 |
|
Title
|
|
The role of contortrostatin, a snake venom disintegrin, in the inhibition of tumor progression and prolongation of survival in a rodent glioma model.
|
|
|
Authors
|
|
P.Pyrko,
W.Wang,
F.S.Markland,
S.D.Swenson,
S.Schmitmeier,
A.H.Schönthal,
T.C.Chen.
|
|
|
Ref.
|
|
J Neurosurg, 2005,
103,
526-537.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
OBJECT: Malignant gliomas are not curable because of diffuse brain invasion. The
tumor cells invade the surrounding brain tissue without a clear tumor-brain
demarcation line, making complete resection impossible. Therapy aimed at
inhibition of invasion is crucial not only for prevention of tumor spread, but
also for selectively blocking migrating cells that may be more resistant to
chemotherapy and radiation. Recently, investigations have shown that the snake
venom disintegrin contortrostatin specifically binds to certain integrins on the
surface of glioma cells and thereby inhibits their interaction with the
extracellular matrix (ECM), resulting in a blockage of cell motility and
invasiveness. To translate these in vitro findings into clinical settings, the
authors examined the effect of contortrostatin on glioma progression in a rodent
model. METHODS: Athymic mice were intracranially or subcutaneously injected with
U87 glioma cells, and the effect of intratumorally administered contortrostatin
on tumor progression and animal survival was then studied. In addition, the
authors evaluated the pharmacological safety of contortrostatin use in the
brains of tumor-free animals. CONCLUSIONS: The results demonstrate that
contortrostatin is able to inhibit tumor growth and angiogenesis and to prolong
survival in a rodent glioma model. Moreover, contortrostatin appears to be well
tolerated by the animal and lacks obvious neurotoxic side effects. Thus,
contortrostatin may have potential as a novel therapeutic agent for the
treatment of malignant gliomas.
|
|
|
|