0000000000707886
AUTHOR
Ivana Dokic
High resistance to X-rays and therapeutic carbon ions in glioblastoma cells bearing dysfunctional ATM associates with intrinsic chromosomal instability
To investigate chromosomal instability and radiation response mechanisms in glioblastoma cells.We undertook a comparative analysis of two patient-derived glioblastoma cell lines. Their resistance to low and high linear energy transfer (LET) radiation was assessed using clonogenic survival assay and their intrinsic chromosome instability status using fluorescence in situ hybridization. DNA damage was analyzed by pulsed-field gel electrophoresis and by γ-H2AX foci quantification. Expression of DNA damage response proteins was assessed by immunoblot.Increased radioresistance to X-rays as well as carbon ions was observed in glioblastoma cells exhibiting high levels of naturally occurring chromo…
Glutathione peroxidase 1 activity dictates the sensitivity of glioblastoma cells to oxidative stress.
The high intratumoral and intertumoral heterogeneity of glioblastoma (GBM) leads to resistance to different therapies, and hence, selecting an effective therapy is very challenging. We hypothesized that the antioxidant enzyme status is a significant feature of GBM heterogeneity. The most important reactive oxygen/nitrogen species (ROS/RNS) detoxification mechanisms include superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx). Expression and activity of these enzymes and the cellular response to induced oxidative stress were systematically analyzed and compared between GBM cells and nontransformed glial cells of both human and murine origin. Regardless of cell type or speci…
Comparative analysis of the effects of a sphingosine kinase inhibitor to temozolomide and radiation treatment on glioblastoma cell lines.
ABSTRACT Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell heterogeneity. Accordingly, there is a need to target alternative molecules enhancing specific GBM autocrine or paracrine mechanisms and amplifying the effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid target molecule with an important role in cell invasion and proliferation. Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased production of reactive oxygen species (ROS), which may potentiate radiation cytotoxicity. We analyzed the effect of SKI singular versus combined treat…