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New Treatments and New Strategies

  • Edward M. BarksdaleJr.

Abstract

Recent advances in molecular and cell biology have opened new avenues for the understanding of the genetic nature of cancer. Emergence of novel treatment approaches over the last 50 years has resulted in significant improvement in the prognosis of childhood cancer. The long-term survival rate for pediatric cancer patients in the 1960s was approximately 20% and currently is in the range of greater than 75% [1]. Specifically, the survival in patients with Wilm’s tumor has dramatically increased from 30% to 90% during this period [2]. Despite these impressive trends in survival, little progress has been made in the therapy of many pediatric brain tumors, neuroblastoma, and soft-tissue sarcomas. Furthermore, the focus of mainstream cancer therapies to target the proliferating cells has led to significant side-effects in normal developing tissues, organs, and bone marrow predisposing children to growth delay, cognitive impairments, and secondary malignancies [3]. Clearly, strategies that are both more targeted and effective are mandated in these patients.

Keywords

Major Histocompatibility Complex Gene Therapy Cancer Gene Therapy Purine Nucleoside Phosphorylase Angiogenic Switch 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Pearson HA (2002) History of pediatric hematology oncology. Pediatr Res 52:979–992PubMedGoogle Scholar
  2. 2.
    Poplack DG (2002) Principles and practice of pediatric oncology. In: Pizzo PA, Poplack DG (eds) Principles and practice of pediatric oncology. Lippincott Williams & Wil-kins, PhiladelphiaGoogle Scholar
  3. 3.
    Feig SA (2001) Second malignant neoplasms after successful treatment of childhood cancers. Blood Cells Mol Dis 27:662–666PubMedCrossRefGoogle Scholar
  4. 4.
    Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70PubMedCrossRefGoogle Scholar
  5. 5.
    Zitvogel L, Tesniere A, Kroemer G (2006) Cancer despite immunosurveillance: Immunoselection and immunosubversion. Nat Rev Immunol 6(10):715–727PubMedCrossRefGoogle Scholar
  6. 6.
    Nauts HC (1989) Bacteria and cancer: Antagonisms and benefits. Cancer Surv 8:713–723PubMedGoogle Scholar
  7. 7.
    Burnet FM (1970) The concept of immunological surveillance. Prog Exp Tumor Res 13:1–27PubMedGoogle Scholar
  8. 8.
    Everson TC, Cole WH (1966) Spontaneous regression of cancer. Saunders, Philadelphia, pp 88–163Google Scholar
  9. 9.
    Penn I (1988) Tumors of the immunocompromised patient. Annu Rev Med 39:63–73PubMedCrossRefGoogle Scholar
  10. 10.
    Penn I (1994) De novo malignancy in pediatric organ transplant recipients. J Pediatr Surg 29:221–226PubMedCrossRefGoogle Scholar
  11. 11.
    Matzinger P (1994) Tolerance, danger and the extended family. Annu Rev Immunol 12:991–1045PubMedGoogle Scholar
  12. 12.
    Offringa R (2006) Cancer. Cancer immunotherapy is more than a numbers game. Science 314:68–69PubMedCrossRefGoogle Scholar
  13. 13.
    Rosenberg SA, Yang JC, Restifo NP (2004) Cancer immunotherapy: Moving beyond current vaccines. Nat Med 10(9):909–915PubMedCrossRefGoogle Scholar
  14. 14.
    Dunn GP, Bruce AT, Ikeda H, Old LJ, Schhreiber RD (2002) Cancer immunoediting: From immunosurveillance to tumor escape. Nat Immunol 3:991–998PubMedCrossRefGoogle Scholar
  15. 15.
    Kim R, Emi M, Tanabe K, Arihiro K (2006) Tumor-driven evolution of immunosuppressive networks during malignant progression Cancer Res 66:5527–5536PubMedCrossRefGoogle Scholar
  16. 16.
    Drake CG, Jaffee EE, Pardoll DM (2006) Mechanisms of immune evasion by tumors. Adv Immunol 90:51–81PubMedCrossRefGoogle Scholar
  17. 17.
    Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497PubMedCrossRefGoogle Scholar
  18. 18.
    Carter P (2001) Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer 1:118–129PubMedCrossRefGoogle Scholar
  19. 19.
    vonMehren M, Adams GP, Weiner LM, et al. (2003) Monoclonal antibody therapy for cancer. Annu Rev Med 54:343–369CrossRefGoogle Scholar
  20. 20.
    Waldmann TA (2006) Effective cancer therapy through immunomodulation. Annu Rev Med 57:65–81PubMedCrossRefGoogle Scholar
  21. 21.
    Kohzoh I, Akinori T, (2006) Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer 6:714–727CrossRefGoogle Scholar
  22. 22.
    Hank JA, Surfus J, Gan J, et al. (1994) Treatment of neuroblastoma patients with antiganglioside GD2 antibody plus interleukin-2 induces antibody-dependent cellular cytotoxicity against neuroblastoma detected in vitro. J Immunother 15:29–37CrossRefGoogle Scholar
  23. 23.
    Mujoo K, Kipps TJ, Yang HM, et al. (1989) Functional properties and effect on growth suppression of human neuroblastoma tumors by isotype switch variants of monoclonal antiganglioside GD2 antibody 14.18. Cancer Res 49:2857–2861PubMedGoogle Scholar
  24. 24.
    Kushner BH, Kramer K, Cheung NK (2001) Phase II trial of the anti-G(D2) monoclonal antibody 3F8 and granulocyte-macrophage colony-stimulating factor for neuroblastoma. J Clin Oncol 19(22):4189–4194PubMedGoogle Scholar
  25. 25.
    Sondel PM, Hank JA (2001) Antibody-directed, effector cell-mediated tumor destruction. Hematol Oncol Clin North Am 15(4):703–721PubMedCrossRefGoogle Scholar
  26. 26.
    Cheung NK, Kushner BH, Kramer K (2001) Monoclonal antibody-based therapy of neuroblastoma. Hematol Oncol Clin North Am. 15:853–866PubMedCrossRefGoogle Scholar
  27. 27.
    Stacy KM (2005) Therapeutic mabs: Saving lives and making billions. Scientist 19:17–19.Google Scholar
  28. 28.
    Boon T, Coulie PG, Van den Eynde B (1997) Tumor antigens recognized by T cells. Immunol Today 18:267–268PubMedCrossRefGoogle Scholar
  29. 29.
    Rosenberg SA (1999) A new era for cancer immunotherapy based on the genes that encode cancer antigens. Immunity 10:281–287PubMedCrossRefGoogle Scholar
  30. 30.
    Shastri N, Schwab S, Serwold T (2002), Producing natures gene-chips: The generation of peptides for display by MHC Class I molecules. Annu Rev Immunol 20:463–493PubMedCrossRefGoogle Scholar
  31. 31.
    Rosenberg SA (2001) Progress in human tumour immunology and immunotherapy. Nature 411:380–384PubMedCrossRefGoogle Scholar
  32. 32.
    Pardoll DM (2002) Spinning molecular immunology into successful immunotherapy. Nat Rev Immunol 2:227–238PubMedCrossRefGoogle Scholar
  33. 33.
    Wang RF, Rosenberg SA (1996) Human tumor antigens recognized by T lymphocytes: Implications for cancer therapy. J Leukoc Biol 60:296–309PubMedGoogle Scholar
  34. 34.
    Dudley ME, Wunderlich JR, Yang JC, et al. (2002) A phase I study of non-myeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother 25:243–251PubMedCrossRefGoogle Scholar
  35. 35.
    Stewart BW, Kleihues P (eds) (2003) World cancer report. IARC Press, LyonGoogle Scholar
  36. 36.
    Chang MH, Shau WY, Chen CJ, et al. (2000) Hepatitis B vaccination and hepatocellular carcinoma rates in boys and girls. JAMA 284:3040–3042PubMedCrossRefGoogle Scholar
  37. 37.
    Villa LL, Costa RL, Petta CA, et al. (2005) Prophylactic quadrivalent human papillomavirus (types 6, 11, 16 and 18) L1 virus-like particle vaccine in young women: A randomized double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 6:271–278PubMedCrossRefGoogle Scholar
  38. 38.
    Lollini PL, Cavallo F, Nanni P, Forni G (2006) Vaccines for tumour prevention. Nat Rev Cancer 206–214Google Scholar
  39. 39.
    Palena C, Abrams SI, Schlom J, Hodge JW (2006) Cancer vaccines: Preclinical studies and novel strategies. Adv Cancer Res 95:115–145PubMedCrossRefGoogle Scholar
  40. 40.
    Pietersz GA, Pouniotis DS, Apostolopoulos V (2006) Design of peptide-based vaccines. Curr Med Chem 13:1591–1607PubMedCrossRefGoogle Scholar
  41. 41.
    Reilly RT, Machiels JP, Emens LA, Jaffee EM (2002) Cytokine gene-modified cell-based cancer vaccines. Methods Mol Med 69:233–257PubMedGoogle Scholar
  42. 42.
    Gilboa E (2004) The promise of cancer vaccines. Nat Rev Cancer 4:401–411PubMedCrossRefGoogle Scholar
  43. 43.
    Saito H, Frieta D, Dubsky P, Palucka AK (2006) Dendritic cell-based vaccination against cancer. Hematol Oncol Clin North Am 20:689–710PubMedCrossRefGoogle Scholar
  44. 44.
    Fong L, Engelman EG (2000) Dendritic cells in cancer immunotherapy. Annu Rev Immunol 18:245–273PubMedCrossRefGoogle Scholar
  45. 45.
    Geiger JD, Hutchinson RJ, Hohenkirk LF, et al. (2001) Vaccination of pediatric solid tumor with tumor lysate-pulsed dendritic cells can expand specific T cells and mediate tumor regression. Cancer Res 61(23):8513–8519PubMedGoogle Scholar
  46. 46.
    Iinuma H, Okinaga K, Fukushima R, et al. (2006) Superior protective and therapeutic effects of IL-12 and IL-18 gene transduced dendritic neuroblastoma fusion cells on liver metastasis of murine neuroblastoma. J Immunol 176(6):3461–3469PubMedGoogle Scholar
  47. 47.
    Redlinger RE Jr, Mailliard RB, Lotze MT, et al. (2003) Synergistic interleukin-18 and low-dose interleukin 2-promote regression of established murine neuroblastoma in vivo. J Pediatr Surg 38(3):301–307PubMedCrossRefGoogle Scholar
  48. 48.
    Redlinger RE Jr, Shimizu T, Remy T, et al. (2003) Cellular mechanisms of interleukin-12 mediated neuroblastoma regression. J Pediatr Surg 38(2):199–204PubMedCrossRefGoogle Scholar
  49. 49.
    Maki RG (2006) Future directions for immunotherapeutic intervention against sarcomas. Curr Opin Oncol 18(4):363–368PubMedCrossRefGoogle Scholar
  50. 50.
    Alegre ML, Frauwirth KA, Thompson CB (2001) T-cell regulation by CD28 and CTLA-4. Nat Rev Immunol 1:220–228.PubMedCrossRefGoogle Scholar
  51. 51.
    Salomon B, Bluestone JA (2001) Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 19 2225–2252CrossRefGoogle Scholar
  52. 52.
    Chambers CA, Kuhns MS, Egen JG, Allison JP (2001) CTLA-4 mediated inhibition in regulation of T cell responses: Mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol 19:565–594PubMedCrossRefGoogle Scholar
  53. 53.
    Lengauer C, Krinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396:642–649CrossRefGoogle Scholar
  54. 54.
    Kerbel RS (1991) Inhibition of tumor angiogenesis as a strategy to circumvent acquired resistance to anti-cancer therapeutic agents. Bioessays 13:31–36PubMedCrossRefGoogle Scholar
  55. 55.
    Davidoff AM, Kandel JJ (2004) Antiangiogenic therapy for the treatment of pediatric solid malignancies. Semin Pediatr Surg 13(1):53–60PubMedCrossRefGoogle Scholar
  56. 56.
    Knudson AG (1971) Mutation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68:820–823PubMedCrossRefGoogle Scholar
  57. 57.
    Carmeliet P (2000) Mechanisms of angiogenesis and arteriogenesis. Nat Med 6:389–395PubMedCrossRefGoogle Scholar
  58. 58.
    Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364PubMedCrossRefGoogle Scholar
  59. 59.
    Brooks PC, Silletti S, von Schalscha TL, et al. (1998) Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell 92:391–400PubMedCrossRefGoogle Scholar
  60. 60.
    Ruegg C, Yilmaz A, Bieler G, et al. (1998) Evidence for the involvement of endothelial cell integrin alpha Vbeta 3 in the disruption of tumor vasculature induced by TNF and IFN-gamma. Nat Med 4:408–414PubMedCrossRefGoogle Scholar
  61. 61.
    Relf M, LeJeune S, Fox S, Smith K, Leek R, Moghaddam A, Whitehouse R, Bicknell R, Harris AL(1997) Expression of the angiogenic factors vascular endothelial growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial growth factor, placenta growth factor and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 57:963–969PubMedGoogle Scholar
  62. 62.
    Meitar D, Crawford SE, Rademaker AW, et al. (1996) Tumor angiogenesis correlates with metastatic disease, Nmyc amplification, and poor outcome in human neuroblastoma. J Clin Oncol 14:405–414PubMedGoogle Scholar
  63. 63.
    Abrahamson LP, Grundy PE, Rademaker AW, et al. (2003) Increased microvascular density predicts relapse in Wilm’s tumor. J Pediatr Surg 38:325–330CrossRefGoogle Scholar
  64. 64.
    Folkman J (2006) Antiangiogenesis in cancer therapyendostatin and its mechanisms of action. Exp Cell Res 312:594–607PubMedCrossRefGoogle Scholar
  65. 65.
    Folkman J (2006) Angiogenesis. Annu Rev Med 57:1–18PubMedCrossRefGoogle Scholar
  66. 66.
    Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2:727–739PubMedCrossRefGoogle Scholar
  67. 67.
    Hanahan D, Bergers G, Bergsland E (2000) Less is more, regularly: Metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 105:1045–1047PubMedCrossRefGoogle Scholar
  68. 68.
    Abdollahi A, Hahnfeldt P, Maercker C, Grone HJ, De-bus J, Ansorge W, Folkman J, Hlatky L, Huer PE (2004) Endostatin’s antiangiogenic signaling network. Mol Cell 13:649–663PubMedCrossRefGoogle Scholar
  69. 69.
    McCormick F (2001) Cancer gene therapy: Fringe or cutting edge? Nat Rev Cancer 1:130–141PubMedCrossRefGoogle Scholar
  70. 70.
    Nathwani AC, Benjamin R, Nienhuis AW, Davidoff AM (2004) Current status and prospects for gene therapy. Vox Sang 87:73–81PubMedCrossRefGoogle Scholar
  71. 71.
    Roth JA, Nhuyen D, Lawrence DD, et al. (1996) Retrovirus-Mediated wild-type of p53 gene transfer to tumors of patients with lung cancer. Nat Med 2:985–991PubMedCrossRefGoogle Scholar
  72. 72.
    Cowan KH, Moscow JA, Huang H, et al. (1999) Paclitaxel chemotherapy after autologous stem cell transplantation and engraftment of hematopoietic cells transduced with a retrovirus containing the multidrug resistance complementary DNA (MDR1) in metastatic breast cancer patients. Clin Cancer Res 5:1619–1628PubMedGoogle Scholar
  73. 73.
    Hanania EG, Giles RE, Kavanagh J, et al. (1997) Results of MDR-1 vector modification trial indicate that granulocyte/ macrophage colony-forming unit cells do not contribute to post-transplant hematopoietic recovery following intensive systemic therapy. Proc Natl Acad Sci USA 93:15346–15351CrossRefGoogle Scholar
  74. 74.
    Kim DH, McCormick F (1996) Replicating viruses as selective cancer therapeutics. Mol Med Today 2:519–527CrossRefGoogle Scholar
  75. 75.
    Barker DD, Berk A (1987) Adenovirus proteins from both E1B reading frames are required for transformation of rodent cells by viral infection and DNA transfection. Virology 156:107–120PubMedCrossRefGoogle Scholar
  76. 76.
    Fueyo J, Gomez-Manzano C, Alemany R, et al. (2000) A mutant oncolytic adenovirus targeting the RB pathway produces anti-glioma effect in vivo. Oncogene 19:2–12PubMedCrossRefGoogle Scholar
  77. 77.
    Rodriguez R, Schuur ER, Lim HY, et al. (1997) Prostate attenuated replication competent adenovirus (ARCA) CN706: A selective cytotoxic prostate specific antigen-positive prostate cancer cells. Cancer Res 57:2559–2563PubMedGoogle Scholar
  78. 78.
    Moolten FL (1986) Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: Paradigm for a prospective cancer control strategy. Cancer Res. 46:5276–5281PubMedGoogle Scholar
  79. 79.
    Gleave ME, Monia BP (2005) Antisense therapy of cancer. Nat Rev Cancer 5:468–479PubMedCrossRefGoogle Scholar
  80. 79.
    Orr RM, Monica BP (1998) Antisense therapy for cancer. Curr Opin Investig Drugs 1:199–205Google Scholar
  81. 80.
    Crooke ST (1998) Molecular mechanisms of antisense drugs: RNase H. Antisense Nucleic Acid Drug Dev 8:33–134Google Scholar
  82. 81.
    Monia BP, et al. (1993) Evaluation of 2’-modified oligonucleotides containing 2’-deoxy gaps as antisense inhibitors of gene expression. J Biol Chem 269:4514–4522Google Scholar
  83. 82.
    Carpentier AF, Chen L, Maltonti F, et al. (1999) Oligodeoxynucleotides containing CpG motifs can induce rejection of a neuroblastoma in mice. Cancer Res 59:5429–5432PubMedGoogle Scholar
  84. 83.
    Ameyar-Zazoua M, Guasconi V, Ait-Si-Ali S (2005) siRNA as a route to new cancer therapies. Expert Opin Biol Ther 5:221–224PubMedCrossRefGoogle Scholar
  85. 84.
    Reed JC (1994) Bcl-2 and the regulation of programmed cell death. J Cell Biol 124:1–6PubMedCrossRefGoogle Scholar
  86. 85.
    Zangemeister-Wittke U, Leech SH, Olie RA, et al. (2000) A novel bispecific antisense oligonucleotide inhibiting both bcl-2 and bcl-xl expression efficiently induces apoptosis in tumor cells. Clin Cancer Res 6:2547–2555PubMedGoogle Scholar
  87. 86.
    Gleave ME, Tolcher A, Miyake H, et al. (1999) Progression to androgen independence is delayed by adjuvant treatment with antisense Bcl-2 oligodeoxynucleotides after castration in the LNCaP prostate tumor model. Clin Cancer Res 6:2891–2898Google Scholar
  88. 87.
    Webb A, Cunningham D, Cotter F, et al. (1997) BCL-2 antisense therapy in patients with non-Hodgkin lymphoma. Lancet 349:1137–1141PubMedCrossRefGoogle Scholar
  89. 88.
    Miyake H, Monia BP, Gleave ME (2000) Inhibition of progression to androgen-independence by antisense bcl-2 oligonucleotides plus taxol after castration in the Shionogi tumor model. Int J Cancer 86:855–862PubMedCrossRefGoogle Scholar
  90. 89.
    Gautschi O, Tschopp S, Olie RA, et al. (2001) Activity of a novel bcl-2/bcl-xl bispecific antisense oligonucleotide against tumors of diverse histologic origins. J Natl Cancer Inst 93:463–471PubMedCrossRefGoogle Scholar
  91. 90.
    Newton AC (1997) Regulation of protein kinase C. Curr Opin Cell Biol 9:161–167PubMedCrossRefGoogle Scholar
  92. 91.
    Swannie HC, Kaye SB (2002) Protein kinase C inhibitors. Curr Oncol Rep 4:47–46CrossRefGoogle Scholar
  93. 92.
    Wang XY, Repasky E, Liu HT (1999) Antisense inhibition of protein kinase Ca reverses the transformed phenotype in human lung carcinoma cells. Exp Cell Res 250:253–263PubMedCrossRefGoogle Scholar
  94. 93.
    Geiger T, Muller M, Dean NM, et al.(1998) Antitumor activity of PKC-a antisense oligonucleotide in combination with standard chemotherapeutic agents against various human tumors transplanted intonude mice. Anticancer Drug Des 13:35–45PubMedGoogle Scholar
  95. 94.
    Altieri DC (2003) Survivin versatile modulation of cell division and apoptosis in cancer. Oncogene 22:8581–8589PubMedCrossRefGoogle Scholar
  96. 95.
    Ambrosini G, Adida C, Altieri DC (1997) A novel antiapoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3:917–921PubMedCrossRefGoogle Scholar
  97. 96.
    Fukuda S, Pelus L (2006) Survivin, a cancer target with an emerging role in normal adult tissues. Mol Cancer Ther 5:1087–1098PubMedCrossRefGoogle Scholar
  98. 97.
    LaCasse EC, Baird S, Korneluk RG, et al. (1998) The inhibitors of apoptosis (IAPS) and their emerging role in cancer. Oncogene 17:3247–3259PubMedCrossRefGoogle Scholar
  99. 98.
    Fangusaro JR, Caldas H, Jiang Y, Altura R (2006) Survivin: An inhibitor of apoptosis in pediatric cancer. Pediatr Blood Cancer 47:4–13PubMedCrossRefGoogle Scholar
  100. 99.
    Chen J, Wu W, Tahir SK, et al. (2000) Down-regulation of survivin by antisense oligonucleotides increases apoptosis, inhibits cyokinesis and anchorage-independent growth. Neoplasia 2:235–241PubMedCrossRefGoogle Scholar
  101. 100.
    Ciocca DR, Oesterreich S, Chamness GC, et al. (1993) Biological and clinical implications of heat shock protein 27,000 (Hsp27): A review. J Natl Cancer Inst 85:1558–1570PubMedCrossRefGoogle Scholar
  102. 101.
    Ehrlich P (1956). On immunity with special reference to cell life: Croonian lecture. In: B Himmelweir (ed) The collected papers of Paul Ehrlich: Immunology and cancer research. 148–192Google Scholar
  103. 102.
    Friedl P, den Boer A, Gunzer M (2005) Tuning immune responses: Diversity and adaptation of the immunological synapse. Nat Rev Immunol 5:532–545PubMedCrossRefGoogle Scholar
  104. 103.
    Lake RA, Robinson BWS (2005) Immunotherapy and chemotherapy-A practical partnership. Nat Rev Cancer 5:397–405PubMedCrossRefGoogle Scholar
  105. 104.
    Tarassoff CR Arlen PM, Gulley JL (2006) Therapeutic vaccines for prostate cancer. Oncologist 11:451–462PubMedCrossRefGoogle Scholar
  106. 105.
    O’Neill DW, Adams S, Bhardwaj N (2004) Manipulating dendritic cell biology for the active immunotherapy of cancer. Blood 104:2235–2246PubMedCrossRefGoogle Scholar
  107. 106.
    Bergers G, Benjamin LE (2003) Tumorigenesis and the angiogenic switch. Nat Rev Cancer 3:401–410PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Edward M. BarksdaleJr.
    • 1
  1. 1.Department of Pediatric SurgeryChildren’s Hospital of PittsburghPittsburghUSA

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