Mechanisms of programmed cell death DOI Open Access
Tian Li, Guido Kroemer

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 5 - 6

Published: Dec. 14, 2023

The present volume of Immunological Reviews deals with the mechanisms programmed cell death, obviously from an immunological perspective. What are consequences death on organism and, in particular, immune recognition stressed and dying cells? long-distance effects therapeutic manipulations resulting cancer cells surprisingly vast, as this has been documented for treatment clinically approved or experimental chemotherapeutic agents. For example, can cause neuropathic pain through neuroinflammation.1 In addition, induction result production Type I interferons by tumor that then mediate ambiguous adaptive responses ranging enhancement stemness exhaustion anticancer response within microenvironment to stimulation responses. interferon even trigger a systemic sickness flu-like symptoms state depression.2 Such long-range certainly also relevant pathophysiology viral infections. If induced appropriate fashion, one major positive stress is against tumor-associated antigen, thus sensitizing tumors immunotherapy checkpoint inhibitors.3-5 This important implications because chemotherapeutics induce immunogenic be used first-line treatments sensitize types (exemplified KRAS-mutated colorectal cancer, non-small lung triple-negative breast cancer) subsequent antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), 1 (PD-1), PD-1 ligand-1 (PD-L1), confirmed several clinical trials. Of note, there multiple different subroutines if not all them immunogenic, apoptosis (which involves mitochondrial membrane permeabilization activation caspases 3 7)2, but necroptosis (with implication specific effector molecules including receptor-interacting kinase (RIP3) mixed lineage domain-like pseudokinase (MLKL1)),6 pyroptosis (involving inflammasome/caspase-1-mediated pore-forming gasdermins),7 mixture pyroptosis, apoptosis, dubbed PANoptosis,8 ferroptosis lethal damage peroxidation),9, 10 cuproptosis (due copper-induced aggregation lipoylated dihydrolipoamide S-acetyltransferase).11 cases, preceded favors emission danger-associated molecular patterns (DAMPs) appearing surface secreted into extracellular space. It sum stress-associated DAMPs (that surface-exposed released before disintegrate) death-associated become accessible passively when plasma internal permeable) dictates immunogenicity hence capacity system detect dead antigens. antigens microbial (for instance context infection viruses intracellular bacteria), tumor-associated, autoantigens. Immunogenic only drugs occur radiation therapy,12 photodynamic, photothermal therapy,13 well upon microbes oncolytic viruses.14 Logically, attempts underway create novel galenic formulation nanoparticle-based drug delivery systems administer tumors, yet do any effects.13, 15 Interestingly, accompanied release nanoscale vesicles exosomes constitute potential biomarkers ongoing events establish short- communication neighboring distant tissues.16 As possibility, such might engineered nanodelivery When undergo they interact primarily dendritic cells,17 particular Type-1 conventional (cDC1) appear particularly competent eliciting antigens.18 Dendritic loaded prophylactic vaccines.17 Moreover, manipulated pharmacologically enhance their T cells.18 educate lymphocytes recognize lyse malignant cells. Importantly, process T-cell-mediated cytotoxicity elicit amplifying phenomenon protracting response.19 However, affecting may play down desirable immunosurveillance. Specifically, it appears neutrophil granulocytes produce so-called traps (NETs) shield immunity, impairing clearance.20 neutrophils stimulate unwarranted inflammatory autoimmune responses.21 Altogether, illustrates which extent modalities cells, pathogen-infected innate cognate vast whole-body physiology. processes long have studied exclusively biologists acquired dimension already yields tangible impact respect management diseases. Future will tell whether knowledge generated field contribute prevention infectious authors declare no conflicts interest.

Language: Английский

Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation DOI Creative Commons
Fei Ren, Qian Fei,

Kun Qiu

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: April 1, 2024

Abstract Lung cancer stands as the most prevalent form of globally, posing a significant threat to human well-being. Due lack effective and accurate early diagnostic methods, many patients are diagnosed with advanced lung cancer. Although surgical resection is still potential means eradicating cancer, usually miss best chance for treatment, even after may experience tumor recurrence. Additionally, chemotherapy, mainstay treatment has be chemo-resistant, resulting in poor clinical outcomes. The emergence liquid biopsies garnered considerable attention owing their noninvasive nature ability continuous sampling. Technological advancements have propelled circulating cells (CTCs), DNA (ctDNA), extracellular vesicles (EVs), metabolites, tumor-educated platelets (TEPs), tumor-associated antigens (TAA) forefront key biopsy biomarkers, demonstrating intriguing encouraging results diagnosis prognostic evaluation This review provides an overview molecular biomarkers assays utilized encompassing CTCs, ctDNA, non-coding RNA (ncRNA), EVs, TAAs TEPs. Furthermore, we expound on practical applications biopsies, including diagnosis, response monitoring, evaluation, recurrence monitoring context

Language: Английский

Citations

39
CircKIAA0182 Enhances Lung Cancer Progression and Chemoresistance through Interaction with YBX1 DOI
Masha Huang,

Jingyi Sun,

Qingqing Jiang

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: 612, P. 217494 - 217494

Published: Jan. 23, 2025

Language: Английский

Citations

2
Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence DOI Open Access
Jin Zhang, Yue Ma

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116909 - 116909

Published: June 8, 2024

Lung cancer is a prevalent malignant tumor and leading cause of cancer-related fatalities globally. However, current treatments all have limitations. Therefore, there an urgent need to identify readily available therapeutic agent counteract lung development progression. Luteolin flavonoid derived from vegetables herbs that possesses preventive effects on various cancers. With the goal providing new directions for treatment cancer, we review here recent findings luteolin so as provide ideas anti-lung drugs. The search focused studies published between January 1995 2024 explored use in cancer. A comprehensive literature was conducted SCOPUS, Google Scholar, PubMed, Web Science databases using keywords "luteolin" "lung cancer." By collecting previous literature, found has multiple mechanisms effects, including promotion apoptosis cells; inhibition cell proliferation, invasion metastasis; modulation immune responses. In addition, it can be used adjuvant radio-chemotherapy helps ameliorate complications. This summarizes structure, natural sources, physicochemical properties pharmacokinetics luteolin, focuses mechanism

Language: Английский

Citations

11
GTPase GPN3 facilitates cell proliferation and migration in non-small cell lung cancer by impeding clathrin-mediated endocytosis of EGFR DOI Creative Commons
Linlin Xu,

Jiankun Guo,

Xinsheng Xie

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 1, 2025

Small GTPases play a critical role as regulatory molecules in signaling transduction and various cellular processes, contributing to the development of human diseases, including cancers. GPN3, an evolutionarily conserved member GPN-loop GTPase subfamily classified 2007 according its structure, has limited knowledge regarding functions molecular mechanisms. In this study, we demonstrate that GPN3 interacts with clathrin light chain A (CLTA), vesicle coat protein, well clathrin-mediated endocytosis associated modulators AP2B1 AP2S1. Upregulation leads inhibition clathrin-coated pit invagination. Furthermore, discovered epidermal growth factor receptor (EGFR) regulates co-localization EGFR CLTA, localization early endosomes upon EGF stimulation. As result, decrease endocytic levels increase accumulation on cell membrane surface, thereby prolonging activation signaling. The functional effects exerted by are dependent GTP abundance. our findings indicate aberrant overexpression is observed non-small lung cancer (NSCLC) tissues compared adjacent normal tissues, high expression poor prognosis for NSCLC patients. Collectively, these reveal acts oncogene promoting proliferation migration through regulation clathrin-dependent endocytosis. These results suggest targeting could serve novel prognostic biomarker therapeutic strategy treatment.

Language: Английский

Citations

1
Targeting regulated cell death: Apoptosis, necroptosis, pyroptosis, ferroptosis, and cuproptosis in anticancer immunity DOI
Ziyu Guo,

Yihuang Liu,

Danyao Chen

et al.

Journal of Translational Internal Medicine, Journal Year: 2025, Volume and Issue: 13(1), P. 10 - 32

Published: Feb. 1, 2025

In the evolving landscape of cancer treatment, strategic manipulation regulated cell death (RCD) pathways has emerged as a crucial component effective anti-tumor immunity. Evidence suggests that tumor cells undergoing RCD can modify immunogenicity microenvironment (TME), potentially enhancing its ability to suppress progression and metastasis. this review, we first explore mechanisms apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, along with crosstalk between these modalities. We then discuss how processes activate antigen-presenting cells, facilitate cross-priming CD8+ T trigger immune responses, highlighting complex effects novel forms on TME biology. Furthermore, summarize potential drugs nanoparticles induce or inhibit emerging their therapeutic roles in treatment. Finally, put forward existing challenges future prospects for targeting anti-cancer Overall, review enhances our understanding molecular biological impacts RCD-based therapies, providing new perspectives strategies

Language: Английский

Citations

1
Exosomal circ_0000735 contributes to non‐small lung cancer malignant progression DOI
Sijie Liu, Xun Wu, Yanjie Wang

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 38(4)

Published: March 25, 2024

Circular RNA is an important regulator for non-small cell lung cancer (NSCLC). Circ_0000735 has been found to be significantly overexpressed in NSCLC tissues. Therefore, its role and mechanism progression need further explored. The expression levels of circ_0000735, miR-345-5p A disintegrin metalloprotease 19 (ADAM19) were determined using quantitative real-time PCR. EdU staining, wound healing transwell assays utilized detect proliferation metastasis. protein metastasis markers, exosome markers ADAM19 western blot. Animal experiments performed confirm the circ_0000735 tumorigenesis. exosomes from cells serum identified transmission electron microscopy nanoparticle tracking analysis. We that was upregulated NSCLC, knockdown repressed In terms mechanism, targeted regulate ADAM19. MiR-345-5p inhibitor reversed suppressive effect on progression, overexpression abolished inhibition progression. Also, animal showed silencing reduced addition, mediated intercellular exosomal might indicator diagnosis NSCLC. conclusion, facilitated via miR-345-5p/ADAM19 pathway, a potential biomarker diagnosis.

Language: Английский

Citations

6
Inducing ferroptosis by traditional medicines: a novel approach to reverse chemoresistance in lung cancer DOI Creative Commons
Yumin Wang, Jing Hu, Joshua S. Fleishman

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 23, 2024

Lung cancer is the leading cause of global cancer-related deaths. Platinum-based chemotherapy first-line treatment for most common type lung cancer, i.e., non-small-cell (NSCLC), but its therapeutic efficiency limited by chemotherapeutic resistance. Therefore, it vital to develop effective modalities that bypass molecular mechanisms associated with Ferroptosis a form non-apoptotic regulated cell death characterized iron-dependent lipid peroxidation (LPO). crucial proper efficacy cancer-associated chemotherapies. If targeted as novel mechanism, ferroptosis modulators present new opportunities increasing chemotherapy. Emerging studies have revealed pharmacological induction using natural compounds boosts in or drug-resistant cancer. In this review, we first discuss resistance (or chemoresistance) and introduce core behind ferroptosis. Then, comprehensively summarize small-molecule sourced from traditional medicines may boost anti-tumor activity current agents overcome NSCLC. Cumulatively, suggest ferroptosis-related anticancer could serve starting point NSCLC inducing ferroptosis, highlighting potential regimens used chemoresistance

Language: Английский

Citations

5
Human Embryonic Kidney HEK293 Cells as a Model to Study SMVT-Independent Transport of Biotin and Biotin-Furnished Nanoparticles in Targeted Therapy DOI Open Access
Magdalena Twardowska, Andrzej Łyskowski, Maria Misiorek

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1594 - 1594

Published: Feb. 13, 2025

The aim of this study was to investigate the usefulness human embryonic kidney HEK293 cells as a model normal in biotin-mediated therapy. expression and role sodium multivitamin transporter (SMVT) uptake accumulation free biotin, well cationic neutral biotinylated PAMAM dendrimers fourth generation synthesized our laboratory, were assessed comparison other immortalized (HaCaT) cancer (HepG2, U-118 MG). obtained data showed that higher level SMVT not associated with stronger biotin dendrimers. Biotinylation increased selective an inversely proportional manner concentration used; however, lower than cell lines. time-dependent profiles differed significantly. Therefore, it should be assumed efficiency nanoparticles' depends on multiple cellular transport mechanisms. Toxicity tests significantly sensitivity conjugates for HepG2 HaCaT cells. Molecular modeling studies profile suggest only but also monocarboxylate 1 (MCT-1) may play important nanoparticles into Due complexity problem, further are necessary. In summary, can considered valuable biotin- targeted therapy using based

Language: Английский

Citations

0
Therapeutic Potential of Biotoxins and Biotechnological Innovations DOI
Prince Kumar Singh,

Gereraj Sen Gupta,

Indrajeet Kumar

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
NSUN4 Facilitates the Activity of Oncogenic Protein CDC20 to Promote NSCLC Development by Mediating m5C Modification of CDC20 mRNA DOI Creative Commons
Zhilong Li,

Wu Xianzhen

Thoracic Cancer, Journal Year: 2025, Volume and Issue: 16(5)

Published: March 1, 2025

5-methylcytosine (m5C) methylation is the crucial posttranscriptional modification of RNA. NSUN4, a methyltransferase for m5C methylation, contributes to lung tumorigenesis. Here, we determined precise action NSUN4 on development non-small cell cancer (NSCLC). and CDC20 mRNA expression was detected by quantitative PCR. Western blot immunohistochemistry were used analysis protein expression. Cell growth, apoptosis, invasiveness, migratory ability, stemness potential evaluated colony formation, flow cytometry, transwell, sphere formation assays. The influence in analyzed using RNA immunoprecipitation (RIP) assay Actinomycin D (Act D) treatment. Subcutaneous xenograft studies performed analyze function vivo. In human NSCLC tumors lines, levels upregulated. inhibition diminished stemness, ability vitro, while increase had opposite effects. A positive association between observed samples. Mechanistically, enhanced stability through modification. depletion significantly counteracted NSUN4-driven phenotype alterations vitro. Additionally, impeded growth A549 subcutaneous xenografts Our findings identify pro-tumorigenic property NSUN4/CDC20 cascade NSCLC. Targeting novel may be promising way combating this deadly disease.

Language: Английский

Citations

0