Age-related macular degeneration (AMD) is a blinding eye disease, whose incidence strongly increases with ages. The etiology of AMD is complex, including aging, abnormal lipid metabolism, chronic inflammation and oxidative stress. Long-chain polyunsaturated fatty acids (LCPUFA) are essential for ocular structures and functions. This review summarizes the regulatory effects of LCPUFA on inflammation in AMD. LCPUFA are related to aging, autophagy and chronic inflammation. They are metabolized to pro-and anti-inflammatory metabolites by various enzymes. These metabolites stimulate inflammation in response to oxidative stress, causing innate and acquired immune responses. This review also discusses the possible clinical applications, which provided novel targets for the prevention and treatment of AMD and other age-related diseases.
Purpose. Complete resection and adjuvant chemotherapy are recommended as the standard strategy for patients with stage I-IIA small cell lung cancer (SCLC). However, the role of additional postoperative radiotherapy (PORT) in treatment remains controversial. Methods. Patients with stage I-IIA SCLC undergoing surgery and adjuvant chemotherapy were extracted from the Surveillance, Epidemiology, and End Results database. Stage I-IIA, defined as T1-2N0M0, was recalculated according to the 8th AJCC TNM staging system. Propensity score matching (PSM) was conducted to identify the therapeutic impact of PORT. Univariate Cox hazards regression and least absolute shrinkage and selection operator regression were utilized for primary screening of prognostic variables for I-IIA SCLC disease. A nomogram to predict overall survival (OS) was constructed based on the multivariate Cox proportional hazards model, evaluated with area under the curve, calibration curve, and decision curve analysis, and validated with bootstrap resampling. Results. Our results demonstrated that compared with no PORT, PORT significantly prolonged the median OS (8.58 vs. 5.17 years, HR = 0.61 [0.39–0.96], P = 0.032 ) and median cancer-specific survival (11.33 vs. 8.08, HR = 0.47 [0.27–0.82], P = 0.0086 ) after PSM. The 5-year OS rate was 61.56% vs. 46.60%. Five variables including age at diagnosis, gender, T stage, surgical type, and PORT were elucidated to impact on prognosis and included in a nomogram to predict 3-/5-/10-year OS probability. The area under the curve values were 0.72, 0.71, and 0.81, respectively. The nomogram also exhibited satisfactory accuracy and clinical usefulness. Conclusion. PORT was verified to improve the OS of patients with T1-2N0M0 SCLC after surgery and chemotherapy. A prognostic nomogram was developed and validated for OS prediction for these patients.
Background The WD40-encoding RNA antisense to p53 (WRAP53) is an antisense gene of TP53 with three transcriptional start sites producing three transcript variants involved in the progression of non-small cell lung cancer. However, the mechanism by which these different transcript variants regulate non-small cell lung cancer cell behaviors is to be elucidated. Methods Two non-small cell lung cancer cell lines, A549 cells with wild-type p53 and H1975 with mutated p53, were transfected with WRAP53-1α and WRAP53-1β siRNA. The biological effects were assessed via colony formation, cell viability, apoptosis, cell cycle, wound healing and cell invasion assays, as well as immunoblotting. Results Knockdown of WRAP53-1α increased the mRNA and protein levels of p53; suppressed colony formation and proliferation of A549 cells but promoted them in H1975 cells; increased the proportion of cells in the G0/G1 phase in A549 cells but decreased that in H1975 cells; and suppressed migration and invasion in A549 cells but not in H1975 cells. Conversely, knockdown of WRAP53-1β had no effect on p53 expression; promoted the growth of A549 cells but not of H1975 cells; decreased the proportion of cells in the G0/G1 phase in A549 cells but not in H1975 cells; and promoted migration and invasion in A549 cells but not in H1975 cells. Knockdown of both WRAP53-1α and WRAP53-1β promoted apoptosis in A549 cells but not in H1975 cells. Conclusions WRAP53 transcript variants exerted different functions in non-small cell lung cancer cells and regulated non-small cell lung cancer cell behaviors depending on the p53 expression.
Editorial on the Research Topic Epigenetic regulation and non-histone post-translational modification in cancerEpigenetic changes are essentially involved in both normal organism function and disease progression (Deans and Maggert, 2015). Epigenetic regulation includes DNA methylation or demethylation, chromatin remodeling, histone modifications and noncoding RNAs, which are broadly reported to dysfunction in cancer. Of noted, it is increasingly clear that epigenetic regulation parallels with gene expression modulation. Currently, significant progress has been made in the development of drugs targeting key enzymes involved in epigenetic regulation and post-translational modification without histone. Several drugs have been approved for therapeutic application, and many more are in clinical and preclinical testing (Ferreira and Esteller, 2018;Lu et al., 2020). The aim of this Research Topic is to provide an overview of the current understanding and fundamental findings in the field of epigenetic regulation and non-histone post-translational modifications in cancer. We collected 14 articles including the effects of m6A modifications, non-coding RNAs and SELENBP1 in cancer progression.DNA methylation is strongly associated with cancer, and hypermethylation of some genes in the promoter region interferes with the reading of DNA information thereby altering epigenetics, thus it has the potential to be a promising target for cancer therapy (Smith and Meissner, 2013). Liexi Xu et al. used the methylation and clinical data of lung adenocarcinoma (LUAD) patients from TCGA. They found 11 differential methylation genes and established a methylation scoring model to assess prognosis, suggesting that these genes could be used as biomarkers of methylation in LUAD. Dong-Mei Hu et al. focused on the relationship between Forkhead box P (FOXP) family DNA methylation and immunerelated factors in non-small cell lung cancer (NSCLC) patients. FOXP family is widely involved in regulating immune molecules and influencing immune infiltration in NSCLC, and FOXP family DNA methylation is associated with NSCLC prognosis. In addition to lung
Background: Lung cancer is the main cause of cancer-related mortality, of which non-small cell lung cancer (NSCLC) accounts for 85%. Abemaciclib, a selective CDK4/6 inhibitor, enhanced the radiosensitivity of NSCLC in vivo and in vitro and improved the prognosis of advanced NSCLC patients according to a Phase Ⅰ clinical trial. This study aimed to explore the impact of CDK4/6 inhibition combined with irradiation and immunotherapy on NSCLC.Methods: The in vivo xenograft tumor mouse model was used to investigate the synergistic effects of CDK4/6 inhibitor abemaciclib and irradiation together with anti-PD-1 antibodies. The tumor infiltrating lymphocytes (TILs) in tumor microenvironment (TME) were analyzed by flow cytometry. The complete blood count and serum tests were used to determine the safety of this combination therapy. The human phospho-kinase array and dual-luciferase report assay were used to study the regulatory mechanisms of abemaciclib and irradiation combination on PD-L1 transcription in NSCLC cells in vitro.Results: Our results indicated the significantly synergistic effects of abemaciclib, irradiation and anti-PD-1 antibodies on NSCLC growth in vivo, accompanied by increased CD8+ T cell infiltration and decreased regulatory T cells and myeloid-derived suppressor cells (MDSCs), suggesting a strong anti-tumor combination of CDK4/6 inhibition, radiotherapy and immunotherapy. This synergistic effect could be partially impaired by CD8 depletion, and alleviated the anemia and inflammation caused by tumor burden without hepatorenal toxicity. Abemaciclib induced PD-L1 transcription through JNK/c-Jun pathway in vitro, which might elevate PD-L1 expression synergistically with irradiation through TBK1/IRF3 pathway.Conclusions: Our studies suggested that CDK4/6 inhibition plus irradiation enhanced anti-tumor immune responses in NSCLC. Together with immunotherapy, the combination of CDK4/6 inhibitors and radiotherapy could lower the doses of individual treatment, thus alleviating the potential toxicity and side effects of CDK4/6 inhibition and irradiation on normal cells. Citation Format: Zhengrong Huang, Hongxin Xie, Mengqin Wang, Conghua Xie, Yan Gong. CDK4/6 inhibition plus radiotherapy enhances anti-tumor immune responses in non-small cell lung cancer [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A31.
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