Glioblastoma: An Update in Pathology, Molecular Mechanisms and Biomarkers

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 3040 - 3040

Published: March 6, 2024

Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances understanding molecular pathogenesis biology this past decade, prognosis for GBM patients remains poor. characterized by aggressive biological behavior high degrees inter-tumor intra-tumor heterogeneity. Increased cellular heterogeneity may not only help more accurately define specific subgroups precise diagnosis but also lay groundwork successful implementation targeted therapy. Herein, we systematically review key achievements pathogenesis, mechanisms, biomarkers decade. We discuss pathology GBM, including genetics, epigenetics, transcriptomics, signaling pathways. that have potential clinical roles. Finally, new strategies, current challenges, future directions discovering therapeutic targets will be discussed.

Language: Английский

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Emerging role of exosomes in cancer therapy: progress and challenges

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 13, 2025

This review highlights recent progress in exosome-based drug delivery for cancer therapy, covering exosome biogenesis, cargo selection mechanisms, and their application across multiple types. As small extracellular vesicles, exosomes exhibit high biocompatibility low immunogenicity, making them ideal vehicles capable of efficiently targeting cells, minimizing off-target damage side effects. aims to explore the potential with a focus on applications chemotherapy, gene immunomodulation. Additionally, challenges related production standardization are analyzed, highlighting importance addressing these issues clinical application. In conclusion, systems offer promising future therapies. Further research should aim enhance efficiency facilitate translation, paving way innovative treatment strategies.

Language: Английский

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Single‐cell RNA sequencing reveals tumor heterogeneity, microenvironment, and drug‐resistance mechanisms of recurrent glioblastoma

Cancer Science, Journal Year: 2023, Volume and Issue: 114(6), P. 2609 - 2621

Published: Feb. 28, 2023

Glioblastomas are highly heterogeneous brain tumors. Despite the availability of standard treatment for glioblastoma multiforme (GBM), i.e., Stupp protocol, which involves surgical resection followed by radiotherapy and chemotherapy, remains refractory to recurrence is inevitable. Moreover, biology recurrent unclear. Increasing evidence has shown that intratumoral heterogeneity tumor microenvironment contribute therapeutic resistance. However, interaction between intracellular drug resistance in GBMs controversial. The aim this study was map transcriptome landscape cancer cells drug-resistant at a single-cell resolution further explore mechanism GBMs. We analyzed six tissue samples from three patients with primary GBM developed after protocol using RNA sequencing. Using unbiased clustering, nine major cell clusters were identified. Upregulation expression stemness-related cell-cycle-related genes observed cells. Compared initial tissues, tissues showed decreased proportion microglia, consistent previous reports. Finally, vascular endothelial growth factor A blood-brain barrier permeability high, O6 -methylguanine DNA methyltransferase-related signaling pathway activated GBM. Our results delineate glioblastoma, heterogeneity, microenvironment, drug-resistance mechanisms, providing new insights into strategies glioblastomas.

Language: Английский

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Emerging applications of machine learning in genomic medicine and healthcare

Critical Reviews in Clinical Laboratory Sciences, Journal Year: 2023, Volume and Issue: 61(2), P. 140 - 163

Published: Oct. 10, 2023

AbstractThe integration of artificial intelligence technologies has propelled the progress clinical and genomic medicine in recent years. The significant increase computing power facilitated ability models to analyze extract features from extensive medical data images, thereby contributing advancement intelligent diagnostic tools. Artificial (AI) have been utilized field personalized integrate information patients. This allows for identification customized treatment recommendations, ultimately leading enhanced patient outcomes. Notwithstanding notable advancements, application is impeded by various obstacles such as limited availability data, diversity datasets, ethical implications, inconclusive interpretation AI models' results. In this review, a comprehensive evaluation multiple machine learning algorithms fields conducted. Furthermore, we present an overview implementation medicine, drug discovery, medicine. Finally, number constraints pertaining within healthcare industry are examined.Keywords: Genomic medicineclinical medicineartificial intelligencemachine learningdeep Disclosure statementNo potential conflict interest was reported author(s).Additional informationFundingThe author(s) there no funding associated with work featured article.

Language: Английский

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Enhancing cancer immunotherapy: Nanotechnology-mediated immunotherapy overcoming immunosuppression

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(9), P. 3834 - 3854

Published: June 3, 2024

Immunotherapy is an important cancer treatment method that offers hope for curing patients. While immunotherapy has achieved initial success, a major obstacle to its widespread adoption the inability benefit majority of The success or failure closely linked tumor's immune microenvironment. Recently, there been significant attention on strategies regulate tumor microenvironment in order stimulate anti-tumor responses immunotherapy. distinctive physical properties and design flexibility nanomedicines have extensively utilized target cells (including tumor-associated macrophages (TAMs), T cells, myeloid-derived suppressor (MDSCs), fibroblasts (TAFs)), offering promising advancements In this article, we reviewed aimed at targeting various focus models are based nanomedicines, with goal inducing enhancing improve It worth noting combining other treatments, such as chemotherapy, radiotherapy, photodynamic therapy, can maximize therapeutic effects. Finally, identified challenges nanotechnology-mediated needs overcome more effective nanosystems.

Language: Английский

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The Interplay between Glioblastoma Cells and Tumor Microenvironment: New Perspectives for Early Diagnosis and Targeted Cancer Therapy

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(4), P. 331 - 331

Published: March 29, 2024

Glioblastoma multiforme (GBM) stands out as the most tremendous brain tumor, constituting 60% of primary cancers, accompanied by dismal survival rates. Despite advancements in research, therapeutic options remain limited to chemotherapy and surgery. GBM molecular heterogeneity, intricate interaction with tumor microenvironment (TME), non-selective treatments contribute neoplastic relapse. Diagnostic challenges arise from advanced-stage detection, necessitating exploration novel biomarkers for early diagnosis. Using data literature a bioinformatic tool, current manuscript delineates interplay between human GBM, astrocytes, myeloid cells, underscoring selected protein pathways belonging astroglia lineage, which can be considered targeted therapies. Moreover, pivotal role extracellular vesicles (EVs) orchestrating favorable cancer progression is highlighted, suggesting their utility identifying

Language: Английский

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The Advancement and Application of the Single-Cell Transcriptome in Biological and Medical Research

Biology, Journal Year: 2024, Volume and Issue: 13(6), P. 451 - 451

Published: June 19, 2024

Single-cell RNA sequencing technology (scRNA-seq) has been steadily developing since its inception in 2009. Unlike bulk RNA-seq, scRNA-seq identifies the heterogeneity of tissue cells and reveals gene expression changes individual at microscopic level. Here, we review development scRNA-seq, which gone through iterations reverse transcription, vitro smart-seq, drop-seq, 10 × Genomics, spatial single-cell transcriptome technologies. The Genomics widely applied medicine biology, producing rich research results. Furthermore, this presents a summary analytical process for data integration with other omics analyses, including genomes, epigenomes, proteomes, metabolomics. wide range applications biology medicine. This analyzes cancer, stem cell research, developmental microbiology, fields. In essence, provides means elucidating patterns single cells, thereby offering valuable tool scientific research. Nevertheless, current is still imperfect, shortcomings anticipates future developments. objective to facilitate deeper comprehension biological medical as well identify avenues alignment practical needs.

Language: Английский

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Breaking the barrier: Nanoparticle-enhanced radiotherapy as the new vanguard in brain tumor treatment

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 3, 2024

The pursuit of effective treatments for brain tumors has increasingly focused on the promising area nanoparticle-enhanced radiotherapy (NERT). This review elucidates context and significance NERT, with a particular emphasis its application in tumor therapy—a field where traditional often encounter obstacles due to blood-brain barrier (BBB) cells’ inherent resistance. aims this include synthesizing recent advancements, analyzing action mechanisms, assessing clinical potential challenges associated nanoparticle (NP) use enhancement. Preliminary preclinical studies have established foundation demonstrating that nanoparticles (NPs) can serve as radiosensitizers, thereby intensifying radiotherapy’s efficacy. Investigations into various NP types, such metallic, magnetic, polymeric, each unveiled distinct interactions ionizing radiation, leading an augmented destruction cells. These interactions, encompassing physical dose enhancement biological chemical radio sensitization, are crucial NERT strategy. Although their early phases, initial trials shown results terms response rates survival, albeit mindful consideration toxicity profiles. examines pivotal affirming NERT’s efficacy safety. NPs revolutionize by overcoming targeted delivery, reducing off-target effects, harmonizing other modalities. Future directions refining formulations, personalizing therapies, navigating regulatory pathways. holds promise transform treatment provide hope patients.

Language: Английский

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The diversity and dynamics of tumor-associated macrophages in recurrent glioblastoma

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 4, 2023

Despite tremendous efforts to exploit effective therapeutic strategies, most glioblastoma (GBM) inevitably relapse and become resistant therapies, including radiotherapy immunotherapy. The tumor microenvironment (TME) of recurrent GBM (rGBM) is highly immunosuppressive, dominated by tumor-associated macrophages (TAMs). TAMs consist tissue-resident microglia monocyte-derived (MDMs), which are essential for favoring growth, invasion, angiogenesis, immune suppression, resistance; however, restricted the absence potent methods, heterogeneity plasticity in rGBM remain incompletely investigated. Recent application single-cell technologies, such as RNA-sequencing has enabled us decipher unforeseen diversity dynamics identify new subsets regulate anti-tumor immunity. Here, we first review hallmarks TME, progress challenges immunotherapy, biology context rGBM, their origins, categories, functions. Next, from a perspective, highlight recent findings regarding distinctions between MDMs, identification characterization specific TAM subsets, dynamic alterations during progression treatment. Last, briefly discuss potential TAM-targeted strategies combination immunotherapy rGBM. We anticipate comprehensive understanding will shed light on further improvement immunotherapeutic efficacy

Language: Английский

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Single-cell RNA sequencing identifies a subtype of FN1 + tumor-associated macrophages associated with glioma recurrence and as a biomarker for immunotherapy

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Oct. 7, 2024

Abstract Background Glioma is the most common primary malignant tumor in brain, and even with standard treatments including surgical resection, radiotherapy, chemotherapy, long-term survival rate of patients remains unsatisfactory. Recurrence one leading causes death glioma patients. The molecular mechanisms underlying recurrence remain unclear. Methods Our study utilized single-cell sequencing, spatial transcriptomics, RNA-seq data to identify a subtype FN1 + tumor-associated macrophages (FN1 TAMs) associated recurrence. Results This revealed an increased abundance TAMs recurrent gliomas, indicating their potential involvement as critical factor A negative correlation was observed between gliomas interval time recurrence, suggesting poor prognosis for high levels TAMs. Further investigation showed that were enriched hypoxic regions, implying metabolic changes tumors drive production recruitment Additionally, found contribute regulation immunosuppressive microenvironment might serve indicator patients’ sensitivity immunotherapy. Finally, we developed user-friendly website, PRIMEG ( http://www.szflab.site/PRIMEG/ ), exploring immune gliomas. Conclusion findings highlight providing new insights into therapeutic targets. Moreover, hold promise predicting therapy response aiding more precise risk stratification

Language: Английский

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