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|Title:||Non-targeted radiation effects in esophageal adenocarcinomas|
|Abstract:||The primary aim of this thesis is to investigate non-targeted radiation effects (NTE) in cancer patients undergoing radiotherapy. One of the main NTE being studied was radiation- induced bystander effects (RIBE). A pre-existing research project was being conducted on esophageal adenocarcinoma cancer (EAC) patients at our local Juravinski Cancer Centre (JCC). High dose-rate (HDR) brachytherapy is a specific type of radiotherapy used to treat advanced stages of esophageal cancer. One study followed 15 esophageal cancer patients throughout their entire fractionated brachytherapy by using a number of sample based colony-forming assays. Another study investigated 60 esophageal cancer patients’ responses to a single exposure of brachytherapy by using a blood serum based colony-forming assay. The mechanisms underlying RIBE have remained elusive to date. Serotonin dependent mechanisms have been shown to have a role in radiation-induced bystander signaling and response pathways for human keratinocytes and breast cancer cells, but there are no previous studies investigating bystander effects in esophageal cancer. Overall thesis findings are summarized below: Q1:Are bystander effects produced in brachytherapy patients? Yes, they are produced in non-smokers Q2:Are they detectable in non-tumour samples such as blood and urine? Yes, best in blood samples Q3:Is serotonin involved in the mechanism in patient samples and EAC cells ? Serotonin was important in some patient samples but not in the two cell lines Q4:Do they persist during fractionated treatments? Yes, an adaptive response initiated in bystander cells Q5:Are available esophageal cell lines useful for studying bystander effects? Yes, EAC cells produce bystander signals ￼￼￼This thesis may contribute to the knowledge on bystander or even abscopal effects in radio- therapy. The investigations presented in this thesis motivates other research to identify the propagated soluble factors that promote radiation-induced signaling pathways in esophageal cancer, to develop risk based radiation exposure guidelines, and to develop clear bioassays and biomarkers for bystander effects.|
|Appears in Collections:||Open Access Dissertations and Theses|
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|Hanu_Christine_L_2016March_PhD.pdf||PhD Thesis||21.88 MB||Adobe PDF||View/Open|
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