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- Title
Release of Interferon-β (IFN-β) from Probiotic Limosilactobacillus reuteri -IFN-β (LR-IFN-β) Mitigates Gastrointestinal Acute Radiation Syndrome (GI-ARS) following Whole Abdominal Irradiation.
- Authors
Hamade, Diala F.; Epperly, Michael W.; Fisher, Renee; Hou, Wen; Shields, Donna; van Pijkeren, Jan-Peter; Mukherjee, Amitava; Yu, Jian; Leibowitz, Brian J.; Vlad, Anda M.; Coffman, Lan; Wang, Hong; Huq, M. Saiful; Huang, Ziyu; Rogers, Claude J.; Greenberger, Joel S.
- Abstract
Simple Summary: The aim of our study was to assess the efficacy of a novel approach that combines whole abdomen irradiation (WAI) with genetically engineered Limosilactobacillus reuteri, known as Lactobacillus reuteri until recently, releasing interferon-beta (IFN-β; LR-IFN-β). We established that LR-IFN-β is a potent intestinal radioprotector and mitigator, and engineered bacteria are rapidly cleared from the digestive tract following WAI. The impact of our proposal is to improve the survival of ovarian cancer (OC) patients by adding WAI combined with other treatments as a possible treatment. We plan to further increase the survival and quality of life for OC patients. Irradiation can be an effective treatment for ovarian cancer, but its use is limited by intestinal toxicity. Thus, strategies to mitigate toxicity are important and can revitalize the current standard of care. We previously established that LR-IL-22 protects the intestine from WAI. We now hypothesize that LR-IFN-β is an effective radiation protector and mitigator and is rapidly cleared from the digestive tract, making it an option for intestinal radioprotection. We report that the gavage of LR-IFN-β during WAI provides improved intestinal barrier integrity and significantly preserves the numbers of Lgr5+GFP+ intestinal stem cells, improving survival. The rapid clearance of the genetically engineered probiotic from the digestive tract renders it a safe and feasible radiation mitigator. Therefore, the above genetically engineered probiotic is both a feasible and effective radiation mitigator that could potentially revolutionize the management of OC patients. Furthermore, the subsequent addition of platinum/taxane-based chemotherapy to the combination of WAI and LR-IFN-β should reduce tumor volume while protecting the intestine and should improve the overall survival in OC patients.
- Subjects
GASTROINTESTINAL disease prevention; OVARIAN tumors; GASTRIC intubation; CANCER chemotherapy; BACILLUS (Bacteria); INTERFERONS; PROBIOTICS; HYDROCARBONS; GENETIC engineering; STEM cells; RADIOTHERAPY; COMBINED modality therapy; OVERALL survival
- Publication
Cancers, 2023, Vol 15, Issue 6, p1670
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers15061670