ArticleJournal of biomedical science2012
The treatment of glioblastoma multiforme through activation of microglia and TRAIL induced by rAAV2-mediated IL-12 in a syngeneic rat model.
Article in Journal of biomedical science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
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- The Dynamics of Tumor-Infiltrating Myeloid Cell Activation and the Cytokine Expression Profile in a Glioma Resection Site during the Post-Surgical Period in Mice.Brain sciences · 2022Article
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- Advances in immunotherapy for glioblastoma multiforme.Frontiers in immunology · 2022Review
- Against the Resilience of High-Grade Gliomas: Gene Therapies (Part II).Brain sciences · 2021Review
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- Combination immunotherapy strategies for glioblastoma.Journal of neuro-oncology · 2021Review
- Immune Escape in Glioblastoma Multiforme and the Adaptation of Immunotherapies for Treatment.Frontiers in immunology · 2020Review
- Discovering genetic interactions bridging pathways in genome-wide association studies.Nature communications · 2019Article
- Novel window for cancer nanotheranostics: non-invasive ocular assessments of tumor growth and nanotherapeutic treatment efficacyBiomedical optics express · 2019Article
- Advances in immunotherapeutic research for glioma therapy.Journal of neurology · 2018Review
- Current state and future prospects of immunotherapy for glioma.Immunotherapy · 2018Review
- Adeno-associated virus (AAV) vectors in cancer gene therapy.Journal of controlled release : official journal of the Controlled Release Society · 2016Review
- Histone deacetylase inhibitor SAHA attenuates post-seizure hippocampal microglia TLR4/MYD88 signaling and inhibits TLR4 gene expression via histone acetylation.BMC neuroscience · 2016Article
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMicroglial cells are the predominant immune cells in malignant brain tumors, but tumors may release some factors to reduce their defensive functions. Restoration of the anti-cancer function of microglia has been proposed as a treatment modality for glioblastoma. We examined the effect of intra-cranially administered recombinant adeno-associated virus encoding interleukin-12 (rAAV2/IL12) on transfection efficiency, local immune activity and survival in a rat model of glioblastoma multiforme.
methodsF344 rats were injected with rAAV2/IL12 and implanted with syngeneic RG2 cells (glioblastoma cell line). Intracerebral interleukin-12 and interferon-γ concentrations were determined by ELISA. Activation of microglia was determined by expressions of ED1 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) which were evaluated by Western blotting and immunohistochemistry. The proliferation of cancer cells was evaluated with Ki67 immunohistochemistry and apoptosis of cancer cells with TUNEL.
resultsThe brains treated with rAAV2/IL-12 maintained high expression of interleukin-12 and interferon-γ for at least two months. In syngeneic tumor model, brains treated with rAAV2/IL12 exhibited more infiltration of activated microglia cells as examined by ED1 and TRAIL stains in the tumor. In addition, the volume of tumor was markedly smaller in AAV2/IL12-treated group and the survival time was significantly longer in this group too.
conclusionThe intra-cerebrally administered rAAV2/IL-12 efficiently induces long lasting expression of IL-12, the greater infiltration of activated microglia cells in the tumor associated improved immune reactions, resulting in the inhibited growth of implanted glioblastoma and the increased survival time of these rats.
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