Advancing Glioblastoma Therapy: Learning From the Past and Innovations for the Future

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217601 - 217601

Published: March 1, 2025

Language: Английский

---

Role of GPX3+ astrocytes in breast cancer brain metastasis activated by circulating tumor cell exosomes

npj Precision Oncology, Journal Year: 2025, Volume and Issue: 9(1)

Published: March 7, 2025

Brain metastasis from breast cancer (BMBC) contributes significantly to mortality, yet its mechanisms remain unclear. This study investigates the activation of GPX3+ astrocytes by circulating tumor cell (CTC)-derived exosomes in metastatic process. Using a mouse model BMBC, we performed single-cell RNA sequencing (scRNA-seq) and metabolomics explore role brain microenvironment. We found that CTCs activate these astrocytes, promoting IL-1β production Th17 differentiation, crucial for formation niche. Conditional knockout GPX3 reduced extended survival, highlighting importance metastasis. Our findings uncover novel mechanism which drive metastasis, suggesting new therapeutic targets intervention.

Language: Английский

---

Cortical thickness deviations as biomarker for subtyping and prognosis in pediatric brainstem tumors

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 16, 2025

Language: Английский

---

Assessment of Cognitive Functioning in Glioma Patients

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

---

Ion Channels and Ionotropic Receptors in Astrocytes: Physiological Functions and Alterations in Alzheimer’s Disease and Glioblastoma

Life, Journal Year: 2023, Volume and Issue: 13(10), P. 2038 - 2038

Published: Oct. 11, 2023

The human brain is composed of nearly one hundred billion neurons and an equal number glial cells, including macroglia, i.e., astrocytes oligodendrocytes, microglia, the resident immune cells brain. In last few decades, compelling evidence has revealed that are far more active complex than previously thought. particular, astrocytes, most abundant cell population, not only take part in development, metabolism, defense against pathogens insults, but they also affect sensory, motor, cognitive functions by constantly modulating synaptic activity. Not surprisingly, actively involved neurodegenerative diseases (NDs) other neurological disorders like tumors, which rapidly become reactive mediate neuroinflammation. Reactive acquire or lose specific differently modulate disease progression symptoms, impairments. Astrocytes express several types ion channels, K+, Na+, Ca2+ transient receptor potential channels (TRP), aquaporins, mechanoreceptors, anion whose properties partially understood, particularly small processes contact synapses. addition, ionotropic receptors for neurotransmitters. Here, we provide extensive up-to-date review roles astrocyte physiology pathology. As examples two different pathologies, focus on Alzheimer’s (AD), diffuse disorders, glioblastoma (GBM), common tumor. Understanding how participate NDs tumors necessary developing new therapeutic tools these increasingly conditions.

Language: Английский

---

Inhibition of exosome biogenesis affects cell motility in heterogeneous sub-populations of paediatric-type diffuse high-grade gliomas

Cell & Bioscience, Journal Year: 2023, Volume and Issue: 13(1)

Published: Nov. 13, 2023

Abstract Background Paediatric-type diffuse High-Grade Gliomas (PDHGG) are highly heterogeneous tumours which include distinct cell sub-populations co-existing within the same tumour mass. We have previously shown that primary patient-derived and optical barcoded single-cell-derived clones function as interconnected networks. Here, we investigated role of exosomes a route for inter-clonal communication mediating PDHGG migration invasion. Results A comprehensive characterisation seven obtained from two lines was performed. These analyses highlighted extensive intra-tumour heterogeneity in terms genetic transcriptional profiles between well marked phenotypic differences including distinctive motility patterns. Live single-cell tracking analysis 3D invasion assays showed display higher speed longer travelled distance when co-culture compared to mono-culture conditions. To determine cross-talks, isolated released by different characterised them marker expression, size concentration. demonstrated actively internalized cells inhibition their biogenesis, using phospholipase inhibitor GW4689, significantly reduced more prominently were co-culture. Analysis exosomal miRNAs, performed with miRNome PCR panel, identified clone-specific miRNAs set miRNA target genes involved regulation motility/invasion/migration. found differentially expressed versus conditions expression levels modulated upon exosome biogenesis. Conclusions In conclusion, our study highlights first time key suggests interfering biogenesis pathway may be valuable strategy inhibit dissemination these specific diseases.

Language: Английский

---

Normative Growth Modeling of Cortical Thickness Identify Neuroanatomical Variability and Distinct Subtypes in Brainstem Tumor Patients

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 2, 2024

Abstract Background Brainstem tumors can cause structural brain changes, but the resulting heterogeneity within wholebrain structure is not well-studied. This study examines cortical thickness to identify patterns of alterations and explore underlying biological subtypes their associations with clinical factors. Materials Methods involved 124 pediatric brainstem tumor patients, aged 4-18 years. Cortical was measured using CAT12 segmentation 3D T1-weighted MRI. A normative model established data from 849 healthy children. Deviations in were estimated, patients classified into two spectral clustering. Clinical statistical analyses conducted SPSS 26.0. Results The revealed significant deviations, which correlated size growth patterns. Focal primarily caused negative deviations (t = 3.14, p 0.02). There a positive correlation between extreme volume (r 0.214, 0.010), progression-free survival 0.39, 0.008). Two identified: Subtype 1, consisting diffuse 2, focal deviations. pattern significantly influenced duration (p < 0.01). Kaplan-Meier curves for 1 2 demonstrated difference probabilities over time 0.03). Conclusion Overall, this identifies major changes enhancing our understanding relationship morphology. findings suggest that could serve as valuable biomarkers predicting survival, crucial assessment personalized treatment strategies. research provides new insights physiological mechanisms by affect structure, supporting more precise interventions efficacy monitoring future.

Language: Английский

---

Wnt signaling in the tumor microenvironment: A driver of brain tumor dynamics

Life Sciences, Journal Year: 2024, Volume and Issue: unknown, P. 123174 - 123174

Published: Oct. 1, 2024

Language: Английский

---

Insights from a multiscale framework on metabolic rate variation driving glioblastoma multiforme growth and invasion

Communications Engineering, Journal Year: 2024, Volume and Issue: 3(1)

Published: Nov. 25, 2024

Non-physiological levels of oxygen and nutrients within the tumors result in heterogeneous cell populations that exhibit distinct necrotic, hypoxic, proliferative zones. Among these zonal cellular properties, metabolic rates strongly affect overall growth invasion tumors. Here, we report on a hybrid discrete-continuum (HDC) mathematical framework uses data from biomimetic two-dimensional (2D) in-vitro cancer model to predict three-dimensional (3D) behaviour human glioblastoma (hGB). The integrates modules continuum, discrete, neurons. Results indicated HDC is capable quantitatively predicting growth, length, asymmetric finger-type pattern hGB Additionally, could reduction length tumoroids response temozolomide (TMZ). This has potential incorporate additional modules, including immune cells signaling pathways governing cancer/immune interactions, can be used investigate targeted therapies. Meitham Amereh colleagues cancerous invasion, treatment tumours. Their in-silico glioblastoma.

Language: Английский

---

Nuancing the Limitations of Axonal Plasticity in World Health Organization Grade II Gliomas: White Matter Tracts Compensation Is Driven by Cortical Remodeling

Neurosurgery, Journal Year: 2023, Volume and Issue: 93(4), P. e85 - e91

Published: April 19, 2023

Diffuse World Health Organization grade II glioma (GIIG) is a slow-growing brain cancer that migrates along the white matter (WM) tracts. Neuroplastic changes were described in reaction to GIIG progression, opening window extensive cerebral surgical resection patients able resume an active life with no functional consequences. However, atlases of cortico-subcortical neural plasticity emphasized limited potential axonal reorganization. Yet, removal WM involved by can be possible, at least some extent, without generating permanent neurological disturbances. Here, aim was discuss mechanisms underlying compensation which make feasible subcortical component and propose new model adaptative reconfiguration level connectivity. In this model, 2 parts tracts are considered: (1) stem bundle represents actual limitation plastic potential, as supported reproducible behavioral disorders elicited intraoperative electrostimulation mapping (ESM) (2) terminations/origins may longer critical case reallocation cortex to/from these fibers run-thus inducing troubles during direct ESM. Understanding certain degree specific portions driven cortical remodeling enable rethink concept refine preoperative estimation extent for GIIG. Identifying eloquent ESM, especially their convergence depth, essential achieve individualized connectome-based resection.

Language: Английский

---