title: Glioblastoma stem cells: radiobiological response to ionising radiations of different qualities.
abstract: Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumour, with very poor prognosis. The high recurrence rate and failure of conventional treatments are expected to be related to the presence of radio-resistant cancer stem cells (CSCs) inside the tumour mass. CSCs can both self-renew and differentiate into the heterogeneous lineages of cancer cells. Recent evidence showed a higher effectiveness of C-ions and protons in inactivating CSCs, suggesting a potential advantage of Hadrontherapy compared with conventional radiotherapy for GBM treatment. To investigate the mechanisms involved in the molecular and cellular responses of CSCs to ionising radiations, two GBM stem cell (GSC) lines, named lines 1 and 83, which were derived from patients with different clinical outcomes and having different metabolic profiles (as shown by NMR spectroscopy), were irradiated with (137)Cs photons and with protons or C-ions of 62 MeV u(-1) in the dose range of 5-40 Gy. The biological effects investigated were: cell death, cell cycle progression, and DNA damage induction and repair. Preliminary results show a different response to ionising radiation between the two GSC lines for the different end points investigated. Further experiments are in progress to consolidate the data and to get more insights on the influence of radiation quality.
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, viale Regina Elena 299, Rome 00161, Italy ilaria.pecchia@iss.it.
authors.forename: I
authors.initials: I
authors.lastname: Pecchia
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, viale Regina Elena 299, Rome 00161, Italy Sez. Roma1-Gruppo collegato Sanità, INFN, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Dini
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ricci-Vitiani
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Biffoni
authors.affiliation: Sez. Roma1-Gruppo collegato Sanità, INFN, Rome, Italy ENEA-CASACCIA, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Balduzzi
authors.affiliation: Sez. Roma1-Gruppo collegato Sanità, INFN, Rome, Italy Museo storico della fisica e Centro Studi e Ricerche 'E. Fermi', Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Fratini
authors.affiliation: Sez. Roma1-Gruppo collegato Sanità, INFN, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Belli
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, viale Regina Elena 299, Rome 00161, Italy Sez. Roma1-Gruppo collegato Sanità, INFN, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Campa
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, viale Regina Elena 299, Rome 00161, Italy Sez. Roma1-Gruppo collegato Sanità, INFN, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Esposito
authors.affiliation: Laboratori Nazionali del Sud (LNS) - INFN, Catania, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cirrone
authors.affiliation: Laboratori Nazionali del Sud (LNS) - INFN, Catania, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Romano
authors.affiliation: Laboratori Nazionali del Sud (LNS) - INFN, Catania, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Stancampiano
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pelacchi
authors.affiliation: Department of Neurosurgery, Catholic University of Rome, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Pallini
authors.affiliation: Department of Technology and Health, Istituto Superiore di Sanità, viale Regina Elena 299, Rome 00161, Italy Sez. Roma1-Gruppo collegato Sanità, INFN, Rome, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Tabocchini
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002244:Carbon / Q000627:therapeutic use*; D002453:Cell Cycle / Q000528:radiation effects; D002588:Cesium Radioisotopes / Q000627:therapeutic use*; D004249:DNA Damage / Q000528:radiation effects; D005909:Glioblastoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D011379:Prognosis; D061766:Proton Therapy; D011839:Radiation, Ionizing; D011853:Radiobiology; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D002588:Cesium Radioisotopes; C468783:H2AX protein, human; D006657:Histones; D002244:Carbon