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The
contributions of cyclooxygenase-2 to tumor angiogenesis
Gately
S
Department
of Medicine, Northwestern University Medical School, Chicago, IL, USA. sg@northwestern.edu
Cyclooxygenase-2
(COX-2) is an immediate early response gene that can be induced by a variety of
tumor promoters, cytokines, growth factors and hypoxia.
COX-2 overexpression is linked to all stages of carcinogenesis with the enzyme
localized to the neoplastic cells, microvascular endothelial cells, and stromal
fibroblasts.
The contributions of COX-2 in tumor angiogenesis include:
(a) the increased expression of the proangiogenic growth factor VEGF;
(b) the production of the eicosanoid products thromboxane A2, PGE2 and PGI2 that
can directly stimulate endothelial cell migration and growth factor-induced
angiogenesis; and potentially,
(c) the inhibition of endothelial cell apoptosis by stimulation of Bcl-2 or Akt
activation.
Selective pharmacological inhibitors of COX-2 as angiosuppressive agents could
have therapeutic benefit in the treatment of neoplastic disease from prevention
through treatment of advanced metastatic disease.
These agents are safe and well tolerated and can be added to chemotherapy and
radiation therapy where angiogenesis inhibitors appear to provide at least
additive therapeutic benefit.
PMID:
11191059 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11191059&dopt=Abstract
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