title: Schedule-dependent interaction between vinblastine and irradiation in experimental sarcoma.
abstract: OBJECTIVE
  Prolonged vinblastine (VLB) infusion and irradiation (IR) lead to favourable results in certain tumours types; however the underlying biological mechanisms of interaction are not well known. The aim of our study was to evaluate the dose- and time-dependent interactions between split-dose VLB treatment (mimicking prolonged infusion) and IR of sarcoma SA-1 tumours in A/J mice.
  
  
  METHODS
  Antitumor effectiveness of different VLB-IR schedules was determined by a tumour growth delay assay, the VLB amount in the tumours by liquid chromatography coupled to mass spectrometry and DNA cell cycle analysis.
  
  
  RESULTS
  A positive antitumor effect was obtained when tumours were irradiated immediately after the first (0 h) or second (4 h) injection of VLB treatment, despite the lower amount of VLB in the tumours as well as decreased number of cells in the IR-sensitive G2M phase at these times points as opposed to the second half of VLB split-dose scheduling.
  
  
  CONCLUSIONS
  Preferential binding of VLB to microtubules (with consequent lack of available VLB to bind to DNA where it acts as a radioprotector) and the absence of radiobiologically relevant hypoxia are presumably leading to the observed therapeutic benefit of applying IR at the beginning of the prolonged VLB infusion.
authors.affiliation: Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia, mcemazar@onko-i.si.
authors.forename: Maja
authors.initials: M
authors.lastname: Cemazar
authors.forename: Tanja
authors.initials: T
authors.lastname: Dolinsek
authors.forename: Tina
authors.initials: T
authors.lastname: Kosjek
authors.forename: Bostjan
authors.initials: B
authors.lastname: Markelc
authors.forename: Gregor
authors.initials: G
authors.lastname: Sersa
authors.forename: Veronika
authors.initials: V
authors.lastname: Kloboves
authors.forename: Primoz
authors.initials: P
authors.lastname: Strojan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy; D011836:Radiation Tolerance / Q000187:drug effects; D020266:Radiotherapy, Conformal / Q000379:methods; D012509:Sarcoma / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine