Abstract
Transformation of breast cells occurs through loss or mutation of tumor suppressor genes, or activation or amplification of oncogenes, leading to deregulation of signal transduction pathways, abnormal amplification of growth signals, and aberrant expression of genes that ultimately transform the cells into invasive cancer. The goal of cancer preventive therapy, or “chemoprevention,” is to eliminate premalignant cells or to block the progression of normal cells into cancer. Multiple alterations in signal pathways and transcription factors are observed in mammary gland tumorigenesis. In particular, estrogen receptor (ER) deregulation plays a critical role in breast cancer development and progress, and targeting ER with selective ER modulators (SERMs) has achieved significant reduction of breast cancer incidence in women at high risk for breast cancer. However, not all breast cancer is prevented by SERMs, because 30–40% of the tumors are ER-negative. Other receptors for retinoids, vitamin D analogs and peroxisome proliferator–activiator, along with transcription factors such as AP-1, NF-κB, and STATs (signal transducers and activators of transcription) affect breast tumorigenesis. This is also true for the signal transduction pathways, for example cyclooxygenase 2 (Cox-2), HER2/neu, mitogen-activated protein kinase (MAPK), and PI3K/Akt. Therefore, proteins in pathways that are altered during the process of mammary tumorigenesis may be promising targets of future chemopreventive drugs. Many newly-developed synthetic or natural compounds/agents are now under testing in preclinical studies and clinical trials. Receptor selective retinoids, receptor tyrosine kinase inhibitors (TKIs), SERMs, Cox-2 inhibitors, and others are some of the promising novel agents for the prevention of breast cancer. The chemopreventive activity of these agents and other novel signal transduction inhibitors are discussed in this chapter.
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REFERENCES
M. B. Sporn and N. Suh (2000). Chemoprevention of cancer. Carcinogenesis 21:525-530.
J. A. O'Shaughnessy, G. J. Kelloff, G. B. Gordon, A. J. Dannenberg, W. K. Hong, C. J. Fabian, C. C. Sigman, M. M. Bertagnolli, S. P. Stratton, S. Lam, W. G. Nelson, F. L. Meyskens, D. S. Alberts, M. Follen, A. K. Rustgi, V. Papadimitrakopoulou, P. T. Scardino, A. F. Gazdar, L. W. Wattenberg, M. B. Sporn, W. A. Sakr, S. M. Lippman, and D. D. Von Hoff (2002). Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. Clin. Cancer Res. 8:314-346.
(1999). Prevention of cancer in the next millennium: Report of the Chemoprevention Working Group to the American Association for Cancer Research. Cancer Res. 59:4743-4758.
S. M. Lippman and W. K. Hong (2002). Cancer prevention science and practice. Cancer Res. 62:5119-5125.
P. Greenwald (2002). Cancer chemoprevention. BMJ 324:714-718.
A. C. Society (2002). Estimated New Cancer Cases and Deaths by Gender, US, 2002.
S. M. Townson, M. Ivanova, A. V. Lee and S. Oesterreich (2002). The role of estrogen in normal breast development and breast cancer. In E. Dopp, H. Stopper and G. M. Alink (Ed). Natural and Synthetic Estrogens: Aspects of the Cellular and Molecular Activity. Research Signpost, Kerala, India.
S. Nilsson, S. Makela, E. Treuter, M. Tujague, J. Thomsen, G. Andersson, E. Enmark, K. Pettersson, M. Warner, and J. A. Gustafsson (2001). Mechanisms of estrogen action. Physiol Rev. 81:1535-1565.
C. K. Osborne (1998). Tamoxifen in the treatment of breast cancer. N. Engl. J. Med. 339:1609-1618.
T. A. Grese, J. P. Sluka, H. U. Bryant, G. J. Cullinan, A. L. Glasebrook, C. D. Jones, K. Matsumoto, A. D. Palkowitz, M. Sato, J. D. Termine, M. A. Winter, N. N. Yang, and J. A. Dodge (1997). Molecular determinants of tissue selectivity in estrogen receptor modulators. Proc. Natl. Acad. Sci. U. S. A. 94:14105-14110.
J. I. Schafer, H. Liu, D. A. Tonetti, and V. C. Jordan (1999). The interaction of raloxifene and the active metabolite of the antiestrogen EM-800 (SC 5705) with the human estrogen receptor. Cancer Res. 59:4308-4313.
R. M. O'Regan, A. Cisneros, G. M. England, J. I. MacGregor, H. D. Muenzner, V. J. Assikis, M. M. Bilimoria, M. Piette, Y. P. Dragan, H. C. Pitot, R. Chatterton, and V. C. Jordan (1998). Effects of the antiestrogens tamoxifen, toremifene, and ICI 182,780 on endometrial cancer growth. J. Natl. Cancer Inst. 90:1552-1558.
B. Fisher, J. P. Costantino, D. L. Wickerham, C. K. Redmond, M. Kavanah, W. M. Cronin, V. Vogel, A. Robidoux, N. Dimitrov, J. Atkins, M. Daly, S. Wieand, E. Tan-Chiu, L. Ford, and N. Wolmark (1998). Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl. Cancer Inst. 90:1371-1388.
S. R. Cummings, S. Eckert, K. A. Krueger, D. Grady, T. J. Powles, J. A. Cauley, L. Norton, T. Nickelsen, N. H. Bjarnason, M. Morrow, M. E. Lippman, D. Black, J. E. Glusman, A. Costa, and V. C. Jordan (1999). The effect of raloxifene on risk of breast cancer in postmenopausal women: Results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 281:2189-2197.
T. J. Powles (2001). The Royal Marsden Hospital (RMH) trial: Key points and remaining questions. Ann. N. Y. Acad. Sci. 949:109-112.
U. Veronesi, P. Maisonneuve, A. Costa, V. Sacchini, C. Maltoni, C. Robertson, N. Rotmensz, and P. Boyle (1998). Prevention of breast cancer with tamoxifen: Preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Lancet 352:93-97.
IBIS Investigators (2002). First results from the International Breast Cancer Intervention Study (IBIS-I): A randomised prevention trial. Lancet 360:817-824.
K. Wu, H. T. Kim, J. L. Rodriquez, D. Munoz-Medellin, S. K. Mohsin, S. G. Hilsenbeck, W. W. Lamph, M. M. Gottardis, M. A. Shirley, J. G. Kuhn, J. E. Green, and P. H. Brown (2000). 9-cis-Retinoic acid suppresses mammary tumorigenesis in C3(1)-simian virus 40 T antigen-transgenic mice. Clin. Cancer Res. 6:3696-3704.
J. E. Green, M. A. Shibata, K. Yoshidome, M. L. Liu, C. Jorcyk, M. R. Anver, J. Wigginton, R. Wiltrout, E. Shibata, S. Kaczmarczyk, W. Wang, Z. Y. Liu, A. Calvo, and C. Couldrey (2000). The C3(1)/SV40 T-antigen transgenic mouse model of mammary cancer: Dsssuctal epithelial cell targeting with multistage progression to carcinoma. Oncogene 19:1020-1027.
V. A. Miller, F. M. Benedetti, J. R. Rigas, A. L. Verret, D. G. Pfister, D. Straus, M. G. Kris, M. Crisp, R. Heyman, G. R. Loewen, J. A. Truglia, and R. P. Warrell Jr. (1997). Initial clinical trial of a selective retinoid X receptor ligand, LGD1069. J. Clin. Oncol. 15:790-795.
N. A. Rizvi, J. L. Marshall, W. Dahut, E. Ness, J. A. Truglia, G. Loewen, G. M. Gill, E. H. Ulm, R. Geiser, D. Jaunakais, and M. J. Hawkins (1999). A Phase I study of LGD1069 in adults with advanced cancer. Clin. Cancer Res. 5:1658-1664.
M. Duvic, K. Hymes, P. Heald, D. Breneman, A. G. Martin, P. Myskowski, C. Crowley, and R. C. Yocum (2001). Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: Multinational phase II–III trial results. J. Clin. Oncol. 19:2456-2471.
K. J. Pienta, P. S. Esper, F. Zwas, R. Krzeminski, and L. E. Flaherty (1997). Phase II chemoprevention trial of oral fenretinide in patients at risk for adenocarcinoma of the prostate. Am. J. Clin. Oncol. 20:36-39.
T. Gulliford, J. English, K. W. Colston, P. Menday, S. Moller, and R. C. Coombes (1998). A phase I study of the vitamin D analogue EB 1089 in patients with advanced breast and colorectal cancer. Br. J. Cancer 78:6-13.
G. Liu, K. Oettel, G. Ripple, M. J. Staab, D. Horvath, D. Alberti, R. Arzoomanian, R. Marnocha, R. Bruskewitz, R. Mazess, C. Bishop, A. Bhattacharya, H. Bailey, and G. Wilding (2002). Phase I trial of 1alpha-hydroxyvitamin d(2) in patients with hormone refractory prostate cancer. Clin. Cancer Res. 8:2820-2827.
T. R. Evans, K. W. Colston, F. J. Lofts, D. Cunningham, D. A. Anthoney, H. Gogas, J. S. de Bono, K. J. Hamberg, T. Skov, and J. L. Mansi (2002). A phase II trial of the vitamin D analogue Seocalcitol (EB1089) in patients with inoperable pancreatic cancer. Br. J. Cancer 86:680-685.
L. Verlinden, A. Verstuyf, M. Quack, M. Van Camp, E. Van Etten, P. De Clercq, M. Vandewalle, C. Carlberg, and R. Bouillon (2001). Interaction of two novel 14-epivitamin D3 analogs with vitamin D3 receptor-retinoid X receptor heterodimers on vitamin D3 responsive elements. J. Bone Miner. Res. 16:625-638.
P. Bortman, M. A. Folgueira, M. L. Katayama, I. M. Snitcovsky, and M. M. Brentani (2002). Antiproliferative effects of 1,25-dihydroxyvitamin D3 on breast cells: A mini review. Braz. J. Med. Biol. Res. 35:1-9.
J. Hisatake, J. O'Kelly, M. R. Uskokovic, S. Tomoyasu, and H. P. Koeffler (2001). Novel vitamin D(3) analog, 21-(3-methyl-3-hydroxy-butyl)-19-nor D(3), that modulates cell growth, differentiation, apoptosis, cell cycle, and induction of PTEN in leukemic cells. Blood 97:2427-2433.
M. Chaudhry, S. Sundaram, C. Gennings, H. Carter, and D. A. Gewirtz (2001). The vitamin D3 analog, ILX-23-7553, enhances the response to adriamycin and irradiation in MCF-7 breast tumor cells. Cancer Chemother. Pharmacol. 47:429-436.
M. Chodynski, J. Wietrzyk, E. Marcinkowska, A. Opolski, W. Szelejewski, and A. Kutner (2002). Synthesis and antiproliferative activity of side-chain unsaturated and homologated analogs of 1,25-dihydroxyvitamin D(2). (24E)-(1S)-24-Dehydro-24a-homo-1,25-dihydroxyergocalciferol and congeners. Steroids 67:789-798.
A. B. Jones (2001). Peroxisome proliferator-activated receptor (PPAR) modulators: Diabetes and beyond. Med. Res. Rev. 21:540-552.
B. A. Stoll (2002). Linkage between retinoid and fatty acid receptors: Implications for breast cancer prevention. Eur. J. Cancer Prev. 11:319-325.
E. Elstner, E. A. Williamson, C. Zang, J. Fritz, D. Heber, M. Fenner, K. Possinger, and H. P. Koeffler (2002). Novel therapeutic approach: Ligands for PPARgamma and retinoid receptors induce apoptosis in bcl-2-positive human breast cancer cells. Breast Cancer Res. Treat. 74:155-165.
G. M. Pighetti, W. Novosad, C. Nicholson, D. C. Hitt, C. Hansens, A. B. Hollingsworth, M. L. Lerner, D. Brackett, S. A. Lightfoot, and J. M. Gimble (2001). Therapeutic treatment of DMBA-induced mammary tumors with PPAR ligands. Anticancer Res. 21:825-829.
M. R. Young, L. Farrell, P. Lambert, P. Awasthi, and N. H. Colburn (2002). Protection against human papillomavirus type 16-E7 oncogene-induced tumorigenesis by in vivo expression of dominant-negative c-jun. Mol. Carcinog. 34:72-77.
E. J. Thompson, J. MacGowan, M. R. Young, N. Colburn, and G. T. Bowden (2002). A dominant negative c-jun specifically blocks okadaic acid-induced skin tumor promotion. Cancer Res. 62:3044-3047.
A. L. Cheng, C. H. Hsu, J. K. Lin, M. M. Hsu, Y. F. Ho, T. S. Shen, J. Y. Ko, J. T. Lin, B. R. Lin, W. Ming-Shiang, H. S. Yu, S. H. Jee, G. S. Chen, T. M. Chen, C. A. Chen, M. K. Lai, Y. S. Pu, M. H. Pan, Y. J. Wang, C. C. Tsai, and C. Y. Hsieh (2001). Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 21:2895-2900.
Z. M. Shao, Z. Z. Shen, C. H. Liu, M. R. Sartippour, V. L. Go, D. Heber, and M. Nguyen (2002). Curcumin exerts multiple suppressive effects on human breast carcinoma cells. Int. J. Cancer 98:234-240.
T. Choudhuri, S. Pal, M. L. Agwarwal, T. Das, and G. Sa (2002). Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction. FEBS Lett. 512:334-340.
H. Inano, M. Onoda, N. Inafuku, M. Kubota, Y. Kamada, T. Osawa, H. Kobayashi, and K. Wakabayashi (2000). Potent preventive action of curcumin on radiation-induced initiation of mammary tumorigenesis in rats. Carcinogenesis 21:1835-1841.
C. C. Lin, Y. P. Lu, Y. R. Lou, C. T. Ho, H. H. Newmark, C. MacDonald, K. W. Singletary, and M. T. Huang (2001). Inhibition by dietary dibenzoylmethane of mammary gland proliferation, formation of DMBA-DNA adducts in mammary glands, and mammary tumorigenesis in Sencar mice. Cancer Lett. 168:125-132.
T. J. Huang, I. M. Adcock, and K. F. Chung (2001). A novel transcription factor inhibitor, SP100030, inhibits cytokine gene expression, but not airway eosinophilia or hyperresponsiveness in sensitized and allergen-exposed rat. Br. J. Pharmacol. 134:1029-1036.
K. Gunawardena, D. K. Murray, R. E. Swope, and A. W. Meikle (2002). Inhibition of nuclear factor kappaB induces apoptosis following treatment with tumor necrosis factor alpha and an antioxidant in human prostate cancer cells. Cancer Detect. Prev. 26:229-237.
Q. G. Dong, G. M. Sclabas, S. Fujioka, C. Schmidt, B. Peng, T. Wu, M. S. Tsao, D. B. Evans, J. L. Abbruzzese, T. J. McDonnell, and P. J. Chiao (2002). The function of multiple IkappaB: NF-kappaB complexes in the resistance of cancer cells to Taxol-induced apoptosis. Oncogene 21:6510-6519.
B. D. Cheson (2002). Hematologic malignancies: New developments and future treatments. Semin. Oncol. 29:33-45.
J. A. Bonner, K. P. Raisch, H. Q. Trummell, F. Robert, R. F. Meredith, S. A. Spencer, D. J. Buchsbaum, M. N. Saleh, M. A. Stackhouse, A. F. LoBuglio, G. E. Peters, W. R. Carroll, and H. W. Waksal (2000). Enhanced apoptosis with combination C225/radiation treatment serves as the impetus for clinical investigation in head and neck cancers. J. Clin. Oncol. 18:47S-53S.
W. M. Burke, X. Jin, H. J. Lin, M. Huang, R. Liu, R. K. Reynolds, and J. Lin (2001). Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells. Oncogene 20:7925-7934.
L. Li and P. E. Shaw (2002). Autocrine-mediated activation of STAT3 correlates with cell proliferation in breast carcinoma lines. J. Biol. Chem. 277:17397-17405.
S. Alas and B. Bonavida (2003). Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin's lymphoma and multiple myeloma to chemotherapeutic drug-mediated apoptosis. Clin. Cancer Res. 9:316-326.
L. Burdelya, R. Catlett-Falcone, A. Levitzki, F. Cheng, L. B. Mora, E. Sotomayor, D. Coppola, J. Sun, S. Sebti, W. S. Dalton, R. Jove, and H. Yu (2002). Combination therapy with AG-490 and interleukin 12 achieves greater antitumor effects than either agent alone. Mol. Cancer Ther. 1:893-899.
A. Aranda and A. Pascual (2001). Nuclear hormone receptors and gene expression. Physiol. Rev. 81:1269-1304.
L. Yang, H. T. Kim, D. Munoz-Medellin, P. Reddy, and P. H. Brown (1997). Induction of retinoid resistance in breast cancer cells by overexpression of cJun. Cancer Res. 57:4652-4661.
M. Rubin, E. Fenig, A. Rosenauer, C. Menendez-Botet, C. Achkar, J. M. Bentel, J. Yahalom, J. Mendelsohn, and W. H. Miller Jr. (1994). 9-Cis retinoic acid inhibits growth of breast cancer cells and down-regulates estrogen receptor RNA and protein. Cancer Res. 54:6549-6556.
M. A. Anzano, S. W. Byers, J. M. Smith, C. W. Peer, L. T. Mullen, C. C. Brown, A. B. Roberts, and M. B. Sporn (1994). Prevention of breast cancer in the rat with 9-cis-retinoic acid as a single agent and in combination with tamoxifen. Cancer Res. 54:4614-4617.
V. A. Miller, J. R. Rigas, F. M. Benedetti, A. L. Verret, W. P. Tong, M. G. Kris, G. M. Gill, G. R. Loewen, J. A. Truglia, E. H. Ulm, and R. P. Warrell Jr. (1996). Initial clinical trial of the retinoid receptor pan agonist 9-cis retinoic acid. Clin. Cancer Res. 2:471-475.
J. A. Fontana (1987). Interaction of retinoids and tamoxifen on the inhibition of human mammary carcinoma cell proliferation. Exp. Cell Biol. 55:136-144.
E. Ulukaya and E. J. Wood (1999). Fenretinide and its relation to cancer. Cancer Treat. Rev. 25:229-235.
R. C. Moon, H. J. Thompson, P. J. Becci, C. J. Grubbs, R. J. Gander, D. L. Newton, J. M. Smith, S. L. Phillips, W. R. Henderson, L. T. Mullen, C. C. Brown, and M. B. Sporn (1979). N-(4-Hydroxyphenyl)retinamide, a new retinoid for prevention of breast cancer in the rat. Cancer Res. 39:1339-1346.
T. A. Ratko, C. J. Detrisac, N. M. Dinger, C. F. Thomas, G. J. Kelloff, and R. C. Moon (1989). Chemopreventive efficacy of combined retinoid and tamoxifen treatment following surgical excision of a primary mammary cancer in female rats. Cancer Res. 49:4472-4476.
R. C. Moon, G. J. Kelloff, C. J. Detrisac, V. E. Steele, C. F. Thomas, and C. C. Sigman (1992). Chemoprevention of MNU-induced mammary tumors in the mature rat by 4-HPR and tamoxifen. Anticancer Res. 12:1147-1153.
U. Veronesi, G. De Palo, E. Marubini, A. Costa, F. Formelli, L. Mariani, A. Decensi, T. Camerini, M. R. Del Turco, M. G. Di Mauro, M. G. Muraca, M. Del Vecchio, C. Pinto, G. D'Aiuto, C. Boni, T. Campa, A. Magni, R. Miceli, M. Perloff, W. F. Malone, and M. B. Sporn (1999). Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer. J. Natl. Cancer Inst. 91:1847-1856.
Y. Aoyama (2002). Experimental studies on the effects of the combined use of N-(4-hydroxyphenyl)retinamide (4-HPR) and tamoxifen (TAM) for estrogen receptor (ER)-negative breast cancer. Kurume Med. J. 49:27-33.
S. E. Singletary, E. N. Atkinson, A. Hoque, N. Sneige, A. A. Sahin, H. A. Fritsche Jr., R. Lotan, T. Lu, W. N. Hittelman, T. B. Bevers, C. B. Stelling, and S. M. Lippman (2002). Phase II clinical trial of N-(4-Hydroxyphenyl)retinamide and tamoxifen administration before definitive surgery for breast neoplasia. Clin. Cancer Res. 8:2835-2842.
M. M. Gottardis, E. D. Bischoff, M. A. Shirley, M. A. Wagoner, W. W. Lamph, and R. A. Heyman (1996). Chemoprevention of mammary carcinoma by LGD1069 (Targretin): An RXR-selective ligand. Cancer Res. 56:5566-5570.
K. Wu, H. T. Kim, J. L. Rodriquez, S. G. Hilsenbeck, S. K. Mohsin, X. C. Xu, W. W. Lamph, J. G. Kuhn, J. E. Green, and P. H. Brown (2002). Suppression of mammary tumorigenesis in transgenic mice by the RXR-selective retinoid, LGD1069. Cancer Epidemiol. Biomarkers Prev. 11:467-474.
K. Wu, Y. Zhang, X. C. Xu, J. Hill, J. Celestino, H. T. Kim, S. K. Mohsin, S. G. Hilsenbeck, W. W. Lamph, R. Bissonette, and P. H. Brown (2002). The retinoid X receptor-selective retinoid, LGD1069, prevents the development of estrogen receptor-negative mammary tumors in transgenic mice. Cancer Res. 62:6376-6380.
E. D. Bischoff, M. M. Gottardis, T. E. Moon, R. A. Heyman, and W. W. Lamph (1998). Beyond tamoxifen: The retinoid X receptor-selective ligand LGD1069 (TARGRETIN) causes complete regression of mammary carcinoma. Cancer Res. 58:479-484.
N. Suh, W. W. Lamph, A. L. Glasebrook, T. A. Grese, A. D. Palkowitz, C. R. Williams, R. Risingsong, M. R. Farris, R. A. Heyman, and M. B. Sporn (2002). Prevention and treatment of experimental breast cancer with the combination of a new selective estrogen receptor modulator, arzoxifene, and a new rexinoid, LG 100268. Clin. Cancer Res. 8:3270-3275.
R. J. Frampton, L. J. Suva, J. A. Eisman, D. M. Findlay, G. E. Moore, J. M. Moseley, and T. J. Martin (1982). Presence of 1,25-dihydroxyvitamin D3 receptors in established human cancer cell lines in culture. Cancer Res. 42:1116-1119.
J. A. Eisman, L. J. Suva, E. Sher, P. J. Pearce, J. W. Funder, and T. J. Martin (1981). Frequency of 1,25-dihydroxyvitamin D3 receptor in human breast cancer. Cancer Res. 41:5121-5124.
M. Friedrich, R. Axt-Fliedner, C. Villena-Heinsen, W. Tilgen, W. Schmidt, and J. Reichrath (2002). Analysis of vitamin D-receptor (VDR) and retinoid X-receptor alpha in breast cancer. Histochem. J. 34:35-40.
M. T. Escaleira, S. Sonohara, and M. M. Brentani (1993). Sex steroids induced up-regulation of 1,25-(OH)2 vitamin D3 receptors in T 47D breast cancer cells. J. Steroid Biochem. Mol. Biol. 45:257-263.
C. Chouvet, E. Vicard, M. Devonec, and S. Saez (1986). 1,25-Dihydroxyvitamin D3 inhibitory effect on the growth of two human breast cancer cell lines (MCF-7, BT-20). J. Steroid Biochem. 24:373-376.
M. T. Escaleira and M. M. Brentani (1999). Vitamin D3 receptor (VDR) expression in HC-11 mammary cells: Regulation by growth-modulatory agents, differentiation, and Ha-ras transformation. Breast Cancer Res. Treat. 54:123-133.
S. P. Xie, G. Pirianov, and K. W. Colston (1999). Vitamin D analogues suppress IGF-I signalling and promote apoptosis in breast cancer cells. Eur. J. Cancer 35:1717-1723.
R. R. Mehta, L. Bratescu, J. M. Graves, A. Green, and R. G. Mehta (2000). Differentiation of human breast carcinoma cells by a novel vitamin D analog: 1Alpha-hydroxyvitamin D5. Int. J. Oncol. 16:65-73.
L. Verlinden, A. Verstuyf, M. Van Camp, S. Marcelis, K. Sabbe, X. Y. Zhao, P. De Clercq, M. Vandewalle, and R. Bouillon (2000). Two novel 14-Epi-analogues of 1,25-dihydroxyvitamin D3 inhibit the growth of human breast cancer cells in vitro and in vivo. Cancer Res. 60:2673-2679.
R. M. Evans (1988). The steroid and thyroid hormone receptor superfamily. Science 240:889-895.
K. Schoonjans, G. Martin, B. Staels, and J. Auwerx (1997). Peroxisome proliferator-activated receptors, orphans with ligands and functions. Curr. Opin. Lipidol. 8:159-166.
K. Schoonjans, B. Staels, and J. Auwerx (1996). The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation. Biochim. Biophys. Acta. 1302:93-109.
J. Berger and D. E. Moller (2002). The mechanisms of action of PPARs. Annu. Rev. Med. 53:409-435.
J. Auwerx (1999). PPARgamma, the ultimate thrifty gene. Diabetologia 42:1033-1049.
S. Theocharis, H. Kanelli, E. Politi, A. Margeli, C. Karkandaris, T. Philippides, and A. Koutselinis (2002). Expression of peroxisome proliferator activated receptor-gamma in non-small cell lung carcinoma: Correlation with histological type and grade. Lung Cancer 36:249-255.
Y. Segawa, R. Yoshimura, T. Hase, T. Nakatani, S. Wada, Y. Kawahito, T. Kishimoto, and H. Sano (2002). Expression of peroxisome proliferator-activated receptor (PPAR) in human prostate cancer. Prostate 51:108-116.
K. M. Suchanek, F. J. May, J. A. Robinson, W. J. Lee, N. A. Holman, G. R. Monteith, and S. J. Roberts-Thomson (2002). Peroxisome proliferator-activated receptor alpha in the human breast cancer cell lines MCF-7 and MDA-MB-231. Mol. Carcinog. 34:165-171.
K. M. Suchanek, F. J. May, W. J. Lee, N. A. Holman, and S. J. Roberts-Thomson (2002). Peroxisome proliferator-activated receptor beta expression in human breast epithelial cell lines of tumorigenic and non-tumorigenic origin. Int. J. Biochem. Cell Biol. 34:1051-1058.
A. F. Badawi and M. Z. Badr (2002). Chemoprevention of breast cancer by targeting cyclooxygenase-2 and peroxisome proliferator-activated receptor-gamma (Review). Int. J. Oncol. 20:1109-1122.
X. Wang and M. W. Kilgore (2002). Signal cross-talk between estrogen receptor alpha and beta and the peroxisome proliferator-activated receptor gamma1 in MDA-MB-231 and MCF-7 breast cancer cells. Mol. Cell Endocrinol. 194:123-133.
M. Pignatelli, M. Cortes-Canteli, C. Lai, A. Santos, and A. Perez-Castillo (2001). The peroxisome proliferator-activated receptor gamma is an inhibitor of ErbBs activity in human breast cancer cells. J. Cell Sci. 114:4117-4126.
P. Sarraf, E. Mueller, D. Jones, F. J. King, D. J. DeAngelo, J. B. Partridge, S. A. Holden, L. B. Chen, S. Singer, C. Fletcher, and B. M. Spiegelman (1998). Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat. Med. 4:1046-1052.
T. Kubota, K. Koshizuka, E. A. Williamson, H. Asou, J. W. Said, S. Holden, I. Miyoshi, and H. P. Koeffler (1998). Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res. 58:3344-3352.
E. Elstner, C. Muller, K. Koshizuka, E. A. Williamson, D. Park, H. Asou, P. Shintaku, J. W. Said, D. Heber, and H. P. Koeffler (1998). Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc. Natl. Acad. Sci. U. S. A. 95:8806-8811.
T. Tanaka, H. Kohno, S. Yoshitani, S. Takashima, A. Okumura, A. Murakami, and M. Hosokawa (2001). Ligands for peroxisome proliferator-activated receptors alpha and gamma inhibit chemically induced colitis and formation of aberrant crypt foci in rats. Cancer Res. 61:2424-2428.
E. Saez, P. Tontonoz, M. C. Nelson, J. G. Alvarez, U. T. Ming, S. M. Baird, V. A. Thomazy, and R. M. Evans (1998). Activators of the nuclear receptor PPARgamma enhance colon polyp formation. Nat. Med. 4:1058-1061.
A. M. Lefebvre, I. Chen, P. Desreumaux, J. Najib, J. C. Fruchart, K. Geboes, M. Briggs, R. Heyman, and J. Auwerx (1998). Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin/+ mice. Nat. Med. 4:1053-1057.
M. B. Sporn, N. Suh, and D. J. Mangelsdorf (2001). Prospects for prevention and treatment of cancer with selective PPARgamma modulators (SPARMs). Trends Mol. Med. 7:395-400.
E. Osawa, A. Nakajima, K. Wada, S. Ishimine, N. Fujisawa, T. Kawamori, N. Matsuhashi, T. Kadowaki, M. Ochiai, H. Sekihara, and H. Nakagama (2003). Peroxisome proliferator-activated receptor gamma ligands suppress colon carcinogenesis induced by azoxymethane in mice. Gastroenterology 124:361-367.
R. G. Mehta, E. Williamson, M. K. Patel, and H. P. Koeffler (2000). A ligand of peroxisome proliferator-activated receptor gamma, retinoids, and prevention of preneoplastic mammary lesions. J. Natl. Cancer Inst. 92:418-423.
J. T. Holt, T. V. Gopal, A. D. Moulton, and A. W. Nienhuis (1986). Inducible production of c-fos antisense RNA inhibits 3T3 cell proliferation. Proc. Natl. Acad. Sci. U. S. A. 83:4794-4798.
E. Szabo, L. H. Preis, P. H. Brown, and M. J. Birrer (1991). The role of jun and fos gene family members in 12-O-tetradecanoylphorbol-13-acetate induced hemopoietic differentiation. Cell Growth Differ. 2:475-482.
J. Ham, C. Babij, J. Whitfield, C. M. Pfarr, D. Lallemand, M. Yaniv, and L. L. Rubin (1995). A c-Jun dominant negative mutant protects sympathetic neurons against programmed cell death. Neuron 14:927-939.
P. H. Brown, R. Alani, L. H. Preis, E. Szabo, and M. J. Birrer (1993). Suppression of oncogene-induced transformation by a deletion mutant of c-jun. Oncogene 8:877-886.
P. H. Brown, T. K. Chen, and M. J. Birrer (1994). Mechanism of action of a dominant-negative mutant of c-Jun. Oncogene 9:791-799.
L. M. Matrisian (1994). Matrix metalloproteinase gene expression. Ann. N. Y. Acad. Sci. 732:42-50.
P. Angel, I. Baumann, B. Stein, H. Delius, H. J. Rahmsdorf, and P. Herrlich (1987). 12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5′-flanking region. Mol. Cell. Biol. 7:2256-2266.
S. E. McDonnell, L. D. Kerr, and L. M. Matrisian (1990). Epidermal growth factor stimulation of stromelysin mRNA in rat fibroblasts requires induction of proto-oncogenes c-fos and c-jun and activation of protein kinase C. Mol. Cell. Biol. 10:4284-4293.
A. R. Mackay, M. Ballin, M. D. Pelina, A. R. Farina, A. M. Nason, J. L. Hartzler, and U. P. Thorgeirsson (1992). Effect of phorbol ester and cytokines on matrix metalloproteinase and tissue inhibitor of metalloproteinase expression in tumor and normal cell lines. Invasion Metastasis 12:168-184.
T. K. Chen, L. M. Smith, D. K. Gebhardt, M. J. Birrer, and P. H. Brown (1996). Activation and inhibition of the AP-1 complex in human breast cancer cells. Mol. Carcinog. 15:215-226.
J. H. Ludes-Meyers, Y. Liu, D. Munoz-Medellin, S. G. Hilsenbeck, and P. H. Brown (2001). AP-1 blockade inhibits the growth of normal and malignant breast cells. Oncogene 20:2771-2780.
J. M. Gee, A. F. Barroso, I. O. Ellis, J. F. Robertson, and R. I. Nicholson (2000). Biological and clinical associations of c-jun activation in human breast cancer. Int. J. Cancer 89:177-186.
A. M. Bamberger, C. Methner, B. W. Lisboa, C. Stadtler, H. M. Schulte, T. Loning, and K. Milde-Langosch (1999). Expression pattern of the AP-1 family in breast cancer: association of fosB expression with a well-differentiated, receptor-positive tumor phenotype. Int. J. Cancer 84:533-538.
Z. Tang, I. Treilleux, and M. Brown (1997). A transcriptional enhancer required for the differential expression of the human estrogen receptor in breast cancers. Mol. Cell. Biol. 17:1274-1280.
L. M. Smith, S. C. Wise, D. T. Hendricks, A. L. Sabichi, T. Bos, P. Reddy, P. H. Brown, and M. J. Birrer (1999). cJun overexpression in MCF-7 breast cancer cells produces a tumorigenic, invasive and hormone resistant phenotype. Oncogene 18:6063-6070.
R. Schiff, P. Reddy, M. Ahotupa, E. Coronado-Heinsohn, M. Grim, S. G. Hilsenbeck, R. Lawrence, S. Deneke, R. Herrera, G. C. Chamness, S. A. Fuqua, P. H. Brown, and C. K. Osborne (2000). Oxidative stress and AP-1 activity in tamoxifen-resistant breast tumors in vivo. J. Natl. Cancer Inst. 92:1926-1934.
S. R. Johnston, B. Lu, G. K. Scott, P. J. Kushner, I. E. Smith, M. Dowsett, and C. C. Benz (1999). Increased activator protein-1 DNA binding and c-Jun NH2-terminal kinase activity in human breast tumors with acquired tamoxifen resistance. Clin. Cancer Res. 5:251-256.
P. J. Daschner, H. P. Ciolino, C. A. Plouzek, and G. C. Yeh (1999). Increased AP-1 activity in drug resistant human breast cancer MCF-7 cells. Breast Cancer Res. Treat. 53:229-240.
Y. Liu, J. Ludes-Meyers, Y. Zhang, D. Munoz-Medellin, H. T. Kim, C. Lu, G. Ge, R. Schiff, S. G. Hilsenbeck, C. K. Osborne, and P. H. Brown (2002). Inhibition of AP-1 transcription factor causes blockade of multiple signal transduction pathways and inhibits breast cancer growth. Oncogene 21:7680-7689.
M. R. Young, J. J. Li, M. Rincon, R. A. Flavell, B. K. Sathyanarayana, R. Hunziker, and N. Colburn (1999). Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion. Proc. Natl. Acad. Sci. U. S. A. 96:9827-9832.
M. Morikawa, R. A. Shorthouse, M. J. Suto, M. E. Goldman, and R. E. Morris (1997). A novel inhibitor of nuclear factor-kappa B and activator protein-1 transcription factors in T cells suppresses host-versus-graft alloreactivity in vivo. Transplant. Proc. 29:1269-1270.
J. Ishida, H. Ohtsu, Y. Tachibana, Y. Nakanishi, K. F. Bastow, M. Nagai, H. K. Wang, H. Itokawa, and K. H. Lee (2002). Antitumor agents. Part 214: Synthesis and evaluation of curcumin analogues as cytotoxic agents. Bioorg Med. Chem. 10:3481-3487.
H. Inano, M. Onoda, N. Inafuku, M. Kubota, Y. Kamada, T. Osawa, H. Kobayashi, and K. Wakabayashi (1999). Chemoprevention by curcumin during the promotion stage of tumorigenesis of mammary gland in rats irradiated with gamma-rays. Carcinogenesis 20:1011-1018.
K. Singletary and C. MacDonald (2000). Inhibition of benzo[a]pyrene-and 1,6-dinitropyrene-DNA adduct formation in human mammary epithelial cells by dibenzoylmethane and sulforaphane. Cancer Lett. 155:47-54.
F. Chen, V. Castranova, and X. Shi (2001). New insights into the role of nuclear factor-kappaB in cell growth regulation. Am. J. Pathol. 159:387-397.
M. Karin and Y. Ben-Neriah (2000). Phosphorylation meets ubiquitination: The control of NF-[kappa]B activity. Annu. Rev. Immunol. 18:621-663.
H. L. Pahl (1999). Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18:6853-6866.
T. D. Gilmore (1999). The Rel/NF-kappaB signal transduction pathway: Introduction. Oncogene 18:6842-6844.
J. C. Pena, C. B. Thompson, W. Recant, E. E. Vokes, and C. M. Rudin (1999). Bcl-xL and Bcl-2 expression in squamous cell carcinoma of the head and neck. Cancer 85:164-170.
S. Kondo, Y. Shinomura, S. Kanayama, Y. Higashimoto, J. I. Miyagawa, T. Minami, T. Kiyohara, S. Zushi, S. Kitamura, K. Isozaki, and Y. Matsuzawa (1996). Over-expression of bcl-xL gene in human gastric adenomas and carcinomas. Int. J. Cancer 68:727-730.
S. Nasi, R. Ciarapica, R. Jucker, J. Rosati, and L. Soucek (2001). Making decisions through Myc. FEBS Lett. 490:153-162.
I. V. Boiko, M. F. Mitchell, W. Hu, D. K. Pandey, P. Mathevet, A. Malpica, and W. N. Hittelman (1998). Epidermal growth factor receptor expression in cervical intraepithelial neoplasia and its modulation during an alpha-difluoromethylornithine chemoprevention trial. Clin. Cancer Res. 4:1383-1391.
J. Langenfeld, H. Kiyokawa, D. Sekula, J. Boyle, and E. Dmitrovsky (1997). Posttranslational regulation of cyclin D1 by retinoic acid: A chemoprevention mechanism. Proc. Natl. Acad. Sci. U. S. A. 94:12070-12074.
S. Philip, A. Bulbule, and G. C. Kundu (2001). Osteopontin stimulates tumor growth and activation of promatrix metalloproteinase-2 through nuclear factor-kappa B-mediated induction of membrane type 1 matrix metalloproteinase in murine melanoma cells. J. Biol. Chem. 276:44926-44935.
E. Heiss, C. Herhaus, K. Klimo, H. Bartsch, and C. Gerhauser (2001). Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J. Biol. Chem. 276:32008-32015.
R. Romieu-Mourez, E. Landesman-Bollag, D. C. Seldin, and G. E. Sonenshein (2002). Protein kinase CK2 promotes aberrant activation of nuclear factor-kappaB, transformed phenotype, and survival of breast cancer cells. Cancer Res. 62:6770-6778.
V. Deregowski, S. Delhalle, V. Benoit, V. Bours, and M. P. Merville (2002). Identification of cytokine-induced nuclear factor-kappaB target genes in ovarian and breast cancer cells. Biochem. Pharmacol. 64:873-881.
D. Sliva, C. Labarrere, V. Slivova, M. Sedlak, F. P. Lloyd Jr., and N. W. Ho (2002). Ganoderma lucidum suppresses motility of highly invasive breast and prostate cancer cells. Biochem. Biophys. Res. Commun. 298:603-612.
D. M. Brantley, C. L. Chen, R. S. Muraoka, P. B. Bushdid, J. L. Bradberry, F. Kittrell, D. Medina, L. M. Matrisian, L. D. Kerr, and F. E. Yull (2001). Nuclear factor-kappaB (NF-kappaB) regulates proliferation and branching in mouse mammary epithelium. Mol. Biol. Cell. 12:1445-1455.
L. M. Varela, N. C. Stangle-Castor, S. F. Shoemaker, W. K. Shea-Eaton, and M. M. Ip (2001). TNFalpha induces NFkappaB/p50 in association with the growth and morphogenesis of normal and transformed rat mammary epithelial cells. J. Cell. Physiol. 188:120-131.
A. C. Bharti and B. B. Aggarwal (2002). Nuclear factor-kappa B and cancer: its role in prevention and therapy. Biochem. Pharmacol. 64:883-888.
J. S. Kang, Y. J. Jeon, H. M. Kim, S. H. Han, and K. H. Yang (2002). Inhibition of inducible nitric-oxide synthase expression by silymarin in lipopolysaccharide-stimulated macrophages. J. Pharmacol. Exp. Ther. 302:138-144.
S. K. Manna, N. K. Sah, R. A. Newman, A. Cisneros, and B. B. Aggarwal (2000). Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase. Cancer Res. 60:3838-3847.
K. Ashikawa, S. Majumdar, S. Banerjee, A. C. Bharti, S. Shishodia, and B. B. Aggarwal (2002). Piceatannol inhibits TNF-induced NF-kappaB activation and NF-kappaB-mediated gene expression through suppression of IkappaBalpha kinase and p65 phosphorylation. J. Immunol. 169:6490-6497.
A. Kumar, S. Dhawan, and B. B. Aggarwal (1998). Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits TNF-induced NF-kappaB activation, IkappaB degradation, and expression of cell surface adhesion proteins in human vascular endothelial cells. Oncogene 17:913-918.
C. Tan and T. A. Waldmann (2002). Proteasome inhibitor PS-341, a potential therapeutic agent for adult T-cell leukemia. Cancer Res. 62:1083-1086.
N. Mitsiades, C. S. Mitsiades, V. Poulaki, D. Chauhan, P. G. Richardson, T. Hideshima, N. C. Munshi, S. P. Treon, and K. C. Anderson (2002). Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: Therapeutic implications. Blood 99:4525-4530.
C. Schindler and J. E. Darnell Jr. (1995). Transcriptional responses to polypeptide ligands: The JAK-STAT pathway. Annu. Rev. Biochem. 64:621-651.
J. N. Ihle and I. M. Kerr (1995). Jaks and Stats in signaling by the cytokine receptor superfamily. Trends Genet. 11:69-74.
D. E. Levy and J. E. Darnell Jr. (2002). Stats: Transcriptional control and biological impact. Nat. Rev. Mol. Cell. Biol. 3:651-662.
R. Garcia, T. L. Bowman, G. Niu, H. Yu, S. Minton, C. A. Muro-Cacho, C. E. Cox, R. Falcone, R. Fairclough, S. Parsons, A. Laudano, A. Gazit, A. Levitzki, A. Kraker, and R. Jove (2001). Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 20:2499-2513.
L. Hennighausen, G. W. Robinson, K. U. Wagner, and X. Liu (1997). Developing a mammary gland is a stat affair. J. Mam. Gland Biol. Neoplasia 2:365-372.
G. Berclaz, H. J. Altermatt, V. Rohrbach, A. Siragusa, E. Dreher, and P. D. Smith (2001). EGFR dependent expression of STAT3 (but not STAT1) in breast cancer. Int. J. Oncol. 19:1155-1160.
E. Iavnilovitch, B. Groner, and I. Barash (2002). Overexpression and forced activation of stat5 in mammary gland of transgenic mice promotes cellular proliferation, enhances differentiation, and delays postlactational apoptosis. Mol. Cancer Res. 1:32-47.
X. Liu, G. W. Robinson, K. U. Wagner, L. Garrett, A. Wynshaw-Boris, and L. Hennighausen (1997). Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev. 11:179-186.
S. Ren, H. R. Cai, M. Li, and P. A. Furth (2002). Loss of Stat5a delays mammary cancer progression in a mouse model. Oncogene 21:4335-4339.
G. L. Johnson and R. Lapadat (2002). Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298:1911-1912.
G. Pearson, F. Robinson, T. Beers Gibson, B. E. Xu, M. Karandikar, K. Berman, and M. H. Cobb (2001). Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions. Endocr. Rev. 22:153-183.
G. Zhou, Z. Q. Bao, and J. E. Dixon (1995). Components of a new human protein kinase signal transduction pathway. J. Biol. Chem. 270:12665-12669.
M. K. Abe, M. P. Saelzler, R. Espinosa, 3rd, K. T. Kahle, M. B. Hershenson, M. M. Le Beau, and M. R. Rosner (2002). ERK8, a new member of the mitogen-activated protein kinase family. J. Biol. Chem. 277:16733-16743.
M. K. Abe, K. T. Kahle, M. P. Saelzler, K. Orth, J. E. Dixon, and M. R. Rosner (2001). ERK7 is an autoactivated member of the MAPK family. J. Biol. Chem. 276:21272-21279.
C. R. Weinstein-Oppenheimer, W. L. Blalock, L. S. Steelman, F. Chang, and J. A. McCubrey (2000). The Raf signal transduction cascade as a target for chemotherapeutic intervention in growth factor-responsive tumors. Pharmacol. Ther. 88:229-279.
P. W. Janes, R. J. Daly, A. deFazio, and R. L. Sutherland (1994). Activation of the Ras signalling pathway in human breast cancer cells overexpressing erbB-2. Oncogene 9:3601-3608.
B. Salh, A. Marotta, C. Matthewson, M. Ahluwalia, J. Flint, D. Owen, and S. Pelech (1999). Investigation of the Mek-MAP kinase-Rsk pathway in human breast cancer. Anticancer Res. 19:731-740.
L. R. Howe, K. Subbaramaiah, A. M. Brown, and A. J. Dannenberg (2001). Cyclooxygenase-2: A target for the prevention and treatment of breast cancer. Endocr. Relat. Cancer 8:97-114.
R. D. Nolan, R. M. Danilowicz, and T. E. Eling (1988). Role of arachidonic acid metabolism in the mitogenic response of BALB/c 3T3 fibroblasts to epidermal growth factor. Mol. Pharmacol. 33:650-656.
G. K. Bandyopadhyay, W. Imagawa, D. Wallace, and S. Nandi (1987). Linoleate metabolites enhance the in vitro proliferative response of mouse mammary epithelial cells to epidermal growth factor. J. Biol. Chem. 262:2750-2756.
Y. Takahashi, F. Kawahara, M. Noguchi, K. Miwa, H. Sato, M. Seiki, H. Inoue, T. Tanabe, and T. Yoshimoto (1999). Activation of matrix metalloproteinase-2 in human breast cancer cells overexpressing cyclooxygenase-1 or-2. FEBS Lett. 460:145-148.
P. H. Rolland, P. M. Martin, J. Jacquemier, A. M. Rolland, and M. Toga (1980). Prostaglandin in human breast cancer: Evidence suggesting that an elevated prostaglandin production is a marker of high metastatic potential for neoplastic cells. J. Natl. Cancer Inst. 64:1061-1070.
E. M. Gilhooly and D. P. Rose (1999). The association between a mutated ras gene and cyclooxygenase-2 expression in human breast cancer cell lines. Int. J. Oncol. 15:267-270.
R. A. Soslow, A. J. Dannenberg, D. Rush, B. M. Woerner, K. N. Khan, J. Masferrer, and A. T. Koki (2000). COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 89:2637-2645.
J. L. Masferrer, K. M. Leahy, A. T. Koki, B. S. Zweifel, S. L. Settle, B. M. Woerner, D. A. Edwards, A. G. Flickinger, R. J. Moore, and K. Seibert (2000). Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res. 60:1306-1311.
F. M. Robertson, M. L. Parrett, F. S. Joarder, M. Ross, H. M. Abou-Issa, G. Alshafie, and R. E. Harris (1998). Ibuprofen-induced inhibition of cyclooxygenase isoform gene expression and regression of rat mammary carcinomas. Cancer Lett. 122:165-175.
S. Nakatsugi, T. Ohta, T. Kawamori, M. Mutoh, T. Tanigawa, K. Watanabe, S. Sugie, T. Sugimura, and K. Wakabayashi (2000). Chemoprevention by nimesulide, a selective cyclooxygenase-2 inhibitor, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary gland carcinogenesis in rats. Jpn. J. Cancer Res. 91:886-892.
G. A. Alshafie, H. M. Abou-Issa, K. Seibert, and R. E. Harris (2000). Chemotherapeutic evaluation of Celecoxib, a cyclooxygenase-2 inhibitor, in a rat mammary tumor model. Oncol. Rep. 7:1377-1381.
R. E. Harris, G. A. Alshafie, H. Abou-Issa, and K. Seibert (2000). Chemoprevention of breast cancer in rats by celecoxib, a cyclooxygenase 2 inhibitor. Cancer Res. 60:2101-2103.
L. R. Howe, K. Subbaramaiah, J. Patel, J. L. Masferrer, A. Deora, C. Hudis, H. T. Thaler, W. J. Muller, B. Du, A. M. Brown, and A. J. Dannenberg (2002). Celecoxib, a selective cyclooxygenase 2 inhibitor, protects against human epidermal growth factor receptor 2 (HER-2)/neu-induced breast cancer. Cancer Res. 62:5405-5407.
H. M. Abou-Issa, G. A. Alshafie, K. Seibert, A. T. Koki, J. L. Masferrer, and R. E. Harris (2001). Dose-response effects of the COX-2 inhibitor, celecoxib, on the chemoprevention of mammary carcinogenesis. Anticancer Res. 21:3425-3432.
D. O. Stichtenoth and J. C. Frolich (2003). The second generation of COX-2 Inhibitors: What advantages do the newest offer? Drugs 63:33-45.
C. W. Ryan, W. M. Stadler, and N. J. Vogelzang (2001). Docetaxel and exisulind in hormone-refractory prostate cancer. Semin. Oncol. 28:56-61.
G. J. Griffiths (2000). Exisulind cell pathways. Curr. Opin. Investig. Drugs 1:386-391.
P. A. Bunn Jr., D. C. Chan, K. Earle, T. L. Zhao, B. Helfrich, K. Kelly, G. Piazza, C. M. Whitehead, R. Pamukcu, W. Thompson, and H. Alila (2002). Preclinical and clinical studies of docetaxel and exisulind in the treatment of human lung cancer. Semin. Oncol. 29:87-94.
R. S. Herbst and M. S. Kies (2002). ZD1839 (Iressa) in non-small cell lung cancer. Oncologist 7(Suppl 4):9-15.
A. E. Wakeling, S. P. Guy, J. R. Woodburn, S. E. Ashton, B. J. Curry, A. J. Barker, and K. H. Gibson (2002). ZD1839 (Iressa): An orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res. 62:5749-5754.
C. Lu, C. Speers, Y. Zhang, X. Xu, J. Hill, E. Steinbis, J. Celestino, Q. Shen, H. Kim, S. G. Hilsenbeck, S. K. Mohsin, A. Wakeling, K. Osborne, and P. H. Brown (in press). The EGFR inhibitor ZD1839 (Gefitinib, “Iressa”) suppresses the development of estrogen receptor-negative mammary tumors in transgenic mice. J. Natl. Cancer Inst.
J. S. de Bono and E. K. Rowinsky (2002). The ErbB receptor family: A therapeutic target for cancer. Trends Mol. Med. 8:S19-S26.
S. S. Ng, M. S. Tsao, T. Nicklee, and D. W. Hedley (2002). Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma. Mol. Cancer Ther. 1:777-783.
J. Baselga and L. A. Hammond (2002). HER-targeted tyrosine-kinase inhibitors. Oncology 63(Suppl. 1):6-16.
H. Q. Xiong and J. L. Abbruzzese (2002). Epidermal growth factor receptor-targeted therapy for pancreatic cancer. Semin. Oncol. 29:31-37.
L. F. Allen, P. F. Lenehan, I. A. Eiseman, W. L. Elliott, and D. W. Fry (2002). Potential benefits of the irreversible pan-erbB inhibitor, CI-1033, in the treatment of breast cancer. Semin. Oncol. 29:11-21.
A. Wissner, M. B. Brawner Floyd, S. K. Rabindran, R. Nilakantan, L. M. Greenberger, R. Shen, Y. F. Wang, and H. R. Tsou (2002). Syntheses and EGFR and HER-2 kinase inhibitory activities of 4-anilinoquinoline-3-carbonitriles: Analogues of three important 4-anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agents. Bioorg. Med. Chem. Lett. 12:2893-2897.
J. Baselga, D. Rischin, M. Ranson, H. Calvert, E. Raymond, D. G. Kieback, S. B. Kaye, L. Gianni, A. Harris, T. Bjork, S. D. Averbuch, A. Feyereislova, H. Swaisland, F. Rojo, and J. Albanell (2002). Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J. Clin. Oncol. 20:4292-4302.
M. A. Gieseg, C. de Bock, L. R. Ferguson, and W. A. Denny (2001). Evidence for epidermal growth factor receptor-enhanced chemosensitivity in combinations of cisplatin and the new irreversible tyrosine kinase inhibitor CI-1033. Anticancer Drugs 12:683-690.
R. J. Gilbertson, L. Bentley, R. Hernan, T. T. Junttila, A. J. Frank, H. Haapasalo, M. Connelly, C. Wetmore, T. Curran, K. Elenius, and D. W. Ellison (2002). ERBB receptor signaling promotes ependymoma cell proliferation and represents a potential novel therapeutic target for this disease. Clin. Cancer Res. 8:3054-3064.
G. K. Dy and A. A. Adjei (2002). Farnesyltransferase inhibitors in breast cancer therapy. Cancer Invest. 20(Suppl 2):30-37.
F. Caponigro (2002). Farnesyl transferase inhibitors: A major breakthrough in anticancer therapy? Naples, 12 April 2002. Anticancer Drugs 13:891-897.
J. E. Lancet, J. D. Rosenblatt, and J. E. Karp (2002). Farnesyltransferase inhibitors and myeloid malignancies: Phase I evidence of Zarnestra activity in high-risk leukemias. Semin. Hematol. 39:31-35.
M. Crul, G. J. de Klerk, M. Swart, L. J. van't Veer, D. de Jong, L. Boerrigter, P. A. Palmer, C. J. Bol, H. Tan, G. C. de Gast, J. H. Beijnen, and J. H. Schellens (2002). Phase I clinical and pharmacologic study of chronic oral administration of the farnesyl protein transferase inhibitor R115777 in advanced cancer. J. Clin. Oncol. 20:2726-2735.
A. Awada, F. A. Eskens, M. Piccart, D. L. Cutler, A. van der Gaast, H. Bleiberg, J. Wanders, M. N. Faber, P. Statkevich, P. Fumoleau, and J. Verweij (2002). Phase I and pharmacological study of the oral farnesyltransferase inhibitor SCH 66336 given once daily to patients with advanced solid tumours. Eur. J. Cancer 38:2272-2278.
P. Norgaard, B. Law, H. Joseph, D. L. Page, Y. Shyr, D. Mays, J. A. Pietenpol, N. E. Kohl, A. Oliff, R. J. Coffey Jr., H. S. Poulsen, and H. L. Moses (1999). Treatment with farnesyl-protein transferase inhibitor induces regression of mammary tumors in transforming growth factor (TGF) alpha and TGF alpha/neu transgenic mice by inhibition of mitogenic activity and induction of apoptosis. Clin. Cancer Res. 5:35-42.
R. A. Alcock, S. Dey, D. Chendil, M. S. Inayat, M. Mohiuddin, G. Hartman, L. K. Chatfield, V. S. Gallicchio, and M. M. Ahmed (2002). Farnesyltransferase inhibitor (L-744,832) restores TGF-beta type II receptor expression and enhances radiation sensitivity in K-ras mutant pancreatic cancer cell line MIA PaCa-2. Oncogene 21:7883-7890.
L. Sepp-Lorenzino, G. Tjaden, M. M. Moasser, N. Timaul, Z. Ma, N. E. Kohl, J. B. Gibbs, A. Oliff, N. Rosen, and H. I. Scher (2001). Farnesyl: Protein transferase inhibitors as potential agents for the management of human prostate cancer. Prostate Cancer Prostatic Dis. 4:33-43.
K. L. van Golen, L. Bao, M. M. DiVito, Z. Wu, G. C. Prendergast, and S. D. Merajver (2002). Reversion of RhoC GTPase-induced inflammatory breast cancer phenotype by treatment with a farnesyl transferase inhibitor. Mol. Cancer Ther. 1:575-583.
W. G. McKenna, R. J. Muschel, A. K. Gupta, S. M. Hahn, and E. J. Bernhard (2002). Farnesyltransferase inhibitors as radiation sensitizers. Semin. Radiat. Oncol. 12:27-32.
S. M. Hahn, E. J. Bernhard, W. Regine, M. Mohiuddin, D. G. Haller, J. P. Stevenson, D. Smith, B. Pramanik, J. Tepper, T. F. DeLaney, K. D. Kiel, B. Morrison, P. Deutsch, R. J. Muschel, and W. G. McKenna (2002). A Phase I trial of the farnesyltransferase inhibitor L-778,123 and radiotherapy for locally advanced lung and head and neck cancer. Clin. Cancer Res. 8:1065-1072.
M. J. Donaldson, V. Skoumas, M. Watson, P. A. Ashworth, H. Ryder, M. Moore, and R. C. Coombes (1999). XR3054, structurally related to limonene, is a novel inhibitor of farnesyl protein transferase. Eur. J. Cancer 35:1014-1019.
J. F. Lyons, S. Wilhelm, B. Hibner, and G. Bollag (2001). Discovery of a novel Raf kinase inhibitor. Endocr. Relat. Cancer 8:219-225.
S. J. Hotte and H. W. Hirte (2002). BAY 43-9006: early clinical data in patients with advanced solid malignancies. Curr. Pharm. Des. 8:2249-2253.
C. M. Rudin, J. Holmlund, G. F. Fleming, S. Mani, W. M. Stadler, P. Schumm, B. P. Monia, J. F. Johnston, R. Geary, R. Z. Yu, T. J. Kwoh, F. A. Dorr, and M. J. Ratain (2001). Phase I Trial of ISIS 5132, an antisense oligonucleotide inhibitor of c-raf-1, administered by 24-hour weekly infusion to patients with advanced cancer. Clin. Cancer Res. 7:1214-1220.
A. W. Tolcher, L. Reyno, P. M. Venner, S. D. Ernst, M. Moore, R. S. Geary, K. Chi, S. Hall, W. Walsh, A. Dorr, and E. Eisenhauer (2002). A randomized phase II and pharmacokinetic study of the antisense oligonucleotides ISIS 3521 and ISIS 5132 in patients with hormone-refractory prostate cancer. Clin. Cancer Res. 8:2530-2535.
M. C. Cripps, A. T. Figueredo, A. M. Oza, M. J. Taylor, A. L. Fields, J. T. Holmlund, L. W. McIntosh, R. S. Geary, and E. A. Eisenhauer (2002). Phase II randomized study of ISIS 3521 and ISIS 5132 in patients with locally advanced or metastatic colorectal cancer: A National Cancer Institute of Canada clinical trials group study. Clin. Cancer Res. 8:2188-2192.
B. Coudert, A. Anthoney, W. Fiedler, J. P. Droz, V. Dieras, M. Borner, J. F. Smyth, R. Morant, M. J. de Vries, M. Roelvink, and P. Fumoleau (2001). Phase II trial with ISIS 5132 in patients with small-cell (SCLC) and non-small cell (NSCLC) lung cancer. A European Organization for Research and Treatment of Cancer (EORTC) Early Clinical Studies Group report. Eur. J. Cancer 37:2194-2198.
S. Soga, S. V. Sharma, Y. Shiotsu, M. Shimizu, H. Tahara, K. Yamaguchi, Y. Ikuina, C. Murakata, T. Tamaoki, J. Kurebayashi, T. W. Schulte, L. M. Neckers, and S. Akinaga (2001). Stereospecific antitumor activity of radicicol oxime derivatives. Cancer Chemother. Pharmacol. 48:435-445.
A. D. Basso, D. B. Solit, P. N. Munster, and N. Rosen (2002). Ansamycin antibiotics inhibit Akt activation and cyclin D expression in breast cancer cells that overexpress HER2. Oncogene 21:1159-1166.
A. S. Clark, K. West, S. Streicher, and P. A. Dennis (2002). Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol. Cancer Ther. 1:707-717.
F. Wang, R. K. Hansen, D. Radisky, T. Yoneda, M. H. Barcellos-Hoff, O. W. Petersen, E. A. Turley, and M. J. Bissell (2002). Phenotypic reversion or death of cancer cells by altering signaling pathways in three-dimensional contexts. J. Natl. Cancer Inst. 94:1494-1503.
S. Semba, N. Itoh, M. Ito, E. M. Youssef, M. Harada, T. Moriya, W. Kimura, and M. Yamakawa (2002). Down-regulation of PIK3CG, a catalytic subunit of phosphatidylinositol 3-OH kinase, by CpG hypermethylation in human colorectal carcinoma. Clin. Cancer Res. 8:3824-3831.
J. Matsumoto, M. Kaneda, M. Tada, J. Hamada, S. Okushiba, S. Kondo, H. Katoh, and T. Moriuchi (2002). Differential mechanisms of constitutive Akt/PKB activation and its influence on gene expression in pancreatic cancer cells. Jpn. J. Cancer Res. 93:1317-1326.
L. P. Weng, W. M. Smith, P. L. Dahia, U. Ziebold, E. Gil, J. A. Lees, and C. Eng (1999). PTEN suppresses breast cancer cell growth by phosphatase activity-dependent G1 arrest followed by cell death. Cancer Res. 59:5808-5814.
T. G. Ram, H. L. Hosick, and S. P. Ethier (2000). Heregulin-beta is especially potent in activating phosphatidylinositol 3-kinase in nontransformed human mammary epithelial cells. J. Cell. Physiol. 183:301-313.
U. Hermanto, C. S. Zong, and L. H. Wang (2000). Inhibition of mitogen-activated protein kinase kinase selectively inhibits cell proliferation in human breast cancer cells displaying enhanced insulin-like growth factor I-mediated mitogen-activated protein kinase activation. Cell Growth Differ. 11:655-664.
R. Jaster, G. Sparmann, J. Emmrich, and S. Liebe (2002). Extracellular signal regulated kinases are key mediators of mitogenic signals in rat pancreatic stellate cells. Gut 51:579-584.
K. Kingsley, J. L. Huff, W. L. Rust, K. Carroll, A. M. Martinez, M. Fitchmun, and G. E. Plopper (2002). ERK1/2 mediates PDGF-BB stimulated vascular smooth muscle cell proliferation and migration on laminin-5. Biochem. Biophys. Res. Commun. 293:1000-1006.
F. Romerio and D. Zella (2002). MEK and ERK inhibitors enhance the anti-proliferative effect of interferon-alpha2b. Faseb J 16:1680-1682.
S. B. Gauld, D. Blair, C. A. Moss, S. D. Reid, and M. M. Harnett (2002). Differential roles for extracellularly regulated kinase-mitogen-activated protein kinase in B cell antigen receptor-induced apoptosis and CD40-mediated rescue of WEHI-231 immature B cells. J. Immunol. 168:3855-3864.
H. Xin, Y. Geng, R. Pramanik, and D. Choubey (2003). Induction of p202, a modulator of apoptosis, during oncogenic transformation of NIH 3T3 cells by activated H-Ras (Q61L) contributes to cell survival. J. Cell Biochem. 88:191-204.
J. S. Sebolt-Leopold, D. T. Dudley, R. Herrera, K. Van Becelaere, A. Wiland, R. C. Gowan, H. Tecle, S. D. Barrett, A. Bridges, S. Przybranowski, W. R. Leopold, and A. R. Saltiel (1999). Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat. Med. 5:810-816.
M. Guo, A. Joiakim, D. T. Dudley, and J. J. Reiners (2001). Suppression of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated CYP1A1 and CYP1B1 induction by 12-O-tetradecanoylphorbol-13-acetate: Role of transforming growth factor beta and mitogen-activated protein kinases. Biochem. Pharmacol. 62:1449-1457.
S. Chow, H. Patel, and D. W. Hedley (2001). Measurement of MAP kinase activation by flow cytometry using phospho-specific antibodies to MEK and ERK: Potential for pharmacodynamic monitoring of signal transduction inhibitors. Cytometry 46:72-78.
N. Zhang, B. Wu, N. Eudy, Y. Wang, F. Ye, D. Powell, A. Wissner, L. R. Feldberg, S. C. Kim, R. Mallon, E. D. Kovacs, L. Toral-Barza, and C. A. Kohler (2001). MEK (MAPKK) inhibitors. Part 2: structure-activity relationships of 4-anilino-3-cyano-6,7-dialkoxyquinolines. Bioorg. Med. Chem. Lett. 11:1407-1410.
N. Zhang, B. Wu, A. Wissner, D. W. Powell, S. K. Rabindran, C. Kohler, and F. Boschelli (2002). 4-Anilino-3-cyanobenzo[g]quinolines as kinase inhibitors. Bioorg. Med. Chem. Lett. 12:423-425.
N. Zhang, B. Wu, D. Powell, A. Wissner, M. B. Floyd, E. D. Kovacs, L. Toral-Barza, and C. Kohler (2000). Synthesis and structure-activity relationships of 3-cyano-4-(phenoxyanilino)quinolines as MEK (MAPKK) inhibitors. Bioorg. Med. Chem. Lett. 10:2825-2828.
T. van der Bruggen, S. Nijenhuis, E. van Raaij, J. Verhoef, and B. S. van Asbeck (1999). Lipopolysaccharide-induced tumor necrosis factor alpha production by human monocytes involves the raf-1/MEK1-MEK2/ERK1-ERK2 pathway. Infect. Immun. 67:3824-3829.
A. Zhao, S. H. Lee, M. Mojena, R. G. Jenkins, D. R. Patrick, H. E. Huber, M. A. Goetz, O. D. Hensens, D. L. Zink, D. Vilella, A. W. Dombrowski, R. B. Lingham, and L. Huang (1999). Resorcylic acid lactones: Naturally occurring potent and selective inhibitors of MEK. J. Antibiot. (Tokyo) 52:1086-1094.
K. Takehana, S. Sato, T. Kobayasi, and T. Maeda (1999). A radicicol-related macrocyclic nonaketide compound, antibiotic LL-Z1640-2, inhibits the JNK/p38 pathways in signal-specific manner. Biochem. Biophys. Res. Commun. 257:19-23.
B. Sanna, M. Debidda, G. Pintus, B. Tadolini, A. M. Posadino, F. Bennardini, G. Sava, and C. Ventura (2002). The anti-metastatic agent imidazolium trans-imidazoledimethylsulfoxide-tetrachlororuthenate induces endothelial cell apoptosis by inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway. Arch. Biochem. Biophys. 403:209-218.
K. Y. Horiuchi, P. A. Scherle, J. M. Trzaskos, and R. A. Copeland (1998). Competitive inhibition of MAP kinase activation by a peptide representing the alpha C helix of ERK. Biochemistry 37:8879-8885.
L. Montero and Y. Nagamine (1999). Regulation by p38 mitogen-activated protein kinase of adenylate-and uridylate-rich element-mediated urokinase-type plasminogen activator (uPA) messenger RNA stability and uPA-dependent in vitro cell invasion. Cancer Res. 59:5286-5293.
P. W. Tsai, S. G. Shiah, M. T. Lin, C. W. Wu, and M. L. Kuo (2003). Up-regulation of vascular endothelial growth factor C in breast cancer cells by heregulin-beta 1. A critical role of p38/nuclear factor-kappa B signaling pathway. J. Biol. Chem. 278:5750-5759.
J. C. Boehm, Adams J. L. (2000). new inhibitors of p38 kinase. Expert Opin. Ther. Pat. 10:25-37.
J. C. Lee, S. Kumar, D. E. Griswold, D. C. Underwood, B. J. Votta, and J. L. Adams (2000). Inhibition of p38 MAP kinase as a therapeutic strategy. Immunopharmacology 47:185-201.
M. S. Saporito, R. L. Hudkins, and A. C. Maroney (2002). Discovery of CEP-1347/KT-7515, an inhibitor of the JNK/SAPK pathway for the treatment of neurodegenerative diseases. Prog. Med. Chem. 40:23-62.
Z. Han, D. L. Boyle, L. Chang, B. Bennett, M. Karin, L. Yang, A. M. Manning, and G. S. Firestein (2001). c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J. Clin. Invest. 108:73-81.
B. L. Bennett, D. T. Sasaki, B. W. Murray, E. C. O'Leary, S. T. Sakata, W. Xu, J. C. Leisten, A. Motiwala, S. Pierce, Y. Satoh, S. S. Bhagwat, A. M. Manning, and D. W. Anderson (2001). SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc. Natl. Acad. Sci. U. S. A. 98:13681-13686.
H. M. Abou-Issa, G. A. Alshafie, K. Seibert, A. T. Koki, J. L. Masferrer, and R. E. Harris (2001). Dose-response effects of the COX-2 inhibitor, celecoxib, on the chemoprevention of mammary carcinogenesis. Anticancer Res. 21:3425-3432.
M. M. Moasser, A. Basso, S. D. Averbuch, and N. Rosen (2001). The tyrosine kinase inhibitor ZD1839 (“Iressa”) inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res. 61:7184-7188.
J. Mendelsohn and J. Baselga (2000). The EGF receptor family as targets for cancer therapy. Oncogene 19:6550-6565.
W. D. Klohs, D. W. Fry, and A. J. Kraker (1997). Inhibitors of tyrosine kinase. Curr. Opin. Oncol. 9:562-568.
S. L. Moulder, F. M. Yakes, S. K. Muthuswamy, R. Bianco, J. F. Simpson, and C. L. Arteaga (2001). Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Res. 61:8887-8895.
K. C. Chan, W. F. Knox, J. M. Gee, J. Morris, R. I. Nicholson, C. S. Potten, and N. J. Bundred (2002). Effect of epidermal growth factor receptor tyrosine kinase inhibition on epithelial proliferation in normal and premalignant breast. Cancer Res. 62:122-128.
J. F. R. Robertson, E. Gutteridge, K. L. Cheung, R. Owers, M. Koehler, and L. Hamilton (2002). A phase II study of ZD1839 (“Iressa”) in tamoxifen-resistant ER-positive and endocrine-insensitive (ER-negative) breast cancer. Breast Cancer Res. Treat. 76:S96.
K. Albain, R. Ellege, W. J. Gradishar, D. F. Hayes, E. Rowinsky, C. Hudis, L. Pusztai, D. Tripathy, S. Modi, and S. Rubi (2002). Open-label, phase II, multicenter trial of ZD1839 (“Iressa”) in patients with advanced breast cancer. Breast Cancer Res. Treat. 76:S33.
J. D. Moyer, E. G. Barbacci, K. K. Iwata, L. Arnold, B. Boman, A. Cunningham, C. DiOrio, J. Doty, M. J. Morin, M. P. Moyer, M. Neveu, V. A. Pollack, L. R. Pustilnik, M. M. Reynolds, D. Sloan, A. Theleman, and P. Miller (1997). Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res. 57:4838-4848.
V. A. Pollack, D. M. Savage, D. A. Baker, K. E. Tsaparikos, D. E. Sloan, J. D. Moyer, E. G. Barbacci, L. R. Pustilnik, T. A. Smolarek, J. A. Davis, M. P. Vaidya, L. D. Arnold, J. L. Doty, K. K. Iwata, and M. J. Morin (1999). Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358,774: Dynamics of receptor inhibition in situ and antitumor effects in athymic mice. J. Pharmacol. Exp. Ther. 291:739-748.
C. C. Solorzano, C. H. Baker, R. Tsan, P. Traxler, P. Cohen, E. Buchdunger, J. J. Killion, and I. J. Fidler (2001). Optimization for the blockade of epidermal growth factor receptor signaling for therapy of human pancreatic carcinoma. Clin. Cancer Res. 7:2563-2572.
C. H. Baker, C. C. Solorzano, and I. J. Fidler (2002). Blockade of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling for therapy of metastatic human pancreatic cancer. Cancer Res. 62:1996-2003.
R. Brandt, A. M. Wong, and N. E. Hynes (2001). Mammary glands reconstituted with Neu/ErbB2 transformed HC11 cells provide a novel orthotopic tumor model for testing anti-cancer agents. Oncogene 20:5459-5465.
J. B. Smaill, H. D. Showalter, H. Zhou, A. J. Bridges, D. J. McNamara, D. W. Fry, J. M. Nelson, V. Sherwood, P. W. Vincent, B. J. Roberts, W. L. Elliott, and W. A. Denny (2001). Tyrosine kinase inhibitors. 18. 6-Substituted 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as soluble, irreversible inhibitors of the epidermal growth factor receptor. J. Med. Chem. 44:429-440.
G. S. Rao, S. Murray, and S. P. Ethier (2000). Radiosensitization of human breast cancer cells by a novel ErbB family receptor tyrosine kinase inhibitor. Int. J. Radiat. Oncol. Biol. Phys. 48:1519-1528.
D. W. Rusnak, K. Lackey, K. Affleck, E. R. Wood, K. J. Alligood, N. Rhodes, B. R. Keith, D. M. Murray, W. B. Knight, R. J. Mullin, and T. M. Gilmer (2001). The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol. Cancer Ther. 1:85-94.
S. R. Johnston and L. R. Kelland (2001). Farnesyl transferase inhibitors–a novel therapy for breast cancer. Endocr. Relat. Cancer 8:227-235.
S. N. Khleif, S. I. Abrams, J. M. Hamilton, E. Bergmann-Leitner, A. Chen, A. Bastian, S. Bernstein, Y. Chung, C. J. Allegra, and J. Schlom (1999). A phase I vaccine trial with peptides reflecting ras oncogene mutations of solid tumors. J. Immunother. 22:155-165.
F. C. von Lintig, A. D. Dreilinger, N. M. Varki, A. M. Wallace, D. E. Casteel, and G. R. Boss (2000). Ras activation in human breast cancer. Breast Cancer Res. Treat. 62:51-62.
S. Malaney and R. J. Daly (2001). The ras signaling pathway in mammary tumorigenesis and metastasis. J. Mam. Gland Biol. Neoplasia 6:101-113.
M. Asamoto, T. Ota, H. Toriyama-Baba, N. Hokaiwado, A. Naito, and H. Tsuda (2002). Mammary carcinomas induced in human c-Ha-ras proto-oncogene transgenic rats are estrogen-independent, but responsive to d-limonene treatment. Jpn. J. Cancer Res. 93:32-35.
J. Hulit, D. Di Vizio, and R. G. Pestell (2001). Inducible transgenics. New lessons on events governing the induction and commitment in mammary tumorigenesis. Breast Cancer Res. 3:209-212.
D. W. End, G. Smets, A. V. Todd, T. L. Applegate, C. J. Fuery, P. Angibaud, M. Venet, G. Sanz, H. Poignet, S. Skrzat, A. Devine, W. Wouters, and C. Bowden (2001). Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res. 61:131-137.
L. R. Kelland, V. Smith, M. Valenti, L. Patterson, P. A. Clarke, S. Detre, D. End, A. J. Howes, M. Dowsett, P. Workman, and S. R. Johnston (2001). Preclinical antitumor activity and pharmacodynamic studies with the farnesyl protein transferase inhibitor R115777 in human breast cancer. Clin. Cancer Res. 7:3544-3550.
T. Petit, E. Izbicka, R. A. Lawrence, W. R. Bishop, S. Weitman, and D. D. Von Hoff (1999). Activity of SCH 66336, a tricyclic farnesyltransferase inhibitor, against human tumor colony-forming units. Ann. Oncol. 10:449-453.
W. C. Rose, F. Y. Lee, C. R. Fairchild, M. Lynch, T. Monticello, R. A. Kramer, and V. Manne (2001). Preclinical antitumor activity of BMS-214662, a highly apoptotic and novel farnesyltransferase inhibitor. Cancer Res. 61:7507-7517.
R. Kurzrock, J. Cortes, and H. Kantarjian (2002). Clinical development of farnesyltransferase inhibitors in leukemias and myelodysplastic syndrome. Semin. Hematol. 39:20-24.
C. A. Buser, C. J. Dinsmore, C. Fernandes, I. Greenberg, K. Hamilton, S. D. Mosser, E. S. Walsh, T. M. Williams, and K. S. Koblan (2001). High-performance liquid chromatography/mass spectrometry characterization of Ki4B-Ras in PSN-1 cells treated with the prenyltransferase inhibitor L-778,123. Anal. Biochem. 290:126-137.
J. B. Gibbs, N. E. Kohl, K. S. Koblan, C. A. Omer, L. Sepp-Lorenzino, N. Rosen, N. J. Anthony, M. W. Conner, S. J. deSolms, T. M. Williams, S. L. Graham, G. D. Hartman, and A. Oliff (1996). Farnesyltransferase inhibitors and anti-Ras therapy. Breast Cancer Res. Treat. 38:75-83.
C. R. Weinstein-Oppenheimer, C. Burrows, L. S. Steelman, and J. A. McCubrey (2002). The Effects of beta-Estradiol on Raf Activity, Cell Cycle Progression and Growth Factor Synthesis in the MCF-7 Breast Cancer Cell Line. Cancer Biol. Ther. 1:256-262.
M. Maemura, Y. Iino, Y. Koibuchi, T. Yokoe, and Y. Morishita (1999). Mitogen-activated protein kinase cascade in breast cancer. Oncology 57(Suppl 2):37-44.
F. McPhillips, P. Mullen, B. P. Monia, A. A. Ritchie, F. A. Dorr, J. F. Smyth, and S. P. Langdon (2001). Association of c-Raf expression with survival and its targeting with antisense oligonucleotides in ovarian cancer. Br. J. Cancer 85:1753-1758.
P. J. O'Dwyer, J. P. Stevenson, M. Gallagher, A. Cassella, I. Vasilevskaya, B. P. Monia, J. Holmlund, F. A. Dorr, and K. S. Yao (1999). c-raf-1 depletion and tumor responses in patients treated with the c-raf-1 antisense oligodeoxynucleotide ISIS 5132 (CGP 69846A). Clin. Cancer Res. 5:3977-3982.
L. Neckers (2002). Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol. Med. 8:S55-S61.
T. W. Schulte, M. V. Blagosklonny, L. Romanova, J. F. Mushinski, B. P. Monia, J. F. Johnston, P. Nguyen, J. Trepel, and L. M. Neckers (1996). Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway. Mol. Cell. Biol. 16:5839-5845.
T. W. Schulte, M. V. Blagosklonny, C. Ingui, and L. Neckers (1995). Disruption of the Raf-1-Hsp90 molecular complex results in destabilization of Raf-1 and loss of Raf-1-Ras association. J. Biol. Chem. 270:24585-24588.
W. Xu, M. Marcu, X. Yuan, E. Mimnaugh, C. Patterson, and L. Neckers (2002). Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2/Neu. Proc. Natl. Acad. Sci. U. S. A. 99:12847-12852.
M. A. Krasilnikov (2000). Phosphatidylinositol-3 kinase dependent pathways: The role in control of cell growth, survival, and malignant transformation. Biochemistry (Mosc) 65:59-67.
R. Katso, K. Okkenhaug, K. Ahmadi, S. White, J. Timms, and M. D. Waterfield (2001). Cellular function of phosphoinositide 3-kinases: Implications for development, homeostasis, and cancer. Annu. Rev. Cell Dev. Biol. 17:615-675.
I. Vivanco and C. L. Sawyers (2002). The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat. Rev. Cancer 2:489-501.
P. Blume-Jensen and T. Hunter (2001). Oncogenic kinase signalling. Nature 411:355-365.
S. R. Datta, A. Brunet, and M. E. Greenberg (1999). Cellular survival: A play in three Akts. Genes Dev. 13:2905-2927.
J. Hutchinson, J. Jin, R. D. Cardiff, J. R. Woodgett, and W. J. Muller (2001). Activation of Akt (protein kinase B) in mammary epithelium provides a critical cell survival signal required for tumor progression. Mol. Cell. Biol. 21:2203-2212.
G. J. Kops, N. D. de Ruiter, A. M. De Vries-Smits, D. R. Powell, J. L. Bos, and B. M. Burgering (1999). Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature 398:630-634.
B. P. Zhou, Y. Liao, W. Xia, B. Spohn, M. H. Lee, and M. C. Hung (2001). Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat. Cell Biol. 3:245-252.
R. H. Medema, G. J. Kops, J. L. Bos, and B. M. Burgering (2000). AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 404:782-787.
M. Sun, J. E. Paciga, R. I. Feldman, Z. Yuan, D. Coppola, Y. Y. Lu, S. A. Shelley, S. V. Nicosia, and J. Q. Cheng (2001). Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K. Cancer Res. 61:5985-5991.
M. Sun, G. Wang, J. E. Paciga, R. I. Feldman, Z. Q. Yuan, X. L. Ma, S. A. Shelley, R. Jove, P. N. Tsichlis, S. V. Nicosia, and J. Q. Cheng (2001). AKT1/PKBalpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells. Am. J. Pathol. 159:431-437.
L. Shayesteh, Y. Lu, W. L. Kuo, R. Baldocchi, T. Godfrey, C. Collins, D. Pinkel, B. Powell, G. B. Mills, and J. W. Gray (1999). PIK3CA is implicated as an oncogene in ovarian cancer. Nat. Genet. 21:99-102.
A. J. Philp, I. G. Campbell, C. Leet, E. Vincan, S. P. Rockman, R. H. Whitehead, R. J. Thomas, and W. A. Phillips (2001). The phosphatidylinositol 3'-kinase p85alpha gene is an oncogene in human ovarian and colon tumors. Cancer Res. 61:7426-7429.
M. D. Ringel, N. Hayre, J. Saito, B. Saunier, F. Schuppert, H. Burch, V. Bernet, K. D. Burman, L. D. Kohn, and M. Saji (2001). Overexpression and overactivation of Akt in thyroid carcinoma. Cancer Res. 61:6105-6111.
H. Cho, J. L. Thorvaldsen, Q. Chu, F. Feng, and M. J. Birnbaum (2001). Akt1/PKBalpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice. J. Biol. Chem. 276:38349-38352.
V. Stambolic, M. S. Tsao, D. Macpherson, A. Suzuki, W. B. Chapman, and T. W. Mak (2000). High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in pten+/-mice. Cancer Res. 60:3605-3611.
K. L. Schwertfeger, M. M. Richert, and S. M. Anderson (2001). Mammary gland involution is delayed by activated Akt in transgenic mice. Mol. Endocrinol. 15:867-881.
K. Moelling, K. Schad, M. Bosse, S. Zimmermann, and M. Schweneker (2002). Regulation of Raf-Akt Cross-talk. J. Biol. Chem. 277:31099-31106.
S. G. Ward, C. H. June, and D. Olive (1996). PI 3-kinase: A pivotal pathway in T-cell activation? Immunol. Today 17:187-197.
C. J. Vlahos, W. F. Matter, K. Y. Hui, and R. F. Brown (1994). A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J. Biol. Chem. 269:5241-5248.
A. V. Bakin, A. K. Tomlinson, N. A. Bhowmick, H. L. Moses, and C. L. Arteaga (2000). Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration. J. Biol. Chem. 275:36803-36810.
M. P. Wymann, G. Bulgarelli-Leva, M. J. Zvelebil, L. Pirola, B. Vanhaesebroeck, M. D. Waterfield, and G. Panayotou (1996). Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate transfer reaction. Mol. Cell. Biol. 16:1722-1733.
S. J. Mansour, J. M. Candia, K. K. Gloor, and N. G. Ahn (1996). Constitutively active mitogen-activated protein kinase kinase 1 (MAPKK1) and MAPKK2 mediate similar transcriptional and morphological responses. Cell Growth Differ. 7:243-250.
J. C. Donovan, A. Milic, and J. M. Slingerland (2001). Constitutive MEK/MAPK activation leads to p27(Kip1) deregulation and antiestrogen resistance in human breast cancer cells. J. Biol. Chem. 276:40888-40895.
J. Pinkas and P. Leder (2002). MEK1 signaling mediates transformation and metastasis of EpH4 mammary epithelial cells independent of an epithelial to mesenchymal transition. Cancer Res. 62:4781-4790.
M. F. Favata, K. Y. Horiuchi, E. J. Manos, A. J. Daulerio, D. A. Stradley, W. S. Feeser, D. E. Van Dyk, W. J. Pitts, R. A. Earl, F. Hobbs, R. A. Copeland, R. L. Magolda, P. A. Scherle, and J. M. Trzaskos (1998). Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J. Biol. Chem. 273:18623-18632.
E. K. Lobenhofer, G. Huper, J. D. Iglehart, and J. R. Marks (2000). Inhibition of mitogen-activated protein kinase and phosphatidylinositol 3-kinase activity in MCF-7 cells prevents estrogen-induced mitogenesis. Cell Growth Differ. 11:99-110.
Y. Hu, W. H. Dragowska, A. Wallis, V. Duronio, and L. Mayer (2001). Cytotoxicity induced by manipulation of signal transduction pathways is associated with down-regulation of Bcl-2 but not Mcl-1 in MCF-7 human breast cancer. Breast Cancer Res. Treat. 70:11-20.
H. Fukazawa, K. Noguchi, Y. Murakami, and Y. Uehara (2002). Mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitors restore anoikis sensitivity in human breast cancer cell lines with a constitutively activated extracellular-regulated kinase (ERK) pathway. Mol. Cancer Ther. 1:303-309.
M. S. Squires, P. M. Nixon, and S. J. Cook (2002). Cell-cycle arrest by PD184352 requires inhibition of extracellular signal-regulated kinases (ERK) 1/2 but not ERK5/BMK1. Biochem. J. 366:673-680.
S. P. Davies, H. Reddy, M. Caivano, and P. Cohen (2000). Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351:95-105.
J. S. Sebolt-Leopold (2000). Development of anticancer drugs targeting the MAP kinase pathway. Oncogene 19:6594-6599.
M. Milella, S. M. Kornblau, Z. Estrov, B. Z. Carter, H. Lapillonne, D. Harris, M. Konopleva, S. Zhao, E. Estey, and M. Andreeff (2001). Therapeutic targeting of the MEK/MAPK signal transduction module in acute myeloid leukemia. J. Clin. Invest. 108:851-859.
D. H. Williams, S. E. Wilkinson, T. Purton, A. Lamont, H. Flotow, and E. J. Murray (1998). Ro 09-2210 exhibits potent anti-proliferative effects on activated T cells by selectively blocking MKK activity. Biochemistry 37:9579-9585.
J. M. Kyriakis (1999). Making the connection: Coupling of stress-activated ERK/MAPK (extracellular-signal-regulated kinase/mitogen-activated protein kinase) core signalling modules to extracellular stimuli and biological responses. Biochem. Soc. Symp. 64:29-48.
K. Mishima, K. Inoue, and Y. Hayashi (2002). Overexpression of extracellular-signal regulated kinases on oral squamous cell carcinoma. Oral Oncol. 38:468-474.
L. L. Licato and D. A. Brenner (1998). Analysis of signaling protein kinases in human colon or colorectal carcinomas. Dig. Dis. Sci. 43:1454-1464.
R. Hoshino, Y. Chatani, T. Yamori, T. Tsuruo, H. Oka, O. Yoshida, Y. Shimada, S. Ari-i, H. Wada, J. Fujimoto, and M. Kohno (1999). Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors. Oncogene 18:813-822.
R. J. Santen, R. X. Song, R. McPherson, R. Kumar, L. Adam, M. H. Jeng, and W. Yue (2002). The role of mitogen-activated protein (MAP) kinase in breast cancer. J. Steroid Biochem. Mol. Biol. 80:239-256.
C. Xing and W. Imagawa (1999). Altered MAP kinase (ERK1,2) regulation in primary cultures of mammary tumor cells: Elevated basal activity and sustained response to EGF. Carcinogenesis 20:1201-1208.
H. Enslen, D. M. Brancho, and R. J. Davis (2000). Molecular determinants that mediate selective activation of p38 MAP kinase isoforms. EMBO J. 19:1301-1311.
C. C. Zhang and D. J. Shapiro (2000). Activation of the p38 mitogen-activated protein kinase pathway by estrogen or by 4-hydroxytamoxifen is coupled to estrogen receptor-induced apoptosis. J. Biol. Chem. 275:479-486.
M. Hori, S. Inagawa, J. Shimazaki, and M. Itabashi (2000). Overexpression of mitogen-activated protein kinase superfamily proteins unrelated to Ras and AF-1 of estrogen receptor alpha mutation in advanced stage human breast cancer. Pathol. Res. Pract. 196:817-826.
E. Cocolakis, S. Lemay, S. Ali, and J. J. Lebrun (2001). The p38 MAPK pathway is required for cell growth inhibition of human breast cancer cells in response to activin. J. Biol. Chem. 276:18430-18436.
R. Seidman, I. Gitelman, O. Sagi, S. B. Horwitz, and M. Wolfson (2001). The role of ERK 1/2 and p38 MAP-kinase pathways in taxol-induced apoptosis in human ovarian carcinoma cells. Exp. Cell Res. 268:84-92.
Z. Wang, B. J. Canagarajah, J. C. Boehm, S. Kassisa, M. H. Cobb, P. R. Young, S. Abdel-Meguid, J. L. Adams, and E. J. Goldsmith (1998). Structural basis of inhibitor selectivity in MAP kinases. Structure 6:1117-1128.
J. C. Lee, S. Kassis, S. Kumar, A. Badger, and J. L. Adams (1999). p38 mitogen-activated protein kinase inhibitors--mechanisms and therapeutic potentials. Pharmacol. Ther. 82:389-397.
J. J. Haddad (2001). VX-745. Vertex Pharmaceuticals. Curr. Opin. Investig. Drugs 2:1070-1076.
T. Hideshima, M. Akiyama, T. Hayashi, P. Richardson, R. Schlossman, D. Chauhan, and K. C. Anderson (2003). Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu. Blood 101:703-705.
J. E. Stelmach, L. Liu, S. B. Patel, J. V. Pivnichny, G. Scapin, S. Singh, C. E. Hop, Z. Wang, J. R. Strauss, P. M. Cameron, E. A. Nichols, S. J. O'Keefe, E. A. O'Neill, D. M. Schmatz, C. D. Schwartz, C. M. Thompson, D. M. Zaller, and J. B. Doherty (2003). Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase. Bioorg. Med. Chem. Lett. 13:277-280.
Y. M. Yang, F. Bost, W. Charbono, N. Dean, R. McKay, J. S. Rhim, C. Depatie, and D. Mercola (2003). C-Jun NH(2)-terminal kinase mediates proliferation and tumor growth of human prostate carcinoma. Clin. Cancer Res. 9:391-401.
H. J. Kang, Y. Soh, M. S. Kim, E. J. Lee, Y. J. Surh, H. R. Kim, S. H. Kim, and A. Moon (2003). Roles of JNK-1 and p38 in selective induction of apoptosis by capsaicin in ras-transformed human breast epithelial cells. Int. J. Cancer 103:475-482.
W. Yu, Q. Y. Liao, F. M. Hantash, B. G. Sanders, and K. Kline (2001). Activation of extracellular signal-regulated kinase and c-Jun-NH(2)-terminal kinase but not p38 mitogen-activated protein kinases is required for RRR-alpha-tocopheryl succinate-induced apoptosis of human breast cancer cells. Cancer Res. 61:6569-6576.
A. C. Maroney, M. A. Glicksman, A. N. Basma, K. M. Walton, E. Knight Jr., C. A. Murphy, B. A. Bartlett, J. P. Finn, T. Angeles, Y. Matsuda, N. T. Neff, and C. A. Dionne (1998). Motoneuron apoptosis is blocked by CEP-1347 (KT 7515), a novel inhibitor of the JNK signaling pathway. J. Neurosci. 18:104-111.
A. Bodner, A. C. Maroney, J. P. Finn, G. Ghadge, R. Roos, and R. J. Miller (2002). Mixed lineage kinase 3 mediates gp120IIIB-induced neurotoxicity. J. Neurochem. 82:1424-1434.
C. A. Harris, M. Deshmukh, B. Tsui-Pierchala, A. C. Maroney, and E. M. JohnsonJr. (2002). Inhibition of the c-Jun N-terminal kinase signaling pathway by the mixed lineage kinase inhibitor CEP-1347 (KT7515) preserves metabolism and growth of trophic factor-deprived neurons. J. Neurosci. 22:103-113.
Z. Xu, A. C. Maroney, P. Dobrzanski, N. V. Kukekov, and L. A. Greene (2001). The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis. Mol. Cell. Biol. 21:4713-4724.
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Shen, Q., Brown, P.H. Novel Agents for the Prevention of Breast Cancer: Targeting Transcription Factors and Signal Transduction Pathways. J Mammary Gland Biol Neoplasia 8, 45–73 (2003). https://doi.org/10.1023/A:1025783221557
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DOI: https://doi.org/10.1023/A:1025783221557