PMID- 19360338
OWN - NLM
STAT- MEDLINE
DCOM- 20090803
LR  - 20191210
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 34
IP  - 5
DP  - 2009 May
TI  - Human precision-cut liver tumor slices as a tumor patient-individual predictive 
      test system for oncolytic measles vaccine viruses.
PG  - 1247-56
AB  - 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.
FAU - Zimmermann, Martina
AU  - Zimmermann M
AD  - Department of Gastroenterology and Hepatology, Medical University Hospital, 
      D-72076 Tubingen, Germany.
FAU - Armeanu, Sorin
AU  - Armeanu S
FAU - Smirnow, Irina
AU  - Smirnow I
FAU - Kupka, Susan
AU  - Kupka S
FAU - Wagner, Silvia
AU  - Wagner S
FAU - Wehrmann, Manfred
AU  - Wehrmann M
FAU - Rots, Marianne G
AU  - Rots MG
FAU - Groothuis, Geny M M
AU  - Groothuis GM
FAU - Weiss, Thomas S
AU  - Weiss TS
FAU - Konigsrainer, Alfred
AU  - Konigsrainer A
FAU - Gregor, Michael
AU  - Gregor M
FAU - Bitzer, Michael
AU  - Bitzer M
FAU - Lauer, Ulrich M
AU  - Lauer UM
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Measles Vaccine)
SB  - IM
MH  - Animals
MH  - Biopsy/methods
MH  - Carcinoma, Hepatocellular/*diagnosis/pathology/*therapy
MH  - Cells, Cultured
MH  - Chlorocebus aethiops
MH  - HT29 Cells
MH  - Humans
MH  - Individuality
MH  - Liver/*pathology/virology
MH  - Liver Neoplasms/*diagnosis/pathology/*therapy
MH  - Measles/pathology/virology
MH  - Measles Vaccine/*therapeutic use
MH  - Microdissection/*methods
MH  - *Oncolytic Virotherapy
MH  - Prognosis
MH  - Vero Cells
EDAT- 2009/04/11 09:00
MHDA- 2009/08/04 09:00
CRDT- 2009/04/11 09:00
PHST- 2009/04/11 09:00 [entrez]
PHST- 2009/04/11 09:00 [pubmed]
PHST- 2009/08/04 09:00 [medline]
PST - ppublish
SO  - Int J Oncol. 2009 May;34(5):1247-56.