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A living ex vivo platform for functional, personalized brain cancer diagnosis.
Mann, Breanna; Zhang, Xiaopei; Bell, Noah; Adefolaju, Adebimpe; Thang, Morrent; Dasari, Rajaneekar; Kanchi, Krishna; Valdivia, Alain; Yang, Yang; Buckley, Andrew; Lettry, Vivien; Quinsey, Carolyn; Rauf, Yasmeen; Kram, David; Cassidy, Noah; Vaziri, Cyrus; Corcoran, David L; Rego, Stephen; Jiang, Yuchao; Graves, Lee M; Dunn, Denise; Floyd, Scott; Baldwin, Albert; Hingtgen, Shawn; Satterlee, Andrew B.
Afiliación
  • Mann B; Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Zhang X; Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Bell N; Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Adefolaju A; Eshelman Institute for Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Thang M; Department of Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Dasari R; Eshelman Institute for Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Kanchi K; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Valdivia A; Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Yang Y; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Buckley A; Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Lettry V; Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Quinsey C; Department of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Rauf Y; Department of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Kram D; Division of Pediatric Hematology-Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Cassidy N; School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Vaziri C; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Corcoran DL; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Rego S; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Jiang Y; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Graves LM; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Dunn D; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
  • Floyd S; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
  • Baldwin A; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Hingtgen S; Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: hingtgen@email.unc.edu.
  • Satterlee AB; Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman Institute for Innovation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: satterle@email.unc.ed
Cell Rep Med ; 4(6): 101042, 2023 06 20.
Article en En | MEDLINE | ID: mdl-37192626
ABSTRACT
Functional precision medicine platforms are emerging as promising strategies to improve pre-clinical drug testing and guide clinical decisions. We have developed an organotypic brain slice culture (OBSC)-based platform and multi-parametric algorithm that enable rapid engraftment, treatment, and analysis of uncultured patient brain tumor tissue and patient-derived cell lines. The platform has supported engraftment of every patient tumor tested to this point high- and low-grade adult and pediatric tumor tissue rapidly establishes on OBSCs among endogenous astrocytes and microglia while maintaining the tumor's original DNA profile. Our algorithm calculates dose-response relationships of both tumor kill and OBSC toxicity, generating summarized drug sensitivity scores on the basis of therapeutic window and allowing us to normalize response profiles across a panel of U.S. Food and Drug Administration (FDA)-approved and exploratory agents. Summarized patient tumor scores after OBSC treatment show positive associations to clinical outcomes, suggesting that the OBSC platform can provide rapid, accurate, functional testing to ultimately guide patient care.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Encefálicas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Child / Humans Idioma: En Revista: Cell Rep Med Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Encefálicas Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Child / Humans Idioma: En Revista: Cell Rep Med Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos