This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tumor microcirculation and oxygenation play important roles in malignant progression and metastasis, as well as response to various therapies. This project investigates two types of cancer, glioblastoma multiform (GBM) and breast cancer. GBM is the most common and lethal intracranial cancer. These tumors are characterized by profound angiogenesis, disrupted blood-brain-barrier (BBB), vasogenic edema, as well as regions of hypoxia and necrosis, which have been shown to correlate negatively with local tumor control, disease free survival and overall survival. There is considerable anecdotal evidence that intra-tumoral hypoxia confers radiation resistance. However, in the absence of a reliable method of monitoring, in vivo, the dynamic intra-tumoral oxygen status, has remained untested in GBM. Similarly, in breast cancer we hypothesize that tumor hypoxia is major driving force for progression of breast cancer brain metastasis and represents a critical target for therapeutic strategies.
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