title: In Vitro Validation of Intratumoral Modulation Therapy for Glioblastoma.
abstract: OBJECTIVE
  This proof-of-concept study evaluated the antitumor impact of a direct electrical stimulation technique, termed intratumoral modulation therapy (IMT) on glioblastoma (GBM) cells.
  
  
  METHODS
  An in vitro IMT model comprised of a calibrated electrode to deliver continuous, low-intensity stimulation within GBM preparations. Viability and apoptosis assays were performed in treated immortalized and patient-derived GBM cells, and post-mitotic neurons. IMT was delivered alone and with temozolomide, or gene silencing of the tumor-promoting chaperone, heat-shock protein 27 (HSP27).
  
  
  RESULTS
  GBM cells, but not neurons, exhibited >40% loss of viability, caspase-3 activation and apoptosis with IMT. Cell death was modest with temozolomide alone (30%) but increased significantly with concomitant IMT (70%). HSP27 silencing alone produced 30% viability loss, with significant enhancement of target knockdown and GBM cell death (65%), when combined with IMT.
  
  
  CONCLUSIONS
  These findings warrant further evaluation of IMT as a potential novel therapeutic strategy for GBM.
authors.affiliation: Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: H U
authors.initials: HU
authors.lastname: Xu
authors.affiliation: Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: Bihari
authors.affiliation: Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Shawn
authors.initials: S
authors.lastname: Whitehead
authors.affiliation: Department of Physics and Astronomy, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Eugene
authors.initials: E
authors.lastname: Wong
authors.affiliation: Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schmid
authors.affiliation: Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada mhebb@uwo.ca.
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Hebb
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004599:Electric Stimulation Therapy / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods*; D000077204:Temozolomide; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Glioma; chemotherapy; electrotherapy; heat-shock proteins; neuromodulation