Section: New Results
Highlights of the Year
Glioblastoma multiforme (GBM) causes significant neurological morbidity and short survival times. Brain invasion by GBM is associated with poor prognosis. Recent clinical trials of bevacizumab in newly-diagnosed GBM found no beneficial effects on overall survival times; however, the baseline health-related quality of life and performance status were maintained longer in the bevacizumab group and the glucocorticoid requirement was lower. In a recent work in collaboration with UAB, we have constructed a clinical-scale model of GBM whose predictions uncover a new pattern of recurrence in 11/70 bevacizumab-treated patients. The findings support an exception to the Folkman hypothesis: GBM grows in the absence of angiogenesis by a cycle of proliferation and brain invasion that expands necrosis. Furthermore, necrosis is positively correlated with brain invasion in 26 newly-diagnosed GBM. The unintuitive results explain the unusual clinical effects of bevacizumab and suggest new hypotheses on the dynamic clinical effects of migration by active transport, a mechanism of hypoxia-driven brain invasion.
Based on the new discovery of the team of Vectorolgy and anti-cancerous therapies on the membrane lipid oxidation during the pulse delivery, we have provided a model of cell permeabilization that makes it possible to explain the process of electroporation : pore formation during the pulse and surface diffusion of altered lipids after the pulse. Our model explains the long-term effect of electroporation (the permeable state of the membrane lasts a few minutes after the pulse delivery). A 3D-code in C++ has been implemented during the PhD thesis of M. Leguèbe. The team MC2 is now part of the European Lab EBAM on electroporation modeling. An international workshop on Electroporation and Biophysical Therapies was held in Bordeaux the 15th and 16th December.