Frontiers of MedicinePub Date : 2024-10-01Epub Date: 2024-09-28DOI: 10.1007/s11684-024-1104-4
Yimin Liu, Haitao Li
{"title":"Epigenetic modifiers: catalytic or noncatalytic, that is the question.","authors":"Yimin Liu, Haitao Li","doi":"10.1007/s11684-024-1104-4","DOIUrl":"10.1007/s11684-024-1104-4","url":null,"abstract":"","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"941-943"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers of MedicinePub Date : 2024-10-01Epub Date: 2024-09-28DOI: 10.1007/s11684-024-1090-6
Yingying Huang, Zhigang Tian, Jiacheng Bi
{"title":"Intracellular checkpoints for NK cell cancer immunotherapy.","authors":"Yingying Huang, Zhigang Tian, Jiacheng Bi","doi":"10.1007/s11684-024-1090-6","DOIUrl":"10.1007/s11684-024-1090-6","url":null,"abstract":"<p><p>Natural killer (NK) cells are key innate immune lymphocytes, which play important roles against tumors. However, tumor-infiltrating NK cells are always hypofunctional/exhaustive. On the one hand, this state is contributed by context-dependent interactions between inhibitory NK cell checkpoint receptors and their ligands, which usually vary in different tumor types and stages during tumor development. On the other hand, the inhibitory functions of intracellular checkpoint molecules of NK cells are more similar across different tumor types, representing common mechanisms limiting the potential of NK cell therapy. In this review, representative NK cell intracellular checkpoint molecules in different aspects of NK cell biology were reviewed, and therapeutic potentials were discussed by targeting these molecules to promote antitumor NK cell therapy.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"763-777"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haihua Zhang, Xinli Liu, Junqiang Li, Jin Meng, Wan Huang, Xuan Su, Xutao Zhang, Guizhou Gao, Xiaodong Wang, Haichuan Su, Feng Zhang, Tao Zhang
{"title":"ING5 inhibits aerobic glycolysis of lung cancer cells by promoting TIE1-mediated phosphorylation of pyruvate dehydrogenase kinase 1 at Y163","authors":"Haihua Zhang, Xinli Liu, Junqiang Li, Jin Meng, Wan Huang, Xuan Su, Xutao Zhang, Guizhou Gao, Xiaodong Wang, Haichuan Su, Feng Zhang, Tao Zhang","doi":"10.1007/s11684-024-1057-7","DOIUrl":"https://doi.org/10.1007/s11684-024-1057-7","url":null,"abstract":"<p>Aerobic glycolysis is critical for tumor growth and metastasis. Previously, we have found that the overexpression of the inhibitor of growth 5 (ING5) inhibits lung cancer aggressiveness and epithelial–mesenchymal transition (EMT). However, whether ING5 regulates lung cancer metabolism reprogramming remains unknown. Here, by quantitative proteomics, we showed that ING5 differentially regulates protein phosphorylation and identified a new site (Y163) of the key glycolytic enzyme PDK1 whose phosphorylation was upregulated 13.847-fold. By clinical study, decreased p-PDK1Y163 was observed in lung cancer tissues and correlated with poor survival. p-PDK1Y163 represents the negative regulatory mechanism of PDK1 by causing PDHA1 dephosphorylation and activation, leading to switching from glycolysis to oxidative phosphorylation, with increasing oxygen consumption and decreasing lactate production. These effects could be impaired by PDK1Y163F mutation, which also impaired the inhibitory effects of ING5 on cancer cell EMT and invasiveness. Mouse xenograft models confirmed the indispensable role of p-PDK1Y163 in ING5-inhibited tumor growth and metastasis. By siRNA screening, ING5-upregulated TIE1 was identified as the upstream tyrosine protein kinase targeting PDK1Y163. TIE1 knockdown induced the dephosphorylation of PDK1Y163 and increased the migration and invasion of lung cancer cells. Collectively, ING5 overexpression—upregulated TIE1 phosphorylates PDK1Y163, which is critical for the inhibition of aerobic glycolysis and invasiveness of lung cancer cells.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":"10 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dronedarone inhibits the proliferation of esophageal squamous cell carcinoma through the CDK4/CDK6-RB1 axis in vitro and in vivo","authors":"Bo Li, Jing Zhang, Yin Yu, Yinhua Li, Yingying Chen, Xiaokun Zhao, Ang Li, Lili Zhao, Mingzhu Li, Zitong Wang, Xuebo Lu, Wenjie Wu, Yueteng Zhang, Zigang Dong, Kangdong Liu, Yanan Jiang","doi":"10.1007/s11684-024-1062-x","DOIUrl":"https://doi.org/10.1007/s11684-024-1062-x","url":null,"abstract":"<p>Treatment options for patients with esophageal squamous cell carcinoma (ESCC) often result in poor prognosis and declining health-related quality of life. Screening FDA-approved drugs for cancer chemoprevention is a promising and cost-efficient strategy. Here, we found that dronedarone, an antiarrhythmic drug, could inhibit the proliferation of ESCC cells. Moreover, we conducted phosphorylomics analysis to investigate the mechanism of dronedarone-treated ESCC cells. Through computational docking models and pull-down assays, we demonstrated that dronedarone could directly bind to CDK4 and CDK6 kinases. We also proved that dronedarone effectively inhibited ESCC proliferation by targeting CDK4/CDK6 and blocking the G0/G1 phase through RB1 phosphorylation inhibition by <i>in vitro</i> kinase assays and cell cycle assays. Subsequently, we found that knocking out CDK4 and CDK6 decreased the susceptibility of ESCC cells to dronedarone. Furthermore, dronedarone suppressed the growth of ESCC in patient-derived tumor xenograft models <i>in vivo.</i> Thus, our study demonstrated that dronedarone could be repurposed as a CDK4/6 inhibitor for ESCC chemoprevention.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":"109 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of molecular residual disease in operable non-small cell lung cancer with gene fusions, MET exon skipping or de novo MET amplification.","authors":"Rui Fu, Yuanyuan Xiong, Miao Cai, Fang Li, Rongrong Chen, Yilong Wu, Wenzhao Zhong","doi":"10.1007/s11684-024-1060-z","DOIUrl":"10.1007/s11684-024-1060-z","url":null,"abstract":"<p><p>Gene fusions and MET alterations are rare and difficult to detect in plasma samples. The clinical detection efficacy of molecular residual disease (MRD) based on circulating tumor DNA (ctDNA) in patients with non-small cell lung cancer (NSCLC) with these mutations remains unknown. This prospective, non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions (ALK, ROS1, RET, and FGFR1), MET exon 14 skipping or de novo MET amplification. We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021- and 338-gene panels, respectively. Detectable MRD correlated with a significantly higher recurrence rate (P < 0.001), yielding positive predictive values of 100% and 90.9%, and negative predictive values of 82.4% and 86.4% at landmark and longitudinal time points, respectively. Patients with detectable MRD showed reduced disease-free survival (DFS) compared to those with undetectable MRD (P < 0.001). Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not (P = 0.05). To our knowledge, this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations. Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"735-743"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers of MedicinePub Date : 2024-08-01Epub Date: 2024-07-16DOI: 10.1007/s11684-024-1063-9
Yihui Chen, Qiaozhi Cao, Cong Peng, Bingjing Zhou, Yu Jiang, Xiang Chen, Jie Li
{"title":"Real-world effectiveness and safety of Janus kinase 1 inhibitors for the treatment of moderate-to-severe atopic dermatitis: a single-center, prospective study in China.","authors":"Yihui Chen, Qiaozhi Cao, Cong Peng, Bingjing Zhou, Yu Jiang, Xiang Chen, Jie Li","doi":"10.1007/s11684-024-1063-9","DOIUrl":"10.1007/s11684-024-1063-9","url":null,"abstract":"","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"752-756"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers of MedicinePub Date : 2024-08-01Epub Date: 2024-06-04DOI: 10.1007/s11684-024-1071-9
Fan Zou, Jialiang Wei, Jialang Zhuang, Yafang Liu, Jizhou Tan, Xianzhang Huang, Ting Liu
{"title":"Moderate expression of CD39 in GPC3-CAR-T cells shows high efficacy against hepatocellular carcinoma.","authors":"Fan Zou, Jialiang Wei, Jialang Zhuang, Yafang Liu, Jizhou Tan, Xianzhang Huang, Ting Liu","doi":"10.1007/s11684-024-1071-9","DOIUrl":"10.1007/s11684-024-1071-9","url":null,"abstract":"<p><p>CD39 serves as a crucial biomarker for neoantigen-specific CD8<sup>+</sup> T cells and is associated with antitumor activity and exhaustion. However, the relationship between CD39 expression levels and the function of chimeric antigen receptor T (CAR-T) cells remains controversial. This study aimed to investigate the role of CD39 in the functional performance of CAR-T cells against hepatocellular carcinoma (HCC) and explore the therapeutic potential of CD39 modulators, such as mitochondrial division inhibitor-1 (mdivi-1), or knockdown CD39 through short hairpin RNA. Our findings demonstrated that glypican-3-CAR-T cells with moderate CD39 expression exhibited a strong antitumor activity, while high and low levels of CD39 led to an impaired cellular function. Methods modulating the proportion of CD39 intermediate (CD39<sup>int</sup>)-phenotype CAR-T cells such as mdivi-1 and CD39 knockdown enhanced and impaired T cell function, respectively. The combination of mdivi-1 and CD39 knockdown in CAR-T cells yielded the highest proportion of infiltrated CD39<sup>int</sup> CAR-T cells and demonstrated a robust antitumor activity in vivo. In conclusion, this study revealed the crucial role of CD39 in CAR-T cell function, demonstrated the potential therapeutic efficacy of combining mdivi-1 with CD39 knockdown in HCC, and provided a novel treatment strategy for HCC patients in the field of cellular immunotherapy.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"708-720"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers of MedicinePub Date : 2024-08-01Epub Date: 2024-07-03DOI: 10.1007/s11684-024-1073-7
Jun Zhao, Hui Zheng, Xin Wang, Xuefei Wang, Yunzhou Shi, Chaorong Xie, Qingfeng Tao, Da Li, Jingwen Sun, Junjian Tian, Junxia Gao, Huimin Liu, Suhua Shi, Jinxia Ni, Rongdan Xue, Hui Hu, Min Chen, Shuguang Yu, Zhigang Li
{"title":"Efficacy of acupuncture in refractory irritable bowel syndrome patients: a randomized controlled trial.","authors":"Jun Zhao, Hui Zheng, Xin Wang, Xuefei Wang, Yunzhou Shi, Chaorong Xie, Qingfeng Tao, Da Li, Jingwen Sun, Junjian Tian, Junxia Gao, Huimin Liu, Suhua Shi, Jinxia Ni, Rongdan Xue, Hui Hu, Min Chen, Shuguang Yu, Zhigang Li","doi":"10.1007/s11684-024-1073-7","DOIUrl":"10.1007/s11684-024-1073-7","url":null,"abstract":"<p><p>Previous studies have confirmed that acupuncture for irritable bowel syndrome (IBS) provided an additional benefit over usual care alone. Therefore, we performed a multicenter, randomized, sham-controlled trial to assess the efficacy and safety of acupuncture versus sham acupuncture for refractory IBS in patients in the context of conventional treatments. Patients in the acupuncture and sham acupuncture groups received real or sham acupuncture treatment in 3 sessions per week for a total of 12 sessions. The primary outcome was a change in the IBS-Symptom Severity Scale (IBS-SSS) score from baseline to week 4. A total of 521 participants were screened, and 170 patients (85 patients per group) were enrolled and included in the intention-to-treat analysis. Baseline characteristics were comparable across the two groups. From baseline to 4 weeks, the IBS-SSS total score decreased by 140.0 (95% CI: 126.0 to 153.9) in the acupuncture group and 64.4 (95% CI: 50.4 to 78.3) in the sham acupuncture group. The between-group difference was 75.6 (95% CI: 55.8 to 95.4). Acupuncture efficacy was maintained during the 4-week follow-up period. There were no serious adverse events. In conclusion, acupuncture provided benefits when combined with treatment as usual, providing more options for the treatment of refractory IBS.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"678-689"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers of MedicinePub Date : 2024-08-01Epub Date: 2024-07-23DOI: 10.1007/s11684-024-1092-4
Juan Wang, Dongni Shi, Yaochen Wang, Xuanqi Zhang, Han Li, Xihong Wang, Shufeng Luo, Lihan Hu, Jiashuai Deng, Lin Zhang, Chung Tai Lau, Chung Wah Cheng, Fei Han, Ji Li, Ping Wang, Aiping Lyu, Zhaoxiang Bian, Xuan Zhang
{"title":"Transparency and reporting characteristics of randomized controlled trials with Chinese herbal medicine formulas interventions.","authors":"Juan Wang, Dongni Shi, Yaochen Wang, Xuanqi Zhang, Han Li, Xihong Wang, Shufeng Luo, Lihan Hu, Jiashuai Deng, Lin Zhang, Chung Tai Lau, Chung Wah Cheng, Fei Han, Ji Li, Ping Wang, Aiping Lyu, Zhaoxiang Bian, Xuan Zhang","doi":"10.1007/s11684-024-1092-4","DOIUrl":"10.1007/s11684-024-1092-4","url":null,"abstract":"","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"757-761"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frontiers of MedicinePub Date : 2024-08-01Epub Date: 2024-06-27DOI: 10.1007/s11684-023-1053-3
Yuanxin Yao, Honghui Lv, Meiying Zhang, Yuan Li, James G Herman, Malcolm V Brock, Aiai Gao, Qian Wang, Francois Fuks, Lirong Zhang, Mingzhou Guo
{"title":"Epigenetic silencing of BEND4, a novel DNA damage repair gene, is a synthetic lethal marker for ATM inhibitor in pancreatic cancer.","authors":"Yuanxin Yao, Honghui Lv, Meiying Zhang, Yuan Li, James G Herman, Malcolm V Brock, Aiai Gao, Qian Wang, Francois Fuks, Lirong Zhang, Mingzhou Guo","doi":"10.1007/s11684-023-1053-3","DOIUrl":"10.1007/s11684-023-1053-3","url":null,"abstract":"<p><p>Synthetic lethality is a novel model for cancer therapy. To understand the function and mechanism of BEN domain-containing protein 4 (BEND4) in pancreatic cancer, eight cell lines and a total of 492 cases of pancreatic neoplasia samples were included in this study. Methylation-specific polymerase chain reaction, CRISPR/Cas9, immunoprecipitation assay, comet assay, and xenograft mouse model were used. BEND4 is a new member of the BEN domain family. The expression of BEND4 is regulated by promoter region methylation. It is methylated in 58.1% (176/303) of pancreatic ductal adenocarcinoma (PDAC), 33.3% (14/42) of intraductal papillary mucinous neoplasm, 31.0% (13/42) of pancreatic neuroendocrine tumor, 14.3% (3/21) of mucinous cystic neoplasm, 4.3% (2/47) of solid pseudopapillary neoplasm, and 2.7% (1/37) of serous cystic neoplasm. BEND4 methylation is significantly associated with late-onset PDAC (> 50 years, P < 0.01) and tumor differentiation (P < 0.0001), and methylation of BEND4 is an independent poor prognostic marker (P < 0.01) in PDAC. Furthermore, BEND4 plays tumor-suppressive roles in vitro and in vivo. Mechanistically, BEND4 involves non-homologous end joining signaling by interacting with Ku80 and promotes DNA damage repair. Loss of BEND4 increased the sensitivity of PDAC cells to ATM inhibitor. Collectively, the present study revealed an uncharacterized tumor suppressor BEND4 and indicated that methylation of BEND4 may serve as a potential synthetic lethal marker for ATM inhibitor in PDAC treatment.</p>","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":" ","pages":"721-734"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}