2022
Tirgar, Fatemeh; Azizi, Zahra; Hosseindoost, Saereh; Hadjighassem, Mahmoudreza
Preclinical gene therapy in glioblastoma multiforme: using olfactory ensheathing cells containing a suicide gene Journal Article
In: Life Sciences, vol. 311, no. Pt A, pp. 121132, 2022, ISSN: 1879-0631.
Abstract | Links | BibTeX | Tags: Animals, Antiviral Agents, Cancer, Cultured, Ganciclovir, GCV: gancyclovir, Genetic Therapy, Glioblastoma, Glioblastoma multiforme, Olfactory ensheathing cells, Rats, Simplexvirus, Suicide gene therapy, Thymidine Kinase, Thymidine kinase gene, Tumor Cells
@article{tirgar_preclinical_2022,
title = {Preclinical gene therapy in glioblastoma multiforme: using olfactory ensheathing cells containing a suicide gene},
author = {Fatemeh Tirgar and Zahra Azizi and Saereh Hosseindoost and Mahmoudreza Hadjighassem},
doi = {10.1016/j.lfs.2022.121132},
issn = {1879-0631},
year = {2022},
date = {2022-12-01},
journal = {Life Sciences},
volume = {311},
number = {Pt A},
pages = {121132},
abstract = {AIMS: Glioblastoma multiforme (GBM) is the most malignant type of brain tumor resistant to current treatments. Recently, suicide gene therapy with the Herpex Simplex Virus thymidine kinase (HSV-tk) gene has been developed with high therapeutic potency, even in clinical trials. The primary challenge to establishing a gene therapy strategy is how to transfer the desired gene into the tumor site. The olfactory ensheathing cells (OECs) secreting neurotropic and anti-inflammatory factors have a high migration capacity, making them applicable for gene therapy. We examined our new construct OECs containing the HSV-tk gene for their migration and tumoricidal ability in animal models of GBM.
MAIN METHODS: Isolated OECs were transduced by the HSV-tk gene (OEC-tks). OEC-tks or PBS were injected ipsilaterally or contralaterally into the tumor-bearing rats, followed by gancyclovir (GCV) or PBS administration. At the end of the treatment, tumor size, apoptosis, and animal survival were assessed.
KEY FINDINGS: Our findings demonstrated that tumor size was significantly decreased in OEC-tks ipsilateral and contralateral groups, followed by GCV injections. Furthermore, both groups' pro-apoptotic protein and gene expressions were up-regulated, whereas Bcl-2 protein expression was down-regulated. Besides, apoptosis in the OEC-tks ipsilateral/GCV group was higher in the intratumoral region, and this percentage was higher in the OEC-tks contralateral/GCV group in the peritumoral region. Interestingly, our new construct increased animal survival rate and reduced body weight loss.
SIGNIFICANCE: OECs could serve as a novel carrier for gene therapy, have a high migration capability to the GBM and eventually suppress tumor progression.},
keywords = {Animals, Antiviral Agents, Cancer, Cultured, Ganciclovir, GCV: gancyclovir, Genetic Therapy, Glioblastoma, Glioblastoma multiforme, Olfactory ensheathing cells, Rats, Simplexvirus, Suicide gene therapy, Thymidine Kinase, Thymidine kinase gene, Tumor Cells},
pubstate = {published},
tppubtype = {article}
}
AIMS: Glioblastoma multiforme (GBM) is the most malignant type of brain tumor resistant to current treatments. Recently, suicide gene therapy with the Herpex Simplex Virus thymidine kinase (HSV-tk) gene has been developed with high therapeutic potency, even in clinical trials. The primary challenge to establishing a gene therapy strategy is how to transfer the desired gene into the tumor site. The olfactory ensheathing cells (OECs) secreting neurotropic and anti-inflammatory factors have a high migration capacity, making them applicable for gene therapy. We examined our new construct OECs containing the HSV-tk gene for their migration and tumoricidal ability in animal models of GBM.
MAIN METHODS: Isolated OECs were transduced by the HSV-tk gene (OEC-tks). OEC-tks or PBS were injected ipsilaterally or contralaterally into the tumor-bearing rats, followed by gancyclovir (GCV) or PBS administration. At the end of the treatment, tumor size, apoptosis, and animal survival were assessed.
KEY FINDINGS: Our findings demonstrated that tumor size was significantly decreased in OEC-tks ipsilateral and contralateral groups, followed by GCV injections. Furthermore, both groups' pro-apoptotic protein and gene expressions were up-regulated, whereas Bcl-2 protein expression was down-regulated. Besides, apoptosis in the OEC-tks ipsilateral/GCV group was higher in the intratumoral region, and this percentage was higher in the OEC-tks contralateral/GCV group in the peritumoral region. Interestingly, our new construct increased animal survival rate and reduced body weight loss.
SIGNIFICANCE: OECs could serve as a novel carrier for gene therapy, have a high migration capability to the GBM and eventually suppress tumor progression.
MAIN METHODS: Isolated OECs were transduced by the HSV-tk gene (OEC-tks). OEC-tks or PBS were injected ipsilaterally or contralaterally into the tumor-bearing rats, followed by gancyclovir (GCV) or PBS administration. At the end of the treatment, tumor size, apoptosis, and animal survival were assessed.
KEY FINDINGS: Our findings demonstrated that tumor size was significantly decreased in OEC-tks ipsilateral and contralateral groups, followed by GCV injections. Furthermore, both groups' pro-apoptotic protein and gene expressions were up-regulated, whereas Bcl-2 protein expression was down-regulated. Besides, apoptosis in the OEC-tks ipsilateral/GCV group was higher in the intratumoral region, and this percentage was higher in the OEC-tks contralateral/GCV group in the peritumoral region. Interestingly, our new construct increased animal survival rate and reduced body weight loss.
SIGNIFICANCE: OECs could serve as a novel carrier for gene therapy, have a high migration capability to the GBM and eventually suppress tumor progression.