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Desferoxamine (DFO) – Mediated Iron Chelation:
Rationale for a Novel Approach to Therapy for Brain Cancer
Pouya N. Dayani,
Maria C. Bishop,
Keith Black,
Paul M. Zeltzer
Northwestern University Medical School, Chicago, IL
(P.N.D.); University of Arizona Cancer Center and Southern Arizona Veterans Administration
Health Care System, Tucson, AZ (P.C.B.);
Maxine Dunitz Neurosurgical Institute, Cedars Sinai Medical Center, Los Angeles,
CA, USA (K.B., P.M.Z).
Iron homeostasis is crucial to normal cell metabolism, and its deficiency
or excess is associated with numerous disease states.
The association of
increased iron load with cancer may be due to several factors including free
radical production, reduction of the body's protective mechanism to combat
oxidative stress, inhibition of immune systems, inhibition of essential nutrient
functions, facilitation of cancer growth, suppression of antitumor actions of
macrophages, and lowering of the ratio of T4–T8
positive lymphocytes.
Antiproliferative effects of desferoxamine (DFO) both in
vitro and in vivo are mediated by an intracellular pool of iron
that is necessary for DNA synthesis rather than prevention of iron uptake from
transferrin.
Several clinical studies have shown it to have antitumor activity
in the treatment of neuroblastoma, leukemia, bladder carcinoma, and
hepatocellular carcinoma.
Human neural tumor cells are susceptible to the
effects of DFO.
Continued study of DFO is necessary to further elucidate its
antineoplastic profile and its use as an adjunct to current chemotherapy
regimens.
Given the lack of satisfactory treatment of central nervous system
neoplasms, DFO could serve as an important tool in the management of such
cancers.
Keywords: brain tumors, chemotherapy, desferoxamine, iron chelation, neuroblastoma,
transferrin receptor
Copyright
©
2004 Kluwer Academic Publishers.
All rights reserved
Source:
doi:10.1023/B:NEON.0000024238.21349.37
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