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Lady Davis Institute for Medical Research and Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal H3T 1E2, Quebec, Canada [W. H. M., H. M. S.]; Ingenix, Basking Ridge, New Jersey 07920 [J. S. L.]; Cell Therapeutics, Inc., Seattle, Washington 89119 [J. S.]; and Rochelle Belfer Chemotherapy Foundation Laboratory, Mt. Sinai School of Medicine, New York, New York 10029 [S. W.]
Arsenic trioxide has shown substantial efficacy in treating both newly diagnosed and relapsedpatients with acute promyelocytic leukemia (APL). As a single agent, it induces complete remissions, causing few adverse effects and only minimal myelosuppression. These successes have prompted investigations to elucidate the mechanisms of action underlying these clinical responses. Substantial data show that arsenic trioxide produces remissions in patients with APL at least in part through a mechanism that results in the degradation of the aberrant PML-retinoic acid receptor 
fusion protein. Studies have also investigated concerns about the toxicity and potential carcinogenicity of long-term exposure to environmental arsenic. Arsenic apparently affects numerous intracellular signal transduction pathways and causes many alterations in cellular function. These actions of arsenic may result in the induction of apoptosis, the inhibition of growth and angiogenesis, and the promotion of differentiation. Such effects have been observed in cultured cell lines and animal models, as well as clinical studies. Because arsenic affects so many cellular and physiological pathways, a wide variety of malignancies, including both hematologic cancer and solid tumors derived from several tissue types, may be susceptible to therapy with arsenic trioxide. These multiple actions of arsenic trioxide also highlight the need for additional mechanistic studies to determine which actions mediate the diverse biological effects of this agent. This information will be critical to realizing the potential for synergy between arsenic trioxide and other chemotherapeutic agents, thus providing enhanced benefit in cancer therapy.
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|
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|
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|
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|
|
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|
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|
|
 |
|
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|
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|
|
|
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|
|
|
|
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|
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|
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|
|
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|
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|
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|
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|
|
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|
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|
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|
|
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|
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|
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|
|
|
|
 |
|
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|
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|
|
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|
|
|
|
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|
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|
|
|
|
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|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 F. Lo-Coco and E. Ammatuna The Biology of Acute Promyelocytic Leukemia and Its Impact on Diagnosis and Treatment Hematology, January 1, 2006; 2006(1): 156 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 A. Chin, S. Liu, J. Ting-Chan, and M. A. Gill Extended stability of ascorbic acid in 5% dextrose injection and 0.9% sodium chloride injection Am. J. Health Syst. Pharm., May 15, 2005; 62(10): 1073 - 1074. [Full Text] [PDF]
|
|
|
|
|
|
N. Karasavvas, J. M. Carcamo, G. Stratis, and D. W. Golde Vitamin C protects HL60 and U266 cells from arsenic toxicity Blood, May 15, 2005; 105(10): 4004 - 4012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
G. McCollum, P. C. Keng, J. C. States, and M. J. McCabe Jr. Arsenite Delays Progression through Each Cell Cycle Phase and Induces Apoptosis following G2/M Arrest in U937 Myeloid Leukemia Cells J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 877 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Douer and M. S. Tallman Arsenic Trioxide: New Clinical Experience With an Old Medication in Hematologic Malignancies J. Clin. Oncol., April 1, 2005; 23(10): 2396 - 2410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
Z. Diaz, M. Colombo, K. K. Mann, H. Su, K. N. Smith, D. S. Bohle, H. M. Schipper, and W. H. Miller Jr Trolox selectively enhances arsenic-mediated oxidative stress and apoptosis in APL and other malignant cell lines Blood, February 1, 2005; 105(3): 1237 - 1245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-H. Yih, S.-W. Hsueh, W.-S. Luu, T. H. Chiu, and T.-C. Lee Arsenite induces prominent mitotic arrest via inhibition of G2 checkpoint activation in CGL-2 cells Carcinogenesis, January 1, 2005; 26(1): 53 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-H. Kang, M.-J. Yi, M.-J. Kim, M.-T. Park, S. Bae, C.-M. Kang, C.-K. Cho, I.-C. Park, M.-J. Park, C. H. Rhee, et al. Caspase-Independent Cell Death by Arsenic Trioxide in Human Cervical Cancer Cells: Reactive Oxygen Species-Mediated Poly(ADP-ribose) Polymerase-1 Activation Signals Apoptosis-Inducing Factor Release from Mitochondria Cancer Res., December 15, 2004; 64(24): 8960 - 8967. [Abstract] [Full Text] [PDF]
|
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 |
|
 D.-R. Hwang, Y.-C. Tsai, J.-C. Lee, K.-K. Huang, R.-K. Lin, C.-H. Ho, J.-M. Chiou, Y.-T. Lin, J. T. A. Hsu, and C.-T. Yeh Inhibition of Hepatitis C Virus Replication by Arsenic Trioxide Antimicrob. Agents Chemother., August 1, 2004; 48(8): 2876 - 2882. [Abstract] [Full Text] [PDF]
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|
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J. Yi, J. Yang, R. He, F. Gao, H. Sang, X. Tang, and R. D. Ye Emodin Enhances Arsenic Trioxide-Induced Apoptosis via Generation of Reactive Oxygen Species and Inhibition of Survival Signaling Cancer Res., January 1, 2004; 64(1): 108 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. List, J. Vardiman, J.-P. J. Issa, and T. M. DeWitte Myelodysplastic Syndromes Hematology, January 1, 2004; 2004(1): 297 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 G M Tozer Measuring tumour vascular response to antivascular and antiangiogenic drugs Br. J. Radiol., December 1, 2003; 76(suppl_1): S23 - S35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-C. Zhang, M. T. Schmitt, and J. L. Mumford Effects of arsenic on telomerase and telomeres in relation to cell proliferation and apoptosis in human keratinocytes and leukemia cells in vitro Carcinogenesis, November 1, 2003; 24(11): 1811 - 1817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kurki, L. Latonen, and M. Laiho Cellular stress and DNA damage invoke temporally distinct Mdm2, p53 and PML complexes and damage-specific nuclear relocalization J. Cell Sci., October 1, 2003; 116(19): 3917 - 3925. [Abstract] [Full Text] [PDF]
|
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|
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|
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|
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|
|
|
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S. Sturlan, M. Baumgartner, E. Roth, and T. Bachleitner-Hofmann Docosahexaenoic acid enhances arsenic trioxide-mediated apoptosis in arsenic trioxide-resistant HL-60 cells Blood, June 15, 2003; 101(12): 4990 - 4997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Ravandi, M. Talpaz, and Z. Estrov Modulation of Cellular Signaling Pathways: Prospects for Targeted Therapy in Hematological Malignancies Clin. Cancer Res., February 1, 2003; 9(2): 535 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Mufti, A. F. List, S. D. Gore, and A. Y.L. Ho Myelodysplastic Syndrome Hematology, January 1, 2003; 2003(1): 176 - 199. |
