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Genetic
and hypoxic regulation of angiogenesis in gliomas
Balveen Kaur,
Chalet Tan, Daniel J. Brat, Erwin G. Van Meir
Laboratory of Molecular
Neuro-Oncology, Department of Neuro-surgery and
Hematology/Oncology, Winship Cancer Institute, Atlanta, GA [B.K.,
C.T., E.G.V.M.]; Department of Pathology and Laboratory Medicine,
Emory University School of Medicine, Atlanta, GA [D.J.B.].
Infiltrative astrocytic
neoplasms are by far the most common malignant brain tumors in
adults.
Clinically, they are highly problematic due to their widely
invasive nature which makes a complete resection almost
impossible.
Biologic progression of these tumors is inevitable and adjuvant
therapies are only moderately effective in prolonging
survival.
Glioblastoma multiforme (GBM WHO grade IV), the most malignant
form of infiltrating astrocytoma, can evolve from a lower grade
precursor tumor (secondary GBM) or can present as high grade
lesion from the outset, so-called de novo GBM.
Molecular
genetic investigations suggest that GBMs are comprised of multiple
molecular genetic subsets.
Notwithstanding
the diversity of genetic alterations leading to the GBM phenotype,
the vascular changes that evolve in this disease, presumably
favoring further growth, are remarkably similar.
Underlying
genetic alterations in GBM may tilt the balance in favor of an
angiogenic phenotype by upregulation of pro-angiogenic factors and
down-regulation of angiogenesis inhibitors.
Increased
vascularity and endothelial cell proliferation in GBMs are also
driven by hypoxia-induced expression of pro-angiogenic cytokines,
such vascular endothelial growth factor (VEGF).
Understanding
the contribution of genetic alterations and hypoxia in angiogenic
dysregulation in astrocytic neoplasms will lead to the development
of better anti-angiogenic therapies for this disease.
This
review will summarize the properties of angiogenic dysregulation
that lead to the highly vascularized nature of these tumors.
Keywords: angiogenesis, angiopoietin,
astrocytoma, fibroblast growth factor, genetics, glioblastoma
multiforme, placenta growth factor, vascular endothelial growth
factor
Copyright © 2004 Kluwer Academic Publishers.
All rights reserved
Source: http://ipsapp007.kluweronline.com/IPS/content/ext/x/J/5042/I/125/A/8/abstract.htm
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