In Vitro Methods for the Study of Glioblastoma Stem-Like Cell Radiosensitivity.

Ionizing radiation is a critical component of glioblastoma (GBM) therapy. Recent data have implicated glioblastoma stem-like cells (GSCs) as determinants of GBM development, maintenance, and treatment response. Understanding the response of GSCs to radiation should thus provide insight into the development of improved GBM treatment strategies.

Detection of glioblastoma intratumor heterogeneity in radiosensitivity using patient-derived neurosphere cultures.

Purpose: Glioblastoma (GBM) is characterized by extensive clonal diversity suggesting the presence of tumor cells with varying degrees of treatment sensitivity. Radiotherapy is an integral part of glioblastoma treatment. Whether GBMs are comprised of spatially distinct cellular populations with uniform or varying degrees of radiosensitivity has not been established.

53BP1 Repair Kinetics for Prediction of In Vivo Radiation Susceptibility in 15 Mouse Strains.

We present a novel mathematical formalism to predict the kinetics of DNA damage repair after exposure to both low- and high-LET radiation (X rays; 350 MeV/n 40Ar; 600 MeV/n 56Fe). Our method is based on monitoring DNA damage repair protein 53BP1 that forms radiation-induced foci (RIF) at locations of DNA double-strand breaks (DSB) in the nucleus and comparing its expression in primary skin fibroblasts isolated from 15 mice strains. We previously reported strong evidence for clustering of nearby DSB into single repair units as opposed to the classic "contact-first" model where DSB are considered immobile.

The Olfactory Bulb Provides a Radioresistant Niche for Glioblastoma Cells.

Purpose: The various microenvironments that exist within the brain combined with the invasive nature of glioblastoma (GBM) creates the potential for a topographic influence on tumor cell radiosensitivity. The aim of this study was to determine whether specific brain microenvironments differentially influence tumor cell radioresponse.

Methods And Materials: GBM stem-like cells were implanted into the right striatum of nude mice.