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Reovirus as an experimental therapeutic for brain and leptomeningeal metastases from breast cancer
- Source :
- Gene Therapy. 11:1579-1589
- Publication Year :
- 2004
- Publisher :
- Springer Science and Business Media LLC, 2004.
-
Abstract
- Brain and leptomeningeal metastases are common in breast cancer patients and our current treatments are ineffective. Reovirus type 3 is a replication competent, naturally occurring virus that usurps the activated Ras-signaling pathway (or an element thereof) of tumor cells and lyses them but leaves normal cells relatively unaffected. In this study we evaluated reovirus as an experimental therapeutic in models of central nervous system (CNS) metastasis from breast cancer. We found all breast cancer cell lines tested were susceptible to reovirus, with > 50% of these cells lysed within 72 h of infection. In vivo neurotoxicity studies showed only mild local inflammation at the injection site and mild communicating hydrocephalus with neither diffuse encephalitis nor behavioral abnormalities at the therapeutically effective dose of reovirus (intracranial) (ie 10(7) plaque-forming units) or one dose level higher. In vivo, a single intratumoral administration of reovirus significantly reduced the size of tumors established from two human breast cancer cell lines and significantly prolonged survival. Intrathecal administration of reovirus also remarkably prolonged survival in an immunocompetent racine model of leptomeningeal metastases. These data suggest that the evaluation of reovirus as an experimental therapeutic for CNS metastases from breast cancer is warranted.
- Subjects :
- Pathology
medicine.medical_specialty
viruses
Genetic enhancement
Green Fluorescent Proteins
Mice, Nude
Breast Neoplasms
Inflammation
Injections, Intralesional
Transfection
Metastasis
Lethal Dose 50
Mice
Breast cancer
In vivo
Cell Line, Tumor
Meningeal Neoplasms
Genetics
medicine
Animals
Humans
Mammalian orthoreovirus 3
Molecular Biology
Cell Death
Brain Neoplasms
business.industry
Neoplasms, Experimental
medicine.disease
Effective dose (pharmacology)
Reoviridae Infections
Models, Animal
Molecular Medicine
Female
medicine.symptom
business
Encephalitis
Brain metastasis
Subjects
Details
- ISSN :
- 14765462 and 09697128
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Gene Therapy
- Accession number :
- edsair.doi.dedup.....5e2608dc952cc879f52576bfe691e08a