title: Chemo-resistant protein expression pattern of glioblastoma cells (A172) to perillyl alcohol.
abstract: Glioblastoma multiform (GBM) is by far the most malignant glioma. We have introduced a new treatment for GBMs that comprises the inhalation of a naturally occurring terpene with chemotherapeutic properties known as perillyl alcohol (POH). Clinical trial results on recurrent GBM patients showed that POH extends the average life by more than eight months, temporarily slows tumor growth, and in some cases even decreases tumor size. After approximately seven months, the tumor continues to grow and leads to a dismal prognosis. To investigate how these tumors become resistant to POH, we generated an A172 human glioblastoma cell culture tolerant to 0.06 mM of POH (A172r). We used Multidimensional Protein Identification Technology (MudPIT) to compare the protein expression profile of A172r cells to the established glioblastoma A172 cell line. Our results include a list of identified proteins unique to either the resistant or the nonresistant cell line. These proteins are related to cellular growth, negative apoptosis regulation, Ras pathway, and other key cellular functions that could be connected to the underlying mechanisms of resistance.
authors.affiliation: Center for Technological Development in Health - Oswaldo Cruz Foundation, Ministry of Health, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: de Saldanha da Gama Fischer
authors.forename: Paulo
authors.initials: P
authors.lastname: Costa Carvalho
authors.forename: Clovis Orlando
authors.initials: CO
authors.lastname: da Fonseca
authors.forename: Lujian
authors.initials: L
authors.lastname: Liao
authors.forename: Wim M
authors.initials: WM
authors.lastname: Degrave
authors.forename: Maria
authors.initials: M
authors.lastname: da Gloria da Costa Carvalho
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Gilberto B
authors.initials: GB
authors.lastname: Domont
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015180:Electrophoresis, Gel, Two-Dimensional; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D039821:Monoterpenes / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D039821:Monoterpenes; D010446:Peptide Fragments; D020543:Proteome; C032208:perillyl alcohol
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