University of Oulu

Ahmad, F., Hyvärinen, A., Pirinen, A., Olsson, V., Rummukainen, J., Immonen, A. ... Ylä‑Herttuala, S. (2021). Lentivirus vector‑mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain. Molecular Medicine Reports, 23, 422. https://doi.org/10.3892/mmr.2021.12061

Lentivirus vector‑mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain

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Author: Ahmad, Farizan1,2; Hyvärinen, Anna1,3,4,5; Pirinen, Agnieszka1;
Organizations: 1A.I Virtanen Institute for Molecular Sciences, University of Eastern Finland, FI‑70211 Kuopio, Finland
2Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia
3Department of Pediatric Surgery, Tampere University Hospital, FI‑33520 Tampere
4Tampere University, FI‑33014 Tampere
5Department of Surgery, North Karelia Central Hospital, FI‑80210 Joensuu
6Department of Pathology, Kuopio University Hospital
7Department of Neurosurgery, Neurocenter in Kuopio University Hospital, FI‑70029 Kuopio
8VTT Technical Research Centre of Finland, FI‑70210 Kuopio
9Department of Clinical Neurophysiology, Kuopio University Hospital, FI‑70029 Kuopio
10Research Unit for Medical Imaging, Physics and Technology, University of Oulu, FI‑90014 Oulu
11Department of Diagnostic Radiology, Oulu University Hospital, FI‑90220 Oulu
12Neuroscience Center, Helsinki Institute of Life Sciences, University of Helsinki, FI‑00014 Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.6 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021051229666
Language: English
Published: Spandidos Publications, 2021
Publish Date: 2021-05-12
Description:

Abstract

Translation of promising experimental therapies from rodent models to clinical success has been complicated as the novel therapies often fail in clinical trials. Existing rodent glioma models generally do not allow for preclinical evaluation of the efficiency of novel therapies in combination with surgical resection. Therefore, the aim of the present study was to develop a larger animal model utilizing lentivirus vector‑mediated oncogenic transformation in the rabbit brain. Lentiviruses carrying constitutively active AKT and H‑Ras oncogenes, and p53 small interfering (si)RNA were introduced into newborn rabbit neural stem cells (NSCs) and intracranially implanted into rabbits' brains to initiate tumor formation. In one of the ten rabbits a tumor was detected 48 days after the implantation of transduced NSCs. Histological features of the tumor mimic was similar to a benign Grade II ganglioglioma. Immunostaining demonstrated that the tissues were positive for AKT and H‑Ras. Strong expression of GFAP and Ki‑67 was also detected. Additionally, p53 expression was notably lower in the tumor area. The implantation of AKT, H‑Ras and p53 siRNA transduced NSCs for tumor induction resulted in ganglioglioma formation. Despite the low frequency of tumor formation, this preliminary data provided a proof of principle that lentivirus vectors carrying oncogenes can be used for the generation of brain tumors in rabbits. Moreover, these results offer noteworthy insights into the pathogenesis of a rare brain tumor, ganglioglioma.

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Series: Molecular medicine reports
ISSN: 1791-2997
ISSN-E: 1791-3004
ISSN-L: 1791-2997
Volume: 23
Issue: 6
Article number: A38
DOI: 10.3892/mmr.2021.12061
OADOI: https://oadoi.org/10.3892/mmr.2021.12061
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Funding: This study was supported by grants from Finnish Academy (grant no. 124222) and Sigrid Juselius Foundation.
Copyright information: © Ahmad et al. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.
  https://creativecommons.org/licenses/by-nc-nd/4.0/