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Lindström, Lina (2005) Enhanced Cellular Uptake of Virus by Increased Expression Levels of the Coxsackie-and Adenovirus Receptor. Other thesis, SLU.

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Abstract

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.

Item Type: Thesis (Other)
Keywords: oncolytic viruses, CAR
Subject (faculty): Faculty of Veterinary Medicine and Animal Science > Department of Biomedical Science and Veterinary Public Health
Divisions: SLU > Faculty of Veterinary Medicine and Animal Science
Depositing User: Lina Lindström
Date Deposited: 26 Aug 2005
Last Modified: 18 Aug 2015 09:35
URI: http://ex-epsilon.slu.se/id/eprint/622

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