The Slovenian translational platform GlioBank for brain tumour research: identification of molecular signatures of glioblastoma progression DOI Creative Commons
Metka Novak, Bernarda Majc, Marta Malavolta

et al.

Neuro-Oncology Advances, Journal Year: 2025, Volume and Issue: 7(1)

Published: Jan. 1, 2025

Abstract Background Glioblastoma (GB) is one of the most lethal solid tumors in humans, with an average patient life expectancy 15 months and a 5-year survival rate 5%–10%. GB still uncurable due to tumor heterogeneity invasive nature as well therapy-resistant cancer cells. Centralized biobanks clinical data corresponding biological material patients facilitate development new treatment approaches search for clinically relevant biomarkers, goal improving outcomes patients. The aim this study was firstly establish Slovenian translation platform, GlioBank, secondly demonstrate its utility through identification molecular signatures associated progression survival. Methods GlioBank contains tissue samples models from diagnosed glioma, focus on GB. Primary cells, glioblastoma stem cells (GSCs), organoids have been established fresh biopsies. We performed expression analyses genes bioinformatics available research obtained subset 91 qPCR determine therapy resistance cell invasion, including markers different subtypes, GSCs, epithelial-to-mesenchymal transition, immunomodulation/chemokine signaling tissues cellular models. Results research, collected SciNote electronic laboratory notebook. To date, more than 240 glioma stored which are (205) were further processed primary (n = 64), GSCs 14), 17). Corresponding blood plasma 103) peripheral mononuclear 101) also stored. classified into 4 subtypes that differed regarding survival; mixed subtype exhibited longest High DAB2, S100A4, STAT3 poor overall survival, DAB2 found be independent prognostic marker analyzed between regions (core vs. rim). STMN4, ERBB3, ACSBG1 upregulated rim, suggesting these Conclusions centralized biobank has built by multidisciplinary network facilitating disease-oriented basic research. advantages include characterization based targeted gene expression, availability diverse (eg, organoids), large number patient-matched core rim samples, all accompanying data. report here first time association low patients, indicative value DAB2.

Language: Английский

The Cytotoxic Effects of Cannabidiol and Cannabigerol on Glioblastoma Stem Cells May Mostly Involve GPR55 and TRPV1 Signalling DOI Open Access

Tamara T. Lah,

Bernarda Majc, Metka Novak

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(23), P. 5918 - 5918

Published: Nov. 30, 2022

Glioblastoma (GBM) is one of the most aggressive cancers, comprising 60-70% all gliomas. The large G-protein-coupled receptor family includes cannabinoid receptors CB1, CB2, GPR55, and non-specific ion protein transporters TRPs. First, we found up-regulated CNR1, TRPV1 expression in glioma patient-derived tissue samples cell lines compared with non-malignant brain samples. CNR1 GPR55 did not correlate grade, whereas negatively correlated grade positively longer overall survival. This suggests a tumour-suppressor role TRPV1. With respect to markers GBM stem cells, preferred targets therapy, but strongly different sets stemness gene markers: NOTCH, OLIG2, CD9, TRIM28, TUFM CD15, SOX2, OCT4, ID1, respectively. line higher genes GSCs differentiated cells. Second, panel GSCs, that CBG CBD exhibited highest cytotoxicity at molar ratio 3:1. We suggest this mixture should be tested experimental animals clinical studies, which currently used Δ9-tetrahydrocannabinol (THC) replaced efficient non-psychoactive adjuvant standard-of-care therapy.

Language: Английский

Citations

19
Characterization of prevalent tyrosine kinase inhibitors and their challenges in glioblastoma treatment DOI Creative Commons
Mahdie Rahban, Sara Joushi, Hamideh Bashiri

et al.

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 11

Published: Jan. 8, 2024

Glioblastoma multiforme (GBM) is a highly aggressive malignant primary tumor in the central nervous system. Despite extensive efforts radiotherapy, chemotherapy, and neurosurgery, there remains an inadequate level of improvement treatment outcomes. The development large-scale genomic proteomic analysis suggests that GBMs are characterized by transcriptional heterogeneity, which responsible for therapy resistance. Hence, knowledge about genetic epigenetic heterogeneity GBM crucial developing effective treatments this form brain cancer. Tyrosine kinases (TKs) can act as signal transducers, regulate important cellular processes like differentiation, proliferation, apoptosis metabolism. Therefore, TK inhibitors (TKIs) have been developed to specifically target these kinases. TKIs categorized into allosteric non-allosteric inhibitors. Irreversible covalent bonds, lead longer-lasting effects. However, also increase risk off-target effects toxicity. therapeutics through computer-aided drug design (CADD) bioinformatic techniques enhance potential improve patients’ survival rates. continued exploration targets expected even more specific future.

Language: Английский

Citations

4
A Dual‐Channel Ca2+ Nanomodulator Induces Intracellular Ca2+ Disorders via Endogenous Ca2+ Redistribution for Tumor Radiosensitization DOI
Dianyu Wang,

Haixue Jia,

Hongmei Cao

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(29)

Published: May 1, 2024

Tumor cells harness Ca

Language: Английский

Citations

4
Tumor initiating cells escape tumor immunity via CCL8 from tumor-associated macrophages in mice DOI Creative Commons
Shuang Chen, Chen‐Song Huang, Kang Li

et al.

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Tumor-initiating cells (TICs) play a key role in cancer progression and immune escape. However, how TICs evade elimination remains poorly characterized. Combining single-cell RNA sequencing (scRNA-seq), dual-recombinase-based lineage tracing, other approaches, we identified WNT-activated subpopulation of malignant that act as vivo. We found intensive reciprocal interactions between regulatory tumor-associated macrophages (Reg-TAMs) via GAS6-AXL/MERTK signaling pathways, which facilitated the escape TICs. Our study employed chemical inhibitors Axl/Mertk conditional double knockout mice to demonstrate inhibiting interaction TIC-derived GAS6 AXL/MERTK Reg-TAMs reactivated anti-tumor responses. CCL8 critical mediator GAS6/AXL/MERTK pathway, primarily by T cell (Treg) infiltration into tumor. Furthermore, blockade sensitized tumor anti-PD-1 treatment. Thus, elucidated detailed mechanism immunity, providing insights strategies eradicate conventional immunotherapy.

Language: Английский

Citations

0
The Slovenian translational platform GlioBank for brain tumour research: identification of molecular signatures of glioblastoma progression DOI Creative Commons
Metka Novak, Bernarda Majc, Marta Malavolta

et al.

Neuro-Oncology Advances, Journal Year: 2025, Volume and Issue: 7(1)

Published: Jan. 1, 2025

Abstract Background Glioblastoma (GB) is one of the most lethal solid tumors in humans, with an average patient life expectancy 15 months and a 5-year survival rate 5%–10%. GB still uncurable due to tumor heterogeneity invasive nature as well therapy-resistant cancer cells. Centralized biobanks clinical data corresponding biological material patients facilitate development new treatment approaches search for clinically relevant biomarkers, goal improving outcomes patients. The aim this study was firstly establish Slovenian translation platform, GlioBank, secondly demonstrate its utility through identification molecular signatures associated progression survival. Methods GlioBank contains tissue samples models from diagnosed glioma, focus on GB. Primary cells, glioblastoma stem cells (GSCs), organoids have been established fresh biopsies. We performed expression analyses genes bioinformatics available research obtained subset 91 qPCR determine therapy resistance cell invasion, including markers different subtypes, GSCs, epithelial-to-mesenchymal transition, immunomodulation/chemokine signaling tissues cellular models. Results research, collected SciNote electronic laboratory notebook. To date, more than 240 glioma stored which are (205) were further processed primary (n = 64), GSCs 14), 17). Corresponding blood plasma 103) peripheral mononuclear 101) also stored. classified into 4 subtypes that differed regarding survival; mixed subtype exhibited longest High DAB2, S100A4, STAT3 poor overall survival, DAB2 found be independent prognostic marker analyzed between regions (core vs. rim). STMN4, ERBB3, ACSBG1 upregulated rim, suggesting these Conclusions centralized biobank has built by multidisciplinary network facilitating disease-oriented basic research. advantages include characterization based targeted gene expression, availability diverse (eg, organoids), large number patient-matched core rim samples, all accompanying data. report here first time association low patients, indicative value DAB2.

Language: Английский

Citations

0