| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Advances in Brief |
Departments of Surgery [A. A., H. R., M. B.] and Molecular Pharmacology and Therapeutics [A. E. W., K. W. S.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021, and The Kenneth Norris Jr. Cancer Research Institute, University of Southern California School of Medicine, Los Angeles, California 90089 [P. V. D.]
Overexpression of P-glycoprotein (Pgp), a multidrug transporter encoded by the MDR1 gene, is associated with chemoresistance in some human solid tumor malignancies. To date, analyses of MDR1 levels in solid tumors have examined constitutive increases in expression at relapse. In the present study, we have evaluated the acute induction of MDR1 gene expression in a solid human tumor as a function of time in response to in vivo exposure to chemotherapy. Five patients with unresectable sarcoma pulmonary metastases underwent isolated single lung perfusion with doxorubicin. Relative MDR1 gene expression was measured in metastatic tumor nodules and normal lung specimens after initiation of chemoperfusion. In four of five patients, a 3–15-fold (median, 6.8) increase in MDR1 RNA levels was detected in tumors at 50 min after administration of doxorubicin. In contrast, normal lung samples had very low levels of MDR1 RNA prior to perfusion, and no acute increases were observed after therapy. These findings demonstrate, for the first time, that MDR1 gene expression can be rapidly activated in human tumors after transient in vivo exposure to cytotoxic chemotherapy.
This article has been cited by other articles:
|
|
 |
|
  R. C-Y. Hui, R. E. Francis, S. K. Guest, J. R. Costa, A. R. Gomes, S. S. Myatt, J. J. Brosens, and E. W-F. Lam Doxorubicin activates FOXO3a to induce the expression of multidrug resistance gene ABCB1 (MDR1) in K562 leukemic cells Mol. Cancer Ther., March 1, 2008; 7(3): 670 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Xiao, Y. Huang, Z. Dai, W. Sadee, J. Chen, S. Liu, G. Marcucci, J. Byrd, J. M. Covey, J. Wright, et al. Chemoresistance to Depsipeptide FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-Ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] Is Mediated by Reversible MDR1 Induction in Human Cancer Cell Lines J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 467 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tanaka, N. Ohshima, M. Ikenoya, K. Komori, F. Katoh, and H. Hidaka HMN-176, an Active Metabolite of the Synthetic Antitumor Agent HMN-214, Restores Chemosensitivity to Multidrug-Resistant Cells by Targeting the Transcription Factor NF-Y Cancer Res., October 15, 2003; 63(20): 6942 - 6947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Yague, A. L. Armesilla, G. Harrison, J. Elliott, A. Sardini, C. F. Higgins, and S. Raguz P-glycoprotein (MDR1) Expression in Leukemic Cells Is Regulated at Two Distinct Steps, mRNA Stabilization and Translational Initiation J. Biol. Chem., March 14, 2003; 278(12): 10344 - 10352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Miller, C. J. Sweeney, and G. W. Sledge The Snark is a Boojum: the continuing problem of drug resistance in the antiangiogenic era Ann. Onc., January 1, 2003; 14(1): 20 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Stein, K. Jurchott, M. Schlafke, and P. Hohenberger Expression of Multidrug Resistance Genes MVP, MDR1, and MRP1 Determined Sequentially Before, During, and After Hyperthermic Isolated Limb Perfusion of Soft Tissue Sarcoma and Melanoma Patients J. Clin. Oncol., August 1, 2002; 20(15): 3282 - 3292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. H. C. Bramwell, D. Morris, D. S. Ernst, I. Hings, M. Blackstein, P. M. Venner, E. I. Ette, M. W. Harding, A. Waxman, and G. D. Demetri Safety and Efficacy of the Multidrug-Resistance Inhibitor Biricodar (VX-710) with Concurrent Doxorubicin in Patients with Anthracycline-resistant Advanced Soft Tissue Sarcoma Clin. Cancer Res., February 1, 2002; 8(2): 383 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-M. Yang, A. D. Vassil, and W. N. Hait Activation of Phospholipase C Induces the Expression of the Multidrug Resistance (MDR1) Gene through the Raf-MAPK Pathway Mol. Pharmacol., October 1, 2001; 60(4): 674 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Cocker, N. Tiffin, K. Pritchard-Jones, C. R. Pinkerton, and L. R. Kelland In Vitro Prevention of the Emergence of Multidrug Resistance in a Pediatric Rhabdomyosarcoma Cell Line Clin. Cancer Res., October 1, 2001; 7(10): 3193 - 3198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Takahashi, W. W. Li, D. Banerjee, K. W. Scotto, and J. R. Bertino Sequence-dependent Enhancement of Cytotoxicity Produced by Ecteinascidin 743 (ET-743) with Doxorubicin or Paclitaxel in Soft Tissue Sarcoma Cells Clin. Cancer Res., October 1, 2001; 7(10): 3251 - 3257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Baekelandt, G. Lehne, C. G. Trope, I. Szanto, P. Pfeiffer, B. Gustavssson, and G. B. Kristensen Phase I/II Trial of the Multidrug-Resistance Modulator Valspodar Combined With Cisplatin and Doxorubicin in Refractory Ovarian Cancer J. Clin. Oncol., June 15, 2001; 19(12): 2983 - 2993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. W. Scotto and R. A. Johnson Transcription of MDR1: A Therapeutic Target Mol. Interv., June 1, 2001; 1(2): 117 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jin, B. Gorfajn, G. Faircloth, and K. W. Scotto Ecteinascidin 743, a transcription-targeted chemotherapeutic that inhibits MDR1 activation PNAS, June 6, 2000; 97(12): 6775 - 6779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Newman, J. C. Rodarte, K. D. Benbatoul, S. J. Romano, C. Zhang, S. Krane, E. J. Moran, R. T. Uyeda, R. Dixon, E. S. Guns, et al. Discovery and Characterization of OC144-093, a Novel Inhibitor of P-Glycoprotein-mediated Multidrug Resistance Cancer Res., June 1, 2000; 60(11): 2964 - 2972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Hu, S. Jin, and K. W. Scotto Transcriptional Activation of the MDR1 Gene by UV Irradiation. ROLE OF NF-Y AND Sp1 J. Biol. Chem., January 28, 2000; 275(4): 2979 - 2985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Bates Drug Resistance: Still on the Learning Curve Clin. Cancer Res., November 1, 1999; 5(11): 3346 - 3348. [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 |
