Lentivirus vector-mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain
| Autor: | Anna Hyvärinen, Jari Koistinaho, Johanna Närväinen, Venla Olsson, Seppo Ylä-Herttuala, Virve Kärkkäinen, Jaana Rummukainen, Farizan Ahmad, Arto Immonen, Pasi I Tuunanen, Timo Liimatainen, Agnieszka Pirinen |
|---|---|
| Přispěvatelé: | Tampere University, Clinical Medicine, Neuroscience Center, Helsinki Institute of Life Science HiLIFE, University of Helsinki |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
3122 Cancers Genetic Vectors Brain tumor Mice Transgenic Mice SCID Biology Biochemistry Ganglioglioma Neural Stem Cells SDG 3 - Good Health and Well-being Glioma Genetics medicine Animals Molecular Biology Protein kinase B Cells Cultured Cell Proliferation Oncogene Brain Neoplasms Lentivirus Lentivirus vector Brain Articles Oncogenes Cell cycle medicine.disease Immunohistochemistry Neural stem cell 3. Good health Disease Models Animal Oncology Rabbit brain tumor model Cancer research Molecular Medicine 1182 Biochemistry cell and molecular biology Female Rabbits 3111 Biomedicine Immunostaining |
| Zdroj: | Molecular Medicine Reports Ahmad, F, Hyvärinen, A, Pirinen, A, Olsson, V, Rummukainen, J, Immonen, A, Närväinen, J, Tuunanen, P, Liimatainen, T, Kärkkäinen, V, Koistinaho, J & Ylä-Herttuala, S 2021, ' Lentivirus vector-mediated genetic manipulation of oncogenic pathways induces tumor formation in rabbit brain ', Molecular Medicine Reports, vol. 23, no. 6, A38 . https://doi.org/10.3892/mmr.2021.12061 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|