Genetic Profiles of Ferroptosis in Malignant Brain Tumors and Off-Target Effects of Ferroptosis Induction DOI Creative Commons
Marc Dahlmanns, Eduard Yakubov, Jana Katharina Dahlmanns

и другие.

Frontiers in Oncology, Год журнала: 2021, Номер 11

Опубликована: Дек. 1, 2021

Glioblastoma represents the most devastating form of human brain cancer, associated with a very poor survival rate patients. Unfortunately, treatment options are currently limited and gold standard pharmacological chemotherapeutic drug temozolomide only slightly increases rate. Experimental studies have shown that efficiency can be improved by inducing ferroptosis – recently discovered cell death, which is different from apoptosis, necrosis, or necroptosis and, characterized lipid peroxidation reactive oxygen species accumulation. Ferroptosis also activated to improve malignant stages neuroblastoma, meningioma, glioma. Due their role in cancer treatment, ferroptosis-gene signatures been evaluated for ability predict Despite positive effects during chemotherapy, drugs used induce such as erastin sorafenib well genetic manipulation key players cystine-glutamate exchanger xCT glutathione peroxidase GPx4 impact neuronal function cognitive capabilities. In this review, we give an update on tumors summarize healthy tissues.

Язык: Английский

Predictive biomarkers of colon cancer immunotherapy: Present and future DOI Creative Commons

Wanting Hou,

Yi Cheng, Hong Zhu

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Ноя. 22, 2022

Immunotherapy has revolutionized colon cancer treatment. Immune checkpoint inhibitors (ICIs) have shown clinical benefits for patients, especially those with high microsatellite instability (MSI-H). In 2020, the US Food and Drug Administration (FDA)-approved ICI pembrolizumab as first-line treatment metastatic MSI-H patients. Additionally, neoadjuvant immunotherapy presented efficacy in treating early-stage Although MSI been thought of an effective predictive biomarker immunotherapy, only a small proportion patients were MSI-H, certain intrinsic or acquired resistance to immunotherapy. Thus, further search biomarkers stratify is meaningful Except MSI, other biomarkers, such PD-L1 expression level, tumor mutation burden (TMB), tumor-infiltrating lymphocytes (TILs), gut microbiota, ctDNA, circulating immune cells also proposed be correlated patient survival some studies. Moreover, developing new diagnostic techniques helps identify accurate this review, we outline reported discuss prospects technological changes development

Язык: Английский

Процитировано

97
Modulating ferroptosis sensitivity: environmental and cellular targets within the tumor microenvironment DOI Creative Commons

Yuze Hua,

Sen Yang, Yalu Zhang

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Янв. 13, 2024

Abstract Ferroptosis, a novel form of cell death triggered by iron-dependent phospholipid peroxidation, presents significant therapeutic potential across diverse cancer types. Central to cellular metabolism, the metabolic pathways associated with ferroptosis are discernible in both cancerous and immune cells. This review begins delving into intricate reciprocal regulation between It subsequently details how factors within tumor microenvironment (TME) such as nutrient scarcity, hypoxia, density modulate sensitivity. We conclude offering comprehensive examination distinct immunophenotypes environmental targets geared towards enhancing responsiveness TME. In sum, tailoring precise interventions combination strategies suit unique TME specific cancers may herald improved patient outcomes.

Язык: Английский

Процитировано

21
SLC1A5 enhances malignant phenotypes through modulating ferroptosis status and immune microenvironment in glioma DOI Creative Commons
Liying Han, Jinpeng Zhou,

Leiyang Li

и другие.

Cell Death and Disease, Год журнала: 2022, Номер 13(12)

Опубликована: Дек. 24, 2022

Abstract Glioma is the most common type of primary malignant tumor in central nervous system with limited treatment satisfaction. Finding new therapeutic targets has remained a major challenge. Ferroptosis novel and distinct programmed cell death, playing regulatory role progression tumors. However, ferroptosis or ferroptosis-related genes (FRGs) glioma not been extensively studied. In our study, prognostic model, including 7 genes, was established, which patients classified into high-risk group had more immuno-suppressive status worse prognosis. Among these we screened solute carrier family 1 member 5 (SLC1A5), an FRG, as possible target for treatment. Our results showed that expression SLC1A5 significantly upregulated glioblastoma tissues compared low-grade gliomas. addition, knockdown could inhibit proliferation invasion, reduce sensitivity via GPX4-dependent pathway. Furthermore, found to be related immune response decreased infiltration M2 polarization tumor-associated macrophages. Pharmacological inhibition by V9302 confirmed promote efficacy anti-PD-1 therapy. Overall, developed model based on seven-FRGs signature, apply prediction. Besides, regulate proliferation, state glioma, applied biomarker potential glioma.

Язык: Английский

Процитировано

47
Nanodrug delivery systems for ferroptosis-based cancer therapy DOI
Yu Wang, Tao Sun,

Chen Jiang

и другие.

Journal of Controlled Release, Год журнала: 2022, Номер 344, С. 289 - 301

Опубликована: Янв. 29, 2022

Язык: Английский

Процитировано

39
Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway DOI Creative Commons
Yingyi Xu, Na Zhang, Cheng Chen

и другие.

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Март 17, 2022

Objective To clarify the function and mechanisms of sevoflurane (Sev) on ferroptosis in glioma cells. Methods Different concentrations Sev were used to treat cells U87 U251. Ferroptosis inducer Erastin was incubate combined with ATF4 siRNA transfection treatment. CCK-8 assay colorimetric performed analyze cell viability Fe + concentration, respectively. The releases reactive oxygen species (ROS) determined by flow cytometry analysis. Transcriptional sequencing screen differential genes affected U251 mRNA protein expression ferroptosis-associated detected qRT-PCR Western blotting. Results could suppress viability, increase ROS levels downregulate GPX4, upregulate transferrin, ferritin, Beclin-1 a dose-dependent manner mitophagy-related gene activating transcription factor 4 (ATF4) identified be enhanced analyzed transcriptional sequencing. ChaC glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1), which is involved ferroptosis, downstream ATF4. Inhibition interrupt CHAC1 induced treatment obviously inhibited elevated 2+ promoted generation level increased Erastin-treated Moreover, interruption Sev-induced suppression reversed Erastin. Conclusions In summary, this study suggested that exposure-induced ATF4-CHAC1 pathway

Язык: Английский

Процитировано

37
Machine learning-based investigation of regulated cell death for predicting prognosis and immunotherapy response in glioma patients DOI Creative Commons
Wei Zhang,

Ruiyue Dang,

Hongyi Liu

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Фев. 20, 2024

Abstract Glioblastoma is a highly aggressive and malignant type of brain cancer that originates from glial cells in the brain, with median survival time 15 months 5-year rate less than 5%. Regulated cell death (RCD) autonomous orderly under genetic control, controlled by precise signaling pathways molecularly defined effector mechanisms, modulated pharmacological or interventions, plays key role maintaining homeostasis internal environment. The comprehensive systemic landscape RCD glioma not fully investigated explored. After collecting 18 RCD-related signatures opening literature, we comprehensively explored landscape, integrating multi-omics data, including large-scale bulk single-cell level lines, proteome data. We also provided machine learning framework for screening potentially therapeutic candidates. Here, based on sequencing samples, phenotypes, profile RCD, developed an gene pair scoring system, named RCD.GP signature, showing reliable robust performance predicting prognosis glioblastoma. Using consisting Lasso, RSF, XgBoost, Enet, CoxBoost Boruta, identified seven genes as potential targets verified SLC43A3 expressed grades lines through qRT-PCR. Our study insights into roles glioma, signature patients, constructed core candidates oncogenic prediction biomarker

Язык: Английский

Процитировано

9
Exploring the relationship between anastasis and mitochondrial ROS-mediated ferroptosis in metastatic chemoresistant cancers: a call for investigation DOI Creative Commons
Yu Cao, Chang Lu, Narasimha M. Beeraka

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 2, 2024

Ferroptosis induces significant changes in mitochondrial morphology, including membrane condensation, volume reduction, cristae alteration, and outer rupture, affecting function cellular fate. Recent reports have described the intrinsic iron metabolism its intricate connection to ferroptosis, a kind of cell death characterized by dependence oxidative stress regulation. Furthermore, updated molecular insights elucidated significance mitochondria ferroptosis implications various cancers. In context cancer therapy, understanding dual role anastasis chemoresistance is crucial. Targeting pathways involved may enhance efficacy inducers, providing synergistic approach overcome chemoresistance. Research into how DNA damage response (DDR) proteins, metabolic changes, redox states interact during can offer new designing combinatorial therapeutic regimens against several cancers associated with stemness. These treatments could potentially inhibit while simultaneously inducing thereby reducing likelihood cells evading developing resistance chemotherapy. The objective this study explore interplay between anastasis, EMT chemoresistance, immunotherapeutics better understand their collective impact on therapy outcomes. We searched public research databases google scholar, PubMed, relemed, national library medicine related topic. review, we discussed tricarboxylic acid cycle glycolysis implicated modulating adding complexity regulatory mechanisms. Additionally, reactive oxygen species (ROS) electron transport chain (ETC) has garnered attention. Lipid metabolism, particularly involving GPX4 System Xc- plays both progression cancer. There need investigate clinical Integrating strategies targeting exploring potential synergy immunotherapy represent promising avenues for advancing chemoresistant treatment. Understanding among mitochondria, ROS, vital oncology, revolutionizing personalized treatment drug development.

Язык: Английский

Процитировано

8
Identification and Verification of the Ferroptosis- and Pyroptosis-Associated Prognostic Signature for low-grade Glioma DOI Open Access
Jie Wang, Jie Ren, Jifeng Liu

и другие.

Bosnian Journal of Basic Medical Sciences, Год журнала: 2022, Номер unknown

Опубликована: Март 9, 2022

Accumulating evidence reveals that ferroptosis and pyroptosis play pivotal roles in tumorigenesis of low-grade glioma (LGG). In this research, we aimed to classify molecular subtypes further identify verify a novel multigene signature LGG on the basis pyroptosis-related genes (FPRGs). Raw sequencing data corresponding clinical samples retrieved from TCGA CGGA databases were obtained for training validation datasets. Non-negative matrix factorization (NMF) clustering defined by FPRGs associated with prognosis was performed patients. LASSO-SVM-Random Forest analysis carried out develop an FPRG predict survival benefit immunotherapy NMF prognostic values acted categorize patients into two different prognosis, traits immune microenvironments. A six-FPRG constructed, accompanied optimal p-value. The AUC our exhibited great performances. Our superior other four well-recognized signatures predicting probability Immune characteristics, tumor mutation profile, stemness indices, MGMT methylation response biomarkers showed significant differences between high- low-risk populations. Finally, nomogram created quantitative prediction patients, being 0.916, 0.888 0.836 1-, 3- 5-year survival, sequentially. Overall, may function as effective indicator

Язык: Английский

Процитировано

27
LncRNA PELATON, a Ferroptosis Suppressor and Prognositic Signature for GBM DOI Creative Commons

Haijuan Fu,

Zhaoyu Zhang,

Danyang Li

и другие.

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Апрель 28, 2022

PELATON is a long noncoding RNA also known as intergenic nonprotein coding 1272 (LINC01272). The reports showed that functions an onco-lncRNA or suppressor lncRNA by suppressing miRNA in colorectal cancer, gastric cancer and lung cancer. In this study, we first found PELATON, onco-lncRNA, alleviates the ferroptosis driven mutant p53 promotes p53-mediated GBM proliferation. We confirmed new inhibitor mainly P53 mediating ROS pathway, which inhibits production of ROS, reduces levels divalent iron ions, expression SLC7A11, ACSL4 COX2.PELATON can inhibit wild-type cells regulate BACH1 CD44, but it has no effect on p53, CD44 cells. form complex through binding protein EIF4A3. Knockdown resulted smaller mitochondria, increased mitochondrial membrane density, enhanced sensitivity to inducers cell proliferation invasion. addition, established favourite prognostic model with NCOA4 PELATON. promising target for prognosis treatment GBM.

Язык: Английский

Процитировано

27
The disulfidptosis-related signature predicts prognosis and immune features in glioma patients DOI Creative Commons

Xiong Wang,

Jijun Yang,

Fengjie Yang

и другие.

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Окт. 20, 2023

Glioma is the most common primary malignant tumor in central nervous system. Disulfidptosis a recently identified programmed cell death cells overexpressing SLC7A11 under glucose starvation. Clinical prognostic significance of disulfidptosis has been reported several tumors, and this study, we explored correlation with clinical prognosis, immune infiltration, immunotherapy response glioma. A total 1592 glioma patients were included including 691 from The Cancer Genomic Atlas (TCGA), 300 Chinese (CGGA) array, 325 CGGA sequencing, 276 Gene Expression Omnibus (GEO) GSE16011. R software (V4.2.2) packages applied to develop risk score model calculation visualization. Three disulfidptosis-related genes, LRPPRC, RPN1, GYS1, screened out establish model. Low-risk exhibit favorable signature significantly correlated clinicopathological properties, molecular subtypes, immunosuppressive microenvironment patients. We developed predict prognosis features patients, may be as an independent factor for

Язык: Английский

Процитировано

16