{"title":"MicroRNA-384 radiosensitizes human non-small cell lung cancer by impairing DNA damage response and repair signaling, which is inhibited by NF-κB.","authors":"Yanchen Sun, Jing Wang, Minghan Qiu, Jinlin Zhao, Fangdi Zou, Maobin Meng, Xiangli Jiang, Zhiyong Yuan, Zeyun Mi, Zhiqiang Wu","doi":"10.20892/j.issn.2095-3941.2024.0146","DOIUrl":"10.20892/j.issn.2095-3941.2024.0146","url":null,"abstract":"<p><strong>Objective: </strong>Radiotherapy has achieved remarkable effects in treating non-small cell lung cancer (NSCLC). However, radioresistance remains the major obstacle to achieving good outcomes. This study aims at identifying potential targets for radiosensitizing NSCLC and elucidating the underlying mechanisms.</p><p><strong>Methods: </strong>Lentivirus-based infection and CRISPR/Cas9 technology were used to modulate the expression of microRNA-384 (miR-384). Cell clonogenic formation assays and a xenograft tumor model were used to analyze radiosensitivity in NSCLC cells. Fluorescence-activated cell sorting was used to assess the cell cycle and cell death. Immunofluorescence staining, Comet assays, and homologous recombination or non-homologous end-joining I-SceI/GFP reporter assays were used to study DNA damage and repair. Western blotting and quantitative real-time polymerase chain reaction were used to identify the targets of miR-384. Chromatin immunoprecipitation and polymerase chain reaction were performed to evaluate upstream regulators of miR-384.</p><p><strong>Results: </strong>MiR-384 was downregulated in NSCLC. Overexpression of miR-384 increased the radiosensitivity of NSCLC cells <i>in vitro</i> and <i>in vivo</i>, whereas knockout of miR-384 led to radioresistance. Upregulation of miR-384 radiosensitized NSCLC cells by decreasing G2/M cell cycle arrest, inhibiting DNA damage repair, and consequently increasing cell death; miR-384 depletion had the opposite effects. Further investigation revealed that ATM, Ku70, and Ku80 were direct targets of miR-384. Moreover, miR-384 was repressed by NF-κB.</p><p><strong>Conclusions: </strong>MiR-384 is an ionizing radiation-responsive gene repressed by NF-κB. MiR-384 enhances the radiosensitivity of NSCLC cells <i>via</i> targeting ATM, Ku80, and Ku70, which impairs DNA damage repair. Therefore, miR-384 may serve as a novel radiosensitizer for NSCLC.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Research progress in tumor angiogenesis and drug resistance in breast cancer.","authors":"Jiancheng Mou, Chenhong Li, Qinghui Zheng, Xuli Meng, Hongchao Tang","doi":"10.20892/j.issn.2095-3941.2023.0515","DOIUrl":"10.20892/j.issn.2095-3941.2023.0515","url":null,"abstract":"<p><p>Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, <i>via</i> exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyu Song, Xiyan Liu, Qiqiang Guo, Hongde Xu, Liu Cao
{"title":"Unraveling the nexus between cellular senescence and malignant transformation: a paradigm shift in cancer research.","authors":"Xiaoyu Song, Xiyan Liu, Qiqiang Guo, Hongde Xu, Liu Cao","doi":"10.20892/j.issn.2095-3941.2024.0157","DOIUrl":"10.20892/j.issn.2095-3941.2024.0157","url":null,"abstract":"","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Zhuang, Yiding Ai, Peng Li, Xin Yue, Yue Li, Luling Shan, Tongtong Wang, Peng Zhao, Xun Jin
{"title":"Amplifying colorectal cancer progression: impact of a PDIA4/SP1 positive feedback loop by circPDIA4 sponging miR-9-5p.","authors":"Yan Zhuang, Yiding Ai, Peng Li, Xin Yue, Yue Li, Luling Shan, Tongtong Wang, Peng Zhao, Xun Jin","doi":"10.20892/j.issn.2095-3941.2024.0112","DOIUrl":"10.20892/j.issn.2095-3941.2024.0112","url":null,"abstract":"<p><strong>Objective: </strong>Colorectal cancer (CRC) is a prevalent malignant tumor with a high fatality rate. CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator. Nevertheless, the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied.</p><p><strong>Methods: </strong>Western blot, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression. The CCK-8 assay was used to assess cell growth. The Transwell assay was used to detect invasion and migration of cells. The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4 (or SP1) bind to one another. An <i>in vivo</i> assay was used to measure tumor growth.</p><p><strong>Results: </strong>It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues. CircPDIA4 knockdown prevented the invasion, migration, and proliferation of cells in CRC. Additionally, the combination of circPDIA4 and miR-9-5p was confirmed, as well as miR-9-5p binding to SP1. Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development of CRC. In addition, SP1 combined with the promoter region of circPDIA4 and induced circPDIA4 transcription. CircPDIA4 was shown to facilitate tumor growth in an <i>in vivo</i> assay.</p><p><strong>Conclusions: </strong>The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression. This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on UK Biobank data.","authors":"Yu Zhang, Chao Sheng, Zhangyan Lyu, Hongji Dai, Fangfang Song, Fengju Song, Yubei Huang, Kexin Chen","doi":"10.20892/j.issn.2095-3941.2024.0096","DOIUrl":"10.20892/j.issn.2095-3941.2024.0096","url":null,"abstract":"<p><strong>Objective: </strong>Few studies have evaluated the benefits of colorectal cancer (CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model (QCancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and mortality.</p><p><strong>Methods: </strong>We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios (HRs) and absolute risk reductions (ARRs) for CRC incidence and mortality according to risk stratification.</p><p><strong>Results: </strong>During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediate- and high-risk groups [incidence: HR: 0.87, 95% confidence interval (CI): 0.81-0.94; 0.81, 0.73-0.90; mortality: 0.75, 0.64-0.87; 0.70, 0.58-0.85], which composed approximately 60% of the study population. The ARRs (95% CI) were 0.17 (0.11-0.24) and 0.43 (0.24-0.61), respectively, for CRC incidence, and 0.08 (0.05-0.11) and 0.24 (0.15-0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk groups.</p><p><strong>Conclusions: </strong>After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuyi Chen, Jing Gu, Kaichun Wu, Xiaodi Zhao, Yuanyuan Lu
{"title":"Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants.","authors":"Shuyi Chen, Jing Gu, Kaichun Wu, Xiaodi Zhao, Yuanyuan Lu","doi":"10.20892/j.issn.2095-3941.2024.0026","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0026","url":null,"abstract":"<p><p>Targeted therapy is crucial for advanced colorectal cancer (CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2 (ERBB2), B-Raf proto-oncogene, serine/threonine kinase (BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase (ALK/ROS1), neurotrophic receptor tyrosine kinases (NTRKs), ret proto-oncogene (RET), fibroblast growth factor receptor 2 (FGFR2), and epidermal growth factor receptor (EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":"21 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Revolutionizing tumor immunotherapy: unleashing the power of progenitor exhausted T cells.","authors":"Zhang Fang, Xinyi Ding, Hao Huang, Hongwei Jiang, Jingting Jiang, Xiao Zheng","doi":"10.20892/j.issn.2095-3941.2024.0105","DOIUrl":"10.20892/j.issn.2095-3941.2024.0105","url":null,"abstract":"<p><p>In exploring persistent infections and malignancies, a distinctive subgroup of CD8<sup>+</sup> T cells, progenitor exhausted CD8<sup>+</sup> T (Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8<sup>+</sup> T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cuicui Zhang, Tianqing Chu, Qiming Wang, Ying Cheng, Yongxiang Zhang, Ruili Wang, Leilei Ma, Chaonan Qian, Baohui Han, Kai Li
{"title":"Enhancement of anti-PD-L1 antibody plus anlotinib efficacy due to downregulation of PD-L1 in the micro-conduit endothelium within the tumor: a randomized double-blind trial.","authors":"Cuicui Zhang, Tianqing Chu, Qiming Wang, Ying Cheng, Yongxiang Zhang, Ruili Wang, Leilei Ma, Chaonan Qian, Baohui Han, Kai Li","doi":"10.20892/j.issn.2095-3941.2023.0423","DOIUrl":"10.20892/j.issn.2095-3941.2023.0423","url":null,"abstract":"<p><strong>Objective: </strong>The possible enhancing effect of anlotinib on programmed death receptor ligand (PD-L1) antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium, including lymphatic endothelial cells (LECs) and blood endothelial cells (BECs), were determined to identify patients who would benefit from this treatment.</p><p><strong>Methods: </strong>PD-L1 positivity in LECs, BECs, and tumor cells (TCs) was assessed using paraffin sections with multicolor immunofluorescence in an investigator's brochure clinical trial of TQB2450 (PD-L1 antibody) alone or in combination with anlotinib in patients with non-small cell lung cancer. Progression-free survival (PFS) with different levels of PD-L1 expression was compared between the two groups.</p><p><strong>Results: </strong>Among 75 patients, the median PFS (mPFS) was longer in patients who received TQB2450 with anlotinib [10 and 12 mg (161 and 194 days, respectively)] than patients receiving TQB2450 alone (61 days) [hazard ratio (HR)<sub>10 mg</sub> = 0.390 (95% confidence interval {CI}, 0.201-0.756), <i>P</i> = 0.005; HR<sub>12 mg</sub> = 0.397 (0.208-0.756), <i>P</i> = 0.005]. The results were similar among 58 patients with high PD-L1 expression in LECs and TCs [159 and 209 <i>vs.</i> 82 days, HR<sub>10 mg</sub> = 0.445 (0.210-0.939), <i>P</i> = 0.034; HR<sub>12 mg</sub> = 0.369 (0.174-0.784), <i>P</i> = 0.009], and 53 patients with high PD-L1 expression in BECs and TCs [161 and 209 <i>vs.</i> 41 days, HR<sub>10 mg</sub> = 0.340 (0.156-0.742), <i>P</i> = 0.007; HR<sub>12 mg</sub> = 0.340 (0.159-0.727), <i>P</i> = 0.005]. No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases.</p><p><strong>Conclusions: </strong>Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs. Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs, which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune checkpoint inhibitors: breakthroughs in cancer treatment.","authors":"Xueqing Kong, Jinyi Zhang, Shuwei Chen, Xianyang Wang, Qing Xi, Han Shen, Rongxin Zhang","doi":"10.20892/j.issn.2095-3941.2024.0055","DOIUrl":"10.20892/j.issn.2095-3941.2024.0055","url":null,"abstract":"<p><p>Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade (ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies (mAbs) are currently available as immune checkpoint inhibitors (ICIs). These ICIs target specific immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Clinical trial results strongly support the feasibility of this immunotherapeutic approach. However, a substantial proportion of patients with cancer develop resistance or tolerance to treatment, owing to tumor immune evasion mechanisms that counteract the host immune response. Consequently, substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1, anti-programmed cell death ligand 1 (anti-PD-L1), and anti-CTLA-4 treatments. Recently, several immune checkpoint molecular targets have been identified, such as T cell immunoreceptor with Ig and ITIM domains (TIGIT), mucin domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), V-domain immunoglobulin suppressor of T cell activation (VISTA), B and T lymphocyte attenuator (BTLA), and signal-regulatory protein α (SIRPα). Functional mAbs targeting these molecules are under development. CTLA-4, PD-1/PD-L1, and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research. This review discusses these structures, as well as clinical progress in mAbs targeting these immune checkpoint molecules and their potential applications.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}