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

Fabrication of pH-responsive temozolomide (TMZ)-clacked tannic acid-altered zeolite imidazole nanoframeworks (ZIF-8) enhance anticancer activity and apoptosis induction in glioma cancer cells DOI

Chongwen Ren,

Qingqing Tu,

Jinchao He

и другие.

Journal of Biomaterials Science Polymer Edition, Год журнала: 2024, Номер 35(13), С. 1978 - 1998

Опубликована: Июль 2, 2024

Glioma cancer is the primary cause of cancer-related fatalities globally for both men and women. Traditional chemotherapy treatments this condition frequently result in reduced efficacy significant adverse effects. This investigation developed a new drug delivery system chemotherapeutic temozolomide (TMZ) using pH-sensitive zeolitic imidazolate frameworks (ZIF-8). These nanoplatforms demonstrate excellent biocompatibility hold potential therapy. Utilizing favorable reaction milieu offered by ZIFs, 'one-pot method' was employed fabrication loading drugs, leading to good capacity loading. TMZ@TA@ZIF-8 NPs exhibit notable response an acidic milieu, resulting enhanced release pattern characterized controlled outcome. The effectiveness inhibiting migration invasion U251 glioma cells, as well promoting apoptosis, confirmed through various tests, including MTT (3-(4,5)-dimethylthiahiazo(-z-y1)) assay, DAPI/PI dual staining, cell scratch assay. biochemical fluorescent staining assays showed that potentially improved ROS, MMP, triggered apoptosis cells. In cells treated with NPs, p53, Bax, Cyt-C, caspase-3, -8, -9 expressions were significantly enhanced, while Bcl-2 expression diminished. outcomes show therapeutic agent anti-glioma properties. Overall, pH-responsive systems we fabricated great treatment. approach has make contributions improvement therapy overcoming problems associated TMZ-based treatments.

Язык: Английский

Процитировано

2

A novel tetrahedral framework nucleic acid‐derived chemodynamic therapy agent for effective glioblastoma treatment DOI Creative Commons

Xiaodie Li,

Li Lei, Xin Fu

и другие.

Cell Proliferation, Год журнала: 2024, Номер unknown

Опубликована: Авг. 24, 2024

Abstract Chemodynamic therapy (CDT) has garnered significant attention for treating diverse malignant tumours due to its minimally invasive nature, reduced damage healthy tissues, and potential mitigation of side effects. However, application in glioblastoma (GBM) is hindered by the diminished capacity CDT agents traverse blood–brain barrier (BBB), inadequate tumour targeting efficiency, restricted availability H 2 O within microenvironment (TME). To address these challenges, we devised a novel agent (Fe@tFNAs‐ANG‐3AT) based on tetrahedral framework nucleic acids (tFNAs). Fe@tFNAs‐ANG‐3AT was constructed anchoring iron ions (Fe 3+ ) onto dual appendages‐modified tFNAs. Specifically, one appendage, Angiopep‐2 (ANG, penetrating peptide), facilitates penetration across BBB selective cells. Simultaneously, second 3‐Amino‐1,2,4‐triazole (3AT, enzyme inhibitor), augments levels required effective treatment. Upon cell internalization, loaded Fe 2+ overexpressed glutathione (GSH) TME, catalysing generation cytotoxic hydroxyl radicals (·OH) inducing death via elevated oxidative stress It anticipated that holds promise as transformative treatment strategy GBM.

Язык: Английский

Процитировано

2

Starting points for the development of new targeted therapies for glioblastoma multiforme DOI Creative Commons
Agnieszka Rusak, Benita Wiatrak, Klaudia Krawczyńska

и другие.

Translational Oncology, Год журнала: 2024, Номер 51, С. 102187 - 102187

Опубликована: Ноя. 11, 2024

Язык: Английский

Процитировано

2

MR Imaging–Guided Focused Ultrasound—Clinical Applications in Managing Malignant Gliomas DOI
Huanwen Chen, Pavlos Anastasiadis,

Graeme F. Woodworth

и другие.

Magnetic Resonance Imaging Clinics of North America, Год журнала: 2024, Номер 32(4), С. 673 - 679

Опубликована: Июнь 22, 2024

Язык: Английский

Процитировано

1

Complete radiographic response after proton radiation therapy in the re-irradiation of a diffuse high-grade glioma: A case report DOI Creative Commons

Jacfar Hassan,

Christian Hyde,

Michael C. Joiner

и другие.

SAGE Open Medical Case Reports, Год журнала: 2024, Номер 12

Опубликована: Янв. 1, 2024

High-grade gliomas (HGGs) are the most aggressive of brain tumors and one common primary intracranial malignancies. The poor prognosis after treatment HGGs makes these a challenge to treat with curative intent. Proton radiation therapy is recent modality that being explored for HGGs. provides improved sparing critical normal structures while giving an ablative dose tumor, which can be performed more accurately than photon beam therapy. We report case diffuse HGG treated proton radiotherapy chemotherapy previously irradiation. A complete radiographic response was seen on MRI imaging

Язык: Английский

Процитировано

1

Structural alterations of the EGFR gene in glioblastoma samples as a prognostic factor and molecular target for therapy DOI Creative Commons
V. O. Varachev, Olga Yu. Susova, A. A. Мitrоfаnоv

и другие.

Advances in molecular oncology, Год журнала: 2024, Номер 11(3), С. 68 - 78

Опубликована: Окт. 11, 2024

Introduction . Epidermal growth factor receptor (EGFR) is a transmembrane protein of the tyrosine kinase family that activated in various cancers (non-small cell lung cancer, colorectal head and neck tumors). In glial brain tumors, increased EGFR expression levels are characteristic most aggressive subtype, glioblastoma. Frequent structural changes glioblastoma amplification chromosome region where gene located, point mutations, as well deletion exons 2–7 leading to formation EGFRvIII transcript. Aim To determine (point mutations gene, transcript) tumor samples using different methods evaluate their potential clinical significance. Materials The study included 75 patients with gliomas (70 them glioblastoma) aged 34 78 years (mean age 56 years). DNA RNA isolation was performed from fresh frozen tissue, peripheral blood leukocytes. were determined by next-generation sequencing (NGS), β allele frequency (BAF) comparative analysis (normal-tumor) copy number 7 regions. Quantitative polymerase chain reaction used confirm samples, reverse transcription-PCR detect variant. Results NGS method revealed 11/70 (16 %) coding regions detected 26/70 (37 cases; no 5 glioma (astrocytoma, oligodendroglioma). All cases confirmed quantitative reaction. search for transcript, 31 examined, which present 12 samples. transcript only – 4/12 (33 %). assess significance alterations, occurrence primary recurrent compared. Conclusion allows both gene. associated mutation 33 % cases. No statistically significant differences between relapsed glioblastomas found.

Язык: Английский

Процитировано

1

Current Combinatorial Therapeutic Aspects: The Future Prospect for Glioblastoma Treatment DOI
Megha Gautam, Reema Gabrani

Current Medical Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 18, 2024

Язык: Английский

Процитировано

1

Calcified Pilocytic Astrocytomas and Calcifying Pseudoneoplasms of the Neuraxis: A Diagnostic Challenge DOI Open Access

Rebeca Hernández-Reséndiz,

Eliezer Villanueva-Castro,

Edgardo de Jesús Mateo-Nouel

и другие.

Cureus, Год журнала: 2024, Номер unknown

Опубликована: Янв. 6, 2024

Pilocytic astrocytoma (PA), recognized as the most prevalent central nervous system (CNS) tumor, has long been associated with calcifications, a characteristic often attributed to benign or indolent growth patterns. In this study, we explored calcified attributes in these tumors that beckon deeper understanding. This is retrospective on set of seven cases, histopathological diagnosis pilocytic calcifications and psammoma bodies (PB). Despite an encouraging overall survival outcome, recurrence four cases cast some doubt conventional classification. The histological study revealed spectrum varying size morphology, all which exhibited positive reactivity glial fibrillary acidic protein (GFAP), osteoconduction, osteopontin. Notably, immunohistochemistry showed hyaline displaying atypical immune profile, strikingly negative for vimentin GFAP, robust positivity epidermal factor receptors (EGFR), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β). These results stimulated speculation identity may have extended potentially embraced realm calcifying pseudoneoplasms neuraxis (CAPNON), underscored by intense pilot gliosis. transcends mere anatomical exploration; it delves into intricacies tumors, casting spotlight dynamic interplay between PA CAPNON. As traverse frontiers neuro-oncology, findings pave way innovative avenues diagnostics therapeutics tumors.

Язык: Английский

Процитировано

0

Advanced Control Models for Glioblastoma Multiforme Management: Optimizing Drug Therapies and Adaptive Tumor Volume Regulation with Fractional-Order Mathematical Modeling DOI Creative Commons
David Amilo, Khadijeh Sadri, Evren Hınçal

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Май 6, 2024

Abstract Glioblastoma Multiforme (GBM) is a highly aggressive and lethal form of brain tumor, presenting significant challenges in treatment management. In this study, we propose advanced control models for the management GBM, focusing on optimization drug therapies adaptive regulation tumor volume. Leveraging fractional-order mathematical modeling, our approach integrates modeling techniques with theory to develop comprehensive strategies GBM The proposed aim optimize by dynamically adjusting parameters based real-time volume monitoring. This allows personalized regimens tailored specific characteristics enhancing therapeutic efficacy while minimizing adverse effects. By harnessing capabilities research provides novel framework advancing offering new insights combating formidable disease MSC Classification: 92C55, 93C95, 92B05, 35R11, 35A22, 92C50, 35Q53, 49N90.

Язык: Английский

Процитировано

0

Pharmacokinetics and Brain Tumor Delivery Studies of Thymoquinone-Encapsulated Eudragit L100-Coated Solid-Lipid Nanoparticles DOI

Jeganpandi Senthamarai Pandi,

Parasuraman Pavadai, Lakshmi Sundar

и другие.

Journal of Cluster Science, Год журнала: 2024, Номер 36(1)

Опубликована: Дек. 19, 2024

Язык: Английский

Процитировано

0