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Communication Dans Un Congrès Année : 2015

Optimization of the use of anti-angiogenics in glioblastoma using mathematical modeling.

Résumé

Glioblastoma is a highly angiogenic type of tumor and glioblastoma patients have a low survival rate in spite of all the therapeutic procedures unleashed (surgical resection, radio- and chemotherapy). According to the literature, anti-angiogenic therapies such as the anti-VEGF bevacizumab, can temporarily induce changes in the tumor vasculature that result in improved tissue oxygenation which is crucial to the success of oxygen-dependent radiation therapy. Combining bevacizumab and radiation therapy seems to be a prospective way to improve patient survival. However, finding the best treatment sequence is not an easy task to achieve and no consensus has yet been established because of the lack of knowledge regarding the time and duration of the increased oxygenation window provided by bevacizumab. Hence it is indispensable to define the morphological and functional effects of bevacizumab on the tumor vascular network that impact on the oxygenation to find the perfect timing for its association with radiation therapy. To provide clinicians with tools to determine the best time to treat with radiation after bevacizumab, our research team is developing mathematical models of the tumor vascularization using in vivo data of the tumor vascular network obtained with non-invasive imaging. Glioblastoma tumor fragments were implanted in skinfold chambers borne by nude mice. The evolution of the vascular network in tumors treated or not with bevacizumab at 10 mg/kg/day was observed using intravital microscopy and analyzed with mathematical algorithms created by our research team to quantify daily the effects of bevacizumab on the vascular network. We showed a significate drop in the vascular density and the apparition of a vascular stabilization in the bevacizumab group that was comforted by immunostaining the blood vessels in formalin-fixed tumors. The vascular density data obtained allowed us to create a prototype behavioral-model of the tumor response that shows a perfect simulation of the experimental data both in the control and treated group (Figure 1). Using our biological data, we present here an original approach to characterize and analyze the anti-angiogenic response with a behavioral-model that will in the future help us predict the therapeutic outcome.

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Dates et versions

hal-01204533 , version 1 (24-09-2015)

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  • HAL Id : hal-01204533 , version 1

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Karima El Alaoui-Lasmaili, Jean-Baptiste Tylcz, El-Hadi Djermoune, Noémie Thomas, Béatrice Faivre. Optimization of the use of anti-angiogenics in glioblastoma using mathematical modeling.. 6th Congress of the French Society of Angiogenesis, Sep 2015, Paris, France. ⟨hal-01204533⟩
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