Late p65 Nuclear Translocation in Glioblastoma Cells Indicates Non-Canonical TLR4 Signaling and Activation of DNA Repair Genes

Scientists analyzed Toll-like receptor 4 (TLR4) expression in different grades of astrocytoma, and observed increased expression in tumors, mainly in glioblastoma, compared to non-neoplastic brain tissue.
[Scientific Reports]
Moretti, I. F., Lerario, A. M., Trombetta-Lima, M., Sola, P. R., da Silva Soares, R., Oba-Shinjo, S. M., & Marie, S. K. N. (2021). Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes. Scientific Reports, 11(1), 1333. https://doi.org/10.1038/s41598-020-79356-1 Cite
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Kintara Announces Initiation of Patient Recruitment for VAL-083’s Study Arm in the GBM AGILE Trial

Kintara Therapeutics, Inc. announced that patient recruitment has commenced in the Global Coalition for Adaptive Research registrational Phase II/III clinical trial for glioblastoma (GBM).
[Kintara Therapeutics, Inc.]
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ADAMTS1 Supports Endothelial Plasticity of Glioblastoma Cells with Relevance for Glioma Progression

The authors performed an in silico study of ADAMTS1 and endothelial markers in human gliomas, providing the basis to further assess these molecules in several primary glioblastoma-initiating cells and established glioblastoma cells with the ability to acquire an endothelial-like phenotype.
[Biomolecules]
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Glioma Stem Cells and Their Roles within the Hypoxic Tumor Microenvironment

Investigators summarize the impact of hypoxia and acidic stress on glioma stem cell signaling and biologic phenotypes, and potential methods to inhibit these pathways.
[Theranostics]
Boyd, N. H., Tran, A. N., Bernstock, J. D., Etminan, T., Jones, A. B., Gillespie, G. Y., Friedman, G. K., & Hjelmeland, A. B. (2021). Glioma stem cells and their roles within the hypoxic tumor microenvironment. Theranostics, 11(2), 665–683. https://doi.org/10.7150/thno.41692 Cite
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Targeting of Glioma Stem-Like Cells with a Parthenolide Derivative ACT001 through Inhibition of AEBP1/PI3K/AKT Signaling

The effects of ACT001 on cell survival of normal human astrocytes and patient-derived glioma stem-like cells were evaluated. RNA-Seq were performed to detect differentially expressed genes.
[Theranostics]
Hou, Y., Sun, B., Liu, W., Yu, B., Shi, Q., Luo, F., Bai, Y., & Feng, H. (2021). Targeting of glioma stem-like cells with a parthenolide derivative ACT001 through inhibition of AEBP1/PI3K/AKT signaling. Theranostics, 11(2), 555–566. https://doi.org/10.7150/thno.49250 Cite
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CCAAT/Enhancer-Binding Protein Delta Mediates Glioma Stem-Like Cell Enrichment and ATP-Binding Cassette Transporter ABCA1 Activation for Temozolomide Resistance in Glioblastoma

Scientists found that the CCAAT/Enhancer-binding protein delta (CEBPD) protein levels in glioblastoma patients were significantly increased and further contributed to temozolamide resistance by promoting glioma-like stem cell formation.
[Cell Death & Discovery]
Wang, S.-M., Lin, W.-C., Lin, H.-Y., Chen, Y.-L., Ko, C.-Y., & Wang, J.-M. (2021). CCAAT/Enhancer-binding protein delta mediates glioma stem-like cell enrichment and ATP-binding cassette transporter ABCA1 activation for temozolomide resistance in glioblastoma. Cell Death Discovery, 7(1), 1–11. https://doi.org/10.1038/s41420-020-00399-4 Cite
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Single-Cell Chromatin Accessibility Profiling of Glioblastoma Identifies an Invasive Cancer Stem Cell Population Associated with Lower Survival

Researchers showed, using single-cell chromatin accessibility, that primary human glioblastomas (GBMs) harbored a heterogeneous self-renewing population whose diversity was captured in patient-derived GBMs stem cells.
[eLife]
Guilhamon, P., Chesnelong, C., Kushida, M. M., Nikolic, A., Singhal, D., MacLeod, G., Madani Tonekaboni, S. A., Cavalli, F. M., Arlidge, C., Rajakulendran, N., Rastegar, N., Hao, X., Hassam, R., Smith, L. J., Whetstone, H., Coutinho, F. J., Nadorp, B., Ellestad, K. I., Luchman, A. H., … Lupien, M. (2021). Single-cell chromatin accessibility profiling of glioblastoma identifies an Invasive cancer stem cell population associated with lower survival. ELife, 10, e64090. https://doi.org/10.7554/eLife.64090 Cite
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Pathway-Based Classification of Glioblastoma Uncovers a Mitochondrial Subtype with Therapeutic Vulnerabilities

A computational approach for unbiased identification of core biological traits of single cells and bulk tumors uncovered four tumor cell states and glioblastoma subtypes distributed along neurodevelopmental and metabolic axes, classified as proliferative/progenitor, neuronal, mitochondrial and glycolytic/plurimetabolic.
[Nature Cancer]
Garofano, L., Migliozzi, S., Oh, Y. T., D’Angelo, F., Najac, R. D., Ko, A., Frangaj, B., Caruso, F. P., Yu, K., Yuan, J., Zhao, W., Luisa Di Stefano, A., Bielle, F., Jiang, T., Sims, P., Suvà, M. L., Tang, F., Su, X.-D., Ceccarelli, M., … Iavarone, A. (2021). Pathway-based classification of glioblastoma uncovers a mitochondrial subtype with therapeutic vulnerabilities. Nature Cancer, 1–16. https://doi.org/10.1038/s43018-020-00159-4 Cite
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The Role of E3 Ubiquitin Ligases in the Development and Progression of Glioblastoma

The authors consider how knowledge of E3 ligase biology may be used for future therapeutic interventions in glioblastoma, including the use of blood-brain barrier permeable proteolysis targeting chimeras.
[Cell Death & Differentiation]
Humphreys, L. M., Smith, P., Chen, Z., Fouad, S., & D’Angiolella, V. (2021). The role of E3 ubiquitin ligases in the development and progression of glioblastoma. Cell Death & Differentiation, 1–16. https://doi.org/10.1038/s41418-020-00696-6 Cite
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EGFR/SRC/ERK-Stabilized YTHDF2 Promotes Cholesterol Dysregulation and Invasive Growth of Glioblastoma

Scientists showed that YTHDF2 overexpression clinically correlated with poor glioma patient prognosis. EGFR that was constitutively activated in the majority of glioblastoma caused YTHDF2 overexpression through the EGFR/SRC/ERK pathway.
[Nature Communications]
Fang, R., Chen, X., Zhang, S., Shi, H., Ye, Y., Shi, H., Zou, Z., Li, P., Guo, Q., Ma, L., He, C., & Huang, S. (2021). EGFR/SRC/ERK-stabilized YTHDF2 promotes cholesterol dysregulation and invasive growth of glioblastoma. Nature Communications, 12(1), 177. https://doi.org/10.1038/s41467-020-20379-7 Cite
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Inhibition of Gli2 Suppresses Tumorigenicity in Glioblastoma Stem Cells Derived from a De Novo Murine Brain Cancer Model

The Sleeping-Beauty transposon-induced glioblastoma model was used in leucine-rich repeat-containing G-protein coupled receptor 5-GFP knock-in mice identify GFP-positive cells in neurosphere cultures from mouse glioblastoma tissues
[Cancer Gene Therapy]
Tanigawa, S., Fujita, M., Moyama, C., Ando, S., Ii, H., Kojima, Y., Fujishita, T., Aoki, M., Takeuchi, H., Yamanaka, T., Takahashi, Y., Hashimoto, N., & Nakata, S. (2021). Inhibition of Gli2 suppresses tumorigenicity in glioblastoma stem cells derived from a de novo murine brain cancer model. Cancer Gene Therapy, 1–14. https://doi.org/10.1038/s41417-020-00282-5 Cite
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