Neuroimaging plays a critical role in the management of patients with gliomas. While conventional magnetic resonance imaging (MRI) remains the standard imaging modality, it is frequently insufficient to inform clinical decision‐making. There is a need for noninvasive strategies for reliably distinguishing low‐grade from high‐grade gliomas, identifying important molecular features of glioma, choosing an appropriate target for biopsy, delineating target area for surgery or radiosurgery, and distinguishing tumor progression (TP) from pseudoprogression (PsP). One recent advance is the identification of the T2/fluid‐attenuated inversion recovery mismatch sign on standard MRI to identify isocitrate dehydrogenase mutant astrocytomas. However, to meet other challenges, neuro‐oncologists are increasingly turning to advanced imaging modalities. Diffusion‐weighted imaging modalities including diffusion tensor imaging and diffusion kurtosis imaging can be helpful in delineating tumor margins and better visualization of tissue architecture. Perfusion imaging including dynamic contrast‐enhanced MRI using gadolinium or ferumoxytol contrast agents can be helpful for grading as well as distinguishing TP from PsP. Positron emission tomography is useful for measuring tumor metabolism, which correlates with grade and can distinguish TP/PsP in the right setting. Magnetic resonance spectroscopy can identify tissue by its chemical composition, can distinguish TP/PsP, and can identify molecular features like 2‐hydroxyglutarate. Finally, amide proton transfer imaging measures intracellular protein content, which can be used to identify tumor grade/progression and distinguish TP/PsP.
Activation of cannabinoid 1 receptors (CB1R) modulates multiple behaviours, including exploration, motor coordination and response to psychostimulants. It is known that CB1R expressed by either excitatory or inhibitory neurons mediates different behavioural responses to CB1R activation, yet the involvement of CB1R expressed by medium spiny neurons (MSNs), the neuronal subpopulation that expresses the highest level of CB1R in the CNS, remains unknown. We report a new genetically modified mouse line that expresses functional CB1R in MSN on a CB1R knockout (KO) background (CB1R(MSN) mice). The absence of cannabimimetic responses measured in CB1R KO mice was not rescued in CB1R(MSN) mice, nor was decreased spontaneous locomotion, impaired instrumental behaviour or reduced amphetamine‐triggered hyperlocomotion measured in CB1R KO mice. Significantly, reduced novel environment exploration of an open field and absence of amphetamine sensitization (AS) measured in CB1R KO mice were fully rescued in CB1R(MSN) mice. Impaired motor coordination in CB1R KO mice measured on the Rotarod was partially rescued in CB1R(MSN) mice. Thus, CB1R expressed by MSN control exploration, motor coordination, and AS. Our study demonstrates a new functional roles for cell specific CB1R expression and their causal link in the control of specific behaviors.
Glioblastoma (GBM) is an intrinsically treatment-resistant tumor and has been shown to upregulate DNA damage response (DDR) components after treatment. DNA damage response signaling mediates treatment resistance by promoting cell cycle arrest in order to allow for DNA damage repair and avoid mitotic catastrophe. Therefore, targeting the DDR pathway is an attractive strategy to combat treatment resistance in GBM. In this review, we discuss the different DDR pathways and then summarize the current preclinical evidence for DDR inhibitors in GBM, as well as completed and ongoing clinical trials.
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