M., Garland, E.M., St. John, M., Okamura, T. & Smith, R.A. (1992).

Acrolein initiates rat urinary bladder carcinogenesis. Cancer Res. 52, 3577-3581.

BIBLIOGRAFIA

199

(102) Kaldor, J.M., Day, N.E., Kittelmann, B., Pettersson, F., Langmark, F., Pedersen, D., Prior, P., Neal, F., Karjalainen, S,, Bell, J., et al. (1995). Bladder tumours following chemotherapy and radiotherapy for ovarian cancer: a case-control study. Int J Cancer. 63, 1-6.

(103) Kleinerman, R.A., Boice, J.D.Jr., Storm, H.H., Sparen, P., Andersen, A.,

Pukkala, E., Lynch, C.F., Hankey, B.F. & Flannery, J.T. (1995). Second primary cancer after treatment for cervical cancer: an international cancer registries study. Cancer. 76, 442-452.

(104) Neugut, A.I., Ahsan, H., Robinson, E. & Ennis, R.D. (1997). Bladder carcinoma

and other second malignancies after radiotherapy for prostate carcinoma. Cancer. 79, 1600-1604.

(105) Shah, S.K., Lui, P.D., Baldwin, D.D. & Ruckle, H.C. (2006). Urothelial carcinoma

after external beam radiation therapy for prostate cancer. J Urol. 175(6), 2063-2066. (106) Quilty, P.M. & Kerr, G.R. (1987). Bladder cancer following low or high dose pelvic

irradiation. Clin Radiol. 38, 583-585. (107) Kiemeney, L.A. & Schoenberg, M. (1996). Familial transitional cell carcinoma. J

Urol. 156, 867-872. (108) Kramer, A.A., Graham, S., Burnett, W.S. & Nasca, P. (1991). Familial aggregation

of bladder cancer stratified by smoking status. Epidemiology. 2, 145-148. (109) Goldgar, D.E., Easton, D.F., Cannon-Albright, L.A. & Skolnick, M.H. (1994).

Systematic population-based assessment of cancer risk in first-degree relative of cancer probands. J Natl Cancer Inst. 86, 1600-1608.

(110) Kiemeney, L.A., Moret, N.C., Witjes, J.A., Schoenberg, M.P. & Tulinius, H.

(1997). Familial transitional cell carcinoma among the population of Iceland. J Urol. 157, 1649-1651.

(111) Jensen, O.M., Esteve, J., Moller, J. T & Renard, H. (1990). Cancer in the European

Community and its Member States. Eur J Cancer. 26, 1167-1177. (112) Ferlay, J., Bray, F., Pisani, P. & Parkin, D.M. (2004). GLOBOCAN 2002: Cancer

Incidence, Mortality and Prevalence Worldwide. IARC CancerBase, No. 5, version 2.0. IARC Press. Lyon. Available at: http://www-dep.iarc.fr/

(113) Silverman, D.T., Hartge, P., Morrison, A.S. & Devesa, S.S. (1992). Epidemiology

of bladder cancer. Hematol Oncol Clin North Am. 6(1), 1-30.

(114) American Cancer Society. (2007). Cancer Facts & Figures 2007. American Cancer Society. Atlanta.

(115) Ferlay, J., Bray, F., Sankila, R. & Parkin, D.M. (1999). EUCAN: Cancer Incidence,

BIBLIOGRAFIA 200

Mortality and Prevalence in the European Union 1998. IARC CancerBase, No. 4, version 5.0. IARC Press. Lyon. Available at: http://www-dep.iarc.fr/eucan/eucan.htm

(116) Tyczynski, J.E. & Parkin, D. M. (2003). Bladder Cancer in Europe. ENCR Cancer Fact Sheets. 3, 1-4.

(117) World Health Statistics Annual. World Health Organization (WHO) Databank.

Geneva, Switzerland. Last updated: November 2001. Available at: http://www.who.int/whosis/

(118) RORENO – Registo Oncológico da Região Norte, edição do Instituto Português de

Oncologia Francisco Gentil – Centro do Porto 38. 1999-2000. (119) Registo de Cancro do Instituto Português de Oncologia – Centro do Porto. 1993-2002. (120) Ro, J.Y., Staerkel, G.A. & Ayala, A.G. (1992). Citologic and Histologic features of

superficial bladder cancer. Urol Clin North Am. 19(3), 435-453. (121) Lee, R. & Droller, M.J. (2000). The natural history of bladder cancer. Implications

for therapy. Urol Clin North Am. 27, 1-13. (122) Greene, F.L., Page, D.L., Fleming, I.D., Fritz, A.G., Balch, C.M., Haller, D.G. &

Morrow, M. (2002). AJCC Cancer Staging Manual. Sixth edition. Springer Verlag. New York.

(123) Sobin, L.H. & Wittekind, C. (1997). TNM Classification of malignant tumors. Fifth

edition. John Wiley & Sons, Inc. New York. (124) van der Meijden, A.P.M. (1998). Bladder Cancer. BMJ. 317,1366-1369. (125) Heney, N.M. (1992). Natural history of superficial bladder cancer. Urol Clin North

Am. 19(3), 429-433. (126) Montironi, R. & Mazzucchelli, R. (2003). Preneoplastic Lesions and Conditions of

the Urinary Bladder. EUA Update Series. 1, 53-63. (127) Montironi, R., Lopez-Beltran, A., Mazzucchelli, R. & Bostwick, D.G. (2003).

Classification and grading of the non-invasive urothelial neoplasms: recent advances and controversies. J Clin Pathol. 56, 91-95.

(128) Mostofi, F.K., Sorbin, L.H. & Torloni, H. (1973). Histological typing of urinary

bladder tumours. International Classification of Tumours, 19. World Health Organization. Geneva.

(129) Epstein, J.I., Amin, M.B., Reuter, V. & Mostofi, F.K. (1998). The World Health

Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol. 22(12), 1435-1448.

BIBLIOGRAFIA

201

(130) Mostofi, F.K., Davis, C.J. & Sesterhenn, I.A. (1999). Histological typing of urinary bladder tumours. World Health Organization, International Histological Classification of Tumours. Second Edition. Springer-Verlag. Berlin.

(131) Ebler, J.N., Sauter, G., Epstein, J.I. & Sesterhenn, I.A., for the International

Agency for Research on Cancer (2004). Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARC Press. Lyon.

(132) Lopez-Beltran, A. & Montironi, R. (2004). Non-Invasive Urothelial Neoplasms :

According to the Most Recent WHO Classification. Eur Urol. 46, 170-176. (133) Holmang, S. & Johansson, S.L. (2005). Urothelial Carcinoma of the Upper Urinary

Tract: comparison between the WHO/ISUP 1998 consensus classification and WHO 1999 classification system. Urology. 66(2), 274-278.

(134) Busch, C. & Algaba, F. (2002). The WHO/ISUP 1998 and WHO 1999 Systems for

malignancy grading of bladder cancer. Scientific foundation and translation to one another and previous systems. Virchows Arch. 441, 105-108.

(135) Bostwick, D.G. & Mikuz, G. (2002). Urothelial papilary (exophytic) neoplasms.

Virchows Arch. 441, 109-116. (136) McKenney, J.K., Amin, M.B. & Young, R.H. (2003). Urothelial (transitional cell)

papilloma of the urinary bladder: a clinicopathologic study of 26 cases. Mod Pathol. 16, 623-629.

(137) Cheng, L., Darson, M., Cheville, J.C., Neumann, R.M., Zincke, H., Nehra, A. &

Bostwick, D.G. (1999). Urothelial papilloma of the bladder. Clinical and biologic aplication. Cancer. 86(10), 2098-2101.

(138) Calais da Silva, F. (editor). (2002). Carcinoma da Bexiga – Perspectiva Actual. 1º

edição. Seleprinter, Artes Gráficas. Lisboa (Patrocínio da Fundação Schering Lusitana).

(139) Jones, T.D. & Cheng, L. (2006). Papillary urothelial neoplasm of low malignant

potential: evolving terminology and concepts. J Urol. 175(6), 1995-2003. (140) Cheng L., Neumann, R.M. & Bostwick, D.G. (1999). Papillary urothelial neoplasms

of low malignant potentional. Clinical and biologic implications. Cancer. 86, 2102-2108.

(141) Oosterhuis, J.W.A., Schapers, R.F.M., Janssen-Heijnen, M.L.G., Pauwels, R.P.E.,

Newling, D.W. & ten Kate, F. (2002). Histological grading of papillary urothelial carcinoma of tha bladder: prognostic value of the 1998 WHO/ISUP classification system and comparison with conventional grading systems. J Clin Pathol. 55, 900-905.

(142) Desai, S., Lim, S.D., Jimenez, R.E., Chun, T., Keane, T.E., McKenney, J.K.,

BIBLIOGRAFIA 202

Zavala-Pompa, A., Cohen, C., Young, R.H. & Amin MB. (2000). Relationship of cytokeratin 20 and CD44 protein expression with WHO/ISUP grade in pTa and pT1 papillary urothelial neoplasia. Mod Pathol. 13, 1315-1323.

(143) Sauter, G., Algaba, F., Amin, M., Busch, C., Cheville, J., Gasser, T., Grignon,

D.J., Hofstadter, F., Lopez-Beltran, A. & Epstein, J.I. (2004). Non-Invasive Urothelial Neoplasias. WHO Classification of Non Invasive Papillary Urothelial Tumors. In Eble, J.N., Sauter, G., Epstein, J.I. & Sesterhenn, I.A., World Health Organization Classification of Tumours. Pathology and Genetics: Tumors of the Urinary System and Male Genital Organs. IARCC Press. Lyon.

(144) Hudson, M.A. & Herr, H.W. (1995). Carcinoma in situ of the bladder. J Urol. 153,

564-572. (145) McKeney, J.K., Gomez, J.A., Desai, S., Lee, M.W. & Amin, M.B. (2001).

Morphologic expressions of urothelial carcinoma in situ: a detailed evaluation of its histologic patterns with emphasis on carcinoma in situ with microinvasion. Am J Surg Pathol. 31, 745-750.

(146) Duque, J.L. & Loughlin, K.R. (2000). An overview of the treatment of superficial

bladder cancer. Intravesical chemotherapy. Urol Clin North Am. 27, 125-135. (147) Sakai, I., Miyake, H., Harada, K., Hara, I., Inoue, T.A. & Fujisawa, M. (2006).

Analysis of factors predicting intravesical recurrence of superficial transitional cell carcinoma of the bladder without concomitant carcinoma in situ. Int J Urol. 13, 1389-1392.

(148) Dutta, S.C., Smith, J.A. Jr., Shappell, S.B., Coffey, C.S., Changt, S.S. & Cookson,

M.S. (2001). Clinical understaging of high risk nonmuscle invasive urothelial carcinoma treated with radical cyctectomy. J Urol. 166, 490-493.

(149) Herr, H.W. (2000). Tumor progression and survival of patients with high grade,

noninvase papillary (TaG3) bladder tumours: 15-year outcome. J Urol. 163, 60-62. (150) Wiesner, C., Pfitzenmaier, J., Faldum, A., Gillitzer, R., Melchior, S.W. &

Thüroff, J.W. (2005). Lymph node metastases in non-muscle invasive bladder cancer are correlated with the number of transurethral ressections and tumour upstaging at radical cystectomy. BJU International. 95, 301-305.

(151) Sleeman, J.P. (2000). The lymph node as a bridgehead in the metastatic dissemination

of tumours. Recent Results Cancer Res. 1654, 3-12. (152) Stacker, S.A., Achen, M.G., Jussila, L., Baldwin, M.E. & Alitalo, K. (2002).

Metastasis: lymphangiogenesis and cancer metastasis. Nat Rev Cancer. 2, 573-583. (153) Abdel-Latif, M. (2005). Which clinical variables are associated with lymph node

metastases in patients with superficial bladder cancer? Nat Clin Pract Urol. 2(5), 214-215.

BIBLIOGRAFIA

203

(154) Solsona, E., Iborra, I., Rubio, J., Casanova, J. & Almenar, S. (2004). The optimum timing of radical cystectomy for patients with recurrent high-risk superficial bladder tumour. BJU Int. 94, 1258-1262.

(155) May, M., Helke, C., Nitzke, T., Vogler, H. & Hoschke, B. (2004) Survival rates

after radical cystectomy according to tumor stage of bladder carcinoma at first presentation. Urol Int. 72(2), 103-111.

(156) Skinner, D.G., Stein, J.P., Lieskovsky, G., Skinner E.C., Boyd S.D., Figueroa A.,

Jones P., Cote R. & Groshen S. (1998). 25-year experience in the management of invasive bladder cancer by radical cistectomy. Eur Urol. 33(4), 25-26.

(157) Quek, M.L., Stein, J.P., Daneshmand, S., Miranda, G., Thangathurai, D., Roffey,

P., Skinner, E.C., Lieskovsky, G. & Skinner, D.G. (2006). A critical analysis ot perioperative mortality from radical cystectomy. J Urol. 175(3), 886-889.

(158) Boccardo, F. & Palmeri, L. (2006). Adjuvant chemotherapy of bladder cancer. Ann

Oncol. 17(5), 129-132. (159) Passaperuma, K., Ash, R., Venkatesan, V., Rodrigues, G. & Winguis, E. (2006).

Pelvic chemoradiotherapy after chemotherapy for metastatic bladder cancer. Can J Urol. 13(2), 3009-3015.

(160) Cohen, S.M., Goel, A., Phillips, J., Ennis, R.D. & Grossbard, M.L. (2006). The

Role of Perioperative Chemotherapy in the Treatment of Urothelial Cancer. Oncologist. 11, 630-640.

(161) Stein, J.P., Lieskovsky, G., Cote, R., Groshen, S., Feng, A.C., Boyd, S., Skinner,

E., Bochner, B., Thangathurai, D., Mikhail, M., Raghavan, D. & Skinner, D.G. (2001). Radical Cystectomy in the treatment of invasive bladder cancer: long term results in 1054 patients. J Clin Oncol. 19, 666-675.

(162) May, M., Nitzke, T., Helke, C., Vogler, H. & Hoschke, B. (2004). Significance of

the time period between diagnosis of muscle invasion and radical cystectomy with regard to the prognosis of transitional cell carcinoma of the urothelium in the bladder. Scand J Urol Nephrol. 38(3), 231-235.

(163) Fradet, Y., Aprikian, A., Dranitsaris, G., Siemens, R., Tsihlias, J., Fleshner, N. &

Canadian surgical wait times (SWAT) initiative. (2006). Does prolonging the time to bladder cancer surgery affect long-term cancer control: a systematic review of the literature. Can J Urol. 13(3), 37-47.

(164) Stein, J.P. & Skinner, D.G. (2005). The role of lymphadenectomy in high-grade

invasive bladder cancer. Urol Clin North Am. 32(2), 187-197. (165) Vieweg, J., Gschwend, J.E., Herr, H.W. & Fair, W.R. (1999). Pelvic lymph node

dissection can be curative in patientts with node positive bladder cancer. J Urol. 161, 449-454.

BIBLIOGRAFIA 204

(166) Leissner, J. Hohenfellner, R., Thuroff, J.W. & Wolf, H.K. (2000). Lymphadenectomy in patients with transitional cell carcinoma of the urinary bladder, significance for staging and prognosis. BJU Int. 85, 817-823.

(167) Ather, M.H., Fatima, S. & Sinanoglu, O. (2005). Extent of lymphadenectomy in

radical cystectomy for bladder cancer. World J Clin Oncol. 3, 43-47. (168) Nagele, U., Anastasiadis, A.G., Merseburger, A.S., Sievert, K.D., Stenzl, A. &

Kuczyk, M. (2006). Clinical outcomes after cystectomy in patients with lymph node-positive bladder cancer. Expert Rev Anticancer Ther. 6(6), 871-876.

(169) Dhar, N.B., Campbell, S.C., Zippe, C.D., Derweesh, I.H., Reuther, A.M.,

Fergany, A. & Klein, E.A. (2006). Outcomes in patients with urothelial carcinoma of the bladder with limited pelvic lymph node dissection. BJU Int. 98(6), 1172-1175.

(170) Abol-Enein, H., El-Baz, M., Abd El-Hameed, M.A., Abdel-Latif, M. & Ghoneim,

M.A. (2004). Lymph node involvement in patients with bladder cancer treated with radical cystectomy: a patho-anatomical study – a single center experience. J Urol. 172(5 Pt 1), 1818-1821.

(171) Poulsen, A.L., Horn, T. & Steven, K. (1998). Radical cystectomy: extending the

limits of pelvic node dissection improved survival for patients with bladder cancer confined to the bladder wall. J Urol. 160, 2015-2019.

(172) Stein, J.P., Cai, J., Groshen, S. & Skinner, D.G. (2003). Risk factors for patients

with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: the concept of lymph node density. J Urol. 170, 35-41.

(173) Ghoneim, M.A. & Abol Enein., H. (2004). Lymphadenectomy with cystectomy: Is it

necessary and what is its extent. Eur Urol. 45, 457-461. (174) Herr, H.W., Faulkner, J.R., Grossman, H.B., Natale, R.B., White, R., Sarosdy, M.

& Crawford, E.D. (2004). Surgical Factores influence Bladder Cancer Outcomes: A Cooperative Group Report. J Clin Oncol. 22(14), 2781-2789.

(175) Stein, J.P. (2006). Lymphadenectomy in bladder cancer : How high is “high enough”?

Urol Oncol. 24, 349-355. (176) Sanderson, K.M., Skinner, D. & Stein, J.P. (2006). The prognostic and staging

value of lymph node dissection in the treatment of invasive bladder cancer. Nat Clin Pract Urol. 3(9), 485-494.

(177) Honma, I., Masumori, N., Sato, E., Maeda, T., Hirobe, M., Kitamura, H.,

Takahashi, A., Itoh, N., Tamakawa, M. & Tsukamoto T. (2006). Removal of more lymph nodes may provide better outcome, as well as more accurate pathologic findings, in patients with bladder cancer – analysis of role of pelvic lymph node dissection. Urology. 68(3), 543-548.

BIBLIOGRAFIA

205

(178) Kassouf, W., Leibovici, D., Munsell, M.F., Dinney, C.P., Grossman, H.B. & Kamat, A.M. (2006). Evaluation of the relevance of lymph node density in a contemporary series of patients undergoing radical cystectomy. J Urol. 176(1), 53-57.

(179) Algaba, F. (2006). Lymphovascular invasion as a prognostic tool for advanced

bladder cancer. Curr Opin Urol. 16(5), 367-371. (180) Siewert, J.R., Bottcher, K., Stein, H.J., Roder, J.D. & the German Gastric

Carcinoma Study Group. (1998). Relevant prognostic factors in gastric cancer. Ann Surg. 228, 449-461.

(181) Caplin, S., Cerottini, J.P., Bosman, F.T., Constanda, M.T. & Givel, J.C. (1998).

For patients with Duke’s B (TNM Stage II) colorectal carcinoma, examination of six or fewer lymph nodes is related to poor prognosis. Cancer. 83, 666-672.

(182) Mathiesen, O., Carl, J., Bonderup, O. & Panduro, J. (1990). Axillary sampling and

the risk of erroneous staging of breast cancer. Acta Oncol. 29, 721-725. (183) Burkhard, F.C., Scumacher, M. & Studer, U.E. (2005). The role of

lymphadenectomy in prostate cancer. Nat Clin Pract Urol. 2(7), 336-342. (184) Denis, F., Garaud, P., Manceau, A., Beuter, P., Garand, G., le Floch, O. & Calais,

G. (2001). Prognostic value of the number of involved nodes after neck dissection in oropharyngeal and oral cavity carcinoma. Cancer Radiother. 5(1), 12-22.

(185) Werner, J.A. & Davis, R.K. (2005). Metastases in Head and Neck Cancer. Springer.

London. (186) Jeltsch, M. (2002). VEGFR-3 Ligands and Lymphangiogenesis. Academic

dissertation. Faculty of Science of the University of Helsinki. (187) Sadler, T.W. (2001). Langman Embriologia Médica. Oitava edição. Guanabara

Koogan. Rio de Janeiro. (188) Saharinen, P., Tammela, T., Karkkainen, M. & Alitalo, K. (2004). Lymphatic

vasculature: development, molecular regulation and role in tumor metastasis and inflammation. TRENDS in Immunol. 25(7), 387-395.

(189) Swartz, M.A. (2001). The physiology of the lymphatic system. Adv Drug Del Rev. 50,

3-20. (190) Oliver, G. & Detmar, M. (2002). The rediscovery of the lymphatic system: old and

new insights into the development and biological function of the lymphatic vasculature. Genes & Develop. 16, 773-783.

(191) Williams, P.L., Warwick, R., Dyson, M. & Bannister, L.H. (1995). Gray Anatomia.

37ª edição. Guanabara Koogan. Rio de Janeiro.

BIBLIOGRAFIA 206

(192) Trzewik, J., Mallipattu, S.K., Artmann, G.M., Delano, F.A. & Schmid-Schonbein, G.W. (2001). Evidence for a second valve system in lymphatics: endothelial microvalves. FASEB J. 15(10), 1711-1717.

(193) Schmid-Schonbein, G.W. (2003). The second valve system in lymphatics. Lymphatic

Res Biol. 1(1), 25-29. (194) Solito, R., Alessandrini, C., Fruschelli, M., Pucci, A.M. & Gerli, R. (1997). An

immunological correlation between the anchoring filaments of initial lymph vessels and the neighboring elastic fibers: a unified morphofunctional concept. Lymphology. 30(4), 194-202.

(195) Rodrigues, C. (2003). Anatomia Aplicada do Sistema Linfático. In Pitta, G.B.B,

Castro, A.A., Burihan, E., Angiologia e Cirurgia Vascular: Guia Ilustrado. UNCISAL/ECMAL & LAVA. Maceió. Disponível em: http://www.lava.med.br/livro.

(196) Gashev, A.A. (2002). Physiologic aspects of lymphatic contractile function: current

perspectives. Ann N Y Acad Sci. 979, 178-187. (197) Bridenbaugh, E.A., Gashev, A.A. & Zawieja, D.C. (2003). Lymphatic muscle: a

review of contractile function. Lymphatic Res Biol. 1(2), 147-158. (198) Widmaier, E.P., Raff, H. & Strang, K. (2006). Vander’s Human Phisiology – The

Mechanisms of Body Function. Tenth edition. McGraw-Hill. New York. (199) Blum, K. & Pabst, R. (2006). Keystones in lymph node development. J Anat. 209,

585-595. (200) Szuba, A., Shin, W.S., Strauss, W. & Rockson, S. (2003). The Third Circulation:

Radionucleotide Lymphoscintigraphy in the Evaluation of Lymphedema. J Nucl Med. 44, 43-57.

(201) Poggi, P., Marchetti, C., Tazzi, A. & Scelsi, R. (1995). The lymphatic vessels and

their relationship to lymph formation in the human urinary bladder. Lymphology. 28(1), 35-40.

(202) Rockson, S.G. (2001) Lymphedema. Am J Med. 110, 288–295. (203) Alitalo, K., Tammela, T. & Petrova, T. (2005). Lymphangiogenesis in development

and human disease. Nature. 438, 946-953. (204) Pepper, M.S. (2001). Lymphangiogenesis and Tumor Metastasis: Myth or Reality.

Clin Can Res. 7, 462-468. (205) Smith, J.A. & Whitmore, W.F.Jr. (1981). Regional lymph node metastasis from

bladder cancer. J Urol. 126, 591-593. (206) Leissner, J., Ghoneim, M.A., Abol-Enein, H., Thuroff, J.W., Franzaring, L.,

BIBLIOGRAFIA

207

Fisch, M., Schulze, H., Managadze, G., Allhoff, E.P., el-Baz, M.A., Kastendieck, H., Buhtz, P., Kropf, S., Hohenfellner, R. & Wolf, H.K. (2004). Extended radical lymphadenectomy in patients with urothelial bladder cancer: Results of a prospective multicenter study. J Urol. 171, 139-144.

(207) Vazina, A., Dugi, D., Shariat, S.F., Evans, J., Link, R. & Lerner, S.P. (2004).

Stage specific lymph node metastasis mapping mapping in radical cystectomy specimens. J Urol. 171, 1830-1834.

(208) Bochner, B.H., Cho, D., Herr, H.W., Donat, M., Kattan, M.W. & Dalbgani, G.

(2004). Prospective packaged lymph node dissections with radical cystectomy: Evaluation of node count variability and node mapping. J Urol. 172, 1286-1290.

(209) Mills, R.D., Turner, W.H., Fleischmann, R., Markwalder, R., Thalmann, G.N. &

Studer, U.E. (2001). Pelvic lymph node metastasis from bladder cancer: Outcome in 83 patients after radical cystectomy and pelvic lymphadenectomy. J Urol. 166, 19-23.

(210) Herr, H.W. (2003). Surgical factors in bladder cancer: More (nodes) + more

(pathology) = less (mortality). BJU Int. 92,187-188. (211) Herr, H., Lee, C., Chang, S., Lerner, S., Bladder Cancer Collaborative Group, et

al. (2004). Standardization of radical cystectomy and pelvic lymph node dissection for bladder cancer; a collaborative group report. J Urol. 171, 1823-1828.

(212) Alitalo, K. & Carmeliet, P. (2002). Molecular mechanisms of lymphangiogenesis in

health and disease. Cancer Cell. 1, 219-227. (213) Karpanen, T. & Mäkinen, T. (2006). Regulation of lymphangiogenesis – From cell

fate determination to vessel remodeling. Exp Cell Res. 312, 575-583. (214) Noh, K.W., Bouras, E.P., Bridges, M.D., Nakhleh, R.E. & Nguyen, J.H. (2005).

Gallbladder lymphangioma: a case report and review of the literature. J Hepatobiliary Pancreat Surg. 12, 405-408.

(215) Janse, A.J, van Coevorden, F., Peterse, H., Keus, R.B. & van Dongen, J.A. (1995).

Lymphedema-induced lymphangiosarcoma. Eur J Surg Oncol. 21(2), 155-158. (216) Jussila, L., Valtola, R., Partanen, T.A., Salven, P., Heikkila, P., Matikainen, M.T.,

Renkonen, R., Kaipainen, A., Detmar, M., Tschachler, E., Alitalo, R. & Alitalo, K. (1998). Lymphatic endothelium and Kaposi’s sarcoma spindle cells detected by antibodies against the vascular endothelial growth factor receptor-3. Cancer Res. 58, 1599-1604.

(217) Weninger, W., Partanen, T.A., Breiteneder-Geleff, S., Mayer, C., Kowalski, H.,

Mildner, M., Pammer, J., Sturzl, M., Kerjaschki, D., Alitalo, K. & Tschachler, E. (1999). Expression of vascular endothelial growth factor receptor-3 and podoplanin suggests a lymphatic endothelial cell origin of Kaposi’s sarcoma tumor cells. Lab Invest. 79, 243-251.

BIBLIOGRAFIA 208

(218) Beasley, N.J.P., Prevo, R., Banerji, S., Leek, R.D., Moore, J., van Trappen, P., Cox, G., Harris, A.L. & Jackson, D.G. (2002). Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer. Cancer Res. 62, 1315-1320.

(219) Hall, F.T., Freeman, J.L., Asa, S.L. Jackson, D.G. & Beasley, N.J. (2003).

Intratumoral lymphatics and lymph node metastases in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 129, 716-719.

(220) Straume, O., Jackson, D.G. & Akslen, L.A. (2003). Independent prognostic impact

of lymphatic vessel density and presence of low-grade lymphangiogenesis in cutaneous melanoma. Clin Cancer Res. 9, 250-256.

(221) McCarter, M.D., Clarke, J.H. & Harken, A.H. (2004). Lymphangiogenesis is

pivotal to the trials of a successful cancer metastasis. Surgery. 135(2), 121-124. (222) Stacker, S.A., Baldwin, M.E. & Achen, M.G. (2002). The role of tumor

lymphangiogenesis in metastatic spread. FASEB J. 16, 922-934. (223) Hirakawa, S. & Detmar, M. (2004). New insights into the biology and pathology of

the cutaneous lymphatic system. J Dermatol Sci. 35, 1-8. (224) Scavelli, C., Weber, E., Aglianò, M., Cirulli, T., Nico, B., Vacca, A. & Ribatti, D.

(2004). Lymphatics at the crossroads of angiogenesis and lymphangiogenesis. J Anat. 204, 433-449.

(225) Oliver, G. (2005). Lymphatic vasculature development. Nature Rev Immunol. 4, 35-

45. (226) Tammela, T., Petrova, T.V. & Alitalo, K. (2005). Molecular lymphangiogenesis:

new players. Trends Cell Biol. 15, 434-441. (227) Risau, W. (1997). Mechanisms of angiogenesis. Nature. 386 (6626), 671-674. (228) Risau, W. (1998). Development and differentiation of endothelium. Kidney Int Suppl.

67, S3-6. (229) Jussila, L. & Alitalo, K. (2002). Vascular Growth Factors and Lymphangiogenesis.

Physiol Rev. 82, 673-700. (230) Folkman, J. (1971). Tumor angiogenesis: therapeutic implications. N Engl J Med.

285, 1182-1186. (231) Folkman, J. (1972). Anti-angiogenesis: new concept for therapy of solid tumors. Ann

Surg. 175, 409-416. (232) Kerbel, R.S. (2000). Tumor angiogenesis: past, present and the near future.

Carcinogenesis. 21(3), 505-515.

BIBLIOGRAFIA

209

(233) National Cancer Institute, available at: http://newscenter.cancer.gov/images/understandingcancer/PDFs/ANGIOGEN.PDF

(234) Kaipainen, A., Korhonen, J., Mustonen, T., van Hinsbergh, V.W., Fang, G.H.,

Dumont, D., Breitman, M. & Alitalo, K. (1995). Expression of the fms-like tyrosine kinase FLT4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci. 92, 3566-3570.

(235) Wigle, J.T. & Oliver, G. (1999). Prox1 function is required for the development of

the murine lymphatic system. Cell. 98, 769-778. (236) Wigle, J.T., Harvey, N., Detmar, M., Lagutina, I., Grosveld, G., Gunn, M.D.,

Jackson, D.G. & Oliver, G. (2002). An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J. 21(7), 1505-1513.

(237) Hong, Y., Harvey, Y.K., Noh, Y.H., Schacht, V., Hirakawa, S., Detmar, M. &

Oliver, G. (2002). Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Dev Dyn. 225 (3), 351-357.

(238) Petrova, T.V., Makinen, T., Makela, T.P., Saarela, I., Vertanen I., Ferrell, R.E.,

Finegold, D.N., Kerjaschki, D., Yla-Hertuala, S. & Alitalo, K. (2002). Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO J. 21, 4593-4599.

(239) Oliver, G.T. & Harvey, N. (2002). A steptwise model of the development of

lymphatic vasculature. Ann N Y Acad Sci. 979, 159-165. (240) Karkkainen, M.J., Haiko, P., Sainio, K., Partanen, J., Taipale, J., Petrova, T.V.,

Jeltsch, M,, Jackson, D.G., Talikka, M., Rauvala, H., Betsholtz, C. & Alitalo, K. (2004). Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol. 5, 74-80.

(241) Paavonen, K., Puolakkainen, P., Jussila, L., Jahkola, T. & Alitalo, K. (2000).

Vascular endothelial growth factor receptor-3 in lymphangiogenesis in wound healing. Am J Pathol. 156(5), 1499-1504.

(242) Jain, R.K. & Fenton, B.T. (2002). Intratumoral lymphatic vessels: a case of mistaken

identity or malfunction? J Natl Cancer Inst. 94, 417-421. (243) Zinovieva, R. D., Duncan, M. K., Johnson, T. R., Torres, R., Polymeropoulos, M.

H. & Tomarev, S. I. (1996). Structure and chromosomal localization of the human homeobox gene Prox 1. Genomics. 35, 517-522.

(244) Ferrara, N. & Davis-Smyth, T. (1997). The Biology of Vascular Endothelial Growth

Factor. End Rev. 18(1), 4-25. (245) McDonald, N.Q. & Hendrickson, W.A. (1993). A structural superfamily of growth

factors containing a cystine knot motif. Cell. 73(3), 421-424.

BIBLIOGRAFIA 210

(246) Shibuya, M. (2001). Structure and Function of VEGF/VEGF-receptor System Involved in Angiogenesis. Cell Struct Func. 26, 25-35.

(247) Byrne, A.M., Bouchier-Hayes, D.J. & Harmey, J.H. (2005). Angiogenic and cell

survival functions of Vascular Endothelial Growth Factor (VEGF). J Cell Mol Med. 9(4), 777-794.

(248) Karkkainen, M.J. & Petrova, T.V. (2000). Vascular endothelial growth factor

receptors in the regulation of angiogenesis and lymphangiogenesis. Oncogene. 19, 5598-5605.

(249) Leung, D.W., Cachianes, G., Kuang, W-J., Goeddel, D.V. & Ferrara, N. (1989).

Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 246, 1306-1309.

(250) Carmeliet, P., Ferreira, V., Breier, G., Pollefeyt, S., Kieckens, L., Gertsenstein,

M., Fahrig, M., Vandenhoeck, A., Harpal, K., Ebenhardt, C., Declercq, C., Pawling, J., Moons, L., Collen, D., Risau, W. & Nagy, A. (1996). Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 380, 435-439.

(251) Ferrara, N., Carver-Moore, K., Chen, H., Dowd M., Lu, L., O’Shea, K.S., Powell-

Braxton, L., Hillan, K.J. & Moore, M.W. (1996). Heterozygous embrionic lethality induced by targeted inactivation of the VEGF gene. Nature. 380, 439-442.

(252) Dvorak, H.F., Harvey, V.S., Estrella, P., Brown, L.F., McDonagh, J. & Dvorak,

A.M. (1987). Fibrin containing gels induce angiogenesis: implications for tumor stroma generation and wound healing. Lab Invest. 57, 673-686.

(253) Dvorak, H.F., Brown, L.F., Detmar, M. & Dvorak, A.M . (1995). Vascular

permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 146, 1029-1039.

(254) Ferrara, N. (2000). VEGF: an updated on biological and therapeutic aspects. Curr

Opin Biotechnol. 11, 617-624. (255) Tischer, E., Mitchell, R., Hartman, T., Silva, M., Gospodarowicz, D., Fiddes, J.C.

& Abraham, J.A. (1991). The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem. 266, 11947-11954.

(256) Olofsson, B., Pajusola, K., Kaipainen, A., von Euler, G., Joukov, V., Saksela, O.,

Orpana, A., Pettersson, R.F., Alitalo, K. & Eriksson, U. (1996). Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci USA. 93, 2576-2581.

(257) Carmeliet, P., Moons, L., Luttun, A., Vincenti, V., Compernolle, V., De Mol, M.,

Wu, Y., Bono, F., Devy, L., Beck, H., Scholz, D., Acker, T., DiPalma, T.,

BIBLIOGRAFIA

211

Dewerchin, M., Noel, A., Stalmans, I., Barra, A., Blacher, S., Vandendriessche, T., Ponten, A., Eriksson, U., Plate, K.H., Foidart, J.M., Schaper, W., Charnock-Jones, D.S., Hicklin, D.J., Herbert, J.M., Collen, D. & Persico, M.G. (2001). Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 7 (5), 575-83.

(258) Luttun, A., Tjwa, M., Moons, L., Wu, Y., Angelillo-Scherrer, A., Liao, F., Nagy,

J.A., Hooper, A., Priller, J., De Klerck, B., Compernolle, V., Daci, E., Bohlen, P., Dewerchin, M., Herbert, J.M., Fava, R., Matthys, P., Carmeliet, G., Collen, D., Dvorak. H.F., Hicklin, D.J. & Carmeliet, P. (2002). Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med. 8 (8), 831-40.

(259) Joukov, V., Sorsa, T., Kumar, V., Jeltsch, M., Claesson-Welsh, L., Cao, Y.,

Saksela, O., Kalkkinen, N. & Alitalo, K. (1997). Proteolytic processing regulates receptor specificity and activity of VEGF-C. EMBO J. 16, 3898-3911.

(260) Stacker, S.A., Stenvers, K., Caesar, C., Vitali, A., Domagala, T., Nice, E., Roufail,

S., Simpson, R.J., Moritz, R., Karpanen, T., Alitalo, K & Achen, M.G. (1999). Biosynthesis of vascular endothelial growth factor-D involves proteolytic processing wich generates non-covalent homodimers. J Biol Chem. 274, 32127-32136.

(261) Kukk, E., Lymboussaki, A., Taira, S., Kaipanen, A., Jeltsch, M., Joukov, V. &

Alitalo, K. (1996). VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Development. 122, 3829-3837.

(262) Baldwin, M.E., Halford, M.M., Roufail, S., Williams , R.A., Hibbs, M.L. Grail, D.,

Kubo, H., Stacker, S.A. & Achen, M.G. (2005). Vascular Endothelial Growth Factor D is dispensable for Development of the Lymphatic System. Mol Cell Biol. 25(6), 2441-2449.

(263) Achen, M.G., Jeltsch, M., Kukk, E., Makinen, T., Vitali, A., Wilks, A.F., Alitalo,

K. & Stacker, S.A. (1998). Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc Natl Acad Sci. 95, 548-553.

(264) Joukov, V., Pajusola, K., Kaipainen, A., Chilov, D., Lahtinen, I., Kukk, E.

Saksela, O., Kalkkinen, N. & Alitalo, K. (1996). A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 15, 290-298.

(265) Makinen, T., Veikkola, T., Mustjoki, S., Karpanen, T., Catimel, B., Nice, E.C.,

Wise, L., Mercer, A., Kowalski, H., Kerjaschki, D., Stacker, S.A., Achen, M.G. & Alitalo, K. (2001b). Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J. 20, 4762-4773.

BIBLIOGRAFIA 212

(266) Fournier, E., Birnbaum, D. & Borg, J.P. (1997). Receptors for factores of the VEGF family. Bull Cancer. 84, 397-403.

(267) Shibuya, M. & Claesson-Welsh, L. (2006). Signal transduction by VEGF receptors

in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res. 312, 549-560. (268) Neufeld, G., Cohen, T, Gengrinovirch, S. & Poltorak, Z. (1999). Vascular

endothelial growth factor (VEGF) and its receptors. FASEB J. 13, 9-22. (269) Al-Rawi, M.A.A., Mansel, R.E. & Jiang, W.G. (2005). Molecular and cellular

mechanisms of lymphangiogenesis. EJSO. 31, 117-121. (270) Dumont, D.J., Jussila, L., Taipale, J., Lymboussaki, A., Mustonen, T., Pajusola,

K., Breitman, M. & Alitalo, K. (1998). Cardiovascular failure in mouse embryos deficient in VEGF receptor-3. Science. 282, 946-949.

(271) Stacker, S.A., Hughes, R.A. & Achen, M.G. (2004). Molecular targeting of

lymphatics for therapy. Curr Pharm Des. 10, 65-74. (272) Makinen, T., Jussila, L., Veikkola, T., Karpanen, T., Ketunen, M.I., Pulkkanen,

K.J., Kauppinen, R., Jackson, D.G., Hubo, H., Nishikawa, S., Yla-Herttuala, S. & Alitalo, K. (2001). Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3. Nat Med. 7, 199-205.

(273) Pytowski, B., Goldman, J., Persaud, K., Wu, L., Witte, L., Hicklin, D.J., Skobe,

M., Boardman, K.C. & Swartz, M.A. (2005). Complete and specific inhibition of adult lymphatic regeneration by a novel VEGFR-3 neutralizing antibody. J Natl Cancer Inst. 97, 14-21.

(274) Karkkainen, M.J., Ferrell, R.E., Lawrence, E.C., Kimak, M.A., Levinson, K.L.,

McTigue, M.A., Alitalo, K. & Finegold, D.N. (2000). Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Nat Genet. 25, 153-159.

(275) Partanen, T.A., Arola, J., Saaristo, A., Jussila, L., Ora, A., Miettinen, M.,

Stacker, S.A., Achen, M.G. & Alitalo, K. (2000). VEGF-C and VEGF-D expression in neuroendocrine cells and their receptor, VEGFR-3, in fenestrated blood vessels in human tissues. FASEB J. 14, 2087-2096.

(276) Schoppmann, S.F., Birner, P., Stockl, J., Kalt, R., Ullrich, R., Caucig, C.,

Kriehuber, E., Nagy, K., Alitalo, K, & Kerjaschki, D. (2002). Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lynphangiogenesis. Am J Pathol. 161, 947-956.

(277) Hamrah, P., Chen, L., Zhang, Q. & Dana, M.R. (2003). Novel expression of

vascular endothelial growth factor receptor (VEGFR-3) and VEGF-C on corneal dendrit cells. Am J Pathol. 163, 57-68.

(278) Banerji, S., Ni, J., Wang, S-X., Clasper, S., Su, J., Tammi, R., Jones, M. &

BIBLIOGRAFIA

213

Jackson, D.G. (1999). LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluroran. J Cell Biol. 144, 789-801.

(279) Prevo, R., Banerji, S., Ferguson, D.J., Clasper, S. & Jackson, D.G. (2001). Mouse

LYVE-1 is an endocytic receptor for hyaluroran in lymphatic endothelium. J Biol Chem. 276, 19420-19430.

(280) Carreira, C.M., Nasser, S.M., di Tomaso, E., Padera, T.P., Boucher, Y., Tomarev,

S.I. & Jain, R.K. (2001). LYVE-1 is not restricted to the lymph vessels: Expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Cancer Res. 61, 8079-8084.

(281) Makinen, T., Adams, R.H., Bailey, J., Lu, Q., Ziemiecki, A., Alitalo, K., Klein, R.

& Wilkinson, G.A. (2005). PDZ interaction site in ephrinB2 is required for the development of the lymphatic system. Mol Cell Biol. 25, 2441-2449.

(282) Jackson, D.G., Prevo, R., Clasper, S & Banerji, S. (2001). LYVE-1, the lymphatic

system and tumor lymphangiogenesis. Trends Immunol. 22(6), 317-321. (283) Abtahian, F., Guerriero, A., Sebzda, E., Lu, M.M., Zhou, R., Mocsai, A., Myers,

E.E., Huang, B., Jackson, D.G., Ferrari, V.A., Tybulewicz, V., Lowell, C.A., Lepore, J.J., Koretzky, G.A. & Kahn, M.L. (2003). Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science. 299(5604), 247-251.

(284) Yancopoulos, G.D., Davis, S., Gale, N.W., Rudge, J.S., Wiegand, S.J. & Holash, J.

(2000). Vascular-specific growth factors and blood vessel formation. Nature. 407, 242-248.

(285) Gale, N.W., Thurston, G., Hackett, S.F., Renard, R., Wang, Q., McClain, J.,

Martin, C., Witte, C., W itte, M..H., Jackson, D., Suri, C., Campochiaro, P.A., Wiegand, S.J. & Yancopoulos, G.D. (2002). Angiopoietin-2 is required for postnatal angiogenesis and lymphatic patterning, and only the latter role is rescued by Angiopoietin-1. Dev Cell. 3, 411-423.

(286) Morisada, T., Oike, Y., Yamada, Y., Urano, T., Akao, M., Kobota, Y., Maekawa,

H., Kimura, Y., Ohmura, M., Miyamoto, T., Nozawa, S., Koh, G.Y., Alitalo, K. & Suda, T. (2005). Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation. Blood. 105, 4649-4656.

(287) Tammela, T., Saaristo, A., Lohela, M., Morisada, T., Tornberg, J., Norrmen, C.,

Oike, Y., Pajusola, K., Thurston, G., Suda, T., Yla-Herttuala, S. & Alitalo, K. (2005). Angiopoietin-1 promotes lymphatic sprouting and hyperplasia. Blood. 105, 4642-4648.

(288) Poliakov, A., Cotrina, M. & Wilkinson, D.G. (2004). Diverse Roles of Eph

Receptors and Ephrins in the Regulation of Cell Migration and Tissue Assembly. Develop Cell. 7, 465-480.

BIBLIOGRAFIA 214

(289) Mäkinen, T., Adams, R.H., Bailey, J., Lu. Q., Ziemiecki, Z., Alitalo, K., Klein, R. & Wilkinson, G.A. (2005). PDZ interation site in ephrinB2 is required for the remodelilg of lymphatic vasculature. Genes Develop. 19, 397-410.

(290) Cederberg, A., Gronning, L.M., Ahren, B., Tasken, K., Carlsson, P. & Enerback,

S. (2001). FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Cell. 106, 563-573.

(291) Petrova, T.V., Karpanen, T., Norrmen, C., Mellor, R., Tamakoshi, T., Finegold,

D., Ferrell, R., Kerjaschki, D., Mortimer, P., Yla-Herttuala, S., Miura, N. & Alitalo, K. (2004). Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distiachis. Nature Med. 10, 974-981.

(292) Dagenais, S.L., Hartsough, R.L., Erickson, R.P., Witte, M.H., Buttler, M.G. &

Glover, T.W. (2004). Foxc2 is expressed in developing lymphatic vessels and other tissues associated with lymphedema-distichiasis syndrome. Gene Expr Patterns. 4, 611-619.

(293) Matsui, K., Breitender-Geleff, S., Soleiman, A., Kowalski, H. & Kerjaschki, D.

(1999). Podoplanin, a novel-43-kDa membrane protein, controls the shape of podocytes. Nephrol Dial Transplant. 14(Suppl.), 9-11.

(294) Schacht, V., Ramirez, M.I., Hong, Y.K., Hirakawa, S., Feng, D., Harvey, N.,

Williams, M., Dvorak, A.M., Dvorak, H.F., Oliver, G . & Detmar, M. (2003). T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation abd causes lymphedema. EMBO J. 22, 3546-3556.

(295) Powers, C.J., McLeskey, S.W. & Wellstein, A. (2000). Fibroblast growth factors,

their receptors and signaling. End-Rel Cancer. 7, 165-197. (296) Kubo, H., Cao, R., Bräkenhielm, E., Mäkinen, T., Cao, Y. & Alitalo, K. (2002).

Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea. PNAS. 99(13), 8868-8873.

(297) Chang, L.K., Garcia-Cardeña, G., Farnebo, F., Fannon, M., Chen, E.J.,

Butterfield, C., Moses, M.A., Mulligan, R.C., Folkman, J. & Kaipainen, A. (2004). Dose-dependent response of FGF-2 for lymphangiogenesis. PNAS. 101(32), 11658-11663.

(298) Shin, J.W., Michael, Min, Larrieu-Lahargue, F., Canron, X., Kunstfeld, R.,

Nguyen., L., Henderson, J.E., Bikfalvi, A., Detmar, M. & Hong, Y.K. (2006). Prox1 promotes lineage-specific expression of Fibroblast Growth Factor (FGF) Receptor-3 in Lymphatic Endothelium: A role for FGF signaling in Lymphangiogenesis. Mol Biol Cell. 17, 576-584.

(299) Heldin, C-H. & Westermark, B. (1999). Mechanism of Action and In Vivo Role of

Platelet-Derived Growth Factor. Physiol Rev.79(4), 1283-1316.

BIBLIOGRAFIA

215

(300) Cao, R., Bjomdahl, M.A., Religa, P., Clasper, S., Garvin, S., Galter, D., Meister, B., Ikomi, F., Tritsaris, K., Dissing, S., Ohhashi, T., Jackson, D.G. & Cao, Y. (2004). PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis. Cancer Cell. 6, 333-345.

(301) Shweiki, D., Itin, A., Soffer, D. & Keshet, E. (1992). Vascular endothelial growth

factor induced by hipoxia may mediate hypoxia-initiated angiogenesis. Nature. 359, 843-845.

(302) Banai, S., Shweiki, D., Pinson, A., Chandra, M., Lazarovici, G. & Keshet, E.

(1994). Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia: Implications for coronary angiogenesis. Cardiovasc Res. 28, 1176-1179.

(303) Groger, M., Loewe, R., Holnthoner, W., Embacher, R., Pillinger, M., Herron,

G.S., Wolff, K. & Pettselbauer, P. (2004). IL-3 induces expression of lymphatic markers Prox-1 and podoplanin in human endothelial cells. J Immunol. 173, 7161-7169.

(304) Al-Rawi, M.A., Watkins, G., Mansel, R.E. & Jiang, W.G. (2005). The effects of

interleukin-7 on the lymphangiogenic properties of human endothelial cells. Int J Oncol. 27, 721-730.

(305) Pullinger, B.D. & Florey, H.W. (1937). Proliferation of lymphatics in inflammation.

J Pathol Bact. 45, 157-170. (306) Mouta, C. & Heroult, M. (2003). Inflammatory triggers of lymphangiogenesis.

Lymphatic Res Biol. 1(3), 201-218. (307) Ristimaki, A., Narko, K., Enholm, B., Joukov, V. & Alitalo, K. (1998).

Proinflammatory cytokines regulate expression of the lymphatic endothelial mitogen vascular endothelial growth factor-C. J Biol Chem. 273, 8413-8418.

(308) Kerjaschki, D. (2005). The crucial role of macrophages in lymphangiogenesis. J Clin

Invest. 115, 2316-2319. (309) Maruyama, K., Ii, M., Cursiefen, C., Jackson, D.G., Keino, H., Tomita, M., Van

Rooijen, N., Takenaka, H., D’Amore, P.A., Stein-Streilein, J., Losordo, D.W. & Streinlein, J.W. (2005). Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. J Clin Invest. 115, 2363-2372.

(310) Baluk, P., Tammela, T., Ator, E., Lyubynska, N., Achen, M.G., Hicklin, D.J.,

Jeltsch, M., Petrova, T.V., Pytowski, B., Stacker, S.A., Yla-Herttuala, S., Jackson, D.G., Alitalo, K, & McDonald, D.M. (2005). Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Invest. 155, 247-257.

(311) Boardman, K.C. & Swartz, M.A. (2003). Interstitial flow as a guide for

lymphangiogenesis. Circ Res. 92(7), 801-808.

BIBLIOGRAFIA 216

(312) Detmar, M. & Hirakawa, S. (2002). The Formation of Lymphatic Vessels and Its Importance in the Setting of Malignancy. J Exp Med. 196(6), 713-718.

(313) Cao, Y. (2005). Emerging mechanisms of tumour lymphangiogenesis and lymphatic

metastasis. Nat Rev Cancer. 5, 735-743. (314) Achen, M.G., McColl, B.K. & Stacker, S.A. (2005). Focus on lymphangiogenesis in

tumor metastasis. Cancer Cell. 7, 121-127. (315) Shayan, R., Achen, M.G. & Stacker, S. (2006). Lymphatic vessels in cancer:

bridging the gaps. Carcinogenesis. 27(9), 1729-1738. (316) Tobler, N.E. & Detmar, M. (2006). Tumor and lymph node lymphangiogenesis –

impact on cancer metastatis. J Leukoc Biol. 80(4), 691-696. (317) Plate, K.H. (2001). From angiogenesis to lymphangiogenesis. Nat Med. 7(2), 151-

152. (318) Carmeliet, P. & Jain, R.K. (2000). Angiogenesis in cancer and other diseases.

Nature. 407, 249-257. (319) Jain, R.K. & Carmeliet, P.F. (2001). Vessels of death or life. Sci Am. 285, 38-45. (320) Farnsworth, R.H., Achen, M.G. & Stacker, S.A. (2006). Lymphatic endothelium:

An important interactive surface for malignantt cells. Pulm Pharm Ther. 19, 51-60. (321) Padera, T.P., Kadambi, A. & di Tomaso, E. (2002). Lymphatic metastasis in the

absence of functional intratumor lymphatics. Science. 296, 1883-1886. (322) Agarwal, B., Saxena, R., Morimiya, A., Mehrotra, S. & Badve, S. (2005).

Lymphangiogenesis does not occur in breast cancer. Am J Surg Pathol. 29(11), 1449-1455.

(323) Wong, S.Y., Haack, H., Crowley, D., Barry, M., Bronson, R.T. & Hynes, R.O.

(2005). Tumor-secreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis. Cancer Res. 65(21), 9789-9798.

(324) Dadras, S.S., Bertoncini, P.T., Brown, L.F., Muzikansky, A., Jackson, D.G.,

Ellwanger, U., Garbe, C., Mihm, M.C. & Detmar, M. (2004). Tumor lymphangiogenesis: A novel prognostic indicator for cutaneous melanoma metastasis and survival. Am J Surg Pathol. 162, 1951-1960.

(325) Bono, P., Wasenius, V.M., Heikkila, P., Lundin, J., Jackson, D.G. & Joensuu, H.

(2004). LYVE-1-positive lymphatic vessel numbers are associated with poor outcome in breast cancer. Clin Cancer Res. 10, 7144-7149.

(326) Kysas, P.A., Geleff, S., Batistatou, A., Agnantis, N.J. & Stefanou, D. (2005).

BIBLIOGRAFIA

217

Evidence for lymphangiogenesis and its prognostic implications in head and neack squamous cell carcinoma. J Pathol. 206, 170-177.

(327) Schoppmann, S.F., Bayer, G., Aumayar, K., Taucher, S., Geleff, S., Rudas, M.,

Kubista, E., Hausmaninger, H., Samoniqq, H., Gnant, M., Jakesz, R., Horvat, R. & Austrian Breast and Colorectal Cancer Study Group. (2004). Prognostic value of lymphangiogenesis and lymphovascular invasion in invasive breast cancer. Ann Surg. 240, 306-312.

(328) Renyi-Vamos, F., Tovari, J., Fillinger, J., Timar, J., Paku, S., Kenessey, I.,

Ostoros, G., Agocs, L., Soltesz, I., & Dome, B. (2005). Lymphangiogenesis correlates with lymph node metastasis, prognosis, and angiogenic phenotype in human non-small cell lung cancer. Clin Cancer Res. 11, 7344-7353.

(329) Yokoyama, Y., Charnock-Jones, D.S., Licence, D., Yanaihara, A., Hastings, J.M.,

Holland, C.M., Emoto, M., Umemoto, M., Sakamoto, T., Sato, S., Mizunuma, H. & Smith, S.K. (2003). Vascular endothelial growth factor-D is an independent prognostic factor in epithelial ovarian carcinoma. Br J Cancer. 88, 237-244.

(330) Yokoyama, Y., Charnock-Jones, D.S., Licence, D., Yanaihara, A., Hastings, J.M.,

Holland, C.M., Emoto, M., Sakamoto, A., Sakamoto, T., Maruyana, H., Sato, S., Mizunuma, H. & Smith, S.K. (2003). Expression of vascular endothelial growth factor (VEGF)-D and its receptor, VEGF receptor 3, as a prognostic factor in endometrial carcinoma. Clin Cancer Res. 9, 1361-1369.

(331) Wang, T.B., Huang, Y.H., Lan, P., Song, X. M., & Wang, J.P. (2005). Correlation

of lymphangiogenesis to progression of colorectal cancer. Ai Zheng. 24, 1276-1279. (332) Zeng, Y., Opeskin, K., Horvath, L.G., Suttherland, R.L. & Williams, E.D. (2005).

Lymphatic vessel density and lymph node metastasis in prostate cancer. Prostate. 65, 222-230.

(333) Sipos, B., Klapper, W., Kruse, M.L., Kalthoff, H., Kerjaschki, D. & Kloppel, G.

(2004). Expression of lymphangiogenic factors and evidence of intratumoral lymphangiogenesis in pancreatic endocrine tumors. Am J Pathol. 165, 1187-1197.

(334) Wiley, H.E., Gonzalez, E.B., Maki, W., Wu, M.T. & Hwang, S.T. (2001).

Expression of CC chemokine receptor-7 and regional lymph node metastasis of B16 murine melanoma. J Natl Cancer Inst. 93, 1638-1643.

(335) Muller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M.E.,

McClanahan, T., Murphy, E., Yuan, W., Wagner, S.N., Berrera, J.L., Mohar, A., Verastegui, E. & Zlotnik, A. (2001). Involvement od chemokine receptors in breast cancer metastasis. Nature. 410, 50-56.

(336) Nathanson, S.D. (2003). Insights into the Mechanisms of Lymph Node Metastasis.

Cancer. 98, 413-423.

BIBLIOGRAFIA 218

(337) He, Y., Karpanen, T. & Alitalo, K. (2004). Role of lymphangiogenic factors in tumor metastasis. Biochim et Biophys Acta. 1654, 3-12.

(338) Van Trappen, P.O. & Pepper, M.S. (2002). Lymphatic dissemination of tumour

cells and the formation of micrometastases. The Lancet Oncol. 3, 44-52. (339) Martens, J-H., Kzhyshkowska, J., Falkowski-Hansen, M., Schledzewski, K.,

Gratchev, A., Mansmann, U., Schmuttermaier, C., Dippel, E., Koenen, W., Riedel, F., Sankala, M., Tryggvason, K., Kobzik, L., Moldenhauer, B., Arnold, B., & Goerdt, S. (2006). Differential expression of a gene signature for sacavanger/lectin receptors by endothelial cells and macrophages in human lymph node sinuses, the primary sites of regional metastasis. J Pathol. 208, 574-589.

(340) Wilting, J., Hawighorst, T., Hecht, M., Christ, B. & Papoutsi, M. (2005).

Development of lymphatic vessels: tumour lymphangiogenesis and lymphatic invasion. Curr Med Chem. 12(26), 3043-3053.

(341) Poon, R.T., Fan, S.T. & Wong, J. (2001). Clinical implications of circulating

angiogenic factors in cancer patients. J Clin Oncol. 19(4), 1207-1225. (342) Papetti, M. & Herman, I.M. (2002). Mechanisms of normal and tumor-derived

angiogenesis. Am J Physiol. 282, 947-970. (343) Ferrara, N. (2005). VEGF as a Therapeutic Target in Cancer. Oncology. 69(3), 11-

16. (344) Carmeliet, P. (2005). VEGF as a Key Mediator of Angiogenesis in Cancer. Oncol.

69(3), 4-10. (345) GENENTECH, Inc . Avastin® (bevacizumab). Available at:

http://www.gene.com/gene/products(information/oncology/avastin/avastinfacts.jsp (346) Shih, T. & Lindley, C. (2006). Bevacizumab: an angiogenesis inhibitor for the

treatment of solid malignancies. Clin Ther. 28(11), 1779-1802. (347) de Gramont, A. & Van Cutsem, E. (2005). Investigating the potential of

bevacizumab in other indications: metastatic renal cell, non-small cell lung, pancreatic and breast cancer. Oncology. 69(3), 46-56.

(348) Skobe, M., Hawighorst, T., Jackson, D.G., Prevo, R., Janes, L., Velasco, P.,

Riccardi, L., Alitalo, K., Claffey, K. & Detmar, M. (2001). Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 7, 192-198.

(349) Karpanen, T., Egeblad, M., Karkkainen, M.J., Kubo, H., Yla-Herttuala, S.,

Jaattela, M. & Alitalo, K. (2001). Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res. 61, 1786-1790.

BIBLIOGRAFIA

219

(350) Mattila, M. M-T., Ruohola, J.K., Karpanen, T., Jackson, D.G., Alitalo, K. & Härkönen, P.L. (2002). VEGF-C induced lymphangiogenesis is associated with lymph node metastasis in orthotopic MCF-7 tumors. Int J Cancer. 98, 946-951.

(351) Skobe, M., Hamberg, L.M., Hawighorst, T., Schirner, M., Wolf, G.L., Alitalo, K.

& Detmar, M. (2001). Concurrent induction of lymphangiogenesis, angiogenesis, and macrophage recruitment by vascular endothelial growth factor-C in melanoma. Am J Pathol. 159, 893-903.

(352) Stacker, S.A., Caesar, C., Baldwin, M.E., Thornton, G.E., Williams, R.A., Prevo,

R. Jackson, D.G., Nishikawa, S., Kubo, H. & Achen, M.G. (2001). VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med. 7, 186-191.

(353) Li, Y.S., Kaneko, M., Amatya, V.J., Takeshima, Y., Arihiro, K. & Inai, K. (2006).

Expression of vascular endothelial growth factor-C and its receptor in invasive micropapillary carcinoma of the breast. Pathol Int. 56(5), 256-261.

(354) Nakamura, Y., Yasuoka, H., Tsujimoto, M., Yang, Q., Tsukiyama, A., , S.,

Nakahara, M., Nakao, K., Nakamura, M., Mori, I. & K akudo, K. (2003). Clinicopathological significance of vascular endothelial growth factor-C in breast carcinoma with long-term follow-up. Mod Pathol. 16(4), 309-314.

(355) Nakumura, Y., Yasuoka, H., Tsujimoto, Q., Yang, Q., Imabun, S., Nakahara, M.,

Nakao, K., Nakamura, M., Mori, I. & Kakudo, K. (2003). Prognostic significance of vascular endothelial growth factor d in breast carcinoma with long-term follow-up. Clin Cancer Res. 9, 716-721.

(356) Xu, T., Chen. D. & Chen, J. (2004). Expression of vascular endothelial growth factor

C and its correlation with lymph node metastasis in colorectal carcinoma. J Huazhong Univ Sci Technolog Med Sci. 24(6), 596-598.

(357) Jia, Y.T., Li, Z.X., He, Y.T., Liang, W., Yang, H.C. & Ma, H.J. (2004). Expression

of vascular endothelial growth factor-C and the relationship between lymphangiogenesis ans lymphatic metastasis in colorectal cancer. World J Gastroenterol. 10(22), 3261-3263.

(358) White, J.D., Hewet, P.W., Kosuge, D., McCulloch, T., Enholm, B.C., Carmichael,

J. & Murray, J.C. (2002). Vascular endothelial growth factor-D expression is an independent prognostic marker for survival in colorectal carcinoma. Cancer Res. 62, 1669-1675.

(359) Takizawa, H., Kondo, K., Fugino, H., Kenzaki, K., Miyoshi, T., Sakiyama, S. &

Tangoku, A. (2006). The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non-small cell lung cancer. Br J Cancer. 95(1), 75-79.

(360) Kojima, H., Shijubo, N., Yamada, G., Ichimiya, S., Abe, S., Satoh, M. & Sato, N.

(2005). Clinical significance of vascular endothelial growth factor-C and vascular

BIBLIOGRAFIA 220

endothelial growth factor receptor 3 in patients with T1 lung adenocarcinoma. Cancer. 104(8), 1668-1677.

(361) Yang, J., Wu, H.F., Qian, L.X., Zhang, W., Hua, L.X., Yu, M.L., Wang, Z., Xu,

Z.Q., Sui, Y.G. & Wang, X.R. (2006). Increased expressions of vascular endothelial growth factor (VEGF), VEGF-C and VEGF receptor-3 in prostate cancer tissue are associated with tumor progression. Asian J Androl. 8(2), 169-175.

(362) Jennbacken, K., Vallbo, C., Wang, W. & Damber, J.E. (2005). Expression of

vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 in human prostate cancer is associated with regional lymph node metastasis. Prostate. 65(2), 110-116.

(363) Shintani, S., Li, C., Ishikawa, T., Mihara, M., Nakashiro, K. & Hamakawa, H.

(2004). Expression of vascular endothelial growth factor A, B, C, and D in oral squamous cell carcinoma. Oral Oncol. 40(1), 13-20.

(364) Yu, D.H., Wen, Y.M., Sun, J.D., Wei, S.L., Xie, H.P. & Pang, F.H. (2002).

Relationship among expression of vascular endothelial growth factor-C (VEGF-C), angiogenesis, lymphangiogenesis, and lymphatic metastasis in oral cancer. Aizheng. 21, 319-322.

(365) Matsumoto, M., Natsugoe, S., Okumura, H., Arima, H., Yanagita, S., Uchikado,

Y., Yokomakura, N., Setoyama, T,, Ishigami, S., Takao, S. & Aikou, T. (2006). Overexpression of vascular endothelial growth factor-C correlates with lymph node micrometastasis in submucosal esophageal cancer. J Gastrointest Surg. 10(7), 1016-1022.

(366) Kimura, Y., Watanabe, M., Ohga, T., Saeki, H., Kakeji, Y., Baba, H. & Maehara,

Y. (2003). Vascular endothelial growth factor C expression correlates with lymphatic involvement and poor prognosis in patients with esophageal squamous cell carcinoma. Oncol Rep. 10(6), 1747-1751.

(367) Juttner, S., Wissmann, C., Jons, T., Vieth, M., Hertel, J., Gretschel, S., Schlag,

P.M., Kemmner, W. & Hocker, M. (2006). Vascular endothelial growth factor-D ans its receptor VEGFR-3: two novel independent prognostic markers in gastric adenocarcinoma. J Clin Oncol. 24(2), 228-240.

(368) Shida, A., Fujioka, S., Kobayashi, K., Ishibashi, Y., Nimura, H., Mitsumori, N. &

Yanaga, K. (2006). Expression of vascular endothelial growth factor (VEGF)-C and D- in gastric carcinoma. Int J Clin Oncol. 11(1), 38-43.

(369) Yasuoka, H., Nakamura, Y., Zuo, H., Tang, W., Takamura, Y., Miyauchi, A.,

Nakamura, M., Mori, I. & Kakudo, K. (2005). VEGF-D expression and lymph vessels play an important role for lymph node metastasis in papillary thyroid carcinoma. Mod Pathol. 18(8), 1127-1133.

(370) Yu, X.M., Lo, C.Y., Chan, W.F., Lam, K.Y., Leung, P. & Luk, J.M. (2005).

BIBLIOGRAFIA

221

Increased expression of vascular endothelial growth factor C in papillary thyroid carcinoma correlates with cervical lymph node metastases. Clin Cancer Res. 11(22), 8063-8069.

(371) Gombos, Z., Xu, X., Xhu, C.S., Zhang, P.J. & Acs, G. (2005). Peritumoral

lymphatic vessel density and vascular endothelial growth factor C expression in early-stage saquamous cell carcinoma of the uterine cervix. Clin Cancer Res. 11(23), 8364-8371.

(372) Von Marschall, Z., Scholz, A., Stacker, S.A., Achen, M.G., Jackson, D.G., Alves,

F., Schirner, M., Haberey, M., Thierauch, K.H., Wiedenmann, B. & Rosewicz, S. (2005). Vascular endothelial growth factor-D induces lymphangiogenesis and lymphatic metastasis in models of ductal pancreatic cancer. Int J Oncol. 27(3), 669-679.

(373) Bando, H., Weich., H.A., Horiguchi, S., Funata, N., Ogawa, T. & Toi, M. (2006).

The association between vascular endothelial growth factor-C, its corresponding receptor, VEGFR-3, and prognosis in primary breast cancer: a study with 193 cases. Oncol Rep. 15(3), 653-659.

(374) Wobser, M., Siedel, C., Schrama, D., Brocker, E.B., Becker, J.C., Vetter-

Kauczok, C.S. (2006). Expression pattern of the lymphatic and vascular markers VEGFR-3 and CD31 does not predict regional lymph node metastasis in cutaneous melanoma. Arch Dermatol Res. 297(8), 352-357.

(375) Nagy, J.A., Vasile, E., Feng, D., Sundberg, C., Brown, L.F., Detmar, M.J.,

Lawitts, J.A., Benjamin, L., Tan, X., Manseau, E.J., Dvorak, A.M. & Dvorak, H.F. (2002). Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med. 196, 1497-1506.

(376) Hong, Y.K., Lange-Asschenfeldt, B., Velasco, P., Hirakawa, S., Kunstfeld, R.,

Brown, L.F., Bohlen, P., Senger, D.R. & Detmar, M. (2004). VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the alpha1beta1 and alpha2beta1 integrins. FASEB J. 18, 1111-1113.

(377) Kunstesfeld, R., Kirakawa, S., Hong, Y.K., Schacht, V., Lange-Asschenfeldt, B.,

Velasco, P., Lin, C., Fiebiger, E., Wei, X., Wu, Y., Hicklin, D., Bohlen, P. & Detmar, M. (2004). Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia. Blood. 104, 1048-1057.

(378) Hirakawa, S., Kodama, S., Kunstfeld, R., Rajiya, K., Brown, L.F. & Detmar, M.

(2005). VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J Exp Med. 201(7), 1089-1099.

(379) Aoki, Y. & Tosato, G. (2005). Lymphatic Regeneration: New Insights From VEGFR-

3 Blockade. J Natl Cancer Inst. 97(1), 2-3.

BIBLIOGRAFIA 222

(380) Thiele, W. & Sleeman, J.P. (2006). Tumor-induced lymphangiogenesis: A target for cancer therapy? J Biotechnol. 124(1), 224-241.

(381) Achen, M.G., Mann, G.B. & Stacker, S.A. (2006). Targeting lymphangiogenesis to

prevent tumor metastasis. B J Cancer. 94(10), 1355-1360. (382) Achen, M.G., Roufail, S., Domagala, T., Catimel, B., Nice, E.C., Geleick, D.M.,

Murphy, R., Scott, A.M., Caesar, C., Makinen, T., Alitalo, K. & Stacker, S.A. (2000). Monoclonal antibodies to vascular endothelial growth factor-D block its interactions with both VEGF receptor-2 and VEGF receptor-3. Eur J Biochem, 267, 2505-2515.

(383) He, Y., Kozaki, K., Karpanen, T., Koshikawa, K., Yla-Herttuala, S., Takahashi,

T. & Alitalo, K. (2002). Supression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. J Natl Cancer Inst. 94, 819-825.

(384) Lin, J., Lalani, A.S., Harding, T.C., Gonzalez, M., Wu, W.W., Luan, B., Tu, G.H.,

Koprivnikar, K., VanRoey, M.J., He, Y., Alitalo, K. & Jooss, K. (2005). Inhibition of lymphogenous metastasis using adeno-associated virus-mediated gene transfer of a soluble VEGFR-3 decoy receptor. Cancer Res. 65, 6901-6909.

(385) Wilhelm, S.M., Carter, C., Tang, L., Wilkie, D., McNabola, A., Rong, H., Chen,

C., Zhang, X., Vincent, P., McHugh, M., Cao, Y., Shujath, J., Gawlak, S., Eveleigh, D., Rowley, B., Liu, L., Adnane, L., Lynch, M., Auclair, D., Taylor, I., Gedrich, R., Voznesensky, A., Riedl, B., Post, L.E., Bollag, G. & Trail, P.A. (2004). BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64, 7099-7109.

(386) Lin, B., Podar, K., Gupta, D., Tai, Y.-T., Li, S., Wellwe, E., Hideshima, T.,

Lentzsch, S., Davies, F., Li, C., Weisberg, E., Schlossman, R.L., Richardson, P.G., Griffin, J.D., Wood, J., Munshi, N.C. & Anderson, K.C. (2002). The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment. Cancer Res. 62, 5019-5026.

(387) Wedge, S.R., Ogilvie, D.J., Dukes, M., Kenderw, J., Chester, R., Jackson, J.A.,

Boffey, S.J., Valentine, P.J., Curwen, J.O., Musgrove, H.L., Graham, G.A., Hughes, G.D., Thomas, A.P., Stokes, E.S.E., Curry, B., Richmond, G.H.P., Wadsworth, P.F., Bigley, A.L. & Hennequin, L.F. (2002). ZD6474 Inhibits Vascular Endothelial Growth Factor Signaling, Angiogenesis, and Tumor Growth following Oral Administration. Cancer Res. 62, 4645-4655.

(388) Suzuki, K., Morita, T. & Tokue, A. (2005). Vascular endothelial growth factor-C

(VEGF-C) expression predicts lymph node metastasis of transitional cell carcinoma of the bladder. Int J Urol. 12(2), 152-158.

BIBLIOGRAFIA

223

(389) Zu, X., Tang, Z., Li, Y., Gao, N., Ding, J. & Qi, L. (2006). Vascular endothelial growth factor-C expression in bladder transitional cell cancer and its relationship to lymph node metastasis. BJU Int. 98(5), 1090-1093.

(390) Miyata, Y., Kanda, S., Ohba, K., Nomata, K., Yasushi, H., Eguchi, J., Hayashi, T.

& Kanetake, H. (2006). Lymphangiogenesis and Angiogenesis in Bladder Cancer: Prognostic implications and Regulation by Vascular Endothelial Growth Factors-A, -C and -D. Clin Cancer Res. 12(3), 800-806.

(391) Mylona, E., Magkou, C., Gorantonakis, G., Giannopoulou, I., Nomikos, A.,

Zarogiannos, A., Zervas, A. & Nakopoulou, L. (2006). Evaluation of the vascular endothelial growth factor (VEGF)-C role in urothelial carcinomas of the bladder. Anticancer Res. 26(5A), 3567-3571.

(392) Leissner, J., Koeppen, C. & Wolf, H.K. (2003). Prognostic significance of vascular

and perineural invasion in urothelial bladder cancer treated with radical cystectomy. J Urol. 169(3), 955-960.

(393) Hong, S.K., Kwak, C., Jeon, H.G., Lee, E. & Lee, S.E. (2005). Do vascular,

lymphatic, and perineural invasion have prognostic implications for bladder cancer after radical cystectomy? Urology. 65, 697-702.

(394) Quek, M.L., Stein, J.P., Nichols, P.W., Cai, J., Miranda, G., Groshen, S.,

Daneshmand, S., Skinner, E.C. & Skinner, D.G. (2005). Prognostic significance of lymphovascular invasion of bladder cancer treated with radical cistectomy. J Urol. 174(1), 103-106.

(395) Lotan, Y., Gupta, A., Shariat, S.F., Palapattu, G.S., Vazina, A., Karakiewicz, P.I.,

Bastian, P.J., Rogers, C.G., Amiel, G., Perotte, P., Schoenberg, M.P., Lerner, S.P. & Sagalowsky, A.I. (2005). Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy. J Clin Oncol. 23(27), 6533-6539.

(396) Inoue, K., Slaton, J.W., Karashima, T., Yoshikawa, C., Shuin, T., Sweeney, P.,

Millikan, R. & Dinney, C.P. (1997). The prognostic value of angiogenesis factor expression for predicting recurrence and metastasis of bladder cancer after neoadjuvant chemotherapy and radical cystectomy. Clin Cancer Res. 2000. 6, 4866-4873.

(397) Santos, L., Costa, C., Pereira, S., Koch, M., Amaro, T., Cardoso, F., Guimarães,

T., Bento, M.J., Lobo, F., Pinto, S. & Lopes, C. (2003). Neovascularization is a prognostic factor for early recurrence in T1/G2 urothelial bladder tumours. Ann Oncol. 14, 1419-1424.

(398) Canoğlu, A., Göğüs, C., Bedük, Y., Orhan, D., Tulunay, O. & Baltaci, S. (2004).

Microvessel density as a prognostic marker in bladder carcinoma: correlation with tumor grade, stage and prognosis. Int Urol Nephrol. 36(3), 401-405.

BIBLIOGRAFIA 224

(399) Crew, J.P., O’Brien, T., Bradburn, M., Fuggle, S., Bicknell, R., Cranston, D. & Harris, A.L. (1997). Vascular endothelial growth factor is a predictor of relapse and stage progression in superficial bladder cancer. Cancer Res. 57, 5281-5285.

(400) Inoue, K, Slaton, J.W., Davis, D.W., Hicklin, D.J., McConkey, D.J., Karashima,

T., Radinsky, R. & Dinney, C.P.N. (2000). Treatment of Human Metastatic Transitional Cell Carcinoma of the Bladder in a Murine Model with the Anti-Vascular Endothelial Growth Factor Receptor Monoclonal Antibody DC101 and Paclitaxel. Clin Cancer Res. 6, 2635-2643.

(401) Davis, D.W., Inoue, K., Dinney, C.P.N., Hicklin, D.J., Abbruzzese, J.L. &

McConkey, D.J. (2004). Regional Effects of an Antivascular Endothelial Growth Factor Receptor Monoclonal Antibody on Receptor Phosphorylation and Apoptosis in Human 253J B-V Bladder Cancer Xenografts. Cancer Res. 64, 4601-4610.

(402) DeLisser, H.M., Newman, P.J. & Albelda, S.M. (1994). Molecular and functional

aspects of PECAM-1/CD31. Immunology Today. 15 (10), 490-495. (403) Engel, C.J., Bennett, S.T., Chambers, A.F., Doig, G.S., Kerkvliet, N. & O’Malley,

F.P. (1996). Tumor angiogenesis predicts recurrence in invasive colorectal cancer when controlled for Dukes staging. Am J Surg Pathol. 20, 1260-1265.

(404) Fox, S.B., Leek, R.D., Bliss, J., Mansi, J.L., Gusterson, B., Gatter, K.C. & Harris,

A.L. (1997). Association of tumor angiogenesis with bone marrow micrometastases in breast cancer patients. J Natl Cancer Inst. 89, 1044-1049.

(405) Giatromanolaki, A., Koukourakis, M., O’Byrne, K., F ox, S., Whitehouse, R.,

Talbot, D.C., Harris, A.L. & Gatter, K.C. (1996). Prognostic value of angiogenesis in operable non-small cell lung cancer. J Pathol. 179, 80-88.

(406) Marks, A., Sutherland, D.R., Bailey, D., Iglesias, J., Law, J., Lei, M., Yeger, H.,

Banerjee, D. & Baumal, R. (1999). Characterization and distribution of an oncofetal antigen (M2A antigen) expressed on testicular germ cell tumours. Br J Cancer. 80, 569-578.

(407) Kahn, H.J., Bailey, D. & Marks, A. (2002). Monoclonal antibody D2-40, a new

marker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol. 15(4), 434-440.

(408) Kahn, H.J. & Marks, A. (2002). A new monoclonal antibody, D2-40, for detection

of lymphatic invasion in primary tumors. Lab Invest. 82(9), 1255-1257. (409) Van der Auwera, I., Cao, Y., Tille, J.C., Pepper, M.S., Jackson, D.G., Fox, S.B.,

Harris, A.L., Dirix, L.Y. & Vermeulen, P.B. (2006). First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours. Br J Cancer. 95, 1611-1625.

(410) Longatto-Filho, A., Martins, A., Costa, S.M.A. & Schmitt, F.C. (2005). VEGFR-3

BIBLIOGRAFIA

225

expression in breast cancer tissue is not restricted to lymphatic vessels. Pathol Res Pract. 201, 93-99.

(411) Mcneil, B.J., Keeler, E. & Adelstein. S.J. (1975). Primer on certain elements of

medical decision making. N Engl Med. 293, 211-215. (412) Detsky, A.S., Baker, J.P. & Mendelson, R.A. (1984). Evaluating the accuracy of

nutritional assessment techniques applied to hospitalized patients: methodology and comparisons. J Parenter Enteral Nutr. 8, 153-159.

(413) Folkman, J. (2000). Incipient Angiogenesis. J NCI. 92(2), 94-95. (414) Barton Grossman, H., Tangen, C.M., Condon-Cardo, C., Cote, R., Waldman,

F.M., De Vere White, R.W., Karnad, A.B., Glode, M. & Crawford, E.D. (2006). Evaluation of Ki67, p53 and angiogenesis in patients enrolled in a randomized study of neoadjuvant chemotherapy with or without cystectomy: A Southwest Oncology Group Study. Oncol Rep. 16(4), 807-810.

(415) Santos, L. Lameiras, C., Afonso, J., Palmeira, C., Pereira, S., Costa, C., Amaro,

T., Bento, M.J., Morais, A., Criado, B. & Lopes, C. (2003). Is DNA content alteration a consequence of proloferative and differentiation changes in urothelial bladder tumours? Acta Urol. 20(1), 9-17.

(416) Frazier, H.A., Robertson, J.E., Dodge, R.K. & Paulson, D.F. (1993). The value of

pathologic factors in predicting cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate. Cancer. 71(12), 3993-4001.

(417) Thrasher, J.B., Frazier, H.A., Robertson, J.E., Dodge, R.K. & Paulson, D.F.

(1994). Clinical variables which serve as predictors of cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate. Cancer. 73(6), 1708-1715.

(418) Honma, I., Masumori, N., Sato, E., Takayanagi, A., Takahashi, A., Itoh, N.,

Tamagawa, M., Sato, M.A. & Tsukamoto, T. (2004). Local recurrence after radical cystectomy for invasive bladder cancer: an analysis of predictive factors. Urology. 64(4), 744-748.

(419) Harada, K., Sakai, I., Hara, I., Eto, H. & Miyake, H. (2005). Prognostic

significance of vascular invasion in patients with bladder cancer who underwent radical cystectomy. Int J Urol. 12, 250-255.

(420) Yu, R.J., Stein, J.P., Cai, J., Miranda, G., Groshen, S. & Skinner, D.G. (2006).

Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of bladder cancer following radical cystectomy. J Urol. 176(2), 493-498.

(421) Antunes, A.A., Nesrallah, L.J., Dall’Oglio, M.F., Ferreira, Y.A., Passerotti, C.C.,

Leite, K.R., Ortiz, V. & Srougi, M. (2006). Analysis of Prognostic Factors in

BIBLIOGRAFIA 226

Patients with Transitional Cell Carcinoma of the Bladder Treated with Radical Cystectomy. Int Braz J Urol. 32(1), 35-42.

(422) Campbell, S.C. (1997). Update on angiogenesis research: relevance to urologic

oncology. J Urol. 158, 1663-1674. (423) Goddard, J.C., Sutton, C.D., Furness, P.N., O’Byrne, K.J. & Kockelbergh, R.C.

(2003). Microvessel Density at Presentation Predicts Subsequent Muscle Invasion in Superficial Bladder Cancer. Clin Cancer Res. 9, 2583-2586.

(424) O’Brien, T., Cranston, D., Fuggle, S., Bicknell, R. & Harris, A.L. (1995). Different

Angiogenic Pathways Characterize Superficial and Invasive Bladder Cancer. Cancer Res. 55, 510-513.

(425) Crew, J.P., O’Brien, T., Bicknell, R., Fuggle, S., Cranston, D. & Harris, A.L.

(1999). Urinary vascular endothelial growth factor and its correlation with bladder cancer recurrence rates. J Urol. 161(3), 799-804.

(426) Jeon, S.H., Lee, S.J. & Chang, S.G. (2001). Clinical significance of urinary vascular

endothelial growth factor in patients with superficial bladder tumors. Oncol Rep. 8(6), 1265-1267.

(427) Habuchi, T., Takahashi, R., Yamada, H., Kakehi, Y., Sugiyama, T. & Yoshida, O.

(1993). Metachronous multifocal development of urothelial cancers by intraluminal seeding. Lancet. 342, 1087-1088.

(428) Dinney, C.P.N., Babkowski, R.C., Antelo, M., Perrotte, P., Liebert, M., Zhang,

H.Z., Palmer, J., Veltri, R.W., Katz, R.L. & Grossman, H.B. (1998). Relationship among cystectomy, microvessel density and prognosis in stage T1 transitional cell carcinoma of the bladder. J Urol. 160, 1285-1290.

(429) Chow, N.H., Liu, H.S., Chan, S.H., Cheng, H.L. & Tzai, T.S. (1999). Expression of

vascular endothelial growth factor in primary superficial bladder cancer. Anticancer Res. 19(5C), 4593-4597.

(430) Sağol, O., Yörükoğlu, K., Sis, B., Tuna, B., Ozer, E., Güray, M., Mungan, U. &

Kirkali, K. (2001). Does angiogenesis predict recurrence in superficial transitional cell carcinoma of the bladder? Urology. 57(5), 895-899.

(431) Stavropoulos, N.E., Bouropoulos, C., Ioachim, I.E., Michael, M., Hastazeris, K.,

Tsimaris, I., Kalogeras, D., Liamis, Z., Stefanaki, S. & Agnantis, N.I. (2004). Prognostic significance of angiogenesis in superficial bladder cancer. Int Urol Nephrol. 36(2), 163-167.

(432) Oliveira-Ferrer, L., Tilki, D., Ziegeler, G., Hauschild, J., Loges, S., Irmak, S.,

Kilic, E., Huland, H., Friedrich, M. & Ergun, S. (2004). Dual role of carcinoembryonic antigen-related cell adhesion molecule 1 in angiogenesis and invasion of human urinary bladder cancer. Cancer Res. 64, 8932-8938.

BIBLIOGRAFIA

227

(433) Beecken, W.D., Engl, T., Hofmann, J., Jonas, D. & Blaheta, R. (2005). Clinical relevance of serum angiogenic activity in patients with transitional cell carcinoma of the bladder. J Cell Mol Med. 9(3), 655-661.

(434) Dickinson, A.J., Fox, S.B., Persad, R.A., Hollyer, J., Sibley, G.N. & Harris, A.L.

(1994). Quantification of angiogenesis as an independent predictor of prognosis in invasive bladder carcinomas. Br J Urol. 74, 762-766.

(435) Jaeger, T.M., Weidner, N. & Chew, K. (1995). Tumor angiogenesis correlates with

lymph node metastases in invasive bladder cancer. J Urol. 154, 69-71. (436) Chaudhary, R., Bromley, M., Clarke, N.W., Betts, C.D., Barnard, R.J., Ryder,

W.D. & Kumar, S. (1999). Prognostic relevance of microvessel density in cancer of the urinary bladder. Anticancer Res. 19(4C), 3479-3484.

(437) Yang, C.C., Chu, K.C. & Yeh, W.M. (2004). The expression of vascular endothelial

growth factor in transitional cell carcinoma of urinary bladder is correlated with cancer progression. Urol Oncol. 22(1), 1-6.

(438) Sato, K., Sasaki, R., Ogura, Y., Shimoda, N., Togashi, H., Terada, K., Sugiyama,

T., Kakinuma, H., Ogawa, O. & Kato, T. (1998). Expression of vascular endothelial growth factor gene and its receptor (flt-1) gene in urinary bladder cancer. Tohoku J Exp Med. 185(3), 173-184.

(439) Izawa, J.I., Slaton, J.W., Kedar, D., Karashima, T., Perrote, P., Czerniak, B.,

Grossman, H.B. & Dinney, C.P. (2001). Differential expression of progression-related genes in the evolution of superficial to invasive transitional cell carcinoma of the bladder. Oncol Rep. 8(1), 9-15.

(440) Jones, A., Fujiyama, C., Blanche, C., Moore, J.W., Fuggle, S., Cranston, D.,

Bicknell, R. & Harris, A.L. (2001). Relation of Vascular Endothelial Growth Factor Production to Expression and Regulation of Hypoxia-inducible Factor-1α and Hypoxia-inducible Factor-2α in Human Bladder Tumors and Cell Lines. Clin Cancer Res. 7, 1263-1272.

(441) Reiher, F.K., Ivanovich, M., Huang, H., Smith, N.D., Bouck, N.P. & Campbell,

S.C. (2001). The role of hypoxia and p53 in the regulation of angiogenesis in bladder cancer. J Urol. 165, 2075-2081.

(442) Turner, K.J., Crew, J.P., Wykoff, C.C., Watson, P.H., Poulsom, R., Pastorek, J.,

Ratcliffe, P.J., Cranston, D. & Harris, A.L. (2002). The hypoxia-inducible genes VEGF and CA9 are differencially regulated in superficial vs invasive bladder cancer. Br J Cancer. 86, 1276-1282.

(443) Brown, N.S., Streeter, E.H., Jones, A., Harris, A.L. & Bicknell, R. (2005).

Cooperative stimulation of vascular endothelial growth factor expression by hypoxia and reative oxigen species: the effect of targeting vascular endothelial growth factor and oxidative stress in an orthopic xenograft model of bladder carcinoma. Br J

BIBLIOGRAFIA 228

Cancer. 92(9), 1696-1701. (444) American Cancer Society. (2007). Cancer Facts & Figures 2007. American Cancer

Society. Atlanta. (445) Lee, J.H., Miele, M.E., Hicks, D.J., Phillips, K.K., Trent, J.M., Weissmen, B.E. &

Welch, D.R. (1996). KiSS-1, a novel human malignant melanoma metastasis-supressor gene. J Natl Cancer Inst. 88, 1731-1737.

(446) Lee, J.H. & Welch, D.R. (1997). Supression of metastasis in human breast carcinoma

MDA-MB-435 cells after transfection with the metastasis supressor gene, KiSS-1. Cancer Res. 57, 2384-2387.

(447) Masui, T., Doi, R., Mori, T., Toyoda, E., Koizumi, M., Kami, K., Ito, D., Peiper,

S.G., Broach, J.R., Oishi, S., Niida, A., Fujii, N. & Imamura, M. (2004). Metastin and its variant forms supresse migration of pancreatic cancer cells. Biochem Biophys Res Commun. 315(1), 85-92.

(448) Ikeguchi, M., Yamaguchi, K. & Kaibara, N. (2004). Clinical significance of the loss

of KiSS-1 and orphan G-protein-coupled receptor (hOT7T175) gene expression in esophageal squamous cell carcinoma. Clin Cancer Res. 10, 1379-1383.

(449) Sanchez-Carbayo, M., Capodieci, P. & Cordon-Cardo, C. (2003). Tumor

Supressor Role of KiSS-1 in Bladder Cancer: Loss of KiSS-1 Expression is associated with Bladder Cancer Progression and Clinical Outcome. Am J Pathol. 162(2), 609-617.

(450) Inai, T., Mancuso, M., Hashizume, H., Baffert, F., Haskell, A., Baluk, P., Hu-

Lowe, D.D., Shalinsky, D.R., Thurston, G., Yancopoulos, G.D. & McDonald, D.M. (2004). Inhibition of Vascular Endothelial Growth Factor (VEGF) Signaling in Cancer causes Loss of Endothelial Fenestrations, Regression of Tumor Vessels, and Appearance of Basement Membrane Ghosts. Am J Pathol. 165(1), 35-52.

(451) Inoue, K., Chikazawa, M., Fukata, S., Yoshikawa, C. & Shuin, T. (2003).

Docetaxel Enhances the Therapeutic Effect of the Angiogenesis Inhibitor TNP-470 (AGM-1470) in Metastatic Human Transitional Cell Carcinoma. Clin Cancer Res. 9, 886-899.

(452) Krause, S., Förster, Y., Kraemer, K., Fuessel, S., Kotzsch, M., Schmidt, U.,

Wirth, M.P., Meye, A. & Schwenzer, B. (2005). Vascular endothelial growth factor antisense pretreatment of bladder cancer cells significantly enhances the citotoxicity of mitomycin C, gemcitabine and cisplatin. J Urol. 174(1), 328-331.

(453) Inoue, K., Chikazawa, M., Fukata, S., Yoshikawa, C. & Shuin, T. (2002). Frequent

Administration of Angiogenesis Inhibitor TNP-470 (AGM-1470) at an Optimal Biological Dose Inhibits Tumor Growth and Metastasis of Metastatic Human Transitional Cell Carcinoma in the Urinary Bladder. Clin Cancer Res. 8, 2389-2398.

BIBLIOGRAFIA

229

(454) Eastern Cooperative Oncology Group. Sorafenib in Treating Patients With Regional or Metastatic Cancer of the Urothelium. Available at: http://clinicaltrials.gov

(455) Memorial Sloan-Kettering Cancer Center. Sunitinib in Treating Patients with

Progressive Metastatic Transitional Cell Cancer of the Urothelium. Available at: http://clinicaltrials.gov

(456) Morabito, A., De Maio, E., Di Maio, M., Normanno, N. & Perrone, F. (2006).

Tyrosine Kinase Inhibitors of Vascular Endothelial Growth Factor Receptors in Clinical Trials: Current Status and Future Directions. The Oncologist. 11, 753-764.

(457) Homsi, J. & Daud, A.I. (2007). Spectrum of Activity and Mechanism of Action of

VEGF/PDFG Inhibitors. Cancer Control. 14(3), 285-294. (458) California Cancer Consortium. VEGF Trap in Treating Patients with Recurrent,

Locally Advanced, or Metastatic Cancer of the Urothelium. Available at: http://clinicaltrials.gov

(459) M.D. Anderson Cancer Center. Neodjuvant Chemotherapy With M-VAC Plus

Avastin in Patients with Urothelial Cancer. Available at: http://clinicaltrials.gov (460) Das, K., Zhao, Y., Sugiono, M., Lau, W., Tan, P.H. & Cheng, C. (2007).

Differential expression of vascular endothelial growth factor(165)β in transitional cell carcinoma of the bladder. Urol Oncol. 25(4), 317-321.

(461) García-Closas, M., Malats, N., Real, F.X., Yeager, M., Welch, R.., Silverman, D.,

Kogevinas, M., Dosemeci, M., Figueroa, J., Chatterjee, N., Tardón, A., Serra, C., Carrato, A., García-Closas, R., Murta-Nascimento, C., Rothman, N. & Chanock, S.J. (2007). Large-Scale Evaluation of Candidate Genes Identifies Associations between VEGF Polymorphisms and Bladder Cancer Risk. PloS Genetics. 3(2), 287-293.

(462) Limbourg, F.P., Takeshita, K., Radtke, F., Bronson, R.T., Chin, M.T. & Liao,

J.K. (2005). Essential role of endothelial Notch1 in angiogenesis. Circulation. 111, 1826-1832.

(463) Takeshita, K., Satoh, M., Ii, M., Silver, M., Limbourg, F.P., Mukai, Y., Rikitake,

Y., Radtke, F., Gridley, T., Losordo, D.W. & Liao, J.K. (2007). Critical Role of Endothelial Notch1 Signaling in Postnatal Angiogenesis. Circ Res. 100, 70-78.

(464) Liu, Z-J., Shirakawa, T., Li, Y., Soma, A., Oka, M., Dotto, G.P., Fairman, R.M.,

Velazquez, O.C. & Herlyn, M. (2003). Regulation of Notch1 and Dll4 by Vascular Endothelial Growth Factor in Arterial Endothelial Cells: Implications for Modulating Arteriogenesis and Angiogenesis. Mol Cell Biol. 23(1), 14-25.

(465) Hainaud, P., Contrerès, J.O., Villemain, A., Liu, L.X., Plouët, J., Tobelem, G. &

Dupuy, E. (2006). The Role of the Vascular Endothelial Growth Factor-Delta-like 4 ligand/Notch4-Ephrin B2 Cascade in Tumor Vessel Remodeling and Endothelial Cell

BIBLIOGRAFIA 230

Functions. Cancer Res. 66(17), 8501-8510. (466) Williams, C.K., Li, J-L., Murga, M., Harris, A.L. & Tosato, G. (2006). Up-

regulation of the Notch ligand Delta-like 4 inhibitts VEGF-induced endothelial cell function. Blood. 107(3), 931-939.

(467) Hellström, M., Phng, L.K., Hofmann, J.J., Wallgard, E., Coultas, L., Lindblom,

P., Alva, J., Nilsson, A.K., Karlsson, L., Gaiano, N., Yoon, K., Rossant, J., Iruela-Arispe, M.L., Kalén, M., Gerhardt, H. & Betsholtz, C. (2007). Dll4 signaling through Notch1 regulates formation of tip cells during angiogenesis. Nature. 445(7129), 776-780.

(468) Suchting, S., Freitas, C., le Noble, F., Benedito, R., Bréant, C., Duarte, A. &

Eichmann, A. (2007). The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proc Natl Acad Sci U S A. 104(9), 3225-3230.

(469) Lobov, I.B., Renard, R.A., Papadopoulos, N., Gale, N.W., Thurston, G.,

Yancopoulos, G.D. & Wiegand, S.J. (2007). Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting. Proc Natl Acad Sci U S A. 104(9), 3219-3224.

(470) Noguera-Troise, I., Daly, C., Papadopoulos, N.J., Coetzee, S., Boland, P., Gale,

N.W., Lin, H.C., Yancopoulos, G.D. & Thurston, G. (2006). Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature. 444(7122), 1032-1037.

(471) Patel, N.S., Li, J-L., Generali, D., Poulsom, R., Cranston, D.W. & Harris, A.L.

(2005). Up-regulation of Delta-like 4 ligand in Human Tumor Vasculature and the Role of Basal Expression in Endothelial Cell Function. Cancer Res. 65(19), 8690-8697.

(472) Patel, N.S., Dobbie, M.S., Rochester, M., Steers, G., Poulsom, R., Le Monnier, K.,

Cranston, D.W., Li, J.L. & Harris, A.L. (2006). Up-regulation of endothelial delta-like 4 expression correlates with vessel maturation in bladder cancer. Clin Cancer Res. 12(16), 4836-4844.

(473) Fernández, M.I., Bolenz, C., Trojan, L., Steidler, A., Weiss, C., Alken, P.,

Grobholz, R., Michel, M.S. (2007). Prognostic Implications of Lymphangiogenesis in Muscle-Invasive Transitional Cell Carcinoma of the Bladder. Eur Urol. [Epub ahead of print].

(474) Miyahara, M., Tanuma, J.I., Sugihara, K. & Semba, I. (2007). Tumor

lymphangiogenesis correlates with lympg node metastasis and clinicopathologic parameters in oral squamous cell carcinoma. Cancer. 110(6), 1287-1294.

(475) Nakamura, Y., Yasuoka, H., Tsujimoto, M., Kurozumi, K., Nakahara, M.,

Nakao, K. & Kakudo, K. (2006). Importance of lymph vessels in gastric cancer: a prognostic indicator and a predictor for lymph node metastasis in early stage cancer. J

BIBLIOGRAFIA

231

Clin Pathol. 59(1), 77-82. (476) Miyata, Y., Kanda, S., Ohba, K., Nomata, K., Eguchi. J., Hayashida, Y. &

Kametake, H. (2006). Tumor Lymphangiogenesis in Transitional Cell Carcinoma of the Upper Urinary Tract: Association with Clinicopathological Features and Prognosis. J Urol. 176, 348-353.

(477) Gao, P., Zhou, G.Y., Yin, G., Liu, Y., Liu, Z.Y., Zhang, J. & Hao, C.Y. (2006).

Lymphatic vessel density as a prognostic indicator for patients with stage I cervical carcinoma. Hum Pathol. 37(6), 719-725.

(478) Adachi, Y., Nakamura, H., Kitamura, Y., Taniguchi, Y., Araki, K., Shomori, K.,

Horie, Y., Kurozawa, Y., Ito, H. & Hayashi, K. (2007). Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastases. Pathol Int. 57(4), 171-177.

(479) Zeng, Y., Opeskin, K., Horvath, L.G., Sutherland, R.L. & Williams, E.D. (2005).

Lymphatic vessel density and lymph node metastasis in prostate cancer. Prostate. 65(3), 222-230.

(480) Matsumoto, K., Nakayama, Y., Inoue, Y., Minagawa, N., Katsuki, T., Shibao, K.,

Tsurudome, Y., Hirata, K., Nagata, N. & Itoh, H. (2007). Lymphatic microvessel density is an independent prognostic factor in colorectal cancer. Dis Colon Rectum. 50(3), 308-314.

(481) Saintigny, P., Kambouchner, M., Ly, M., Gomes, N., Sainte-Catherine, O., Vassy,

R., Czernichow, S., Letoumelin, P., Breau, J.L., Bernaudin, J.F. & Kraemer, M. (2007). Vascular endothelial growth factor-C and its receptor VEGFR-3, in non-small-cell lung cancer: Concurrent expression in cancer cells from primary tumour and metastatic lymph node. Lung Cancer. [Epub ahead of print].

(482) Mylona, E., Alexandrou, P., Mpakali, A., Giannopoulou, I., Liapis, G., Markaki,

S., Keramopoulos, A. & Nakopoulou, L. (2007). Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)-C and –D and VEGF receptor 3 in invasive breast carcinoma. Eur J Surg Oncol. 33(3), 294-300.

(483) Gurleyik, G., Gurleyik, E., Aker, F., Aktekin, A., Emir, S., Gungor, O. & Saglam,

A. (2007). Lymphovascular invasion, as a prognostic marker in patients with invasive breast cancer. Acta Chir Belg. 107(3), 284-287.

(484) Hong, B., Park, S., Hong, J.H., Kim, C.S., Ro, J.Y. & Aha, H. (2005). Prognostic

value of lymphovascular invasion in transitional cell carcinoma of upper urinary tract. Urology. 65(4), 692-696.

(485) Kim, J.M., Kim, T.Y., Kim, W.B., Gong, G., Kim, S.C., Hong, S.J. & Shong, Y.K.

(2006). Lymphovascular invasion is associated witth lateral cervical lymph node metastasis in papillary thyroid carcinoma. Laryngoscope. 116(11), 2081-2085.

BIBLIOGRAFIA 232

(486) Tezuka, K., Onoda, N., Takashima, T., Takagaki, K., Ishikawa, T., Wakasa, T., Wakasa, K. & Hirakawa, K. (2007). Prognostic significance of lymphovascular invasion diagnosed by lymphatic endothelium immunostaining in breast cancer patients. Oncol Rep. 17(5), 997-1003.

(487) Arnaout-Alkarain, A., Kahn, H.J., Narod, S.A., Sun, P.A. & Marks, A.N. (2007).

Significance of lymph vessel invasion identified by the endothelial lymphatic marker D2-40 in node negative breast cancer. Mod Pathol. 20(2), 183-191.

(488) Kobayashi, S., Kishimoto, T., Kamata, S., Otsuka, M., Miyazaki, M. & Ishikura,

H. (2007). Rapamycin, a specific inhibitor of the mammalian target of rapamycin, supresses lymphangiogenesis and lymphatic metastasis. Cancer Sci. 98(5), 726-733.

(489) Huber, S., Bruns, C.J., Schmid, G., Hermann, P.C., Conrad, C., Niess, H., Huss,

R., Graeb, C., Jauch, K.W., Heeschen, C. & Guba, M. (2007). Inhibition of the mammalian target of rapamycin impedes lymphangiogenesis. Kidney Int. 71(8), 771-777.

(490) Price, D.J., Grove, J.R., Calvo, V., Avruch, J. & Bierer, B.E. (1992). Rapamycin-

induced inhibition of the 70-kilodalton S6 protein kinase. Science. 257, 973-977. (491) Berretta, L., Gingras, A.C., Svitkin, Y.V., Hall, M.N. & Sonenberg, N. (1996).

Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. EMBO J. 15, 658-664.

(492) Rousseau, D., Gingras, A.C., Pause, A. & Sonenberg, N. (1996). Te eIF4E-binding

proteins 1 and 2 are negative regulators of cell growth. Oncogene. 13, 2415-2420. (493) Mita, M.M., Mita, A. & Rowinsky, E.K. (2003). The Molecular Target of

Rapamycin (mTOR) as a Therapeutic Target Against Cancer. Cancer Biol Ther. 2(1), 169-177.

(494) Stephan, S., Datta, K., Wang, E., Li, J., Brekken, R.A., Parangi, S., Thorpe, P.E.

& Mukhopadhyay, D. (2004). Effect of Rapamycin Alone and in Combination with Antiangiogenesis Therapy in an Orthopic Model of Human Pancreatic Cancer. Clin Cancer Res. 10, 6993-7000.