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Integrin Inhibitor Suppresses Bevacizumab-Induced Glioma Invasion.

Al's Comment:

 When I first heard about the drug Cilengitide, I thought it would be perfect to use with a treatment like Avastin.  I hope to see human trials of this soon.  My thoughts:  as shown in this article, Avastin cuts off the blood supply to the tumor, and stops a new blood supply from forming, so the only way the tumor can survive is to invade surrounding areas looking for a new blood supply.  It makes sense to combine it with a drug that stops that invasion.

Posted on: 04/08/2014

8.  Transl Oncol. 2014 Mar 4. pii: S1936-5233(14)00017-5. doi: 10.1016/j.tranon.2014.02.016. [Epub ahead of print]
Integrin Inhibitor Suppresses Bevacizumab-Induced Glioma Invasion.
Ishida J1, Onishi M1, Kurozumi K2, Ichikawa T1, Fujii K1, Shimazu Y1, Oka T1, Date I1.
Author information: 
1Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
2Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address:
Glioblastoma is known to secrete high levels of vascular endothelial growth factor (VEGF), and clinical studies with bevacizumab, a monoclonal antibody to VEGF, have demonstrated convincing therapeutic benefits in glioblastoma patients. However, its induction of invasive proliferation has also been reported. We examined the effects of treatment with cilengitide, an integrin inhibitor, on bevacizumab-induced invasive changes in glioma. U87ΔEGFR cells were stereotactically injected into the brain of nude mice or rats. Five days after tumor implantation, cilengitide and bevacizumab were administered intraperitoneally three times a week. At 18 days after tumor implantation, the brains were removed and observed histopathologically. Next, the bevacizumab and cilengitide combination group was compared to the bevacizumab monotherapy group using microarray analysis. Bevacizumab treatment led to increased cell invasion in spite of decreased angiogenesis. When the rats were treated with a combination of bevacizumab and cilengitide, the depth of tumor invasion was significantly less than with only bevacizumab. Pathway analysis demonstrated the inhibition of invasion-associated genes such as the integrin-mediated cell adhesion pathway in the combination group. This study showed that the combination of bevacizumab with cilengitide exerted its anti-invasive effect. The elucidation of this mechanism might contribute to the treatment of bevacizumab-refractory glioma.
Copyright © 2014 Elsevier Inc. All rights reserved.
 PMID: 24704537 [PubMed - as supplied by publisher] 


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