Abstract
Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC) xenografts in a nude rat model irradiation (2 + 2 Gy) from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.
Highlights
Lung cancer presenting in about 85% by non-small cell lung cancer (NSCLC) is the leading cause of death among human malignancies [1]
The ability to establish consistent human tumour xenografts in small animals is a crucial part of preclinical NSCLC therapy investigations [2], and whole body irradiation (WBI) serves as the classic method for experimentally inducing immunosuppression in rodents improving tumor take rates for human lung cancer models in nude mice [3, 4] and nude rats [5,6,7,8,9]
The presented results show that the conventional X-ray system could provide acceptable dose uniformity across rats of typical thicknesses by irradiation of animals (2 + 2 Gy) from opposite sides using a new cage which was created for irradiation of 2 rats at the same time
Summary
Lung cancer presenting in about 85% by non-small cell lung cancer (NSCLC) is the leading cause of death among human malignancies [1]. The ability to establish consistent human tumour xenografts in small animals is a crucial part of preclinical NSCLC therapy investigations [2], and whole body irradiation (WBI) serves as the classic method for experimentally inducing immunosuppression in rodents improving tumor take rates for human lung cancer models in nude mice [3, 4] and nude rats [5,6,7,8,9]. At the same time the size of rats causes an inhomogeneous distribution of radiation dose due to the absorption of X-rays within the animal’s body reducing the effectiveness of WBI for immunosuppression. In this paper a new design of WBI improving radiation mediated immunosuppression of rats is described and its application for the generation of human NSCLC xenografts in nude rat model is discussed. The principles of human tumour xenograft engraftment in the nude rat model illustrated here for NSCLC may be useful for research applications involving other types of human tumours
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