title: Preclinical evaluation of radiosensitizing activity of Pluronic block copolymers.
abstract: OBJECTIVE
  Pluronic block copolymers are non-ionic surfactants with demonstrated sensitizing activity in chemotherapy and hyperthermia in various tumor cell lines. In the current study we investigated the potential activity of Pluronic as a radiosensitizing agent.
  
  
  METHODS
  As a possible mechanism, the effect of Pluronic on Hsp70 and Hsp90 was examined. Gli36 human glioma cells were treated with radiation alone as well as with a combination treatment of Pluronic and radiation.
  
  
  RESULTS
  Clonogenic cell survival assays show that Pluronic has an elevated effect on radiosensitization (50% high, p < 0.01), even with radiation doses as low as 2 Gy. The Hsp90 level was reduced 24 h after the combined treatment in both in vitro and in vivo. Similarly, Hsp70 levels were also decreased 24 h post treatment. When Gli36 cells were exposed to Pluronic before and during irradiation, DNA DSB: double-strand breaks repair was reduced, and elevated apoptosis was also seen in tumor xenografts.
  
  
  CONCLUSIONS
  Data suggest the potential use of L10 as a radiosensitizer. While the mechanism of sensitization requires additional investigation, the presented results indicate that the effect may be due, in part, to a decrease in Hsp90 and 70 levels and increased DNA damage.
authors: Department of Radiology, Case Western Reserve University , Cleveland, Ohio , USA.
authors: Reshani H
authors: RH
authors: Perera
authors: Ravi
authors: R
authors: Patel
authors: Hanping
authors: H
authors: Wu
authors: Mihika
authors: M
authors: Gangolli
authors: Bryan
authors: B
authors: Traughber
authors: Nancy
authors: N
authors: Oleinick
authors: Agata A
authors: AA
authors: Exner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D020442:Poloxamer / Q000737:chemistry* / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry* / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D011838:Radiation-Sensitizing Agents; D020442:Poloxamer
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