How to Overcome (and Exploit) Tumor Hypoxia for Targeted Gene Therapy

Journal of Cellular Physiology

Volumn 197, Issue 3, 2003, Pages 312-325

  Greco, Olga ^a   Marples, Brian ^a   Joiner, Michael C ^a   Scott, Simon D ^a  

^a WAYNE STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBOGEN; CYTOTOXIC AGENT; HYPOXIA INDUCIBLE FACTOR 1; NICOTINAMIDE; OXYGEN; PRODRUG; RADIOSENSITIZING AGENT; TRANSCRIPTION FACTOR;

ANAEROBIC METABOLISM; ANGIOGENESIS; BLOOD VESSEL PERMEABILITY; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER SURGERY; CLINICAL PROTOCOL; DRUG ACTIVATION; GENE ACTIVATION; GENE AMPLIFICATION; GENE EXPRESSION; GENE TARGETING; GENE THERAPY; GENETIC TRANSCRIPTION; HUMAN; HYPERBARIC OXYGEN; HYPOXIA; INFLAMMATION; IONIZING RADIATION; MOLECULAR GENETICS; OXYGEN TRANSPORT; PRIORITY JOURNAL; PROTEIN BINDING; REVIEW; SUICIDE GENE; TRANSGENE; TREATMENT OUTCOME;

ANIMALS; ANOXIA; DNA-BINDING PROTEINS; DRUG RESISTANCE, NEOPLASM; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE THERAPY; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; NEOPLASMS; NUCLEAR PROTEINS; RADIOTHERAPY, ADJUVANT; TRANS-ACTIVATION (GENETICS); TRANSCRIPTION FACTORS;

EID: 0345257217     PISSN: 00219541     EISSN: None     Source Type: Journal    
DOI: 10.1002/jcp.10374     Document Type: Review

References (202)

1. Adams GE, Cooke MS. 1969. Electron-affinic sensitization. A structural basis for chemical radiosensitizers in bacteria. Int J Radiat Biol 15:457-471.
2. Adams GE, Asquith JC, Watts ME, Smithen CE. 1972. Radiosensitization of hypoxic cells in vitro: A water-soluble derivative of paranitroacetophenone. Nat New Biol 239:23-24.
3. Aebersold DM, Burri P, Beer KT, Laissue J, Djonov V, Greiner RH, Semenza GL. 2001. Expression of hypoxia-inducible factor-1alpha: A novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer. Cancer Res 61:2911-2916.
4. Airley R, Loncaster J, Davidson S, Bromley M, Roberts S, Patterson A. Hunter R, Stratford I, West C. 2001. Glucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis free survival in advanced carcinoma of the cervix. Clin Cancer Res 7:928-934.
5. Airley RE, Loncaster J, Raleigh JA, Harris AL, Davidson SE, Hunter RD, West CM, Stratford IJ. 2003. GLUT-1 and CAIX as intrinsic markers of hypoxia in carcinoma of the cervix: Relationship to pimonidazole binding. Int J Cancer 104:85-91.
6. Alarcon RM, Rupnow BA, Graeber TG, Knox SJ, Giaccia AJ. 1996. Modulation of c-Myc activity and apoptosis in vivo. Cancer Res 56:4315-4319.
7. Amellem O, Pettersen EO. 1991. Cell inactivation and cell cycle inhibition as induced by extreme hypoxia: The possible role of cell cycle arrest as a protection against hypoxia-induced lethal damage. Cell Prolif 24:127-141.
8. Arteel GE, Thurman RG, Yates JM, Raleigh JA. 1995. Evidence that hypoxia markers detect oxygen gradients in liver: Pimonidazole and retrograde perfusion of rat liver. Br J Cancer 72:889-895.
9. Beck I, Weinmann R, Caro J. 1993. Characterization of hypoxia-responsive enhancer in the human erythropoietin gene shows presence of hypoxia-inducible 120-kDa nuclear DNA-binding protein in erythropoietin-producing and nonproducing cells. Blood 82:704-711.
10. Becker A, Hansgen G, Bloching M, Weigel C, Lautenschlager C, Dunst J. 1998. Oxygenation of squamous cell carcinoma of the head and neck: Comparison of primary tumors, neck node metastases, and normal tissue. Int J Radiat Oncol Biol Phys 42:35-41.
11. Benjamin IJ, Kroger B, Williams RS. 1990. Activation of the heat shock transcription factor by hypoxia in mammalian cells. Proc Natl Acad Sci USA 87:6263-6267.
12. Bernier J, Denekamp J, Rojas A, Minatel E, Horiot J, Hamers H, Antognoni P, Dahl O, Richaud P, van Glabbeke M, Pierart M. 2000. ARCON: Accelerated radiotherapy with carbogen and nicotinamide in head and neck squamous cell carcinomas. The experience of the co-operative group of radiotherapy of the european organization for research and treatment of cancer (EORTC). Radiother Oncol 55:111-119.
13. Binley K, Askham Z, Martin L, Spearman H, Day D, Kingsman S, Naylor S. 2003. Hypoxia-mediated tumour targeting. Gene Ther 10:540-549.
14. Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Oberhuber G. 2000. Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res 60:4693-4696.
15. Birner P, Schindl M, Obermair A, Breiteneeker G, Oberhuber G. 2001. Expression of hypoxia-inducible factor 1alpha in epithelial ovarian tumors: Its impact on prognosis and on response to chemotherapy. Clin Cancer Res 7:1661-1668.
16. Blancher C, Moore JW, Talks KL, Houlbrook S, Harris AL. 2000. Relationship of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression to vascular endothelial growth factor induction and hypoxia survival in human breast cancer cell lines. Cancer Res 60:7106-7113.
17. Boast K, Binley K, Iqball S, Price T, Spearman H, Kingsman S, Kingsman A, Naylor S. 1999. Characterization of physiologically regulated vectors for the treatment of ischemic disease. Hum Gene Ther 10:2197-2208.
18. Boyer P, Chance B, Ernester L, Mitchell P, Racker E, Slater EC. 1977. Oxidative phosphorylation and photo phosphorylation. Annu Rev Biochem 46:955-1026.
19. Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Bean JM, Prosnitz LR, Dewhirst MW. 1996. Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56:941-943.
20. Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW. 1997. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 38:285-289.
21. Brizel DM, Dodge RK, Clough RW, Dewhirst MW. 1999. Oxygenation of head and neck cancer: Changes during radiotherapy and impact on treatment outcome. Radiother Oncol 53:113-117.
22. Brizel DM, Schroeder T, Scher RL, Walenta S, Clough RW, Dewhirst MW, Mueller-Klieser W. 2001. Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol Biol Phys 51:349-353.
23. Brown JM. 1975. Selective radiosensitization of the hypoxic cells of mouse tumours with the nitroimidazoles metronidazole and Ro 7-0582. Radiat Res 64:633-647.
24. Brown JM. 1979. Evidence for autely hypoxic cells in mouse tumours and a possible mechanism of reoxygenation. 52:650-656.
25. Brown JM, Giaccia AJ. 1998. The unique physiology of solid tumors: Opportunities (and problems) for cancer therapy. Cancer Res 58:1408-1416.
26. Brown JM, Wang LH. 1998. Tirapazamine: Laboratory data relevant to clinical activity. Anticancer Drug Des 13:529-539.
27. Burke B, Tang N, Corke KP, Tazzyman D, Ameri K, Wells M, Lewis CE. 2002. Expression of HIF-1alpha by human macrophages: Implications for the use of macrophages in hypoxia-regulated cancer gene therapy. J Pathol 196:204-212.
28. Cairns RA, Kalliomaki T, Hill RP. 2001. Acute (cyclic) hypoxia enhances spontaneous metastasis of KHT murine tumors. Cancer Res 61:8903-8908.
29. Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R, Maxwell P, Koch CJ, Ratcliffe P, Moons L, Jain RK, Collen D, Keshert E, Keshet E. 1998. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394:485-490.
30. Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, Schumacker PT. 1998. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci USA 95:11715-11720.
31. Chaplin DJ, Olive PL, Durand RE. 1987. Intermittent blood flow in a murine tumor: Radiobiological effects. Cancer Res 47:597-601.
32. Chaplin DJ, Acker B, Olive PL. 1989. Potentiation of the tumor cytotoxicity of melphalan by vasodilating drugs. Int J Radiat Oncol Biol Phys 16:1131-1135.
33. Chaplin DJ, Horsman MR, Trotter MJ. 1990. Effect of nicotinamide on the microregional heterogeneity of oxygen delivery within a murine tumor. J Natl Cancer Inst 82:672-676.
34. Chaplin DJ, Horsman MR, Trotter M, Siemann D. 1998. Therapeutic significance of microenvironmental factors. In: Molls M, Vaupel P, editors. Blood perfusion and microenvironment of human tumours. Berlin: Springer-Verlag, pp 133-143.
35. Chapman JD, Baer K, Lee J. 1983. Characteristics of the metabolism-induced binding of misonidazole to hypoxic mammalian cells. Cancer Res 43:1523-1528.
36. Churchill-Davidson I. 1968. Hyperbaric oxygen and radiotherapy: Clinical experiences. Front Radiat Ther Oncol 1:156-161.
37. Collingridge DR, Young WK, Vojnovic B, Wardman P, Lynch EM, Hill SA, Chaplin DJ. 1997. Measurement of tumor oxygenation: A comparison between polarographic needle electrodes and a time-resolved luminescence-based optical sensor. Radiat Res 147:329-334.
38. Collingridge DR, Hill SA, Chaplin DJ. 2001. Proportion of infiltrating IgG-binding immune cells predict for tumour hypoxia. Br J Cancer 84:626-630.
39. Craighead PS, Pearcey R, Stuart G. 2000. A phase I/II evaluation of tirapazamine administered intravenously concurrent with cisplatin and radiotherapy in women with locally advanced cervical cancer. Int J Radiat Oncol Biol Phys 48:791-795.
40. Dachs GU, Patterson AV, Firth JD, Ratcliffe PJ, Townsend KM, Stratford IJ, Harris AL. 1997. Targeting gene expression to hypoxic tumor cells. Nat Med 3:515-520.
41. Dark GG, Hill SA, Prise VE, Tozer GM, Pettit GR, Chaplin DJ. 1997. Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. Cancer Res 57:1829-1834.
42. Datta R, Rubin E, Sukhatme V, Qureshi S, Hallahan D, Weichselbaum RR, Kufe DW. 1992. Ionizing radiation activates transcription of the EGR1 gene via CArG elements. Proc Natl Acad Sci USA 89:10149-10153.
43. Datta R, Taneja N, Sukhatme VP, Qureshi SA, Weichselbaum R, Kufe DW. 1993. Reactive oxygen intermediates target CC(A/T)6GG sequences to mediate activation of the early growth response 1 transcription factor gene by ionizing radiation. Proc Natl Acad Sci USA 90:2419-2422.
44. Del Rowe J, Scott C, Werner-Wasik M, Bahary JP, Curran WJ, Urtasun RC, Fisher B. 2000. Single-arm, open-label phase II study of intravenously administered tirapazamine and radiation therapy for glioblastoma multiforme. J Clin Oncol 18:1254-1259.
45. Dische S. 1985. Chemical sensitizers for hypoxic cells: A decade of experience in clinical radiotherapy. Radiother Oncol 3:97-115.
46. Durand RE, Raleigh JA. 1998. Identification of nonproliferating but viable hypoxic tumor cells in vivo. Cancer Res 58:3547-3550.
47. Evans SM, Hahn SM, Magarelli DP, Zhang PJ, Jenkins WT, Fraker DL, Hsi RA, McKenna WG, Koch CJ. 2001. Hypoxia in human intraperitoneal and extremity sarcomas. Int J Radiat Oncol Biol Phys 49:587-596.
48. Firth JD, Ebert BL, Pugh CW, Ratcliffe PJ. 1994. Oxygen-regulated control elements in the phosphoglycerate kinase 1 and lactate dehydrogenase A genes: Similarities with the erythropoietin 3′ enhancer. Proc Natl Acad Sci USA 91:6496-6500.
49. Fox ME, Lemmon MJ, Mauchline ML, Davis TO, Giaccia AJ, Minton NP, Brown JM. 1996. Anaerobic bacteria as a delivery system for cancer gene therapy: In vitro activation of 5-fluorocytosine by genetically engineered clostridia. Gene Ther 3:173-178.
50. Freytag SO, Khil M, Stricker H, Peabody J, Menon M, DePeralta-Venturina M, Nafziger D, Pegg J, Paielli D, Brown S, Barton K, Lu M, Aguilar-Cordova E, Kim JH. 2002. Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. Cancer Res 62:4968-4976.
51. Fyles AW, Milosevic M, Wong R, Kavanagh MC, Pintilie M, Sun A, Chapman W, Levin W, Manchul L, Keane TJ, Hill RP. 1998. Oxygenation predicts radiation response and survival in patients with cervix cancer. Radiother Oncol 48:149-156.
52. Fyles A, Milosevic M, Hedley D, Pintilie M, Levin W, Manchul L, Hill RP. 2002. Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer. J Clin Oncol 20:680-687.
53. Giaccia AJ. 1996. Hypoxic stress proteins: Survival of the fittest. Semin Radiat Oncol 6:46-58.
54. Giatromanolaki A, Koukourakis MI, Sivridis E, Turley H, Talks K, Pezzella F, Gatter KC, Harris AL. 2001. Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non-small cell lung cancer to angiogenic/ molecular profile of tumours and survival. Br J Cancer 85:881-890.
55. Goldberg MA, Glass GA, Cunningham JM, Bunn HF. 1987. The regulated expression of erythropoietin by two human hepatoma cell lines. Proc Natl Acad Sci USA 84:7972-7976.
56. 1-phase checkpoint by low-oxygen conditions is independent of p53 status. Mol Cell Biol 14:6264-6277.
57. Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ. 1996. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379:88-91.
58. Graham CH, Forsdike J, Fitzgerald CJ, Macdonald-Goodfellow S. 1999. Hypoxia-mediated stimulation of carcinoma cell invasiveness via upregulation of urokinase receptor expression. Int J Cancer 80:617-623.
59. Grau C, Overgaard J. 1988. Effect of cancer chemotherapy on the hypoxic fraction of a solid tumor measured using a local tumor control assay. Radiother Oncol 13:301-309.
60. Gray LH, Conger AO, Ebert M, Hornsey S, Scott OCA. 1953. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 26:638-648.
61. Greco O, Dachs GU. 2001. Gene directed enzyme/prodrug therapy of cancer: Historical appraisal and future prospectives. J Cell Physiol 187:22-36.
62. Greco O, Folkes LK, Wardman P, Tozer GM, Dachs GU. 2000a. Development of a novel enzyme/prodrug combination for gene therapy of cancer: Horseradish peroxidase/indole-3-acetic acid. Cancer Gene Ther 7:1414-1420.
63. Greco O, Patterson AV, Dachs GU. 2000b. Can gene therapy overcome the problem of hypoxia in radiotherapy? J Radiat Res 41:201-212.
64. Greco O, Rossiter S, Kanthou C, Folkes LK, Wardman P, Tozer GM, Dachs GU. 2001. Horseradish peroxidase-mediated gene therapy: Choice of prodrugs in oxic and anoxic tumour conditions. Mol Cancer Therap 1:151-160.
65. Greco O, Marples B, Dachs GU, Williams KJ, Patterson AV, Scott SD. 2002a. Novel chimeric gene promoters responsive to hypoxia and ionizing radiation. Gene Ther 9:1403-1411.
66. Greco O, Tozer GM, Dachs GU. 2002b. Oxic and anoxic enhancement of radiation-mediated toxicity by horseradish peroxidase/indole-3-acetic acid gene therapy. Int J Radiat Biol 78:173-181.
67. Greco O, Scott SD, Marples B, Dachs GU. 2002c. Cancer gene therapy: 'Delivery, delivery, delivery.' Front Biosci 7:d1516-d1524.
68. Greco O, Marples B, Joiner MC, Scott SD. 2003. Gene therapy vectors activated by hypoxia and ionizing radiation. Proc Am Assoc Cancer Res 44:1263.
69. Griffiths JR. 1991. Are cancer cells acidic? Br J Cancer 64:425-427.
70. Griffiths L, Binley K, Iqball S, Kan O, Maxwell P, Ratcliffe P, Lewis C, Harris A, Kingsman S, Naylor S. 2000. The macrophage - A novel system to deliver gene therapy to pathological hypoxia. Gene Ther 7:255-262.
71. Gu YZ, Moran SM, Hogenesch JB, Wartman L, Bradfield CA. 1998. Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha. Gene Expr 7:205-213.
72. Haensgen G, Krause U, Becker A, Stadler P, Lautenschlaeger C, Wohlrab W, Rath FW, Molls M, Dunst J. 2001. Tumor hypoxia, p53, and prognosis in cervical cancers. Int J Radiat Oncol Biol Phys 50:865-872.
73. Haffty BG, Son YH, Papac R, Sasaki CT, Weissberg JB, Fischer D, Rockwell S, Sartorelli AC, Fischer JJ. 1997. Chemotherapy as an adjunct to radiation in the treatment of squamous cell carcinoma of the head and neck: Results of the Yale mitomycin randomized trials. J Clin Oncol 15:268-276.
74. Hall EJ. 2000. Radiobiology for the radiologist. Philadelphia: Lippincott Williams and Wilkins. 588 p.
75. Hallahan DE, Mauceri HJ, Seung LP, Dunphy EJ, Wayne JD, Hanna NN, Toledano A, Hellman S, Kufe DW, Weichselbaum RR. 1995. Spatial and temporal control of gene therapy using ionizing radiation. Nat Med 1:786-791.
76. Hasan NM, Adams GE, Joiner MC, Marshall JF, Hart IR. 1998. Hypoxia facilitates tumour cell detachment by reducing expression of surface adhesion molecules and adhesion to extracellular matrices without loss of cell viability. Br J Cancer 77:1799-1805.
77. Haugland HK, Vukovic V, Pintilie M, Fyles AW, Milosevic M, Hill RP, Hedley DW. 2002. Expression of hypoxia-inducible factor-1alpha n cervical carcinomas: Correlation with tumor oxygenation. Int J Radiat Oncol Biol Phys 53:854-861.
78. Hill RP, Gulyas S, Whitmore GF. 1986. Studies of the in vivo and in vitro cytotoxicity of the drug RSU-1069. Br J Cancer 53:743-751.
79. Hill SA, Pigott KH, Saunders MI, Powell ME, Arnold S, Obeid A, Ward G, Leahy M, Hoskin PJ, Chaplin DJ. 1996. Microregional blood flow in murine and human tumours assessed using laser Doppler microprobes. Br J Cancer Suppl 27:S260-S263.
80. Hockel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P. 1996. Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56:4509-4515.
81. Hockel M, Schlenger K, Hockel S, Vaupel P. 1999. Hypoxic cervical cancers with low apoptotic index are highly aggressive. Cancer Res 59:4525-4528.
82. Hollander AP, Corke KP, Freemont AJ, Lewis CE. 2001. Expression of hypoxia-inducible factor 1alpha by macrophages in the rheumatoid synovium: Implications for targeting of therapeutic genes to the inflamed joint. Arthritis Rheum 44:1540-1544.
83. Hopfl G, Wenger RH, Ziegler U, Stallmach T, Gardelle O, Achermann R, Wergin M, Kaser-Hotz B, Saunders HM, Williams KJ, Stratford IJ, Gassmann M, Desbaillets I. 2002. Rescue of hypoxia-inducible factor-1alpha-deficient tumor growth by wild-type cells is indepen- dent of vascular endothelial growth factor. Cancer Res 62:2962-2970.
84. Hoskin PJ, Saunders MI, Phillips H, Cladd H, Powell ME, Goodchild K, Stratford MR, Rojas A. 1997. Carbogen and nicotinamide in the treatment of bladder cancer with radical radiotherapy. Br J Cancer 76:260-263.
85. Hoskin PJ, Saunders MI, Dische S. 1999. Hypoxic radiosensitizers in radical radiotherapy for patients with bladder carcinoma: Hyper- baric oxygen, misonidazole, and accelerated radiotherapy, carbogen, and nicotinamide. Cancer 86:1322-1328.
86. Huang LE, Arany Z, Livingston DM, Bunn HF. 1996. Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit. J Biol Chem 271:32253-32259.
87. 2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci USA 95:7987-7992.
88. Hughes CS, Shen JW, Subjeck JR. 1989. Resistance to etopos de induced by three glucose-regulated stresses in Chinese hamster ovary cells. Cancer Res 49:4452-4454.
89. 2 sensing. Science 292:464-468.
90. 2-regulated prolyl hydroxylation. Science 292:468-472.
91. 1H-indole-4,7-dioneprop-2-en-1-ol (EO9, NSC 382459) and their regioisomers as hypoxia-selective agents: Structure-cytotoxicity in vitro. Anticancer Drug Des 13:105-123.
92. Jain RK. 1987. Transport of molecules in the tumor interstitium: A review. 47:3039-3051.
93. Janssen YM, Van Houten B, Borm PJ, Mossman BT. 1993. Cell and tissue responses to oxidative damage. Lab Invest 69:261-274.
94. Jiang BH, Agani F, Passaniti A, Semenza GL. 1997. V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: Involvement of HIF-1 in tumor progression. Cancer Res 57:5328-5335.
95. Joki T, Nakamura M, Ohno T. 1995. Activation of the radiosensitive EGR-1 promoter induces expression of the herpes simplex virus thymidine kinase gene and sensitivity of human glioma cells to ganciclovir. Hum Gene Ther 6:1507-1513.
96. Kaanders JH, Pop LA, Marres HA, Bruaset I, van den Hoogen FJ, Merkx MA, van der Kogel AJ. 2002. ARCON: Experience in 215 patients with advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 52:769-778.
97. Kallio PJ, Wilson WJ, O'Brien S, Makino Y, Poellinger L. 1999. Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin-proteasome pathway. J Biol Chem 274:6519-6525.
98. Kim CY, Tsai MH, Osmanian C, Graeber TG, Lee JE, Giffard RG, DiPaolo JA, Peehl DM, Giaccia AJ. 1997. Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions. Cancer Res 57:4200-4204.
99. Kimura H, Braun RD, Ong ET, Hsu R, Secomb TW, Papahadjopoulos D, Hong K, Dewhirst MW. 1996. Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma. Cancer Res 56:5522-5528.
100. Kjellen E, Joiner MC, Collier JM, Johns H, Rojas A. 1991. A therapeutic benefit from combining normobaric carbogen or oxygen with nicotinamide in fractionated X-ray treatments. Radiother Oncol 22:81-91.
101. 2-measurements as predictive assay in the treatment of carcinoma of the uterine cervix. Radiother Oncol 53:99-104.
102. Koong AC, Chen EY, Giaccia AJ. 1994. Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Cancer Res 54:1425-1430.
103. Koshikawa N, Takenaga K, Tagawa M, Sakiyama S. 2000. Therapeutic efficacy of the suicide gene driven by the promoter of vascular endothelial growth factor gene against hypoxic tumor cells. Cancer Res 60:2936-2941.
104. Koukourakis MI, Giatromanolaki A, Skarlatos J, Corti L, Blandamura S, Piazza M, Gatter KC, Harris AL. 2001. Hypoxia inducible factor (HIF-1a and HIF-2a) expression in early esophageal cancer and response to photodynamic therapy and radiotherapy. Cancer Res 61:1830-1832.
105. Koukourakis MI, Giatromanolaki A, Sivridis E, Simopoulos C, Turley H, Talks K, Gatter KC, Harris AL. 2002. Hypoxia-inducible factor (HIF1A and HIF2A), angiogenesis, and chemoradiotherapy outcome of squamous cell head-and-neck cancer. Int J Radiat Oncol Biol Phys 53:1192-1202.
106. Kourembanas S, Hannan RL, Faller DV. 1990. Oxygen tension regulates the expression of the platelet-derived growth factor-B chain gene in human endothelial cells. J Clin Invest 86:670-674.
107. Kourembanas S, Marsden PA, McQuillan LP, Faller DV. 1991. Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. J Clin Invest 88:1054-1057.
108. Krtolica A, Ludlow JW. 1996. Hypoxia arrests ovarian carcinoma cell cycle progression, but invasion is unaffected. Cancer Res 56:1168-1173.
109. Kung AL, Wang S, Klco JM, Kaelin WG, Livingston DM. 2000. Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nat Med 6:1335-1340.
110. Lambin P, Theys J, Landuyt W, Rijken P, van der Kogel AJ, Van der Schueren E, Hodgkiss RJ, Fowler JF, Nuyts S, de Bruijn E, van Mellaert L, Anne J. 1998. Colonisation of Clostridium in the body is restricted to hypoxic cells and necrotic areas of tumours. Anaerobe 4:183-188.
111. Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL. 1996. Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56:4625-4629.
112. Leek RD, Landers RJ, Harris AL, Lewis CE. 1999. Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. Br J Cancer 79:991-995.
113. Leek RD, Talks KL, Pezzella F, Turley H, Campo L, Brown NS, Bicknell R, Taylor M, Gatter KC, Harris AL. 2002. Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in human breast cancer. Cancer Res 62:1326-1329.
114. Lemmon MJ, van Zijl P, Fox ME, Mauchline ML, Giaccia AJ, Minton NP, Brown JM. 1997. Anaerobic bacteria as a gene delivery system that is controlled by the tumor microenvironment. Gene Ther 4:791-796.
115. Liu SC, Minton NP, Giaccia AJ, Brown JM. 2002. Anticancer efficacy of systemically delivered anaerobic bacteria as gene therapy vectors targeting tumor hypoxia/necrosis. Gene Ther 9:291-296.
116. Madan A, Curtin PT. 1993. A 24-base-pair sequence 3′ to the human erythropoietin gene contains a hypoxia-responsive transcriptional enhancer. Proc Natl Acad Sci USA 90:3928-3932.
117. Maltepe E, Schmidt JV, Baunoch D, Bradfield CA, Simon MC. 1997. Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nature 386:403-407.
118. Marples B, Scott SD, Hendry JH, Embleton MJ, Lashford LS, Margison GP. 2000. Development of synthetic promoters for radiation-mediated gene therapy. Gene Ther 7:511-517.
119. Maxwell PH, Pugh CW, Ratcliffe PJ. 1993. Inducible operation of the erythropoietin 3′ enhancer in multiple cell lines: Evidence for a widespread oxygen-sensing mechanism. Proc Natl Acad Sci USA 90:2423-2427.
120. Maxwell PH, Dachs GU, Gleadle JM, Nicholls LG, Harris AL, Stratford IJ, Hankinson O, Pugh CW, Ratcliffe PJ. 1997. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA 94:8104-8109.
121. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ. 1999. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271-275.
122. Melillo G, Musso T, Sica A, Taylor LS, Cox GW, Varesio L. 1995. A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J Exp Med 182:1683-1693.
123. Minchinton AI, Durand RE, Chaplin DJ. 1990. Intermittent blood flow in the KHT sarcoma-flow cytometry studies using Hoechst 33342. Br J Cancer 62:195-200.
124. Miralbell R, Mornex F, Greiner R, Bolla M, Storme G, Hulshof M, Bernier J, Denekamp J, Rojas AM, Pierart M, van Glabbeke M, Mirimanoff RO. 1999. Accelerated radiotherapy, carbogen, and nicotinamide in glioblastoma multiforme: Report of European Organization for Research and Treatment of Cancer Trial 22933. J Clin Oncol 17:3143-3149.
125. Mohindra JK, Rauth AM. 1976. Increased cell killing by metronidazole and nitrofurazone of hypoxic compared to aerobic mammalian cells. Cancer Res 36:930-936.
126. Niizeki H, Kobayashi M, Horiuchi I, Akakura N, Chen J, Wang J, Hamada JI, Seth P, Katoh H, Watanabe H, Raz A, Hosokawa M. 2002. Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells. Br J Cancer 86:1914-1919.
127. Nordsmark M, Overgaard J. 2000. A confirmatory prognostic study on oxygenation status and loco-regional control in advanced head and neck squamous cell carcinoma treated by radiation therapy. Radiother Oncol 57:39-43.
128. Nordsmark M, Overgaard M, Overgaard J. 1996. Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck. Radiother Oncol 41:31-39.
129. Nordsmark M, Alsner J, Keller J, Nielsen OS, Jensen OM, Horsman MR, Overgaard J. 2001a. Hypoxia in human soft tissue sarcomas: Adverse impact on survival and no association with p53 mutations. Br J Cancer 84:1070-1075.
130. Nordsmark M, Loncaster J, Chou SC, Havsteen H, Lindegaard JC, Davidson SE, Varia M, West C, Hunter R, Overgaard J, Raleigh JA. 2001b. Invasive oxygen measurements and pimonidazole labeling in human cervix carcinoma. Int J Radiat Oncol Biol Phys 49:581-586.
131. Nuyts S, Van Mellaert L, Theys J, Landuyt W, Bosmans E, Anne J, Lambin P. 2001. Radio-responsive recA promoter significantly increases TNFalpha production in recombinant clostridia after 2 Gy irradiation. Gene Ther 8:1197-1201.
132. Overgaard J, Horsman MR. 1997. Overcoming hypoxic cell radio-resistance. In: Steel GG, editor. Basic clinical radiobiology. London: Arnold. pp 141-151.
133. Overgaard J, Hansen HS, Overgaard M, Bastholt L, Berthelsen A, Specht L, Lindelov B, Jorgensen K. 1998. A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85. Radiother Oncol 46:135-146.
134. Partridge SE, Aquino-Parsons C, Luo C, Green A, Olive PL. 2001. A pilot study comparing intratumoral oxygenation using the comet assay following 2.5% and 5% carbogen and 100% oxygen. Int J Radiat Oncol Biol Phys 49:575-580.
135. Pastorino S, Massazza S, Cilli M, Varesio L, Bosco MC. 2001. Generation of high-titer retroviral vector-producing macrophages as vehicles for in vivo gene transfer. Gene Ther 8:431-441.
136. Patterson AV, Saunders MP, Chinje EC, Talbot DC, Harris AL, Strafford IJ. 1997. Overexpression of human NADPH: Cytochrome c (P450) reductase confers enhanced sensitivity to both tirapazamine (SR 4233) and RSU 1069. Br J Cancer 76:1338-1347.
137. Patterson AV, Williams KJ, Cowen RL, Jaffar M, Telfer BA, Saunders M, Airley R, Honess D, van der Kogel AJ, Wolf CR, Stratford IJ. 2002. Oxygen-sensitive enzyme-prodrug gene therapy for the eradication of radiation-resistant solid tumours. Gene Ther 9:946-954.
138. Pawelek JM, Low KB, Bermudes D. 1997. Tumor-targeted Salmonella as a novel anticancer vector. Cancer Res 57:4537-4544.
139. Pigott KH, Hill SA, Chaplin DJ, Saunders MI. 1996. Microregional fluctuations in perfusion within human tumours detected using laser Doppler flowmetry. Radiother Oncol 40:45-50.
140. Pitson G, Fyles A, Milosevic M, Wylie J, Pintilie M, Hill R. 2001. Tumor size and oxygenation are independent predictors of nodal diseases in patients with cervix cancer. Int J Radiat Oncol Biol Phys 51:699-703.
141. Pugh CW, O'Rourke JF, Nagao M, Gleadle JM, Ratcliffe PJ. 1997. Activation of hypoxia-inducible factor-1; definition of regulatory domains within the alpha subunit. J Biol Chem 272:11205-11214.
142. Raleigh JA, Calkins-Adams DP, Rinker LH, Ballenger CA, Weissler MC, Fowler WC, Jr., Novotny DB, Varia MA. 1998. Hypoxia and vascular endothelial growth factor expression in human squamous cell carcinomas using pimonidazole as a hypoxia marker. Cancer Res 58:3765-3768.
143. Rauth AM, Mohindra JK, Tannock IF. 1983. Activity of mitomycin C for aerobic and hypoxic cells in vitro and in vivo. Cancer Res 43:4154-4158.
144. Reynolds TY, Rockwell S, Glazer PM. 1996. Genetic instability induced by the tumor microenvironment. Cancer Res 56:5754-5757.
145. Rischin D, Peters L, Hicks R, Hughes P, Fisher R, Hart R, Sexton M, D'Costa I, von Roemeling R. 2001. Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer. J Clin Oncol 19:535-542.
146. Rodriguez R, Ritter MA, Fowler JF, Kinsella TJ. 1994. Kinetics of cell labeling and thymidine replacement after continuous infusion of halogenated pyrimidines in vivo. Int J Radiat Oncol Biol Phys 29:105-113.
147. Rofstad EK. 2000. Microenvironment-induced cancer metastasis. Int J Radiat Biol 76:589-605.
148. Rofstad EK, Rasmussen H, Galappathi K, Mathiesen B, Nilsen K, GraffBA. 2002. Hypoxia promotes lymph node metastasis in human melanoma xenografts by up-regulating the urokinase-type plasminogen activator receptor. Cancer Res 62:1847-1853.
149. Russo CA, Weber TK, Volpe CM, Stoler DL, Petrelli NJ, Rodriguez-Bigas M, Burhans WC, Anderson GR. 1995. An anoxia inducible endonuclease and enhanced DNA breakage as contributors to genomic instability in cancer. Cancer Res 55:1122-1128.
150. Ryan HE, Lo J, Johnson RS. 1998. HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J 17:3005-3015.
151. Salloum RM, Mauceri HJ, Hanna NN, Gorski DH, Posner MC, Weichselbaum RR. 2003. Dual induction of the Epo-Egr-TNF-alpha-plasmid in hypoxic human colon adenocarcinoma produces tumor growth delay. Am Surg 69:24-27.
152. Sanna K, Rofstad EK. 1994. Hypoxia-induced resistance to doxorubicin and methotrexate in human melanoma cell lines in vitro. Int J Cancer 58:258-262.
153. Saunders MP, Patterson AV, Chinje EC, Harris AL, Stratford IJ. 2000. NADPH: Cytochrome c (P450) reductase activates tirapazamine (SR4233) to restore hypoxic and oxic cytotoxicity in an aerobic resistant derivative of the A549 lung cancer cell line. Br J Cancer 82:651-656.
154. Schindl M, Schoppmann SF, Samonigg H, Hausmaninger H, Kwasny W, Gnant M, Jakesz R, Kubista E, Birner P, Oberhuber G. 2002. Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer. Clin Cancer Res 8:1831-1837.
155. Schmaltz C, Hardenbergh PH, Wells A, Fisher DE. 1998. Regulation of proliferation-survival decisions during tumor cell hypoxia. Mol Cell Biol 18:2845-2854.
156. Scott SD, Marples B, Hendry JH, Lashford LS, Embleton MJ, Hunter RD, Howell A, Margison GP. 2000. A radiation-controlled molecular switch for use in gene therapy of cancer. Gene Ther 7:1121-1125.
157. Scott SD, Joiner MC, Marples B. 2002. Optimizing radiation-responsive gene promoters for radiogenetic cancer therapy. Gene Ther 9:1403-1411.
158. Semenza GL, Wang GL. 1992. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 12:5447-5454.
159. Semenza GL, Roth PH, Fang HM, Wang GL. 1994. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem 269:23757-23763.
160. Semenza GL, Jiang BH, Leung SW, Passantino R, Concordet JP, Maire P, Giallongo A. 1996. Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem 271:32529-32537.
161. Shalev M, Kadmon D, Teh BS, Butler EB, Aguilar-Cordova E, Thompson TC, Herman JR, Adler HL, Scardino PT, Miles BJ. 2000. Suicide gene therapy toxicity after multiple and repeat injections in patients with localized prostate cancer. J Urol 163:1747-1750.
162. Sheldon PW, Foster JL, Fowler JF. 1974. Radiosensitisation of C3H mouse mammary tumours by a 2-nitroimidazole. 30:560-565.
163. Shen J, Hughes C, Chao C, Cai J, Bartels C, Gessner T, Subjeck J. 1987. Coinduction of glucose-regulated proteins and doxorubicin resistance in Chinese hamster cells. Proc Natl Acad Sci USA 84:3278-3282.
164. Sheridan MT, West CM, Cooper RA, Stratford IJ, Logue JP, Davidson SE, Hunter RD. 2000. Pretreatment apoptosis in carcinoma of the cervix correlates with changes in tumour oxygenation during radiotherapy. Br J Cancer 82:1177-1182.
165. Shibata T, Giaccia AJ, Brown JM. 2000. Development of a hypoxia-responsive vector for tumor-specific gene therapy. Gene Ther 7:493-498.
166. Shibata T, Giaccia AJ, Brown JM. 2002. Hypoxia-inducible regulation of a prodrug-activating enzyme for tumor-specific gene therapy Neoplasia 4:40-48.
167. Shimizu S, Eguchi Y, Kosaka H, Kamiike W, Matsuda H, Tsujimoto Y 1995. Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL Nature 374:811-813.
168. Shweiki D, Itin A, Soffer D, Keshet E. 1992. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843-845.
169. Sivitz WI, Lund DD, Yorek B, Grover-McKay M, Schmid PG. 1992 Pretranslational regulation of two cardiac glucose transporters in rats exposed to hypobaric hypoxia. Am J Physiol 263:E562-E569.
170. Soengas MS, Alarcon RM, Yoshida H, Giaccia AJ, Hakem R, Mak TW, Lowe SW. 1999. Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science 284:156-159.
171. Staba MJ, Mauceri HJ, Kufe DW, Hallahan DE, Weichselbaum RR. 1998. Adenoviral TNF-alpha gene therapy and radiation damage tumor vasculature in a human malignant glioma xenograft. Gene Ther 5:293-300.
172. Stone HB, Brown JM, Phillips TL, Sutherland RM. 1993. Oxygen in human tumors: Correlations between methods of measurement and response to therapy. Radiat Res 136:422-434.
173. Stratford IJ, Workman P. 1998. Bioreductive drugs into the next millennium. Anticancer Drug Des 13:519-528.
174. Stratford IJ, O'Neill P, Sheldon PW, Silver AR, Walling JM, Adams GE. 1986. RSU 1069, a nitroimidazole containing an aziridine group. Bioreduction greatly increases cytotoxicity under hypoxic conditions. Biochem Pharmacol 35:105-109.
175. Sundfor K, Lyng H, Rofstad EK. 1998. Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix. Br J Cancer 78:822-827.
176. Tang Y, Jackson M, Qian K, Phillips MI. 2002a. Hypoxia inducible double plasmid system for myocardial ischemia gene therapy. Hypertension 39:695-698.
177. Tang Y, Schmitt-Ott K, Qian K, Kagiyama S, Phillips MI. 2002b. Vigilant vectors: Adeno-associated virus with a biosensor to switch on amplified therapeutic genes in specific tissues in life-threatening diseases. Methods 28:259-266.
178. Tannock IF. 1968. The relation between cell proliferationand the vacular system in a transplanted mouse mammary tumour. Br J Cancer 22:258-273.
179. Teh BS, Aguilar-Cordova E, Kernen K, Chou CC, Shalev M, Vlachaki MT, Miles B, Kadmon D, Mai WY, Caillouet J, Davis M, Ayala G, Wheeler T, Brady J, Carpenter LS, Lu HH, Chiu JK, Woo SY, Thompson T, Butler EB. 2001. Phase I/II trial evaluating combined radiotherapy and in situ gene therapy with or without hormonal therapy in the treatment of prostate cancer-A preliminary report Int J Radiat Oncol Biol Phys 51:605-613.
180. Teicher BA, Lazo JS, Sartorelli AC. 1981. Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells. Cancer Res 41:73-81.
181. Theys J, Landuyt W, Nuyts S, Van Mellaert L, van Oosterom A, Lambin P, Anne J. 2001. Specific targeting of cytosine deaminase to solid tumors by engineered Clostridium acetobutylicum. Cancer Gene Ther 8:294-297.
182. Thomlinson RH, Gray LH. 1955. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9:539-549.
183. Vaupel P, Hockel M. 1998. Oxygenation of human tumours. In: Molls M, Vaupel P, editors. Blood perfusion and microenvironment of human tumours. Berlin: Springer-Verlag. pp 63-72.
184. Vaupel P, Kallinowski F, Okunieff P. 1989. Blood flow, oxygen and nutrient supply, and metabolic microenviroment of human tumors: A review. 49:6449-6465.
185. 2 tension measurements. Cancer Res 51:3316-3322.
186. Veikkola T, Karkkainen M, Claesson-Welsh L, Alitalo K. 2000. Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res 60:203-212.
187. Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfor K, Rofstad EK, Mueller-Klieser W. 2000. High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res 60:916-921.
188. Wang GL, Semenza GL. 1993. General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci USA 90:4304-4308.
189. Wang GL, Semenza GL. 1996. Oxygen sensing and response to hypoxia by mammalian cells. Redox Report 2:89-96.
190. 2 tension. Proc Natl Acad Sci USA 92:5510-5514.
191. Weichselbaum RR, Hallahan DE, Beckett MA, Mauceri HJ, Lee H, Sukhatme VP, Kufe DW. 1994. Gene therapy targeted by radiation preferentially radiosensitizes tumor cells. Cancer Res 54:4266-4269.
192. Wenger RH, Gassmann M. 1997. Oxygen(es) and the hypoxia-inducible factor-1. Biol Chem 378:609-616.
193. West CM, Cooper RA, Loncaster JA, Wilks DP, Bromley M. 2001. Tumor vascularity: A histological measure of angiogenesis and hypoxia. Cancer Res 61:2907-2910.
194. Wiener CM, Booth G, Semenza GL. 1996. In vivo expression of mRNAs encoding hypoxia-inducible factor 1. Biochem Biophys Res Commun 225:485-488.
195. Wiesener MS, Turley H, Allen WE, Willam C, Eckardt KU, Talks KL, Wood SM, Gatter KC, Harris AL, Pugh CW, Ratcliffe PJ, Maxwell PH. 1998. Induction of endothelial PAS domain protein-1 by hypoxia: Characterization and comparison with hypoxia-inducible factor-1alpha. Blood 92:2260-2268.
196. Wykoff CC, Beasley NJ, Watson PH, Turner KJ, Pastorek J, Sibtain A, Wilson GD, Turley H, Talks KL, Maxwell PH, Pugh CW, Ratcliffe PJ, Harris AL. 2000. Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res 60:7075-7083.
197. Yao KS, Xanthoudakis S, Curran T, O'Dwyer PJ. 1994. Activation of AP-1 and of a nuclear redox factor, Ref-1, in the response of HT29 colon cancer cells to hypoxia. Mol Cell Biol 14:5997-6003.
198. Yao KS, Clayton M, O'Dwyer PJ. 1995. Apoptosis in human adenocarcinoma HT29 cells induced by exposure to hypoxia. J Natl Cancer Inst 87:117-122.
199. Yazawa K, Fujimori M, Amano J, Kano Y, Taniguchi S. 2000. Bifidobacterium longum as a delivery system for cancer gene therapy: Selective localization and growth in hypoxic tumors. Cancer Gene Ther 7:269-274.
200. Zander R, Vaupel P. 1985. Proposal for using a standardized terminology on oxygen transport to tissue. Adv Exp Med Biol 191:965-970.
201. Zhong H, Agani F, Baccala AA, Laughner E, Rioseco-Camacho N, Isaacs WB, Simons JW, Semenza GL. 1998. Increased expression of hypoxia inducible factor-1alpha in rat and human prostate cancer. Cancer Res 58:5280-5284.
202. Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, Simons JW. 1999. Over-expression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 59:5830-5835.