Summary: | 碩士 === 中國醫藥大學 === 臨床醫學研究所碩士班 === 99 === Hypoxia is a common characteristic of solid tumors. It contributes to local and systemic tumor progression, as well as the lack of response to radio and chemotherapy, therefore increasing the probability of tumor recurrence. Tumor hypoxia has been classified into two models. Acute, intermittent or cycling hypoxia is associated with inadequate blood flow while chronic hypoxia is the consequence of the increased oxygen diffusion distance due to tumor expansion. It has known for many years that hypoxia renders cells to become more chemoresistance. However, these studies focused mainly on the effects of chronic hypoxia on drug resistance. Only a few results derived from in vitro studies demonstrated that the possibility of death-resistant cell selection by the repetition of hypoxia episodes. Such selected cells were shown to be resistant to cell death induced by different types of cytotoxicity drugs, such as azide, cisplatin and staurosporine. However, the lack of direct evidence from in vivo tumor microenvironment is a significant impediment for supporting this notion. Furthermore, some of the recent results suggest that some differences in mechanisms and phenotypes can be seen between chronic hypoxia and cycling hypoxia in tumor progression. Therefore, the biosignatures and mechanisms of cycling hypoxia-mediated tumor progression are interesting for oncologist and biologist. However, the lack of technologies for translational imaging of the dynamics and spatial heterogeneity of cycling hypoxic area in vivo is a significant impediment for such studies. In our study, we develop the magnetic resonance imaging(MRI) based-translational imaging platform for monitoring the dynamics and spatial characteristics of cycling hypoxia within tumors in living subjects. Furthermore we also explore the biosignatures of cycling hypoxia-mediated tumor progression in glioma.
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