We employed lentivirus-based doublecortin (DCX), as a glioma suppressor gene therapy in an intracranial glioma tumor xenograft model in nude rats. Single DCX-expressing lentivirus was directly administered into the tumor on day 8 after U87 tumor cell implantation. DCX treatment significantly reduced U87 glioma tumor volume (approximately 60%) on day 14 after DCX lentivirus injection and significantly improved median survival of tumor-bearing nude rats. DCX synthesis induced neuronal markers MAP2, TUJ1, and PSA-NCAM and the glial marker glial fibrillary acidic protein (GFAP) in the implanted U87 glioma tumors. DCX synthesis induced GFAP that colocalized with tubulin in the mitotic stage, inhibited cleavage furrow during cytokinesis, and blocked mitosis in glioma cells. DCX lentivirus infection did not induce apoptosis but significantly inhibited expression of the proliferation marker Ki-67 and the blood vessel marker von-Willebrand factor (vWF). U87 and other glioma cells except for brain tumor stem cells (BTSCs) do not express neuronal markers or both neuronal and glial markers. DCX-synthesizing glioma cells express a phenotype of antiangiogenic BTSC-like cells with terminal differentiation that causes remission of glioma cells by blocking mitosis via a novel DCX/GFAP pathway. Direct local delivery of lentivirus-based DCX gene therapy is a potential differentiation-based therapeutic approach for the treatment of glioma.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795007 | PMC |
| http://dx.doi.org/10.1002/jnr.22207 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Clinical confocal laser endomicroscopy for imaging of autofluorescence signals of human brain tumors and non-tumor brain.
J Cancer Res Clin Oncol
December 2024
Department of Neurosurgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Purpose: Analysis of autofluorescence holds promise for brain tumor delineation and diagnosis. Therefore, we investigated the potential of a commercial confocal laser scanning endomicroscopy (CLE) system for clinical imaging of brain tumors.
Methods: A clinical CLE system with fiber probe and 488 nm laser excitation was used to acquire images of tissue autofluorescence.
The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis.
Front Cell Dev Biol
December 2024
Department of Medical Chemistry, Biochemistry and Clinical Chemistry, School of Medicine, University of Zagreb, Zagreb, Croatia.
Gliomas are highly aggressive primary brain tumors, with glioblastoma multiforme being the most severe and the most common one. Aberrations in sphingolipid metabolism are a hallmark of glioma cells. The sphingolipid rheostat represents the balance between the pro-apoptotic ceramide and pro-survival sphingosine-1-phosphate (S1P), and in gliomas it is shifted toward cell survival and proliferation, promoting gliomas' aggressiveness, cellular migration, metastasis, and invasiveness.
View Article and Find Full Text PDFMigrasome regulator TSPAN4 shapes the suppressive tumor immune microenvironment in pan-cancer.
Front Immunol
December 2024
Trauma Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Article Synopsis
- Migrasomes are new organelles important for cell signaling and communication that involve the protein TSPAN4, whose role in cancer is not well understood.
- Researchers studied TSPAN4 across multiple cancer types, examining its expression levels and connections to tumor characteristics using large datasets.
- Findings indicate TSPAN4 is irregularly expressed in tumors, affecting tumor growth and immune response, particularly in glioma, where it encourages an immunosuppressive environment.
FSTL1 Sustains Glioma Stem Cell Stemness and Promotes Immunosuppressive Macrophage Polarization in Glioblastoma.
Cancer Lett
December 2024
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address:
Tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) play a crucial role in glioblastoma (GBM) progression by interacting with glioma stem cells (GSCs). These interactions lead to the polarization of TAMs toward an M2 phenotype, which, in turn, enhances the stem-like traits and malignant progression of GSCs. Our study shows that FSTL1, a protein released by GSCs, is significantly elevated in gliomas and linked to the progression of the disease.
View Article and Find Full Text PDFIdentification of Brain Cell Type-Specific Therapeutic Targets for Glioma From Genetics.
CNS Neurosci Ther
December 2024
The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Background: Previous research has demonstrated correlations between the complex types and functions of brain cells and the etiology of glioma. However, the causal relationship between gene expression regulation in specific brain cell types and glioma risk, along with its therapeutic implications, remains underexplored.
Methods: Utilizing brain cell type-specific cis-expression quantitative trait loci (cis-eQTLs) and glioma genome-wide association study (GWAS) datasets in conjunction with Mendelian randomization (MR) and colocalization analyses, we conducted a systematic investigation to determine whether an association exists between the gene expression of specific brain cell types and the susceptibility to glioma, including its subtypes.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!