Nuclear factor-κB as a predictor of treatment response in breast cancer

Current Opinion in Oncology

Volumn 15, Issue 6, 2003, Pages 405-411

  Garg, Amit K ^a   Hortobagyi, Gabriel N ^a   Aggarwal, Bharat B ^a   Sahin, Aysegul A ^b   Buchholz, Thomas A ^a,b  

^a Department of Radiation Oncology ^*  (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Chemotherapy; I B ; NF B; Radiotherapy

Indexed keywords

ACETYLSALICYLIC ACID; ANTINEOPLASTIC AGENT; BIOLOGICAL MARKER; BORTEZOMIB; CISPLATIN; CURCUMIN; CYCLOPHOSPHAMIDE; DEXAMETHASONE; ERBSTATIN; GEMCITABINE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IRINOTECAN; LACTACYSTIN; PACLITAXEL; PARTHENOLIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PERVANADATE; PROTEIN KINASE INHIBITOR;

APOPTOSIS; BREAST CARCINOMA; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; DRUG RESPONSE; DRUG SENSITIZATION; DRUG TARGETING; HUMAN; MULTIPLE MYELOMA; PREDICTION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RADIOSENSITIZATION; REVIEW; TRANSCRIPTION REGULATION; TREATMENT OUTCOME; TUMOR GROWTH;

ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; DRUG RESISTANCE, NEOPLASM; HUMANS; NF-KAPPA B; PREDICTIVE VALUE OF TESTS; RADIOTHERAPY; TREATMENT OUTCOME;

EID: 0742269868     PISSN: 10408746     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001622-200311000-00001     Document Type: Review

References (111)

1. Malin JL, Schuster MA, Kahn KA, et al.: Quality of breast cancer care: what do we know? J Clin Oncol 2002, 20:4381-4393.
2. Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet 1998, 352:930-942.
3. Kennedy S, Merino MJ, Swain SM, et al.: The effects of hormonal and chemotherapy on tumoral and nonneoplastic breast tissue. Hum Pathol 1990, 21:192-198.
4. Aktepe F, Kapucuoglu N, Pak I: The effects of chemotherapy on breast cancer tissue in locally advanced breast cancer. Histopathology 1996, 29:63-67.
5. Miller KE, Ostrowski JL, Quinn CM: Effects of chemotherapy on breast cancer tissue. Histopathology 1997, 30:397-398.
6. Gajdos C, Tartter PI, Estabrook A, et al.: Relationship of clinical and pathologic response to neoadjuvant chemotherapy and outcome of locally advanced breast cancer. J Surg Oncol 2002, 80:4-11.
7. Garg A, Aggarwal BB: Nuclear transcription factor-kappaB as a target for cancer drug development. Leukemia 2002, 16:1053-1068. A systematic review of the evidence linking NF-κB to tumorigenesis.
8. Pahl HL: Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 1999, 18:6853-6866.
9. Kim DW, Sovak MA, Zanieski G, et al.: Activation of NF-kappaB/Rel occurs early during neoplastic transformation of mammary cells. Carcinogenesis 2000, 21:871-879.
10. Gillett C, Fantl V, Smith R, et al.: Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res 1994, 54:1812-1817.
11. Yamamoto M, Fukushima T, Hayashi S, et al.: Correlation of the expression of nuclear factor-kappa B, tumor necrosis factor receptor type 1 (TNFR 1) and c-Myc with the clinical course in the treatment of malignant astrocytomas with recombinant mutant human tumor necrosis factor-alpha (TNF-SAM2). Anti-cancer Res 2000, 20:611-618.
12. Umekita Y, Ohi Y, Sagara Y, et al.: Overexpression of cyclinD1 predicts for poor prognosis in estrogen receptor-negative breast cancer patients. Int J Cancer 2002, 98:415-418.
13. Yu Q, Geng Y, Sicinski P: Specific protection against breast cancers by cyclin D1 ablation. Nature 2001, 411:1017-1021.
14. Hinz M, Krappmann D, Echten A, et al.: NF-kappaB function in growth control: regulation of cyclin D1 expression and GO/G1-to-S-phase transition. Mol Cell Biol 1999, 19:2690-2698.
15. Guttridge DC, Albanese C, Reuther JY, et al.: NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol 1999, 19:5785-5799.
16. Karin M, Cao Y, Greten FR, et al.: NF-kappaB in cancer: from innocent by-stander to major culprit. Nat Rev Cancer 2002, 2:301-310.
17. Ghosh S, Karin M: Missing pieces in the NF-kappaB puzzle. Cell 2002, 109(suppl):S81-S96. Offers a concise overview of NF-κB and an interesting perspective on future directions.
18. Meng F, Liu L, Chin PC, et al.: Akt is a downstream target of NF-kappa B. J Biol Chem 2002, 277:29674-29680.
19. Hutchinson J, Jin J, Cardiff RD, et al.: Activation of Akt (protein kinase B) in mammary epithelium provides a critical cell survival signal required for tumor progression. Mol Cell Biol 2001, 21:2203-2212.
20. Bellacosa A, de Feo D, Godwin AK, et al.: Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int J Cancer 1995, 64:280-285.
21. Nakatani K, Thompson DA, Barthel A, et al.: Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines. J Biol Chem 1999, 274:21528-21532.
22. Benezra M, Chevallier N, Morrison DJ, et al.: BRCA1 augments transcription by the NF-kappaB transcription factor by binding to the Rel domain of the p65/RelA subunit. J Biol Chem 2003, 278:26333-26341. The first significant link between BRCA1 signaling and NF-κB.
23. Ravi R, Mookerjee B, van Hensbergen Y, et al.: p53-mediated repression of nuclear factor-kappaB RelA via the transcriptional integrator p300. Cancer Res 1998, 58:4531-4536.
24. Tergaonkar V, Pando M, Vafa O, et al.: p53 Stabilization is decreased upon NFkappaB activation: a role for NFkappaB in acquisition of resistance to chemotherapy. Cancer Cell 2002, 1:493-503.
25. Ryan KM, Ernst MK, Rice NR, et al.: Role of NF-kappaB in p53-mediated programmed cell death. Nature 2000, 404:892-897.
26. Nozaki S, Sledge GW Jr, Nakshatri H: Repression of GADD153/CHOP by NF-kappaB: a possible cellular defense against endoplasmic reticulum stress-induced cell death. Oncogene 2001, 20:2178-2185.
27. Nakshatri H, Bhat-Nakshatri P, Martin DA, et al.: Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol Cell Biol 1997, 17:3629-3639.
28. Sovak MA, Bellas RE, Kim DW, et al.: Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer. J Clin Invest 1997, 100:2952-2960.
29. Cogswell PC, Guttridge DC, Funkhouser WK, et al.: Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3. Oncogene 2000, 19:1123-1131.
30. Dejardin E, Bonizzi G, Bellahcene A, et al.: Highly-expressed p100/p52 (NFKB2) sequesters other NF-kappa B-related proteins in the cytoplasm of human breast cancer cells. Oncogene 1995, 11:1835-1841.
31. Bhat-Nakshatri P, Sweeney CJ, Nakshatri H: Identification of signal transduction pathways involved in constitutive NF-kappaB activation in breast cancer cells. Oncogene 2002, 21:2066-2078.
32. Slamon DJ, Clark GM, Wong SG, et al.: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987, 235:177-182.
33. Biswas DK, Cruz AP, Gansberger E, et al.: Epidermal growth factor-induced nuclear factor kappa B activation: a major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells. Proc Natl Acad Sci USA 2000, 97:8542-8547.
34. van 't Veer LJ, Dai H, van de Vijver MJ, et al.: Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002, 415:530-536. This report is important in demonstrating the potential clinical significance of molecular markers in breast cancer research.
35. Bhat-Nakshatri P, Newton TR, Goulet R Jr, et al.: NF-kappaB activation and interleukin 6 production in fibroblasts by estrogen receptor-negative breast cancer cell-derived interleukin 1alpha. Proc Natl Acad Sci U S A 1998, 95:6971-6976.
36. Biswas DK, Dai SC, Cruz A, et al.: The nuclear factor kappa B (NF-kappaB): a potential therapeutic target for estrogen receptor negative breast cancers. Proc Natl Acad Sci U S A 2001, 98:10386-10391.
37. Nozaki S, Sledge GW Jr, Nakshatri H: Cancer cell-derived interleukin 1alpha contributes to autocrine and paracrine induction of pro-metastatic genes in breast cancer. Biochem Biophys Res Commun 2000, 275:60-62.
38. Lee ZH, Kim HH: Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts. Biochem Biophys Res Commun 2003, 305:211-214.
39. Deng J, Miller SA, Wang HY, et al.: beta-Catenin interacts with and inhibits NF-kappa B in human colon and breast cancer. Cancer Cell 2002, 2:323-334.
40. Dong G, Chen Z, Kato T, et al.: The host environment promotes the constitutive activation of nuclear factor-kappaB and proinflammatory cytokine expression during metastatic tumor progression of murine squamous cell carcinoma. Cancer Res 1999, 59:3495-3504.
41. Rayet B, Gelinas C: Aberrant rel/nfkb genes and activity in human cancer. Oncogene 1999, 18:6938-6947.
42. Bharti AC, Aggarwal BB: Nuclear factor-kappa B and cancer: its role in prevention and therapy. Biochem Pharmacol 2002, 64:883-888.
43. Younes A, Garg A, Aggarwal BB: Nuclear transcription factor-kappaB in Hodgkin's disease. Leuk Lymphoma 2003, 44:929-935.
44. Viatour P, Bentires-Alj M, Chariot A, et al.: NF-kappa B2/p100 induces Bcl-2 expression. Leukemia 2003, 17:1349-1356.
45. Buchholz TA, Davis DW, McConkey DJ, et al.: Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy. Cancer J 2003, 9:33-41. This report illustrates the concept of measuring marker levels shortly after treatment initiation. Further studies that use this measurement scheme will likely be available soon.
46. Symmans WF, Volm MD, Shapiro RL, et al.: Paclitaxel-induced apoptosis and mitotic arrest assessed by serial fine-needle aspiration: implications for early prediction of breast cancer response to neoadjuvant treatment. Clin Cancer Res 2000, 6:4610-4617.
47. Chang J, Ormerod M, Powles TJ, et al.: Apoptosis and proliferation as predictors of chemotherapy response in patients with breast carcinoma. Cancer 2000, 89:2145-2152.
48. Bottini A, Berruti A, Bersiga A, et al.: p53 But not bcl-2 immunostaining is predictive of poor clinical complete response to primary chemotherapy in breast cancer patients. Clin Cancer Res 2000, 6:2751-2758.
49. Charpin C, Garcia S, Bonnier P, et al.: bcl-2 Automated and quantitative immunocytochemical assays in breast carcinomas: correlation with 10-year follow-up. J Clin Oncol 1998, 16:2025-2031.
50. Bonetti A, Zaninelli M, Leone R, et al.: bcl-2 But not p53 expression is associated with resistance to chemotherapy in advanced breast cancer. Clin Cancer Res 1998, 4:2331-2336.
51. Jansen RL, Joosten-Achjanie SR, Volovics A, et al.: Relevance of the expression of bcl-2 in combination with p53 as a prognostic factor in breast cancer. Anticancer Res 1998, 18:4455-4462.
52. Ellis PA, Smith IE, Detre S, et al.: Reduced apoptosis and proliferation and increased Bcl-2 in residual breast cancer following preoperative chemotherapy. Breast Cancer Res Treat 1998, 48:107-116.
53. Collecchi P, Baldini E, Giannessi P, et al.: Primary chemotherapy in locally advanced breast cancer (LABC) : effects on tumour proliferative activity, bcl-2 expression and the relationship between tumour regression and biological markers. Eur J Cancer 1998, 34:1701-1704.
54. Glasgow JN, Qiu J, Rassin D, et al.: Transcriptional regulation of the BCL-X gene by NF-kappaB is an element of hypoxic responses in the rat brain. Neurochem Res 2001, 26:647-659.
55. Shou Y, Li N, Li L, et al.: NF-kappaB-mediated up-regulation of Bcl-X(S) and Bax contributes to cytochrome c release in cyanide-induced apoptosis. J Neurochem 2002, 81:842-852.
56. Liu R, Page C, Beidler DR, et al.: Overexpression of Bcl-x(L) promotes chemotherapy resistance of mammary tumors in a syngeneic mouse model. Am J Pathol 1999, 155:1861-1867.
57. Krajewski S, Blomqvist C, Franssila K, et al.: Reduced expression of proapoptotic gene BAX is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. Cancer Res 1995, 55:4471-4478.
58. Sjostrom J, Krajewski S, Franssila K, et al.: A multivariate analysis of tumour biological factors predicting response to cytotoxic treatment in advanced breast cancer. Br J Cancer 1998, 78:812-815.
59. Gupta S, Afaq F, Mukhtar H: Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Oncogene 2002, 21:3727-3738.
60. Webster GA, Perkins ND: Transcriptional cross talk between NF-kappaB and p53. Mol Cell Biol 1999, 19:3485-3495.
61. Piret B, Schoonbroodt S, Piette J: The ATM protein is required for sustained activation of NF-kappaB following DNA damage. Oncogene 1999, 18:2261-2271.
62. Khanna KK, Jackson SP: DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 2001, 27:247-254.
63. Lowe SW, Ruley HE, Jacks T, et al.: p53-Dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 1993, 74:957-967.
64. Lowe SW, Bodis S, McClatchey A, et al.: p53 Status and the efficacy of cancer therapy in vivo. Science 1994, 266:807-810.
65. Wallace-Brodeur RR, Lowe SW: Clinical implications of p53 mutations. Cell Mol Life Sci 1999, 55:64-75.
66. Overgaard J, Yilmaz M, Guldberg P, et al.: TP53 mutation is an independent prognostic marker for poor outcome in both node-negative and node-positive breast cancer. Acta Oncol 2000, 39:327-333.
67. Rozan S, Vincent-Salomon A, Zafrani B, et al.: No significant predictive value of c-erbB-2 or p53 expression regarding sensitivity to primary chemotherapy or radiotherapy in breast cancer. Int J Cancer 1998, 79:27-33.
68. Geisler S, Lonning PE, Aas T, et al.: Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer. Cancer Res 2001, 61:2505-2512.
69. Kandioler-Eckersberger D, Ludwig C, Rudas M, et al.: TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients. Clin Cancer Res 2000, 6:50-56.
70. Pharoah PD, Day NE, Caldas C: Somatic mutations in the p53 gene and prognosis in breast cancer: a meta-analysis. Br J Cancer 1999, 80:1968-1973.
71. Manna SK, Zhang HJ, Yan T, et al.: Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappaB and activated protein-1. J Biol Chem 1998, 273:13245-13254.
72. Guo G, Yan-Sanders Y, Lyn-Cook BD, et al.: Manganese superoxide dismutase-mediated gene expression in radiation-induced adaptive responses. Mol Cell Biol 2003, 23:2362-2378. This report links NF-κB-mediated Mn-SOD to radiation resistance.
73. Van Antwerp DJ, Martin SJ, Kafri T, et al.: Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science 1996, 274:787-789.
74. Beg AA, Baltimore D: An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 1996, 274:782-784.
75. Wang CY, Mayo MW, Baldwin AS Jr: TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science 1996, 274:784-787.
76. Bharti AC, Aggarwal BB: Chemopreventive agents induce suppression of nuclear factor-kappaB leading to chemosensitization. Ann N Y Acad Sci 2002, 973:392-395.
77. Newton TR, Patel NM, Bhat-Nakshatri P, et al.: Negative regulation of transactivation function but not DNA binding of NF-kappaB and AP-1 by Ikappa-Bbeta1 in breast cancer cells. J Biol Chem 1999, 274:18827-18835.
78. Barkett M, Gilmore TD: Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene 1999, 18:6910-6924.
79. Chuang SE, Yeh PY, Lu YS, et al.: Basal levels and patterns of anticancer drug-induced activation of nuclear factor-kappaB (NF-kappaB), and its attenuation by tamoxifen, dexamethasone, and curcumin in carcinoma cells. Biochem Pharmacol 2002, 63:1709-1716. This report uses several different chemotherapies and tumor types to demonstrate the role of NF-κB in chemoresistance.
80. Kuo ML, Shen SC, Yang CH, et al.: Bcl-2 prevents topoisomerase II inhibitor GL331-induced apoptosis is mediated by down-regulation of poly(ADP-ribose)polymerase activity. Oncogene 1998, 17:2225-2234.
81. Basu S, Rosenzweig KR, Youmell M, et al.: The DNA-dependent protein kinase participates in the activation of NF kappa B following DNA damage. Biochem Biophys Res Commun 1998, 247:79-83.
82. Zandstra PW, Jervis E, Haynes CA, et al.: Concentration-dependent internalization of a cytokine/cytokine receptor complex in human hematopoietic cells. Biotechnol Bioeng 1999, 63:493-501.
83. Patel NM, Nozaki S, Shortle NH, et al.: Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor and parthenolide. Oncogene 2000, 19:4159-4169.
84. Cusack JC Jr, Liu R, Baldwin AS Jr: Inducible chemoresistance to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11) in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor-kappaB activation. Cancer Res 2000, 60:2323-2330.
85. Wang CY, Cusack JC Jr, Liu R, et al.: Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat Med 1999, 5:412-417.
86. Weaver KD, Yeyeodu S, Cusack JC Jr, et al.: Potentiation of chemotherapeutic agents following antagonism of nuclear factor kappa B in human gliomas. J Neurooncol 2003, 61:187-196.
87. Arlt A, Gehrz A, Muerkoster S, et al.: Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death. Oncogene 2003, 22:3243-3251.
88. Biswas DK, Martin KJ, McAlister C, et al.: Apoptosis caused by chemotherapeutic inhibition of nuclear factor-kappaB activation. Cancer Res 2003, 63:290-295.
89. Mitchell BS: The proteasome-an emerging therapeutic target in cancer. N Engl J Med 2003, 348:2597-2598. An important overview of the proteasome inhibitor as a major topic for cancer treatment. The relevance of NF-κB in the mechanism of the 26S proteosome is also discussed.
90. Lenz HJ: Clinical update: proteasome inhibitors in solid tumors. Cancer Treat Rev 2003, 29(suppl 1):41-48.
91. Cusack JC, Liu R, Baldwin AS: NF-kappa B and chemoresistance: potentiation of cancer drugs via inhibition of NF-kappa B. Drug Resist Updat 1999, 2:271-273.
92. Oyaizu H, Adachi Y, Okumura T, et al.: Proteasome inhibitor 1 enhances paclitaxel-induced apoptosis in human lung adenocarcinoma cell line. Oncol Rep 2001, 8:825-829.
93. Teicher BA, Ara G, Herbst R, et al.: The proteasome inhibitor PS-341 in cancer therapy. Clin Cancer Res 1999, 5:2638-2645.
94. Russo SM, Tepper JE, Baldwin AS Jr, et al.: Enhancement of radiosensitivity by proteasome inhibition: implications for a role of NF-kappaB. Int J Radiat Oncol Biol Phys 2001, 50:183-193.
95. Adams J: Proteasome inhibitors as new anticancer drugs. Curr Opin Oncol 2002, 14:628-634.
96. Bharti AC, Donato N, Singh S, et al.: Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaB-alpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 2003, 101:1053-1062.
97. Aggarwal BB, Kumar A, Bharti AC: Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 2003, 23:363-398.
98. Mehta RG, Williamson E, Patel MK, et al.: A ligand of peroxisome proliferator-activated receptor gamma, retinoids, and prevention of preneoplastic mammary lesions. J Natl Cancer Inst 2000, 92:418-423.
99. Badawi AF, Badr MZ: Chemoprevention of breast cancer by targeting cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma (review). Int J Oncol 2002, 20:1109-1122.
100. May MJ, D'Acquisto F, Madge LA, et al.: Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex. Science 2000, 289:1550-1554.
101. Weldon CB, Burow ME, Rolfe KW, et al.: NF-kappa B-mediated chemoresistance in breast cancer cells. Surgery 2001, 130:143-150.
102. Sommer SS, Jiang Z, Feng J, et al.: ATM missense mutations are frequent in patients with breast cancer. Cancer Genet Cytogenet 2003, 145:115-120.
103. Jung M, Dritschilo A: NF-kappa B signaling pathway as a target for human tumor radiosensitization. Semin Radiat Oncol 2001, 11:346-351.
104. Brach MA, Mass R, Sherman ML, et al.: Ionizing radiation induces expression and binding activity of the nuclear factor kappa B. J Clin Invest 1991,88:691-695.
105. Russell JS, Raju U, Gumin GJ, et al.: Inhibition of radiation-induced nuclear factor-kappaB activation by an anti-Ras single-chain antibody fragment: lack of involvement in radiosensitization. Cancer Res 2002, 62:2318-2326.
106. Kurland JF, Meyn RE: Protease inhibitors restore radiation-induced apoptosis to Bcl-2-expressing lymphoma cells. Int J Cancer 2001, 96:327-333.
107. Kurland JF, Voehringer DW, Meyn RE: The MEK/ERK pathway acts upstream of NF kappa B1 (p50) homodimer activity and Bcl-2 expression in a murine B-cell lymphoma cell line: MEK inhibition restores radiation-induced apoptosis. J Biol Chem 2003, 278:32465-32470.
108. Niederberger E, Tegeder I, Schafer C, et al.: Opposite effects of rofecoxib on nuclear factor-kappaB and activating protein-1 activation. J Pharmacol Exp Ther 2003, 304:1153-1160.
109. Milas L, Mason KA, Liao Z, et al.: Chemoradiotherapy: emerging treatment improvement strategies. Head Neck 2003, 25:152-167.
110. Milas I, Komaki R, Hachiya T, et al.: Epidermal growth factor receptor, cyclooxygenase-2, and BAX expression in the primary non-small cell lung cancer and brain metastases. Clin Cancer Res 2003, 9:1070-1076.
111. Milas L, Mason KA, Crane CH, et al.: Improvement of radiotherapy or chemoradiotherapy by targeting COX-2 enzyme. Oncology (Huntingt) 2003, 17:15-24.