| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Cancer Research, Vol 4, Issue 12 2957-2966, Copyright © 1998 by American Association for Cancer Research
ARTICLES |
M Prewett, M Rothman, H Waksal, M Feldman, NH Bander and DJ Hicklin
Department of Immunology, ImClone Systems Incorporated, New York, New York 10014, USA.
The epidermal growth factor (EGF) receptor and its ligand transforming growth factor-alpha (TGF-alpha) are overexpressed in human renal cell carcinoma (RCC). The chimeric anti-EGF receptor monoclonal antibody C225 was used to determine the effects of blocking the EGF receptor on RCC growth both in vitro and in vivo. A panel of RCC cell lines all tested positive at various levels for EGF receptor cell surface expression. C225 inhibited DNA synthesis of cultured A498, Caki-1, SK-RC-4, SK-RC-29, and SW839 cells in a dose-dependent manner, ranging from 20 to 45% inhibition compared with untreated controls. C225 also inhibited exogenous ligand-stimulated tyrosine phosphorylation of EGF receptor on RCC cells. The antitumor effects of C225 on RCC tumor growth were evaluated in ascites, s.c., and orthotopic RCC xenograft models. Mice treated with C225 in a Caki-1 ascites xenograft model showed a significant increase in survival (P = 0.002). All control mice died with ascites tumors by week 9, whereas >70% of C225-treated mice survived beyond 12 weeks. C225 also inhibited the growth of s.c. SK-RC-29 tumors in a dose-dependent manner. Mice treated with C225 (1 mg/dose) displayed a significant decrease in tumor volume compared with mice treated with control antibody (P < 0.05) or vehicle alone (P < 0.01). Lastly, C225 inhibited the growth and metastasis of RCC tumors growing orthotopically in the renal subcapsule of nude mice. Histological examination of RCC tumors from mice treated with C225 showed a substantial decrease in proliferating cell nuclear antigen staining and an increase in tumor cell apoptosis. These data suggest that C225 affects growth of RCC tumors by inhibiting EGF receptor-dependent proliferation and demonstrate the potential for therapeutic application of C225 in the treatment of human renal cancer.
This article has been cited by other articles:
|
|
 |
|
  A. Ravaud, R. Hawkins, J. P. Gardner, H. von der Maase, N. Zantl, P. Harper, F. Rolland, B. Audhuy, J.-P. Machiels, F. Petavy, et al. Lapatinib Versus Hormone Therapy in Patients With Advanced Renal Cell Carcinoma: A Randomized Phase III Clinical Trial J. Clin. Oncol., May 10, 2008; 26(14): 2285 - 2291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-P. Kim, S.-W. Han, S.-H. Kim, S.-A. Im, D.-Y. Oh, Y.-J. Bang, and T.-Y. Kim Combined lapatinib and cetuximab enhance cytotoxicity against gefitinib-resistant lung cancer cells Mol. Cancer Ther., March 1, 2008; 7(3): 607 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Mahtani and J. S. Macdonald Synergy Between Cetuximab and Chemotherapy in Tumors of the Gastrointestinal Tract Oncologist, January 1, 2008; 13(1): 39 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tabernero, E. Van Cutsem, E. Diaz-Rubio, A. Cervantes, Y. Humblet, T. Andre, J.-L. Van Laethem, P. Soulie, E. Casado, C. Verslype, et al. Phase II Trial of Cetuximab in Combination With Fluorouracil, Leucovorin, and Oxaliplatin in the First-Line Treatment of Metastatic Colorectal Cancer J. Clin. Oncol., November 20, 2007; 25(33): 5225 - 5232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Barnes, K. Ohshiro, S. K. Rayala, A. K. El-Naggar, and R. Kumar Insulin-like Growth Factor Receptor as a Therapeutic Target in Head and Neck Cancer Clin. Cancer Res., July 15, 2007; 13(14): 4291 - 4299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tabernero The Role of VEGF and EGFR Inhibition: Implications for Combining Anti-VEGF and Anti-EGFR Agents Mol. Cancer Res., March 1, 2007; 5(3): 203 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Steiner, C. Joynes, R. Bassi, S. Wang, J. R. Tonra, Y. R. Hadari, and D. J. Hicklin Tumor Growth Inhibition with Cetuximab and Chemotherapy in Non-Small Cell Lung Cancer Xenografts Expressing Wild-type and Mutated Epidermal Growth Factor Receptor Clin. Cancer Res., March 1, 2007; 13(5): 1540 - 1551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Perez-Torres, M. Guix, A. Gonzalez, and C. L. Arteaga Epidermal Growth Factor Receptor (EGFR) Antibody Down-regulates Mutant Receptors and Inhibits Tumors Expressing EGFR Mutations J. Biol. Chem., December 29, 2006; 281(52): 40183 - 40192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kim, C. N. Prichard, M. N. Younes, Y. D. Yazici, S. A. Jasser, B. N. Bekele, and J. N. Myers Cetuximab and Irinotecan Interact Synergistically to Inhibit the Growth of Orthotopic Anaplastic Thyroid Carcinoma Xenografts in Nude Mice Clin. Cancer Res., January 15, 2006; 12(2): 600 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wild, K. Fager, C. Flefleh, D. Kan, I. Inigo, S. Castaneda, F. Luo, A. Camuso, K. McGlinchey, and W. C. Rose Cetuximab preclinical antitumor activity (monotherapy and combination based) is not predicted by relative total or activated epidermal growth factor receptor tumor expression levels Mol. Cancer Ther., January 1, 2006; 5(1): 104 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Luo, Z. Yang, H. Dong, A. Camuso, K. McGlinchey, K. Fager, C. Flefleh, D. Kan, I. Inigo, S. Castaneda, et al. Prediction of Active Drug Plasma Concentrations Achieved in Cancer Patients by Pharmacodynamic Biomarkers Identified from the Geo Human Colon Carcinoma Xenograft Model Clin. Cancer Res., August 1, 2005; 11(15): 5558 - 5565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Raspollini, F. Castiglione, F. Garbini, A. Villanucci, G. Amunni, G. Baroni, V. Boddi, and G. L. Taddei Correlation of Epidermal Growth Factor Receptor Expression with Tumor Microdensity Vessels and with Vascular Endothelial Growth Factor Expression in Ovarian Carcinoma International Journal of Surgical Pathology, April 1, 2005; 13(2): 135 - 142. [Abstract] [PDF]
|
|
|
|
|
|
E. R. Camp, J. Summy, T. W. Bauer, W. Liu, G. E. Gallick, and L. M. Ellis Molecular Mechanisms of Resistance to Therapies Targeting the Epidermal Growth Factor Receptor Clin. Cancer Res., January 1, 2005; 11(1): 397 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P M Harari Epidermal growth factor receptor inhibition strategies in oncology Endocr. Relat. Cancer, December 1, 2004; 11(4): 689 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Potti and D. J. George Tyrosine Kinase Inhibitors in Renal Cell Carcinoma Clin. Cancer Res., September 15, 2004; 10(18): 6371S - 6376S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Dancey Epidermal Growth Factor Receptor and Epidermal Growth Factor Receptor Therapies in Renal Cell Carcinoma: Do We Need a Better Mouse Trap? J. Clin. Oncol., August 1, 2004; 22(15): 2975 - 2977. [Full Text] [PDF]
|
|
|
|
|
|
L. Gunaratnam, M. Morley, A. Franovic, N. de Paulsen, K. Mekhail, D. A. E. Parolin, E. Nakamura, I. A. J. Lorimer, and S. Lee Hypoxia Inducible Factor Activates the Transforming Growth Factor-{alpha}/Epidermal Growth Factor Receptor Growth Stimulatory Pathway in VHL-/- Renal Cell Carcinoma Cells J. Biol. Chem., November 7, 2003; 278(45): 44966 - 44974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Weber, M. Doucet, J. E. Price, C. Baker, S. J. Kim, and I. J. Fidler Blockade of Epidermal Growth Factor Receptor Signaling Leads to Inhibition of Renal Cell Carcinoma Growth in the Bone of Nude Mice Cancer Res., June 1, 2003; 63(11): 2940 - 2947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Ciardiello and G. Tortora A Novel Approach in the Treatment of Cancer: Targeting the Epidermal Growth Factor Receptor Clin. Cancer Res., October 1, 2001; 7(10): 2958 - 2970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Ryan and B. A. Chabner On Receptor Inhibitors and Chemotherapy Clin. Cancer Res., December 1, 2000; 6(12): 4607 - 4609. [Full Text]
|
|
|
|
|
|
K. Inoue, J. W. Slaton, P. Perrotte, D. W. Davis, C. J. Bruns, D. J. Hicklin, D. J. McConkey, P. Sweeney, R. Radinsky, and C. P. N. Dinney Paclitaxel Enhances the Effects of the Anti-Epidermal Growth Factor Receptor Monoclonal Antibody ImClone C225 in Mice with Metastatic Human Bladder Transitional Cell Carcinoma Clin. Cancer Res., December 1, 2000; 6(12): 4874 - 4884. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. TERZI, M. BURTIN, and G. FRIEDLANDER Using Transgenic Mice to Analyze the Mechanisms of Progression of Chronic Renal Failure J. Am. Soc. Nephrol., November 1, 2000; 11(90002): 144S - 148. [Abstract] [Full Text]
|
|
|
|
|
|
A. D. Perera, E. V. Kleymenova, and C. L. Walker Requirement for the von Hippel-Lindau Tumor Suppressor Gene for Functional Epidermal Growth Factor Receptor Blockade by Monoclonal Antibody C225 in Renal Cell Carcinoma Clin. Cancer Res., April 1, 2000; 6(4): 1518 - 1523. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. de Paulsen, A. Brychzy, M.-C. Fournier, R. D. Klausner, J. R. Gnarra, A. Pause, and S. Lee Role of transforming growth factor-alpha in von Hippel- Lindau (VHL)-/- clear cell renal carcinoma cell proliferation: A possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis PNAS, February 13, 2001; 98(4): 1387 - 1392. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
