A novel defined pyroptosis-related gene signature for predicting the prognosis of ovarian cancer

Cell Death Discovery, Journal Year: 2021, Volume and Issue: 7(1)

Published: April 7, 2021

Abstract Ovarian cancer (OC) is a highly malignant gynaecological tumour that has very poor prognosis. Pyroptosis been demonstrated in recent years to be an inflammatory form of programmed cell death. However, the expression pyroptosis-related genes OC and their correlations with prognosis remain unclear. In this study, we identified 31 pyroptosis regulators were differentially expressed between normal ovarian tissues. Based on these (DEGs), all cases could divided into two subtypes. The prognostic value each gene for survival was evaluated construct multigene signature using Cancer Genome Atlas (TCGA) cohort. By applying least absolute shrinkage selection operator (LASSO) Cox regression method, 7-gene built classified patients TCGA cohort low- or high-risk group. low-risk group showed significantly higher possibilities than those ( P < 0.001). Utilizing median risk score from cohort, Gene Expression Omnibus (GEO) subgroups, had increased overall (OS) time = 0.014). Combined clinical characteristics, found independent factor predicting OS patients. ontology (GO) Kyoto Encylopedia Genes Genomes (KEGG) analyses indicated immune-related enriched immune status decreased conclusion, play important roles immunity can used predict OCs.

Language: Английский

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Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment

Theranostics, Journal Year: 2021, Volume and Issue: 11(18), P. 8813 - 8835

Published: Jan. 1, 2021

In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or bypassing apoptotic cell death. Several novel types of programmed death, such as ferroptosis, necroptosis, pyroptosis, recently been reported to play significant roles in the modulation cancer progression are considered a promising strategy for treatment. Thus, switch between pyroptosis also discussed. Cancer immunotherapy gained increasing attention due breakthroughs immune checkpoint inhibitors; moreover, highly correlated with immunity tumor microenvironment. Compared necroptosis primary mechanism host defense crucial bridging innate adaptive immunity. Furthermore, exerts benefits on immunotherapies, including inhibitors (ICIs) chimeric antigen receptor T-cell therapy (CAR-T). Hence, this review, we elucidate role We summarize potential small molecules nanomaterials target pyroptotic death mechanisms their therapeutic effects cancer.

Language: Английский

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Programmed Cell Death Tunes Tumor Immunity

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 30, 2022

The demise of cells in various ways enables the body to clear unwanted cells. Studies over years revealed distinctive molecular mechanisms and functional consequences several key cell death pathways. Currently, most intensively investigated programmed (PCD) includes apoptosis, necroptosis, pyroptosis, ferroptosis, PANoptosis, autophagy, which has been discovered play crucial roles modulating immunosuppressive tumor microenvironment (TME) determining clinical outcomes cancer therapeutic approaches. PCD can dual roles, either pro-tumor or anti-tumor, partly depending on intracellular contents released during process. also regulates enrichment effector regulatory immune cells, thus participating fine-tuning anti-tumor immunity TME. In this review, we focused primarily discussed messengers regulating their intricate crosstalk with response TME, explored immunological consequence its implications future therapy developments.

Language: Английский

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Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: Nov. 18, 2021

Chimeric antigen receptor (CAR) T-cell therapy has yielded impressive outcomes and transformed treatment algorithms for hematological malignancies. To date, five CAR products have been approved by the US Food Drug Administration (FDA). Nevertheless, some significant toxicities pose great challenges to development of therapy, most notably cytokine release syndrome (CRS) immune effector cell-associated neurotoxicity (ICANS). Understanding mechanisms underlying these establishing prevention strategies are important. In this review, we summarize CRS ICANS provide potential strategies.

Language: Английский

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Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: June 9, 2021

Pyroptosis is a lytic cell death form executed by gasdermins family proteins. Induction of tumor pyroptosis promotes anti-tumor immunity and potential cancer treatment strategy. Triptolide (TPL) natural product isolated from the traditional Chinese herb which possesses potent activity in human cancers. However, its role remains to be elucidated.Cell survival was measured colony formation assay. Cell apoptosis determined Annexin V evaluated morphological features release interleukin 1β lactate dehydrogenase A (LDHA). Immunofluorescence staining employed measure subcellular localization Tumorigenicity assessed xenograft model. Expression levels mRNAs or proteins were qPCR western blot assay, respectively.Triptolide eliminates head neck cells through inducing gasdermin E (GSDME) mediated pyroptosis. Silencing GSDME attenuates cytotoxicity TPL against cells. suppresses expression c-myc mitochondrial hexokinase II (HK-II) cells, leading activation BAD/BAX-caspase 3 cascade cleavage active caspase 3. HK-II sensitizes induced pyroptosis, whereas enforced prevents Mechanistically, translocation BAD, BAX 3, thus attenuating upon treatment. Furthermore, NRF2/SLC7A11 (also known as xCT) axis induces reactive oxygen species (ROS) accumulation, regardless status GSDME. Combination with erastin, an inhibitor SLC7A11, exerts robust synergistic effect suppression vitro nude mice model.This study not only provides new paradigm therapy, but also highlights crucial linking glucose metabolism

Language: Английский

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GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 18, 2023

Abstract Pyroptosis, a type of Gasdermin-mediated cell death, contributes to an exacerbation inflammation. To test the hypothesis that GSDME-mediated pyroptosis aggravates progression atherosclerosis, we generate ApoE and GSDME dual deficiency mice. As compared with control mice, −/− /ApoE mice show reduction atherosclerotic lesion area inflammatory response when induced high-fat diet. Human atherosclerosis single-cell transcriptome analysis demonstrates is mainly expressed in macrophages. In vitro, oxidized low-density lipoprotein (ox-LDL) induces expression Mechanistically, ablation macrophages represses ox-LDL-induced inflammation macrophage pyroptosis. Moreover, signal transducer activator transcription 3 (STAT3) directly correlates positively regulates expression. This study explores transcriptional mechanisms during development indicates could be potential therapeutic approach for atherosclerosis.

Language: Английский

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Traditional Chinese medicine for precancerous lesions of gastric cancer: A review

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 146, P. 112542 - 112542

Published: Dec. 20, 2021

Gastric cancer (GC) is the fifth most common type of and third leading cause death due to worldwide. The gastric mucosa often undergoes many years precancerous lesions (PLGC) stages before progressing malignancy. Unfortunately, there are no effective Western drugs for patients with PLGC. In recent years, traditional Chinese medicine (TCM) has been proven in treating Classical TCM formulas chemical components isolated from some herbal medicines have administered treat PLGC, main advantage their comprehensive intervention multiple approaches targets. this review, we focus on studies using treatment including clinical observations experimental research, a targets mechanisms drugs. This review provides ideas theoretical basis applying PLGC prevent GC.

Language: Английский

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The Versatile Gasdermin Family: Their Function and Roles in Diseases

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Nov. 11, 2021

The gasdermin (GSDM) family, a novel group of structure-related proteins, consists GSDMA, GSDMB, GSDMC, GSDMD, GSDME/DNFA5, and PVJK/GSDMF. GSDMs possess C-terminal repressor domain, cytotoxic N-terminal flexible linker domain (except for GSDMF). GSDM-NT can be cleaved released to form large oligomeric pores in the membrane that facilitate pyroptosis. emerging roles include regulation various physiological pathological processes, such as cell differentiation, coagulation, inflammation, tumorigenesis. Here, we introduce basic structure, activation, expression patterns GSDMs, summarize their biological functions, explore regulatory mechanisms health disease. This review provides reference development GSDM-targeted drugs treat inflammatory tissue damage-related conditions.

Language: Английский

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The pyroptotic role of Caspase-3/GSDME signalling pathway among various cancer: A Review

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 242, P. 124832 - 124832

Published: May 15, 2023

Language: Английский

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Tumor Microenvironment-Activable Manganese-Boosted Catalytic Immunotherapy Combined with PD-1 Checkpoint Blockade

ACS Nano, Journal Year: 2022, Volume and Issue: 16(12), P. 20400 - 20418

Published: Nov. 28, 2022

Immune checkpoint blockade (ICB) therapy has attracted widespread attention in cancer treatment. Due to the low immunogenicity and immune suppression state tumor microenvironment (TME), therapeutic effects are only moderate. Herein, a TME-activable manganese-boosted catalytic immunotherapy is designed for synergism with ICB kill tumors efficiently. The cell membrane (CM)-wrapping multienzyme-mimic manganese oxide (MnOx) nanozyme termed CM@Mn showed intrinsic peroxidase oxidase-like activities an acidic TME. These can generate toxic hydroxyl (•OH) superoxide radicals (•O2-) killing evoking immunogenic death (ICD). Furthermore, TME-responsive release of Mn2+ directly promotes dendritic maturation macrophage M1 repolarization, resulting reversal immunosuppressive TME into immune-activating environment. Additionally, hypoxia relief caused by catalase-like activity also contributes process reversal. Finally, robust tumor-specific T cell-mediated antitumor response occurs support PD-1 blockade. proliferation primary metastatic was inhibited, long-term memory effect induced. strategy outlined here may serve as promising candidate tumor-integrated

Language: Английский

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