Image-guided radiotherapy platform using single nodule conditional lung cancer mouse models.

Autor:	Herter-Sprie GS; 1] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [3] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA., Korideck H; Division of Medical Physics and Biophysics, Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA., Christensen CL; 1] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [3] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA., Herter JM; Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA., Rhee K; 1] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [3] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA., Berbeco RI; Division of Medical Physics and Biophysics, Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA., Bennett DG; Department of Radiology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA., Akbay EA; 1] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [3] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA., Kozono D; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA., Mak RH; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA., Mike Makrigiorgos G; Division of Medical Physics and Biophysics, Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA., Kimmelman AC; Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215, USA., Wong KK; 1] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [3] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2014 Dec 18; Vol. 5, pp. 5870. Date of Electronic Publication: 2014 Dec 18.
DOI:	10.1038/ncomms6870
Abstrakt:	Close resemblance of murine and human trials is essential to achieve the best predictive value of animal-based translational cancer research. Kras-driven genetically engineered mouse models of non-small-cell lung cancer faithfully predict the response of human lung cancers to systemic chemotherapy. Owing to development of multifocal disease, however, these models have not been usable in studies of outcomes following focal radiotherapy (RT). We report the development of a preclinical platform to deliver state-of-the-art image-guided RT in these models. Presence of a single tumour as usually diagnosed in patients is modelled by confined injection of adenoviral Cre recombinase. Furthermore, three-dimensional conformal planning and state-of-the-art image-guided dose delivery are performed as in humans. We evaluate treatment efficacies of two different radiation regimens and find that Kras-driven tumours can temporarily be stabilized upon RT, whereas additional loss of either Lkb1 or p53 renders these lesions less responsive to RT.
Databáze:	MEDLINE
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