Abstract
The prognosis for patients with high-grade glioma remains dismal illustrating the need for the development of chemotherapeutic strategies intended to synergize with treatment modalities of proven efficacy such as radiation therapy
Highlights
In spite of extensive efforts, minimal improvements in the treatment Glioblastoma Multiforme (GBM) have been realized
Higher concentrations of Karenitecin ranging between 20–100nM resulted in a substantial reduction of the surviving fraction and radiosensitization experiments were performed with Karenitecin concentrations in a subtoxic range between 0.1-10nM
In the present study we demonstrate that the topoisomerase I (topo I) inhibitor Karenitecin is an effective radio sensitizer of T98G and MO59K glioma cell lines
Summary
In spite of extensive efforts, minimal improvements in the treatment Glioblastoma Multiforme (GBM) have been realized. Response rates as high as 15% have been reported, most studies have reported more modest results[9,10,11,12] Both in vitro and in vivo studies have demonstrated that Topotecan has radiosensitizing properties with a dose enhancement ratio of ≥2.0. The mechanism of the observed synergy between radiation and topotecan results from altered DNA lesion modification and enhanced apoptosis[5,13,14,15,16] This promising preclinical data was the basis for a phase II study performed by the Radiation Therapy Oncology Group in adult GBM evaluating daily Topotecan as a radiosensitizer[7]. The in vitro data presented in this report support the use Karenitecin has as a potential radiosensitizer in the treatment of grade 4 glioma
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