The development of drug resistance is a nearly universal phenomenon in patients with glioblastoma multiforme (GBM) brain tumors. Upon treatment, GBM cancer cells may initially undergo a drug-induced cell-state change to a drug-tolerant, slow-cycling state. The kinetics of that process are not well understood, in part due to the heterogeneity of GBM tumors and tumor models, which can confound the interpretation of kinetic data. Here, we resolve drug-adaptation kinetics in a patient-derived in vitro GBM tumor model characterized by the epithelial growth factor receptor (EGFR) variant(v)III oncogene treated with an EGFR inhibitor. We use radiolabeled 18F-fluorodeoxyglucose (FDG) to monitor the glucose uptake trajectories of single GBM cancer cells over a 12 h period of drug treatment. Autocorrelation analysis of the single-cell glucose uptake trajectories reveals evidence of a drug-induced cell-state change from a high- to low-glycolytic phenotype after 5-7 h of drug treatment. Information theoretic analysis of a bulk transcriptome kinetic series of the GBM tumor model delineated the underlying molecular mechanisms driving the cellular state change, including a shift from a stem-like mesenchymal state to a more differentiated, slow-cycling astrocyte-like state. Our results demonstrate that complex drug-induced cancer cell-state changes of cancer cells can be captured via measurements of single cell metabolic trajectories and reveal the extremely facile nature of drug adaptation.
There is a rapidly growing interest by resource managers to utilize environmental DNA technology (eDNA) as a tool to enhance current management efforts. However, the technology remains relatively specialized, since it requires specific expertise and equipment to perform. To begin to overcome some of the obstacles restricting the widespread, routine adoption of eDNA technology, we evaluated the use of CRISPR Cas12a detection technology for in-the-field eDNA detection using Chinook salmon (Oncorhynchus tshawytscha) as a target species. By targeting a highly variable region in the salmonid mitochondrial DNA D-loop, we were able to demonstrate that CRISPR Cas12a detection technology is both sensitive and specific for Chinook salmon eDNA. Engineering of the technology to work in the field was accomplished by employing rapid eDNA purification and visual readout of results using visual lateral flow or fluorescent detection methods. The technology was piloted on the fall Chinook salmon run in the Snake River of Washington State, USA, and proved to be a viable approach for streamside eDNA monitoring. With the improvement of the technology, CRISPR eDNA detection methods hold great promise in expanding the reach of eDNA as a commonly used resource management tool.
Supplementary Figures 1-4 from <sup>18</sup>F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers
Supplementary Figures 1-4 from 18F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers
Supplementary Figures 1-4 from <sup>18</sup>F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers
Supplementary Video legend from Integrated Microfluidic and Imaging Platform for a Kinase Activity Radioassay to Analyze Minute Patient Cancer Samples
Supplementary Methods, Figures 1-14 from A Microfluidic Platform for Systems Pathology: Multiparameter Single-Cell Signaling Measurements of Clinical Brain Tumor Specimens
Johannes Czernin合作论文数178
Jorge Barrio合作论文数Department of Molecular and Medical Pharmacology, University of California Los Angeles;Jonsson Comprehensive Cancer Center, University of California Los Angeles149Nagichettiar Satyamurthy合作论文数110
Heinrich R. Schelbert合作论文数Department of Molecular and Medical Pharmacology, University of California Los Angeles86
John Mazziotta合作论文数Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California;Brain Mapping Center, University of California, Los Angeles53David E. Kuhl合作论文数52P. Ehrens合作论文数52G. Billingsley合作论文数46
Gary W. Small合作论文数David Geffen School of Medicine at UCLASemel Institute for Neuroscience and Human45Evan Ochsner合作论文数43Adam J. Mullavey合作论文数Australian National University40
Michael L. Gorodetsky合作论文数Faculty of Physics, Lomonosov Moscow State University/Russian Quantum Center40M. Pedraza合作论文数LIGO - California Institute of Technology39
Anamaria Effler合作论文数LIGO Livingston;California Institute of Technology39M Barsuglia合作论文数38
Michal Was合作论文数37Randall A. Hawkins合作论文数36Edward J. Hoffman合作论文数36T. Nash合作论文数LIGO - California Institute of Technology34S. Rowan合作论文数34
Stanislav Babak合作论文数Astroparticule et Cosmologie33R. Cavalieri合作论文数32Patrick R. Brady合作论文数31
Carlo Nicola Colacino合作论文数Ministero dell'Istruzione, Università e Ricerca31
Simon R. Cherry合作论文数Department of Biomedical Engineering, College of Engineering, University of California, Davis30
Magnus Dahlbom合作论文数University of California29
Harvey R. Herschman合作论文数Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles28Belynda Abbott合作论文数28E. Maros合作论文数28
Rana Adhikari合作论文数Department of Applied Physics and Materials Science, Division of Engineering and Applied Science, California Institute of Technology28
J. D. E. Creighton合作论文数Dept . of Physics;University of Waterloo;Dept . of Physics, University of Waterloo28M. Araya合作论文数28M. Mageswaran合作论文数LIGO-California Institute of Technology28Christiaan Schiepers合作论文数28
David H. Reitze合作论文数Laser Interferometer Gravitational-wave Observatory Laboratory, California Institute of Technology;The Division of Physics, Mathematics and Astronomy, California Institute of Technology28
Lutz Winkelmann合作论文数Max-Planck-Institut für Gravitationsphysik, Albert-Einstein-Institut28Daniel H. S. Silverman合作论文数28E. K. Gustafson合作论文数28
Ronald W. P. Drever合作论文数California Institute of Technology27
Jameson Rollins合作论文数The Division of Physics, Mathematics and Astronomy, California Institute of Technology27P. J. King合作论文数27Lu Wen合作论文数26
K. Mailand合作论文数University of Glasgow26
