Design, Synthesis and Biological Evaluation of Benzo[D]Thiazole with Dimethylpyrazol Derivatives

Liu, Dachuan; Cheng, Xiangdong; Wang, Ying

doi:10.31557/apjcp.2019.20.11.3487

Cited by 1 publication

(1 citation statement)

References 21 publications

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“…[87] Furthermore, EVs from murine GL261 glioma cells have shown to promote tumor growth by inhibiting CD8+ T-cells. [88] More recently, van der Vos et al demonstrated that GBM-derived EVs transfer functional RNA to microglia/macrophages in the brain. Exposure of microglia to GBM-EVs lead to downregulation of miR-21/miR-451 target c-Myc mRNA.…”

Section: Evs and The Tumor Microenvironmentmentioning

confidence: 99%

Small but Fierce: Tracking the Role of Extracellular Vesicles in Glioblastoma Progression and Therapeutic Resistance

Schweiger

Tannous

2020

Adv. Biosys.

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(30%), mouse double minute 2 (MDM2) amplifications (<10%) and/ or overexpression (50%), p16INK4a deletions (30-40%), and loss of heterozygosity on chromosome 10 in 50-80% of all cases. [3] Around 5-10% of all GBMs harbor isocitrate dehydrogenase (IDH) mutations with a better prognosis compared to tumors carrying the wildtype form known to exhibit a much more aggressive clinical behavior, particularly in adults. [4,5] It is now appreciated that IDH-wildtype and IDH-mutant gliomas represent distinct clinical and genetic entities, and efforts have been made to restrict the term "glioblastoma" to tumors without IDH mutations. [6,7] The standard-of-care treatment consists of maximal surgical resection of the tumor in combination with radiation and temozolomide (TMZ) chemotherapy. However, GBM is insidious and treatments have not been effective in preventing eventual disease progression as recurrence remains inevitable. [8-11] Transcriptomic, genomic, and epigenomic characterization have unveiled the highly heterogeneous nature of GBM with complex interactions among different cells within as well as cells surrounding the tumor. [3,12-17] Comprehensive longitudinal analyses of the tumor transcriptome have uncovered intricate intertumoral heterogeneity and classified GBM into three distinct subtypes: classical (CL), proneural (PN), and mesenchymal (MES). [18] In addition to this intertumoral heterogeneity, single-cell RNA sequencing demonstrated the presence of numerous transcriptome subtypes within the same tumor. [14] Further, single-cell lineage tracking and expression analysis of specimens from The Cancer Genome Atlas (TCGA) revealed that malignant cells in GBM exist in four main cellular states: neural-progenitor-like, oligodendrocyte-progenitor-like, astrocyte-like, and mesenchymal-like. [19] The number and frequency of cells in each defined state varies between patients and is influenced by mutations in the neurofibromin 1 (NF1) locus and copy number amplifications of EGFR, cyclin dependent kinase 4 (CDK4), and platelet-derived growth factor receptor alpha (PDGFRA) loci. The intricate combination of inter-as well as intratumoral heterogeneity plays a key role in rendering conventional and experimental targeted therapy approaches ultimately ineffective. [20-22] The majority of glioma cells lack the capacity to recapitulate a phenocopy of the original tumor and only a small subpopulation of neural stem-like cells within the tumor, called glioma stem cells (GSCs) or tumor initiating cells, have that ability upon xenotransplantation in immunocompromised mice. [23-25] Evidence suggests that these GSCs act as a driving Glioblastoma is the most common and aggressive brain tumor in adults. Most patients die within a year and long-term survival remains rare, owing to a combination of rapid progression/degeneration, lack of successful treatments, and high recurrence rates. Extracellular vesicles are cell-derived membranous structures involved in numerous physiological and pathological processes. In the context of cancer, th...

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Section: Evs and The Tumor Microenvironmentmentioning

confidence: 99%