The role of IDH1 mutated tumour cells in secondary glioblastomas: an evolutionary game theoretical view.

Recent advances in clinical medicine have elucidated two significantly different subtypes of glioblastoma which carry very different prognoses, both defined by mutations in isocitrate dehydrogenase-1 (IDH-1). The mechanistic consequences of this mutation have not yet been fully clarified, with conflicting opinions existing in the literature; however, IDH-1 mutation may be used as a surrogate marker to distinguish between primary and secondary glioblastoma multiforme (sGBM) from malignant progression of a lower grade glioma. We develop a mathematical model of IDH-1 mutated secondary glioblastoma using evolutionary game theory to investigate the interactions between four different phenotypic populations within the tumor: autonomous growth, invasive, glycolytic, and the hybrid invasive/glycolytic cells.

Magnetic resonance imaging characteristics of glioblastoma multiforme: implications for understanding glioma ontogeny.

Background: Identifying the origin of gliomas carries important implications for advancing the treatment of these recalcitrant tumors. Recent research promotes the hypothesis of a subventricular zone (SVZ) origin for the stemlike gliomagenic cells identified within human glioma specimens. However, conflicting evidence suggests that SVZ-like cells are not uniquely gliomagenic but this capacity may be shared by cycling progenitors distributed throughout the subcortical white matter (SCWM).

Prognostic significance of growth kinetics in newly diagnosed glioblastomas revealed by combining serial imaging with a novel biomathematical model.

Glioblastomas are the most aggressive primary brain tumors, characterized by their rapid proliferation and diffuse infiltration of the brain tissue. Survival patterns in patients with glioblastoma have been associated with a number of clinicopathologic factors including age and neurologic status, yet a significant quantitative link to in vivo growth kinetics of each glioma has remained elusive. Exploiting a recently developed tool for quantifying glioma net proliferation and invasion rates in individual patients using routinely available magnetic resonance images (MRI), we propose to link these patient-specific kinetic rates of biological aggressiveness to prognostic significance.

Quantitative metrics of net proliferation and invasion link biological aggressiveness assessed by MRI with hypoxia assessed by FMISO-PET in newly diagnosed glioblastomas.

Glioblastoma multiforme (GBM) are aggressive and uniformly fatal primary brain tumors characterized by their diffuse invasion of the normal-appearing parenchyma peripheral to the clinical imaging abnormality. Hypoxia, a hallmark of aggressive tumor behavior often noted in GBMs, has been associated with resistance to therapy, poorer survival, and more malignant tumor phenotypes. Based on the existence of a set of novel imaging techniques and modeling tools, our objective was to assess a hypothesized quantitative link between tumor growth kinetics [assessed via mathematical models and routine magnetic resonance imaging (MRI)] and the hypoxic burden of the tumor [assessed via positron emission tomography (PET) imaging].