Translational Oncology, Journal Year: 2024, Volume and Issue: 47, P. 102005 - 102005
Published: May 23, 2024
Language: Английский
Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)
Published: May 7, 2024
Abstract Background Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence development a variety tumors. The aim this study was to investigate effects circ_PPAPDC1A Osimertinib resistance NSCLC. Methods Human circRNAs microarray analysis conducted identify differentially expressed (DE) Osimertinib-acquired tissues effect on cell proliferation, invasion, migration, apoptosis assessed both vitro vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, rescue assay were employed confirm interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. Results results revealed significantly upregulated acquired reduced sensitivity PC9 HCC827 cells promoted while inhibiting Osimertinib-resistant PC9/OR HCC829/OR cells, Silencing partially reversed resistance. Additionally, acted as competing endogenous (ceRNA) by targeting miR-30a-3p, Insulin-like Growth Factor 1 Receptor (IGF1R) identified functional gene for miR-30a-3p Furthermore, confirmed axis plays role activating PI3K/AKT/mTOR signaling pathway NSCLC with Conclusions Therefore, first time we exerts an oncogenic sponging active IGF1R/PI3K/AKT/mTOR pathway. may serve novel diagnostic biomarker therapeutic target patients Graphical
Language: Английский
Citations
7
npj Metabolic Health and Disease, Journal Year: 2024, Volume and Issue: 2(1)
Published: May 23, 2024
Abstract Obesity, a condition of excess adiposity usually defined by BMI > 30, can have profound effects on both metabolism and immunity, connecting the with broad range diseases, including cancer negative outcomes. Obesity been associated increased incidence, progression, poorer outcomes multiple types in part due to pro-inflammatory state that arises. Surprisingly, obesity has also recently demonstrated preclinical models clinical be improved response immune checkpoint inhibition (ICI). These observations laid foundation for what termed “obesity paradox”. The mechanisms underlying these augmented immunotherapy responses are still unclear given pleiotropic exerts cells tissues. Other important variables such as age sex being examined further affecting effect. Sex-linked factors exert significant influences biology, well differential different cell-types. Age another confounding factor contributing sex-linked changes, status, obesity. This review aims revisit current body literature describing metabolic changes mediated obesity, role immunotherapy, highlight questions how differences may influence outcome.
Language: Английский
Citations
5
Cancers, Journal Year: 2024, Volume and Issue: 16(16), P. 2882 - 2882
Published: Aug. 19, 2024
Lung cancer, including both non-small cell lung cancer and small remains the leading cause of cancer-related mortality worldwide, representing 18% total deaths in 2020. Many patients are identified already at an advanced stage with metastatic disease have a worsening prognosis. Recent advances genetic understanding opened new avenues for personalized treatments targeted therapies. This review examines latest discoveries genetics discusses key biomarkers, analyzes current clinical therapies based on this information. It will conclude discussion future prospects potential research directions.
Language: Английский
Citations
5
Critical Reviews in Biotechnology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 28
Published: Sept. 22, 2024
CRISPR-based diagnostics (CRISPR/Dx) have revolutionized the field of molecular diagnostics. It enables home self-test, field-deployable, and point-of-care testing (POCT). Despite great potential CRISPR/Dx in diagnoses biologically complex diseases, preamplification template often is required for sensitive detection low-abundance nucleic acids. Various amplification-free systems were recently developed to enhance signal at sufficient sensitivity. Broadly, these are classified into five groups depending on enhancement strategies employed: CRISPR/Cas12a and/or CRISPR/Cas13a integrated with: (1) other catalytic enzymes (Cas14a, Csm6, Argonaute, duplex-specific nuclease, nanozyme, or T7 exonuclease), (2) rational-designed oligonucleotides (multivalent aptamer, tetrahedral DNA framework, RNA G-quadruplexes, roller machine, switchable-caged guide RNA, hybrid locked RNA/DNA probe, hybridized cascade "U" rich stem-loop RNA), (3) nanomaterials (nanophotonic structure, gold nanoparticle, micromotor, microbeads), (4) electrochemical piezoelectric plate biosensors (SERS nanoprobes, graphene field-effect transistor, redox primer exchange reaction), (5) cutting-edge technology platforms (digital bioanalysis, droplet microfluidic, smartphone camera, single nanoparticle counting). Herein, we critically discuss advances, pitfalls future perspectives acids detection. The continued refinement will pave road rapid, cost-effective, ultrasensitive, ultraspecific on-site without resorting target amplification, with ultimate goal establishing as paragon
Language: Английский
Citations
4
Regulatory Mechanisms in Biosystems, Journal Year: 2024, Volume and Issue: 15(1), P. 83 - 91
Published: Feb. 17, 2024
Immune checkpoint inhibitors have opened up new possibilities in clinical oncology. Monoclonal antibodies shown their high efficiency. They block CTLA-4, PD-1, and PD-L1 receptors activate the immune response. Many patients stable even complete responses. However, some primary or acquired resistance. Therefore, treatment results this category of are not predictable. Mechanisms resistance to been definitively studied. theories try explain mechanisms phenomenon. Our study aimed structure combine data into groups depending on etiological factor that reduces In addition, based understanding recent studies, we identify main ways overcome it. lead may be associated with tumor properties, microenvironment, patient characteristics. Tumor properties reduce response include a) low mutation burden loss neoantigens, b) changes processing presentation c) signaling pathways development epigenetic modifications genes. The microenvironment is represented by stromal cells, extracellular matrix, cytokines, blood vessels. Each can enhance contribute inhibitors. effectiveness depends only cells but also metabolic background. basic characteristics ( gender, gut microbiota, HLA-I genotype) modify Based knowledge about inhibitors, several therapeutic strategies at activating antitumor activity evaluated. All them combining other drugs. One most common options a combination PD-1/PD-L1 CTLA-4 Alternative checkpoints TIM-3, LAG-3, TIGIT VISTA. Combining immunotherapy chemotherapy, targeted therapy, neoangiogenesis modifiers, PARP TGF-β enhances preventing depletion effector T enhancing cell infiltration tumor, decreasing accumulation immunosuppressive cells. This review explores biological potential solving problem.
Language: Английский
Citations
3
Personalized Medicine, Journal Year: 2023, Volume and Issue: 21(1), P. 45 - 57
Published: Dec. 13, 2023
The results of genomic and molecular profiling cancer patients can be effectively applied to immunotherapy agents, including immune checkpoint inhibitors, select the most appropriate treatment. In addition, accurate prediction neoantigens facilitates development individualized vaccines T-cell therapy. This review summarizes biomarker(s) predicting responses inhibitors focuses on current strategies identify isolate neoantigen-reactive T cells as well clinical neoantigen-based therapeutics. suggest that maximal stimulation expansion achieved with combination therapies enhance antigen-presenting cells' function optimal priming in lymph nodes.
Language: Английский
Citations
8
Current Oncology, Journal Year: 2024, Volume and Issue: 31(2), P. 1113 - 1128
Published: Feb. 19, 2024
The reference to vitiligo-like lesions (VLLs) induced by immune checkpoint inhibitors (ICIs) as a valuable predictive marker of treatment success immunotherapy with ICIs in melanoma has been mentioned the literature. Its role non-small cell lung cancer (NSCLC)-treated patients remains poorly recognized phenomenon uncertain significance regarding its value. A retrospective, observational, single-center report was performed, descriptive analysis clinicopathological and characteristics stage IV NSCLC who developed ICI-induced VLL between January 2018 December 2022, contextualized comprehensive review literature reported cases this phenomenon. During first 5 years’ experience ICI use treatment, three VLLs were diagnosed. In line previous reports, two presented exhibited response favorable prognosis. recognition understanding pathophysiological processes underlying may represent promising opportunity identify tumor ICIs, impact selection patient management. It also contribute new patterns molecular expression that could lead improvements therapeutic development.
Language: Английский
Citations
2
Journal of Cancer, Journal Year: 2024, Volume and Issue: 15(9), P. 2460 - 2474
Published: Jan. 1, 2024
Background: Neural Precursor Cell Expressed Developmentally Down-Regulated Protein 1 (NEDD1) serves as a crucial factor in promoting cellular mitosis by directly facilitating wheel assembly and daughter centriole biogenesis at the lateral site of parent centrioles, ultimately driving centrosome replication.The amplification centrosomes abnormal expression centrosome-associated proteins contribute to invasion metastasis non-small cell lung cancer cells.However, specific mechanism which NEDD1 contributes progression adenocarcinoma (LUAD) remains unexplored.Therefore, objective this study is uncover role played LUAD.Methods: To verify pan-carcinoma.The feasibility prognostic marker for LUAD TCGA GEO databases was verified.Subsequently, Cox proportional hazard regression analysis used screen factors LUAD, so analyze correlation between expression.For another, NEDD1-related genes were screened pathway enrichment their possible functions.In addition, verified qPCR IHC, then siRNA construct NEDD1-knocked cells subsequent cytobehavioral experiments.Finally, distribution single-cell samples revealed, its overexpression immune escape drug resistance analyzed.Results: exhibits upregulation NEDD1, turn promotes proliferation, migration, invasion, epithelial-mesenchymal transition cells, thereby contributing poor prognosis.Furthermore, closely associated with LUAD.Conclusion: reliable increased resistance.Given these findings, holds potential novel therapeutic target treatment LUAD.
Language: Английский
Citations
2
Translational Lung Cancer Research, Journal Year: 2024, Volume and Issue: 13(8), P. 2023 - 2037
Published: Aug. 1, 2024
Notwithstanding the rapid developments in precision medicine recent years, lung cancer still has a low survival rate, especially squamous cell (LUSC). The tumor microenvironment (TME) plays an important role progression of cancer, which high neutrophil levels are correlated with poor prognosis, potentially due to their interactions cells via pro-inflammatory cytokines and chemokines. However, precise mechanisms how neutrophils influence remain unclear. This study aims explore these develop prognosis predictive model LUSC, addressing knowledge gap neutrophil-related pathogenesis.
Language: Английский
Citations
2
Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14
Published: Feb. 8, 2024
Objective Increasing studies have highlighted the potential utility of non-invasive prognostic biomarkers in advanced lung cancer patients receiving immune checkpoint inhibitor (ICI) based anti-cancer therapies. Here, a novel predictor named as C-PLAN integrating C-reactive protein (CRP), Performance status (PS), Lactate dehydrogenase (LDH), Albumin (ALB), and derived Neutrophil-to-lymphocyte ratio (dNLR) was identified validated single-center retrospective cohort. Methods The clinical data 192 ICI-treated retrospectively analyzed. pretreatment levels CRP, PS, LDH, ALB dNLR were scored respectively then their scores added up to form index. correlation index with progression-free survival (PFS) or overall (OS) analyzed by Kaplan–Meier model. multivariate analysis used identify whether an independent predictor. Results A total 88 104 included low high group respectively. High significantly correlated worse PFS OS (both p<0.001). revealed unfavorable factor affecting (hazard (HR)=1.821; 95%confidence interval (CI)=1.291-2.568) (HR=2.058, 95%CI=1.431-2.959). had lower disease control rate than (p=0.024), while no significant difference found for objective response (p=0.172). subgroup on features (pathological type, therapy strategy, TNM stage age) confirmed value index, except ICI monotherapy age ranging from 18 65 years old. Finally, nomogram constructed age, gender, smoking status, which could predict well 1-, 2- 3-year patients. Conclusion has great be utilized non-invasive, inexpensive reliable ICI-based
Language: Английский
Citations
1