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Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats

Glioblastoma (GBM) is a highly aggressive primary brain tumor that is especially difficult to treat. The tumor's ability to withstand hypoxia leads to enhanced cancer cell survival and therapy resistance, but also yields a microenvironment that is in many aspects unique within the human body, t...

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Autores principales: Staedtke, Verena, Bai, Ren-Yuan, Sun, Weiyun, Huang, Judy, Kibler, Kathleen Kazuko, Tyler, Betty M., Gallia, Gary L., Kinzler, Kenneth, Vogelstein, Bert, Zhou, Shibin, Riggins, Gregory J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467385/
https://www.ncbi.nlm.nih.gov/pubmed/25849940
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author Staedtke, Verena
Bai, Ren-Yuan
Sun, Weiyun
Huang, Judy
Kibler, Kathleen Kazuko
Tyler, Betty M.
Gallia, Gary L.
Kinzler, Kenneth
Vogelstein, Bert
Zhou, Shibin
Riggins, Gregory J.
author_facet Staedtke, Verena
Bai, Ren-Yuan
Sun, Weiyun
Huang, Judy
Kibler, Kathleen Kazuko
Tyler, Betty M.
Gallia, Gary L.
Kinzler, Kenneth
Vogelstein, Bert
Zhou, Shibin
Riggins, Gregory J.
author_sort Staedtke, Verena
collection PubMed
description Glioblastoma (GBM) is a highly aggressive primary brain tumor that is especially difficult to treat. The tumor's ability to withstand hypoxia leads to enhanced cancer cell survival and therapy resistance, but also yields a microenvironment that is in many aspects unique within the human body, thus offering potential therapeutic opportunities. The spore-forming anaerobic bacterium Clostridium novyi-NT(C. novyi-NT) has the ability to propagate in tumor-generated hypoxia, leading to oncolysis. Here, we show that intravenously injected spores of C. novyi-NT led to dramatic tumor destructions and significant survival increases in implanted, intracranial syngeneic F98 and human xenograft 060919 rat GBM models. C. novyi-NT germination was specific and confined to the neoplasm, with sparing of the normal brain parenchyma. All animals tolerated the bacteriolytic treatment, but edema and increased intracranial pressure could quickly be lethal if not monitored and medically managed with hydration and antibiotics. These results provide pre-clinical data supporting the development of this therapeutic approach for the treatment of patients with GBM.
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spelling pubmed-44673852015-06-22 Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats Staedtke, Verena Bai, Ren-Yuan Sun, Weiyun Huang, Judy Kibler, Kathleen Kazuko Tyler, Betty M. Gallia, Gary L. Kinzler, Kenneth Vogelstein, Bert Zhou, Shibin Riggins, Gregory J. Oncotarget Priority Research Paper Glioblastoma (GBM) is a highly aggressive primary brain tumor that is especially difficult to treat. The tumor's ability to withstand hypoxia leads to enhanced cancer cell survival and therapy resistance, but also yields a microenvironment that is in many aspects unique within the human body, thus offering potential therapeutic opportunities. The spore-forming anaerobic bacterium Clostridium novyi-NT(C. novyi-NT) has the ability to propagate in tumor-generated hypoxia, leading to oncolysis. Here, we show that intravenously injected spores of C. novyi-NT led to dramatic tumor destructions and significant survival increases in implanted, intracranial syngeneic F98 and human xenograft 060919 rat GBM models. C. novyi-NT germination was specific and confined to the neoplasm, with sparing of the normal brain parenchyma. All animals tolerated the bacteriolytic treatment, but edema and increased intracranial pressure could quickly be lethal if not monitored and medically managed with hydration and antibiotics. These results provide pre-clinical data supporting the development of this therapeutic approach for the treatment of patients with GBM. Impact Journals LLC 2015-03-18 /pmc/articles/PMC4467385/ /pubmed/25849940 Text en Copyright: © 2015 Staedtke et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Priority Research Paper
Staedtke, Verena
Bai, Ren-Yuan
Sun, Weiyun
Huang, Judy
Kibler, Kathleen Kazuko
Tyler, Betty M.
Gallia, Gary L.
Kinzler, Kenneth
Vogelstein, Bert
Zhou, Shibin
Riggins, Gregory J.
Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats
title Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats
title_full Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats
title_fullStr Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats
title_full_unstemmed Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats
title_short Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats
title_sort clostridium novyi-nt can cause regression of orthotopically implanted glioblastomas in rats
topic Priority Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467385/
https://www.ncbi.nlm.nih.gov/pubmed/25849940
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