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

и другие.

Neuro-Oncology Advances, Год журнала: 2025, Номер 7(1)

Опубликована: Янв. 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.

Язык: Английский

Lysine catabolism reprograms tumour immunity through histone crotonylation DOI
Huairui Yuan, Xujia Wu, Qiulian Wu

и другие.

Nature, Год журнала: 2023, Номер 617(7962), С. 818 - 826

Опубликована: Май 17, 2023

Язык: Английский

Процитировано

94
Nanoparticles for Drug and Gene Delivery in Pediatric Brain Tumors’ Cancer Stem Cells: Current Knowledge and Future Perspectives DOI Creative Commons
Luana Abballe, Zaira Spinello, Celeste Antonacci

и другие.

Pharmaceutics, Год журнала: 2023, Номер 15(2), С. 505 - 505

Опубликована: Фев. 2, 2023

Primary malignant brain tumors are the most common solid neoplasm in childhood. Despite recent advances, many children affected by aggressive or metastatic still present poor prognosis, therefore development of more effective therapies is urgent. Cancer stem cells (CSCs) have been discovered and isolated both pediatric adult patients with (e.g., medulloblastoma, gliomas ependymoma). CSCs a small clonal population cancer responsible for tumor initiation, maintenance progression, displaying resistance to conventional anticancer therapies. characterized specific repertoire surface markers intracellular pathways. These unique features biology offer opportunity build therapeutic approaches specifically target these complex bulk. Treatment classical chemotherapeutic regimen poses challenges location presence blood-brain barrier (BBB). Lastly, application chemotherapy developing followed long-term sequelae, especially on cognitive abilities. Novel avenues emerging panorama taking advantage nanomedicine. In this review we will summarize nanoparticle-based efficacy that NPs intrinsically demonstrated how they also decorated biomolecules. Furthermore, propose novel cargoes together advances nanoparticle design/synthesis final aim insidious

Язык: Английский

Процитировано

30
Kunitz-type protease inhibitor TFPI2 remodels stemness and immunosuppressive tumor microenvironment in glioblastoma DOI
Lizhi Pang, Madeline Dunterman,

Songlin Guo

и другие.

Nature Immunology, Год журнала: 2023, Номер 24(10), С. 1654 - 1670

Опубликована: Сен. 4, 2023

Язык: Английский

Процитировано

29
Circulating Liquid Biopsy Biomarkers in Glioblastoma: Advances and Challenges DOI Open Access
Attila A. Seyhan

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7974 - 7974

Опубликована: Июль 21, 2024

Gliomas, particularly glioblastoma (GBM), represent the most prevalent and aggressive tumors of central nervous system (CNS). Despite recent treatment advancements, patient survival rates remain low. The diagnosis GBM traditionally relies on neuroimaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scans postoperative confirmation via histopathological molecular analysis. Imaging techniques struggle to differentiate between tumor progression treatment-related changes, leading potential misinterpretation delays. Similarly, tissue biopsies, while informative, are invasive not suitable for monitoring ongoing treatments. These challenges have led emergence liquid biopsy, through blood samples, a promising alternative monitoring. Presently, cerebrospinal fluid (CSF) sampling offers minimally means obtaining tumor-related information guide therapy. idea that any biofluid tests can be used screen many cancer types has huge potential. Tumors release various components into bloodstream other biofluids, including cell-free nucleic acids microRNAs (miRNAs), circulating DNA (ctDNA), cells (CTCs), proteins, extracellular vesicles (EVs) exosomes, metabolites, factors. factors been shown cross blood-brain barrier (BBB), presenting an opportunity well real-time assessment distinct genetic, epigenetic, transcriptomic, proteomic, metabolomic changes associated with brain tumors. their potential, clinical utility biopsy-based biomarkers is somewhat constrained by limitations absence standardized methodologies CSF collection, analyte extraction, analysis methods, small cohort sizes. Additionally, biopsies offer more precise insights morphology microenvironment. Therefore, objective biopsy should complement enhance diagnostic accuracy patients providing additional alongside traditional biopsies. Moreover, utilizing combination diverse biomarker may effectiveness compared solely relying one category, potentially improving sensitivity specificity addressing some existing GBM. This review presents overview latest research found in discusses diagnostic, predictive, prognostic indicators, future perspectives.

Язык: Английский

Процитировано

13
Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming DOI
Xujia Wu, Huairui Yuan,

Qiulian Wu

и другие.

Nature Cancer, Год журнала: 2024, Номер 5(7), С. 1024 - 1044

Опубликована: Март 22, 2024

Язык: Английский

Процитировано

11
Microenvironmental reorganization in brain tumors following radiotherapy and recurrence revealed by hyperplexed immunofluorescence imaging DOI Creative Commons
Spencer S. Watson,

Benoît Duc,

Ziqi Kang

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 15, 2024

Abstract The tumor microenvironment plays a crucial role in determining response to treatment. This involves series of interconnected changes the cellular landscape, spatial organization, and extracellular matrix composition. However, assessing these alterations simultaneously is challenging from perspective, due limitations current high-dimensional imaging techniques extent intratumoral heterogeneity over large lesion areas. In this study, we introduce proteomic workflow termed Hyperplexed Immunofluorescence Imaging (HIFI) that overcomes limitations. HIFI allows for simultaneous analysis > 45 markers fragile tissue sections at high magnification, using cost-effective high-throughput workflow. We integrate with machine learning feature detection, graph-based network analysis, cluster-based neighborhood analyze radiation therapy preclinical model glioblastoma, compare mouse breast-to-brain metastasis. Here show glioblastomas undergo extensive reorganization immune cell populations structural architecture treatment, while brain metastases no comparable reorganization. Our integrated analyses reveal highly divergent responses between models, despite equivalent radiotherapy benefit.

Язык: Английский

Процитировано

11
Lactate reprograms glioblastoma immunity through CBX3-regulated histone lactylation DOI Creative Commons
Shuai Wang, Tengfei Huang, Qiulian Wu

и другие.

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(22)

Опубликована: Ноя. 14, 2024

Glioblastoma (GBM), an aggressive brain malignancy with a cellular hierarchy dominated by GBM stem cells (GSCs), evades antitumor immunity through mechanisms that remain incompletely understood. Like most cancers, GBMs undergo metabolic reprogramming toward glycolysis to generate lactate. Here, we show lactate production patient-derived GSCs and microglia/macrophages induces tumor cell epigenetic histone lactylation, activating modification leads immunosuppressive transcriptional programs suppression of phagocytosis via upregulation CD47, "don't eat me" signal, in cells. Leveraging these findings, pharmacologic targeting augments efficacy anti-CD47 therapy. Mechanistically, lactylated interacts the heterochromatin component chromobox protein homolog 3 (CBX3). Although CBX3 does not possess direct lactyltransferase activity, binds acetyltransferase (HAT) EP300 induce increased substrate specificity lactyl-CoA shift cytokine profile. Targeting inhibits growth both cell–intrinsic phagocytosis. Collectively, results suggest mediates metabolism-induced contributes CD47-dependent immune evasion, which can be leveraged augment immuno-oncology therapies.

Язык: Английский

Процитировано

11
Glioblastoma cells increase expression of notch signaling and synaptic genes within infiltrated brain tissue DOI Creative Commons
Dylan Harwood, Vilde Pedersen,

Nicolai S. Bager

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Сен. 9, 2024

Язык: Английский

Процитировано

9
CYP3A5 promotes glioblastoma stemness and chemoresistance through fine-tuning NAD+/NADH ratio DOI Creative Commons
Wentao Hu, Xing Cui, Hongyu Liu

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Янв. 3, 2025

Язык: Английский

Процитировано

1
Lysine-specific histone demethylase 1A (KDM1A/LSD1) inhibition attenuates DNA double-strand break repair and augments the efficacy of temozolomide in glioblastoma DOI
Salvador Alejo, Bridgitte E. Palacios,

Prabhakar Pitta Venkata

и другие.

Neuro-Oncology, Год журнала: 2023, Номер 25(7), С. 1249 - 1261

Опубликована: Янв. 18, 2023

Abstract Background Efficient DNA repair in response to standard chemo and radiation therapies often contributes glioblastoma (GBM) therapy resistance. Understanding the mechanisms of resistance identifying drugs that enhance therapeutic efficacy may extend survival GBM patients. In this study, we investigated role KDM1A/LSD1 double-strand break (DSB) a combination KDM1A inhibitor temozolomide (TMZ) vitro vivo using patient-derived glioma stem cells (GSCs). Methods Brain bioavailability (NCD38) was established LS-MS/MS. The effect knockdown or inhibition with TMZ studied cell viability self-renewal assays. Mechanistic studies were conducted CUT&Tag-seq, RNA-seq, RT-qPCR, western blot, homologous recombination (HR) non-homologous end joining (NHEJ) reporter, immunofluorescence, comet Orthotopic murine models used study vivo. Results TCGA analysis showed is highly expressed TMZ-treated Knockdown knockout enhanced reducing GSCs. Pharmacokinetic NCD38 readily crosses blood-brain barrier. CUT&Tag-seq enriched at promoters genes RNA-seq confirmed reduced their expression. attenuated HR NHEJ-mediated capacity TMZ-mediated damage. A treatment significantly tumor-bearing mice. Conclusions Our results provide evidence sensitizes via attenuation DSB pathways.

Язык: Английский

Процитировано

17