title: Modulation of PPIX synthesis and accumulation in various normal and glioma cell lines by modification of the cellular signaling and temperature.
abstract: Effective therapies for malignant gliomas are still elusive and limited survival improvements are provided only by Temozolomide or fluorescence guided resection. The efficacy of photodynamic therapy (PDT) in this indication is limited by the higher sensitivity of normal brain structures compared to glioma necessitating a modulation of its sensitivity. We evaluate the influence of hypothermia and the tyrosine kinase inhibitor Erlotinib on cell's ability to synthesize PPIX following the administration of ALA which was not previously investigated. We demonstrate that both hypothermia and Erlotinib are favorable in PPIX selectivity as only glioma cell lines demonstrate an increased PPIX synthesis, whereas the neuronal and astrocytic synthesis is remaining unaffected. The results are encouraging to consider hypothermia and Erlotinib as adjuvant therapies to increase the PDT therapeutic index between GBM and normal intracranial tissues, as well as to improve contrast in fluorescence guided resection.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Fisher
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Niu
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lai
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Chen
authors.forename: Victoria
authors.initials: V
authors.lastname: Kuta
authors.forename: Lothar D
authors.initials: LD
authors.lastname: Lilge
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007036:Hypothermia, Induced; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011524:Protoporphyrins / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor; D017319:Photosensitizing Agents; D047428:Protein Kinase Inhibitors; D011524:Protoporphyrins; D011799:Quinazolines; C028025:protoporphyrin IX; D000069347:Erlotinib Hydrochloride
keywords: hypothermia; life cell imaging; mitochondria; photodynamic therapy; tyrosine kinase inhibitors