Xianliang Shi, Jiangning Li, Anqiang Huang, Shaohua Song, Zaili Yang
Assessing the Outbreak Risk of Epidemics Using Fuzzy Evidential Reasoning
Risk analysis : an official publication of the Society for Risk Analysis
inhibitors dnapk sensitize cancers radiotherapy dnadamaging chemotherapies candidates clinical trials however degree dnapk inhibitors also sensitize normal tissues remains poorly characterized study compare tumor growth control normal tissue sensitization following dnapk inhibitors combination radiation etoposide fadu tumor xenografts implanted mice treated 10 15gy irradiation 3 100 mgkg azd7648 dosedependent increase time tumor volume doubling following azd7648 proportional increase toxicity scores overlying skin similar effects seen intestinal jejunum tongue fadu tumor xenografts mice assessed proliferation rates 35 days treatment etoposide 5gy whole body irradiation dnapk inhibitors azd7648 peposertib m3814 additional organs examined sensitivity dnapk inhibitor activity atmdeficient mice dnapk activity indicated surrogate marker h2ax inhibition observed heart brain pancreas thymus tongue salivary glands atmdeficient mice treated dnapk inhibitors relative radiation alone similar reductions also seen atmdeficient fadu tumor xenografts pdnapk h2ax staining could performed conclusions dnapk inhibitormediated sensitization radiation dnadamaging chemotherapy limited tumor tissues also extends normal tissues sustaining dna damage data useful interpretation sensitizing effects dna damage repair inhibitors therapeutic index showing greater cellkilling effects cancer cells crucial optimal clinical translation