Integrative Multi-Omic Profiling of the Neoantigen Landscape of Glioblastoma and its Inherent Tumor Microenvironment Reveals Vast Heterogeneity in Immunogenic Signatures DOI
Lin Q,

Yukui Wei,

Geng Xu

и другие.

Опубликована: Янв. 1, 2023

Background: Glioblastoma (GBM) is the most common primary brain malignant tumor and one of lethal human cancers with very limited effective therapeutics. A few neoantigens that have been tested in trials as cancer immunotherapeutic vaccines against GBM demonstrated promising but ambiguous results. However, there no systemic exploration neoantigen landscape its related microenvironment.Methods: An integrated multi-omic approach consisting WES, RNA sequencing, bioinformatic algorisms was applied to comprehensively profile mutation, HLA typing, TCR/BCR repertoire, immune cell components on tissue peripheral blood mononuclear (PMBC) specimen 24 patients. The characterized a cluster peptides designed for this patient cohort.Findings: On average, 148 mutated genes 200 sites per were identified, predominant cohort. Diversified genotypes expression rate across A, B, C alleles, A30:01&A11:01, B13:02, C06:02, frequent at respective alleles. Clustered CDR3 existed decreased richness compared PMBC. NKT Th1 cells revealed within TMB. Neoantigens feasible predicted each patient, an average number 107. Very shared by more than two patients dominant could be identified. minimum 11-peptide bulk required cover 24-patient cohort, guaranteeing least neoantigen.Interpretation: Our study reveals inherent TME heterogeneous immunogenic signatures, which should facilitate optimized design therapeutic terms target selection strategy.Funding: This received support from Beijing Municipal Nature Science Foundation (Grant No. Z191100007619018).Declaration Interest: authors declare competing interests.Ethical Approval: All provided written informed consent sample collection data analyses. approved Ethical Committee Xuanwu Hospital, Beijing, China.

Язык: Английский

Exploring ncRNA-mediated regulation of EGFR signalling in glioblastoma: From mechanisms to therapeutics DOI
Riya Thapa, Muhammad Afzal, Ahsas Goyal

и другие.

Life Sciences, Год журнала: 2024, Номер 345, С. 122613 - 122613

Опубликована: Апрель 4, 2024

Язык: Английский

Процитировано

24

CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review DOI Creative Commons
Emir Begagić, Hakija Bečulić, Nermin Đuzić

и другие.

Biomedicines, Год журнала: 2024, Номер 12(1), С. 238 - 238

Опубликована: Янв. 21, 2024

This scoping review examines the use of CRISPR/Cas9 gene editing in glioblastoma (GBM), a predominant and aggressive brain tumor. Categorizing targets into distinct groups, this explores their roles cell cycle regulation, microenvironmental dynamics, interphase processes, therapy resistance reduction. The complexity CRISPR-Cas9 applications GBM research is highlighted, providing unique insights apoptosis, proliferation, immune responses within tumor microenvironment. studies challenge conventional perspectives on specific genes, emphasizing potential therapeutic implications manipulating key molecular players dynamics. Exploring GBMs yields significant regulation cellular spanning interphase, renewal, migration. Researchers, by precisely targeting uncover orchestration governing growth, differentiation during critical phases cycle. findings underscore technology unraveling complex dynamics microenvironment, offering promising avenues for targeted therapies to curb growth. also outlines addressing GBM, employing target genes associated with chemotherapy resistance, showcasing its transformative effective treatments.

Язык: Английский

Процитировано

15

DNA nanomachine‐driven chemodynamic therapy against glioblastoma DOI Creative Commons

Xiaodie Li,

Yufei Lan, Xin Fu

и другие.

Aggregate, Год журнала: 2024, Номер unknown

Опубликована: Июль 8, 2024

Abstract Chemodynamic therapy (CDT) has shown promising antitumor effects in various malignant tumors. However, its application for glioblastoma (GBM) is significantly hindered by the challenge of delivering CDT agents across blood‐brain barrier (BBB) and achieving efficient tumor targeting. To overcome these obstacles, this study presents a novel DNA nanomachine (Cu@tFNAs‐G‐A NM) loading copper ions (Cu 2+ ) onto tetrahedral framework nucleic acids (tFNAs) functionalized with dual aptamers. The aptamers (GS24 BBB penetration AS1411 targeting) empowered Cu@tFNAs‐G‐A NM ability to effectively penetrate selectively accumulate cells. Upon internalization, loaded Cu reacted tumor‐overexpressed reductive glutathione (GSH) hydrogen peroxide (H 2 O ), generating hydroxyl radicals (·OH) inducing cell death. Additionally, was found be rapidly cleared from brain normal tissues within 24 h, minimizing potential systemic toxic side effects. These findings demonstrate effective against GBM open up new avenues development targeted therapies GBM.

Язык: Английский

Процитировано

8

Challenges and Promise for Glioblastoma Treatment through Extracellular Vesicle Inquiry DOI Creative Commons
Giovanna L. Liguori

Cells, Год журнала: 2024, Номер 13(4), С. 336 - 336

Опубликована: Фев. 13, 2024

Glioblastoma (GB) is a rare but extremely aggressive brain tumor that significantly impacts patient outcomes, affecting both duration and quality of life. The protocol established by Stupp colleagues in 2005, based on radiotherapy chemotherapy with Temozolomide, following maximum safe surgical resection remains the gold standard for GB treatment; however, it evident nowadays extreme intratumoral intertumoral heterogeneity, as well invasiveness tendency to recur, are not compatible routine unfortunately ineffective treatment. This review article summarizes main challenges search new valuable therapies focuses impact extracellular vesicle (EV) research exploitation may have field. EVs natural particles delimited lipidic bilayer filled functional cellular content released uptaken cells key means cell communication. Furthermore, stable body fluids tolerated immune system, able cross physiological, interspecies, interkingdom barriers target specific cells, releasing inherent or externally loaded functionally active molecules. Therefore, potential be ideal allies fight against improve prognosis patients. present work describes preclinical results obtained so far use treatment, focusing EV sources molecular cargo used various studies, primarily vivo. Finally, SWOT analysis performed, highlighting advantages pitfalls developing EV-based therapeutic strategies. also suggests directions explore realize possibility exploiting treatment GB.

Язык: Английский

Процитировано

7

Augmented Reality Integration in Skull Base Neurosurgery: A Systematic Review DOI Creative Commons
Emir Begagić, Hakija Bečulić, Ragib Pugonja

и другие.

Medicina, Год журнала: 2024, Номер 60(2), С. 335 - 335

Опубликована: Фев. 16, 2024

To investigate the role of augmented reality (AR) in skull base (SB) neurosurgery.

Язык: Английский

Процитировано

7

Understanding the Significance of Hypoxia-Inducible Factors (HIFs) in Glioblastoma: A Systematic Review DOI Open Access
Emir Begagić, Hakija Bečulić,

Amina Džidić-Krivić

и другие.

Cancers, Год журнала: 2024, Номер 16(11), С. 2089 - 2089

Опубликована: Май 30, 2024

Background: The study aims to investigate the role of hypoxia-inducible factors (HIFs) in development, progression, and therapeutic potential glioblastomas. Methodology: study, following PRISMA guidelines, systematically examined hypoxia HIFs glioblastoma using MEDLINE (PubMed), Web Science, Scopus. A total 104 relevant studies underwent data extraction. Results: Among studies, global contributions were diverse, with China leading at 23.1%. most productive year was 2019, accounting for 11.5%. Hypoxia-inducible factor 1 alpha (HIF1α) frequently studied, followed by 2 (HIF2α), osteopontin, cavolin-1. Commonly associated pathways include glucose transporter (GLUT1) 3 (GLUT3) receptors, vascular endothelial growth (VEGF), phosphoinositide 3-kinase (PI3K)-Akt-mechanistic target rapamycin (mTOR) pathway, reactive oxygen species (ROS). HIF expression correlates various hallmarks, including survival, neovascularization, metabolism, migration, invasion. Conclusion: Overcoming challenges such as treatment resistance absence biomarkers is critical effective integration HIF-related therapies into aim optimizing patient outcomes.

Язык: Английский

Процитировано

5

Integrative multi-omic profiling of the neoantigen landscape of glioblastoma for the development of therapeutic vaccines reveals vast heterogeneity in immunogenic signatures DOI Creative Commons
Lin Q,

Yukui Wei,

Geng Xu

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Март 21, 2025

Introduction Glioblastoma (GBM) is the most common primary brain malignancy. Few neoantigens have been tested in trials as cancer vaccine against GBM. Methods To better understand neoantigen landscape and its associated tumor microenvironment (TME) for optimized design of our initiated GBM trial, we apply integrative multi-omics approach to comprehensively profile mutation, HLA typing, TCR/BCR repertoire, immune cell components on tissue peripheral blood mononuclear (PMBC) specimen 24 patients. Results On average, 148 mutated genes 200 sites per patient were identified, with no predominant this cohort. Diversified genotypes expression rate across A, B, C alleles, A30:01&A11:01, B13:02, C06:02, frequent at respective alleles. Clustered CDR3 existed decreased richness compared PMBC. NK Th1 cells revealed within (TME). Neoantigens feasible predicted designed each patient, an average number 107. Very few shared by more than two patients dominant could be identified. A minimum 11-peptide bulk was required cover 24-patient cohort, guaranteeing least one neoantigen. Discussion In summary, data reveals a heterogeneous TME GBM, based which peptide feasibly developed these

Язык: Английский

Процитировано

0

Exploring Multi-Target Therapeutic Strategies for Glioblastoma via Endogenous Network Modeling DOI Open Access
Meng-Chao Yao, Xiaomei Zhu, Yong-Cong Chen

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3283 - 3283

Опубликована: Апрель 1, 2025

Medical treatment of glioblastoma presents a significant challenge. A conventional medication has limited effectiveness, and single-target therapy is usually effective only in the early stage treatment. Recently, there been increasing focus on multi-target therapies, but vast range possible combinations makes clinical experimentation implementation difficult. From perspective systems biology, this study conducted simulations for based dynamic analysis previously established endogenous networks, validated with single-cell RNA sequencing data. Several potentially target were identified. The findings also highlight necessity rather than intervention strategies cancer treatment, as well promise applications personalized therapies.

Язык: Английский

Процитировано

0

Progress in Glioma Stem Cell Research DOI Open Access
Ramar Vanajothi, Shanchun Guo,

B. J. F. Hudson

и другие.

Cancers, Год журнала: 2023, Номер 16(1), С. 102 - 102

Опубликована: Дек. 24, 2023

Glioblastoma multiforme (GBM) represents a diverse spectrum of primary tumors notorious for their resistance to established therapeutic modalities. Despite aggressive interventions like surgery, radiation, and chemotherapy, these tumors, due factors such as the blood–brain barrier, tumor heterogeneity, glioma stem cells (GSCs), drug efflux pumps, DNA damage repair mechanisms, persist beyond complete isolation, resulting in dismal outcomes patients. Presently, standard initial approach comprises surgical excision followed by concurrent where temozolomide (TMZ) serves foremost option managing GBM Subsequent adjuvant chemotherapy follows this regimen. Emerging approaches encompass immunotherapy, including checkpoint inhibitors, targeted treatments, bevacizumab, aiming exploit vulnerabilities within cells. Nevertheless, there exists pressing imperative devise innovative strategies both diagnosing treating GBM. This review emphasizes current knowledge GSC biology, molecular associations with various signals and/or pathways, epidermal growth factor receptor, PI3K/AKT/mTOR, HGFR/c-MET, NF-κB, Wnt, Notch, STAT3 pathways. Metabolic reprogramming GSCs has also been reported prominent activation glycolytic pathway, comprising aldehyde dehydrogenase family genes. We discuss potential targets currently used well mode action on targets.

Язык: Английский

Процитировано

9

Glioblastoma: a comprehensive approach combining bibliometric analysis, Latent Dirichlet Allocation, and HJ-Biplot DOI
Karime Montes Escobar, Javier de la Hoz-M,

Paul Castillo-Cordova

и другие.

Neurosurgical Review, Год журнала: 2024, Номер 47(1)

Опубликована: Май 10, 2024

Язык: Английский

Процитировано

3