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Chemotherapy causes delayed severe neural damage
Date:4/21/2008

Cancer treatment with chemotherapeutic agents is often associated with delayed adverse neurological consequences - an occurrence often referred to as chemobrain - that may compromise the quality of life of a proportion of cancer survivors. Now, research published in the open access Journal of Biology demonstrates that treatment with a single chemotherapeutic agent, 5-fluorouracil (5-FU), by itself is sufficient to cause a syndrome of delayed degeneration in the central nervous system (CNS). 5-FU is a widely used chemotherapeutic agent that is employed, alone or in combination with other agents, in the treatment of cancers of the colon, rectum, breast, stomach, pancreas, ovaries and bladder.

Little is known about the side-effects of chemotherapy on the CNS, despite their obvious clinical importance. Until now researchers have not fully understood the underlying biology, including whether these effects require: exposure to multiple chemotherapeutic agents; chemotherapeutic agents plus the bodys own response to cancer; blood-brain barrier damage; or inflammation. Clinicians have also lacked animal models to study this important problem.

Professor Mark Noble and colleagues of the University of Rochester Stem Cell and Regenerative Medicine Institute and the Harvard Medical School, Boston discovered that short-term systemic administration of 5-FU to mice caused both acute CNS damage and a syndrome of progressively worsening delayed damage. This damage was not self-repairing, and instead became worse over time. In addition, Noble and colleagues also demonstrated that treatment with chemotherapy also had delayed effects on the speed with which information is transferred from the ear to the brain.

Myelin sheaths are necessary for normal neuronal function. One key finding of the study was that clinically relevant concentrations of 5-FU were toxic not only for dividing cells of the CNS but also for the cells that produce the insulating myelin sh
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Contact: Charlotte Webber
charlotte.webber@biomedcentral.com
44-020-763-19980
BioMed Central
Source:Eurekalert

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