RGD Reference Report - Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors. - Rat Genome Database

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Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors.

Authors: Wong, HK  Lahdenranta, J  Kamoun, WS  Chan, AW  McClatchey, AI  Plotkin, SR  Jain, RK  Di Tomaso, E 
Citation: Wong HK, etal., Cancer Res. 2010 May 1;70(9):3483-93. doi: 10.1158/0008-5472.CAN-09-3107. Epub 2010 Apr 20.
RGD ID: 8547955
Pubmed: PMID:20406973   (View Abstract at PubMed)
PMCID: PMC4785015   (View Article at PubMed Central)
DOI: DOI:10.1158/0008-5472.CAN-09-3107   (Journal Full-text)

Patients with bilateral vestibular schwannomas associated with neurofibromatosis type 2 (NF2) experience significant morbidity such as complete hearing loss. We have recently shown that treatment with bevacizumab provided tumor stabilization and hearing recovery in a subset of NF2 patients with progressive disease. In the current study, we used two animal models to identify the mechanism of action of anti-vascular endothelial growth factor (VEGF) therapy in schwannomas. The human HEI193 and murine Nf2(-/-) cell lines were implanted between the pia and arachnoid meninges as well as in the sciatic nerve to mimic central and peripheral schwannomas. Mice were treated with bevacizumab (10 mg/kg/wk i.v.) or vandetanib (50 mg/kg/d orally) to block the VEGF pathway. Using intravital and confocal microscopy, together with whole-body imaging, we measured tumor growth delay, survival rate, as well as blood vessel structure and function at regular intervals. In both models, tumor vessel diameter, length/surface area density, and permeability were significantly reduced after treatment. After 2 weeks of treatment, necrosis in HEI193 tumors and apoptosis in Nf2(-/-) tumors were significantly increased, and the tumor growth rate decreased by an average of 50%. The survival of mice bearing intracranial schwannomas was extended by at least 50%. This study shows that anti-VEGF therapy normalizes the vasculature of schwannoma xenografts in nude mice and successfully controls the tumor growth, probably by reestablishing a natural balance between VEGF and semaphorin 3 signaling.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
vestibular schwannomatosis  ISOVegfa (Mus musculus)8547955; 8547955 RGD 
vestibular schwannomatosis  IMP 8547955 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Vegfa  (vascular endothelial growth factor A)

Genes (Mus musculus)
Vegfa  (vascular endothelial growth factor A)

Genes (Homo sapiens)
VEGFA  (vascular endothelial growth factor A)


Additional Information