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Advances and Technical Standards in Neurosurgery was conceived in 1972byitsfoundingfathersJeanBrihaye,BernardPertuiset,FritzLoew andHugoKrayenbuuhlatacombinedmeetingoftheItalianandGerman NeurosurgicalSocietiesinTaormina. Itwasdesignedtocomplementthe Europeanpost-graduatetrainingsystemforyoungneurosurgeonsandwas ?rst published in 1974 initially through sponsorship by the European AssociationofNeurosurgicalSocieties. Allcontributionshavebeenp- lishedinEnglishtofacilitateinternationalunderstanding. Theambitionofallsuccessiveeditorialboardshasbeentoprovidean opportunityformaturescholarshipandre?ection,notconstrainedbyar- ?ciallimitsonspace. Theseriesprovidesaremarkableaccountofprogress overthepast35years,bothwithregardtoadvances,detaileddescriptions of standard operative procedures and in- depth reviews of established knowledge. Thepresentvolumeisnoexceptionandshouldappealtoboth experiencedneurosurgeonsandyoungneurosurgeonsintrainingalike. TheEditors Contents Listofcontributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XIII Advances Present and potential future adjuvant issues in high-grade astrocytic glioma 1,2 1 1 2 1 treatment. F. LEFRANC ,M. RYNKOWSKI,O. DEWITTE,andR. KISS, Department ofNeurosurgery,ErasmeUniversityHospital,FreeUniversityofBrussels(U. L. B. ), 2 Brussels,Belgium, LaboratoryofToxicology,InstituteofPharmacy,FreeUniversity ofBrussels(U. L. B. ),Brussels,Belgium Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Naturalresistanceofmigratingmalignantgliomacellstoapoptosis (radiotherapyandchemotherapy). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Patternsofcelldeath. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Autophagy:apotentialTrojanhorseformalignantgliomas. . . . . . . . . . . . . . . . 11 Therapeuticbene?tsoftemozolomide. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Localtherapiesforglioblastomas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Ongoingclinicaltrialsforglioblastomas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Growthfactorreceptorinhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 PI3K=Akt,mTORandNF- Binhibitors. . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Matrixmetalloproteinase(MMP)inhibitors(MMPI). . . . . . . . . . . . . . . . . . . 18 Angiogenesistargeting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Cellularandvaccinationtherapies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Genetherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Reducingmalignantgliomacellmotilityinordertorestore pro-apoptoticdrugsensitivity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Thesodiumpumpconstitutesapotentialtargettocombat malignantgliomas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Thesodiumpump. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Cardiotonicsteroids:ligandsofthesodiumpump. . . . . . . . . . . . . . . . . . . . 24 VIII Contents Thesodiumpumpisinvolvedincancercellproliferation, migrationanddeath. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Braintumorstemcellsapotentialtargettocombatmalignantgliomas. . . . . . . 26 Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Deepbrainstimulationforpsychiatricdisorders stateoftheart. T. E. SCHLA APFER and B. H. BEWERNICK, Brain Stimulation Group, Department of Psychiatr
