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Role of Tumour Microenvironment in Chemoresistance

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Integration/Interaction of Oncologic Growth

Part of the book series: Cancer Growth and Progression ((CAGP,volume 15))

Abstract

Preclinical and clinical findings indicate multiple tumour micro-environmental factors, including growth factors, cytokines, cell-cell and cell-matrix adhesion molecules and hypoxia, protect solid tumours from therapeutic interventions. Experimental evidence have defined some of the resistance mechanisms, which have led to the development of innovative approaches aiming at specific targets. While some of these newer approaches have yielded therapeutic benefits in selected tumour types, considerable challenges remain in the management of the majority of patients with solid tumours. This chapter reviews the various tumour microenvironmental factors that contribute to drug resistance. These factors exert their effects through direct promoting resistance effectors and/or indirectly modulating other environmental factors. Furthermore, cooperative regulation, cross-talk and redundancy at different levels of signaling cascades affect the tumour progression and drug resistance, and can diminish the effectiveness of the single target therapeutic approach. A better understanding of the intersecting resistance pathways has the potential of leading to new therapeutic paradigms aiming at multiple targets, in order to overcome the microenvironment-conferred survival advantage to tumour cells.

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References

  1. Farber, S., Diamond, L.K., Mercer, R.D., Sylvester, R.F., and Wolff, R.D., 1948, Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid (aminopterin). N Engl J, 238:787–793.

    Google Scholar 

  2. Nygren, P., 2001, What is cancer chemotherapy? Acta Oncol, 40:166–174.

    PubMed  Google Scholar 

  3. Borges-Walmsley, M. I., McKeegan, K. S., and Walmsley, A. R., 2003, Structure and function of efflux pumps that confer resistance to drugs. Biochem J, 376:313–338.

    Article  PubMed  Google Scholar 

  4. Leonessa, F., and Clarke, R., 2003, ATP binding cassette transporters and drug resistance in breast cancer. Endocr Relat Cancer, 10:43–73.

    PubMed  Google Scholar 

  5. Varadi, A., Szakacs, G., Bakos, E., and Sarkadi, B., 2002, P glycoprotein and the mechanism of multidrug resistance. Novartis Found Symp, 243:54–65.

    PubMed  Google Scholar 

  6. Gottesman, M.M., Fojo, T., and Bates, S.E., 2002, Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer, 2:48–58.

    Article  PubMed  Google Scholar 

  7. Litman, T., Druley, T.E., Stein, W. D., and Bates, S.E., 2001, From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance. Cell Mol Life Sci, 58:931–959.

    PubMed  Google Scholar 

  8. Persidis, A., 1999, Cancer multidrug resistance. Nat Biotechnol, 17:94–95.

    PubMed  Google Scholar 

  9. Townsend, D.M., and Tew, K.D., 2003, The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene, 22:7369–7375.

    Article  PubMed  Google Scholar 

  10. Hayes, J.D., and Pulford, D.J., 1995, The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol, 30:445–600.

    PubMed  Google Scholar 

  11. Rasheed, Z.A., and Rubin, E.H., 2003, Mechanisms of resistance to topoisomerase I-targeting drugs. Oncogene, 22:7296–7304.

    Article  PubMed  Google Scholar 

  12. Dingemans, A.M., Pinedo, H.M., and Giaccone, G., 1998, Clinical resistance to topoisomerase-targeted drugs. Biochim Biophys Acta, 1400:275–288.

    PubMed  Google Scholar 

  13. Orr, G. A., Verdier-Pinard, P., McDaid, H., and Horwitz, S.B., 2003, Mechanisms of Taxol resistance related to microtubules. Oncogene, 22:7280–7295.

    Article  PubMed  Google Scholar 

  14. Drukman, S., and Kavallaris, M., 2002, Microtubule alterations and resistance to tubulin-binding agents (review). Int J Oncol, 21:621–628.

    PubMed  Google Scholar 

  15. Sangrajrang, S., and Fellous, A., 2000, Taxol resistance. Chemotherapy, 46:327–334.

    Article  PubMed  Google Scholar 

  16. Hersey, P., and Zhang, X. D., 2003, Overcoming resistance of cancer cells to apoptosis. J Cell Physiol, 196:9–18.

    Article  Google Scholar 

  17. Tolomeo, M., and Simoni, D., 2002, Drug resistance and apoptosis in cancer treatment: development of new apoptosis-inducing agents active in drug resistant malignancies. Curr Med Chem Anti-Canc Agents, 2:387–401.

    Article  PubMed  Google Scholar 

  18. Reed, J.C., 1995, Bcl-2: prevention of apoptosis as a mechanism of drug resistance. Hematol Oncol Clin North Am, 9:451–473.

    PubMed  Google Scholar 

  19. Nygren, P., and Larsson, R., 2003, Overview of the clinical efficacy of investigational anticancer drugs. J Intern Med, 253:46–75.

    Article  Google Scholar 

  20. Teicher, B.A., Herman, T.S., Holden, S.A., Wang, Y.Y., Pfeffer, M.R., Crawford, J.W., and Frei, III, E., 1990, Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. Science, 247:1457–1461.

    PubMed  Google Scholar 

  21. Hoffman, R.M., 1999, Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: a bridge to the clinic. Invest New Drugs, 17:343–359.

    Article  PubMed  Google Scholar 

  22. Kuo, T.H., Kubota, T., Watanabe, M., Furukawa, T., Kase, S., Tanino, H., Saikawa, Y., Ishibiki, K., Kitajima, M., and Hoffman, R. M., 1993, Site-specific chemosensitivity of human small-cell lung carcinoma growing orthotopically compared to subcutaneously in SCID mice: the importance of orthotopic models to obtain relevant drug evaluation data. Anticancer Res, 13:627–630.

    PubMed  Google Scholar 

  23. Wilmanns, C., Fan, D., O'Brian, C.A., Bucana, C.D., and Fidler, I.J., 1992, Orthotopic and ectopic organ environments differentially influence the sensitivity of murine colon carcinoma cells to doxorubicin and 5-fluorouracil. Int J Cancer, 52:98–104.

    PubMed  Google Scholar 

  24. Fidler, I.J., Wilmanns, C., Staroselsky, A., Radinsky, R., Dong, Z., and Fan, D., 1994, Modulation of tumor cell response to chemotherapy by the organ environment. Cancer Metastasis Rev, 13:209–222.

    Article  PubMed  Google Scholar 

  25. Ahn, K.S., Jung, Y.S., Kim, J., Lee, H., and Yoon, S.S., 2001, Behavior of murine renal carcinoma cells grown in ectopic or orthotopic sites in syngeneic mice. Tumour Biol, 22:146–153.

    Article  PubMed  Google Scholar 

  26. Song, S., Wientjes, M.G., Gan, Y., and Au, J.L., 2000, Fibroblast growth factors: an epigenetic mechanism of broad spectrum resistance to anticancer drugs. Proc Natl Acad Sci USA, 97:8658–8663.

    Article  PubMed  Google Scholar 

  27. Paull, K.D., Shoemaker, R.H., Hodes, L., Monks, A., Scudiero, D.A., Rubinstein, L., Plowman, J., and Boyd, M.R., 1989, Display and analysis of patterns of differential activity of drugs against human tumor cell lines: development of mean graph and COMPARE algorithm. J Natl Cancer Inst, 81:1088–1092.

    PubMed  Google Scholar 

  28. Laskin, J.J., and Sandler, A.B., 2004, Epidermal growth factor receptor: a promising target in solid tumours. Cancer Treat Rev, 30:1–17.

    Article  PubMed  Google Scholar 

  29. Ciardiello, F. and Tortora, G., 2003, Epidermal growth factor receptor (EGFR) as a target in cancer therapy: understanding the role of receptor expression and other molecular determinants that could influence the response to anti-EGFR drugs. Eur J Cancer, 39:1348–1354.

    Article  PubMed  Google Scholar 

  30. Holbro, T., Civenni, G., and Hynes, N.E., 2003, The ErbB receptors and their role in cancer progression. Exp Cell Res, 284:99–110

    Article  PubMed  Google Scholar 

  31. Lichtner, R.B., 2003, Estrogen/EGF receptor interactions in breast cancer: rationale for new therapeutic combination strategies. Biomed Pharmacother, 57:447–451.

    Article  PubMed  Google Scholar 

  32. Nicholson, R.I., Gee, J.M., and Harper, M.E., 2001, EGFR and cancer prognosis. Eur J Cancer, 37Suppl 4:S9–15.

    Article  PubMed  Google Scholar 

  33. Lorenzo, G.D., Bianco, R., Tortora, G., and Ciardiello, F., 2003, Involvement of growth factor receptors of the epidermal growth factor receptor family in prostate cancer development and progression to androgen independence. Clin Prostate Cancer, 2:50–57.

    PubMed  Google Scholar 

  34. Sartor, C.I., 2003, Epidermal growth factor family receptors and inhibitors: radiation response modulators. Semin.Radiat.Oncol., 13: 22–30.

    Article  PubMed  Google Scholar 

  35. Ang, K.K., Andratschke, N.H., and Milas, L., 2004, Epidermal growth factor receptor and response of head-and-neck carcinoma to therapy. Int J Radiat Oncol Biol Phys, 58:959–965.

    Article  PubMed  Google Scholar 

  36. Meden, H., Marx, D., Roegglen, T., Schauer, A., and Kuhn, W., 1998, Overexpression of the oncogene c-erbB-2 (HER2/neu) and response to chemotherapy in patients with ovarian cancer. Int J Gynecol Pathol, 17:61–65.

    PubMed  Google Scholar 

  37. Felip, E., Del Campo, J.M., Rubio, D., Vidal, M.T., Colomer, R., and Bermejo, B., 1995, Overexpression of c-erbB-2 in epithelial ovarian cancer. Prognostic value and relationship with response to chemotherapy. Cancer, 75:2147–2152.

    PubMed  Google Scholar 

  38. Niibe, Y., Nakano, T., Ohno, T., Suzuki, Y., Oka, K., and Tsujii, H., 2003, Prognostic significance of c-erbB-2/HER2 expression in advanced uterine cervical carcinoma with para-aortic lymph node metastasis treated with radiation therapy. Int J Gynecol Cancer, 13: 849–855.

    Article  PubMed  Google Scholar 

  39. Chakravarti, A., Dicker, A., and Mehta, M., 2004, The contribution of epidermal growth factor receptor (EGFR) signaling pathway to radioresistance in human gliomas: a review of preclinical and correlative clinical data. Int J Radiat Oncol Biol Phys, 58:927–931.

    Article  PubMed  Google Scholar 

  40. Kari, C., Chan, T. O., Rocha, d. Q., and Rodeck, U. 2003, Targeting the epidermal growth factor receptor in cancer: apoptosis takes center stage. Cancer Res, 63:1–5.

    PubMed  Google Scholar 

  41. Kumar, R., Mandal, M., Lipton, A., Harvey, H., and Thompson, C.B., 1996, Overexpression of HER2 modulates bcl-2, bcl-XL, and tamoxifen-induced apoptosis in human MCF-7 breast cancer cells. Clin Cancer Res, 2:1215–1219.

    PubMed  Google Scholar 

  42. Golubovskaya, V., Beviglia, L., Xu, L. H., Earp, III, H. S., Craven, R., and Cance, W., 2002, Dual inhibition of focal adhesion kinase and epidermal growth factor receptor pathways cooperatively induces death receptor-mediated apoptosis in human breast cancer cells. J Biol Chem, 277:38978–38987.

    Article  Google Scholar 

  43. Cao, L., Yao, Y., Lee, V., Kiani, C., Spaner, D., Lin, Z., Zhang, Y., Adams, M.E., and Yang, B.B., 2000, Epidermal growth factor induces cell cycle arrest and apoptosis of squamous carcinoma cells through reduction of cell adhesion. J Cell Biochem, 77:569–583.

    Article  PubMed  Google Scholar 

  44. Kottke, T.J., Blajeski, A.L., Martins, L.M., Mesner, Jr., P.W., Davidson, N.E., Earnshaw, W.C., Armstrong, D.K., and Kaufmann, S.H., 1999, Comparison of paclitaxel-, 5-fluoro-2′-deoxyuridine-, and epidermal growth factor (EGF)-induced apoptosis. Evidence for EGF-induced anoikis. J Biol Chem, 274:15927–15936.

    Article  PubMed  Google Scholar 

  45. Allen, G. C., Lubas, S., Wax, M. K., and Devore, R. F., III 1996. Epidermal growth factor regulates topoisomerase II activity and drug sensitivity in human KB cells. Otolaryngol.Head Neck Surg., 114:785–792.

    Article  PubMed  Google Scholar 

  46. Boudny, V., Murakami, Y., Nakano, S., and Niho, Y., 1999, Expression of activated c-erbB-2 oncogene induces sensitivity to cisplatin in human gallbladder adenocarcinoma cells. Anticancer Res, 19:5203–5206.

    PubMed  Google Scholar 

  47. Kroning, R., Jones, J.A., Hom, D.K., Chuang, C. C., Sanga, R., Los, G., Howell, S. B., and Christen, R. D., 1995, Enhancement of drug sensitivity of human malignancies by epidermal growth factor. Br J Cancer, 72:615–619.

    PubMed  Google Scholar 

  48. Amagase, H., Tamura, K., Hashimoto, K., Fuwa, T., Murakami, T., and Yata, N., 1990, Response of A431 experimental human solid xenograft to mitomycin C in combination with human epidermal growth factor in mice. J Pharmacobiodyn, 13:263–268.

    PubMed  Google Scholar 

  49. Ling, Y.H., Donato, N.J., and Perez-Soler, R., 2001, Sensitivity to topoisomerase I inhibitors and cisplatin is associated with epidermal growth factor receptor expression in human cervical squamous carcinoma ME180 sublines. Cancer Chemother Pharmacol, 47:473–480.

    Article  PubMed  Google Scholar 

  50. Thor, A.D., Berry, D.A., Budman, D.R., Muss, H.B., Kute, T., Henderson, I.C., Barcos, M., Cirrincione, C., Edgerton, S., Allred, C., Norton, L., and Liu, E.T., 1998, erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. J Natl Cancer Inst, 90:1346–1360.

    Article  PubMed  Google Scholar 

  51. Campiglio, M., Somenzi, G., Olgiati, C., Beretta, G., Balsari, A., Zaffaroni, N., Valagussa, P., and Menard, S., 2003, Role of proliferation in HER2 status predicted response to doxorubicin. Int J Cancer, 105:568–573.

    Article  PubMed  Google Scholar 

  52. Paik, S., Bryant, J., Park, C., Fisher, B., Tan-Chiu, E., Hyams, D., Fisher, E.R., Lippman, M.E., Wickerham, D.L., and Wolmark, N., 1998, erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst, 90:1361–1370.

    Article  Google Scholar 

  53. Clark, G.M., 1998, Should selection of adjuvant chemotherapy for patients with breast cancer be based on erbB-2 status?. J Natl Cancer Inst, 90:1320–1321.

    Article  PubMed  Google Scholar 

  54. Muss, H.B., Thor, A.D., Berry, D.A., Kute, T., Liu, E.T., Koerner, F., Cirrincione, C.T., Budman, D.R., Wood, W.C., and Barcos, M., 1994, c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med, 330:1260–1266.

    Article  PubMed  Google Scholar 

  55. Gandour-Edwards, R., Lara, Jr., P.N., Folkins, A.K., LaSalle, J.M., Beckett, L., Li, Y., Meyers, F.J., and DeVere-White, R., 2002, Does HER2/neu expression provide prognostic information in patients with advanced urothelial carcinoma?. Cancer, 95: 1009–1015.

    Article  Google Scholar 

  56. Baselga, J., Seidman, A.D., Rosen, P.P., and Norton, L., 1997, HER2 overexpression and paclitaxel sensitivity in breast cancer: therapeutic implications. Oncology (Huntingt), 11:43–48.

    Google Scholar 

  57. Koizumi, F., Kanzawa, F., Ueda, Y., Koh, Y., Tsukiyama, S., Taguchi, F., Tamura, T., Saijo, N., and Nishio, K., 2004, Synergistic interaction between the EGFR tyrosine kinase inhibitor gefitinib (“Iressa”) and the DNA topoisomerase I inhibitor CPT-11 (irinotecan) in human colorectal cancer cells. Int J Cancer, 108:464–472.

    Article  PubMed  Google Scholar 

  58. Montemurro, F., Valabrega, G., and Aglietta, M., 2004, Trastuzumab-based combination therapy for breast cancer. Expert Opin Pharmacother, 5:81–96.

    Article  PubMed  Google Scholar 

  59. Ligibel, J.A. and Winer, E.P., 2002, Trastuzumab/chemotherapy combinations in metastatic breast cancer. Semin Oncol, 29:38–43.

    Article  Google Scholar 

  60. Vogel, C.L., Cobleigh, M.A., Tripathy, D., Gutheil, J.C., Harris, L.N., Fehrenbacher, L., Slamon, D.J., Murphy, M., Novotny, W.F., Burchmore, M., Shak, S., and Stewart, S.J., 2001, First-line Herceptin monotherapy in metastatic breast cancer. Oncology, 61Suppl2: 37–42.

    Article  PubMed  Google Scholar 

  61. Cobleigh, M.A., Vogel, C.L., Tripathy, D., Robert, N.J., Scholl, S., Fehrenbacher, L., Wolter, J.M., Paton, V., Shak, S., Lieberman, G., and Slamon, D.J., 1999, Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol, 17:2639–2648.

    PubMed  Google Scholar 

  62. Baselga, J., Tripathy, D., Mendelsohn, J., Baughman, S., Benz, C.C., Dantis, L., Sklarin, N.T., Seidman, A.D., Hudis, C.A., Moore, J., Rosen, P.P., Twaddell, T., Henderson, I.C., and Norton, L., 1996, Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol, 14:737–744.

    PubMed  Google Scholar 

  63. Slamon, D.J., Leyland-Jones, B., Shak, S., Fuchs, H., Paton, V., Bajamonde, A., Fleming, T., Eiermann, W., Wolter, J., Pegram, M., Baselga, J., and Norton, L., 2001, Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Eng J Med, 344:783–792.

    Article  Google Scholar 

  64. Tan, A.R. and Swain, S.M., 2003, Ongoing adjuvant trials with trastuzumab in breast cancer. Semin Oncol, 30:54–64.

    Article  Google Scholar 

  65. Piccart-Gebhart, M.J., 2001, Herceptin: the future in adjuvant breast cancer therapy. Anticancer Drugs, 12Suppl 4:S27–S33.

    PubMed  Google Scholar 

  66. Slamon, D. and Pegram, M., 2001, Rationale for trastuzumab (Herceptin) in adjuvant breast cancer trials. Semin Oncol, 28:13–19.

    Article  Google Scholar 

  67. Bunn, Jr., P.A., Helfrich, B., Soriano, A.F., Franklin, W.A., Varella-Garcia, M., Hirsch, F. R., Baron, A., Zeng, C., and Chan, D.C., 2001, Expression of Her-2/neu in human lung cancer cell lines by immunohistochemistry and fluorescence in situ hybridization and its relationship to in vitro cytotoxicity by trastuzumab and chemotherapeutic agents. Clin Cancer Res, 7:3239–3250.

    PubMed  Google Scholar 

  68. Hirsch, F.R., Helfrich, B., Franklin, W.A., Varella-Garcia, M., Chan, D.C., and Bunn, Jr., P.A., 2002, Preclinical studies of gemcitabine and trastuzumab in breast and lung cancer cell lines. Clin Breast Cancer, 3Suppl 1:12–16

    PubMed  Google Scholar 

  69. Gatzemeier, U., Groth, G., Butts, C., Van Zandwijk, N., Shepherd, F., Ardizzoni, A., Barton, C., Ghahramani, P., and Hirsh, V., 2004, Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer. Ann Oncol, 15:19–27

    Article  PubMed  Google Scholar 

  70. Lara, Jr., P.N., Chee, K.G., Longmate, J., Ruel, C., Meyers, F.J., Gray, C.R., Edwards, R.G., Gumerlock, P.H., Twardowski, P., Doroshow, J.H., and Gandara, D.R., 2004, Trastuzumab plus docetaxel in HER-2/neu-positive prostate carcinoma: final results from the California Cancer Consortium Screening and Phase II Trial. Cancer, 100:2125–2131

    Article  Google Scholar 

  71. Ziada, A., Barqawi, A., Glode, L.M., Varella-Garcia, M., Crighton, F., Majeski, S., Rosenblum, M., Kane, M., Chen, L., and Crawford, E.D., 2004, The use of trastuzumab in the treatment of hormone refractory prostate cancer; phase II trial. Prostate, 60:332–337

    Article  PubMed  Google Scholar 

  72. Andre, F., Le Chevalier, T., and Soria, J.C., 2004, Her2-neu: a target in lung cancer? Ann Oncol, 15 3–4.

    Article  PubMed  Google Scholar 

  73. Fernandes, A., Hamburger, A.W., and Gerwin, B.I., 1999, ErbB-2 kinase is required for constitutive stat 3 activation in malignant human lung epithelial cells. Int J Cancer, 83:564–570.

    Article  PubMed  Google Scholar 

  74. Thomas, M., 2003, Epidermal growth factor receptor tyrosine kinase inhibitors: application in non-small cell lung cancer. Cancer Nurs, 26:21S–25S.

    PubMed  Google Scholar 

  75. Giaccone, G., 2004, The role of gefitinib in lung cancer treatment. Clin Cancer Res, 10:4233s–4237s.

    Article  PubMed  Google Scholar 

  76. Perez-Soler, R., 2004, The role of erlotinib (Tarceva, OSI 774) in the treatment of non-small cell lung cancer. Clin Cancer Res, 10:4238s–4240s.

    Article  PubMed  Google Scholar 

  77. Xiong, H.Q., Rosenberg, A., LoBuglio, A., Schmidt, W., Wolff, R.A., Deutsch, J., Needle, M., and Abbruzzese, J.L., 2004, Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial. J Clin Oncol, 22:2610–2616.

    Article  PubMed  Google Scholar 

  78. Saltz, L.B., Meropol, N.J., Loehrer, Sr., P.J., Needle, M.N., Kopit, J., and Mayer, R.J., 2004, Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol, 22:1201–1208.

    Article  PubMed  Google Scholar 

  79. Reynolds, N.A. and Wagstaff, A.J., 2004, Cetuximab: in the treatment of metastatic colorectal cancer. Drugs, 64:109–118.

    PubMed  Google Scholar 

  80. Herbst, R.S. and Hong, W.K., 2002, IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody for treatment of head and neck cancer. Semin Oncol, 29:18–30.

    Article  Google Scholar 

  81. Herbst R.S., Prager D., Hermann R., Miller V., Fehrenbacher L., Hoffman P., Johnson B., Sandler A.B., Mass R., and Johnson D.H., 2004, TRIBUTE-A phase III trial of erlotinib HCl (OSI-774) combined with carboplatin and paclitaxel (CP) chemotherapy in advanced non-small cell lung cancer (NSCLC). [Abstract]. Journal of Clinical Oncology, ASCO Annual Meeting Proceedings (Post-Meeting Edition), 22:#7011.

    Google Scholar 

  82. Gatzemeier U., Pluzanska A., Szczensna A., Kaukel E., Roubec J., Brennscheidt U., De Rosa F., Muller B., and Von Pawel J., 2004, Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC). [Abstract]. Journal of Clinical Oncology, ASCO Annual Meeting Proceedings (Post-Meeting Edition), 22:#7010.

    Google Scholar 

  83. Paez, J.G., Janne, P.A., Lee, J.C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F.J., Lindeman, N., Boggon, T.J., Naoki, K., Sasaki, H., Fujii, Y., Eck, M.J., Sellers, W.R., Johnson, B.E., and Meyerson, M., 2004, EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science, 304:1497–1500.

    Article  PubMed  Google Scholar 

  84. Lynch, T.J., Bell, D.W., Sordella, R., Gurubhagavatula, S., Okimoto, R.A., Brannigan, B.W., Harris, P.L., Haserlat, S.M., Supko, J.G., Haluska, F.G., Louis, D.N., Christiani, D.C., Settleman, J., and Haber, D.A., 2004, Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Eng J Med, 350:2129–2139.

    Article  Google Scholar 

  85. Sordella, R., Bell, D.W., Haber, D.A., and Settleman, J., 2004, Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science, 305:1163–1167.

    Article  Google Scholar 

  86. Bikfalvi, A., Klein, S., Pintucci, G., and Rifkin, D.B., 1997, Biological roles of fibroblast growth factor-2. Endocr Rev, 18: 26–45.

    Article  PubMed  Google Scholar 

  87. Ornitz, D.M. and Itoh, N., 2001, Fibroblast growth factors. Genome Biol, 2:REVIEWS3005.

    Google Scholar 

  88. Burgess, W.H. and Maciag, T., 1989, The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem, 58:575–606.

    Article  PubMed  Google Scholar 

  89. Fuks, Z., Persaud, R.S., Alfieri, A., McLoughlin, M., Ehleiter, D., Schwartz, J.L., Seddon, A.P., Cordon-Cardo, C., and Haimovitz-Friedman, A., 1994, Basic fibroblast growth factor protects endothelial cells against radiation-induced programmed cell death in vitro and in vivo. Cancer Res, 54:2582–2590

    PubMed  Google Scholar 

  90. Yayon, A. and Klagsbrun, M., 1990, Autocrine regulation of cell growth and transformation by basic fibroblast growth factor. Cancer Metastasis Rev, 9:191–202.

    Article  PubMed  Google Scholar 

  91. Johnson, D.E. and Williams, L.T., 1993, Structural and functional diversity in the FGF receptor multigene family. Adv Cancer Res, 60:1–41.

    PubMed  Google Scholar 

  92. Ornitz, D.M., Xu, J., Colvin, J.S., McEwen, D.G., MacArthur, C.A., Coulier, F., Gao, G., and Goldfarb, M., 1996, Receptor specificity of the fibroblast growth factor family. J Biol Chem, 271:15292–15297.

    Article  PubMed  Google Scholar 

  93. Valve, E.M., Nevalainen, M.T., Nurmi, M.J., Laato, M.K., Martikainen, P.M., and Harkonen, P.L., 2001, Increased expression of FGF-8 isoforms and FGF receptors in human premalignant prostatic intraepithelial neoplasia lesions and prostate cancer. Lab Invest, 81:815–826.

    PubMed  Google Scholar 

  94. Dell'Era, P., Mohammadi, M., and Presta, M., 1999, Different tyrosine autophosphorylation requirements in fibroblast growth factor receptor-1 mediate urokinase-type plasminogen activator induction and mitogenesis. Mol Biol Cell, 10:23–33.

    PubMed  Google Scholar 

  95. Spivak-Kroizman, T., Lemmon, M.A., Dikic, I., Ladbury, J.E., Pinchasi, D., Huang, J., Jaye, M., Crumley, G., Schlessinger, J., and Lax, I., 1994, Heparin-induced oligomerization of FGF molecules is responsible for FGF receptor dimerization, activation, and cell proliferation. Cell, 79:1015–1024.

    Article  PubMed  Google Scholar 

  96. Friesel, R.E. and Maciag, T., 1995, Molecular mechanisms of angiogenesis: fibroblast growth factor signal transduction. FASEB J, 9:919–925.

    PubMed  Google Scholar 

  97. Xing, J., Ginty, D.D., and Greenberg, M.E., 1996, Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science, 273:959–963.

    PubMed  Google Scholar 

  98. Tan, Y., Ruan, H., Demeter, M.R., and Comb, M.J., 1999, p90(RSK) blocks bad-mediated cell death via a protein kinase C-dependent pathway. J Biol Chem, 274:34859–34867.

    Article  PubMed  Google Scholar 

  99. Shimamura, A., Ballif, B.A., Richards, S.A., and Blenis, J., 2000, Rsk1 mediates a MEK-MAP kinase cell survival signal. Curr Biol, 10:127–135.

    Article  PubMed  Google Scholar 

  100. Zong, W.X., Edelstein, L.C., Chen, C., Bash, J., and Gelinas, C., 1999, The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-kappaB that blocks TNFalpha-induced apoptosis. Genes Dev., 13:382–387.

    PubMed  Google Scholar 

  101. Ghoda, L., Lin, X., and Greene, W.C., 1997, The 90-kDa ribosomal S6 kinase (pp90rsk) phosphorylates the N-terminal regulatory domain of IkappaBalpha and stimulates its degradation in vitro. J Biol Chem, 272 21281–21288.

    Article  PubMed  Google Scholar 

  102. Bertolotto, C., Maulon, L., Filippa, N., Baier, G., and Auberger, P., 2000, Protein kinase C theta and epsilon promote T-cell survival by a rsk-dependent phosphorylation and inactivation of BAD. J Biol Chem, 275:37246–37250.

    Article  PubMed  Google Scholar 

  103. Delehedde, M., Seve, M., Sergeant, N., Wartelle, I., Lyon, M., Rudland, P.S., and Fernig, D.G., 2000, Fibroblast growth factor-2 stimulation of p42/44MAPK phosphorylation and IkappaB degradation is regulated by heparan sulfate/heparin in rat mammary fibroblasts. J Biol Chem, 275:33905–33910.

    Article  Google Scholar 

  104. Du, K., and Montminy, M., 1998, CREB is a regulatory target for the protein kinase Akt/PKB. J Biol Chem, 273:32377–32379.

    Article  PubMed  Google Scholar 

  105. Chen, C., Edelstein, L.C., and Gelinas, C., 2000, The Rel/NF-kappaB family directly activates expression of the apoptosis inhibitor Bcl-x(L). Mol Cell Biol, 20:2687–2695.

    Article  PubMed  Google Scholar 

  106. Bonni, A., Brunet, A., West, A.E., Datta, S.R., Takasu, M.A., and Greenberg, M.E., 1999, Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and-independent mechanisms. Science, 286:1358–1362.

    Article  PubMed  Google Scholar 

  107. Cardone, M.H., Roy, N., Stennicke, H.R., Salvesen, G.S., Franke, T.F., Stanbridge, E., Frisch, S., and Reed, J.C., 1998, Regulation of cell death protease caspase-9 by phosphorylation. Science, 282:1318–1321.

    Article  PubMed  Google Scholar 

  108. Fenig, E., Wieder, R., Paglin, S., Wang, H., Persaud, R., Haimovitz-Friedman, A., Fuks, Z., and Yahalom, J., 1997, Basic fibroblast growth factor confers growth inhibition and mitogen-activated protein kinase activation in human breast cancer cells. Clin Cancer Res, 3:135–142.

    PubMed  Google Scholar 

  109. Wang, H., Rubin, M., Fenig, E., DeBlasio, A., Mendelsohn, J., Yahalom, J., and Wieder, R., 1997, Basic fibroblast growth factor causes growth arrest in MCF-7 human breast cancer cells while inducing both mitogenic and inhibitory G1 events. Cancer Res, 57:1750–1757.

    PubMed  Google Scholar 

  110. Schweigerer, L., Neufeld, G., and Gospodarowicz, D., 1987, Basic fibroblast growth factor as a growth inhibitor for cultured human tumor cells. J Clin Ivest, 80:1516–1520.

    Google Scholar 

  111. Coleman, A.B., 2003, Positive and negative regulation of cellular sensitivity to anti-cancer drugs by FGF-2. Drug Resist Updat, 6:85–94.

    Article  Google Scholar 

  112. Huang, A., Jin, H., and Wright, J.A., 1994, Aberrant expression of basic fibroblast growth factor in NIH-3T3 cells alters drug resistance and gene amplification potential. Exp Cell Res, 213:335–339.

    Article  PubMed  Google Scholar 

  113. Huang, A. and Wright, J.A., 1994, Fibroblast growth factor mediated alterations in drug resistance, and evidence of gene amplification. Oncogene, 9:491–499.

    PubMed  Google Scholar 

  114. Linderholm, B.K., Lindh, B., Beckman, L., Erlanson, M., Edin, K., Travelin, B., Bergh, J., Grankvist, K., and Henriksson, R., 2003, Prognostic correlation of basic fibroblast growth factor and vascular endothelial growth factor in 1307 primary breast cancers. Clin Breast Cancer, 4:340–347.

    PubMed  Google Scholar 

  115. Smith, K., Fox, S.B., Whitehouse, R., Taylor, M., Greenall, M., Clarke, J., and Harris, A.L., 1999, Upregulation of basic fibroblast growth factor in breast carcinoma and its relationship to vascular density, oestrogen receptor, epidermal growth factor receptor and survival. Ann Oncol, 10:707–713.

    Article  PubMed  Google Scholar 

  116. Blanckaert, V.D., Hebbar, M., Louchez, M.M., Vilain, M.O., Schelling, M.E., and Peyrat, J.P., 1998, Basic fibroblast growth factor receptors and their prognostic value in human breast cancer. Clin Cancer Res, 4:2939–2947.

    PubMed  Google Scholar 

  117. Colomer, R., Aparicio, J., Montero, S., Guzman, C., Larrodera, L., and Cortes-Funes, H., 1997, Low levels of basic fibroblast growth factor (bFGF) are associated with a poor prognosis in human breast carcinoma. Br J Cancer, 76:1215–1220.

    PubMed  Google Scholar 

  118. Yiangou, C., Gomm, J.J., Coope, R.C., Law, M., Luqmani, Y.A., Shousha, S., Coombes, R. C., and Johnston, C.L., 1997, Fibroblast growth factor 2 in breast cancer: occurrence and prognostic significance. Br J Cancer, 75:28–33.

    PubMed  Google Scholar 

  119. Obermair, A., Speiser, P., Reisenberger, K., Ullrich, R., Czerwenka, K., Kaider, A., Zeillinger, R., and Miksche, M., 1998, Influence of intratumoral basic fibroblast growth factor concentration on survival in ovarian cancer patients. Cancer Lett, 130:69–76.

    Article  Google Scholar 

  120. Bredel, M., Pollack, I.F., Campbell, J.W., and Hamilton, R.L., 1997, Basic fibroblast growth factor expression as a predictor of prognosis in pediatric high-grade gliomas. Clin Cancer Res, 3:2157–2164.

    PubMed  Google Scholar 

  121. Faridi, A., Rudlowski, C., Biesterfeld, S., Schuh, S., Rath, W., and Schroder, W., 2002, Long-term follow-up and prognostic significance of angiogenic basic fibroblast growth factor (bFGF) expression in patients with breast cancer. Pathol Res Pract, 198:1–5.

    Article  PubMed  Google Scholar 

  122. Tabone, M.D., Landman-Parker, J., Arcil, B., Coudert, M.C., Gerota, I., Benbunan, M., Leverger, G., and Dosquet, C., 2001, Are basic fibroblast growth factor and vascular endothelial growth factor prognostic indicators in pediatric patients with malignant solid tumors?. Clin Cancer Res, 7:538–543.

    PubMed  Google Scholar 

  123. Nguyen, M., Watanabe, H., Budson, A.E., Richie, J.P., Hayes, D.F., and Folkman, J., 1994, Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst, 86:356–361.

    PubMed  Google Scholar 

  124. Iwasaki, A., Kuwahara, M., Yoshinaga, Y., and Shirakusa, T., 2004, Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC. Eur J Cardiothorac Surg, 25:443–448.

    Article  PubMed  Google Scholar 

  125. Ruotsalainen, T., Joensuu, H., Mattson, K., and Salven, P., 2002, High pretreatment serum concentration of basic fibroblast growth factor is a predictor of poor prognosis in small cell lung cancer. Cancer Edpdemiol Biomarkers Prev, 11:1492–1495.

    Google Scholar 

  126. Joensuu, H., Anttonen, A., Eriksson, M., Makitaro, R., Alfthan, H., Kinnula, V., and Leppa, S., 2002, Soluble syndecan-1 and serum basic fibroblast growth factor are new prognostic factors in lung cancer. Cancer Res, 62:5210–5217.

    PubMed  Google Scholar 

  127. Ito, H., Oshita, F., Kameda, Y., Suzuki, R., Ikehara, M., Arai, H., Mitsuda, A., Saito, H., Yamada, K., Noda, K., and Nakayama, H., 2002, Expression of vascular endothelial growth factor and basic fibroblast growth factor in small adenocarcinomas. Oncol Rep, 9:119–123.

    PubMed  Google Scholar 

  128. Kos, M. and Dabrowski, A., 2002, Tumour's angiogenesis—the function of VEGF and bFGF in colorectal cancer. Ann Univ Mariae Curie Sklodowska [Med], 57:556–561.

    Google Scholar 

  129. Rasmuson, T., Grankvist, K., Jacobsen, J., and Ljungberg, B., 2001, Impact of serum basic fibroblast growth factor on prognosis in human renal cell carcinoma. Eur J Cancer, 37:2199–2203.

    Article  PubMed  Google Scholar 

  130. Dietz, A., Rudat, V., Conradt, C., Weidauer, H., Ho, A., and Moehler, T., 2000, Prognostic relevance of serum levels of the angiogenic peptide bFGF in advanced carcinoma of the head and neck treated by primary radiochemotherapy. Head Neck, 22:666–673.

    Article  PubMed  Google Scholar 

  131. Anzai, H., Kitadai, Y., Bucana, C.D., Sanchez, R., Omoto, R., and Fidler, I.J., 1998, Expression of metastasis-related genes in surgical specimens of human gastric cancer can predict disease recurrence. Eur J Cancer, 34:558–565.

    Article  PubMed  Google Scholar 

  132. Noda, M., Hattori, T., Kimura, T., Naitoh, H., Kodama, T., Kashima, K., and Pignatelli, M. 1997, Expression of fibroblast growth factor 2 mRNA in early and advanced gastric cancer. Acta Oncol, 36:695–700.

    PubMed  Google Scholar 

  133. Pazgal, I., Zimra, Y., Tzabar, C., Okon, E., Rabizadeh, E., Shaklai, M., and Bairey, O., 2002, Expression of basic fibroblast growth factor is associated with poor outcome in non-Hodgkin's lymphoma. Br J Cancer, 86:1770–1775.

    Article  PubMed  Google Scholar 

  134. Salven, P., Orpana, A., Teerenhovi, L., and Joensuu, H., 2000, Simultaneous elevation in the serum concentrations of the angiogenic growth factors VEGF and bFGF is an independent predictor of poor prognosis in non-Hodgkin lymphoma: a single-institution study of 200 patients. Blood, 96:3712–3718.

    PubMed  Google Scholar 

  135. Tanaka, S., Ueo, H., Mafune, K., Mori, M., Wands, J.R., and Sugimachi, K., 2001, A novel isoform of human fibroblast growth factor 8 is induced by androgens and associated with progression of esophageal carcinoma. Dig Dis Sci, 46:1016–1021.

    Article  PubMed  Google Scholar 

  136. Boelaert, K., McCabe, C.J., Tannahill, L.A., Gittoes, N.J., Holder, R.L., Watkinson, J.C., Bradwell, A.R., Sheppard, M.C., and Franklyn, J.A., 2003, Pituitary tumor transforming gene and fibroblast growth factor-2 expression: potential prognostic indicators in differentiated thyroid cancer. J Clin Endocrinol Metab, 88:2341–2347.

    Article  PubMed  Google Scholar 

  137. Sun, Y., Naito, Z., Ishiwata, T., Maeda, S., Sugisaki, Y., and Asano, G., 2003, Basic FGF and Ki-67 proteins useful for immunohistological diagnostic evaluations in malignant solitary fibrous tumor. Pathol Int, 53:284–290.

    Article  Google Scholar 

  138. Strizzi, L., Vianale, G., Catalano, A., Muraro, R., Mutti, L., and Procopio, A., 2001, Basic fibroblast growth factor in mesothelioma pleural effusions: correlation with patient survival and angiogenesis. Int J Oncol, 18:1093–1098.

    PubMed  Google Scholar 

  139. Lin, R.Y., Argenta, P.A., Sullivan, K.M., and Adzick, N.S., 1995, Diagnostic and prognostic role of basic fibroblast growth factor in Wilms’ tumor patients. Clin Cancer Res, 1:327–331.

    PubMed  Google Scholar 

  140. Ohta, T., Yamamoto, M., Numata, M., Iseki, S., Tsukioka, Y., Miyashita, T., Kayahara, M., Nagakawa, T., Miyazaki, I., Nishikawa, K., and Yoshitake, Y., 1995, Expression of basic fibroblast growth factor and its receptor in human pancreatic carcinomas. Br J Cancer, 72:824–831.

    PubMed  Google Scholar 

  141. Volm, M., Koomagi, R., Mattern, J., and Stammler, G., 1997, Prognostic value of basic fibroblast growth factor and its receptor (FGFR-1) in patients with non-small cell lung carcinomas. Eur J Cancer, 33:691–693.

    Article  PubMed  Google Scholar 

  142. Bange, J., Prechtl, D., Cheburkin, Y., Specht, K., Harbeck, N., Schmitt, M., Knyazeva, T., Muller, S., Gartner, S., Sures, I., Wang, H., Imyanitov, E., Haring, H.U., Knayzev, P., Iacobelli, S., Hofler, H., and Ullrich, A., 2002, Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele. Cancer Res, 62:840–847.

    PubMed  Google Scholar 

  143. Morimoto, Y., Ozaki, T., Ouchida, M., Umehara, N., Ohata, N., Yoshida, A., Shimizu, K., and Inoue, H., 2003, Single nucleotide polymorphism in fibroblast growth factor receptor 4 at codon 388 is associated with prognosis in high-grade soft tissue sarcoma. Cancer, 98:2245–2250.

    Article  PubMed  Google Scholar 

  144. Cappellen, D., De Oliveira, C., Ricol, D., de Medina, S., Bourdin, J., Sastre-Garau, X., Chopin, D., Thiery, J.P., and Radvanyi, F., 1999, Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet, 23:18–20.

    PubMed  Google Scholar 

  145. Ueno, K., Inoue, Y., Kawaguchi, T., Hosoe, S., and Kawahara, M., 2001, Increased serum levels of basic fibroblast growth factor in lung cancer patients: relevance to response of therapy and prognosis. Lung Cancer, 31:213–219.

    Article  PubMed  Google Scholar 

  146. Pardo, O.E., Arcaro, A., Salerno, G., Raguz, S., Downward, J., and Seckl, M.J., 2002, Fibroblast growth factor-2 induces translational regulation of Bcl-XL and Bcl-2 via a MEK-dependent pathway: correlation with resistance to etoposide-induced apoptosis. J Biol Chem, 277:12040–12046.

    Article  PubMed  Google Scholar 

  147. Pardo, O.E., Lesay, A., Arcaro, A., Lopes, R., Ng, B.L., Warne, P.H., McNeish, I.A., Tetley, T.D., Lemoine, N.R., Mehmet, H., Seckl, M.J., and Downward, J., 2003, Fibroblast growth factor 2-mediated translational control of IAPs blocks mitochondrial release of Smac/DIABLO and apoptosis in small cell lung cancer cells. Mol Cell Biol, 23:7600–7610.

    Article  PubMed  Google Scholar 

  148. Shaulian, E., Resnitzky, D., Shifman, O., Blandino, G., Amsterdam, A., Yayon, A., and Oren, M., 1997, Induction of Mdm2 and enhancement of cell survival by bFGF. Oncogene, 15:2717–2725.

    Article  PubMed  Google Scholar 

  149. Maloof, P., Wang, Q., Wang, H., Stein, D., Denny, T.N., Yahalom, J., Fenig, E., and Wieder, R., 1999, Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells. Breast Cancer Res Treat, 56:153–167.

    Article  PubMed  Google Scholar 

  150. Wang, Q., Maloof, P., Wang, H., Fenig, E., Stein, D., Nichols, G., Denny, T.N., Yahalom, J., and Wieder, R., 1998, Basic fibroblast growth factor downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells. Exp Cell Res, 238:177–187.

    Article  Google Scholar 

  151. Bisping, G., Leo, R., Wenning, D., Dankbar, B., Padro, T., Kropff, M., Scheffold, C., Kroger, M., Mesters, R.M., Berdel, W.E., and Kienast, J., 2003, Paracrine interactions of basic fibroblast growth factor and interleukin-6 in multiple myeloma. Blood, 101:2775–2783.

    Article  PubMed  Google Scholar 

  152. El Hariry, I., Pignatelli, M., and Lemoine, N., 2001, R. FGF-1 and FGF-2 regulate the expression of E-cadherin and catenins in pancreatic adenocarcinoma. Int J Cancer, 94:652–661.

    Article  PubMed  Google Scholar 

  153. El Hariry, I., Pignatelli, M., and Lemoine, N. R., 2001, FGF-1 and FGF-2 modulate the E-cadherin/catenin system in pancreatic adenocarcinoma cell lines. Br J Cancer, 84:1656–1663.

    Article  PubMed  Google Scholar 

  154. Qiao, D., Meyer, K., Mundhenke, C., Drew, S. A., and Friedl, A., 2003, Heparan sulfate proteoglycans as regulators of fibroblast growth factor-2 signaling in brain endothelial cells. Specific role for glypican-1 in glioma angiogenesis. J Biol Chem, 278:16045–16053.

    Article  PubMed  Google Scholar 

  155. Mundhenke, C., Meyer, K., Drew, S., and Friedl, A., 2002, Heparan sulfate proteoglycans as regulators of fibroblast growth factor-2 receptor binding in breast carcinomas. Am J Pathol, 160:185–194.

    PubMed  Google Scholar 

  156. Lambrecht, V., Le, B., X, Toillon, R.A., Boilly, B., and Hondermarck, H., 1998, Alterations in both heparan sulfate proteoglycans and mitogenic activity of fibroblast growth factor-2 are triggered by inhibitors of proliferation in normal and breast cancer epithelial cells. Exp Cell Res, 245:239–244.

    Article  PubMed  Google Scholar 

  157. Delehedde, M., Deudon, E., Boilly, B., and Hondermarck, H., 1996, Heparan sulfate proteoglycans play a dual role in regulating fibroblast growth factor-2 mitogenic activity in human breast cancer cells. Exp Cell Res, 229:398–406.

    Article  PubMed  Google Scholar 

  158. Genersch, E., Ferletta, M., Virtanen, I., Haller, H., and Ekblom, P., 2003, Integrin alphavbeta3 binding to human alpha5-laminins facilitates FGF-2-and VEGF-induced proliferation of human ECV304 carcinoma cells. Eur J Cell Biol, 82:105–117.

    Article  PubMed  Google Scholar 

  159. De Medina, S.G., Popov, Z., Chopin, D.K., Southgate, J., Tucker, G.C., Delouvee, A., Thiery, J.P., and Radvanyi, F., 1999, Relationship between E-cadherin and fibroblast growth factor receptor 2b expression in bladder carcinomas. Oncogene, 18:5722–5726.

    Article  Google Scholar 

  160. Cavallaro, U., Niedermeyer, J., Fuxa, M., and Christofori, G., 2001, N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling. Nat Cell Biol, 3:650–657.

    Article  PubMed  Google Scholar 

  161. Boyer, B., Dufour, S., and Thiery, J.P., 1992, E-cadherin expression during the acidic FGF-induced dispersion of a rat bladder carcinoma cell line. Exp Cell Res, 201:347–357.

    Article  PubMed  Google Scholar 

  162. Zhang, Y., Song, S., Yang, F., Au, J.L., and Wientjes, M.G., 2001, Nontoxic doses of suramin enhance activity of doxorubicin in prostate tumors. J Pharmacol Exp Ther, 299:426–433.

    PubMed  Google Scholar 

  163. Song, S., Wientjes, M.G., Walsh, C., and Au, J.L., 2001, Nontoxic doses of suramin enhance activity of paclitaxel against lung metastases. Cancer Res, 61:6145–6150.

    PubMed  Google Scholar 

  164. Xin Y., Chen D., Song S., Lyness G., Wientjes G., and Au J., 2004, Low-dose suramin enhances antitumor activity of mitomycin C in bladder tumors. [Abstract]. Proceedings of the AACR, 45:#2002.

    Google Scholar 

  165. Ogden A., Song S., Wientjes G., and Au J., 2004, Nontoxic doses of suramin enhance the activity of gemcitabine and paclitaxel in pancreatic tumors. [Abstract]. Proceedings of the AACR, 45:#2148.

    Google Scholar 

  166. Yu B., Song S., Wientjes G., and Au J., 2003, Suramin enhances activity of CPT-11 in human colorectal xenograft tumors [Abstract]. Proceedings of the AACR, 44:#763.

    Google Scholar 

  167. Lyness G., Jang S., Gan Y., Zhang Y., Wientjes G., and Au J., 2003, Fibroblast growth factors and chemoresistance in renal cell carcinomas [Abstract]. Proceedings of the AACR, 44:#4718.

    Google Scholar 

  168. Villalona-Calero M.A., Otterson G.A., Wientjes G., Kobayashi K., Jensen R., Young D., Yeh T., Song S., Grever M., and Au J., 2004, Phase II study of low dose suramin as a sensitizer of paclitaxel/carboplatin (P/C) in non small cell lung cancer (NSCLC). [Abstract]. Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition), 22:#7108.

    Google Scholar 

  169. Yu, H., and Rohan, T., 2000, Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst, 92:1472–1489.

    Article  PubMed  Google Scholar 

  170. LeRoith, D. and Roberts, Jr., C.T., 2003, The insulin-like growth factor system and cancer. Cancer Lett, 195:127–137.

    PubMed  Google Scholar 

  171. Samani, A.A., and Brodt, P., 2001, The receptor for the type I insulin-like growth factor and its ligands regulate multiple cellular functions that impact on metastasis. Surg Oncol Clin N Am, 10:289–312,viii.

    PubMed  Google Scholar 

  172. Lee, A.V., Hilsenbeck, S.G., and Yee, D., 1998, IGF system components as prognostic markers in breast cancer. Breast Cancer Res Treat, 47:295–302.

    Article  PubMed  Google Scholar 

  173. Kaaks, R. 2002. Nutrition, energy balance and colon cancer risk: the role of insulin and insulin-like growth factor-I. IARC Sci Publ, 156:289–293.

    PubMed  Google Scholar 

  174. Chan, J.M., Stampfer, M.J., Giovannucci, E., Ma, J., and Pollak, M., 2000, Insulin-like growth factor I (IGF-I), IGF-binding protein-3 and prostate cancer risk: epidemiological studies. Growth Horm IGF Res, 10Suppl A:S32–S33.

    Article  PubMed  Google Scholar 

  175. Giovannucci, E., 1999, Insulin-like growth factor-I and binding protein-3 and risk of cancer. Horm Res, 51Suppl3:34–41.

    Article  Google Scholar 

  176. Spitz, M.R., Barnett, M.J., Goodman, G.E., Thornquist, M.D., Wu, X., and Pollak, M., 2002, Serum insulin-like growth factor (IGF) and IGF-binding protein levels and risk of lung cancer: a case-control study nested in the beta-Carotene and Retinol Efficacy Trial Cohort. Cancer Edpdemiol Biomarkers Prev, 11:1413–1418.

    Google Scholar 

  177. Schernhammer, E.S., 2002, In-utero exposures and breast cancer risk: joint effect of estrogens and insulin-like growth factor? Cancer Causes Control, 13:505–508.

    Article  PubMed  Google Scholar 

  178. Pollak, M., 2000, Insulin-like growth factor physiology and cancer risk. Eur J Cancer, 36:1224–1228.

    Article  PubMed  Google Scholar 

  179. Baron-Hay, S., Boyle, F., Ferrier, A., and Scott, C., 2004, Elevated serum insulin-like growth factor binding protein-2 as a prognostic marker in patients with ovarian cancer. Clin Cancer Res, 10:1796–1806.

    Article  PubMed  Google Scholar 

  180. Gu, L., Shigemasa, K., and Ohama, K., 2004, Increased expression of IGF II mRNA-binding protein 1 mRNA is associated with an advanced clinical stage and poor prognosis in patients with ovarian cancer. Int J Oncol, 24:671–678.

    PubMed  Google Scholar 

  181. Peters, G., Gongoll, S., Langner, C., Mengel, M., Piso, P., Klempnauer, J., Ruschoff, J., Kreipe, H., and von Wasielewski, R., 2003, IGF-1R, IGF-1 and IGF-2 expression as potential prognostic and predictive markers in colorectal-cancer. Virchows Arch, 443:139–145.

    Article  PubMed  Google Scholar 

  182. Kawamoto, K., Onodera, H., Kondo, S., Kan, S., Ikeuchi, D., Maetani, S., and Imamura, M., 1998, Expression of insulin-like growth factor-2 can predict the prognosis of human colorectal cancer patients: correlation with tumor progression, proliferative activity and survival. Oncology, 55:242–248.

    Article  Google Scholar 

  183. Jamieson, T.A., Brizel, D.M., Killian, J.K., Oka, Y., Jang, H.S., Fu, X., Clough, R.W., Vollmer, R.T., Anscher, M.S., and Jirtle, R.L., 2003, M6P/IGF2R loss of heterozygosity in head and neck cancer associated with poor patient prognosis. BMC Cancer, 3:4.

    Article  PubMed  Google Scholar 

  184. Chang, Y.S., Wang, L., Liu, D., Mao, L., Hong, W.K., Khuri, F.R., and Lee, H.Y., 2002, Correlation between insulin-like growth factor-binding protein-3 promoter methylation and prognosis of patients with stage I non-small cell lung cancer. Clin Cancer Res, 8:3669–3675.

    PubMed  Google Scholar 

  185. Standal, T., Borset, M., Lenhoff, S., Wisloff, F., Stordal, B., Sundan, A., Waage, A., and Seidel, C., 2002, Serum insulinlike growth factor is not elevated in patients with multiple myeloma but is still a prognostic factor. Blood, 100:3925–3929.

    Article  PubMed  Google Scholar 

  186. Rocha, R.L., Hilsenbeck, S.G., Jackson, J.G., Lee, A.V., Figueroa, J.A., and Yee, D., 1996, Correlation of insulin-like growth factor-binding protein-3 messenger RNA with protein expression in primary breast cancer tissues: detection of higher levels in tumors with poor prognostic features. J Natl Cancer Inst, 88:601–606.

    PubMed  Google Scholar 

  187. Holdaway, I.M., Mason, B.H., Lethaby, A.E., Singh, V., Harvey, V.J., Thompson, P.I., and Evans, B.D., 2003, Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 following chemotherapy for advanced breast cancer. ANZ J Surg, 73:905–908.

    Article  PubMed  Google Scholar 

  188. Railo, M.J., von Smitten, K., and Pekonen, F., 1994, The prognostic value of insulin-like growth factor-I in breast cancer patients. Results of a follow-up study on 126 patients. Eur J Cancer, 30A:307–311.

    Article  PubMed  Google Scholar 

  189. Bonneterre, J., Peyrat, J.P., Beuscart, R., and Demaille, A., 1990, Prognostic significance of insulin-like growth factor 1 receptors in human breast cancer. Cancer Res, 50:6931–6935.

    PubMed  Google Scholar 

  190. Turner, B.C., Haffty, B.G., Narayanan, L., Yuan, J., Havre, P.A., Gumbs, A.A., Kaplan, L., Burgaud, J.L., Carter, D., Baserga, R., and Glazer, P.M., 1997, Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation. Cancer Res, 57:3079–3083.

    PubMed  Google Scholar 

  191. Takanami, I., Imamuma, T., Hashizume, T., Kikuchi, K., Yamamoto, Y., Yamamoto, T., and Kodaira, S., 1996, Insulin-like growth factor-II as a prognostic factor in pulmonary adenocarcinoma. J Surg Oncol, 61:205–208.

    Article  PubMed  Google Scholar 

  192. Grothey, A., Voigt, W., Schober, C., Muller, T., Dempke, W., and Schmoll, H.J., 1999, The role of insulin-like growth factor I and its receptor in cell growth, transformation, apoptosis, and chemoresistance in solid tumors. J Cancer Res Clin Oncol, 125:166–173.

    Article  PubMed  Google Scholar 

  193. Hadsell, D.L. and Abdel-Fattah, G., 2001, Regulation of cell apoptosis by insulin-like growth factor I. Adv Exp Med Biol, 501:79–85.

    PubMed  Google Scholar 

  194. Vincent, A.M. and Feldman, E.L. 2002. Control of cell survival by IGF signaling pathways. Growth Horm IGF Res, 12:193–197.

    Article  Google Scholar 

  195. Le Roith, D., 2000, Regulation of proliferation and apoptosis by the insulin-like growth factor I receptor. Growth Horm IGF Res, 10SupplA:S12–S13.

    Article  PubMed  Google Scholar 

  196. Isgaard, J., and Tivesten, A., 1999, The role of growth hormone and insulin-like growth factor I in the regulation of apoptosis. Growth Horm IGF Res, 9SupplA:125–128.

    Article  PubMed  Google Scholar 

  197. Garrouste, F., Remacle-Bonnet, M., Fauriat, C., Marvaldi, J., Luis, J., and Pommier, G., 2002, Prevention of cytokine-induced apoptosis by insulin-like growth factor-I is independent of cell adhesion molecules in HT29-D4 colon carcinoma cells-evidence for a NF-kappaB-dependent survival mechanism. Cell Death Differ, 9:768–779.

    Article  PubMed  Google Scholar 

  198. Gil-Ad, I., Shtaif, B., Luria, D., Karp, L., Fridman, Y., and Weizman, A., 1999, Insulin-like-growth-factor-I (IGF-I) antagonizes apoptosis induced by serum deficiency and doxorubicin in neuronal cell culture. Growth Horm IGF Res, 9:458–464.

    Article  PubMed  Google Scholar 

  199. Geier, A., Hemi, R., Haimsohn, M., Beery, R., Malik, Z., and Karasik, A., 1994, Epidermal growth factor and insulin-like growth factor-1 protect MDA-231 cells from death induced by actinomycin D: the involvement of growth factors in drug resistance. In Vitro Cell Dev Biol Anim, 30A:336–343.

    PubMed  Google Scholar 

  200. Gooch, J.L., Van Den Berg, C.L., and Yee, D., 1999, Insulin-like growth factor (IGF)-I rescues breast cancer cells from chemotherapy-induced cell death—proliferative and anti-apoptotic effects. Breast Cancer Res Treat, 56:1–10.

    Article  PubMed  Google Scholar 

  201. Guo, Y.S., Jin, G.F., Houston, C.W., Thompson, J.C., and Townsend, Jr., C.M., 1998, Insulin-like growth factor-I promotes multidrug resistance in MCLM colon cancer cells. J Cell Physiol, 175:141–148.

    Article  PubMed  Google Scholar 

  202. Sekharam, M., Zhao, H., Sun, M., Fang, Q., Zhang, Q., Yuan, Z., Dan, H.C., Boulware, D., Cheng, J.Q., and Coppola, D., 2003, Insulin-like growth factor 1 receptor enhances invasion and induces resistance to apoptosis of colon cancer cells through the Akt/Bcl-x(L) pathway. Cancer Res, 63:7708–7716.

    PubMed  Google Scholar 

  203. Levitt, R.J. and Pollak, M., 2002, Insulin-like growth factor-I antagonizes the antiproliferative effects of cyclooxygenase-2 inhibitors on BxPC-3 pancreatic cancer cells. Cancer Res, 62:7372–7376.

    PubMed  Google Scholar 

  204. Liu, Y.C., Leu, C.M., Wong, F.H., Fong, W.S., Chen, S.C., Chang, C., and Hu, C.P., 2002, Autocrine stimulation by insulin-like growth factor I is involved in the growth, tumorigenicity and chemoresistance of human esophageal carcinoma cells. J Biomed Sci, 9:665–674.

    Article  PubMed  Google Scholar 

  205. Wan, X. and Helman, L.J., 2002, Effect of insulin-like growth factor II on protecting myoblast cells against cisplatin-induced apoptosis through p70 S6 kinase pathway. Neoplasia, 4:400–408.

    Article  PubMed  Google Scholar 

  206. Sun, H.Z., Wu, S.F., and Tu, Z.H., 2001, Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity. Cell Res, 11:107–115.

    PubMed  Google Scholar 

  207. Butt, A.J., Firth, S.M., and Baxter, R.C., 1999, The IGF axis and programmed cell death. Immunol Cell Biol, 77:256–262.

    Article  Google Scholar 

  208. Werner, H. and Le Roith, D., 1997, The insulin-like growth factor-I receptor signaling pathways are important for tumorigenesis and inhibition of apoptosis. Crit Rev Oncog, 8:71–92.

    PubMed  Google Scholar 

  209. Bohula, E.A., Playford, M.P., and Macaulay, V.M., 2003, Targeting the type 1 insulin-like growth factor receptor as anti-cancer treatment. Anticancer Drugs, 14:669–682.

    Article  PubMed  Google Scholar 

  210. Salisbury, A.J. and Macaulay, V.M., 2003, Development of molecular agents for IGF receptor targeting. Horm Metab Res, 35:843–849.

    Article  PubMed  Google Scholar 

  211. Andrews, D.W., Resnicoff, M., Flanders, A.E., Kenyon, L., Curtis, M., Merli, G., Baserga, R., Iliakis, G., and Aiken, R.D., 2001, Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol, 19:2189–2200.

    PubMed  Google Scholar 

  212. Liu, X., Turbyville, T., Fritz, A., and Whitesell, L., 1998, Inhibition of insulin-like growth factor I receptor expression in neuroblastoma cells induces the regression of established tumors in mice. Cancer Res, 58:5432–5438.

    PubMed  Google Scholar 

  213. Birchmeier, C., Birchmeier, W., Gherardi, E., and Vande Woude, G.F., 2003, Met, metastasis, motility and more. Nat.Rev.Mol Cell Biol, 4:915–925.

    Article  PubMed  Google Scholar 

  214. Zhang, Y.W. and Vande Woude, G.F., 2003, HGF/SF-met signaling in the control of branching morphogenesis and invasion. J Cell Biochem, 88:408–417.

    Article  PubMed  Google Scholar 

  215. Danilkovitch-Miagkova, A. and Zbar, B., 2002, Dysregulation of Met receptor tyrosine kinase activity in invasive tumors. J Clin Invest, 109:863–867.

    Article  PubMed  Google Scholar 

  216. Haddad, R., Lipson, K.E., and Webb, C.P., 2001, Hepatocyte growth factor expression in human cancer and therapy with specific inhibitors. AntiCancer Res, 21:4243–4252.

    PubMed  Google Scholar 

  217. Trusolino, L. and Comoglio, P.M., 2002, Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer, 2:289–300.

    Article  PubMed  Google Scholar 

  218. Birchmeier, C. and Gherardi, E., 1998, Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. Trends Cell Biol, 8:404–410.

    Article  PubMed  Google Scholar 

  219. Vadnais, J., Nault, G., Daher, Z., Amraei, M., Dodier, Y., Nabi, I. R., and Noel, J., 2002, Autocrine activation of the hepatocyte growth factor receptor/met tyrosine kinase induces tumor cell motility by regulating pseudopodial protrusion. J Biol Chem, 277:48342–48350.

    Article  PubMed  Google Scholar 

  220. Yi, S. and Tsao, M.S., 2000, Activation of hepatocyte growth factor-met autocrine loop enhances tumorigenicity in a human lung adenocarcinoma cell line. Neoplasia, 2:226–234.

    PubMed  Google Scholar 

  221. Jeffers, M., Rong, S., Anver, M., and Vande Woude, G.F., 1996, Autocrine hepatocyte growth factor/scatter factor-Met signaling induces transformation and the invasive/metastastic phenotype in C127 cells. Oncogene, 13:853–856.

    PubMed  Google Scholar 

  222. Tsao, M.S., Yang, Y., Marcus, A., Liu, N., and Mou, L., 2001, Hepatocyte growth factor is predominantly expressed by the carcinoma cells in non-small-cell lung cancer. Hum Pathol, 32:57–65.

    Article  PubMed  Google Scholar 

  223. Chen, Y.S., Wang, J.T., Chang, Y.F., Liu, B.Y., Wang, Y.P., Sun, A., and Chiang, C.P., 2004, Expression of hepatocyte growth factor and c-met protein is significantly associated with the progression of oral squamous cell carcinoma in Taiwan. J Oral Pathol Med, 33:209–217.

    Article  PubMed  Google Scholar 

  224. Parr, C., Watkins, G., Mansel, R.E., and Jiang, W.G., 2004, The hepatocyte growth factor regulatory factors in human breast cancer. Clin Cancer Res, 10:202–211.

    Article  PubMed  Google Scholar 

  225. Nardone, H.C., Ziober, A.F., LiVolsi, V.A., Mandel, S.J., Baloch, Z.W., Weber, R.S., Mick, R., and Ziober, B.L., 2003, c-Met expression in tall cell variant papillary carcinoma of the thyroid. Cancer, 98:1386–1393.

    Article  PubMed  Google Scholar 

  226. Takeuchi, H., Bilchik, A., Saha, S., Turner, R., Wiese, D., Tanaka, M., Kuo, C., Wang, H.J., and Hoon, D.S., 2003, c-MET expression level in primary colon cancer: a predictor of tumor invasion and lymph node metastases. Clin Cancer Res, 9:1480–1488.

    PubMed  Google Scholar 

  227. Tolgay, O., I, Dolled-Filhart, M., D'Aquila, T.G., Camp, R.L., and Rimm, D.L., 2003, Tissue microarray-based studies of patients with lymph node negative breast carcinoma show that met expression is associated with worse outcome but is not correlated with epidermal growth factor family receptors. Cancer, 97:1841–1848.

    Article  PubMed  Google Scholar 

  228. Maulik, G., Shrikhande, A., Kijima, T., Ma, P. C., Morrison, P.T., and Salgia, R., 2002, Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition. Cytokine Growth Factor Rev, 13:41–59.

    Article  PubMed  Google Scholar 

  229. Furukawa, T., Duguid, W.P., Kobari, M., Matsuno, S., and Tsao, M.S., 1995, Hepatocyte growth factor and Met receptor expression in human pancreatic carcinogenesis. Am J Pathol, 147:889–895.

    PubMed  Google Scholar 

  230. Baykal, C., Ayhan, A., Al, A., Yuce, K., and Ayhan, A., 2003, Overexpression of the c-Met/HGF receptor and its prognostic significance in uterine cervix carcinomas. Gynecol Oncol, 88:123–129.

    Article  PubMed  Google Scholar 

  231. Gohji, K., Nomi, M., Niitani, Y., Kitazawa, S., Fujii, A., Katsuoka, Y., and Nakajima, M., 2000, Independent prognostic value of serum hepatocyte growth factor in bladder cancer. J Clin Oncol, 18:2963–2971.

    PubMed  Google Scholar 

  232. Tsarfaty, I., Alvord, W.G., Resau, J.H., Altstock, R.T., Lidereau, R., Bieche, I., Bertrand, F., Horev, J., Klabansky, R.L., Keydar, I., and Vande Woude, G.F., 1999, Alteration of Met protooncogene product expression and prognosis in breast carcinomas. Anal.Quant.Cytol.Histol., 21:397–408.

    PubMed  Google Scholar 

  233. Nakajima, M., Sawada, H., Yamada, Y., Watanabe, A., Tatsumi, M., Yamashita, J., Matsuda, M., Sakaguchi, T., Hirao, T., and Nakano, H., 1999, The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer, 85:1894–1902.

    PubMed  Google Scholar 

  234. Porte, H., Triboulet, J.P., Kotelevets, L., Carrat, F., Prevot, S., Nordlinger, B., DiGioia, Y., Wurtz, A., Comoglio, P., Gespach, C., and Chastre, E., 1998, Overexpression of stromelysin-3, BM-40/SPARC, and MET genes in human esophageal carcinoma: implications for prognosis. Clin Cancer Res, 4:1375–1382.

    PubMed  Google Scholar 

  235. Tokunou, M., Niki, T., Eguchi, K., Iba, S., Tsuda, H., Yamada, T., Matsuno, Y., Kondo, H., Saitoh, Y., Imamura, H., and Hirohashi, S., 2001, c-MET expression in myofibroblasts: role in autocrine activation and prognostic significance in lung adenocarcinoma. Am J Pathol, 158:1451–1463.

    PubMed  Google Scholar 

  236. Cheng, H.L., Trink, B., Tzai, T.S., Liu, H.S., Chan, S.H., Ho, C.L., Sidransky, D., and Chow, N.H., 2002, Overexpression of c-met as a prognostic indicator for transitional cell carcinoma of the urinary bladder: a comparison with p53 nuclear accumulation. J Clin Oncol, 20:1544–1550.

    Article  PubMed  Google Scholar 

  237. Rasola, A., Anguissola, S., Ferrero, N., Gramaglia, D., Maffe, A., Maggiora, P., Comoglio, P.M., and Di Renzo, M.F., 2004, Hepatocyte growth factor sensitizes human ovarian carcinoma cell lines to paclitaxel and cisplatin. Cancer Res, 64:1744–1750.

    Article  PubMed  Google Scholar 

  238. Bowers, D.C., Fan, S., Walter, K.A., Abounader, R., Williams, J.A., Rosen, E.M., and Laterra, J., 2000, Scatter factor/hepatocyte growth factor protects against cytotoxic death in human glioblastoma via phosphatidylinositol 3-kinase-and AKT-dependent pathways. Cancer Res, 60:4277–4283.

    PubMed  Google Scholar 

  239. Aebersold, D.M., Kollar, A., Beer, K.T., Laissue, J., Greiner, R.H., and Djonov, V., 2001, Involvement of the hepatocyte growth factor/scatter factor receptor c-met and of Bcl-xL in the resistance of oropharyngeal cancer to ionizing radiation. Int J Cancer, 96:41–54.

    Article  PubMed  Google Scholar 

  240. Jankowski, K., Kucia, M., Wysoczynski, M., Reca, R., Zhao, D., Trzyna, E., Trent, J., Peiper, S., Zembala, M., Ratajczak, J., Houghton, P., Janowska-Wieczorek, A., and Ratajczak, M.Z., 2003, Both hepatocyte growth factor (HGF) and stromal-derived factor-1 regulate the metastatic behavior of human rhabdomyosarcoma cells, but only HGF enhances their resistance to radiochemotherapy. Cancer Res, 63:7926–7935.

    PubMed  Google Scholar 

  241. Wang, X., Zhou, Y., Kim, H.P., Song, R., Zarnegar, R., Ryter, S.W., and Choi, A.M., 2004, Hepatocyte growth factor protects against hypoxia/reoxygenation-induced apoptosis in endothelial cells. J Biol Chem, 279:5237–5243.

    Article  PubMed  Google Scholar 

  242. Derksen, P.W., de Gorter, D.J., Meijer, H.P., Bende, R.J., van Dijk, M., Lokhorst, H.M., Bloem, A.C., Spaargaren, M., and Pals, S.T., 2003, The hepatocyte growth factor/Met pathway controls proliferation and apoptosis in multiple myeloma. Leukemia, 17:764–774.

    Article  PubMed  Google Scholar 

  243. Nakagami, H., Morishita, R., Yamamoto, K., Taniyama, Y., Aoki, M., Yamasaki, K., Matsumoto, K., Nakamura, T., Kaneda, Y., and Ogihara, T., 2002, Hepatocyte growth factor prevents endothelial cell death through inhibition of bax translocation from cytosol to mitochondrial membrane. Diabetes, 51:2604–2611.

    PubMed  Google Scholar 

  244. Ma, H., Calderon, T.M., Fallon, J.T., and Berman, J.W., 2002, Hepatocyte growth factor is a survival factor for endothelial cells and is expressed in human atherosclerotic plaques. Atherosclerosis, 164:79–87.

    Article  PubMed  Google Scholar 

  245. Gao, M., Fan, S., Goldberg, I.D., Laterra, J., Kitsis, R.N., and Rosen, E.M., 2001, Hepatocyte growth factor/scatter factor blocks the mitochondrial pathway of apoptosis signaling in breast cancer cells. J Biol Chem, 276:47257–47265.

    Article  PubMed  Google Scholar 

  246. Fan, S., Ma, Y.X., Gao, M., Yuan, R.Q., Meng, Q., Goldberg, I.D., and Rosen, E.M., 2001, The multisubstrate adapter Gab1 regulates hepatocyte growth factor (scatter factor)-c-Met signaling for cell survival and DNA repair. Mol Cell Biol, 21:4968–4984.

    Article  PubMed  Google Scholar 

  247. Aebersold, D.M., Kollar, A., Beer, K.T., Laissue, J., Greiner, R.H., and Djonov, V., 2001, Involvement of the hepatocyte growth factor/scatter factor receptor c-met and of Bcl-xL in the resistance of oropharyngeal cancer to ionizing radiation. Int J Cancer, 96:41–54.

    Article  PubMed  Google Scholar 

  248. Fan, S., Ma, Y.X., Wang, J.A., Yuan, R.Q., Meng, Q., Cao, Y., Laterra, J.J., Goldberg, I.D., and Rosen, E.M., 2000, The cytokine hepatocyte growth factor/scatter factor inhibits apoptosis and enhances DNA repair by a common mechanism involving signaling through phosphatidyl inositol 3′ kinase. Oncogene, 19:2212–2223

    Article  PubMed  Google Scholar 

  249. Date, K., Matsumoto, K., Shimura, H., Tanaka, M., and Nakamura, T., 1997, HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor. FEBS Lett, 420: 1–6

    Article  PubMed  Google Scholar 

  250. Dranoff, G., 2004, Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer, 4:11–22.

    Article  PubMed  Google Scholar 

  251. Cohen, Jr., M.M., 2003, TGF beta/Smad signaling system and its pathologic correlates. Am.J Med.Genet., 116A:1–10.

    Article  Google Scholar 

  252. Cordeiro, M.F., 2002, Beyond Mitomycin: TGF-beta and wound healing. Prog Retin Eye Res, 21:75–89.

    Article  PubMed  Google Scholar 

  253. Moustakas, A., Pardali, K., Gaal, A., and Heldin, C.H., 2002, Mechanisms of TGF-beta signaling in regulation of cell growth and differentiation. Immunol Lett, 82:85–91.

    Article  PubMed  Google Scholar 

  254. Siegel, P.M. and Massague, J., 2003, Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer, 3:807–821.

    Article  PubMed  Google Scholar 

  255. Verrecchia, F. and Mauviel, A., 2002, Transforming growth factor-beta signaling through the Smad pathway: role in extracellular matrix gene expression and regulation. J Invest Dermatol, 118:211–215.

    Article  PubMed  Google Scholar 

  256. Massague, J., Blain, S.W., and Lo, R.S., 2000, TGFbeta signaling in growth control, cancer, and heritable disorders. Cell, 103:295–309.

    Article  PubMed  Google Scholar 

  257. Derynck, R., Akhurst, R.J., and Balmain, A., 2001, TGF-beta signaling in tumor suppression and cancer progression. Nat Genet, 29:117–129.

    Article  PubMed  Google Scholar 

  258. Derynck, R. and Zhang, Y.E., 2003, Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature, 425:577–584.

    Article  PubMed  Google Scholar 

  259. Massague, J., 2000, How cells read TGF-beta signals. Nat Rev Mol Cell Biol, 1:169–178.

    Article  Google Scholar 

  260. Massague, J., 1998, TGF-beta signal transduction. Annu Rev Biochem, 67:753–791.

    Article  PubMed  Google Scholar 

  261. Shibuya, H., Yamaguchi, K., Shirakabe, K., Tonegawa, A., Gotoh, Y., Ueno, N., Irie, K., Nishida, E., and Matsumoto, K., 1996, TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction. Science, 272:1179–1182.

    PubMed  Google Scholar 

  262. Yue, J., and Mulder, K.M., 2000, Requirement of Ras/MAPK pathway activation by transforming growth factor beta for transforming growth factor beta 1 production in a smad-dependent pathway. J Biol Chem, 275:35656.

    Google Scholar 

  263. Park, B.J., Park, J.I., Byun, D.S., Park, J.H., and Chi, S.G., 2000, Mitogenic conversion of transforming growth factor-beta1 effect by oncogenic Ha-Ras-induced activation of the mitogen-activated protein kinase signaling pathway in human prostate cancer. Cancer Res, 60:3031–3038.

    PubMed  Google Scholar 

  264. Mulder, K.M., 2000, Role of Ras and Mapks in TGFbeta signaling. Cytokine Growth Factor Rev, 11:23–35.

    Article  PubMed  Google Scholar 

  265. Kivinen, L., and Laiho, M., 1999, Ras-and mitogen-activated protein kinase kinase-dependent and-independent pathways in p21Cip1/Waf1 induction by fibroblast growth factor-2, platelet-derived growth factor, and transforming growth factor-beta1. Cell Growth Differ, 10:621–628.

    PubMed  Google Scholar 

  266. Yamamoto, H., Atsuchi, N., Tanaka, H., Ogawa, W., Abe, M., Takeshita, A., and Ueno, H., 1999, Separate roles for H-Ras and Rac in signaling by transforming growth factor (TGF)-beta. H-Ras is essential for activation of MAP kinase, partially required for transcriptional activation by TGF-beta, but not required for signaling of growth suppression by TGF-beta. Eur.J Biochem., 264:110–119.

    Article  PubMed  Google Scholar 

  267. Reimann, T., Hempel, U., Krautwald, S., Axmann, A., Scheibe, R., Seidel, D., and Wenzel, K.W., 1997, Transforming growth factor-beta1 induces activation of Ras, Raf-1, MEK and MAPK in rat hepatic stellate cells. FEBS Lett, 403:57–60.

    Article  PubMed  Google Scholar 

  268. Atfi, A., Djelloul, S., Chastre, E., Davis, R., and Gespach, C., 1997, Evidence for a role of Rho-like GTPases and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in transforming growth factor beta-mediated signaling. J Biol Chem, 272:1429–1432.

    Article  PubMed  Google Scholar 

  269. Petritsch, C., Beug, H., Balmain, A., and Oft, M., 2000, TGF-beta inhibits p70 S6 kinase via protein phosphatase 2A to induce G(1) arrest. Genes Dev, 14:3093–3101.

    Article  PubMed  Google Scholar 

  270. Griswold-Prenner, I., Kamibayashi, C., Maruoka, E.M., Mumby, M.C., and Derynck, R., 1998, Physical and functional interactions between type I transforming growth factor beta receptors and Balpha, a WD-40 repeat subunit of phosphatase 2A. Mol Cell Biol, 18:6595–6604.

    PubMed  Google Scholar 

  271. Horowitz, J.C., Lee, D.Y., Waghray, M., Keshamouni, V.G., Thomas, P.E., Zhang, H., Cui, Z., and Thannickal, V.J., 2004, Activation of the pro-survival phosphatidylinositol 3-kinase/AKT pathway by transforming growth factor-beta1 in mesenchymal cells is mediated by p38 MAPK-dependent induction of an autocrine growth factor. J Biol Chem, 279:1359–1367.

    Article  PubMed  Google Scholar 

  272. Shin, I., Bakin, A.V., Rodeck, U., Brunet, A., and Arteaga, C.L., 2001, Transforming growth factor beta enhances epithelial cell survival via Akt-dependent regulation of FKHRL1. Mol Biol Cell, 12:3328–3339.

    PubMed  Google Scholar 

  273. Wakefield, L.M. and Roberts, A.B., 2002, TGF-beta signaling: positive and negative effects on tumorigenesis. Curr Opin Genet Dev, 12:22–29.

    Article  PubMed  Google Scholar 

  274. Sun, L., 2004, Tumor-suppressive and promoting function of transforming growth factor beta. Front Biosci, 9:1925–1935.

    PubMed  Google Scholar 

  275. Roberts, A.B. and Wakefield, L.M., 2003, The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci USA, 100:8621–8623.

    Article  PubMed  Google Scholar 

  276. Wikstrom, P., Stattin, P., Franck-Lissbrant, I., Damber, J.E., and Bergh, A. 1998, Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer. Prostate, 37:19–29.

    Article  PubMed  Google Scholar 

  277. Eastham, J.A., Truong, L.D., Rogers, E., Kattan, M., Flanders, K.C., Scardino, P.T., and Thompson, T.C., 1995, Transforming growth factor-beta 1: comparative immunohistochemical localization in human primary and metastatic prostate cancer. Lab Invest, 73:628–635.

    PubMed  Google Scholar 

  278. Steiner, M.S., Zhou, Z.Z., Tonb, D.C., and Barrack, E.R., 1994, Expression of transforming growth factor-beta 1 in prostate cancer. Endocrinology, 135:2240–2247.

    Article  PubMed  Google Scholar 

  279. Muir, G.H., Butta, A., Shearer, R.J., Fisher, C., Dearnaley, D.P., Flanders, K.C., Sporn, M.B., and Colletta, A.A., 1994, Induction of transforming growth factor beta in hormonally treated human prostate cancer. Br J, Cancer, 69:130–134.

    Google Scholar 

  280. Knabbe, C., Klein, H., Zugmaier, G., and Voigt, K.D., 1993, Hormonal regulation of transforming growth factor beta-2 expression in human prostate cancer. J Steroid Biochem Mol Biol, 47:137–142.

    Article  PubMed  Google Scholar 

  281. Truong, L.D., Kadmon, D., McCune, B.K., Flanders, K.C., Scardino, P.T., and Thompson, T.C., 1993, Association of transforming growth factor-beta 1 with prostate cancer: an immunohistochemical study. Hum Pathol, 24:4–9.

    Article  PubMed  Google Scholar 

  282. Wikstrom, P., Damber, J., and Bergh, A., 2001, Role of transforming growth factor-beta1 in prostate cancer. Microsc Res Tech, 52:411–419.

    Article  PubMed  Google Scholar 

  283. Kim, I.Y., Ahn, H.J., Lang, S., Oefelein, M.G., Oyasu, R., Kozlowski, J.M., and Lee, C., 1998, Loss of expression of transforming growth factor-beta receptors is associated with poor prognosis in prostate cancer patients. Clin Cancer Res, 4:1625–1630.

    PubMed  Google Scholar 

  284. Shariat, S.F., Menesses-Diaz, A., Kim, I.Y., Muramoto, M., Wheeler, T.M., and Slawin, K.M., 2004, Tissue expression of transforming growth factor-beta1 and its receptors: correlation with pathologic features and biochemical progression in patients undergoing radical prostatectomy. Urology, 63:1191–1197.

    Article  Google Scholar 

  285. Wikstrom, P., Bergh, A., and Damber, J.E., 2000, Transforming growth factor-beta1 and prostate cancer. Scand J Urol Nephrol, 34:85–94.

    Article  PubMed  Google Scholar 

  286. MacCallum, J., Bartlett, J.M., Thompson, A.M., Keen, J.C., Dixon, J.M., and Miller, W.R., 1994, Expression of transforming growth factor beta mRNA isoforms in human breast cancer. Br J Cancer, 69:1006–1009.

    PubMed  Google Scholar 

  287. Auvinen, P., Lipponen, P., Johansson, R., and Syrjanen, K., 1995, Prognostic significance of TGF-beta 1 and TGF-beta 2 expressions in female breast cancer. AntiCancer Res, 15:2627–2631.

    PubMed  Google Scholar 

  288. Kong, F.M., Anscher, M.S., Murase, T., Abbott, B.D., Iglehart, J.D., and Jirtle, R.L., 1995, Elevated plasma transforming growth factor-beta 1 levels in breast cancer patients decrease after surgical removal of the tumor. Ann Surg, 222:155–162.

    PubMed  Google Scholar 

  289. Auvinen, P., Lipponen, P., Johansson, R., and Syrjanen, K., 1995, Prognostic significance of TGF-beta 2 expression in female breast cancer. Eur J Cancer, 31A: 851.

    Article  PubMed  Google Scholar 

  290. Thompson, A.M., Kerr, D.J., and Steel, C.M., 1991, Transforming growth factor beta 1 is implicated in the failure of tamoxifen therapy in human breast cancer. Br J Cancer, 63:609–614.

    PubMed  Google Scholar 

  291. Ghellal, A., Li, C., Hayes, M., Byrne, G., Bundred, N., and Kumar, S., 2000, Prognostic significance of TGF beta 1 and TGF beta 3 in human breast carcinoma. AntiCancer Res, 20:4413–4418.

    PubMed  Google Scholar 

  292. Hasegawa, Y., Takanashi, S., Kanehira, Y., Tsushima, T., Imai, T., and Okumura, K., 2001, Transforming growth factor-beta1 level correlates with angiogenesis, tumor progression, and prognosis in patients with nonsmall cell lung carcinoma. Cancer, 91:964–971.

    Article  PubMed  Google Scholar 

  293. Saji, H., Nakamura, H., Awut, I., Kawasaki, N., Hagiwara, M., Ogata, A., Hosaka, M., Saijo, T., Kato, Y., and Kato, H., 2003, Significance of expression of TGF-beta in pulmonary metastasis in non-small cell lung cancer tissues. Ann Thorac Cardiovasc Surg, 9:295–300.

    PubMed  Google Scholar 

  294. Gold, L.I., 1999, The role for transforming growth factor-beta (TGF-beta) in human cancer. Crit Rev Oncog, 10:303–360.

    PubMed  Google Scholar 

  295. Bennett, W.P., el Deiry, W.S., Rush, W.L., Guinee, Jr., D.G., Freedman, A.N., Caporaso, N.E., Welsh, J.A., Jones, R.T., Borkowski, A., Travis, W.D., Fleming, M.V., Trastek, V., Pairolero, P.C., Tazelaar, H.D., Midthun, D., Jett, J.R., Liotta, L.A., and Harris, C.C., 1998, p21waf1/cip1 and transforming growth factor beta 1 protein expression correlate with survival in non-small cell lung cancer. Clin Cancer Res, 4:1499–1506.

    PubMed  Google Scholar 

  296. Takanami, I., Tanaka, F., Hashizume, T., and Kodaira, S., 1997, Roles of the transforming growth factor beta 1 and its type I and II receptors in the development of a pulmonary adenocarcinoma: results of an immunohistochemical study. J Surg Oncol, 64:262–267.

    Article  PubMed  Google Scholar 

  297. Takanami, I., Tanaka, F., Hashizume, T., Kikuchi, K., Yamamoto, Y., Yamamoto, T., and Kodaira, S., 1997, Transforming growth factor-beta isoforms expressions in pulmonary adenocarcinomas as prognostic markers: an immunohistological study of one hundred and twenty patients. Oncology, 54:122–128.

    PubMed  Google Scholar 

  298. de Jonge, R.R., Garrigue-Antar, L., Vellucci, V.F., and Reiss, M., 1997, Frequent inactivation of the transforming growth factor beta type II receptor in small-cell lung carcinoma cells. Oncol Res, 9:89–98.

    PubMed  Google Scholar 

  299. Takanami, I., Imamuma, T., Hashizume, T., Kikuchi, K., Yamamoto, Y., Yamamoto, T., and Kodaira, S., 1996, Expression of PDGF, IGF-II, bFGF and TGF-beta 1 in pulmonary adenocarcinoma. Pathol Res Pract, 192:1113–1120.

    PubMed  Google Scholar 

  300. Takanami, I., Imamura, T., Hashizume, T., Kikuchi, K., Yamamoto, Y., and Kodaira, S., 1994, Transforming growth factor beta 1 as a prognostic factor in pulmonary adenocarcinoma. J Clin Pathol, 47:1098–1100.

    PubMed  Google Scholar 

  301. Okumoto, K., Hattori, E., Tamura, K., Kiso, S., Watanabe, H., Saito, K., Saito, T., Togashi, H., and Kawata, S., 2004, Possible contribution of circulating transforming growth factor-beta1 to immunity and prognosis in unresectable hepatocellular carcinoma. Liver Int, 24:21–28.

    Article  PubMed  Google Scholar 

  302. Tsai, J.F., Chuang, L.Y., Jeng, J.E., Yang, M.L., Chang, W.Y., Hsieh, M.Y., Lin, Z.Y., and Tsai, J.H., 1997, Clinical relevance of transforming growth factor-beta 1 in the urine of patients with hepatocellular carcinoma. Medicine (Baltimore), 76:213–226.

    Article  PubMed  Google Scholar 

  303. Tsai, J.F., Jeng, J.E., Chuang, L.Y., Yang, M.L., Ho, M.S., Chang, W.Y., Hsieh, M.Y., Lin, Z.Y., and Tsai, J.H., 1997, Elevated urinary transforming growth factor-beta1 level as a tumour marker and predictor of poor survival in cirrhotic hepatocellular carcinoma. Br J Cancer, 76:244–250.

    PubMed  Google Scholar 

  304. Robson, H., Anderson, E., James, R.D., and Schofield, P.F., 1996, Transforming growth factor beta 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients. Br J Cancer, 74:753–758.

    PubMed  Google Scholar 

  305. Saito, H., Tsujitani, S., Oka, S., Kondo, A., Ikeguchi, M., Maeta, M., and Kaibara, N., 1999, The expression of transforming growth factor-beta1 is significantly correlated with the expression of vascular endothelial growth factor and poor prognosis of patients with advanced gastric carcinoma. Cancer, 86:1455–1462.

    Article  PubMed  Google Scholar 

  306. Nakamura, M., Katano, M., Kuwahara, A., Fujimoto, K., Miyazaki, K., Morisaki, T., and Mori, M., 1998, Transforming growth factor beta1 (TGF-beta1) is a preoperative prognostic indicator in advanced gastric carcinoma. Br J Cancer, 78:1373–1378.

    PubMed  Google Scholar 

  307. Hulshof, M.C., Sminia, P., Barten-Van Rijbroek, A.D., and Gonzalez, G.D., 2001, Prognostic value of plasma transforming growth factor-beta in patients with glioblastoma multiforme. Oncol Rep, 8:1107–1110.

    PubMed  Google Scholar 

  308. Buck, M.B., Fritz, P., Dippon, J., Zugmaier, G., and Knabbe, C., 2004, Prognostic significance of transforming growth factor beta receptor II in estrogen receptor-negative breast cancer patients. Clin Cancer Res, 10:491–498.

    Article  PubMed  Google Scholar 

  309. Fukai, Y., Fukuchi, M., Masuda, N., Osawa, H., Kato, H., Nakajima, T., and Kuwano, H., 2003, Reduced expression of transforming growth factor-beta receptors is an unfavorable prognostic factor in human esophageal squamous cell carcinoma. Int J Cancer, 104:161–166.

    Article  PubMed  Google Scholar 

  310. Xie, W., Bharathy, S., Kim, D., Haffty, B.G., Rimm, D.L., and Reiss, M., 2003, Frequent alterations of Smad signaling in human head and neck squamous cell carcinomas: a tissue microarray analysis. Oncol Res, 14:61–73.

    PubMed  Google Scholar 

  311. Xie, W., Rimm, D.L., Lin, Y., Shih, W.J., and Reiss, M., 2003, Loss of Smad signaling in human colorectal cancer is associated with advanced disease and poor prognosis. Cancer J, 9:302–312.

    PubMed  Google Scholar 

  312. Fukuchi, M., Fukai, Y., Masuda, N., Miyazaki, T., Nakajima, M., Sohda, M., Manda, R., Tsukada, K., Kato, H., and Kuwano, H., 2002, High-level expression of the Smad ubiquitin ligase Smurf2 correlates with poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Res, 62:7162–7165.

    PubMed  Google Scholar 

  313. Xie, W., Mertens, J.C., Reiss, D.J., Rimm, D.L., Camp, R.L., Haffty, B.G., and Reiss, M., 2002, Alterations of Smad signaling in human breast carcinoma are associated with poor outcome: a tissue microarray study. Cancer Res, 62:497–505.

    PubMed  Google Scholar 

  314. Boulay, J.L., Mild, G., Lowy, A., Reuter, J., Lagrange, M., Terracciano, L., Laffer, U., Herrmann, R., and Rochlitz, C., 2002, SMAD4 is a predictive marker for 5-fluorouracil-based chemotherapy in patients with colorectal cancer. Br J, Cancer, 87:630–634.

    Google Scholar 

  315. Dickson, J., Davidson, S.E., Hunter, R.D., and West, C.M., 2000, Pretreatment plasma TGF beta 1 levels are prognostic for survival but not morbidity following radiation therapy of carcinoma of the cervix. Int J Radiat Oncol Biol Phys, 48:991–995.

    Article  Google Scholar 

  316. Keyes, K., Cox, K., Treadway, P., Mann, L., Shih, C., Faul, M.M., and Teicher, B.A., 2002, An in vitro tumor model: analysis of angiogenic factor expression after chemotherapy. Cancer Res, 62:5597–5602.

    PubMed  Google Scholar 

  317. Teicher, B.A., 2001, Malignant cells, directors of the malignant process: role of transforming growth factor-beta. Cancer Metastasis Rev, 20:133–143.

    Article  PubMed  Google Scholar 

  318. Liu, P., Menon, K., Alvarez, E., Lu, K., and Teicher, B.A., 2000, Transforming growth factor-beta and response to anticancer therapies in human liver and gastric tumors in vitro and in vivo. Int J Oncol, 16:599–610.

    PubMed  Google Scholar 

  319. Teicher, B.A., Ikebe, M., Ara, G., Keyes, S.R., and Herbst, R.S., 1997, Transforming growth factor-beta 1 overexpression produces drug resistance in vivo: reversal by decorin. In Vivo, 11:463–472.

    PubMed  Google Scholar 

  320. Teicher, B.A., Kakeji, Y., Ara, G., Herbst, R. S., and Northey, D., 1997, Prostate carcinoma response to cytotoxic therapy: in vivo resistance. In Vivo, 11:453–461.

    PubMed  Google Scholar 

  321. Teicher, B.A., Maehara, Y., Kakeji, Y., Ara, G., Keyes, S.R., Wong, J., and Herbst, R., 1997, Reversal of in vivo drug resistance by the transforming growth factor-beta inhibitor decorin. Int J Cancer, 71:49–58.

    Article  PubMed  Google Scholar 

  322. Kakeji, Y., Maehara, Y., Ikebe, M., and Teicher, B.A. 1997 Dynamics of tumor oxygenation, CD31 staining and transforming growth factor-beta levels after treatment with radiation or cyclophosphamide in the rat 13762 mammary carcinoma. Int.J Radiat.Oncol.BiolPhys., 37:1115–1123.

    Article  Google Scholar 

  323. Teicher, B.A., Holden, S.A., Ara, G., and Chen, G. 1996. Transforming growth factor-beta in in vivo resistance. Cancer Chemother Pharmacol, 37:601–609.

    Article  PubMed  Google Scholar 

  324. Chen, G., Teicher, B.A., and Frei, III, E., 1998, Biochemical characterization of in vivo alkylating agent resistance of a murine EMT-6 mammary carcinoma. Implication for systemic involvement in the resistance phenotype. Cancer Biochem Biophys, 16:139–155.

    PubMed  Google Scholar 

  325. Teicher, B.A., Ara, G., Keyes, S.R., Herbst, R. S., and Frei, E., III 1998. Acute in vivo resistance in high-dose therapy. Clin Cancer Res, 4:483–491.

    PubMed  Google Scholar 

  326. Chatterjee, D., Liu, C. J., Northey, D., and Teicher, B.A. 1995. Molecular characterization of the in vivo alkylating agent resistant murine EMT-6 mammary carcinoma tumors. Cancer Chemother Pharmacol, 35:423–431.

    Article  PubMed  Google Scholar 

  327. Kobayashi, H., Man, S., Graham, C.H. Kapitain, S. J., Teicher, B.A., and Kerbek, R.S., 1993, Acquired multicellular-mediated resistance to alkylating agents in cancer. Proc Natl Acad Sci, USA, 90:3294–3298.

    PubMed  Google Scholar 

  328. Teicher, B.A., Chatterjee, D., Liu, J.T., Holden, S.A., and Ara, G., 1993, Protection of bone-marrow granulocyte-macrophage colony-forming units in mice bearing in vivo alkylating-agent-resistant EMT-6 tumors. Cancer Chemother Pharmacol, 32:315–319.

    Article  PubMed  Google Scholar 

  329. Xu, Z., Ma, D. Z., Wang, L.Y., Su, J.M., and Zha, X.L., 2003, Transforming growth factor-beta1 stimulated protein kinase B serine-473 and focal adhesion kinase tyrosine phosphorylation dependent on cell adhesion in human hepatocellular carcinoma SMMC-7721 cells. Biochem Biophys Res Commun, 312:388–396.

    Article  PubMed  Google Scholar 

  330. Nakamura, E., Megumi, Y., Kobayashi, T., Kamoto, T., Ishitoya, S., Terachi, T., Tachibana, M., Matsushiro, H., Habuchi, T., Kakehi, Y., and Ogawa, O., 2002, Genetic polymorphisms of the interleukin-4 receptor alpha gene are associated with an increasing risk and a poor prognosis of sporadic renal cell carcinoma in a Japanese population. Clin Cancer Res, 8:2620–2625.

    PubMed  Google Scholar 

  331. De Vita, F., Orditura, M., Auriemma, A., Infusino, S., Roscigno, A., and Catalano, G., 1998, Serum levels of interleukin-6 as a prognostic factor in advanced non-small cell lung cancer. Oncol Rep, 5:649–652.

    PubMed  Google Scholar 

  332. De Vita, F., Romano, C., Orditura, M., Galizia, G., Martinelli, E., Lieto, E., and Catalano, G., 2001, Interleukin-6 serum level correlates with survival in advanced gastrointestinal cancer patients but is not an independent prognostic indicator. J Interferon Cytokine Res, 21:45–52.

    Article  PubMed  Google Scholar 

  333. DeMichele, A., Martin, A.M., Mick, R., Gor, P., Wray, L., Klein-Cabral, M., Athanasiadis, G., Colligan, T., Stadtmauer, E., and Weber, B., 2003, Interleukin-6-174G—>C polymorphism is associated with improved outcome in high-risk breast cancer. Cancer Res, 63:8051–8056.

    PubMed  Google Scholar 

  334. Drachenberg, D.E., Elgamal, A.A., Rowbotham, R., Peterson, M., and Murphy, G.P., 1999, Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer. Prostate, 41:127–133.

    Article  PubMed  Google Scholar 

  335. Gado, K., Domjan, G., Hegyesi, H., and Falus, A., 2000, Role of INTERLEUKIN-6 in the pathogenesis of multiple myeloma. Cell BiolInt, 24:195–209.

    Article  Google Scholar 

  336. Plante, M., Rubin, S.C., Wong, G.Y., Federici, M.G., Finstad, C.L., and Gastl, G.A., 1994, Interleukin-6 level in serum and ascites as a prognostic factor in patients with epithelial ovarian cancer. Cancer, 73:1882–1888.

    PubMed  Google Scholar 

  337. Thiounn, N., Pages, F., Flam, T., Tartour, E., Mosseri, V., Zerbib, M., Beuzeboc, P., Deneux, L., Fridman, W.H., and Debre, B., 1997, IL-6 is a survival prognostic factor in renal cell carcinoma. Immunol Lett, 58:121–124.

    Article  PubMed  Google Scholar 

  338. Yokoe, T., Iino, Y., and Morishita, Y., 2000,Trends of IL-6 and IL-8 levels in patients with recurrent breast cancer: preliminary report. Breast Cancer, 7:187–190.

    PubMed  Google Scholar 

  339. Kozlowski, L., Zakrzewska, I., Tokajuk, P., and Wojtukiewicz, M.Z., 2003, Concentration of interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood serum of breast cancer patients. Rocz Akad Med Bialymst, 48:82–84.

    PubMed  Google Scholar 

  340. Lech-Maranda, E., Baseggio, L., Bienvenu, J., Charlot, C., Berger, F., Rigal, D., Warzocha, K., Coiffier, B., and Salles, G., 2003, The interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma, Blood.

    Google Scholar 

  341. Hattori, E., Okumoto, K., Adachi, T., Takeda, T., Ito, J., Sugahara, K., Watanabe, H., Saito, K., Saito, T., Togashi, H., and Kawata, S., 2003, Possible contribution of circulating interleukin-10 (IL-10) to anti-tumor immunity and prognosis in patients with unresectable hepatocellular carcinoma. Hepatol Res, 27:309–314.

    Article  PubMed  Google Scholar 

  342. Salgami, E.V., Efstathiou, S.P., Vlachakis, V., Sekara, E. V., Syrigos, K.N., and Roussou, P.P., 2002, High pretreatment interleukin-10 is an independent predictor of poor failure-free survival in patients with Hodgkin's lymphoma. Haematologia (Budap), 32:377–387.

    PubMed  Google Scholar 

  343. Aydin, F., Yilmaz, M., Ozdemir, F., Kavgaci, H., Yavuz, M.N., and Yavuz, A.A., 2002, Correlation of serum IL-2, IL-6 and IL-10 levels with International Prognostic Index in patients with aggressive non-Hodgkin's lymphoma. Am J Clin Oncol, 25:570–572.

    Article  PubMed  Google Scholar 

  344. Martinez-Escribano, J.A., Moya-Quiles, M.R., Muro, M., Montes-Ares, O., Hernandez-Caselles, T., Frias, J.F., and Alvarez-Lopez, M.R., 2002, Interleukin-10, interleukin-6 and interferon-gamma gene polymorphisms in melanoma patients. Melanoma Res, 12:465–469.

    Article  PubMed  Google Scholar 

  345. Chandler, S.W., Rassekh, C.H., Rodman, S.M., and Ducatman, B.S., 2002, Immunohistochemical localization of interleukin-10 in human oral and pharyngeal carcinomas. Laryngoscope, 112:808–815.

    Article  PubMed  Google Scholar 

  346. Galizia, G., Lieto, E., De Vita, F., Romano, C., Orditura, M., Castellano, P., Imperatore, V., Infusino, S., Catalano, G., and Pignatelli, C., 2002, Circulating levels of interleukin-10 and interleukin-6 in gastric and colon cancer patients before and after surgery: relationship with radicality and outcome. J Interferon Cytokine Res, 22:473–482.

    Article  PubMed  Google Scholar 

  347. Galizia, G., Orditura, M., Romano, C., Lieto, E., Castellano, P., Pelosio, L., Imperatore, V., Catalano, G., Pignatelli, C., and De Vita, F., 2002, Prognostic significance of circulating IL-10 and IL-6 serum levels in colon cancer patients undergoing surgery. Clin Immunol, 102:169–178.

    Article  PubMed  Google Scholar 

  348. Vassilakopoulos, T.P., Nadali, G., Angelopoulou, M.K., Siakantaris, M.P., Dimopoulou, M.N., Kontopidou, F.N., Rassidakis, G.Z., Doussis-Anagnostopoulou, I.A., Hatzioannou, M., Vaiopoulos, G., Kittas, C., Sarris, A.H., Pizzolo, G., and Pangalis, G.A., 2001, Serum interleukin-10 levels are an independent prognostic factor for patients with Hodgkin's lymphoma. Haematologica, 86:274–281.

    PubMed  Google Scholar 

  349. Hatanaka, H., Abe, Y., Kamiya, T., Morino, F., Nagata, J., Tokunaga, T., Oshika, Y., Suemizu, H., Kijima, H., Tsuchida, T., Yamazaki, H., Inoue, H., Nakamura, M., and Ueyama, Y., 2000, Clinical implications of interleukin (IL)-10 induced by non-small-cell lung cancer. Ann Oncol, 11:815–819.

    Article  PubMed  Google Scholar 

  350. De Vita, F., Orditura, M., Galizia, G., Romano, C., Lieto, E., Iodice, P., Tuccillo, C., and Catalano, G., 2000, Serum interleukin-10 is an independent prognostic factor in advanced solid tumors. Oncol Rep, 7:357–361.

    PubMed  Google Scholar 

  351. De Vita, F., Orditura, M., Galizia, G., Romano, C., Roscigno, A., Lieto, E., and Catalano, G., 2000, Serum interleukin-10 levels as a prognostic factor in advanced non-small cell lung cancer patients. Chest, 117:365–373.

    Article  PubMed  Google Scholar 

  352. Sarris, A.H., Kliche, K.O., Pethambaram, P., Preti, A., Tucker, S., Jackow, C., Messina, O., Pugh, W., Hagemeister, F.B., McLaughlin, P., Rodriguez, M.A., Romaguera, J., Fritsche, H., Witzig, T., Duvic, M., Andreeff, M., and Cabanillas, F., 1999, Interleukin-10 levels are often elevated in serum of adults with Hodgkin's disease and are associated with inferior failure-free survival. Ann Oncol, 10:433–440.

    Article  PubMed  Google Scholar 

  353. Cortes, J., and Kurzrock, R., 1997, Interleukin-10 in non-Hodgkin's lymphoma. Leuk.Lymphoma, 26:251–259.

    PubMed  Google Scholar 

  354. Blay, J.Y., Burdin, N., Rousset, F., Lenoir, G., Biron, P., Philip, T., Banchereau, J., and Favrot, M.C., 1993, Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor. Blood, 82:2169–2174.

    PubMed  Google Scholar 

  355. Soria, J.C., Moon, C., Kemp, B.L., Liu, D.D., Feng, L., Tang, X., Chang, Y.S., Mao, L., and Khuri, F.R., 2003, Lack of interleukin-10 expression could predict poor outcome in patients with stage I non-small cell lung cancer. Clin Cancer Res, 9:1785–1791.

    PubMed  Google Scholar 

  356. Stassi, G., Todaro, M., Zerilli, M., Ricci-Vitiani, L., Di Liberto, D., Patti, M., Florena, A., Di Gaudio, F., Di Gesu, G., and De Maria, R., 2003, Thyroid cancer resistance to chemotherapeutic drugs via autocrine production of interleukin-4 and interleukin-10. Cancer Res, 63:6784–6790.

    PubMed  Google Scholar 

  357. Sredni, B., Weil, M., Khomenok, G., Lebenthal, I., Teitz, S., Mardor, Y., Ram, Z., Orenstein, A., Kershenovich, A., Michowiz, S., Cohen, Y.I., Rappaport, Z.H., Freidkin, I., Albeck, M., Longo, D.L., and Kalechman, Y., 2004, Ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) sensitizes tumors to chemotherapy by inhibiting the tumor interleukin 10 autocrine loop. Cancer Res, 64:1843–1852.

    Article  PubMed  Google Scholar 

  358. Sredni, B., Albeck, M., Tichler, T., Shani, A., Shapira, J., Bruderman, I., Catane, R., Kaufman, B., and Kalechman, Y., 1995, Bone marrow-sparing and prevention of alopecia by AS101 in non-small-cell lung cancer patients treated with carboplatin and etoposide. J Clin Oncol, 13:2342–2353.

    PubMed  Google Scholar 

  359. Mizutani, Y., Bonavida, B., Koishihara, Y., Akamatsu, K., Ohsugi, Y., and Yoshida, O., 1995, Sensitization of human renal cell carcinoma cells to cis-diamminedichloroplatinum(II) by anti-interleukin 6 monoclonal antibody or anti-interleukin 6 receptor monoclonal antibody. Cancer Res, 55:590–596.

    PubMed  Google Scholar 

  360. Borsellino, N., Belldegrun, A., and Bonavida, B., 1995, Endogenous interleukin 6 is a resistance factor for cis-diamminedichloroplatinum and etoposide-mediated cytotoxicity of human prostate carcinoma cell lines. Cancer Res, 55:4633–4639.

    PubMed  Google Scholar 

  361. Honemann, D., Chatterjee, M., Savino, R., Bommert, K., Burger, R., Gramatzki, M., Dorken, B., and Bargou, R.C., 2001, The IL-6 receptor antagonist SANT-7 overcomes bone marrow stromal cell-mediated drug resistance of multiple myeloma cells. Int J Cancer, 93:674–680.

    Article  PubMed  Google Scholar 

  362. Borsellino, N., Bonavida, B., Ciliberto, G., Toniatti, C., Travali, S., and D'Alessandro, N., 1999, Blocking signaling through the Gp130 receptor chain by interleukin-6 and oncostatin M inhibits PC-3 cell growth and sensitizes the tumor cells to etoposide and cisplatin-mediated cytotoxicity. Cancer, 85:134–144.

    Article  PubMed  Google Scholar 

  363. Cavallaro, U. and Christofori, G., 2004, Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer, 4:118–132.

    PubMed  Google Scholar 

  364. Persad, S. and Dedhar, S., 2003, The role of integrin-linked kinase (ILK) in cancer progression. Cancer Metastasis Rev, 22:375–384.

    Article  PubMed  Google Scholar 

  365. Felding-Habermann, B., 2003, Integrin adhesion receptors in tumor metastasis. Clin Exp Metastasis, 20:203–213.

    Article  PubMed  Google Scholar 

  366. Lozano, E., Betson, M., and Braga, V.M., 2003, Tumor progression: Small GTPases and loss of cell-cell adhesion. Bioessays, 25:452–463.

    Article  PubMed  Google Scholar 

  367. Pupa, S.M., Menard, S., Forti, S., and Tagliabue, E., 2002, New insights into the role of extracellular matrix during tumor onset and progression. J Cell Physiol, 192:259–267.

    Article  PubMed  Google Scholar 

  368. Hirohashi, S. and Kanai, Y., 2003, Cell adhesion system and human cancer morphogenesis. Cancer Sci., 94:575–581.

    Article  PubMed  Google Scholar 

  369. Christofori, G., 2003, Changing neighbours, changing behaviour: cell adhesion molecule-mediated signalling during tumour progression. EMBO J, 22:2318–2323.

    Article  PubMed  Google Scholar 

  370. Hecker, T.P. and Gladson, C.L., 2003, Focal adhesion kinase in cancer. Front Biosci, 8:s705–s714.

    PubMed  Google Scholar 

  371. Conacci-Sorrell, M., Zhurinsky, J., and Ben Ze'ev, A., 2002, The cadherin-catenin adhesion system in signaling and cancer. J Clin Ivest, 109:987–991.

    Article  Google Scholar 

  372. Stracke, M.L., Murata, J., Aznavoorian, S., and Liotta, L.A., 1994, The role of the extracellular matrix in tumor cell metastasis. In Vivo, 8:49–58.

    PubMed  Google Scholar 

  373. Mason, M.D., Davies, G., and Jiang, W.G., 2002, Cell adhesion molecules and adhesion abnormalities in prostate cancer. Crit Rev Oncol Hematol, 41:11–28.

    PubMed  Google Scholar 

  374. Cavallaro, U. and Christofori, G., 2001, Cell adhesion in tumor invasion and metastasis: loss of the glue is not enough. Biochim Biophys Acta, 1552:39–45.

    PubMed  Google Scholar 

  375. Maeda, K., Kang, S.M., Sawada, T., Nishiguchi, Y., Yashiro, M., Ogawa, Y., Ohira, M., Ishikawa, T., and Hirakawa-YS, C.K., 2002, Expression of intercellular adhesion molecule-1 and prognosis in colorectal cancer. Oncol Rep, 9:511–514.

    PubMed  Google Scholar 

  376. Hoffmann, R., Franzke, A., Buer, J., Sel, S., Oevermann, K., Duensing, A., Probst, M., Duensing, S., Kirchner, H., Ganser, A., and Atzpodien, J., 1999, Prognostic impact of in vivo soluble cell adhesion molecules in metastatic renal cell carcinoma. Br J, Cancer, 79:1742–1745.

    Google Scholar 

  377. Tacyildiz, N., Yavuz, G., Gozdasoglu, S., Unal, E., Ertem, U., Duru, F., Ikinciogullari, A., Babacan, E., Ensari, A., and Okcuoglu-Cavdar, A., 1999, Serum levels and differential expression of intercellular adhesion molecule-1 in childhood leukemia and malignant lymphoma: prognostic importance and relationship with survival. Pediatr Hematol Oncol, 16:149–158.

    Article  PubMed  Google Scholar 

  378. Zhang, G.J. and Adachi, I., 1999, Serum levels of soluble intercellular adhesion molecule-1 and E-selectin in metastatic breast carcinoma: correlations with clinicopathological features and prognosis. Int J Oncol, 14:71–77.

    PubMed  Google Scholar 

  379. Dosquet, C., Coudert, M.C., Lepage, E., Cabane, J., and Richard, F., 1997, Are angiogenic factors, cytokines, and soluble adhesion molecules prognostic factors in patients with renal cell carcinoma? Clin Cancer Res, 3:2451–2458.

    PubMed  Google Scholar 

  380. Terol, M.J., Lopez-Guillermo, A., Bosch, F., Villamor, N., Cid, M.C., Rozman, C., Campo, E., and Montserrat, E., 1998, Expression of the adhesion molecule ICAM-1 in non-Hodgkin's lymphoma: relationship with tumor dissemination and prognostic importance. J Clin Oncol, 16:35–40.

    PubMed  Google Scholar 

  381. Shimizu, Y., Minemura, M., Tsukishiro, T., Kashii, Y., Miyamoto, M., Nishimori, H., Higuchi, K., and Watanabe, A., 1995, Serum concentration of intercellular adhesion molecule-1 in patients with hepatocellular carcinoma is a marker of the disease progression and prognosis. Hepatology, 22:525–531.

    Article  PubMed  Google Scholar 

  382. Ogawa, Y., Hirakawa, K., Nakata, B., Fujihara, T., Sawada, T., Kato, Y., Yoshikawa, K., and Sowa, M., 1998, Expression of intercellular adhesion molecule-1 in invasive breast cancer reflects low growth potential, negative lymph node involvement, and good prognosis. Clin Cancer Res, 4:31–36.

    PubMed  Google Scholar 

  383. Archimbaud, E., Thomas, X., Campos, L., Magaud, J.P., Dore, J.F., and Fiere, D., 1992, Expression of surface adhesion molecules CD54 (ICAM-1) and CD58 (LFA-3) in adult acute leukemia: relationship with initial characteristics and prognosis. Leukemia, 6:265–271.

    PubMed  Google Scholar 

  384. Gonzalez-Moles, M.A., Bravo, M., Ruiz-Avila, I., Esteban, F., Rodriguez-Archilla, A., Gonzalez-Moles, S., and Arias, B., 2003, Adhesion molecule CD44 as a prognostic factor in tongue cancer. AntiCancer Res, 23:5197–5202.

    PubMed  Google Scholar 

  385. Vis, A.N., Noordzij, M.A., Fitoz, K., Wildhagen, M.F., Schroder, F.H., and van der Kwast, T.H., 2000, Prognostic value of cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44s in surgically treated patients with prostate cancer. J Urol, 164:2156–2161.

    Article  PubMed  Google Scholar 

  386. Horst, E., Meijer, C.J., Radaszkiewicz, T., Ossekoppele, G.J., Van Krieken, J.H., and Pals, S.T., 1990, Adhesion molecules in the prognosis of diffuse large-cell lymphoma: expression of a lymphocyte homing receptor (CD44), LFA-1 (CD11a/18), and ICAM-1 (CD54). Leukemia, 4:595–599.

    PubMed  Google Scholar 

  387. Hage, R., Elbers, H.R., Brutel, d.l.R., and van den Bosch, J.M., 1998, Neural cell adhesion molecule expression: prognosis in 889 patients with resected non-small cell lung cancer. Chest, 114:1316–1320.

    PubMed  Google Scholar 

  388. Poley, S., Stieber, P., Nussler, V., Pahl, H., and Fateh-Moghadam, A., 1997, Evaluation of serum neural cell adhesion molecule as a prognostic marker in multiple myeloma. AntiCancer Res, 17:3021–3024.

    PubMed  Google Scholar 

  389. Pujol, J.L., Simony, J., Demoly, P., Charpentier, R., Laurent, J.C., Daures, J.P., Lehmann, M., Guyot, V., Godard, P., and Michel, F.B., 1993, Neural cell adhesion molecule and prognosis of surgically resected lung cancer. Am Rev Respir Dis, 148:1071–1075.

    PubMed  Google Scholar 

  390. Kibbelaar, R.E., Moolenaar, K.E., Michalides, R.J., Van Bodegom, P.C., Vanderschueren, R.G., Wagenaar, S.S., Dingemans, K.P., Bitter-Suermann, D., Dalesio, O., and Van Zandwijk, N., 1991, Neural cell adhesion molecule expression, neuroendocrine differentiation and prognosis in lung carcinoma. Eur J Cancer, 27:431–435.

    PubMed  Google Scholar 

  391. Bremnes, R.M., Veve, R., Hirsch, F.R., and Franklin, W.A., 2002, The E-cadherin cell-cell adhesion complex and lung cancer invasion, metastasis, and prognosis. Lung Cancer, 36:115–124.

    Article  PubMed  Google Scholar 

  392. Kuniyasu, H., Ellis, L.M., Evans, D.B., Abbruzzese, J.L., Fenoglio, C.J., Bucana, C.D., Cleary, K.R., Tahara, E., and Fidler, I.J., 1999, Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma. Clin Cancer Res, 5:25–33.

    PubMed  Google Scholar 

  393. Stefansson, I.M., Salvesen, H.B., and Akslen, L.A., 2004, Prognostic impact of alterations in P-cadherin expression and related cell adhesion markers in endometrial cancer. J Clin Oncol, 22:1242–1252.

    Article  PubMed  Google Scholar 

  394. Oshita, F., Kameda, Y., Ikehara, M., Tanaka, G., Yamada, K., Nomura, I., Noda, K., Shotsu, A., Fujita, A., Arai, H., Ito, H., Nakayama, H., and Mitsuda, A., 2002, Increased expression of integrin beta1 is a poor prognostic factor in small-cell lung cancer. AntiCancer Res, 22:1065–1070.

    PubMed  Google Scholar 

  395. Vihinen, P., Nikkola, J., Vlaykova, T., Hahka-Kemppinen, M., Talve, L., Heino, J., and Pyrhonen, S., 2000, Prognostic value of beta1 integrin expression in metastatic melanoma. Melanoma Res, 10:243–251.

    PubMed  Google Scholar 

  396. Ohira, T., Akutagawa, S., Usuda, J., Nakamura, T., Hirano, T., Tsuboi, M., Nishio, K., Taguchi, F., Ikeda, N., Nakamura, H., Konaka, C., Saijo, N., and Kato, H., 2002, Up-regulated gene expression of angiogenesis factors in post-chemotherapeutic lung cancer tissues determined by cDNA macroarray. Oncol Rep, 9:723–728.

    PubMed  Google Scholar 

  397. Turner, J.R., Torres, C.M., Wang, H.H., Shahsafaei, A., Richards, W.G., Sugarbaker, D., and Odze, R.D., 2000, Preoperative chemoradiotherapy alters the expression and prognostic significance of adhesion molecules in Barrett's-associated adenocarcinoma. Hum Pathol, 31:347–353.

    Article  PubMed  Google Scholar 

  398. Kraus, A.C., Ferber, I., Bachmann, S.O., Specht, H., Wimmel, A., Gross, M.W., Schlegel, J., Suske, G., and Schuermann, M., 2002, In vitro chemo-and radio-resistance in small cell lung cancer correlates with cell adhesion and constitutive activation of AKT and MAP kinase pathways. Oncogene, 21:8683–8695.

    Article  PubMed  Google Scholar 

  399. Rintoul, R.C. and Sethi, T., 2002, Extracellular matrix regulation of drug resistance in small-cell lung cancer. Clin.Sci (Lond), 102:417–424.

    Article  PubMed  Google Scholar 

  400. Liang, Y., Meleady, P., Cleary, I., McDonnell, S., Connolly, L., and Clynes, M., 2001, Selection with melphalan or paclitaxel (Taxol) yields variants with different patterns of multidrug resistance, integrin expression and in vitro invasiveness. Eur J Cancer, 37:1041–1052.

    Article  PubMed  Google Scholar 

  401. Sherman-Baust, C.A., Weeraratna, A.T., Rangel, L.B., Pizer, E.S., Cho, K.R., Schwartz, D.R., Shock, T., and Morin, P.J., 2003, Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells. Cancer Cell, 3:377–386.

    Article  PubMed  Google Scholar 

  402. Miyamoto, H., Murakami, T., Tsuchida, K., Sugino, H., Miyake, H., and Tashiro, S., 2004, Tumor-stroma interaction of human pancreatic cancer: acquired resistance to anticancer drugs and proliferation regulation is dependent on extracellular matrix proteins. Pancreas, 28:38–44.

    Article  PubMed  Google Scholar 

  403. Cordes, N., Blaese, M.A., Plasswilm, L., Rodemann, H.P., and Van Beuningen, D., 2003, Fibronectin and laminin increase resistance to ionizing radiation and the cytotoxic drug Ukrain in human tumour and normal cells in vitro. Int J Radiat Biol, 79:709–720.

    Article  PubMed  Google Scholar 

  404. Vincent, T., Molina, L., Espert, L., and Mechti, N., 2003, Hyaluronan, a major non-protein glycosaminoglycan component of the extracellular matrix in human bone marrow, mediates dexamethasone resistance in multiple myeloma. Br J, Haematol, 121:259–269.

    Google Scholar 

  405. de la Fuente, M.T., Casanova, B., Moyano, J. V., Garcia-Gila, M., Sanz, L., Garcia-Marco, J., Silva, A., and Garcia-Pardo, A., 2002, Engagement of alpha4beta1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine. J Leukoc Biol, 71:495–502.

    PubMed  Google Scholar 

  406. Damiano, J.S., Hazlehurst, L.A., and Dalton, W.S., 2001, Cell adhesion-mediated drug resistance (CAM-DR) protects the K562 chronic myelogenous leukemia cell line from apoptosis induced by BCR/ABL inhibition, cytotoxic drugs, and gamma-irradiation. Leukemia, 15:1232–1239.

    Article  PubMed  Google Scholar 

  407. Elliott, T. and Sethi, T., 2002, Integrins and extracellular matrix: a novel mechanism of multidrug resistance. Expert Rev Anticancer Ther, 2:449–459.

    Article  PubMed  Google Scholar 

  408. Shain, K.H., and Dalton, W.S., 2001, Cell adhesion is a key determinant in de novo multidrug resistance (MDR): new targets for the prevention of acquired MDR. Mol Cancer Ther, 1:69–78.

    PubMed  Google Scholar 

  409. Hazlehurst, L.A., and Dalton, W.S., 2001, Mechanisms associated with cell adhesion mediated drug resistance (CAM-DR) in hematopoietic malignancies. Cancer Metastasis Rev, 20:43–50.

    Article  PubMed  Google Scholar 

  410. Shain, K.H., Landowski, T.H., and Dalton, W.S., 2000, The tumor microenvironment as a determinant of cancer cell survival: a possible mechanism for de novo drug resistance. Curr Opin Oncol, 12:557–563.

    Article  PubMed  Google Scholar 

  411. Hazlehurst, L.A., Landowski, T.H., and Dalton, W.S., 2003, Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death. Oncogene, 22:7396–7402.

    Article  PubMed  Google Scholar 

  412. Dalton, W.S., 1999, The tumor microenvironment as a determinant of drug response and resistance. Drug Resist Updat, 2:285–288.

    Article  Google Scholar 

  413. Nefedova, Y., Landowski, T.H., and Dalton, W.S., 2003, Bone marrow stromal-derived soluble factors and direct cell contact contribute to de novo drug resistance of myeloma cells by distinct mechanisms. Leukemia, 17:1175–1182.

    Article  PubMed  Google Scholar 

  414. Morin, P.J., 2003, Drug resistance and the microenvironment: nature and nurture. Drug Resist Updat, 6:169–172.

    Article  PubMed  Google Scholar 

  415. Green, S.K., Francia, G., Isidoro, C., and Kerbek, R.S., 2004, Antiadhesive antibodies targeting E-cadherin sensitize multicellular tumor spheroids to chemotherapy in vitro. Mol Cancer Ther, 3:149–159.

    PubMed  Google Scholar 

  416. Gray, L.H., Conger, A.D., Ebert, M., Hornsey, S., and Scott, O.C., 1953, The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J, Radiol, 26:638–648.

    Google Scholar 

  417. Crabtree, H.G. and Cramer, W., 1933, The action of radium on cancer cells I. II. Some factors determining the susceptibility of cancer cells to radium. Proc R Soc Ser B, 113:238–250.

    Google Scholar 

  418. Harris, A. L., 2002, Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer, 2:38–47.

    Article  PubMed  Google Scholar 

  419. Hockel, M., and Vaupel, P., 2001, Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst, 93:266–276.

    PubMed  Google Scholar 

  420. Vaupel, P., Thews, O., and Hoeckel, M., 2001, Treatment resistance of solid tumors: role of hypoxia and anemia. Med.Oncol, 18:243–259.

    Article  PubMed  Google Scholar 

  421. Evans, S.M., Judy, K.D., Dunphy, I., Jenkins, W.T., Nelson, P.T., Collins, R., Wileyto, E.P., Jenkins, K., Hahn, S.M., Stevens, C.W., Judkins, A.R., Phillips, P., Geoerger, B., and Koch, C.J., 2004, Comparative measurements of hypoxia in human brain tumors using needle electrodes and EF5 binding. Cancer Res, 64:1886–1892.

    Article  PubMed  Google Scholar 

  422. Choi, N., Baumann, M., Flentjie, M., Kellokumpu-Lehtinen, P., Senan, S., Zamboglou, N., and Kosmidis, P., 2001, Predictive factors in radiotherapy for non-small cell lung cancer: present status. Lung Cancer, 31:43–56.

    Article  PubMed  Google Scholar 

  423. Saunders, M.I., 1994, Predictive testing of radiosensitivity in non-small cell carcinoma of the lung. Lung Cancer, 10Suppl 1:S83–S90.

    Article  PubMed  Google Scholar 

  424. Swinson, D.E., Jones, J.L., Richardson, D., Cox, G., Edwards, J.G., and O'Byrne, K.J., 2002, Tumour necrosis is an independent prognostic marker in non-small cell lung cancer: correlation with biological variables. Lung Cancer, 37:235–240.

    Article  Google Scholar 

  425. Cruickshank, G.S. and Rampling, R., 1994, Does tumour related oedema contribute to the hypoxic fraction of human brain tumours? Acta Neurochir.Suppl (Wien.), 60:378–380.

    Google Scholar 

  426. Raza, S.M., Lang, F.F., Aggarwal, B.B., Fuller, G.N., Wildrick, D.M., and Sawaya, R., 2002, Necrosis and glioblastoma: a friend or a foe? A review and a hypothesis. Neurosurgery, 51:2–12.

    Article  PubMed  Google Scholar 

  427. Spence, A.M., Muzi, M., and Krohn, K.A., 2002, Molecular imaging of regional brain tumor biology. J Cell Biochem.Suppl, 39:25–35.

    Article  PubMed  Google Scholar 

  428. Brown, J.M., 1999, The hypoxic cell: a target for selective cancer therapy—eighteenth Bruce F. Cain Memorial Award lecture. Cancer Res, 59:5863–5870.

    PubMed  Google Scholar 

  429. Pugh, C.W., and Ratcliffe, P.J., 2003, Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med, 9:677–684.

    Article  PubMed  Google Scholar 

  430. Pugh, C.W. and Ratcliffe, P.J., 2003, The von Hippel-Lindau tumor suppressor, hypoxia-inducible factor-1 (HIF-1) degradation, and cancer pathogenesis. Semin Cancer Biol, 13:83–89.

    Article  PubMed  Google Scholar 

  431. Semenza, G.L., Agani, F., Feldser, D., Iyer, N., Kotch, L., Laughner, E., and Yu, A. 2000. Hypoxia, HIF-1, and the pathophysiology of common human diseases. Adv Exp Med Biol, 475:123–130.

    PubMed  Google Scholar 

  432. Semenza, G.L., 2000, HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol, 88:1474–1480.

    PubMed  Google Scholar 

  433. Maxwell, P. H., Pugh, C.W., and Ratcliffe, P.J., 2001, Activation of the HIF pathway in cancer. Curr Opin Genet Dev, 11:293–299.

    Article  PubMed  Google Scholar 

  434. Royds, J.A., Dower, S.K., Qwarnstrom, E.E., and Lewis, C.E., 1998, Response of tumour cells to hypoxia: role of p53 and NFkB. Mol Pathol, 51:55–61.

    PubMed  Google Scholar 

  435. Kao, K.S., Xanthoudakis, S., Curran, T., and O'Dwyer, P.J., 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.

    PubMed  Google Scholar 

  436. Minet, E., Michel, G., Mottet, D., Piret, J.P., Barbieux, A., Raes, M., and Michiels, C., 2001, c-JUN gene induction and AP-1 activity is regulated by a JNK-dependent pathway in hypoxic HepG2 cells. Exp Cell Res, 265:114–124.

    Article  PubMed  Google Scholar 

  437. Flaherty, D.M., Monick, M.M., and Hunninghake, G.W., 2001, AP endonucleases and the many functions of Ref-1. Am J Respir Cell Mol Biol, 25:664–667.

    PubMed  Google Scholar 

  438. Hall, J.L., Wang, X., Van, A., Zhao, Y., and Gibbons, G.H., 2001, Overexpression of Ref-1 inhibits hypoxia and tumor necrosis factor-induced endothelial cell apoptosis through nuclear factor-kappab-independent and-dependent pathways. Circ Res, 88:1247–1253.

    PubMed  Google Scholar 

  439. Wang, N. and Stemerman, M.B., 2001, Ref-1 and transcriptional control of endothelial apoptosis. Circ Res, 88:1223–1225.

    PubMed  Google Scholar 

  440. Kelley, M.R., Cheng, L., Foster, R., Tritt, R., Jiang, J., Broshears, J., and Koch, M., 2001, Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer. Clin Cancer Res, 7:824–830.

    PubMed  Google Scholar 

  441. Wang, G., Reisdorph, R., Clark, Jr., R.E., Miskimins, R., Lindahl, R., and Miskimins, W.K., 2003, Cyclin dependent kinase inhibitor p27(Kip1) is upregulated by hypoxia via an ARNT dependent pathway. J Cell Biochem, 90:548–560.

    Article  PubMed  Google Scholar 

  442. Goda, N., Ryan, H.E., Khadivi, B., McNulty, W., Rickert, R.C., and Johnson, R.S., 2003, Hypoxia-inducible factor 1alpha is essential for cell cycle arrest during hypoxia. Mol Cell Biol, 23:359–369.

    Article  PubMed  Google Scholar 

  443. Fujii, T., Otsuki, T., Moriya, T., Sakaguchi, H., Kurebayashi, J., Yata, K., Uno, M., Kobayashi, T., Kimura, T., Jo, Y., Kinugawa, K., Furukawa, Y., Morioka, M., Ueki, A., and Tanaka, H., 2002, Effect of hypoxia on human seminoma cells. Int J Oncol, 20:955–962.

    PubMed  Google Scholar 

  444. Krtolica, A., Krucher, N.A., and Ludlow, J.W., 1999, Molecular analysis of selected cell cycle regulatory proteins during aerobic and hypoxic maintenance of human ovarian carcinoma cells. Br J, Cancer, 80:1875–1883.

    Google Scholar 

  445. Krtolica, A., Krucher, N.A., and Ludlow, J.W., 1998, Hypoxia-induced pRB hypophosphorylation results from downregulation of CDK and upregulation of PP1 activities. Oncogene, 17:2295–2304.

    Article  PubMed  Google Scholar 

  446. Carmeliet, P., Dor, Y., Herbert, J.M., Fukumura, D., Brusselmans, K., Dewerchin, M., Neeman, M., Bono, F., Abramovitch, R., Maxwell, P., Koch, C.J., Ratcliffe, P., Moons, L., Jain, R.K., Collen, D., Keshert, E., and Keshet, E., 1998, Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature, 394:485–490.

    Article  PubMed  Google Scholar 

  447. Sowter, H.M., Ratcliffe, P.J., Watson, P., Greenberg, A.H., and Harris, A.L., 2001, HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res, 61:6669–6673.

    PubMed  Google Scholar 

  448. Bruick, R.K., 2000, Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci, USA, 97:9082–9087.

    Article  PubMed  Google Scholar 

  449. Sowter, H.M., Ferguson, M., Pym, C., Watson, P., Fox, S.B., Han, C., and Harris, A.L., 2003, Expression of the cell death genes BNip3 and NIX in ductal carcinoma in situ of the breast; correlation of BNip3 levels with necrosis and grade. J Pathol, 201:573–580.

    Article  PubMed  Google Scholar 

  450. Kothari, S., Cizeau, J., McMillan-Ward, E., Israels, S.J., Bailes, M., Ens, K., Kirshenbaum, L.A., and Gibson, S.B., 2003, BNIP3 plays a role in hypoxic cell death in human epithelial cells that is inhibited by growth factors EGF and IGF. Oncogene, 22:4734–4744.

    Article  PubMed  Google Scholar 

  451. Regula, K.M., Ens, K., and Kirshenbaum, L.A., 2002, Inducible expression of BNIP3 provokes mitochondrial defects and hypoxia-mediated cell death of ventricular myocytes. Circ Res, 91:226–231.

    Article  PubMed  Google Scholar 

  452. Guo, K., Searfoss, G., Krolikowski, D., Pagnoni, M., Franks, C., Clark, K., Yu, K.T., Jaye, M., and Ivashchenko, Y., 2001, Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Differ, 8:367–376.

    Article  Google Scholar 

  453. Park, S.Y., Billiar, T.R., and Seol, D.W., 2002, Hypoxia inhibition of apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Biochem Biophys Res Commun, 291:150–153.

    Article  PubMed  Google Scholar 

  454. Erler, J.T., Cawthorne, C.J., Williams, K.J., Koritzinsky, M., Wouters, B.G., Wilson, C., Miller, C., Demonacos, C., Stratford, I.J., and Dive, C., 2004, 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, 24:2875–2889.

    Article  PubMed  Google Scholar 

  455. Wartenberg, M., Ling, F.C., Muschen, M., Klein, F., Acker, H., Gassmann, M., Petrat, K., Putz, V., Hescheler, J., and Sauer, H., 2003, Regulation of the multidrug resistance transporter P-glycoprotein in multicellular tumor spheroids by hypoxia-inducible factor (HIF-1) and reactive oxygen species. FASEB J, 17:503–505.

    PubMed  Google Scholar 

  456. Comerford, K.M., Wallace, T.J., Karhausen, J., Louis, N.A., Montalto, M.C., and Colgan, S.P., 2002, Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res, 62:3387–3394.

    PubMed  Google Scholar 

  457. Liang, B.C., 1996, Effects of hypoxia on drug resistance phenotype and genotype in human glioma cell lines. J Neurooncol, 29:149–155.

    Article  PubMed  Google Scholar 

  458. Sakata, K., Kwok, T.T., Murphy, B.J., Laderoute, K.R., Gordon, G.R., and Sutherland, R.M., 1991, Hypoxia-induced drug resistance: comparison to P-glycoprotein-associated drug resistance. Br J, Cancer, 64:809–814.

    Google Scholar 

  459. Krishnamurthy, P., Ross, D.D., Nakanishi, T., Bailey-Dell, K., Zhou, S., Mercer, K.E., Sarkadi, B., Sorrentino, B.P., and Schuetz, J.D., 2004, The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J Biol Chem, 279:24218–24225.

    Article  PubMed  Google Scholar 

  460. Brinkmann, U., 2002, Functional polymorphisms of the human multidrug resistance (MDR1) gene: correlation with P glycoprotein expression and activity in vivo. Novartis Found Symp, 243:207–210.

    PubMed  Google Scholar 

  461. Doyle, L.A. and Ross, D.D., 2003, Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene, 22:7340–7358.

    Article  PubMed  Google Scholar 

  462. Germann, U.A., 1996, P-glycoprotein—a mediator of multidrug resistance in tumour cells. Eur J Cancer, 32A:927–944.

    Article  PubMed  Google Scholar 

  463. Gottesman, M.M., Pastan, I., and Ambudkar, S.V., 1996, P-glycoprotein and multidrug resistance. Curr Opin Genet Dev, 6:610–617.

    Article  PubMed  Google Scholar 

  464. Mazure, N.M., Brahimi-Horn, M.C., and Pouyssegur, J., 2003, Protein kinases and the hypoxia-inducible factor-1, two switches in angiogenesis. Curr Pharm Des, 9:531–541.

    Article  PubMed  Google Scholar 

  465. Choi, K.S., Bae, M.K., Jeong, J.W., Moon, H.E., and Kim, K.W., 2003, Hypoxia-induced angiogenesis during carcinogenesis. J Biochem Mol Biol, 36:120–127.

    PubMed  Google Scholar 

  466. Berra, E., Pages, G., and Pouyssegur, J., 2000, MAP kinases and hypoxia in the control of VEGF expression. Cancer Metastasis Rev, 19:139–145.

    Article  PubMed  Google Scholar 

  467. Levy, A.P., Levy, N.S., Iliopoulos, O., Jiang, C., Kaplin, Jr., W.G., and Goldberg, M.A., 1997, Regulation of vascular endothelial growth factor by hypoxia and its modulation by the von Hippel-Lindau tumor suppressor gene. Kidney Int, 51:575–578.

    PubMed  Google Scholar 

  468. Ishibashi, H., Shiratuchi, T., Nakagawa, K., Onimaru, M., Sugiura, T., Sueishi, K., and Shirasuna, K., 2001, Hypoxia-induced angiogenesis of cultured human salivary gland carcinoma cells enhances vascular endothelial growth factor production and basic fibroblast growth factor release. Oral Oncol, 37:77–83.

    Article  PubMed  Google Scholar 

  469. Baek, J.H., Jang, J.E., Kang, C.M., Chung, H.Y., Kim, N.D., and Kim, K.W., 2000, Hypoxia-induced VEGF enhances tumor survivability via suppression of serum deprivation-induced apoptosis. Oncogene, 19:4621–4631.

    Article  PubMed  Google Scholar 

  470. Brogi, E., Schatteman, G., Wu, T., Kim, E.A., Varticovski, L., Keyt, B., and Isner, J.M., 1996, Hypoxia-induced paracrine regulation of vascular endothelial growth factor receptor expression. J Clin Ivest, 97:469–476.

    Google Scholar 

  471. Suzuki, H., Seto, K., Shinoda, Y., Mori, M., Ishimura, Y., Suematsu, M., and Ishii, H, 1999, Paracrine upregulation of VEGF receptor mRNA in endothelial cells by hypoxia-exposed hep G2 cells. Am.J Physiol, 276:G92–G97.

    PubMed  Google Scholar 

  472. Le, Y.J. and Corry, P.M., 1999, Hypoxia-induced bFGF gene expression is mediated through the JNK signal transduction pathway. Mol Cell Biochem, 202:1–8.

    Article  PubMed  Google Scholar 

  473. Scarpino, S., Cancellario, d.F., Di Napoli, A., Pasquini, A., Marzullo, A., and Ruco, L.P., 2004, Increased expression of Met protein is associated with up-regulation of hypoxia inducible factor-1 (HIF-1) in tumour cells in papillary carcinoma of the thyroid. J Pathol, 202:352–358.

    Article  PubMed  Google Scholar 

  474. Pennacchietti, S., Michieli, P., Galluzzo, M., Mazzone, M., Giordano, S., and Comoglio, P.M., 2003, Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell, 3:347–361.

    Article  PubMed  Google Scholar 

  475. Bae, S.K., Bae, M.H., Ahn, M.Y., Son, M.J., Lee, Y.M., Bae, M.K., Lee, O.H., Park, B.C., and Kim, K.W., 1999, Egr-1 mediates transcriptional activation of IGF-II gene in response to hypoxia. Cancer Res, 59:5989–5994.

    PubMed  Google Scholar 

  476. Kim, K.W., Bae, S.K., Lee, O.H., Bae, M.H., Lee, M.J., and Park, B.C., 1998, Insulin-like growth factor II induced by hypoxia may contribute to angiogenesis of human hepatocellular carcinoma. Cancer Res, 58:348–351.

    PubMed  Google Scholar 

  477. Sugawara, J., Tazuke, S.I., Suen, L.F., Powell, D.R., Kaper, F., Giaccia, A.J., and Giudice, L.C., 2000, Regulation of insulin-like growth factor-binding protein 1 by hypoxia and 3′,5′-cyclic adenosine monophosphate is additive in HepG2 cells. J Clin Endocrinol Metab, 85:3821–3827.

    Article  PubMed  Google Scholar 

  478. Sugawara, J., Suh, D.S., Faessen, G.H., Suen, L.F., Shibata, T., Kaper, F., Giaccia, A.J., and Giudice, L.C., 2000, Regulation of insulin-like growth factor-binding protein-1 by nitric oxide under hypoxic conditions. J Clin Endocrinol Metab, 85:2714–2721.

    Article  PubMed  Google Scholar 

  479. Patel, B., Khaliq, A., Jarvis-Evans, J., McLeod, D., Mackness, M., and Boulton, M., 1994, Oxygen regulation of TGF-beta 1 mRNA in human hepatoma (Hep G2) cells. Biochem Mol BiolInt, 34:639–644.

    Google Scholar 

  480. Gunaratnam, L., Morley, M., Franovic, A., de Paulsen, N., Mekhail, K., Parolin, D.A., Nakamura, E., Lorimer, I.A., and Lee, S., 2003, Hypoxia inducible factor activates the transforming growth factor-alpha/epidermal growth factor receptor growth stimulatory pathway in VHL(-/-) renal cell carcinoma cells. J Biol Chem, 278:44966–44974.

    Article  PubMed  Google Scholar 

  481. Cooper, A.L. and Beasley, D., 1999, Hypoxia stimulates proliferation and interleukin-1alpha production in human vascular smooth muscle cells. Am J Physiol, 277:H1326–H1337.

    PubMed  Google Scholar 

  482. Hagberg, H., Gilland, E., Bona, E., Hanson, L.A., Hahin-Zoric, M., Blennow, M., Holst, M., McRae, A., and Soder, O., 1996, Enhanced expression of interleukin (IL)-1 and IL-6 messenger RNA and bioactive protein after hypoxia-ischemia in neonatal rats. Pediatr Res, 40:603–609.

    PubMed  Google Scholar 

  483. Liu, M.T., Huang, H.M., Jeng, K.C., Ou, S.C., and Kuo, J.S., 2000, Induction of cytokine genes and IL-1alpha by chemical hypoxia in PC12 cells. Life Sci, 67:2147–2157.

    Article  PubMed  Google Scholar 

  484. Maeda, Y., Matsumoto, M., Hori, O., Kuwabara, K., Ogawa, S., Yan, S.D., Ohtsuki, T., Kinoshita, T., Kamada, T., and Stern, D.M., 1994, Hypoxia/reoxygenation-mediated induction of astrocyte interleukin 6: a paracrine mechanism potentially enhancing neuron survival. J Exp Med, 180:2297–2308.

    Article  PubMed  Google Scholar 

  485. Matsui, H., Ihara, Y., Fujio, Y., Kunisada, K., Akira, S., Kishimoto, T., and Yamauchi-Takihara, K., 1999, Induction of interleukin (IL)-6 by hypoxia is mediated by nuclear factor (NF)-kappa B and NF-IL6 in cardiac myocytes. Cardiovasc Res, 42:104–112.

    Article  PubMed  Google Scholar 

  486. Muraoka, K., Shimizu, K., Sun, X., Zhang, Y.K., Tani, T., Hashimoto, T., Yagi, M., Miyazaki, I., and Yamamoto, K., 1997, Hypoxia, but not reoxygenation, induces interleukin 6 gene expression through NF-kappa B activation. Transplantation, 63:466–470.

    Article  PubMed  Google Scholar 

  487. Grutkoski, P.S., Graeber, C.T., D'Amico, R., Keeping, H., and Simms, H.H., 1999, Regulation of IL-8RA (CXCR1) expression in polymorphonuclear leukocytes by hypoxia/reoxygenation. J Leukoc Biol, 65:171–178.

    PubMed  Google Scholar 

  488. Shi, Q., Abbruzzese, J.L., Huang, S., Fidler, I.J., Xiong, Q., and Xie, K., 1999, Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic. Clin Cancer Res, 5:3711–3721.

    PubMed  Google Scholar 

  489. Xu, L., Xie, K., Mukaida, N., Matsushima, K., and Fidler, I.J., 1999, Hypoxia-induced elevation in interleukin-8 expression by human ovarian carcinoma cells. Cancer Res, 59:5822–5829.

    PubMed  Google Scholar 

  490. Yoshino, O., Osuga, Y., Koga, K., Hirota, Y., Yano, T., Tsutsumi, O., Fujimoto, A., Kugu, K., Momoeda, M., Fujiwara, T., and Taketani, Y., 2003, Upregulation of interleukin-8 by hypoxia in human ovaries. Am J Reprod Immunol, 50:286–290.

    Article  PubMed  Google Scholar 

  491. Reynolds, T.Y., Rockwell, S., and Glazer, P.M., 1996, Genetic instability induced by the tumor microenvironment. Cancer Res, 56:5754–5757.

    PubMed  Google Scholar 

  492. Mihaylova, V.T., Bindra, R.S., Yuan, J., Campisi, D., Narayanan, L., Jensen, R., Giordano, F., Johnson, R.S., Rockwell, S., and Glazer, P.M., 2003, Decreased expression of the DNA mismatch repair gene Mlh1 under hypoxic stress in mammalian cells. Mol Cell Biol, 23:3265–3273.

    Article  Google Scholar 

  493. Kim, C.Y., Tsai, M.H., Osmanian, C., Graeber, T.G., Lee, J.E., Giffard, R.G., DiPaolo, J.A., Peehl, D.M., and Giaccia, A.J., 1997, Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions. Cancer Res, 57:4200–4204.

    PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  495. von Pawel, J., von Roemeling, R., Gatzemeier, U., Boyer, M., Elisson, L.O., Clark, P., Talbot, D., Rey, A., Butler, T.W., Hirsh, V., Olver, I., Bergman, B., Ayoub, J., Richardson, G., Dunlop, D., Arcenas, A., Vescio, R., Viallet, J., and Treat, J., 2000, Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group. Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors. J Clin Oncol, 18:1351–1359.

    PubMed  Google Scholar 

  496. Peters, K.B., and Brown, J.M., 2002, Tirapazamine: a hypoxia-activated topoisomerase II poison. Cancer Res, 62:5248–5253.

    PubMed  Google Scholar 

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Wei, Y., Au, J.LS. (2005). Role of Tumour Microenvironment in Chemoresistance. In: Meadows, G.G. (eds) Integration/Interaction of Oncologic Growth. Cancer Growth and Progression, vol 15. Springer, Dordrecht. https://doi.org/10.1007/1-4020-3414-8_17

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