Acute Large Dose Irradiation Sensitizes Surviving Cells to Subsequent Irradiation; Implications for Stereotactic Body Radiation Therapy.

To determine if the radiation sensitivity of cells that survive acute high-dose radiation exposure used in stereotactic body radiation therapy (SBRT), differs from the sensitivity of non-irradiated cells and cells that survive multiple 2 Gy doses of radiation. Isogenic rodent and two human tumor cell lines were exposed to 14 × 2 Gy of radiation, or a single acute dose of 12 Gy. The most resistant cell line was also exposed to an acute dose of 15 Gy.

Absence of Tissue-Sparing Effects in Partial Proton FLASH Irradiation in Murine Intestine.

Ultra-high dose rate irradiation has been reported to protect normal tissues more than conventional dose rate irradiation. This tissue sparing has been termed the FLASH effect. We investigated the FLASH effect of proton irradiation on the intestine as well as the hypothesis that lymphocyte depletion is a cause of the FLASH effect.

Modeling the impact of tissue oxygen profiles and oxygen depletion parameter uncertainties on biological response and therapeutic benefit of FLASH.

Background: Ultra-high dose rate (FLASH) radiation has been reported to efficiently suppress tumor growth while sparing normal tissue; however, the mechanism of the differential tissue sparing effect is still not known. Oxygen has long been known to profoundly impact radiobiological responses, and radiolytic oxygen depletion has been considered to be a possible cause or contributor to the FLASH phenomenon.

Purpose: This work investigates the impact of tissue pO profiles, oxygen depletion per unit dose (g), and the oxygen concentration yielding half-maximum radiosensitization (the average of its maximum value and one) (k) in tumor and normal tissue.

Proton FLASH effects on mouse skin at different oxygen tensions.

. Irradiation at FLASH dose rates (>40 Gy s) has received great attention due to its reported normal tissue sparing effect. The FLASH effect was originally observed in electron irradiations but has since been shown to also occur with both photon and proton beams.

Combining losartan with radiotherapy increases tumor control and inhibits lung metastases from a HER2/neu-positive orthotopic breast cancer model.

Background: Patients with metastatic HER2/neu-positive (HER2/neu +) breast cancer (BC) often experience treatment resistance, disease recurrences and metastases. Thus, new approaches for improving the treatment of HER2/neu + BC to prevent metastatic dissemination are urgently needed. Our previous studies have shown that losartan, an angiotensin receptor blocker, increases tumor perfusion and decreases hypoxia in a number of tumor models.