Histopathological Tumor and Normal Tissue Responses after 3D-Planned Arc Radiotherapy in an Orthotopic Xenograft Mouse Model of Human Pancreatic Cancer

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 orth...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sophie Dobiasch, Severin Kampfer, Katja Steiger, Daniela Schilling, Julius C. Fischer, Thomas E. Schmid, Wilko Weichert, Jan J. Wilkens, Stephanie E. Combs
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	image-guided high-precision radiation stereotactic irradiation histopathology pancreatic cancer preclinical tumor mouse model small-animal radiation research platform (SARRP) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5a3238eab5a04bdb99915378320bd913
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5a3238eab5a04bdb99915378320bd913
record_format	dspace
spelling	oai:doaj.org-article:5a3238eab5a04bdb99915378320bd9132021-11-25T17:02:18ZHistopathological Tumor and Normal Tissue Responses after 3D-Planned Arc Radiotherapy in an Orthotopic Xenograft Mouse Model of Human Pancreatic Cancer10.3390/cancers132256562072-6694https://doaj.org/article/5a3238eab5a04bdb99915378320bd9132021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5656https://doaj.org/toc/2072-6694Pancreatic 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.Sophie DobiaschSeverin KampferKatja SteigerDaniela SchillingJulius C. FischerThomas E. SchmidWilko WeichertJan J. WilkensStephanie E. CombsMDPI AGarticleimage-guided high-precision radiationstereotactic irradiationhistopathologypancreatic cancerpreclinical tumor mouse modelsmall-animal radiation research platform (SARRP)Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5656, p 5656 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	image-guided high-precision radiation stereotactic irradiation histopathology pancreatic cancer preclinical tumor mouse model small-animal radiation research platform (SARRP) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	image-guided high-precision radiation stereotactic irradiation histopathology pancreatic cancer preclinical tumor mouse model small-animal radiation research platform (SARRP) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Sophie Dobiasch Severin Kampfer Katja Steiger Daniela Schilling Julius C. Fischer Thomas E. Schmid Wilko Weichert Jan J. Wilkens Stephanie E. Combs Histopathological Tumor and Normal Tissue Responses after 3D-Planned Arc Radiotherapy in an Orthotopic Xenograft Mouse Model of Human Pancreatic Cancer
description	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.
format	article
author	Sophie Dobiasch Severin Kampfer Katja Steiger Daniela Schilling Julius C. Fischer Thomas E. Schmid Wilko Weichert Jan J. Wilkens Stephanie E. Combs
author_facet	Sophie Dobiasch Severin Kampfer Katja Steiger Daniela Schilling Julius C. Fischer Thomas E. Schmid Wilko Weichert Jan J. Wilkens Stephanie E. Combs
author_sort	Sophie Dobiasch
title	Histopathological Tumor and Normal Tissue Responses after 3D-Planned Arc Radiotherapy in an Orthotopic Xenograft Mouse Model of Human Pancreatic Cancer
title_short	Histopathological Tumor and Normal Tissue Responses after 3D-Planned Arc Radiotherapy in an Orthotopic Xenograft Mouse Model of Human Pancreatic Cancer
title_full	Histopathological Tumor and Normal Tissue Responses after 3D-Planned Arc Radiotherapy in an Orthotopic Xenograft Mouse Model of Human Pancreatic Cancer
title_fullStr	Histopathological Tumor and Normal Tissue Responses after 3D-Planned Arc Radiotherapy in an Orthotopic Xenograft Mouse Model of Human Pancreatic Cancer
title_full_unstemmed	Histopathological Tumor and Normal Tissue Responses after 3D-Planned Arc Radiotherapy in an Orthotopic Xenograft Mouse Model of Human Pancreatic Cancer
title_sort	histopathological tumor and normal tissue responses after 3d-planned arc radiotherapy in an orthotopic xenograft mouse model of human pancreatic cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5a3238eab5a04bdb99915378320bd913
work_keys_str_mv	AT sophiedobiasch histopathologicaltumorandnormaltissueresponsesafter3dplannedarcradiotherapyinanorthotopicxenograftmousemodelofhumanpancreaticcancer AT severinkampfer histopathologicaltumorandnormaltissueresponsesafter3dplannedarcradiotherapyinanorthotopicxenograftmousemodelofhumanpancreaticcancer AT katjasteiger histopathologicaltumorandnormaltissueresponsesafter3dplannedarcradiotherapyinanorthotopicxenograftmousemodelofhumanpancreaticcancer AT danielaschilling histopathologicaltumorandnormaltissueresponsesafter3dplannedarcradiotherapyinanorthotopicxenograftmousemodelofhumanpancreaticcancer AT juliuscfischer histopathologicaltumorandnormaltissueresponsesafter3dplannedarcradiotherapyinanorthotopicxenograftmousemodelofhumanpancreaticcancer AT thomaseschmid histopathologicaltumorandnormaltissueresponsesafter3dplannedarcradiotherapyinanorthotopicxenograftmousemodelofhumanpancreaticcancer AT wilkoweichert histopathologicaltumorandnormaltissueresponsesafter3dplannedarcradiotherapyinanorthotopicxenograftmousemodelofhumanpancreaticcancer AT janjwilkens histopathologicaltumorandnormaltissueresponsesafter3dplannedarcradiotherapyinanorthotopicxenograftmousemodelofhumanpancreaticcancer AT stephanieecombs histopathologicaltumorandnormaltissueresponsesafter3dplannedarcradiotherapyinanorthotopicxenograftmousemodelofhumanpancreaticcancer
_version_	1718412776407302144

Histopathological Tumor and Normal Tissue Responses after 3D-Planned Arc Radiotherapy in an Orthotopic Xenograft Mouse Model of Human Pancreatic Cancer

Ejemplares similares