Accurate and rapid molecular subgrouping of high-grade glioma via deep learning-assisted label-free fiber-optic Raman spectroscopy DOI Creative Commons
Chang Liu, Jiejun Wang, Jianghao Shen

et al.

PNAS Nexus, Journal Year: 2024, Volume and Issue: 3(6)

Published: May 27, 2024

Molecular genetics is highly related with prognosis of high-grade glioma. Accordingly, the latest WHO guideline recommends that molecular subgroups genes, including IDH, 1p/19q, MGMT, TERT, EGFR, Chromosome 7/10, CDKN2A/B, need to be detected better classify glioma and guide surgery treatment. Unfortunately, there no preoperative or intraoperative technology available for accurate comprehensive subgrouping Here, we develop a deep learning-assisted fiber-optic Raman diagnostic platform rapid Specifically, total 2,354 fingerprint spectra was obtained from 743 tissue sites (astrocytoma: 151; oligodendroglioma: 150; glioblastoma (GBM): 442) 44 patients. The convolutional neural networks (ResNet) model then established optimized subgrouping. mean area under receiver operating characteristic curves (AUC) identifying reached 0.904, sensitivity 83.3%, specificity 85.0%, accuracy time expense 10.6 s. diagnosis performance using ResNet shown superior PCA-SVM UMAP models, suggesting high dimensional information would helpful. In addition, GBM, AUC 0.932, 87.8%, 83.6%, 84.1%. Furthermore, according saliency maps, specific features corresponding tumor-associated biomolecules (e.g. nucleic acid, tyrosine, tryptophan, cholesteryl ester, fatty collagen) were found contribute Collectively, this study opens up new opportunities glioma, which assist optimal surgical resection instant post-operative decision-making.

Language: Английский

The cell biology of ferroptosis DOI
Scott J. Dixon, James A. Olzmann

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(6), P. 424 - 442

Published: Feb. 16, 2024

Language: Английский

Citations

294
Targeting ferroptosis opens new avenues for the development of novel therapeutics DOI Creative Commons

Shumin Sun,

Jie Shen, Jianwei Jiang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 21, 2023

Abstract Ferroptosis is an iron-dependent form of regulated cell death with distinct characteristics, including altered iron homeostasis, reduced defense against oxidative stress, and abnormal lipid peroxidation. Recent studies have provided compelling evidence supporting the notion that ferroptosis plays a key pathogenic role in many diseases such as various cancer types, neurodegenerative disease, involving tissue and/or organ injury, inflammatory infectious diseases. Although precise regulatory networks underlie are largely unknown, particularly respect to initiation progression diseases, recognized bona fide target for further development treatment prevention strategies. Over past decade, considerable progress has been made developing pharmacological agonists antagonists these ferroptosis-related conditions. Here, we provide detailed overview our current knowledge regarding ferroptosis, its pathological roles, regulation during disease progression. Focusing on use chemical tools preclinical studies, also summarize recent advances targeting across growing spectrum ferroptosis-associated Finally, discuss new challenges opportunities potential strategy treating

Language: Английский

Citations

232
Lipid droplets and cellular lipid flux DOI

Alyssa J. Mathiowetz,

James A. Olzmann

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(3), P. 331 - 345

Published: March 1, 2024

Language: Английский

Citations

80
Ferroptosis in health and disease DOI Creative Commons
Carsten Berndt, Hamed Alborzinia,

Vera Skafar Amen

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 75, P. 103211 - 103211

Published: May 30, 2024

Ferroptosis is a pervasive non-apoptotic form of cell death highly relevant in various degenerative diseases and malignancies. The hallmark ferroptosis uncontrolled overwhelming peroxidation polyunsaturated fatty acids contained membrane phospholipids, which eventually leads to rupture the plasma membrane. unique that it essentially spontaneous, uncatalyzed chemical process based on perturbed iron redox homeostasis contributing process, but nonetheless modulated by many metabolic nodes impinge cells' susceptibility ferroptosis. Among affecting sensitivity, several have emerged as promising candidates for pharmacological intervention, rendering ferroptosis-related proteins attractive targets treatment numerous currently incurable diseases. Herein, current members Germany-wide research consortium focusing research, well key external experts who made seminal contributions this rapidly growing exciting field gathered provide comprehensive, state-of-the-art review Specific topics include: basic mechanisms, vivo relevance, specialized methodologies, tools, potential contribution disease etiopathology progression. We hope article will not only established scientists newcomers with an overview multiple facets ferroptosis, also encourage additional efforts characterize further molecular pathways modulating ultimate goal develop novel pharmacotherapies tackle associated - or caused

Language: Английский

Citations

69
Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives DOI Creative Commons

Hao Lin,

Chaxian Liu,

An-Kang Hu

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 8, 2024

Abstract Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, exploration of emerging modalities such as immunotherapy integration medicine engineering technology therapy, efficacy these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny inhibitory milieu within GBM has underscored significance cellular constituents microenvironment their interactions with cells neurons. Novel immune targeted therapy strategies have emerged, offering promising avenues for advancing treatment. One pivotal mechanism orchestrating immunosuppression involves aggregation myeloid-derived suppressor (MDSCs), glioma-associated macrophage/microglia (GAM), regulatory T (Tregs). Among these, MDSCs, though constituting minority (4–8%) CD45 + GBM, play central component fostering evasion propelling tumor progression, angiogenesis, invasion, metastasis. MDSCs deploy intricate mechanisms that adapt dynamic (TME). Understanding interplay between provides compelling basis This review seeks elucidate inherent explore existing targets, consolidate insights into MDSC induction contribution immunosuppression. Additionally, comprehensively surveys ongoing clinical trials potential strategies, envisioning future where targeting could reshape landscape GBM. Through synergistic other modalities, this approach can establish multidisciplinary, multi-target paradigm, ultimately improving prognosis quality life patients

Language: Английский

Citations

62
Ferroptosis: principles and significance in health and disease DOI Creative Commons
Fangquan Chen, Rui Kang, Daolin Tang

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 6, 2024

Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.

Language: Английский

Citations

51
Sensitization of cancer cells to ferroptosis coincident with cell cycle arrest DOI Creative Commons
Jason Rodencal, Nathan G. Kim,

Andrew He

et al.

Cell chemical biology, Journal Year: 2023, Volume and Issue: 31(2), P. 234 - 248.e13

Published: Nov. 13, 2023

Language: Английский

Citations

43
Cell cycle arrest induces lipid droplet formation and confers ferroptosis resistance DOI Creative Commons
Hyemin Lee, Amber D. Horbath, Lavanya Kondiparthi

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 2, 2024

Abstract How cells coordinate cell cycling with survival and death remains incompletely understood. Here, we show that cycle arrest has a potent suppressive effect on ferroptosis, form of regulated induced by overwhelming lipid peroxidation at cellular membranes. Mechanistically, induces diacylglycerol acyltransferase (DGAT)–dependent droplet formation to sequester excessive polyunsaturated fatty acids (PUFAs) accumulate in arrested triacylglycerols (TAGs), resulting ferroptosis suppression. Consequently, DGAT inhibition orchestrates reshuffling PUFAs from TAGs phospholipids re-sensitizes ferroptosis. We some slow-cycling antimitotic drug–resistant cancer cells, such as 5-fluorouracil–resistant have accumulation droplets combined treatment inducers inhibitors effectively suppresses the growth tumors inducing Together, these results reveal role for driving resistance suggest ferroptosis-inducing therapeutic strategy target therapy-resistant cancers.

Language: Английский

Citations

39
Exploiting ferroptosis vulnerabilities in cancer DOI
Toshitaka Nakamura, Marcus Conrad

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(9), P. 1407 - 1419

Published: June 10, 2024

Language: Английский

Citations

27
FADS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer DOI Creative Commons
Nicla Lorito, Angela Subbiani, Alfredo Smiriglia

et al.

EMBO Molecular Medicine, Journal Year: 2024, Volume and Issue: 16(7), P. 1533 - 1559

Published: June 26, 2024

Language: Английский

Citations

18