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Single cell resolution in vivo imaging of DNA damage following PARP inhibition.
Yang, Katherine S; Kohler, Rainer H; Landon, Matthieu; Giedt, Randy; Weissleder, Ralph.
Afiliación
  • Yang KS; Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114.
  • Kohler RH; Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114.
  • Landon M; 1] Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114 [2] Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115.
  • Giedt R; Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114.
  • Weissleder R; 1] Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114 [2] Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115.
Sci Rep ; 5: 10129, 2015 May 18.
Article en En | MEDLINE | ID: mdl-25984718
Targeting DNA repair pathways is a powerful strategy to treat cancers. To gauge efficacy in vivo, typical response markers include late stage effects such as tumor shrinkage, progression free survival, or invasive repeat biopsies. These approaches are often difficult to answer critical questions such as how a given drug affects single cell populations as a function of dose and time, distance from microvessels or how drug concentration (pharmacokinetics) correlates with DNA damage (pharmacodynamics). Here, we established a single-cell in vivo pharmacodynamic imaging read-out based on a truncated 53BP1 double-strand break reporter to determine whether or not poly(ADP-ribose) polymerase (PARP) inhibitor treatment leads to accumulation of DNA damage. Using this reporter, we show that not all PARP inhibitor treated tumors incur an increase in DNA damage. The method provides a framework for single cell analysis of cancer therapeutics in vivo.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Poli(ADP-Ribosa) Polimerasas / Imagen Molecular / Inhibidores de Poli(ADP-Ribosa) Polimerasas Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño del ADN / Poli(ADP-Ribosa) Polimerasas / Imagen Molecular / Inhibidores de Poli(ADP-Ribosa) Polimerasas Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido