A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets - Nature Cancer

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A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets - Nature Cancer
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Rethinking how cancer cells evade targeted therapy ucsf naturecancer

, the rationale for doing these studies is strong. The resource generated by this study broadly informs disparate aspects of glioma biology. Further work will be required to functionally test many of the hypotheses generated from this atlas.Study protocols and sample use were approved by the University of California, San Francisco Institutional Review Board. All clinical samples were analyzed in a de-identified fashion.

For WNT3A inhibition endo-IWR 1 was used. This is a small molecule inhibitor of Axin turnover resulting in stabilization of the β-catenin and suppression of Wnt signal transduction. The diastereomeric form of IWR 1, exo-IWR 1, which exhibits decreased Axin stabilizing activity compared to endo-IWR 1 was used as a control.Cell we seeded at a density of 600 cells per well in the middle wells of six-well plates that were coated with 2% Cultrex TM BME .

. Endpoints were determined by weight loss and neurological symptoms. Upon euthanasia, brain tumors were quickly dissected after perfusion and snap frozen in liquid nitrogen, then stored at −80 °C before use.For the ST assay, FFPE tissue blocks were reviewed for tumor purity and ten 5-µm sections were cut by the UCSF Neurosurgery Tissue Core.

Similarly, for the SP assay, FFPE tissue blocks were reviewed for tumor purity and six 5-µm sections were cut by the UCSF Neurosurgery Tissue Core. Slides were baked at 37 °C overnight, deparaffinized, rehydrated, antigen-retrieved in a pressure cooker for 15 min at 100 °C at high pressure.

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