Enhanced Cellular Uptake of Virus by Increased Expression Levels of the Coxsackie-and Adenovirus Receptor
Replication–selective oncolytic adenoviruses have shown great promise as novel anti-cancer agents. These mutant viruses act through different mechanisms than traditional anti-cancer therapies and consequently do not develop cross-resistance with these drugs. A limiting factor for success with cancer...
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| Formato: | Otro |
| Lenguaje: | sueco Inglés |
| Publicado: |
2005
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| Materias: | |
| Acceso en línea: | https://stud.epsilon.slu.se/11554/ |
| _version_ | 1855571894801006592 |
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| author | Lindström, Lina |
| author_browse | Lindström, Lina |
| author_facet | Lindström, Lina |
| author_sort | Lindström, Lina |
| collection | Epsilon Archive for Student Projects |
| description | Replication–selective oncolytic adenoviruses have shown great promise as novel anti-cancer agents. These mutant viruses act through different mechanisms than traditional anti-cancer therapies and consequently do not develop cross-resistance with these drugs. A limiting factor for success with cancer treatment using oncolytic adenoviruses is the delivery and entry of virus to the correct target cells. An important step in adenoviral adsorption to host cells is the interaction between cellular CAR and viral fibre domains. Reports have indicated a down-regulation of CAR- levels in various cancer cell lines and clinical specimens. Enhancing the expression of CAR could potentially increase the efficacy of treatment with oncolytic adenoviruses. In this project, prostate cancer cell lines have been evaluated for their sensitivity to adenoviral infection, with and without treatment with the MEK-inhibitors PD98059, U0126 and the histone deacetylase inhibitor Trichostatin A. Trichostatin A was found to be a potent enhancer of sensitivity to viral-induced cytopathic effect in prostate cancer cell lines. Furthermore, prostate cancer cell lines have been evaluated for their surface expression of CAR, uptake of adenovirus and adenoviral replication with and without treatment with Trichostatin A. Trichostatin A was found to enhance CAR- expression and adenoviral uptake in some prostate cancer cell lines but did not have any significant effects on adenoviral replication. In conclusion, Trichostatin A could be used to improve the effects of oncolytic adenoviruses in treatment of prostate cancer through enhanced expression of CAR. |
| format | Otro |
| id | RepoSLU11554 |
| institution | Swedish University of Agricultural Sciences |
| language | Swedish Inglés |
| publishDate | 2005 |
| publishDateSort | 2005 |
| record_format | eprints |
| spelling | RepoSLU115542017-10-03T08:38:45Z https://stud.epsilon.slu.se/11554/ Enhanced Cellular Uptake of Virus by Increased Expression Levels of the Coxsackie-and Adenovirus Receptor Lindström, Lina Veterinary science and hygiene - General aspects Replication–selective oncolytic adenoviruses have shown great promise as novel anti-cancer agents. These mutant viruses act through different mechanisms than traditional anti-cancer therapies and consequently do not develop cross-resistance with these drugs. A limiting factor for success with cancer treatment using oncolytic adenoviruses is the delivery and entry of virus to the correct target cells. An important step in adenoviral adsorption to host cells is the interaction between cellular CAR and viral fibre domains. Reports have indicated a down-regulation of CAR- levels in various cancer cell lines and clinical specimens. Enhancing the expression of CAR could potentially increase the efficacy of treatment with oncolytic adenoviruses. In this project, prostate cancer cell lines have been evaluated for their sensitivity to adenoviral infection, with and without treatment with the MEK-inhibitors PD98059, U0126 and the histone deacetylase inhibitor Trichostatin A. Trichostatin A was found to be a potent enhancer of sensitivity to viral-induced cytopathic effect in prostate cancer cell lines. Furthermore, prostate cancer cell lines have been evaluated for their surface expression of CAR, uptake of adenovirus and adenoviral replication with and without treatment with Trichostatin A. Trichostatin A was found to enhance CAR- expression and adenoviral uptake in some prostate cancer cell lines but did not have any significant effects on adenoviral replication. In conclusion, Trichostatin A could be used to improve the effects of oncolytic adenoviruses in treatment of prostate cancer through enhanced expression of CAR. Onkolytiska virus är en ny behandlingsmetod för cancer, som utnyttjar helt andra verkningsmekanismer än gängse läkemedel och behandlingsformer. Adenovirus är små DNA-virus som infekterar epitelceller, replikerar, spränger sin värdcell och sprider sig i vävnaden. Onkolytiska adenovirus är modifierade på sådant sätt att de selektivt angriper tumörceller och lämnar friska celler oskadda. För att adherera till värdcellerna binder adenovirus med sitt ”fibre”-protein till CAR (Coxsackie-adenovirus receptor) och tar sig sedan in genom cellmembranet genom att utnyttja integriner på cellytan. Mycket litet är känt om CA-receptorns fysiologiska funktioner, den tros vara en celladhesionsmolekyl, men kan också vara inblandad i kommunikation celler emellan. Mängden CAR varierar mellan olika celltyper och är genomgående nedreglerad i flera typer av avancerade tumörer. Att kunna uppreglera CAR skulle potentiellt kunna förbättra cancerbehandling med onkolytiska adenovirus. I detta projekt har cellinjer från prostatatumörer screenats för känslighet mot adenovirusinfektion, med och utan behandling av MEK-hämmarna PD98059, U0126 och histone deacetylase-hämmaren Trichostatin A. Trichostatin A visades sig kunna förstärka känsligheten mot virus hos de använda cellinjerna. Därefter undersöktes samma cellinjer för att se om deras uttryck av CAR på cellytan, upptag av virus och virusreplikation förändrades efter behandling med Trichostatin A. Efter behandling ökade både uttrycket av CAR och upptaget av virus i de flesta cellinjer, däremot sågs inga förändringar av virusreplikationen. Sammantaget visade denna studie att Trichostatin A skulle kunna användas för att förbättra behandling av prostatacancer med onkolytiska adenovirus genom att öka uttrycket av CAR hos värdcellerna. 2005-08-26 Other NonPeerReviewed application/pdf sv https://stud.epsilon.slu.se/11554/1/lindstrom_l_171003.pdf Lindström, Lina, 2005. Enhanced Cellular Uptake of Virus by Increased Expression Levels of the Coxsackie-and Adenovirus Receptor. UNSPECIFIED, Uppsala. Uppsala: (VH) > Dept. of Biomedical Sciences and Veterinary Public Health (until 231231) <https://stud.epsilon.slu.se/view/divisions/OID-713.html> urn:nbn:se:slu:epsilon-s-7414 eng |
| spellingShingle | Veterinary science and hygiene - General aspects Lindström, Lina Enhanced Cellular Uptake of Virus by Increased Expression Levels of the Coxsackie-and Adenovirus Receptor |
| title | Enhanced Cellular Uptake of Virus by Increased Expression Levels of the Coxsackie-and Adenovirus Receptor |
| title_full | Enhanced Cellular Uptake of Virus by Increased Expression Levels of the Coxsackie-and Adenovirus Receptor |
| title_fullStr | Enhanced Cellular Uptake of Virus by Increased Expression Levels of the Coxsackie-and Adenovirus Receptor |
| title_full_unstemmed | Enhanced Cellular Uptake of Virus by Increased Expression Levels of the Coxsackie-and Adenovirus Receptor |
| title_short | Enhanced Cellular Uptake of Virus by Increased Expression Levels of the Coxsackie-and Adenovirus Receptor |
| title_sort | enhanced cellular uptake of virus by increased expression levels of the coxsackie-and adenovirus receptor |
| topic | Veterinary science and hygiene - General aspects |
| url | https://stud.epsilon.slu.se/11554/ https://stud.epsilon.slu.se/11554/ |