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The Cycle Between Angiogenesis, Perfusion, and Hypoxia in Tumors

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Antiangiogenic Agents in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Summary

This chapter will present a pathophysiologic paradigm that occurs in solid tumors that is characterized by a self-propagating cycle of abnormally regulated angiogenesis, instability in perfusion, and hypoxia. Interactions between tumor and endothelial cells occur during tumor growth and in response to therapy. These interactions are of central importance in establishing codependence that contributes to promotion of tumor and endothelial cell survival, treatment resistance, enhanced invasion, and metastasis. Results indicate that concurrent targeting of both tumor and endothelial cells may be of central importance in improving treatment responses to both radiation and chemotherapy.

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References

  1. Kraus, R. M., Stallings, H. W., 3rd, Yeager, R. C., and Gavin, T. P. Circulating plasma VEGF response to exercise in sedentary and endurance-trained men. J Appl Physiol, 96: 1445–1450, 2004.

    Article  PubMed  CAS  Google Scholar 

  2. Wilkinson-Berka, J. L. Vasoactive factors and diabetic retinopathy: vascular endothelial growth factor, cycoloxygenase-2 and nitric oxide. Curr Pharm Des, 10: 3331–3348, 2004.

    Article  PubMed  CAS  Google Scholar 

  3. Folkman, J. and Hanahan, D. Switch to the angiogenic phenotype during tumorigenesis. Princess Takamatsu Symp, 22: 339–347, 1991.

    PubMed  CAS  Google Scholar 

  4. Semenza, G. L. Targeting HIF-1 for cancer therapy. Nat Rev Cancer, 3: 721–732, 2003.

    Article  PubMed  CAS  Google Scholar 

  5. Rak, J., Mitsuhashi, Y., Bayko, L., Filmus, J., Shirasawa, S., Sasazuki, T., and Kerbel, R. S. Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer Res, 55: 4575–4580, 1995.

    PubMed  CAS  Google Scholar 

  6. Ohh, M., Park, C. W., Ivan, M., Hoffman, M. A., Kim, T. Y., Huang, L. E., Pavletich, N., Chau, V., and Kaelin, W. G. Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol, 2: 423–427, 2000.

    Article  PubMed  CAS  Google Scholar 

  7. Laughner, E., Taghavi, P., Chiles, K., Mahon, P. C., and Semenza, G. L. HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol Cell Biol, 21: 3995–4004, 2001.

    Article  PubMed  CAS  Google Scholar 

  8. Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A. R., Ryan, H. E., Johnson, R. S., Jefferson, A. B., Stokoe, D., and Giaccia, A. J. Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev, 14: 391–396, 2000.

    PubMed  CAS  Google Scholar 

  9. Arany, Z., Huang, L. E., Eckner, R., Bhattacharya, S., Jiang, C., Goldberg, M. A., Bunn, H. F., and Livingston, D. M. An essential role for p300/CBP in the cellular response to hypoxia. Proc Natl Acad Sci USA, 93: 12969–12973, 1996.

    Article  PubMed  CAS  Google Scholar 

  10. Zhou, J., Fandrey, J., Schumann, J., Tiegs, G., and Brune, B. NO and TNF-alpha released from activated macrophages stabilize HIF-1alpha in resting tubular LLC-PK1 cells. Am J Physiol Cell Physiol, 284: C439–C446, 2003.

    PubMed  CAS  Google Scholar 

  11. Yang, Z. Z., Zhang, A. Y., Yi, F. X., Li, P. L., and Zou, A. P. Redox regulation of HIF-1alpha levels and HO-1 expression in renal medullary interstitial cells. Am J Physiol Renal Physiol, 284: F1207–1215, 2003.

    PubMed  CAS  Google Scholar 

  12. Kuppusamy, P., Li, H., Ilangovan, G., Cardounel, A. J., Zweier, J. L., Yamada, K., Krishna, M. C., and Mitchell, J. B. Noninvasive imaging of tumor redox status and its modification by tissue glutathione levels. Cancer Res, 62: 307–312, 2002.

    PubMed  CAS  Google Scholar 

  13. Kimura, H., Braun, R. D., Ong, E. T., Hsu, R., Secomb, T. W., Papahadjopoulos, D., Hong, K., and Dewhirst, M. W. Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma. Cancer Res, 56: 5522–5528, 1996.

    PubMed  CAS  Google Scholar 

  14. Braun, R. D., Lanzen, J. L., and Dewhirst, M. W. Fourier analysis of fluctuations of oxygen tension and blood flow in R3230Ac tumors and muscle in rats. Am J Physiol, 277: H551–H568, 1999.

    PubMed  CAS  Google Scholar 

  15. Forsythe, J. A., Jiang, B. H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., and Semenza, G. L. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol, 16: 4604–4613, 1996.

    PubMed  CAS  Google Scholar 

  16. Ravi, R., Mookerjee, B., Bhujwalla, Z. M., Sutter, C. H., Artemov, D., Zeng, Q., Dillehay, L. E., Madan, A., Semenza, G. L., and Bedi, A. Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev, 14: 34–44, 2000.

    PubMed  CAS  Google Scholar 

  17. Willam, C., Masson, N., Tian, Y. M., Mahmood, S. A., Wilson, M. I., Bicknell, R., Eckardt, K. U., Maxwell, P. H., Ratcliffe, P. J., and Pugh, C. W. Peptide blockade of HIFalpha degradation modulates cellular metabolism and angiogenesis. Proc Natl Acad Sci USA, 99: 10423–10428, 2002.

    Article  PubMed  CAS  Google Scholar 

  18. Cao, Y., Li, C. Y., Moeller, B. J., Yu, D., Zhao, Y., Dreher, M. R., Shan, S., and Dewhirst, M. W. Observation of incipient tumor angiogenesis that is independent of hypoxia and hypoxia inducible factor-1 activation. Cancer Res, 65: 5498–5505, 2005.

    Article  PubMed  CAS  Google Scholar 

  19. Mizukami, Y., Li, J., Zhang, X., Zimmer, M. A., Iliopoulos, O., and Chung, D. C. Hypoxia-inducible factor-1-independent regulation of vascular endothelial growth factor by hypoxia in colon cancer. Cancer Res, 64: 1765–1772, 2004.

    Article  PubMed  CAS  Google Scholar 

  20. Li, C. Y., Shan, S., Huang, Q., Braun, R. D., Lanzen, J., Hu, K., Lin, P., and Dewhirst, M. W. Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models. J Natl Cancer Inst, 92: 143–147, 2000.

    Article  PubMed  CAS  Google Scholar 

  21. Brown, J. M. and Wilson, W. R. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer, 4: 437–447, 2004.

    Article  PubMed  CAS  Google Scholar 

  22. Buchler, P., Reber, H. A., Buchler, M. W., Friess, H., Lavey, R. S., and Hines, O. J. Antiangiogenic activity of genistein in pancreatic carcinoma cells is mediated by the inhibition of hypoxia-inducible factor-1 and the down-regulation of VEGF gene expression. Cancer, 100: 201–210, 2004.

    Article  PubMed  CAS  Google Scholar 

  23. Patan, S., Munn, L. L., and Jain, R. K. Intussusceptive microvascular growth in a human colon adenocarcinoma xenograft: a novel mechanism of tumor angiogenesis. Microvasc Res, 51: 260–272, 1996.

    Article  PubMed  CAS  Google Scholar 

  24. Burri, P. H., Hlushchuk, R., and Djonov, V. Intussusceptive angiogenesis: its emergence, its characteristics, and its significance. Dev Dyn, 231: 474–488, 2004.

    Article  PubMed  Google Scholar 

  25. Folkman, J. Angiogenesis and angiogenesis inhibition: an overview. EXS, 79: 1–8, 1997.

    PubMed  CAS  Google Scholar 

  26. Holash, J., Wiegand, S. J., and Yancopoulos, G. D. New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene, 18: 5356–5362, 1999.

    Article  PubMed  CAS  Google Scholar 

  27. Dewhirst, M. W. Concepts of oxygen transport at the microcirculatory level. Semin Radiat Oncol, 8: 143–150, 1998.

    Article  PubMed  CAS  Google Scholar 

  28. Gulledge, C. J. and Dewhirst, M. W. Tumor oxygenation: a matter of supply and demand. Anticancer Res, 16: 741–749, 1996.

    PubMed  CAS  Google Scholar 

  29. Kim, E. S., Serur, A., Huang, J., Manley, C. A., McCrudden, K. W., Frischer, J. S., Soffer, S. Z., Ring, L., New, T., Zabski, S., Rudge, J. S., Holash, J., Yancopoulos, G. D., Kandel, J. J., and Yamashiro, D. J. Potent VEGF blockade causes regression of coopted vessels in a model of neuroblastoma. Proc Natl Acad Sci USA, 99: 11399–11404, 2002.

    Article  PubMed  CAS  Google Scholar 

  30. Passalidou, E., Trivella, M., Singh, N., Ferguson, M., Hu, J., Cesario, A., Granone, P., Nicholson, A. G., Goldstraw, P., Ratcliffe, C., Tetlow, M., Leigh, I., Harris, A. L., Gatter, K. C., and Pezzella, F. Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas. Br J Cancer, 86: 244–249, 2002.

    Article  PubMed  CAS  Google Scholar 

  31. Stessels, F., Van den Eynden, G., Van der Auwera, I., Salgado, R., Van den Heuvel, E., Harris, A. L., Jackson, D. G., Colpaert, C. G., van Marck, E. A., Dirix, L. Y., and Vermeulen, P. B. Breast adenocarcinoma liver metastases, in contrast to colorectal cancer liver metastases, display a non-angiogenic growth pattern that preserves the stroma and lacks hypoxia. Br J Cancer, 90: 1429–1436, 2004.

    Article  PubMed  CAS  Google Scholar 

  32. Kunkel, P., Ulbricht, U., Bohlen, P., Brockmann, M. A., Fillbrandt, R., Stavrou, D., Westphal, M., and Lamszus, K. Inhibition of glioma angiogenesis and growth in vivo by systemic treatment with a monoclonal antibody against vascular endothelial growth factor receptor-2. Cancer Res, 61: 6624–6628, 2001.

    PubMed  CAS  Google Scholar 

  33. Holash, J., Davis, S., Papadopoulos, N., Croll, S. D., Ho, L., Russell, M., Boland, P., Leidich, R., Hylton, D., Burova, E., Ioffe, E., Huang, T., Radziejewski, C., Bailey, K., Fandl, J. P., Daly, T., Wiegand, S. J., Yancopoulos, G. D., and Rudge, J. S. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA, 99: 11393–11398, 2002.

    Article  PubMed  CAS  Google Scholar 

  34. Ferrara, N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev, 25: 581–611, 2004.

    Article  PubMed  CAS  Google Scholar 

  35. Peoch, M., Farion, R., Hiou, A., Le Bas, J. F., Pasquier, B., and Remy, C. Immunohistochemical study of VEGF, angiopoietin 2 and their receptors in the neovascularization following microinjection of C6 glioma cells into rat brain. Anticancer Res, 22: 2147–2151, 2002.

    PubMed  CAS  Google Scholar 

  36. Kimura, H. and Esumi, H. Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis. Acta Biochim Pol, 50: 49–59, 2003.

    PubMed  CAS  Google Scholar 

  37. Brekken, R. A. and Thorpe, P. E. VEGF-VEGF receptor complexes as markers of tumor vascular endothelium. J Control Release, 74: 173–181, 2001.

    Article  PubMed  CAS  Google Scholar 

  38. Haroon, Z. A., Lai, T. S., Hettasch, J. M., Lindberg, R. A., Dewhirst, M. W., and Greenberg, C. S. Tissue transglutaminase is expressed as a host response to tumor invasion and inhibits tumor growth. Lab Invest, 79: 1679–1686, 1999.

    PubMed  CAS  Google Scholar 

  39. Hettasch, J. M., Bandarenko, N., Burchette, J. L., Lai, T. S., Marks, J. R., Haroon, Z. A., Peters, K., Dewhirst, M. W., Iglehart, J. D., and Greenberg, C. S. Tissue transglutaminase expression in human breast cancer. Lab Invest, 75: 637–645, 1996.

    PubMed  CAS  Google Scholar 

  40. Iacobuzio-Donahue, C. A., Ashfaq, R., Maitra, A., Adsay, N. V., Shen-Ong, G. L., Berg, K., Hollingsworth, M. A., Cameron, J. L., Yeo, C. J., Kern, S. E., Goggins, M., and Hruban, R. H. Highly expressed genes in pancreatic ductal adenocarcinomas: a comprehensive characterization and comparison of the transcription profiles obtained from three major technologies. Cancer Res, 63: 8614–8622, 2003.

    PubMed  CAS  Google Scholar 

  41. Mehta, K., Fok, J., Miller, F. R., Koul, D., and Sahin, A. A. Prognostic significance of tissue transglutaminase in drug resistant and metastatic breast cancer. Clin Cancer Res, 10: 8068–8076, 2004.

    Article  PubMed  CAS  Google Scholar 

  42. Davis, S., Aldrich, T. H., Jones, P. F., Acheson, A., Compton, D. L., Jain, V., Ryan, T. E., Bruno, J., Radziejewski, C., Maisonpierre, P. C., and Yancopoulos, G. D. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell, 87: 1161–1169, 1996.

    Article  PubMed  CAS  Google Scholar 

  43. Maisonpierre, P. C., Suri, C., Jones, P. F., Bartunkova, S., Wiegand, S. J., Radziejewski, C., Compton, D., McClain, J., Aldrich, T. H., Papadopoulos, N., Daly, T. J., Davis, S., Sato, T. N., and Yancopoulos, G. D. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science, 277: 55–60, 1997.

    Article  PubMed  CAS  Google Scholar 

  44. Papapetropoulos, A., Garcia-Cardena, G., Dengler, T. J., Maisonpierre, P. C., Yancopoulos, G. D., and Sessa, W. C. Direct actions of angiopoietin-1 on human endothelium: evidence for network stabilization, cell survival, and interaction with other angiogenic growth factors. Lab Invest, 79: 213–223, 1999.

    PubMed  CAS  Google Scholar 

  45. Thurston, G., Rudge, J. S., Ioffe, E., Zhou, H., Ross, L., Croll, S. D., Glazer, N., Holash, J., McDonald, D. M., and Yancopoulos, G. D. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med, 6: 460–463, 2000.

    Article  PubMed  CAS  Google Scholar 

  46. Morikawa, S., Baluk, P., Kaidoh, T., Haskell, A., Jain, R. K., and McDonald, D. M. Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol, 160: 985–1000, 2002.

    PubMed  Google Scholar 

  47. Enholm, B., Paavonen, K., Ristimaki, A., Kumar, V., Gunji, Y., Klefstrom, J., Kivinen, L., Laiho, M., Olofsson, B., Joukov, V., Eriksson, U., and Alitalo, K. Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia. Oncogene, 14: 2475–2483, 1997.

    Article  PubMed  CAS  Google Scholar 

  48. Mandriota, S. J. and Pepper, M. S. Regulation of angiopoietin-2 mRNA levels in bovine microvascular endothelial cells by cytokines and hypoxia. Circ Res, 83: 852–859, 1998.

    PubMed  CAS  Google Scholar 

  49. Oh, H., Takagi, H., Suzuma, K., Otani, A., Matsumura, M., and Honda, Y. Hypoxia and vascular endothelial growth factor selectively up-regulate angiopoietin-2 in bovine microvascular endothelial cells. J Biol Chem, 274: 15732–15739, 1999.

    Article  PubMed  CAS  Google Scholar 

  50. Zakrzewicz, A., Secomb, T. W., and Pries, A. R. Angioadaptation: keeping the vascular system in shape. News Physiol Sci, 17: 197–201, 2002.

    PubMed  Google Scholar 

  51. Tong, S. and Yuan, F. Numerical simulations of angiogenesis in the cornea. Microvasc Res, 61: 14–27, 2001.

    Article  PubMed  CAS  Google Scholar 

  52. Li, C. Y., Shan, S., Cao, Y., and Dewhirst, M. W. Role of incipient angiogenesis in cancer metastasis. Cancer Metastasis Rev, 19: 7–11, 2000.

    Article  PubMed  CAS  Google Scholar 

  53. Shan, S., Robson, N. D., Cao, Y., Qiao, T., Li, C. Y., Kontos, C. D., Garcia-Blanco, M., and Dewhirst, M. W. Responses of vascular endothelial cells to angiogenic signaling are important for tumor cell survival. FASEB J, 18: 326–328, 2004.

    PubMed  CAS  Google Scholar 

  54. Krishnamachary, B., Berg-Dixon, S., Kelly, B., Agani, F., Feldser, D., Ferreira, G., Iyer, N., LaRusch, J., Pak, B., Taghavi, P., and Semenza, G. L. Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res, 63: 1138–1143, 2003.

    PubMed  CAS  Google Scholar 

  55. Wong, C. W., Song, C., Grimes, M. M., Fu, W., Dewhirst, M. W., Muschel, R. J., and Al-Mehdi, A. B. Intravascular location of breast cancer cells after spontaneous metastasis to the lung. Am J Pathol, 161: 749–753, 2002.

    PubMed  Google Scholar 

  56. Al-Mehdi, A. B., Tozawa, K., Fisher, A. B., Shientag, L., Lee, A., and Muschel, R. J. Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat Med, 6: 100–102, 2000.

    Article  PubMed  CAS  Google Scholar 

  57. Vlahovic, G., Rabbani, Z. N., Herndon, J. E., 2nd, Dewhirst, M. W., and Vujaskovic, Z. Treatment with Imatinib in NSCLC is associated with decrease of phosphorylated PDGFR-beta and VEGF expression, decrease in interstitial fluid pressure and improvement of oxygenation. Br J Cancer, 95: 1013–1019, 2006.

    Article  PubMed  CAS  Google Scholar 

  58. Nykanen, A. I., Krebs, R., Tikkanen, J. M., Raisky, O., Sihvola, R., Wood, J., Koskinen, P. K., and Lemstrom, K. B. Combined vascular endothelial growth factor and platelet-derived growth factor inhibition in rat cardiac allografts: beneficial effects on inflammation and smooth muscle cell proliferation. Transplantation, 79: 182–189, 2005.

    Article  PubMed  Google Scholar 

  59. Carmeliet, P. Mechanisms of angiogenesis and arteriogenesis. Nat Med, 6: 389–395, 2000.

    Article  PubMed  CAS  Google Scholar 

  60. Heuchel, R., Berg, A., Tallquist, M., Ahlen, K., Reed, R. K., Rubin, K., Claesson-Welsh, L., Heldin, C. H., and Soriano, P. Platelet-derived growth factor beta receptor regulates interstitial fluid homeostasis through phosphatidylinositol-3’ kinase signaling. Proc Natl Acad Sci USA, 96: 11410–11415, 1999.

    Article  PubMed  CAS  Google Scholar 

  61. Ostman, A. PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Cytokine Growth Factor Rev, 15: 275–286, 2004.

    Article  PubMed  CAS  Google Scholar 

  62. Burri, P. H. and Djonov, V. Intussusceptive angiogenesis–the alternative to capillary sprouting. Mol Aspects Med, 23: S1–S27, 2002.

    Article  PubMed  Google Scholar 

  63. Djonov, V., Andres, A. C., and Ziemiecki, A. Vascular remodelling during the normal and malignant life cycle of the mammary gland. Microsc Res Tech, 52: 182–189, 2001.

    Article  PubMed  CAS  Google Scholar 

  64. Djonov, V. G., Kurz, H., and Burri, P. H. Optimality in the developing vascular system: branching remodeling by means of intussusception as an efficient adaptation mechanism. Dev Dyn, 224:391–402, 2002.

    Article  PubMed  Google Scholar 

  65. Djonov, V., Baum, O., and Burri, P. H. Vascular remodeling by intussusceptive angiogenesis. Cell Tissue Res, 314: 107–117, 2003.

    Article  PubMed  Google Scholar 

  66. Pries, A. R., Reglin, B., and Secomb, T. W. Structural response of microcirculatory networks to changes in demand: information transfer by shear stress. Am J Physiol Heart Circ Physiol, 284: H2204–H2212, 2003.

    PubMed  CAS  Google Scholar 

  67. Dewhirst, M. W., Ong, E. T., Klitzman, B., Secomb, T. W., Vinuya, R. Z., Dodge, R., Brizel, D., and Gross, J. F. Perivascular oxygen tensions in a transplantable mammary tumor growing in a dorsal flap window chamber. Radiat Res, 130: 171–182, 1992.

    Article  PubMed  CAS  Google Scholar 

  68. Helmlinger, G., Yuan, F., Dellian, M., and Jain, R. K. Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med, 3: 177–182, 1997.

    Article  PubMed  CAS  Google Scholar 

  69. Dewhirst, M. W., Ong, E. T., Braun, R. D., Smith, B., Klitzman, B., Evans, S. M., and Wilson, D. Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia. Br J Cancer, 79: 1717–1722, 1999.

    Article  PubMed  CAS  Google Scholar 

  70. Secomb, T. W., Hsu, R., Braun, R. D., Ross, J. R., Gross, J. F., and Dewhirst, M. W. Theoretical simulation of oxygen transport to tumors by three-dimensional networks of microvessels. Adv Exp Med Biol, 454: 629–634, 1998.

    PubMed  CAS  Google Scholar 

  71. Dewhirst, M. W., Secomb, T. W., Ong, E. T., Hsu, R., and Gross, J. F. Determination of local oxygen consumption rates in tumors. Cancer Res, 54: 3333–3336, 1994.

    PubMed  CAS  Google Scholar 

  72. Kavanagh, B. D., Coffey, B. E., Needham, D., Hochmuth, R. M., and Dewhirst, M. W. The effect of flunarizine on erythrocyte suspension viscosity under conditions of extreme hypoxia, low pH, and lactate treatment. Br J Cancer, 67: 734–741, 1993.

    PubMed  CAS  Google Scholar 

  73. Haroon, Z. A., Raleigh, J. A., Greenberg, C. S., and Dewhirst, M. W. Early wound healing exhibits cytokine surge without evidence of hypoxia. Ann Surg, 231: 137–147, 2000.

    Article  PubMed  CAS  Google Scholar 

  74. Graeber, T. G., Osmanian, C., Jacks, T., Housman, D. E., Koch, C. J., Lowe, S. W., and Giaccia, A. J. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature, 379: 88–91, 1996.

    Article  PubMed  CAS  Google Scholar 

  75. Dvorak, H. F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med, 315: 1650–1659, 1986.

    Article  PubMed  CAS  Google Scholar 

  76. Teicher, B. A., Sotomayor, E. A., and Huang, Z. D. Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and metastatic disease. Cancer Res, 52: 6702–6704, 1992.

    PubMed  CAS  Google Scholar 

  77. Teicher, B. A., Holden, S. A., Ara, G., Dupuis, N. P., Liu, F., Yuan, F., Ikebe, M., and Kakeji, Y. Influence of an anti-angiogenic treatment on 9L gliosarcoma: oxygenation and response to therapy. Int J Cancer, 61: 732–737, 1995.

    Article  PubMed  CAS  Google Scholar 

  78. Denekamp, J. Review article: angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. Br J Radiol, 66: 181–196, 1993.

    Article  PubMed  CAS  Google Scholar 

  79. Garcia-Barros, M., Paris, F., Cordon-Cardo, C., Lyden, D., Rafii, S., Haimovitz-Friedman, A., Fuks, Z., and Kolesnick, R. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science, 300: 1155–1159, 2003.

    Article  PubMed  CAS  Google Scholar 

  80. Brown, M., Bristow, R., Glazer, P., Hill, R., McBride, W., McKenna, G., and Muschel, R. Comment on “Tumor response to radiotherapy regulated by endothelial cell apoptosis” (II). Science, 302: 1894; author reply 1894, 2003.

    Article  PubMed  CAS  Google Scholar 

  81. Rubin, P. and Casarett, G. Microcirculation of tumors. II. The supervascularized state of irradiated regressing tumors. Clin Radiol, 17: 346–355, 1966.

    Article  PubMed  CAS  Google Scholar 

  82. Hilmas, D. E. and Gillette, E. L. Tumor microvasculature following fractionated x irradiation. Radiology, 116: 165–169, 1975.

    PubMed  CAS  Google Scholar 

  83. Dewhirst, M. W., Oliver, R., Tso, C. Y., Gustafson, C., Secomb, T., and Gross, J. F. Heterogeneity in tumor microvascular response to radiation. Int J Radiat Oncol Biol Phys, 18: 559–568, 1990.

    PubMed  CAS  Google Scholar 

  84. Moeller, B. J., Cao, Y., Li, C. Y., and Dewhirst, M. W. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell, 5: 429–441, 2004.

    Article  PubMed  CAS  Google Scholar 

  85. Gilks, N., Kedersha, N., Ayodele, M., Shen, L., Stoecklin, G., Dember, L. M., and Anderson, P. Stress Granule Assembly Is Mediated by Prion-like Aggregation of TIA-1. Mol Biol Cell, 15: 5383–5398, 2004.

    Article  PubMed  CAS  Google Scholar 

  86. Kedersha, N. and Anderson, P. Stress granules: sites of mRNA triage that regulate mRNA stability and translatability. Biochem Soc Trans, 30: 963–969, 2002.

    Article  PubMed  CAS  Google Scholar 

  87. Milas, L., Hunter, N., Mason, K. A., Milross, C., and Peters, L. J. Tumor reoxygenation as a mechanism of taxol-induced enhancement of tumor radioresponse. Acta Oncol, 34: 409–412, 1995.

    Article  PubMed  CAS  Google Scholar 

  88. Vujaskovic, Z. and Song, C. W. Physiological mechanisms underlying heat-induced radiosensitization. Int J Hyperthermia, 20: 163–174, 2004.

    Article  PubMed  CAS  Google Scholar 

  89. Jones, E. L., Prosnitz, L. R., Dewhirst, M. W., Marcom, P. K., Hardenbergh, P. H., Marks, L. B., Brizel, D. M., and Vujaskovic, Z. Thermochemoradiotherapy improves oxygenation in locally advanced breast cancer. Clin Cancer Res, 10: 4287–4293, 2004.

    Article  PubMed  CAS  Google Scholar 

  90. Williams, K. J., Telfer, B. A., Xenaki, D., Sheridan, M. R., Desbaillets, I., Peters, H. J., Honess, D., Harris, A. L., Dachs, G. U., van der Kogel, A., and Stratford, I. J. Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1. Radiother Oncol, 75: 89–98, 2005.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Mark W. Dewhirst DVM, PhD
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  2. Yiting Cao MD, PhD
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  3. Gordana Vlahovic MD, MHS
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Editor information

Editors and Affiliations

  1. Genzyme Corporation, Framingham, MA

    Beverly A. Teicher PhD

  2. M. D. Anderson Cancer Center, The University of Texas, Houston, TX

    Lee M. Ellis MD

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© 2008 Humana Press

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Dewhirst, M.W., Cao, Y., Vlahovic, G. (2008). The Cycle Between Angiogenesis, Perfusion, and Hypoxia in Tumors. In: Teicher, B.A., Ellis, L.M. (eds) Antiangiogenic Agents in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-184-0_2

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  • DOI: https://doi.org/10.1007/978-1-59745-184-0_2

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-870-6

  • Online ISBN: 978-1-59745-184-0

  • eBook Packages: MedicineMedicine (R0)

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