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| Content Provider | PubMed Central |
|---|---|
| Author | Nakamura, Hideo Kasuya, Hideki Mullen, John T. Yoon, Sam S. Pawlik, Timothy M. Chandrasekhar, Soundararajalu Donahue, James M. Chiocca, E. Antonio Chung, Richard Y. Tanabe, Kenneth K. |
| Copyright Year | 2002 |
| Abstract | Myb34.5 is a herpes simplex virus 1 (HSV-1) mutant deleted in the gene for ribonucleotide reductase (ICP6). It also carries a version of γ134.5 (a viral gene product that promotes the dephosphorylation of eIF-2α) that is under control of the E2F-responsive cellular B-myb promoter, rather than of its endogenous promoter. Myb34.5 replication in tumor cells results in their destruction (oncolysis). γ134.5 expression by HSV-1 subverts an important cell defense mechanism against viral replication by preventing shutoff of protein synthesis after viral infection. Infection of colon carcinoma cells with Myb34.5 results in greater eIF-2α dephosphorylation and viral replication compared with infection with HSV-1 mutants completely defective in γ134.5 expression. In contrast, infection of normal hepatocytes with Myb34.5 results in low levels of eIF-2α dephosphorylation and viral replication that are similar to those observed with HSV-1 mutants completely defective in γ134.5 and ICP6. When administered intravascularly into mice with diffuse liver metastases, Myb34.5 has greater antineoplastic activity than HSV-1 mutants with completely defective γ134.5 expression and more restricted biodistribution compared with HSV-1 mutants with wild-type γ134.5 expression. Myb34.5 displays reduced virulence and toxicity compared to HSV-1 mutants with wild-type γ134.5 expression. Portal venous administration of Myb34.5 significantly reduces liver tumor burden in and prolongs the life of mice with diffuse liver metastases. Preexisting Ab’s to HSV-1 do not reduce the antitumor efficacy of Myb34.5 in vivo. |
| Related Links | http://dx.doi.org/10.1172/jci0210623 |
| Ending Page | 882 |
| Page Count | 12 |
| Starting Page | 871 |
| File Format | |
| ISSN | 00219738 |
| e-ISSN | 15588238 |
| Journal | The Journal of Clinical Investigation |
| Issue Number | 7 |
| Volume Number | 109 |
| Language | English |
| Publisher | American Society for Clinical Investigation |
| Publisher Date | 2002-04-01 |
| Access Restriction | Open |
| Rights Holder | American Society for Clinical Investigation |
| Subject Keyword | Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
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