Enhancement of Classic Kaposi’s Sarcoma Growth after Intralesional Injections of Desferrioxamine

Simonart, Thierry; Boelaert, Johan R.; Vooren, J. P. Van

doi:10.1159/000063361

Cited by 13 publications

(4 citation statements)

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“…HIF-1 transcriptionally activates proangiogenic proteins, including EPO and VEGF, leading to the possibility that chelators might stimulate tumor vascularization. The recent report that DFO unexpectedly stimulated growth of Kaposi's sarcoma suggests that this may be a clinically relevant concern, although whether the effects seen in this report were the result of enhanced vascularization and/or stimulation of HIF-1 was not studied [208]. However, not all iron chelators activate HIF-1 [209], and by judicious design it may be possible to minimize HIF-1 activating activity while preserving anti-tumor properties.…”

Section: Perspectives and Future Directionsmentioning

confidence: 84%

The Role of Iron Chelation in Cancer Therapy

Buss¹,

Torti²,

Torti³

2003

CMC

212

216

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This review focuses on advances and strategies in the use of iron chelators as anti-tumor therapies. Although the development of iron chelators for human disease has focused primarily on their use in the treatment of secondary iron overload, chelators may also be useful anti-tumor agents. They can deplete iron or cause oxidative stress in the tumor due to redox perturbations in its environment. Iron chelators have been tested for their anti-tumor activity in cell culture experiments, animal models and human clinical trials. Largely for pragmatic reasons, clinical studies of the anti-tumor activity of iron chelators have generally focused on desferrioxamine (DFO), a drug approved for the treatment of iron overload. These studies have shown that DFO can retard tumor growth in many different experimental contexts. However, the activity of DFO is modest, and advances in the use of chelators as anti-cancer agents will require the development of new chelators based on new paradigms. Examples of iron chelators that have shown promising anti-tumor activity (in various stages of development) include heterocyclic carboxaldehyde thiosemicarbazones, analogs of pyridoxal isonicotinoyl hydrazone, tachpyridine, O-trensox, desferrithiocin, and other natural and synthetic chelators. Apart from their use as single agents, chelators may also synergize with other anti-cancer therapies. The development of chelators as anticancer agents is largely an unexplored field, but one with extraordinary potential to impact human cancer.

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Section: Perspectives and Future Directionsmentioning

confidence: 84%

The Role of Iron Chelation in Cancer Therapy

Buss¹,

Torti²,

Torti³

2003

CMC

212

216

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show abstract

“…During the past fifteen years, desferrioxamine has been reported to have antineoplastic activity in in-vitro systems, in rodents, and in man. Unfortunately, although the chelator inhibits sarcoma cells in-vitro, it has stimulated their growth when given to a patient by intralesional injection (Simonart et al 2002). Nevertheless, the drug might find utility as an adjunct in some clinical situations.…”

Section: Antineoplastic Activitymentioning

confidence: 99%

Therapeutic potential of iron chelators in diseases associated with iron mismanagement

Weinberg

2006

Journal of Pharmacy and Pharmacology

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A considerable array of diseases are now recognized to be associated with misplacement of iron. Excessive deposits of the metal in sensitive tissue sites can result in formation of destructive hydroxyl radicals as well as in stimulation of growth of neoplastic and microbial cell invaders. To counteract potential iron damage, hosts employ the iron chelators, transferrin and lactoferrin. These proteins have been recently developed into pharmaceutical products. Additionally, a variety of low molecular mass iron chelators are being used/tested to treat whole body iron loading, and specific diseases for which the metal is a known or suspected risk factor.

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“…14 Following in vitro success, DFO was suggested for both malaria and tumor therapy. In human trials, DFO and other iron chelators had a transient beneficial effect on malaria 15,16 and enhanced the development of Kaposi's sarcoma, 17 possibly by affecting immune functions. In addition, metal selectivity of the chelators is important because of the risk of depletion of the patients' stores of essential metals.…”

Section: Deleterious Effectsmentioning

confidence: 99%