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Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats.
- Source :
-
Oncotarget [Oncotarget] 2015 Mar 20; Vol. 6 (8), pp. 5536-46. - Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Animals
Antineoplastic Agents administration & dosage
Brain Neoplasms metabolism
Brain Neoplasms pathology
Cell Hypoxia physiology
Clostridium growth & development
Clostridium metabolism
Clostridium Infections metabolism
Clostridium Infections microbiology
Clostridium Infections pathology
Female
Glioblastoma metabolism
Glioblastoma pathology
Humans
Rats
Rats, Inbred F344
Rats, Nude
Spores, Bacterial
Xenograft Model Antitumor Assays
Brain Neoplasms microbiology
Brain Neoplasms therapy
Clostridium physiology
Glioblastoma microbiology
Glioblastoma therapy
Injections, Intravenous veterinary
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 25849940
- Full Text :
- https://doi.org/10.18632/oncotarget.3627