Sandrine Eimer

Glioblastoma, the most malignant brain tumor in humans, is characterized by being severely angiogenic and an increase in vascularization generally worsens the prognosis of patients. Finding the best approach to characterize glioma blood vessels (BVs) is very important in view of helping to determine any specific biomolecular markers of these tumors. In previous work by conventional FTIR spectroscopy we were able to discriminate some molecular markers in order to differentiate between normal and tumor BVs in glioma tissue sections. The aim of the present study was to assess whether FTIR microspectroscopy using a synchrotron radiation (SR) source could provide advantages over a classical globar IR source for detailed spectral analysis on such small features like micro-BVs. Using chemometric analysis such as PCA and HCA, the results show that a high brilliant SR beam provides a very satisfying quality signal compared with the globar source to study spectral images for relevant analysis of glioma big and micro-BVs and determination of subtle molecular markers characterizing them from the surrounding tissue.

Putative cancer stem cells have been identified in glioblastoma (GBM), associated with resistance to conventional therapies. Overcoming this resistance is a major challenge to manage this deadly brain tumor. Epidermal growth factor receptor (EGFR) is commonly amplified, over-expressed, and/or mutated in GBM, making it a compelling target for therapy. This study investigates the behavior of 3 primary neurosphere (NS) cell lines and their adherent counterparts originated from human GBM resections, when treated with EGFR–tyrosine kinase inhibitor erlotinib, associated or not with cyclopamine, a hedgehog pathway inhibitor. Adherent cells cultured in the presence of serum expressed the glial fibrillary acidic protein, whereas NS-forming cells cultured in serum-free medium expressed CD133, nestin, and Oct-4, markers of neural stem and progenitor cells. For the 3 adherent cell lines, erlotinib has a moderate effect (50% inhibitory concentration [IC50], >10 µM). Conversely, erlotinib induced a strong cell growth inhibition (IC50, EGFR gene amplification and EGFR protein expression. A short exposure to erlotinib reduced nestin-positive cell proliferation, but NS-initiating activity and self-renewal were not altered. EGFR pathway seems essential for GBM progenitor cell proliferation but dispensable for cancer stem-like cell self-renewal. Inhibition of hedgehog pathway with cyclopamine was evaluated in association with erlotinib on NS growth. Although each drug separately had no effect on sphere initiation, their combination significantly decreased the sphere number (P < .001). Our findings show synergic efficiency for erlotinib-cyclopamine association and provide a suitable in vitro model to explore drug combinations on GBM cells.

Gliomas are the most common malignant primary brain tumors in adults. The median survival never exceeds 12 months, owing to inherent resistance to both radio and chemotherapies. Epidermal Growth Fa...