Attenuated reovirus displays oncolysis with reduced host toxicity
| العنوان: | Attenuated reovirus displays oncolysis with reduced host toxicity |
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| المؤلفون: | Stefan J. Urbanski, Katy A. Garant, S D Loken, Derrick E. Rancourt, Patrick W. K. Lee, Manbok Kim, Peter A. Forsyth, Randal N. Johnston, Tommy Alain, N.I. zur Nieden |
| المساهمون: | Publica |
| المصدر: | British journal of cancer, vol 104, iss 2 British Journal of Cancer |
| بيانات النشر: | Springer Science and Business Media LLC, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Cancer Research, Transcription, Genetic, viruses, Mice, SCID, Mice, 0302 clinical medicine, Oncolytic Virotherapy, Microscopy, Heterologous, reduced toxicity, 0303 health sciences, Virulence, Blotting, Immunohistochemistry, 3. Good health, Blot, Oncology, 030220 oncology & carcinogenesis, Public Health and Health Services, Stem cell, Western, Transcription, attenuated, Blotting, Western, Transplantation, Heterologous, Oncology and Carcinogenesis, Biology, SCID, Reoviridae, Electron, Cell Line, 03 medical and health sciences, Genetic, Combination cancer therapy, medicine, Animals, Humans, Oncology & Carcinogenesis, DNA Primers, 030304 developmental biology, Transplantation, persistent infection, Severe combined immunodeficiency, oncolysis, Base Sequence, medicine.disease, Virology, Oncolytic virus, mammalian reovirus, Microscopy, Electron, Cell culture, Protein Biosynthesis, Cancer cell, sigma1, Translational Therapeutics |
| الوصف: | Background: Although the naturally occurring reovirus causes only mild symptoms in humans, it shows considerable potential as an oncolytic agent because of its innate ability to target cancer cells. In immunocompromised hosts, however, wild-type reovirus can target healthy tissues, including heart, liver, pancreas and neural structures. Methods: We characterized an attenuated form of reovirus (AV) derived from a persistently infected cell line through sequence analysis, as well as western blot and in vitro transcription and translation techniques. To examine its pathogenesis and oncolytic potential, AV reovirus was tested on healthy embryonic stem cells, various non-transformed and transformed cell lines, and in severe combined immunodeficiency (SCID) mice with tumour xenografts. Results: Sequence analysis of AV reovirus revealed a premature STOP codon in its sigma 1 attachment protein. Western blot and in vitro translation confirmed the presence of a truncated ?1. In comparison to wild-type reovirus, AV reovirus did not kill healthy stem cells or induce black tail formation in SCID mice. However, it did retain its ability to target cancer cells and reduce tumour size. Conclusion: Despite containing a truncated attachment protein, AV reovirus still preferentially targets cancer cells, and compared with wild-type reovirus it shows reduced toxicity when administered to immunodeficient hosts, suggesting the potential use of AV reovirus in combination cancer therapy. |
| وصف الملف: | application/pdf |
| تدمد: | 1532-1827 0007-0920 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b75e36ee84d24d88d7d40df426190e8e https://doi.org/10.1038/sj.bjc.6606053 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b75e36ee84d24d88d7d40df426190e8e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15321827 00070920 |
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