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Treatment
> Valproic
Acid
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Abstracts for the Seventh Congress of the European Association for Neuro-Oncology
(EANO). Vienna, Austria, September 14-17, 2006. Abstract No. P80.
Neuro-Oncology, October 2006, Page 334.
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Meeting Abstract |
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Valproic Acid is toxic to malignant
glioma cells and increases sensitivity to irradiation and chemotherapy
A.M. Admirant, J. A. Hendricks, P.C.
De Witt Hamer, S. Leenstra, W.P. Vandertop, C.J.F. van Noorden, and
J.P. Medema
Academic Medical Center, Amsterdam,
The Nederlands
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Glioblastoma multiforme is the most
frequent and the most aggressive of glial tumors, with a median
survival of nine months, despite surgical resection, radiotherapy and
temozolomide treatment.
Glioblastoma multiforme can be regarded as an abnormal
"organ" of which the growth is regulated by cancer stem
cells rather than a homogeneous mass of cells with unregulated growth
capacity.
If these cancer stem cells have a different therapeutic response as
compared to their successive cancer cells, then the inefficacy of
conventional therapy, the objective of which is to eliminate tumor
mass, may me explained by remaining cancer stem cells that re-form the
tumor.
Valproic acid (VPA), a well- known anticonvulsant, inhibits histone
diacetylase and has been shown to induce tumor differentiation,
apoptosis, and growth arrest.
In the present study, the therapeutic response to VPA was evaluated in
a number of glioma cell lines (U87, U251, U373, Gli06, and T98G).
The cytotoxicity of VPA was determined at clinically relevant
concentrations in combination with irradiation and chemotherapy.
VPA treatment alone decreased the clonogenic potential of glioma cell
lines.
Glioma cell lines were sensitized to chemotherapy, such as cisplatinum
and temozolomide, after 24 h of pretreatment with VPA, as measured by
MTT essay.
Pretreatment for 24 h with VPA prior to irradiation decreased the
ability to form colonies in a clologenic essay.
These results show that VPA as single treatment it toxic to glioma
cells at clinically relevant concentrations and its machanism of
action may not be the sensitization of cells to conventional therapy
but rather a direct cytotoxic effect.
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Copyright 2006 by Society for Neuro-Oncology
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