Relationship between (31)P metabolites and oncolytic viral therapy sensitivity in human colorectal cancer xenografts Journal Article
| Authors: | Silberhumer, G. R.; Zakian, K.; Malhotra, S.; Brader, P.; Gonen, M.; Koutcher, J.; Fong, Y. |
| Article Title: | Relationship between (31)P metabolites and oncolytic viral therapy sensitivity in human colorectal cancer xenografts |
| Abstract: | Background: Studies using phosphorus magnetic resonance spectroscopy (MRS) have pointed to the significance of phospholipid metabolite alterations as biochemical markers for tumour progression or therapy response. Methods: Spectroscopic imaging was performed in colorectal flank tumours in nudemice. In vivo tumour doubling times for each cell line were measured. In vivo sensitivity of each tumour line to treatment with G207 and NV1020 oncolytic viruses was assessed. Correlations between viral sensitivity and tumour doubling time and phosphorus MRS were estimated. Results: For G207 virus, in vitro cytotoxicity tests showed cell viability at multiplicities of infection (ratio of viral particles per tumour cell) of 0.1 on day 6 as follows: C85, less than 1 per cent; HCT8, 1 per cent; LS174T, 9 per cent; HT29, 18 per cent; and C18, 92 per cent. Respective values for NV1020 were 1, 18, 4, 18 and 86 per cent. The phosphoethanolamine to phosphocholine ratio was significantly lower in virus-sensitive than -insensitive cells, and was dependent on tumour doubling time. Conclusion: Alterations in membrane phospholipid metabolites that relate to proliferation of cancer cells affect the efficacy of oncolytic viral therapy. MRS proved a highly sensitive non-invasive tool for predicting the efficacy of viruses. Copyright © 2009 British Journal of Surgery Society Ltd Published by John Wiley & Sons Ltd. |
| Keywords: | controlled study; human cell; nonhuman; methodology; sensitivity and specificity; radiopharmaceuticals; colorectal cancer; cell proliferation; mouse; animal; metabolism; animals; mice; animal experiment; in vivo study; cytotoxicity; in vitro study; tumor xenograft; drug effect; cell line, tumor; transfection; gene vector; genetic vectors; colorectal neoplasms; genetic transfection; diagnostic agent; xenograft; nude mouse; mice, nude; colorectal tumor; cancer cell; escherichia coli; tumor cell line; radiopharmaceutical agent; oncolytic virus; oncolytic virotherapy; transplantation, heterologous; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; herpesvirus 1, human; neoplasm transplantation; herpes simplex virus 1; nv 1020; virotherapy; phospholipids; cancer transplantation; phosphoethanolamine; phosphorus 31; phosphorylcholine; phospholipid; phosphorus; phosphorus isotopes |
| Journal Title: | British Journal of Surgery |
| Volume: | 96 |
| Issue: | 7 |
| ISSN: | 0007-1323 |
| Publisher: | Oxford University Press |
| Date Published: | 2009-07-01 |
| Start Page: | 809 |
| End Page: | 816 |
| Language: | English |
| DOI: | 10.1002/bjs.6604 |
| PUBMED: | 19526622 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Export Date: 30 November 2010" - "CODEN: BJSUA" - "Source: Scopus" |
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