dc.contributor.author | Wilkinson, MJ | |
dc.contributor.author | Smith, HG | |
dc.contributor.author | McEntee, G | |
dc.contributor.author | Kyula-Currie, J | |
dc.contributor.author | Pencavel, TD | |
dc.contributor.author | Mansfield, DC | |
dc.contributor.author | Khan, AA | |
dc.contributor.author | Roulstone, V | |
dc.contributor.author | Hayes, AJ | |
dc.contributor.author | Harrington, KJ | |
dc.date.accessioned | 2017-01-18T15:14:07Z | |
dc.date.issued | 2016-12-06 | |
dc.identifier.citation | Oncotarget, 2016, 7 (49), pp. 81208 - 81222 | |
dc.identifier.issn | 1949-2553 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/390 | |
dc.identifier.eissn | 1949-2553 | |
dc.identifier.doi | 10.18632/oncotarget.12820 | |
dc.description.abstract | Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity. This effect was not due to increased viral replication, but mediated through induction of intrinsic apoptosis. GLV-1h68 therapy downregulated the anti-apoptotic BCL-2 proteins (MCL-1 and BCL-XL) and the downstream inhibitors of apoptosis, resulting in cleavage of effector caspases 3 and 7. In an in vivo ILP model, the combination of OV and radiotherapy significantly delayed tumour growth and prolonged survival compared to single agent therapy. These data suggest that the virally-mediated down-regulation of anti-apoptotic proteins may increase the sensitivity of tumour cells to the cytotoxic effects of ionizing radiation. Oncolytic virotherapy represents an exciting candidate for clinical development when delivered by ILP. Its ability to overcome anti-apoptotic signals within tumour cells points the way to further development in combination with conventional anti-cancer therapies. | |
dc.format | Print | |
dc.format.extent | 81208 - 81222 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | IMPACT JOURNALS LLC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Rats, Inbred BN | |
dc.subject | Humans | |
dc.subject | Vaccinia virus | |
dc.subject | Fibrosarcoma | |
dc.subject | Radiotherapy, Adjuvant | |
dc.subject | Dose-Response Relationship, Radiation | |
dc.subject | Signal Transduction | |
dc.subject | Apoptosis | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Time Factors | |
dc.subject | Male | |
dc.subject | Oncolytic Virotherapy | |
dc.subject | Oncolytic Viruses | |
dc.subject | Apoptosis Regulatory Proteins | |
dc.subject | bcl-X Protein | |
dc.subject | Caspase 3 | |
dc.subject | Caspase 7 | |
dc.subject | Host-Pathogen Interactions | |
dc.subject | Myeloid Cell Leukemia Sequence 1 Protein | |
dc.title | Oncolytic vaccinia virus combined with radiotherapy induces apoptotic cell death in sarcoma cells by down-regulating the inhibitors of apoptosis. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-10-11 | |
rioxxterms.versionofrecord | 10.18632/oncotarget.12820 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-12 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Oncotarget | |
pubs.issue | 49 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Sarcoma and Melanoma Surgery | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Sarcoma and Melanoma Surgery | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.publication-status | Published | |
pubs.volume | 7 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Sarcoma and Melanoma Surgery | |
icr.researchteam | Targeted Therapy | |
dc.contributor.icrauthor | Mansfield, David | |
dc.contributor.icrauthor | Roulstone, Victoria | |
dc.contributor.icrauthor | Harrington, Kevin | |