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Differential
effects of antiangiogenic compounds in neovascularization, leukocyte
recruitment, VEGF production, and tumor growth in mice
Belo
AV, Barcelos LS, Teixeir MM, Ferreira MA, Andrade SP.
Department
of Physiology and Biophysics, Institute of Biological Sciences, Federal
University of Minas, Gerais/Belo Horizonte, Brazil.
Angiogenesis and inflammation play critical roles in tumor growth.
Using
an in vivo tumor model, we report that thalidomide (100 mg kg(-1)day(-1)) or
clotrimazole (120 mg kg(-1) day(-1)), inhibit blood vessel formation
(determined by hemoglobin content), leukocyte recruitment [myeloperoxidase
(MPO) activity; N-acetylglucosa-minidase (NAG) activity], and vascular
endothelial growth factor production.
Inhibition
of angiogenesis ranged from 35% to 65%.
Clotrimazole
was the most potent antiangiogenic compound and the agent capable of
inhibiting tumor growth.
Thalidomide
was able to reduce the inflammatory reaction (MPO and NAG activities) by 50%
to 70%, but was unable to delay tumor development.
These
results suggest that for this type of solid tumor the degree of
neovascularization, rather than inhibition of inflammatory cell recruitment,
is a determinant factor in tumor development.
As
the contribution of angiogenesis and inflammation to cancer progression vary
markedly among different tumor types, it may be relevant to consider these
factors in cancer therapy using antiangiogenesis/antiinflammatory
approaches.
PMID: 15581054 [PubMed - in process]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15581054
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