title: In vitro evaluation of photon and carbon ion radiotherapy in combination with chemotherapy in glioblastoma cells.
abstract: BACKGROUND
  To evaluate the cytotoxic effect of carbon ion radiotherapy and chemotherapy in glioblastoma cells in vitro.
  
  
  METHODS
  The human glioblastoma (GBM) cell line U87 was irradiated with photon radiotherapy (RT) doses of 2 Gy, 4 Gy and 6 Gy. Likewise, irradiation with carbon ions was performed with single carbon doses of 0.125, 0.5, 2 and 3 Gy. Four chemotherapeutic substances, camptothecin, gemcitabine, paclitaxel and cisplatinum, were used for single and combination experiments. The assessment of the effect of single and double treatment on cell viability was performed using the clonogenic growth assay representing the radiobiological gold standard.
  
  
  RESULTS
  The RBE of carbon ions ranges between 3.3 and 3.9 depending on survival level and dose. All chemotherapeutic substances showed a clear does-response relationhips. in their characteristic concentrations. For subsequent combination experiments, two dose levels leading to low and medium reduction of cell survival were chosen. Combination experiments showed additive effects independently of the drugs' mechanisms of action. Paclitaxel and campthothecin demonstrated the most prominent cytotoxic effect in combination with carbon ion radiotherapy.
  
  
  CONCLUSIONS
  In conclusion, combination of carbon ion radiotherapy with chemotherapies of different mechanisms of action demonstrates additive effects. The most dominant effect was produced by paclitaxel, followed by camptothecin, as espected from previously published work. The present data serve as an important radiobiological basis for further combination experiments, as well as clinical studies on combination treatments.
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. stephanie.combs@med.uni-heidelberg.de
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Combs
authors.forename: Lisa
authors.initials: L
authors.lastname: Zipp
authors.forename: Stefan
authors.initials: S
authors.lastname: Rieken
authors.forename: Daniel
authors.initials: D
authors.lastname: Habermehl
authors.forename: Stefan
authors.initials: S
authors.lastname: Brons
authors.forename: Marcus
authors.initials: M
authors.lastname: Winter
authors.forename: Thomas
authors.initials: T
authors.lastname: Haberer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
authors.forename: Klaus-Josef
authors.initials: KJ
authors.lastname: Weber
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002166:Camptothecin / Q000008:administration & dosage; D002244:Carbon / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004307:Dose-Response Relationship, Radiation; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D066298:In Vitro Techniques; D017239:Paclitaxel / Q000008:administration & dosage; D017785:Photons / Q000627:therapeutic use*; D014410:Tumor Stem Cell Assay; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002244:Carbon; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin; D000093542:Gemcitabine