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Apoptosis in
Gliomas: Molecular Mechanisms and Therapeutic Implications
Joachim
P. Steinbach, Michael Weller
Hertie
Institute for Clinical Brain Research, Department of General
Neurology, School of Medicine, University of Tübingen,
Tübingen,
Germany
Understanding
apoptosis is often considered a key to understand the genesis of
tumors and to devise innovative strategies for their
treatment.
Similar to other types of cancer, essential pathways regulating
apoptosis are also disrupted in malignant gliomas, notably the
cell cycle control mechanisms regulated by the p53 and
retinoblastoma (RB) proteins and their homologs.
Moreover, cultured glioma cells appear not to activate the
extrinsic death receptor-dependent apoptotic pathway in response
to irradiation or cytotoxic drugs.
A preferential expression of antiapoptotic rather than
proapoptotic BCL-2 family proteins and high level expression of
inhibitor-of-apoptosis proteins (IAP) may be responsible for the
failure of glioma cells to activate caspases in response to
apoptotic stimuli.
Although apoptosis does occur spontaneously in malignant gliomas in
vivo,
there is little evidence that the current modes of non-surgical
treatment, radiotherapy and chemotherapy, mediate their effects
via induction of apoptosis, with the possible exception of
anaplastic oligodendrogliomas which often show striking tumor
regression on neuroimaging.
Yet, the induction of apoptosis plays a conceptual role in the
majority of novel experimental approaches to malignant glioma
which are currently evaluated in cell culture and preclinical
rodent models.
Keywords:
Apo2L/TRAIL,
apoptosis, CD95L, EGFR, glioma, hypoxia, p21, p53
Copyright
©
2004 Kluwer Academic Publishers. All rights reserved
Source:
http://ipsapp007.kluweronline.com/IPS/content/ext/x/J/5042/I/125/A/9/abstract.htm
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