Cargando…
Lentivirus vector-mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain
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 s...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047887/ https://www.ncbi.nlm.nih.gov/pubmed/33846766 http://dx.doi.org/10.3892/mmr.2021.12061 |
_version_ | 1783679131497529344 |
---|---|
author | Ahmad, Farizan Hyvärinen, Anna Pirinen, Agnieszka Olsson, Venla Rummukainen, Jaana Immonen, Arto Närväinen, Johanna Tuunanen, Pasi Liimatainen, Timo Kärkkäinen, Virve Koistinaho, Jari Ylä-Herttuala, Seppo |
author_facet | Ahmad, Farizan Hyvärinen, Anna Pirinen, Agnieszka Olsson, Venla Rummukainen, Jaana Immonen, Arto Närväinen, Johanna Tuunanen, Pasi Liimatainen, Timo Kärkkäinen, Virve Koistinaho, Jari Ylä-Herttuala, Seppo |
author_sort | Ahmad, Farizan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8047887 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-80478872021-04-16 Lentivirus vector-mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain Ahmad, Farizan Hyvärinen, Anna Pirinen, Agnieszka Olsson, Venla Rummukainen, Jaana Immonen, Arto Närväinen, Johanna Tuunanen, Pasi Liimatainen, Timo Kärkkäinen, Virve Koistinaho, Jari Ylä-Herttuala, Seppo Mol Med Rep Articles 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. D.A. Spandidos 2021-06 2021-04-06 /pmc/articles/PMC8047887/ /pubmed/33846766 http://dx.doi.org/10.3892/mmr.2021.12061 Text en Copyright: © Ahmad et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Ahmad, Farizan Hyvärinen, Anna Pirinen, Agnieszka Olsson, Venla Rummukainen, Jaana Immonen, Arto Närväinen, Johanna Tuunanen, Pasi Liimatainen, Timo Kärkkäinen, Virve Koistinaho, Jari Ylä-Herttuala, Seppo Lentivirus vector-mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain |
title | Lentivirus vector-mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain |
title_full | Lentivirus vector-mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain |
title_fullStr | Lentivirus vector-mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain |
title_full_unstemmed | Lentivirus vector-mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain |
title_short | Lentivirus vector-mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain |
title_sort | lentivirus vector-mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047887/ https://www.ncbi.nlm.nih.gov/pubmed/33846766 http://dx.doi.org/10.3892/mmr.2021.12061 |
work_keys_str_mv | AT ahmadfarizan lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain AT hyvarinenanna lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain AT pirinenagnieszka lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain AT olssonvenla lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain AT rummukainenjaana lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain AT immonenarto lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain AT narvainenjohanna lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain AT tuunanenpasi lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain AT liimatainentimo lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain AT karkkainenvirve lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain AT koistinahojari lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain AT ylaherttualaseppo lentivirusvectormediatedgeneticmanipulationofoncogenicpathwaysinducestumorformationinrabbitbrain |