Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma

Cell Reports, Journal Year: 2017, Volume and Issue: 21(5), P. 1399 - 1410

Published: Oct. 1, 2017

Glioblastoma (GBM) is the most common primary brain cancer in adults and notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq) on 3,589 cells a cohort four patients. obtained from tumor core as well surrounding peripheral tissue. Our analysis revealed cellular variation tumor's genome transcriptome. were also able identify infiltrating neoplastic regions lesions. Despite existence significant heterogeneity among cells, we found that GBM share consistent gene signature between patients, suggesting mechanism infiltration. Additionally, investigating immunological response tumors, transcriptionally distinct myeloid cell populations residing peritumoral space. data provide detailed dissection types, revealing an abundance information about formation migration.

Language: Английский

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Anticancer drug-loaded hydrogels as drug delivery systems for the local treatment of glioblastoma

Journal of Controlled Release, Journal Year: 2016, Volume and Issue: 243, P. 29 - 42

Published: Sept. 30, 2016

Language: Английский

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Pathological and Molecular Features of Glioblastoma and Its Peritumoral Tissue

Cancers, Journal Year: 2019, Volume and Issue: 11(4), P. 469 - 469

Published: April 3, 2019

Glioblastoma (GBM) is one of the most aggressive and lethal human brain tumors. At present, GBMs are divided in primary secondary on basis mutational status isocitrate dehydrogenase (IDH) genes. In addition, IDH1 IDH2 mutations considered crucial to better define prognosis. Although histologically indistinguishable, they retain distinct genetic alterations that account for different evolution tumor. The high invasiveness, propensity disperse throughout parenchyma, elevated vascularity make these tumors extremely recidivist, resulting a short patient median survival even after surgical resection chemoradiotherapy. Furthermore, GBM an immunologically cold Several studies highlight highly immunosuppressive tumor microenvironment promotes recurrence poor Deeper insight into immune microenvironment, together with recent discovery conventional lymphatic system central nervous (CNS), led new immunotherapeutic strategies. last two decades, experimental evidence from groups proved existence cancer stem cells (CSCs), also known as tumor-initiating cells, may play active role development progression. Recent findings indicated presence infiltrative CSCs peritumoral region GBM. This appears key growing recurrence. However, until recently, few investigated biomolecular characteristics tissue. aim this review recapitulate pathological features associated progression

Language: Английский

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RSL3 Drives Ferroptosis through NF‐κB Pathway Activation and GPX4 Depletion in Glioblastoma

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Glioblastoma, the most aggressive form of malignant glioma, is very difficult to treat because its aggressively invasive nature and high recurrence rates. RAS-selective lethal 3 (RSL3), a well-known inhibitor glutathione peroxidase 4 (GPX4), could effectively induce oxidative cell death in glioblastoma cells through ferroptosis, several signaling pathways are involved this process. However, role nuclear factor kappa-B (NF-κB) pathway ferroptosis has not yet been investigated. Therefore, we aimed clarify underlying mechanism NF-κB RSL3-induced cells. We found that RSL3 led an increase lipid ROS concentration downregulation ferroptosis-related proteins such as GPX4, ATF4, SLC7A11 (xCT) Additionally, was activated by RSL3, inhibition BAY 11-7082 alleviate ferroptosis. The murine xenograft tumor model indicated mitigate antitumor effects vivo. Furthermore, GPX4 knockdown activation coupled with silencing induced ATF4 xCT expression might be regulated pathway. Collectively, our results revealed plays novel provides new therapeutic strategy for treatment.

Language: Английский

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Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration

Nature Nanotechnology, Journal Year: 2022, Volume and Issue: 17(12), P. 1322 - 1331

Published: Oct. 27, 2022

Language: Английский

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Glioblastoma Treatment: State-of-the-Art and Future Perspectives

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 7207 - 7207

Published: June 29, 2022

(1) Background: Glioblastoma is the most frequent and lethal primary tumor of central nervous system. Through many years, research has brought various advances in glioblastoma treatment. At this time, management based on maximal safe surgical resection, radiotherapy, chemotherapy with temozolomide. Recently, bevacizumab been added to treatment arsenal for recurrent scenario. Nevertheless, patients still have a poor prognosis. Therefore, efforts are being made different clinical areas find new alternative improve overall survival, free-progression life quality patients. (2) Methods: Our objective recap actual state-of-the-art treatment, resume future perspectives immunotherapy, as well synthetic molecules natural compounds that represent potential therapies at preclinical stages. (3) Conclusions: Despite great therapeutic research, suffered minimal changes, prognosis remains poor. Combined strategies delivery methods, including molecules, compounds, stem cell inhibition, may potentiate standard care therapy next step research.

Language: Английский

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Immunotherapy in glioblastoma treatment: Current state and future prospects

World Journal of Clinical Oncology, Journal Year: 2023, Volume and Issue: 14(4), P. 138 - 159

Published: April 20, 2023

Glioblastoma remains as the most common and aggressive malignant brain tumor, standing with a poor prognosis treatment prospective. Despite standard care, such surgical resection chemoradiation, median survival rates are low. In this regard, immunotherapeutic strategies aim to become more attractive for glioblastoma, considering its recent advances approaches. review, we provide an overview of current status progress in immunotherapy going through fundamental knowledge on immune targeting promising strategies, Chimeric antigen receptor T-Cell therapy, checkpoint inhibitors, cytokine-based treatment, oncolytic virus vaccine-based techniques. At last, it is discussed innovative methods overcome diverse challenges, future perspectives area.

Language: Английский

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ATRX, a guardian of chromatin

Trends in Genetics, Journal Year: 2023, Volume and Issue: 39(6), P. 505 - 519

Published: March 7, 2023

ATRX (alpha-thalassemia mental retardation X-linked) is one of the most frequently mutated tumor suppressor genes in human cancers, especially glioma, and recent findings indicate roles for key molecular pathways, such as regulation chromatin state, gene expression, DNA damage repair, placing a central player maintenance genome stability function. This has led to new perspectives about functional role its relationship with cancer. Here, we provide an overview interactions functions discuss consequences impairment, including alternative lengthening telomeres therapeutic vulnerabilities that may be exploited cancer cells.

Language: Английский

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D‐type neuropeptide decorated AIEgen/RENP hybrid nanoprobes with light‐driven ROS generation ability for NIR‐II fluorescence imaging‐guided through‐skull photodynamic therapy of gliomas

Aggregate, Journal Year: 2023, Volume and Issue: 5(1)

Published: July 31, 2023

Abstract Glioma is one of the most common malignant tumors central nervous system, leading high mortality rates in human. Aggregation‐induced emission (AIE) photosensitizers‐based photodynamic therapy (PDT) has emerged as a promising therapeutic strategy for least‐invasive treatment glioma, which involves local irradiation tumor using an external near‐infrared (NIR) laser. Unfortunately, AIE photosensitizers suffered from poorly penetration visible light excitation, bad spatiotemporal resolution deep tissues and low efficient blood‐brain barrier (BBB) crossing ability, greatly limited clinical practice especially deep‐seated brain treatment. In this work, we developed multifunctional NIR‐driven theranostic agent through hybrid TIND with rare‐earth doping nanoparticles (RENPs) NaGdF 4 :Nd/Yb/Tm up/down dual‐mode conversion luminescence. The was further decorated D‐type neuropeptide D NPY BBB targeting glioma. Under 808‐nm irradiation, down‐conversion NIR‐II luminescence could indicate position glioma upconversion NIR‐I trigger producing reactive oxygen species to inhibit orthotopic growth situ. These results demonstrate that integration neuropeptide, RENPs be candidates vivo fluorescence image‐guided through‐skull PDT treatments tumors.

Language: Английский

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Brain tumor classification from MRI scans: a framework of hybrid deep learning model with Bayesian optimization and quantum theory-based marine predator algorithm

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 8, 2024

Brain tumor classification is one of the most difficult tasks for clinical diagnosis and treatment in medical image analysis. Any errors that occur throughout brain process may result a shorter human life span. Nevertheless, currently used techniques ignore certain features have particular significance relevance to problem favor extracting choosing deep features. One important area research learning-based categorization tumors using magnetic resonance imaging (MRI). This paper proposes an automated learning model optimal information fusion framework classifying from MRI images. The dataset this work was imbalanced, key challenge training selected networks. imbalance impacts performance models because it causes classifier become biased majority class. We designed sparse autoencoder network generate new images resolve imbalance. After that, two pretrained neural networks were modified hyperparameters initialized Bayesian optimization, which later utilized process. extracted global average pooling layer. contain few irrelevant information; therefore, we proposed improved Quantum Theory-based Marine Predator Optimization algorithm (QTbMPA). QTbMPA selects both networks’ best finally fuses serial-based approach. fused feature set passed classifiers final classification. tested on augmented Figshare accuracy 99.80%, sensitivity rate 99.83%, false negative 17%, precision 99.83% obtained. Comparison ablation study show improvement work.

Language: Английский

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