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Dobiasch, S. ; Kampfer, S.* ; Steiger, K.* ; Schilling, D. ; Fischer, J.C.* ; Schmid, T.E. ; Weichert, W.* ; Wilkens, J.J. ; Combs, S.E.

Histopathological tumor and normal tissue responses after 3d-planned arc radiotherapy in an orthotopic xenograft mouse model of human pancreatic cancer.

Cancers 13:5656 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers. Innovative treatment concepts may enhance oncological outcome. Clinically relevant tumor models are essential in developing new therapeutic strategies. In the present study, we used two human PDAC cell lines for an orthotopic xenograft mouse model and compared treatment characteristics between this in vivo tumor model and PDAC patients. Tumor-bearing mice received stereotactic high-precision irradiation using arc technique after 3D-treatment planning. Induction of DNA damage in tumors and organs at risk (OARs) was histopathologically analyzed by the DNA damage marker γH2AX and compared with results after unprecise whole-abdomen irradiation. Our mouse model and preclinical setup reflect the characteristics of PDAC patients and clinical RT. It was feasible to perform stereotactic high-precision RT after defining tumor and OARs by CT imaging. After stereotactic RT, a high rate of DNA damage was mainly observed in the tumor but not in OARs. The calculated dose distributions and the extent of the irradiation field correlate with histopathological staining and the clinical example. We established and validated 3D-planned stereotactic RT in an orthotopic PDAC mouse model, which reflects the human RT. The efficacy of the whole workflow of imaging, treatment planning, and high-precision RT was proven by longitudinal analysis showing a significant improved survival. Importantly, this model can be used to analyze tumor regression and therapy-related toxicity in one model and will allow drawing clinically relevant conclusions.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Histopathology ; Image-guided High-precision Radiation ; Pancreatic Cancer ; Preclinical Tumor Mouse Model ; Small-animal Radiation Research Platform (sarrp) ; Stereotactic Irradiation ; Survival After High-precision Irradiation ; Translational Research; Body Radiation-therapy
ISSN (print) / ISBN 2072-6694
Zeitschrift Cancers
Quellenangaben Band: 13, Heft: 22, Seiten: , Artikelnummer: 5656 Supplement: ,
Verlag MDPI
Verlagsort St Alban-anlage 66, Ch-4052 Basel, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Medicine (IRM)
Förderungen Deutsche Forschungsgemeinschaft (DFG, German Research foundation)