The sensitivity of normal tissues in our body to radiation damage prevents physicians from delivering high enough doses of radiation to cure patents of their cancer. If we had a way to protect our small intestines from the side-effects of radiation, physicians could use higher doses to eradicate tumors within the abdomen or pelvis, including pancreatic cancer. We showed that short-term fasting of mice confers radioprotection to cells in the small intestine and we demonstrated that the ability of fasting to reduce intestinal radiotoxicity enabled us to expose mice with pancreatic cancer to high doses of radiation, which delayed tumor growth and prolonged survival. Experiments in this proposa...

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The sensitivity of normal tissues in our body to radiation damage prevents physicians from delivering high enough doses of radiation to cure patents of their cancer. If we had a way to protect our small intestines from the side-effects of radiation, physicians could use higher doses to eradicate tumors within the abdomen or pelvis, including pancreatic cancer. We showed that short-term fasting of mice confers radioprotection to cells in the small intestine and we demonstrated that the ability of fasting to reduce intestinal radiotoxicity enabled us to expose mice with pancreatic cancer to high doses of radiation, which delayed tumor growth and prolonged survival. Experiments in this proposal are aimed at determining how fasting protects cells in the small intestine from being killed by high dose radiation. Importantly, we showed that fasting causes certain bacteria in the small intestines of mice to increase and these bacteria make products that have the potential of communicating with cells in the small intestine to change what these cells express. We propose experiments to test if the bacterial changes induced by fasting are able to protect cells in the small intestines as well as the animal from the lethal effects of high dose radiation. If successful, our findings could lead to dose escalation strategies for improved clinical outcomes without the need for patients to fast and fewer side-effects and higher quality of life for cancer patients.

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