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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10046795 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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