Radiotherapy & Oncology
Volume 86, Issue 3 , Pages 300-313 , March 2008

Provascular strategy: Targeting functional adaptations of mature blood vessels in tumors to selectively influence the tumor vascular reactivity and improve cancer treatment

  • Pierre Sonveaux

      Affiliations

    • Corresponding Author InformationCorresponding author. Pierre Sonveaux, Unit of Pharmacology & Therapeutics, Université catholique de Louvain (UCL), 52 Avenue E. Mounier, B-1200 Brussels, Belgium.

Received 14 September 2007 ,Revised 30 January 2008 ,Accepted 30 January 2008.

References 

  1. Peinado MA, Malkhosyan S, Velazquez A, Perucho M. Isolation and characterization of allelic losses and gains in colorectal tumors by arbitrarily primed polymerase chain reaction. Proc Natl Acad Sci USA. 1992;89:10065–10069
  2. Gudkov AV, Komarova EA. The role of p53 in determining sensitivity to radiotherapy. Nat Rev Cancer. 2003;3:117–129
  3. Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol. 1953;26:638–648
  4. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70
  5. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407:249–257
  6. Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med. 2000;6:389–395
  7. Jain RK. Molecular regulation of vessel maturation. Nat Med. 2003;9:685–693
  8. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3:401–410
  9. Folkman J. Tumor angiogenesis. In:  Bast RC,  Kufe DW,  Pollock RE,  Weichselbaum RR,  Holland JF,  Frei E editor. Cancer medicine. 5th ed.. Hamilton, Canada: BC Decker Inc.; 2000;
  10. Kalluri R. Basement membranes: structure, assembly and role in tumour angiogenesis. Nat Rev Cancer. 2003;3:422–433
  11. Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1650–1659
  12. Jain RK. Determinants of tumor blood flow: a review. Cancer Res. 1988;48:2641–2658
  13. Eberhard A, Kahlert S, Goede V, Hemmerlein B, Plate KH, Augustin HG. Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res. 2000;60:1388–1393
  14. Lubbe AS, Huhnt W. Microvessel diameters of human colon adenocarcinoma during acute treatment with serotonin. Int J Microcirc Clin Exp. 1994;14:218–225
  15. Huhnt W, Lubbe AS. Venules and arterioles in xenotransplanted human colon adenocarcinoma critically constrict with hyperthermia and serotonin. J Cancer Res Clin Oncol. 1995;121:267–274
  16. Thews O, Kelleher DK, Vaupel PW. Modulation of spatial O2 tension distribution in experimental tumors by increasing arterial O2 supply. Acta Oncol. 1995;34:291–295
  17. Fukumura D, Yuan F, Endo M, Jain RK. Role of nitric oxide in tumor microcirculation. Blood flow, vascular permeability, and leukocyte–endothelial interactions. Am J Pathol. 1997;150:713–725
  18. Emerich DF, Snodgrass P, Dean RL, et al. Bradykinin modulation of tumor vasculature: I. Activation of B2 receptors increases delivery of chemotherapeutic agents into solid peripheral tumors, enhancing their efficacy. J Pharmacol Exp Ther. 2001;296:623–631
  19. Julien C, Payen JF, Tropres I, et al. Assessment of vascular reactivity in rat brain glioma by measuring regional blood volume during graded hypoxic hypoxia. Br J Cancer. 2004;91:374–380
  20. Kashiwagi S, Izumi Y, Gohongi T, et al. NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels. J Clin Invest. 2005;115:1816–1827
  21. Baudelet C, Cron GO, Ansiaux R, et al. The role of vessel maturation and vessel functionality in spontaneous fluctuations of T2∗-weighted GRE signal within tumors. NMR Biomed. 2006;19:69–76
  22. Mattson J, Appelgren L, Karlsson L, Peterson HI. Influence of vasoactive drugs and ischaemia on intra-tumour blood flow distribution. Eur J Cancer. 1978;14:761–764
  23. Peterson HI, Mattson J. Vasoactive drugs and tumor blood flow. Biorheology. 1984;21:503–508
  24. Dewhirst MW, Kimura H, Rehmus SW, et al. Microvascular studies on the origins of perfusion-limited hypoxia. Br J Cancer Suppl. 1996;27:S247–S251
  25. Helmlinger G, Yuan F, Dellian M, Jain RK. Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med. 1997;3:177–182
  26. Secomb TW, Hsu R, Ong ET, Gross JF, Dewhirst MW. Analysis of the effects of oxygen supply and demand on hypoxic fraction in tumors. Acta Oncol. 1995;34:313–316
  27. West CM, Cooper RA, Loncaster JA, Wilks DP, Bromley M. Tumor vascularity: a histological measure of angiogenesis and hypoxia. Cancer Res. 2001;61:2907–2910
  28. Jain RK, Baxter LT. Mechanisms of heterogeneous distribution of monoclonal antibodies and other macromolecules in tumors: significance of elevated interstitial pressure. Cancer Res. 1988;48:7022–7032
  29. Boucher Y, Baxter LT, Jain RK. Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy. Cancer Res. 1990;50:4478–4484
  30. Netti PA, Hamberg LM, Babich JW, et al. Enhancement of fluid filtration across tumor vessels: implication for delivery of macromolecules. Proc Natl Acad Sci USA. 1999;96:3137–3142
  31. Brekken C, Hjelstuen MH, Bruland OS, de Lange DC. Hyaluronidase-induced periodic modulation of the interstitial fluid pressure increases selective antibody uptake in human osteosarcoma xenografts. Anticancer Res. 2000;20:3513–3519
  32. Bouzin C, Feron O. Targeting tumor stroma and exploiting mature tumor vasculature to improve anti-cancer drug delivery. Drug Resist Updat. 2007;10:109–120
  33. Boyer MJ, Tannock IF. Regulation of intracellular pH in tumor cell lines: influence of microenvironmental conditions. Cancer Res. 1992;52:4441–4447
  34. Gatenby RA, Gawlinski ET. The glycolytic phenotype in carcinogenesis and tumor invasion: insights through mathematical models. Cancer Res. 2003;63:3847–3854
  35. Ide AG, Baker NH, Warren SL. Vascularization of the Brown–Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am J Roentgenol. 1939;42:891–899
  36. Algire GH, Chalkely HW, Legallais FY, Park H. Vascular reactions of normal and malignant tumors in vivo: I. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst. 1945;6:73–85
  37. Algire GH, Legallais FY. Growth rate of transplanted tumors in relation to latent period and host vascular reaction. Cancer Res. 1947;7:724
  38. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182–1186
  39. Good DJ, Polverini PJ, Rastinejad F, et al. A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistinguishable from a fragment of thrombospondin. Proc Natl Acad Sci USA. 1990;87:6624–6628
  40. O’Reilly MS, Holmgren L, Shing Y, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 1994;79:315–328
  41. O’Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997;88:277–285
  42. Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2002;2:795–803
  43. Kane RC, Farrell AT, Saber H, et al. Sorafenib for the treatment of advanced renal cell carcinoma. Clin Cancer Res. 2006;12:7271–7278
  44. Goodman VL, Rock EP, Dagher R, et al. Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin Cancer Res. 2007;13:1367–1373
  45. Mannavola D, Coco P, Vannucchi G, et al. A novel tyrosine-kinase selective inhibitor, sunitinib, induces transient hypothyroidism by blocking iodine uptake. J Clin Endocrinol Metab. 2007;
  46. Grandinetti CA, Goldspiel BR. Sorafenib and sunitinib: novel targeted therapies for renal cell cancer. Pharmacotherapy. 2007;27:1125–1144
  47. Lordick F, Geinitz H, Theisen J, Sendler A, Sarbia M. Increased risk of ischemic bowel complications during treatment with bevacizumab after pelvic irradiation: report of three cases. Int J Radiat Oncol Biol Phys. 2006;64:1295–1298
  48. Ewer MS, O’Shaughnessy JA. Cardiac toxicity of trastuzumab-related regimens in HER2-overexpressing breast cancer. Clin Breast Cancer. 2007;7:600–607
  49. Pande A, Lombardo J, Spangenthal E, Javle M. Hypertension secondary to anti-angiogenic therapy: experience with bevacizumab. Anticancer Res. 2007;27:3465–3470
  50. Sonveaux P, Dessy C, Martinive P, et al. Endothelin-1 is a critical mediator of myogenic tone in tumor arterioles: implications for cancer treatment. Cancer Res. 2004;64:3209–3214
  51. Regina A, Jodoin J, Khoueir P, et al. Down-regulation of caveolin-1 in glioma vasculature: modulation by radiotherapy. J Neurosci Res. 2004;75:291–299
  52. Song CW. Modification of blood flow. In:  Molls M,  Vaupel P editor. Blood perfusion and microenvironment of human tumors. Berlin, Germany: Springer-Verlag; 1998;p. 193–208
  53. Zlotecki RA, Baxter LT, Boucher Y, Jain RK. Pharmacologic modification of tumor blood flow and interstitial fluid pressure in a human tumor xenograft: network analysis and mechanistic interpretation. Microvasc Res. 1995;50:429–443
  54. Dudzinski DM, Michel T. Life history of eNOS: partners and pathways. Cardiovasc Res. 2007;75:247–260
  55. Wood PJ, Sansom JM, Stratford IJ, et al. Changes in energy metabolism and X-ray sensitivity in murine tumours by the nitric oxide donor SIN-1. Br J Cancer Suppl. 1996;27:S177–S180
  56. Jordan BF, Misson P, Demeure R, Baudelet C, Beghein N, Gallez B. Changes in tumor oxygenation/perfusion induced by the NO donor, isosorbide dinitrate, in comparison with carbogen: monitoring by EPR and MRI. Int J Radiat Oncol Biol Phys. 2000;48:565–570
  57. Jordan BF, Beghein N, Aubry M, Gregoire V, Gallez B. Potentiation of radiation-induced regrowth delay by isosorbide dinitrate in FSaII murine tumors. Int J Cancer. 2003;103:138–141
  58. Shan SQ, Rosner GL, Braun RD, Hahn J, Pearce C, Dewhirst MW. Effects of diethylamine/nitric oxide on blood perfusion and oxygenation in the R3230Ac mammary carcinoma. Br J Cancer. 1997;76:429–437
  59. Thews O, Kelleher DK, Vaupel P. No improvement in perfusion and oxygenation of experimental tumors upon application of vasodilator drugs. Int J Oncol. 2001;19:1243–1247
  60. Mitchell JB, Cook JA, Krishna MC, et al. Radiation sensitisation by nitric oxide releasing agents. Br J Cancer Suppl. 1996;27:S181–S184
  61. Mitchell JB, Wink DA, DeGraff W, Gamson J, Keefer LK, Krishna MC. Hypoxic mammalian cell radiosensitization by nitric oxide. Cancer Res. 1993;53:5845–5848
  62. Jordan BF, Sonveaux P, Feron O, et al. Nitric oxide as a radiosensitizer: evidence for an intrinsic role in addition to its effect on oxygen delivery and consumption. Int J Cancer. 2004;109:768–773
  63. Wardman P, Rothkamm K, Folkes LK, Woodcock M, Johnston PJ. Radiosensitization by nitric oxide at low radiation doses. Radiat Res. 2007;167:475–484
  64. Feron O. Targeting the tumor vascular compartment to improve conventional cancer therapy. Trends Pharmacol Sci. 2004;25:536–542
  65. Sonveaux P, Dessy C, Brouet A, et al. Modulation of the tumor vasculature functionality by ionizing radiation accounts for tumor radiosensitization and promotes gene delivery. FASEB J. 2002;16:1979–1981
  66. Tan J, Hallahan DE. Growth factor-independent activation of protein kinase B contributes to the inherent resistance of vascular endothelium to radiation-induced apoptotic response. Cancer Res. 2003;63:7663–7667
  67. Brouet A, Sonveaux P, Dessy C, Balligand JL, Feron O. Hsp90 ensures the transition from the early Ca2+-dependent to the late phosphorylation-dependent activation of the endothelial nitric-oxide synthase in vascular endothelial growth factor-exposed endothelial cells. J Biol Chem. 2001;276:32663–32669
  68. Sonveaux P, Brouet A, Havaux X, et al. Irradiation-induced angiogenesis through the up-regulation of the nitric oxide pathway: implications for tumor radiotherapy. Cancer Res. 2003;63:1012–1019
  69. Sonveaux P, Frerart F, Bouzin C, et al. Irradiation promotes Akt-targeting therapeutic gene delivery to the tumor vasculature. Int J Radiat Oncol Biol Phys. 2007;67:1155–1162
  70. Gorski DH, Beckett MA, Jaskowiak NT, et al. Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res. 1999;59:3374–3378
  71. Moeller BJ, Cao Y, Li CY, Dewhirst MW. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell. 2004;5:429–441
  72. Li F, Sonveaux P, Rabbani ZN, et al. Regulation of HIF-1alpha stability through S-nitrosylation. Mol Cell. 2007;26:63–74
  73. Jia L, Bonaventura C, Bonaventura J, Stamler JS. S-Nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature. 1996;380:221–226
  74. Sonveaux P, Lobysheva II, Feron O, McMahon TJ. Transport and peripheral bioactivities of nitrogen oxides carried by red blood cell hemoglobin: role in oxygen delivery. Physiology. 2007;22:97–112
  75. Lee R, Neya K, Svizzero TA, Vlahakes GJ. Limitations of the efficacy of hemoglobin-based oxygen-carrying solutions. J Appl Physiol. 1995;79:236–242
  76. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA. 1987;84:9265–9269
  77. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524–526
  78. Sonveaux P, Kaz AM, Snyder SA, et al. Oxygen regulation of tumor perfusion by S-nitrosohemoglobin reveals a pressor activity of nitric oxide. Circ Res. 2005;96:1119–1126
  79. Alayash AI. Oxygen therapeutics: can we tame haemoglobin?. Nat Rev Drug Discov. 2004;3:152–159
  80. Moya MP, Gow AJ, McMahon TJ, et al. S-Nitrosothiol repletion by an inhaled gas regulates pulmonary function. Proc Natl Acad Sci USA. 2001;98:5792–5797
  81. Moya MP, Gow AJ, Califf RM, Goldberg RN, Stamler JS. Inhaled ethyl nitrite gas for persistent pulmonary hypertension of the newborn. Lancet. 2002;360:141–143
  82. McMahon TJ, Ahearn GS, Moya MP, et al. A nitric oxide processing defect of red blood cells created by hypoxia: deficiency of S-nitrosohemoglobin in pulmonary hypertension. Proc Natl Acad Sci USA. 2005;102:14801–14806
  83. Vaupel P, Harrison L. Tumor hypoxia: causative factors, compensatory mechanisms, and cellular response. Oncologist. 2004;9:4–9
  84. Jordan BF, Gregoire V, Demeure RJ, et al. Insulin increases the sensitivity of tumors to irradiation: involvement of an increase in tumor oxygenation mediated by a nitric oxide-dependent decrease of the tumor cells oxygen consumption. Cancer Res. 2002;62:3555–3561
  85. Jordan BF, Beghein N, Crokart N, Baudelet C, Gregoire V, Gallez B. Preclinical safety and antitumor efficacy of insulin combined with irradiation. Radiother Oncol. 2006;81:112–117
  86. Jordan BF, Sonveaux P, Feron O, Gregoire V, Beghein N, Gallez B. Nitric oxide-mediated increase in tumor blood flow and oxygenation of tumors implanted in muscles stimulated by electric pulses. Int J Radiat Oncol Biol Phys. 2003;55:1066–1073
  87. Ansiaux R, Baudelet C, Cron GO, et al. Botulinum toxin potentiates cancer radiotherapy and chemotherapy. Clin Cancer Res. 2006;12:1276–1283
  88. Sonveaux P, Feron O. Nitric oxide and tumor biology. In:  Lamas S,  Cadenas E editor. Nitric oxide, cell signaling, and gene expression. Boca Raton, USA: CRC Press; 2005;p. 393–418
  89. Haynes WG, Webb DJ. Contribution of endogenous generation of endothelin-1 to basal vascular tone. Lancet. 1994;344:852–854
  90. Maguire JJ, Davenport AP. ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro. Br J Pharmacol. 1995;115:191–197
  91. Nelson J, Bagnato A, Battistini B, Nisen P. The endothelin axis: emerging role in cancer. Nat Rev Cancer. 2003;3:110–116
  92. Battistini B, Chailler P, D’Orleans-Juste P, Briere N, Sirois P. Growth regulatory properties of endothelins. Peptides. 1993;14:385–399
  93. Andrade SP, Beraldo WT. Pharmacological reactivity of neoplastic and non-neoplastic associated neovasculature to vasoconstrictors. Int J Exp Pathol. 1998;79:425–432
  94. Bell KM, Prise VE, Shaffi KM, Chaplin DJ, Tozer GM. A comparative study of tumour blood flow modification in two rat tumour systems using endothelin-1 and angiotensin II: influence of tumour size on angiotensin II response. Int J Cancer. 1996;67:730–738
  95. Bell KM, Prise VE, Chaplin DJ, Wordsworth S, Tozer GM. Vascular response of tumour and normal tissues to endothelin-1 following antagonism of ET(A) and ET(B) receptors in anaesthetised rats. Int J Cancer. 1997;73:283–289
  96. Rai A, Gulati A. Evidence for the involvement of ET(B) receptors in ET-1-induced changes in blood flow to the rat breast tumor. Cancer Chemother Pharmacol. 2003;51:21–28
  97. Aliev G, Smith MA, Seyidova D, et al. Increased expression of NOS and ET-1 immunoreactivity in human colorectal metastatic liver tumours is associated with selective depression of constitutive NOS immunoreactivity in vessel endothelium. J Submicrosc Cytol Pathol. 2002;34:37–50
  98. Martinive P, De Wever J, Bouzin C, et al. Reversal of temporal and spatial heterogeneities in tumor perfusion identifies the tumor vascular tone as a tunable variable to improve drug delivery. Mol Cancer Ther. 2006;5:1620–1627
  99. Yuan F, Dellian M, Fukumura D, et al. Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Res. 1995;55:3752–3756
  100. Rosano L, Spinella F, Salani D, et al. Therapeutic targeting of the endothelin a receptor in human ovarian carcinoma. Cancer Res. 2003;63:2447–2453
  101. Donckier JE, Mertens-Strijthagen J, Flamion B. Role of the endothelin axis in the proliferation of human thyroid cancer cells. Clin Endocrinol. 2007;
  102. Thakkar SG, Choueiri TK, Garcia JA. Endothelin receptor antagonists: rationale, clinical development, and role in prostate cancer therapeutics. Curr Oncol Rep. 2006;8:108–113
  103. Kefford R, Beith JM, Van Hazel GA, et al. A phase II study of bosentan, a dual endothelin receptor antagonist, as monotherapy in patients with stage IV metastatic melanoma. Invest New Drugs. 2007;25:247–252
  104. Young D. New drug approved for pulmonary arterial hypertension. Am J Health Syst Pharm. 2007;64:1562
  105. Trotter MJ, Chaplin DJ, Olive PL. Effect of angiotensin II on intermittent tumour blood flow and acute hypoxia in the murine SCCVII carcinoma. Eur J Cancer. 1991;27:887–893
  106. Suzuki M, Hori K, Abe I, Saito S, Sato H. A new approach to cancer chemotherapy: selective enhancement of tumor blood flow with angiotensin II. J Natl Cancer Inst. 1981;67:663–669
  107. Thews O, Kelleher DK, Vaupel P. Disparate responses of tumour vessels to angiotensin II: tumour volume-dependent effects on perfusion and oxygenation. Br J Cancer. 2000;83:225–231
  108. Kato T, Murakami Y, Saito Y, et al. New modality of radiation therapy under increased tumor oxygen tension with angiotensin II: a pilot study. Radiat Med. 1993;11:86–90
  109. Ohigashi H, Ishikawa O, Yokayama S, et al. Intra-arterial infusion chemotherapy with angiotensin-II for locally advanced and nonresectable pancreatic adenocarcinoma: further evaluation and prognostic implications. Ann Surg Oncol. 2003;10:927–934
  110. Ishikawa T, Ushiki T, Kamimura H, et al. Angiotensin-II administration is useful for the detection of liver metastasis from pancreatic cancer during pharmacoangiographic computed tomography. World J Gastroenterol. 2007;13:3080–3083
  111. Ino K, Shibata K, Kajiyama H, Nawa A, Nomura S, Kikkawa F. Manipulating the angiotensin system – new approaches to the treatment of solid tumours. Expert Opin Biol Ther. 2006;6:243–255
  112. Wood PJ, Hirst DG. Modification of tumour response by calcium antagonists in the SCVII/St tumour implanted at two different sites. Int J Radiat Biol. 1989;56:355–367
  113. Vaupel P, Menke H. Effects of various calcium antagonists on blood flow and red blood cell flux in malignant tumors. Prog Appl Microcirc. 1989;14:88–103
  114. Dewhirst MW, Ong ET, Madwed D, et al. Effects of the calcium channel blocker flunarizine on the hemodynamics and oxygenation of tumor microvasculature. Radiat Res. 1992;132:61–68
  115. Kavanagh BD, Coffey BE, Needham D, Hochmuth RM, Dewhirst MW. The effect of flunarizine on erythrocyte suspension viscosity under conditions of extreme hypoxia, low pH, and lactate treatment. Br J Cancer. 1993;67:734–741
  116. Jirtle RL. Chemical modification of tumour blood flow. Int J Hyperthermia. 1988;4:355–371
  117. Bellamy WT, Dalton WS, Kailey JM, et al. Verapamil reversal of doxorubicin resistance in multidrug-resistant human myeloma cells and association with drug accumulation and DNA damage. Cancer Res. 1988;48:6365–6370
  118. Ozols RF, Cunnion RE, Klecker RW, et al. Verapamil and adriamycin in the treatment of drug-resistant ovarian cancer patients. J Clin Oncol. 1987;5:641–647
  119. Perez-Tomas R. Multidrug resistance: retrospect and prospects in anti-cancer drug treatment. Curr Med Chem. 2006;13:1859–1876
  120. Trotter MJ, Acker BD, Chaplin DJ. Histological evidence for nonperfused vasculature in a murine tumor following hydralazine administration. Int J Radiat Oncol Biol Phys. 1989;17:785–789
  121. Kalmus J, Okunieff P, Vaupel P. Dose-dependent effects of hydralazine on microcirculatory function and hyperthermic response of murine FSall tumors. Cancer Res. 1990;50:15–19
  122. Belfi CA, Paul CR, Shan S, Ngo FQ. Comparison of the effects of hydralazine on tumor and normal tissue blood perfusion by MRI. Int J Radiat Oncol Biol Phys. 1994;29:473–479
  123. Hasegawa T, Song CW. Effect of hydralazine on the blood flow in tumors and normal tissues in rats. Int J Radiat Oncol Biol Phys. 1991;20:1001–1007
  124. Bremner JC, Stratford IJ, Bowler J, Adams GE. Bioreductive drugs and the selective induction of tumour hypoxia. Br J Cancer. 1990;61:717–721
  125. Patterson LH, McKeown SR, Ruparelia K, et al. Enhancement of chemotherapy and radiotherapy of murine tumours by AQ4N, a bioreductively activated anti-tumour agent. Br J Cancer. 2000;82:1984–1990
  126. Horsman MR, Christensen KL, Overgaard J. Hydralazine-induced enhancement of hyperthermic damage in a C3H mammary carcinoma in vivo. Int J Hyperthermia. 1989;5:123–136
  127. Quinn PK, Bibby MC, Cox JA, Crawford SM. The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours. Br J Cancer. 1992;66:323–330
  128. Guichard M, Lespinasse F, Trotter M, Durand R, Chaplin D. The effect of hydralazine on blood flow and misonidazole toxicity in human tumour xenografts. Radiother Oncol. 1991;20:117–123
  129. Bhujwalla ZM, Tozer GM, Field SB, Maxwell RJ, Griffiths JR. The energy metabolism of RIF-1 tumours following hydralazine. Radiother Oncol. 1990;19:281–291
  130. Stone HB, Minchinton AI, Lemmon M, Menke D, Brown JM. Pharmacological modification of tumor blood flow: lack of correlation between alteration of mean arterial blood pressure and changes in tumor perfusion. Int J Radiat Oncol Biol Phys. 1992;22:79–86
  131. Honess DJ, Bleehen NM. Comparative effects of hydralazine on perfusion of KHT tumor, kidney and liver and on renal function in mice. Int J Radiat Oncol Biol Phys. 1992;22:953–961
  132. Dewhirst MW, Prescott DM, Clegg S, et al. The use of hydralazine to manipulate tumour temperatures during hyperthermia. Int J Hyperthermia. 1990;6:971–983
  133. Rowell NP, Flower MA, McCready VR, Cronin B, Horwich A. The effects of single dose oral hydralazine on blood flow through human lung tumours. Radiother Oncol. 1990;18:283–292
  134. Dewhirst MW, Vujaskovic Z, Jones E, Thrall D. Re-setting the biologic rationale for thermal therapy. Int J Hyperthermia. 2005;21:779–790
  135. Wust P, Hildebrandt B, Sreenivasa G, et al. Hyperthermia in combined treatment of cancer. Lancet Oncol. 2002;3:487–497
  136. Song CW, Shakil A, Osborn JL, Iwata K. Tumour oxygenation is increased by hyperthermia at mild temperatures. Int J Hyperthermia. 1996;12:367–373
  137. Rau B, Wust P, Tilly W, et al. Preoperative radiochemotherapy in locally advanced or recurrent rectal cancer: regional radiofrequency hyperthermia correlates with clinical parameters. Int J Radiat Oncol Biol Phys. 2000;48:381–391
  138. Calcutt G, Ting SM, Preece AV. Tissue NAD levels and the response to irradiation of cytotoxic drugs. Br J Cancer. 1970;24:380–388
  139. Masunaga S, Ono K, Akuta K, et al. Enhancement of chemosensitivity of quiescent cell populations in murine solid tumors using nicotinamide. Chemotherapy. 1994;40:418–426
  140. Kelleher DK, Vaupel PW. Possible mechanisms involved in tumor radiosensitization following nicotinamide administration. Radiother Oncol. 1994;32:47–53
  141. Peters CE, Chaplin DJ, Hirst DG. Nicotinamide reduces tumour interstitial fluid pressure in a dose- and time-dependent manner. Br J Radiol. 1997;70:160–167
  142. Braun RD, Lanzen JL, Snyder SA, Dewhirst MW. Comparison of tumor and normal tissue oxygen tension measurements using OxyLite or microelectrodes in rodents. Am J Physiol Heart Circ Physiol. 2001;280:H2533–H2544
  143. Kaanders JH, Bussink J, van der Kogel AJ. ARCON: a novel biology-based approach in radiotherapy. Lancet Oncol. 2002;3:728–737
  144. Warren K, Jakacki R, Widemann B, et al. Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors: a report from the Children’s Oncology Group. Cancer Chemother Pharmacol. 2006;58:343–347
  145. Emerich DF, Dean RL, Snodgrass P, et al. Bradykinin modulation of tumor vasculature: II. Activation of nitric oxide and phospholipase A2/prostaglandin signaling pathways synergistically modifies vascular physiology and morphology to enhance delivery of chemotherapeutic agents to tumors. J Pharmacol Exp Ther. 2001;296:632–641
  146. Jirtle R, Clifton KH, Rankin JH. Effects of several vasoactive drugs on the vascular resistance of MT-W9B tumors in W/Fu rats. Cancer Res. 1978;38:2385–2390
  147. Fukumura D, Jain RK. Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize. J Cell Biochem. 2007;101:937–949
  148. Kaanders JH, Bussink J, van der Kogel AJ. Clinical studies of hypoxia modification in radiotherapy. Semin Radiat Oncol. 2004;14:233–240
  149. Olive PL, Aquino-Parsons C. Measurement of tumor hypoxia using single-cell methods. Semin Radiat Oncol. 2004;14:241–248
  150. Jordan BF, Galon JP, Gillies RJ. Post-treatment changes in tumor microenvironment: dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. In:  Hayat MA editors. Cancer imaging: instrumentation and applications. Burlington, USA: Academic Press; 2008;p. 235–248

PII: S0167-8140(08)00085-6

doi: 10.1016/j.radonc.2008.01.024

Radiotherapy & Oncology
Volume 86, Issue 3 , Pages 300-313 , March 2008

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