Zimmermann, Martina and Armeanu, Sorin and Smirnow, Irina and Kupka, Susan and Wagner, Silvia and Wehrmann, Manfred and Rots, Marianne G. and Groothuis, Geny M. M. and Weiss, Thomas S. and Koenigsrainer, Alfred and Gregor, Michael and Bitzer, Michael and Lauer, Ulrich M. (2009) Human precision-cut liver tumor slices as a tumor patient-individual predictive test system for oncolytic measles vaccine viruses. INTERNATIONAL JOURNAL OF ONCOLOGY, 34 (5). pp. 1247-1256. ISSN 1019-6439, 1791-2423
Full text not available from this repository. (Request a copy)Abstract
Availability of an individualized preselection of oncolytic viruses to be used for virotherapy of tumor patients would be of great help. Using primary liver tumor resection specimens we evaluated the precision-cut liver slice (PCLS) technology as a novel in vitro test system for characterization of paramount tumor infection parameters of individual patients. PCLS slices from resection specimens of 20 liver tumor patients were cultivated in vitro for up to 5 days and infected with 5 different oncolytic measles vaccine virus (MeV) strains. Effectiveness of tumor infection was monitored by viral nucleocapsid (N) protein detection in immunofluorescence staining or Western blot analysis or by detection of GFP marker gene expression. MeV spreading in PCLS cultures was visualized by confocal microscopy. Oncolytic MeV vaccine particles were demonstrated to efficiently infect PCLS slices originating from different primary and secondary tumors of the liver with MeV strains Moraten/Edmonston Zagreb and AIK-C showing highest infection rates (75% of all tested tumor specimens). Employing mixed liver tissue slices (exhibiting both tumorous and non-tumorous tissue, areas on one and the same sample) a distinct tumor area favouring pattern of MeV infections was observed being in accordance with our finding that primary human hepatocytes are also permissive to MeV particles, albeit at a much lower rate and with a much less pronounced cytopathic effect. Furthermore, confocal microscopy demonstrated virus penetration throughout tumor tissues into deep cell layers. In conclusion, the PCLS technology is suitable to perform a tumor-patient individualized preselection of oncolytic agents prior to clinical virotherapeutic applications.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IN-VITRO PHARMACOTOXICOLOGY; TISSUE-SLICES; HEPATOCELLULAR-CARCINOMA; CANCER-THERAPY; GENE-THERAPY; MODEL SYSTEM; VIVO; AGENTS; ADENOVIRUSES; VIROTHERAPY; liver cancer; oncolytic viruses; measles vaccine viruses; precision-cut liver slices |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Sep 2020 11:10 |
| Last Modified: | 16 Sep 2020 11:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29053 |
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