Development of Molecular Digital Twins Based on Ambient Ionization Mass Spectrometry Imaging for Application in Cancer Surgery DOI Creative Commons
Yanis Zirem, Léa Ledoux, Nina Ogrinc

et al.

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

Published: Dec. 12, 2024

Summary Cancer surgery is a fundamental component of oncology treatment, its quality significantly impacts patient outcomes, influencing both relapse rates and survival. However, achieving this customization contingent upon early collection robust molecular data during surgery, providing accurate information for diagnosis, prognosis, delineating surgical margins. The introduction digital twin (DT) technology has recently opened new era precision effectiveness in cancer surgery. Expanding from successful implementations the industrial sector, DT concept evolved into highly promising breakthrough healthcare. Therefore, our study goal on creating by using high-throughput obtained through mass spectrometry imaging. We developed machine-learning-based pipeline that allow to depict infiltration cells normal tissue offer precise delineation tumor margins thanks SpiderMass. This process also enables prediction relative presence bacterial strains tumoral healthy mammary glands.

Language: Английский

Vagus Nerve Stimulation: Novel Concept for the Treatment of Glioblastoma and Solid Cancers by Cytokine (Interleukin-6) Reduction, Attenuating the SASP, Enhancing Tumor Immunity DOI Creative Commons
Steven Brem

Brain Behavior & Immunity - Health, Journal Year: 2024, Volume and Issue: 42, P. 100859 - 100859

Published: Sept. 17, 2024

Language: Английский

Citations

4
Plasma lipidomic and metabolomic profiles in high‐grade glioma patients before and after 72‐h presurgery water‐only fasting DOI Creative Commons
Iris Divé, Lisa Hahnefeld, Katharina J. Wenger

et al.

Molecular Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Glioblastoma (GB) is the most aggressive primary brain tumor with poor prognosis despite multimodal therapy. Calorie-restricted diets have emerged as putative strategies to augment anticancer therapies. We employed UHPLC-high-resolution mass spectrometry analyses of plasma lipids and polar metabolites assess systemic metabolic effects a 72-h preoperative fasting period in IDH-wild-type glioma patients (n = 9 GB n 1 diffuse pediatric-type high-grade H3/IDH-wildtype) who participated prospective ERGO3 trial (NCT04461938). Fasting reduced lysophosphatidylcholines (LPC, LPC-O), lysophosphatidylethanolamines (LPE, LPE-O), increased free fatty acids carnitines. Triglyceride (TG) profiles shifted from short-chain TGs (42-48 C-atoms) very long-chain (58-60 indicating an exploitation neutral lipid stores. Branched-chain amino acids, aminobutyric acid, uric were increased, glucose after fasting. The comparable men women. To our knowledge, this first study that evaluated on lipid/metabolite levels patients. Our results may hold promise for integrating interventions component potential

Language: Английский

Citations

0
Overcoming immunotherapy resistance in glioblastoma: challenges and emerging strategies DOI Creative Commons
Mengmeng Fu, Bing Xue, Xiangshui Miao

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 28, 2025

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, characterized by rapid proliferation, extensive infiltration, significant intratumoral heterogeneity. Despite advancements conventional treatments, including surgery, radiotherapy, chemotherapy, prognosis for GBM patients remains poor, with a median survival of approximately 15 months. Immunotherapy has emerged as promising alternative; however, unique biological immunological features, its immunosuppressive microenvironment (TME) low mutational burden, render it resistant to many immunotherapeutic strategies. This review explores key challenges immunotherapy, focusing on immune evasion mechanisms, blood-brain barrier (BBB), TME. Immune checkpoint inhibitors CAR-T cells have shown promise preclinical models but limited clinical success due antigen heterogeneity, cell exhaustion, impaired trafficking across BBB. Emerging strategies, dual-targeting cells, engineered secreting therapeutic molecules, advanced delivery systems overcome BBB, show potential enhancing treatment efficacy. Addressing these crucial improving immunotherapy outcomes.

Language: Английский

Citations

0
Artificial Intelligence in Surgery: A Systematic Review of Use and Validation DOI Open Access
Nitzan Kenig, Javier Montón Echeverría,

Aina Muntaner Vives

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(23), P. 7108 - 7108

Published: Nov. 24, 2024

: Artificial Intelligence (AI) holds promise for transforming healthcare, with AI models gaining increasing clinical use in surgery. However, new are developed without established standards their validation and use. Before can be widely adopted, it is crucial to ensure these both accurate safe patients. Without proper validation, there a risk of integrating into practice sufficient evidence safety accuracy, potentially leading suboptimal patient outcomes. In this work, we review the current methods surgical settings propose novel classification system.

Language: Английский

Citations

3
Advances in clinical application of lipidomics in healthy ageing and healthy longevity medicine DOI Creative Commons
Opeyemi Stella Ademowo, Markus R. Wenk, Andrea B. Maier

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 100, P. 102432 - 102432

Published: July 17, 2024

It is imperative to optimise health and healthspan across the lifespan. The accumulation of reactive oxygen species (ROS) has been implicated in hallmarks ageing inhibiting ROS production can potentially delay whilst increasing healthy longevity. Lipids lipid mediators (derivatives lipids) are becoming increasingly recognized as central molecule tissue cellular function susceptible peroxidation; hence linked with ageing. Lipid classes process include sterols, glycerophospholipids, sphingolipids oxidation products polyunsaturated fatty acids but these not yet translated into clinic. Further mechanistic studies required for understanding process. Lipidomics, system level characterisation respect metabolism function, might provide a significant useful biological age profiling tool through longitudinal studies. profiles different ages among individuals could be harnessed biomarkers potential integration development lipid-based clock (lipid clock). includes prediction future morbidity or mortality, which will promote precision longevity medicine.

Language: Английский

Citations

2
Innovative drug delivery strategies for targeting glioblastoma: overcoming the challenges of the tumor microenvironment DOI
Shubham Khot,

A. Krishnaveni,

Sankalp Gharat

et al.

Expert Opinion on Drug Delivery, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 15, 2024

Introduction - Glioblastoma multiforme(GBM) presents a challenging endeavor in therapeutic management because of its highly aggressive tumor microenvironment(TME). This complex TME, characterized by hypoxia, nutrient deprivation, immunosuppression, stromal barriers, increased interstitial fluid pressure and the presence blood-brain barrier(BBB), frequently compromises efficacy promising strategies. Consequently, deeper understanding TME development innovative methods to overcome associated challenges are essential for improving treatment outcomes GBM.

Language: Английский

Citations

2
Detection of IDH mutation in glioma by desorption electrospray ionization (DESI) tandem mass spectrometry DOI Creative Commons
Mahdiyeh Shahi,

Steven Pringle,

Michael Morris

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 6, 2024

Desorption electrospray ionization (DESI) tandem mass spectrometry (MS) is used to assess mutation status of isocitrate dehydrogenase (IDH) in human gliomas. Due the diffuse nature gliomas, total gross resection not normally achieved during surgery, leading tumor recurrence. The IDH has clinical significance due better prognosis IDH-mutant patients. mutant converts alpha-ketoglutaric acid (α-KG) into 2-hydroxyglutarate (2HG), which accumulates abnormally cells. Immunohistochemical staining (IHC) and genetic testing, gold standards, are incompatible with intraoperative applications but DESI (MS/MS) can be enzyme from tissue intraoperatively. Here, on off-line evaluation made performance two different types spectrometers characterization status. intensity 2HG measured against glutamate (Glu), an intrinsic reference molecule, both MS measurements. In cases using clear separation between (mut) IDH-wildtype (wt) samples (p < 0.0001) observed, despite short analysis time. higher detection sensitivity, multiple reaction monitoring experiments a triple quadrupole show slightly compared product ion MS/MS performed simple linear trap. Both DESI-MS platforms capable providing information status, might future at time surgery support decision-making regions, especially margins.

Language: Английский

Citations

1
Development of Molecular Digital Twins Based on Ambient Ionization Mass Spectrometry Imaging for Real-Time Application in Oncological Surgery DOI
Yanis Zirem, Léa Ledoux, Nina Ogrinc

et al.

Published: Jan. 1, 2024

Digital Twins (DT) enable to monitor and predict the behavior of complex systems. They have therefore found a major application in clinics for precision health cancer patient digital twins (CPDT) is fast-growing concept. In solid tumor surgery decision making still concern next breakthrough be taken field. To address surgery, we studied development CPDT based on non-targeted molecular data issued from mass spectrometry (MS). Thanks recently introduced ambient ionization MS technology, SpiderMass, which has proven capable real-time vivo analysis, can produce topographic images vivo. Additionally, developed machine learning-based pipeline process present them 3D maps interpreted surgeon. We demonstrated creation these transgenic mouse model spontaneously mammary gland tumors mimic triple negative breast cancer. Because high specificity sensitivity profile ratio cell population each image pixel accurately find margins as well presence bacterial populations leading bacterioscore. These different representations could made available

Language: Английский

Citations

0
Protocol to analyze 1D and 2D mass spectrometry data from glioblastoma tissues for cancer diagnosis and immune cell identification DOI Creative Commons
Yanis Zirem, Léa Ledoux, Michel Salzet

et al.

STAR Protocols, Journal Year: 2024, Volume and Issue: 5(3), P. 103285 - 103285

Published: Sept. 1, 2024

Language: Английский

Citations

0
Heterogeneity Assessment and Protein Pathway Prediction via Spatial Lipidomic and Proteomic Correlation: Advancing Dry Proteomics concept for Human Glioblastoma Prognosis DOI Open Access
Laurine Lagache, Yanis Zirem, Émilie Le Rhun

et al.

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

Published: Oct. 25, 2024

ABSTRACT Prediction of proteins and associated biological pathways from lipid analyses via MALDI MSI is a pressing challenge. We introduced “dry proteomics,” using to validate spatial localization identified optimal clusters in or protein imaging. Consistent cluster appearance across omics images suggests association with specific pathways, forming the basis dry proteomics. The methodology was refined rat brain tissue as model, then applied human glioblastoma, highly heterogeneous cancer. Sequential sections underwent unsupervised clustering. Differentiated clusters, distinct locations, were identified. Spatial analysis facilitated characterization, leading predictive model identifying any based on unique signatures predicting pathways. Application slices revealed diverse subpopulations, including successfully predicted cerebellum areas. Similar 50 glioblastoma patients confirmed lipid-protein associations, correlating patient prognosis. GRAPHICAL

Language: Английский

Citations

0