CNR - Institute of Neuroscience CNR
Institute of Neuroscience
 

Project

Target identification and antiangiogenic therapies for brain tumors

We are interested in identifying new therapies for the glioblastoma multiform (GBM), one of the most lethal cancers with a mean survival time in the range of only several months. In order to obtain this result our laboratory has recently been associated to the European Laboratory for Angiosgenesis and Translational Medicine (ELAT), an european laboratory formed by the association of INSERM, University of Bordeaux and University of Milano.

The main objectives of the ELAT laboratory are the following:

  1. obtention of better mechanistical insights into the molecular regulation of angiogenesis and invasion, especially in relation to the neural tissue;
  2. elucidation of pathophysiological mechanisms of tumor angiogenesis and invasion in brain malignancies;
  3. identification of markers/targets that may be used for diagnosis/prognosis or the development of new therapeutics;
  4. development of new drugs and therapeutic strategies for the treatment of brain malignancies.
 

We have started to investigate the effect of anti-angiogenic therapy on the cellular proteome in our mouse glioma models. We have recently used high resolution two-dimensional gel electrophoresis (2DE) proteomic analysis to compare profile proteins expression of experimental glioblastoma before and after treatment with PF-4 DLR, a potent antiangiogenic peptide. We have identified 54 proteins whose expression is modified by PF-4 DLR treatment, 39 of them increase their expression after PF-4 DLR treatment and 15 decrease their expression. Several of these proteins are involved in cell proliferation and in invasion control. We are now testing the possibility to reduce in the glioblatomas the expression of some of these proteins by RNA interference in vivo, in order to increase the efficacy of PF-4 DLR antiangiogenetic therapy.

In collaboration with the other ELAT laboratories we are now using extensive proteomic investigation in order to identify differences in proteins expression between low grade and high grade human gliomas or between cancer stem cells lines obtained from human gliomas before an after treatment with chemio- and radio- therapies.

Publications

  • Saidi A, Hagedorn M, Allain N, Verpelli C, Sala C, Bello L, Bikfalvi A, Javerzat S (2009) Combined targeting of interleukin-6 and vascular endothelial growth factor potently inhibits glioma growth and invasiveness. Int. J. Cancer 125:1054-64.

Collaborations

Collaboration inside ELAT

  • A. Bikfalvi, INSERM EMI 0113, Bordeaux, Francia.
  • L. Bello, Istituto di Neurochirurgia, Università degli Studi di Milano, Milan, Italy.
  • R. Galli, DIBIT, San Raffaele Scientific Institute, Milan, Italy.

 

PI photo

Carlo Sala

Contact information

email  E-mail

email  +39 02 5031 7096

Participating staff
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