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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

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 L...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046795/
https://www.ncbi.nlm.nih.gov/pubmed/36980556
http://dx.doi.org/10.3390/cancers15061670
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author 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.
author_facet 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.
author_sort Hamade, Diala F.
collection PubMed
description 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. ABSTRACT: 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.
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spelling pubmed-100467952023-03-29 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 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. Cancers (Basel) Article 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. ABSTRACT: 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. MDPI 2023-03-08 /pmc/articles/PMC10046795/ /pubmed/36980556 http://dx.doi.org/10.3390/cancers15061670 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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.
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046795/
https://www.ncbi.nlm.nih.gov/pubmed/36980556
http://dx.doi.org/10.3390/cancers15061670
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