Targeting the molecular effects of a hypoxic tumor microenvironment

Frontiers in Bioscience

Volumn 12, Issue 11, 2007, Pages 4061-4078

  Isabel Cardenas Navia, L ^a   Richardson, Rachel A ^b   Dewhirst, Mark W ^b  

^a Duke University   (United States)

^b DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Angiopoietins; HIF; MMPs; NF B; Review; VEGF

Indexed keywords

CELL HYPOXIA; GENETICS; HUMAN; NEOPLASM; PATHOLOGY; REVIEW; VASCULARIZATION;

CELL HYPOXIA; HUMANS; NEOPLASMS;

EID: 34347270940     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/2372     Document Type: Article

References (214)

1. Hockel, M., K. Schlenger, B. Aral, M. Mitze, U. Schaffer & P. Vaupel: Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res, 56, 4509-15 (1996) (Pubitemid 26330463)
2. Hockel, M., K. Schlenger, S. Hockel, B. Aral, U. Schaffer & P. Vaupel: Tumor hypoxia in pelvic recurrences of cervical cancer. Int J Cancer, 79, 365-9 (1998) (Pubitemid 28359734)
3. Vaupel, P., K. Schlenger, C. Knoop & M. Hockel: Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. Cancer Res, 51, 3316-22 (1991)
4. Sundfor, K., H. Lyng, U. L. Kongsgard, C. Trope & E. K. Rofstad: Polarographic measurement of pO2 in cervix carcinoma. Gynecol Oncol, 64, 230-6 (1997) (Pubitemid 27097570)
5. Rofstad, E. K., K. Sundfor, H. Lyng & C. G. Trope: Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia-induced radiation resistance rather than hypoxiainduced metastasis. Br J Cancer, 83, 354-9 (2000) (Pubitemid 30453576)
6. Walenta, S., M. Wetterling, M. Lehrke, G. Schwickert, K. Sundfor, E. K. Rofstad & W. Mueller-Klieser: High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res, 60, 916-21 (2000) (Pubitemid 30129526)
7. Brizel, D. M., S. P. Scully, J. M. Harrelson, L. J. Layfield, J. M. Bean, L. R. Prosnitz & M. W. Dewhirst: Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res, 56, 941-3 (1996) (Pubitemid 26065381)
8. Hall, E. J. & A. J. Giaccia: Radiobiology for the Radiologist. Lippincott Williams & Wilkins, (2005)
9. Teicher, B. A., J. S. Lazo & A. C. Sartorelli: Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells. Cancer Res, 41, 73-81 (1981) (Pubitemid 11218796)
10. Teicher, B. A., S. A. Holden, A. al-Achi & T. S. Herman: Classification of antineoplastic treatments by their differential toxicity toward putative oxygenated and hypoxic tumor subpopulations in vivo in the FSaIIC murine fibrosarcoma. Cancer Res, 50, 3339-44 (1990) (Pubitemid 20190142)
11. Durand, R. E.: The influence of microenvironmental factors during cancer therapy. In Vivo, 8, 691-702 (1994)
12. Jiang, B. H., G. L. Semenza, C. Bauer & H. H. Marti: Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. Am J Physiol, 271, C1172-80 (1996)
13. Kavanagh, B. D., B. E. Coffey, D. Needham, R. M. Hochmuth & M. W. Dewhirst: The effect of flunarizine on erythrocyte suspension viscosity under conditions of extreme hypoxia, low pH, and lactate treatment. Br J Cancer, 67, 734-41 (1993) (Pubitemid 23101551)
14. Pries, A. R., T. W. Secomb & P. Gaehtgens: Structural adaptation and stability of microvascular networks: theory and simulations. Am J Physiol, 275, H349-60 (1998)
15. Pries, A. R., B. Reglin & T. W. Secomb: Structural adaptation of microvascular networks: functional roles of adaptive responses. Am J Physiol Heart Circ Physiol, 281, H1015-25 (2001)
16. Vaupel, P., H. P. Fortmeyer, S. Runkel & F. Kallinowski: Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats. Cancer Res, 47, 3496-503 (1987) (Pubitemid 17096009)
17. Freyer, J. P.: Rates of oxygen consumption for proliferating and quiescent cells isolated from multicellular tumor spheroids. Adv Exp Med Biol, 345, 335-42 (1994) (Pubitemid 24145768)
18. Lanzen, J., R. D. Braun, B. Klitzman, D. Brizel, T. W. Secomb & M. W. Dewhirst: Direct demonstration of instabilities in oxygen concentrations within the extravascular compartment of an experimental tumor. Cancer Res, 66, 2219-23 (2006)
19. Kimura, H., R. D. Braun, E. T. Ong, R. Hsu, T. W. Secomb, D. Papahadjopoulos, K. Hong & M. W. Dewhirst: Fluctuations in red cell flux in tumor microvessels can lead to transient hypoxia and reoxygenation in tumor parenchyma. Cancer Res, 56, 5522-8 (1996) (Pubitemid 27011389)
20. Mueller-Klieser, W., P. Vaupel & R. Manz: Tumour oxygenation under normobaric and hyperbaric conditions. Br J Radiol, 56, 559-64 (1983) (Pubitemid 13026653)
21. Hoogsteen, I. J., L. A. Pop, H. A. Marres, M. A. Merkx, F. J. van den Hoogen, A. J. van der Kogel & J. H. Kaanders: Oxygen-modifying treatment with ARCON reduces the prognostic significance of hemoglobin in squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys, 64, 83-9 (2006) (Pubitemid 41831213)
22. van Laarhoven, H. W., J. Bussink, J. Lok, I. Verhagen, C. J. Punt, A. Heerschap, J. H. Kaanders & A. J. van der Kogel: Modulation of hypoxia in murine liver metastases of colon carcinoma by nicotinamide and carbogen. Radiat Res, 164, 245-9 (2005) (Pubitemid 41233777)
23. Gottschalk, A., A. Raabe, M. Hommel, C. Rempf, M. Freitag & T. Standl: Influence of the hemoglobin solution HBOC-201 on tissue oxygenation in the rat R1H-tumor. Artif Cells Blood Substit Immobil Biotechnol, 33, 379-89 (2005) (Pubitemid 41659163)
24. Teicher, B. A., G. Ara, R. Herbst, H. Takeuchi, S. Keyes & D. Northey: PEG-hemoglobin: effects on tumor oxygenation and response to chemotherapy. In Vivo, 11, 301-11 (1997) (Pubitemid 27404243)
25. Jones, E. L., L. R. Prosnitz, M. W. Dewhirst, P. K. Marcom, P. H. Hardenbergh, L. B. Marks, D. M. Brizel & Z. Vujaskovic: Thermochemoradiotherapy improves oxygenation in locally advanced breast cancer. Clin Cancer Res, 10, 4287-93 (2004) (Pubitemid 38878865)
26. Thrall, D. E., S. M. Larue, A. F. Pruitt, B. Case & M. W. Dewhirst: Changes in tumour oxygenation during fractionated hyperthermia and radiation therapy in spontaneous canine sarcomas. Int J Hyperthermia, 22, 365-73 (2006) (Pubitemid 44203532)
27. Griffin, R. J., K. Okajima, A. Ogawa & C. W. Song: Radiosensitization of two murine tumours with mild temperature hyperthermia and carbogen breathing. Int J Radiat Biol, 75, 1299-306 (1999) (Pubitemid 29500013)
28. Griffin, R. J., K. Okajima & C. W. Song: The optimal combination of hyperthermia and carbogen breathing to increase tumor oxygenation and radiation response. Int J Radiat Oncol Biol Phys, 42, 865-9 (1998) (Pubitemid 28559433)
29. Okajima, K., R. J. Griffin, K. Iwata, A. Shakil & C. W. Song: Tumor oxygenation after mild-temperature hyperthermia in combination with carbogen breathing: dependence on heat dose and tumor type. Radiat Res, 149, 294-9 (1998) (Pubitemid 28104291)
30. Brown, J. M. & A. J. Giaccia: Tumour hypoxia: the picture has changed in the 1990s. Int J Radiat Biol, 65, 95-102 (1994) (Pubitemid 24063535)
31. Brown, J. M. & B. G. Siim: Hypoxia-Specific Cytotoxins in Cancer Therapy. Semin Radiat Oncol, 6, 22-36 (1996) (Pubitemid 26029637)
32. Brown, J. M.: The hypoxic cell: a target for selective cancer therapy-eighteenth Bruce F. Cain Memorial Award lecture. Cancer Res, 59, 5863-70 (1999) (Pubitemid 30004940)
33. Brown, J. M. & W. R. Wilson: Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer, 4, 437-47 (2004) (Pubitemid 38745529)
34. Wang, G. L. & G. L. Semenza: Purification and characterization of hypoxia-inducible factor 1. J Biol Chem, 270, 1230-7 (1995)
35. Ema, M., S. Taya, N. Yokotani, K. Sogawa, Y. Matsuda & Y. Fujii-Kuriyama: A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci U S A, 94, 4273-8 (1997)
36. Tian, H., S. L. McKnight & D. W. Russell: Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev, 11, 72-82 (1997) (Pubitemid 27043825)
37. Makino, Y., A. Kanopka, W. J. Wilson, H. Tanaka & L. Poellinger: Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus. J Biol Chem, 277, 32405-8 (2002) (Pubitemid 34984738)
38. Maxwell, P. H., M. S. Wiesener, G. W. Chang, S. C. Clifford, E. C. Vaux, M. E. Cockman, C. C. Wykoff, C. W. Pugh, E. R. Maher & P. J. Ratcliffe: The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygendependent proteolysis. Nature, 399, 271-5 (1999) (Pubitemid 29246458)
39. Huang, L. E., J. Gu, M. Schau & H. F. Bunn: Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitinproteasome pathway. Proc Natl Acad Sci U S A, 95, 7987-92 (1998)
40. Epstein, A. C., J. M. Gleadle, L. A. McNeill, K. S. Hewitson, J. O'Rourke, D. R. Mole, M. Mukherji, E. Metzen, M. I. Wilson, A. Dhanda, Y. M. Tian, N. Masson, D. L. Hamilton, P. Jaakkola, R. Barstead, J. Hodgkin, P. H. Maxwell, C. W. Pugh, C. J. Schofield & P. J. Ratcliffe: C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell, 107, 43-54 (2001) (Pubitemid 32972036)
41. Bruick, R. K. & S. L. McKnight: A conserved family of prolyl-4-hydroxylases that modify HIF. Science, 294, 1337-40 (2001) (Pubitemid 33063099)
42. Maxwell, P. H.: HIF-1's relationship to oxygen: simple yet sophisticated. Cell Cycle, 3, 156-9 (2004) (Pubitemid 40268688)
43. Berra, E., D. E. Richard, E. Gothie & J. Pouyssegur: HIF-1-dependent transcriptional activity is required for oxygen-mediated HIF-1alpha degradation. FEBS Lett, 491, 85-90 (2001) (Pubitemid 32172007)
44. Salceda, S. & J. Caro: Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitinproteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J Biol Chem, 272, 22642-7 (1997) (Pubitemid 27386079)
45. Berra, E., E. Benizri, A. Ginouves, V. Volmat, D. Roux & J. Pouyssegur: HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. Embo J, 22, 4082-90 (2003) (Pubitemid 37021737)
46. Lando, D., D. J. Peet, J. J. Gorman, D. A. Whelan, M. L. Whitelaw & R. K. Bruick: FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev, 16, 1466-71 (2002) (Pubitemid 34686328)
47. Mahon, P. C., K. Hirota & G. L. Semenza: FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev, 15, 2675-86 (2001) (Pubitemid 32988878)
48. Demidenko, Z. N., A. Rapisarda, M. Garayoa, P. Giannakakou, G. Melillo & M. V. Blagosklonny: Accumulation of hypoxia-inducible factor-1alpha is limited by transcription-dependent depletion. Oncogene, 24, 4829-38 (2005) (Pubitemid 41076301)
49. Stroka, D. M., T. Burkhardt, I. Desbaillets, R. H. Wenger, D. A. Neil, C. Bauer, M. Gassmann & D. Candinas: HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia. Faseb J, 15, 2445-53 (2001) (Pubitemid 33063172)
50. Jewell, U. R., I. Kvietikova, A. Scheid, C. Bauer, R. H. Wenger & M. Gassmann: Induction of HIF-1alpha in response to hypoxia is instantaneous. Faseb J, 15, 1312-4 (2001)
51. Semenza, G.: Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol, 64, 993-8 (2002) (Pubitemid 35232274)
52. Hirota, K. & G. L. Semenza: Regulation of angiogenesis by hypoxia-inducible factor 1. Crit Rev Oncol Hematol, 59, 15-26 (2006) (Pubitemid 43903276)
53. Semenza, G. L.: Targeting HIF-1 for cancer therapy. Nat Rev Cancer, 3, 721-32 (2003) (Pubitemid 37328811)
54. Kondo, K., J. Klco, E. Nakamura, M. Lechpammer & W. G. Kaelin, Jr.: Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell, 1, 237-46 (2002) (Pubitemid 41039148)
55. Ohh, M., C. W. Park, M. Ivan, M. A. Hoffman, T. Y. Kim, L. E. Huang, N. Pavletich, V. Chau & W. G. Kaelin: Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol, 2, 423-7 (2000)
56. Gassmann, M., D. Chilov & R. H. Wenger: Regulation of the hypoxia-inducible factor-1 alpha. ARNT is not necessary for hypoxic induction of HIF-1 alpha in the nucleus. Adv Exp Med Biol, 475, 87-99 (2000) (Pubitemid 32197716)
57. Zundel, W., C. Schindler, D. Haas-Kogan, A. Koong, F. Kaper, E. Chen, A. R. Gottschalk, H. E. Ryan, R. S. Johnson, A. B. Jefferson, D. Stokoe & A. J. Giaccia: Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev, 14, 391-6 (2000) (Pubitemid 30131884)
58. Zhong, H., K. Chiles, D. Feldser, E. Laughner, C. Hanrahan, M. M. Georgescu, J. W. Simons & G. L. Semenza: Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res, 60, 1541-5 (2000) (Pubitemid 30183422)
59. Bos, R., P. van der Groep, A. E. Greijer, A. Shvarts, S. Meijer, H. M. Pinedo, G. L. Semenza, P. J. van Diest & E. van der Wall: Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer, 97, 1573-81 (2003) (Pubitemid 36297788)
60. Ryan, H. E., M. Poloni, W. McNulty, D. Elson, M. Gassmann, J. M. Arbeit & R. S. Johnson: Hypoxiainducible factor-1alpha is a positive factor in solid tumor growth. Cancer Res, 60, 4010-5 (2000) (Pubitemid 30636574)
61. Zhong, H., A. M. De Marzo, E. Laughner, M. Lim, D. A. Hilton, D. Zagzag, P. Buechler, W. B. Isaacs, G. L. Semenza & J. W. Simons: Overexpression of hypoxiainducible factor 1alpha in common human cancers and their metastases. Cancer Res, 59, 5830-5 (1999)
62. Shibaji, T., M. Nagao, N. Ikeda, H. Kanehiro, M. Hisanaga, S. Ko, A. Fukumoto & Y. Nakajima: Prognostic significance of HIF-1 alpha overexpression in human pancreatic cancer. Anticancer Res, 23, 4721-7 (2003) (Pubitemid 38173890)
63. Ryan, H. E., J. Lo & R. S. Johnson: HIF-1 alpha is required for solid tumor formation and embryonic vascularization. Embo J, 17, 3005-15 (1998) (Pubitemid 28254373)
64. Carmeliet, P., Y. Dor, J. M. Herbert, D. Fukumura, K. Brusselmans, M. Dewerchin, M. Neeman, F. Bono, R. Abramovitch, P. Maxwell, C. J. Koch, P. Ratcliffe, L. Moons, R. K. Jain, D. Collen & E. Keshert: Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature, 394, 485-90 (1998) (Pubitemid 28373960)
65. Maltepe, E., J. V. Schmidt, D. Baunoch, C. A. Bradfield & M. C. Simon: Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nature, 386, 403-7 (1997) (Pubitemid 27154481)
66. Arany, Z., L. E. Huang, R. Eckner, S. Bhattacharya, C. Jiang, M. A. Goldberg, H. F. Bunn & D. M. Livingston: An essential role for p300/CBP in the cellular response to hypoxia. Proc Natl Acad Sci U S A, 93, 12969-73 (1996) (Pubitemid 26382753)
67. Carrero, P., K. Okamoto, P. Coumailleau, S. O'Brien, H. Tanaka & L. Poellinger: Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1alpha. Mol Cell Biol, 20, 402-15 (2000) (Pubitemid 30002581)
68. Kung, A. L., S. Wang, J. M. Klco, W. G. Kaelin & D. M. Livingston: Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nat Med, 6, 1335-40 (2000) (Pubitemid 32001016)
69. Kung, A. L., S. D. Zabludoff, D. S. France, S. J. Freedman, E. A. Tanner, A. Vieira, S. Cornell-Kennon, J. Lee, B. Wang, J. Wang, K. Memmert, H. U. Naegeli, F. Petersen, M. J. Eck, K. W. Bair, A. W. Wood & D. M. Livingston: Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway. Cancer Cell, 6, 33-43 (2004) (Pubitemid 38903160)
70. Blancher, C., J. W. Moore, N. Robertson & A. L. Harris: Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3'-kinase/Akt signaling pathway. Cancer Res, 61, 7349-55 (2001) (Pubitemid 32946535)
71. Mazure, N. M., E. Y. Chen, P. Yeh, K. R. Laderoute & A. J. Giaccia: Oncogenic transformation and hypoxia synergistically act to modulate vascular endothelial growth factor expression. Cancer Res, 56, 3436-40 (1996) (Pubitemid 26251633)
72. Mabjeesh, N. J., D. Escuin, T. M. LaVallee, V. S. Pribluda, G. M. Swartz, M. S. Johnson, M. T. Willard, H. Zhong, J. W. Simons & P. Giannakakou: 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell, 3, 363-75 (2003) (Pubitemid 38340305)
73. Jung, Y. J., J. S. Isaacs, S. Lee, J. Trepel & L. Neckers: Microtubule disruption utilizes an NFkappa B-dependent pathway to stabilize HIF-1alpha protein. J Biol Chem, 278, 7445-52 (2003) (Pubitemid 36800750)
74. Yeo, E. J., Y. S. Chun, Y. S. Cho, J. Kim, J. C. Lee, M. S. Kim & J. W. Park: YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1. J Natl Cancer Inst, 95, 516-25 (2003) (Pubitemid 36511622)
75. Rapisarda, A., B. Uranchimeg, D. A. Scudiero, M. Selby, E. A. Sausville, R. H. Shoemaker & G. Melillo: Identification of small molecule inhibitors of hypoxia-inducible factor 1 transcriptional activation pathway. Cancer Res, 62, 4316-24 (2002) (Pubitemid 34827288)
76. Carroll, V. A. & M. Ashcroft: Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: implications for targeting the HIF pathway. Cancer Res, 66, 6264-70 (2006)
77. Zhang, X., T. Kon, H. Wang, F. Li, Q. Huang, Z. N. Rabbani, J. P. Kirkpatrick, Z. Vujaskovic, M. W. Dewhirst & C. Y. Li: Enhancement of hypoxia-induced tumor cell death in vitro and radiation therapy in vivo by use of small interfering RNA targeted to hypoxia-inducible factor-1alpha. Cancer Res, 64, 8139-42 (2004) (Pubitemid 39491746)
78. Sun, X., J. R. Kanwar, E. Leung, K. Lehnert, D. Wang & G. W. Krissansen: Gene transfer of antisense hypoxia inducible factor-1 alpha enhances the therapeutic efficacy of cancer immunotherapy. Gene Ther, 8, 638-45 (2001) (Pubitemid 32422058)
79. Folkman, J.: Tumor angiogenesis: therapeutic implications. N Engl J Med, 285, 1182-6 (1971)
80. Ferrara, N.: VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer, 2, 795-803 (2002) (Pubitemid 37328914)
81. Neufeld, G., T. Cohen, S. Gengrinovitch & Z. Poltorak: Vascular endothelial growth factor (VEGF) and its receptors. Faseb J, 13, 9-22 (1999) (Pubitemid 29038270)
82. Ferrara, N., H. P. Gerber & J. LeCouter: The biology of VEGF and its receptors. Nat Med, 9, 669-76 (2003) (Pubitemid 36749215)
83. Tischer, E., R. Mitchell, T. Hartman, M. Silva, D. Gospodarowicz, J. C. Fiddes & J. A. Abraham: The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem, 266, 11947-54 (1991)
84. Kim, K. J., B. Li, K. Houck, J. Winer & N. Ferrara: The vascular endothelial growth factor proteins: identification of biologically relevant regions by neutralizing monoclonal antibodies. Growth Factors, 7, 53-64 (1992)
85. Shibuya, M., S. Yamaguchi, A. Yamane, T. Ikeda, A. Tojo, H. Matsushime & M. Sato: Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene, 5, 519-24 (1990)
86. Terman, B. I., M. E. Carrion, E. Kovacs, B. A. Rasmussen, R. L. Eddy & T. B. Shows: Identification of a new endothelial cell growth factor receptor tyrosine kinase. Oncogene, 6, 1677-83 (1991) (Pubitemid 21924273)
87. de Vries, C., J. A. Escobedo, H. Ueno, K. Houck, N. Ferrara & L. T. Williams: The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science, 255, 989-91 (1992)
88. Gerber, H. P., F. Condorelli, J. Park & N. Ferrara: Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk-1/KDR, is up-regulated by hypoxia. J Biol Chem, 272, 23659-67 (1997) (Pubitemid 27410939)
89. Zeng, H., H. F. Dvorak & D. Mukhopadhyay: Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) peceptor-1 down-modulates VPF/VEGF receptor-2-mediated endothelial cell proliferation, but not migration, through phosphatidylinositol 3-kinase-dependent pathways. J Biol Chem, 276, 26969-79 (2001)
90. Rahimi, N., V. Dayanir & K. Lashkari: Receptor chimeras indicate that the vascular endothelial growth factor receptor-1 (VEGFR-1) modulates mitogenic activity of VEGFR-2 in endothelial cells. J Biol Chem, 275, 16986-92 (2000) (Pubitemid 30398939)
91. Kim, K. J., B. Li, J. Winer, M. Armanini, N. Gillett, H. S. Phillips & N. Ferrara: Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature, 362, 841-4 (1993) (Pubitemid 23132159)
92. Borgstrom, P., D. P. Gold, K. J. Hillan & N. Ferrara: Importance of VEGF for breast cancer angiogenesis in vivo: implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin. Anticancer Res, 19, 4203-14 (1999)
93. Borgstrom, P., M. A. Bourdon, K. J. Hillan, P. Sriramarao & N. Ferrara: Neutralizing anti-vascular endothelial growth factor antibody completely inhibits angiogenesis and growth of human prostate carcinoma micro tumors in vivo. Prostate, 35, 1-10 (1998) (Pubitemid 28158631)
94. Borgstrom, P., K. J. Hillan, P. Sriramarao & N. Ferrara: Complete inhibition of angiogenesis and growth of microtumors by anti-vascular endothelial growth factor neutralizing antibody: novel concepts of angiostatic therapy from intravital videomicroscopy. Cancer Res, 56, 4032-9 (1996) (Pubitemid 26284756)
95. Horstmann, E., M. S. McCabe, L. Grochow, S. Yamamoto, L. Rubinstein, T. Budd, D. Shoemaker, E. J. Emanuel & C. Grady: Risks and benefits of phase 1 oncology trials, 1991 through 2002. N Engl J Med, 352, 895-904 (2005) (Pubitemid 40300298)
96. de Castro Junior, G., F. Puglisi, E. de Azambuja, N. S. El Saghir & A. Awada: Angiogenesis and cancer: A crosstalk between basic science and clinical trials (the "do ut des" paradigm). Crit Rev Oncol Hematol, 59, 40-50 (2006) (Pubitemid 43903280)
97. Holash, J., P. C. Maisonpierre, D. Compton, P. Boland, C. R. Alexander, D. Zagzag, G. D. Yancopoulos & S. J. Wiegand: Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science, 284, 1994-8 (1999) (Pubitemid 29309448)
98. Gale, N. W. & G. D. Yancopoulos: Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev, 13, 1055-66 (1999) (Pubitemid 29233137)
99. Holash, J., S. J. Wiegand & G. D. Yancopoulos: New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene, 18, 5356-62 (1999) (Pubitemid 29462372)
100. Thurston, G., J. S. Rudge, E. Ioffe, H. Zhou, L. Ross, S. D. Croll, N. Glazer, J. Holash, D. M. McDonald & G. D. Yancopoulos: Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med, 6, 460-3 (2000) (Pubitemid 30208166)
101. Papapetropoulos, A., G. Garcia-Cardena, T. J. Dengler, P. C. Maisonpierre, G. D. Yancopoulos & W. C. Sessa: Direct actions of angiopoietin-1 on human endothelium: evidence for network stabilization, cell survival, and interaction with other angiogenic growth factors. Lab Invest, 79, 213-23 (1999) (Pubitemid 29110651)
102. Yu, Q. & I. Stamenkovic: Angiopoietin-2 is implicated in the regulation of tumor angiogenesis. Am J Pathol, 158, 563-70 (2001) (Pubitemid 32158617)
103. Etoh, T., H. Inoue, S. Tanaka, G. F. Barnard, S. Kitano & M. Mori: Angiopoietin-2 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via induction of proteases. Cancer Res, 61, 2145-53 (2001) (Pubitemid 32692040)
104. Tanaka, S., M. Mori, Y. Sakamoto, M. Makuuchi, K. Sugimachi & J. R. Wands: Biologic significance of angiopoietin-2 expression in human hepatocellular carcinoma. J Clin Invest, 103, 341-5 (1999) (Pubitemid 29069983)
105. Visconti, R. P., C. D. Richardson & T. N. Sato: Orchestration of angiogenesis and arteriovenous contribution by angiopoietins and vascular endothelial growth factor (VEGF). Proc Natl Acad Sci U S A, 99, 8219-24 (2002) (Pubitemid 34651033)
106. Tsutsui, S., H. Inoue, K. Yasuda, K. Suzuki, H. Takeuchi, T. Nishizaki, H. Higashi, S. Era & M. Mori: Angiopoietin 2 expression in invasive ductal carcinoma of the breast: its relationship to the VEGF expression and microvessel density. Breast Cancer Res Treat, 98, 261-6 (2006) (Pubitemid 44195595)
107. Hata, K., K. Nakayama, R. Fujiwaki, H. Katabuchi, H. Okamura & K. Miyazaki: Expression of the angopoietin-1, angopoietin-2, Tie2, and vascular endothelial growth factor gene in epithelial ovarian cancer. Gynecol Oncol, 93, 215-22 (2004) (Pubitemid 38429573)
108. Wang, J., K. C. Wu, D. X. Zhang & D. M. Fan: Antisense angiopoietin-1 inhibits tumorigenesis and angiogenesis of gastric cancer. World J Gastroenterol, 12, 2450-4 (2006)
109. Oliner, J., H. Min, J. Leal, D. Yu, S. Rao, E. You, X. Tang, H. Kim, S. Meyer, S. J. Han, N. Hawkins, R. Rosenfeld, E. Davy, K. Graham, F. Jacobsen, S. Stevenson, J. Ho, Q. Chen, T. Hartmann, M. Michaels, M. Kelley, L. Li, K. Sitney, F. Martin, J. R. Sun, N. Zhang, J. Lu, J. Estrada, R. Kumar, A. Coxon, S. Kaufman, J. Pretorius, S. Scully, R. Cattley, M. Payton, S. Coats, L. Nguyen, B. Desilva, A. Ndifor, I. Hayward, R. Radinsky, T. Boone & R. Kendall: Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2. Cancer Cell, 6, 507-16 (2004) (Pubitemid 39469986)
110. Lin, P., J. A. Buxton, A. Acheson, C. Radziejewski, P. C. Maisonpierre, G. D. Yancopoulos, K. M. Channon, L. P. Hale, M. W. Dewhirst, S. E. George & K. G. Peters: Antiangiogenic gene therapy targeting the endotheliumspecific receptor tyrosine kinase Tie2. Proc Natl Acad Sci U S A, 95, 8829-34 (1998) (Pubitemid 28350574)
111. Lin, P., P. Polverini, M. Dewhirst, S. Shan, P. S. Rao & K. Peters: Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth. J Clin Invest, 100, 2072-8 (1997) (Pubitemid 27459362)
112. Lin, P., S. Sankar, S. Shan, M. W. Dewhirst, P. J. Polverini, T. Q. Quinn & K. G. Peters: Inhibition of tumor growth by targeting tumor endothelium using a soluble vascular endothelial growth factor receptor. Cell Growth Differ, 9, 49-58 (1998) (Pubitemid 28049527)
113. Stratmann, A., T. Acker, A. M. Burger, K. Amann, W. Risau & K. H. Plate: Differential inhibition of tumor angiogenesis by tie2 and vascular endothelial growth factor receptor-2 dominant-negative receptor mutants. Int J Cancer, 91, 273-82 (2001) (Pubitemid 32049618)
114. Tanaka, S., K. Sugimachi, Y. Yamashita Yi, T. Ohga, K. Shirabe, M. Shimada & J. R. Wands: Tie2 vascular endothelial receptor expression and function in hepatocellular carcinoma. Hepatology, 35, 861-7 (2002) (Pubitemid 34258380)
115. Egeblad, M. & Z. Werb: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer, 2, 161-74 (2002) (Pubitemid 37328786)
116. Baker, A. H., D. R. Edwards & G. Murphy: Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci, 115, 3719-27 (2002) (Pubitemid 35203598)
117. Troeberg, L., M. Tanaka, R. Wait, Y. E. Shi, K. Brew & H. Nagase: E. coli expression of TIMP-4 and comparative kinetic studies with TIMP-1 and TIMP-2: insights into the interactions of TIMPs and matrix metalloproteinase 2 (gelatinase A). Biochemistry, 41, 15025-35 (2002) (Pubitemid 35470682)
118. Takahashi, C., Z. Sheng, T. P. Horan, H. Kitayama, M. Maki, K. Hitomi, Y. Kitaura, S. Takai, R. M. Sasahara, A. Horimoto, Y. Ikawa, B. J. Ratzkin, T. Arakawa & M. Noda: Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. Proc Natl Acad Sci U S A, 95, 13221-6 (1998) (Pubitemid 28509552)
119. Brew, K., D. Dinakarpandian & H. Nagase: Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta, 1477, 267-83 (2000) (Pubitemid 30119906)
120. Lafleur, M. A., M. M. Handsley, V. Knauper, G. Murphy & D. R. Edwards: Endothelial tubulogenesis within fibrin gels specifically requires the activity of membrane-type-matrix metalloproteinases (MT-MMPs). J Cell Sci, 115, 3427-38 (2002) (Pubitemid 34994032)
121. Anand-Apte, B., M. S. Pepper, E. Voest, R. Montesano, B. Olsen, G. Murphy, S. S. Apte & B. Zetter: Inhibition of angiogenesis by tissue inhibitor of metalloproteinase-3. Invest Ophthalmol Vis Sci, 38, 817-23 (1997) (Pubitemid 27193506)
122. Taraboletti, G., S. D'Ascenzo, P. Borsotti, R. Giavazzi, A. Pavan & V. Dolo: Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. Am J Pathol, 160, 673-80 (2002) (Pubitemid 34160345)
123. Seandel, M., K. Noack-Kunnmann, D. Zhu, R. T. Aimes & J. P. Quigley: Growth factor-induced angiogenesis in vivo requires specific cleavage of fibrillar type I collagen. Blood, 97, 2323-32 (2001) (Pubitemid 32291478)
124. Ye, H., Y. Zheng, W. Ma, D. Ke, X. Jin, S. Liu & D. Wang: Hypoxia down-regulates secretion of MMP-2, MMP-9 in porcine pulmonary artery endothelial and smooth muscle cells and the role of HIF-1. J Huazhong Univ Sci Technolog Med Sci, 25, 382-4, 407 (2005)
125. Ben-Yosef, Y., A. Miller, S. Shapiro & N. Lahat: Hypoxia of endothelial cells leads to MMP-2-dependent survival and death. Am J Physiol Cell Physiol, 289, C1321-31 (2005) (Pubitemid 41456849)
126. Ben-Yosef, Y., N. Lahat, S. Shapiro, H. Bitterman & A. Miller: Regulation of endothelial matrix metalloproteinase-2 by hypoxia/reoxygenation. Circ Res, 90, 784-91 (2002) (Pubitemid 34633894)
127. Rahat, M. A., B. Marom, H. Bitterman, L. Weiss-Cerem, A. Kinarty & N. Lahat: Hypoxia reduces the output of matrix metalloproteinase-9 (MMP-9) in monocytes by inhibiting its secretion and elevating membranal association. J Leukoc Biol, 79, 706-18 (2006) (Pubitemid 44835603)
128. Munoz-Najar, U. M., K. M. Neurath, F. Vumbaca & K. P. Claffey: Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation. Oncogene, 25, 2379-92 (2006)
129. Itoh, T., M. Tanioka, H. Yoshida, T. Yoshioka, H. Nishimoto & S. Itohara: Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res, 58, 1048-51 (1998) (Pubitemid 28182477)
130. Hiratsuka, S., K. Nakamura, S. Iwai, M. Murakami, T. Itoh, H. Kijima, J. M. Shipley, R. M. Senior & M. Shibuya: MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell, 2, 289-300 (2002) (Pubitemid 41043963)
131. Bramhall, S. R., J. Schulz, J. Nemunaitis, P. D. Brown, M. Baillet & J. A. Buckels: A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br J Cancer, 87, 161-7 (2002)
132. Shepherd, F. A., G. Giaccone, L. Seymour, C. Debruyne, A. Bezjak, V. Hirsh, M. Smylie, S. Rubin, H. Martins, A. Lamont, M. Krzakowski, A. Sadura & B. Zee: Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organization for Research and Treatment of Cancer. J Clin Oncol, 20, 4434-9 (2002) (Pubitemid 35334754)
133. Bissett, D., K. J. O'Byrne, J. von Pawel, U. Gatzemeier, A. Price, M. Nicolson, R. Mercier, E. Mazabel, C. Penning, M. H. Zhang, M. A. Collier & F. A. Shepherd: Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer. J Clin Oncol, 23, 842-9 (2005) (Pubitemid 46224184)
134. Leighl, N. B., L. Paz-Ares, J. Y. Douillard, C. Peschel, A. Arnold, A. Depierre, A. Santoro, D. C. Betticher, U. Gatzemeier, J. Jassem, J. Crawford, D. Tu, A. Bezjak, J. S. Humphrey, M. Voi, S. Galbraith, K. Hann, L. Seymour & F. A. Shepherd: Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18. J Clin Oncol, 23, 2831-9 (2005) (Pubitemid 46179474)
135. Mueckler, M.: Facilitative glucose transporters. Eur J Biochem, 219, 713-25 (1994) (Pubitemid 24050938)
136. Brown, G. K.: Glucose transporters: structure, function and consequences of deficiency. J Inherit Metab Dis, 23, 237-46 (2000) (Pubitemid 30330406)
137. Airley, R., J. Loncaster, S. Davidson, M. Bromley, S. Roberts, A. Patterson, R. Hunter, I. Stratford & C. West: Glucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix. Clin Cancer Res, 7, 928-34 (2001) (Pubitemid 32708731)
138. Chang, S., S. Lee, C. Lee, J. I. Kim & Y. Kim: Expression of the human erythrocyte glucose transporter in transitional cell carcinoma of the bladder. Urology, 55, 448-52 (2000) (Pubitemid 30110607)
139. North, P. E., M. Waner, A. Mizeracki & M. C. Mihm, Jr.: GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas. Hum Pathol, 31, 11-22 (2000) (Pubitemid 30054381)
140. Kurata, T., T. Oguri, T. Isobe, S. Ishioka & M. Yamakido: Differential expression of facilitative glucose transporter (GLUT) genes in primary lung cancers and their liver metastases. Jpn J Cancer Res, 90, 1238-43 (1999)
141. Brown, R. S. & R. L. Wahl: Overexpression of Glut-1 glucose transporter in human breast cancer. An immunohistochemical study. Cancer, 72, 2979-85 (1993) (Pubitemid 23335044)
142. Mellanen, P., H. Minn, R. Grenman & P. Harkonen: Expression of glucose transporters in head-and-neck tumors. Int J Cancer, 56, 622-9 (1994) (Pubitemid 24086761)
143. Haber, R. S., K. R. Weiser, A. Pritsker, I. Reder & D. E. Burstein: GLUT1 glucose transporter expression in benign and malignant thyroid nodules. Thyroid, 7, 363-7 (1997)
144. Haber, R. S., A. Rathan, K. R. Weiser, A. Pritsker, S. H. Itzkowitz, C. Bodian, G. Slater, A. Weiss & D. E. Burstein: GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor prognosis. Cancer, 83, 34-40 (1998) (Pubitemid 28299626)
145. Younes, M., P. R. Katikaneni & J. Lechago: Association between mucosal hyperplasia of the appendix and adenocarcinoma of the colon. Histopathology, 26, 33-7 (1995)
146. Kang, S. S., Y. K. Chun, M. H. Hur, H. K. Lee, Y. J. Kim, S. R. Hong, J. H. Lee, S. G. Lee & Y. K. Park: Clinical significance of glucose transporter 1 (GLUT1) expression in human breast carcinoma. Jpn J Cancer Res, 93, 1123-8 (2002) (Pubitemid 35314957)
147. De Schutter, H., W. Landuyt, E. Verbeken, L. Goethals, R. Hermans & S. Nuyts: The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy+/-chemotherapy. BMC Cancer, 5, 42 (2005)
148. Jiang, B. H., E. Rue, G. L. Wang, R. Roe & G. L. Semenza: Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J Biol Chem, 271, 17771-8 (1996) (Pubitemid 26250751)
149. Gatenby, R. A. & R. J. Gillies: Why do cancers have high aerobic glycolysis? Nat Rev Cancer, 4, 891-9 (2004) (Pubitemid 39472955)
150. Schroeder, T., H. Yuan, B. L. Viglianti, C. Peltz, S. Asopa, Z. Vujaskovic & M. W. Dewhirst: Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and fibrosarcomas of the Fischer 344 rat. Cancer Res, 65, 5163-71 (2005) (Pubitemid 40827325)
151. Vera, J. C., A. M. Reyes, J. G. Carcamo, F. V. Velasquez, C. I. Rivas, R. H. Zhang, P. Strobel, R. Iribarren, H. I. Scher, J. C. Slebe & et al.: Genistein is a natural inhibitor of hexose and dehydroascorbic acid transport through the glucose transporter, GLUT1. J Biol Chem, 271, 8719-24 (1996) (Pubitemid 26123289)
152. Vera, J. C., A. M. Reyes, F. V. Velasquez, C. I. Rivas, R. H. Zhang, P. Strobel, J. C. Slebe, J. Nunez-Alarcon & D. W. Golde: Direct inhibition of the hexose transporter GLUT1 by tyrosine kinase inhibitors. Biochemistry, 40, 777-90 (2001) (Pubitemid 32096863)
153. Shaulian, E. & M. Karin: AP-1 in cell proliferation and survival. Oncogene, 20, 2390-400 (2001) (Pubitemid 32531297)
154. Fantozzi, I., S. Zhang, O. Platoshyn, C. V. Remillard, R. T. Cowling & J. X. Yuan: Hypoxia increases AP-1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol, 285, L1233-45 (2003) (Pubitemid 37448794)
155. Minet, E., G. Michel, D. Mottet, J. P. Piret, A. Barbieux, M. Raes & C. Michiels: c-JUN gene induction and AP-1 activity is regulated by a JNK-dependent pathway in hypoxic HepG2 cells. Exp Cell Res, 265, 114-24 (2001) (Pubitemid 32989069)
156. Michiels, C., E. Minet, G. Michel, D. Mottet, J. P. Piret & M. Raes: HIF-1 and AP-1 cooperate to increase gene expression in hypoxia: role of MAP kinases. IUBMB Life, 52, 49-53 (2001) (Pubitemid 33769669)
157. Millhorn, D. E., R. Raymond, L. Conforti, W. Zhu, D. Beitner-Johnson, T. Filisko, M. B. Genter, S. Kobayashi & M. Peng: Regulation of gene expression for tyrosine hydroxylase in oxygen sensitive cells by hypoxia. Kidney Int, 51, 527-35 (1997) (Pubitemid 27088170)
158. Premkumar, D. R., G. Adhikary, J. L. Overholt, M. S. Simonson, N. S. Cherniack & N. R. Prabhakar: Intracellular pathways linking hypoxia to activation of cfos and AP-1. Adv Exp Med Biol, 475, 101-9 (2000) (Pubitemid 32197717)
159. Salnikow, K., T. Kluz, M. Costa, D. Piquemal, Z. N. Demidenko, K. Xie & M. V. Blagosklonny: The regulation of hypoxic genes by calcium involves c-Jun/AP-1, which cooperates with hypoxia-inducible factor 1 in response to hypoxia. Mol Cell Biol, 22, 1734-41 (2002) (Pubitemid 34174991)
160. Meyer, M., R. Schreck & P. A. Baeuerle: H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor. Embo J, 12, 2005-15 (1993) (Pubitemid 23157717)
161. Hoffmann, A., T. Gloe & U. Pohl: Hypoxia-induced upregulation of eNOS gene expression is redox-sensitive: a comparison between hypoxia and inhibitors of cell metabolism. J Cell Physiol, 188, 33-44 (2001) (Pubitemid 32476494)
162. Angel, P., M. Imagawa, R. Chiu, B. Stein, R. J. Imbra, H. J. Rahmsdorf, C. Jonat, P. Herrlich & M. Karin: Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell, 49, 729-39 (1987) (Pubitemid 18094763)
163. Chinenov, Y. & T. K. Kerppola: Close encounters of many kinds: Fos-Jun. interactions that mediate transcription regulatory specificity. Oncogene, 20, 2438-52 (2001) (Pubitemid 32531301)
164. Angel, P. & M. Karin: The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta, 1072, 129-57 (1991) (Pubitemid 121007534)
165. Bland, K. I., M. M. Konstadoulakis, M. P. Vezeridis & H. J. Wanebo: Oncogene protein co-expression. Value of Ha-ras, c-myc, c-fos, and p53 as prognostic discriminants for breast carcinoma. Ann Surg, 221, 706-18; discussion 718-20 (1995)
166. Edwards, J., N. S. Krishna, R. Mukherjee & J. M. Bartlett: The role of c-Jun. and c-Fos expression in androgen-independent prostate cancer. J Pathol, 204, 153-8 (2004) (Pubitemid 39335288)
167. Brown, P. H., R. Alani, L. H. Preis, E. Szabo & M. J. Birrer: Suppression of oncogene-induced transformation by a deletion mutant of c-jun. Oncogene, 8, 877-86 (1993) (Pubitemid 23087418)
168. Dong, Z., M. J. Birrer, R. G. Watts, L. M. Matrisian & N. H. Colburn: Blocking of tumor promoter-induced AP-1 activity inhibits induced transformation in JB6 mouse epidermal cells. Proc Natl Acad Sci U S A, 91, 609-13 (1994) (Pubitemid 24041451)
169. Magne, N., R. A. Toillon, V. Bottero, C. Didelot, P. V. Houtte, J. P. Gerard & J. F. Peyron: NF-kappaB modulation and ionizing radiation: mechanisms and future directions for cancer treatment. Cancer Lett, 231, 158-68 (2006) (Pubitemid 43038726)
170. Chen, F., V. Castranova, X. Shi & L. M. Demers: New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases. Clin Chem, 45, 7-17 (1999) (Pubitemid 29036378)
171. Koong, A. C., E. Y. Chen, N. F. Mivechi, N. C. Denko, P. Stambrook & A. J. Giaccia: Hypoxic activation of nuclear factor-kappa B is mediated by a Ras and Raf signaling pathway and does not involve MAP kinase (ERK1 or ERK2). Cancer Res, 54, 5273-9 (1994) (Pubitemid 24336013)
172. Koong, A. C., E. Y. Chen & A. J. Giaccia: Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Cancer Res, 54, 1425-30 (1994) (Pubitemid 24106401)
173. Zampetaki, A., S. A. Mitsialis, J. Pfeilschifter & S. Kourembanas: Hypoxia induces macrophage inflammatory protein-2 (MIP-2) gene expression in murine macrophages via NF-kappaB: the prominent role of p42/p44 and PI3 kinase pathways. Faseb J, 18, 1090-2 (2004) (Pubitemid 39561533)
174. Chandel, N. S., W. C. Trzyna, D. S. McClintock & P. T. Schumacker: Role of oxidants in NF-kappa B activation and TNF-alpha gene transcription induced by hypoxia and endotoxin. J Immunol, 165, 1013-21 (2000) (Pubitemid 30484771)
175. Schulze-Osthoff, K., M. Los & P. A. Baeuerle: Redox signalling by transcription factors NF-kappa B and AP-1 in lymphocytes. Biochem Pharmacol, 50, 735-41 (1995)
176. Beauparlant, P. & J. Hiscott: Biological and biochemical inhibitors of the NF-kappa B/Rel proteins and cytokine synthesis. Cytokine Growth Factor Rev, 7, 175-90 (1996) (Pubitemid 27198076)
177. Chen, F., Y. Lu, D. C. Kuhn, M. Maki, X. Shi, S. C. Sun & L. M. Demers: Calpain contributes to silica-induced I kappa B-alpha degradation and nuclear factor-kappa B activation. Arch Biochem Biophys, 342, 383-8 (1997) (Pubitemid 27251261)
178. Unlap, T. & R. S. Jope: Dexamethasone attenuates kainate-induced AP-1 activation in rat brain. Brain Res Mol Brain Res, 24, 275-82 (1994) (Pubitemid 24202864)
179. Scheinman, R. I., P. C. Cogswell, A. K. Lofquist & A. S. Baldwin, Jr.: Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science, 270, 283-6 (1995)
180. Auphan, N., J. A. DiDonato, C. Rosette, A. Helmberg & M. Karin: Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science, 270, 286-90 (1995)
181. Bielinska, A., R. A. Shivdasani, L. Q. Zhang & G. J. Nabel: Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. Science, 250, 997-1000 (1990) (Pubitemid 120031808)
182. Vousden, K. H. & X. Lu: Live or let die: the cell's response to p53. Nat Rev Cancer, 2, 594-604 (2002) (Pubitemid 37328926)
183. Meek, D. W.: The p53 response to DNA damage. DNA Repair (Amst), 3, 1049-56 (2004) (Pubitemid 38997947)
184. Vogelstein, B., D. Lane & A. J. Levine: Surfing the p53 network. Nature, 408, 307-10 (2000)
185. Lowe, S. W., E. Cepero & G. Evan: Intrinsic tumour suppression. Nature, 432, 307-15 (2004) (Pubitemid 39551658)
186. Yu, J., L. Zhang, P. M. Hwang, C. Rago, K. W. Kinzler & B. Vogelstein: Identification and classification of p53-regulated genes. Proc Natl Acad Sci U S A, 96, 14517-22 (1999) (Pubitemid 30000682)
187. Polyak, K., Y. Xia, J. L. Zweier, K. W. Kinzler & B. Vogelstein: A model for p53-induced apoptosis. Nature, 389, 300-5 (1997) (Pubitemid 27406646)
188. Laptenko, O. & C. Prives: Transcriptional regulation by p53: one protein, many possibilities. Cell Death Differ, 13, 951-61 (2006)
189. Kim, E. & W. Deppert: The versatile interactions of p53 with DNA: when flexibility serves specificity. Cell Death Differ, 13, 885-9 (2006)
190. Jayaraman, L. & C. Prives: Covalent and noncovalent modifiers of the p53 protein. Cell Mol Life Sci, 55, 76-87 (1999) (Pubitemid 29077856)
191. Lin, J., J. Chen, B. Elenbaas & A. J. Levine: Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev, 8, 1235-46 (1994) (Pubitemid 24163450)
192. Ryan, K. M., A. C. Phillips & K. H. Vousden: Regulation and function of the p53 tumor suppressor protein. Curr Opin Cell Biol, 13, 332-7 (2001) (Pubitemid 32429498)
193. Prives, C. & P. A. Hall: The p53 pathway. J Pathol, 187, 112-26 (1999) (Pubitemid 29009841)
194. Shimizu, H., L. R. Burch, A. J. Smith, D. Dornan, M. Wallace, K. L. Ball & T. R. Hupp: The conformationally flexible S9-S10 linker region in the core domain of p53 contains a novel MDM2 binding site whose mutation increases ubiquitination of p53 in vivo. J Biol Chem, 277, 28446-58 (2002) (Pubitemid 41079269)
195. Hollstein, M., D. Sidransky, B. Vogelstein & C. C. Harris: p53 mutations in human cancers. Science, 253, 49-53 (1991) (Pubitemid 21917115)
196. Graeber, T. G., C. Osmanian, T. Jacks, D. E. Housman, C. J. Koch, S. W. Lowe & A. J. Giaccia: Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature, 379, 88-91 (1996) (Pubitemid 26008141)
197. Weinmann, M., V. Jendrossek, D. Guner, B. Goecke & C. Belka: Cyclic exposure to hypoxia and reoxygenation selects for tumor cells with defects in mitochondrial apoptotic pathways. Faseb J, 18, 1906-8 (2004) (Pubitemid 39602279)
198. Wallace-Brodeur, R. R. & S. W. Lowe: Clinical implications of p53 mutations. Cell Mol Life Sci, 55, 64-75 (1999) (Pubitemid 29077855)
199. Bristow, R. G., S. Benchimol & R. P. Hill: The p53 gene as a modifier of intrinsic radiosensitivity: implications for radiotherapy. Radiother Oncol, 40, 197-223 (1996) (Pubitemid 27314227)
200. Erler, J. T., C. J. Cawthorne, K. J. Williams, M. Koritzinsky, B. G. Wouters, C. Wilson, C. Miller, C. Demonacos, I. J. Stratford & C. Dive: Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and-independent mechanisms and contributes to drug resistance. Mol Cell Biol, 24, 2875-89 (2004) (Pubitemid 38381277)
201. Vassilev, L. T., B. T. Vu, B. Graves, D. Carvajal, F. Podlaski, Z. Filipovic, N. Kong, U. Kammlott, C. Lukacs, C. Klein, N. Fotouhi & E. A. Liu: In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science, 303, 844-8 (2004) (Pubitemid 38174664)
202. Barbieri, E., P. Mehta, Z. Chen, L. Zhang, A. Slack, S. Berg & J. M. Shohet: MDM2 inhibition sensitizes neuroblastoma to chemotherapy-induced apoptotic cell death. Mol Cancer Ther, 5, 2358-65 (2006) (Pubitemid 44530473)
203. Schuler, M., R. Herrmann, J. L. De Greve, A. K. Stewart, U. Gatzemeier, D. J. Stewart, L. Laufman, R. Gralla, J. Kuball, R. Buhl, C. P. Heussel, F. Kommoss, A. P. Perruchoud, F. A. Shepherd, M. A. Fritz, J. A. Horowitz, C. Huber & C. Rochlitz: Adenovirus-mediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-small-cell lung cancer: results of a multicenter phase II study. J Clin Oncol, 19, 1750-8 (2001) (Pubitemid 32230877)
204. Schuler, M., C. Rochlitz, J. A. Horowitz, J. Schlegel, A. P. Perruchoud, F. Kommoss, C. T. Bolliger, H. U. Kauczor, P. Dalquen, M. A. Fritz, S. Swanson, R. Herrmann & C. Huber: A phase I study of adenovirusmediated wild-type p53 gene transfer in patients with advanced non-small cell lung cancer. Hum Gene Ther, 9, 2075-82 (1998) (Pubitemid 28463925)
205. Swisher, S. G., J. A. Roth, R. Komaki, J. Gu, J. J. Lee, M. Hicks, J. Y. Ro, W. K. Hong, J. A. Merritt, K. Ahrar, N. E. Atkinson, A. M. Correa, M. Dolormente, L. Dreiling, A. K. El-Naggar, F. Fossella, R. Francisco, B. Glisson, S. Grammer, R. Herbst, A. Huaringa, B. Kemp, F. R. Khuri, J. M. Kurie, Z. Liao, T. J. McDonnell, R. Morice, F. Morello, R. Munden, V. Papadimitrakopoulou, K. M. Pisters, J. B. Putnam, Jr., A. J. Sarabia, T. Shelton, C. Stevens, D. M. Shin, W. R. Smythe, A. A. Vaporciyan, G. L. Walsh & M. Yin: Induction of p53-regulated genes and tumor regression in lung cancer patients after intratumoral delivery of adenoviral p53 (INGN 201) and radiation therapy. Clin Cancer Res, 9, 93-101 (2003) (Pubitemid 36109720)
206. Bykov, V. J., N. Issaeva, A. Shilov, M. Hultcrantz, E. Pugacheva, P. Chumakov, J. Bergman, K. G. Wiman & G. Selivanova: Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med, 8, 282-8 (2002) (Pubitemid 34250107)
207. Bykov, V. J., N. Zache, H. Stridh, J. Westman, J. Bergman, G. Selivanova & K. G. Wiman: PRIMA-1 (MET) synergizes with cisplatin to induce tumor cell apoptosis. Oncogene, 24, 3484-91 (2005) (Pubitemid 40756249)
208. Cao, Y., C. Y. Li, B. J. Moeller, D. Yu, Y. Zhao, M. R. Dreher, S. Shan & M. W. Dewhirst: Observation of incipient tumor angiogenesis that is independent of hypoxia and hypoxia inducible factor-1 activation. Cancer Res, 65, 5498-505 (2005) (Pubitemid 40911147)
209. Nieder, C., N. Wiedenmann, N. Andratschke & M. Molls: Current status of angiogenesis inhibitors combined with radiation therapy. Cancer Treat Rev, 32, 348-64 (2006) (Pubitemid 44063875)
210. Winkler, F., S. V. Kozin, R. T. Tong, S. S. Chae, M. F. Booth, I. Garkavtsev, L. Xu, D. J. Hicklin, D. Fukumura, E. di Tomaso, L. L. Munn & R. K. Jain: Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell, 6, 553-63 (2004) (Pubitemid 40017699)
211. Moeller, B. J., Y. Cao, C. Y. Li & M. W. Dewhirst: Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell, 5, 429-41 (2004) (Pubitemid 38610245)
212. Moeller, B. J., M. R. Dreher, Z. N. Rabbani, T. Schroeder, Y. Cao, C. Y. Li & M. W. Dewhirst: Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity. Cancer Cell, 8, 99-110 (2005) (Pubitemid 41132739)
213. Williams, K. J., B. A. Telfer, D. Xenaki, M. R. Sheridan, I. Desbaillets, H. J. Peters, D. Honess, A. L. Harris, G. U. Dachs, A. van der Kogel & I. J. Stratford: Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1. Radiother Oncol, 75, 89-98 (2005) (Pubitemid 40616800)
214. Erickson, K., R. D. Braun, D. Yu, J. Lanzen, D. Wilson, D. M. Brizel, T. W. Secomb, J. E. Biaglow & M. W. Dewhirst: Effect of longitudinal oxygen gradients on effectiveness of manipulation of tumor oxygenation. Cancer Res, 63, 4705-12 (2003) (Pubitemid 36951051)