MedComm最新文献 - Book学术

IL-37 Mitigates the Inflammatory Response in Macrophages Induced by SARS-CoV-2 Omicron Infection Through the NF-κB Signaling Pathway IL-37通过NF-κB信号通路减轻SARS-CoV-2组粒感染诱导的巨噬细胞炎症反应

IF 10.7

MedComm Pub Date : 2025-05-31 DOI: 10.1002/mco2.70229

Feifei Qi, Yiwei Yan, Mingya Liu, Qi Lv, Yanfeng Xu, Ming Liu, Fengdi Li, Ran Deng, Xujian Liang, Shuyue Li, Guocui Mou, Linlin Bao

{"title":"IL-37 Mitigates the Inflammatory Response in Macrophages Induced by SARS-CoV-2 Omicron Infection Through the NF-κB Signaling Pathway","authors":"Feifei Qi, Yiwei Yan, Mingya Liu, Qi Lv, Yanfeng Xu, Ming Liu, Fengdi Li, Ran Deng, Xujian Liang, Shuyue Li, Guocui Mou, Linlin Bao","doi":"10.1002/mco2.70229","DOIUrl":"https://doi.org/10.1002/mco2.70229","url":null,"abstract":"The expression levels of macrophage-associated cytokines are significantly greater in COVID-19 patients than in healthy individuals. Exploring strategies to modulate pathological cytokine storms can effectively prevent the development of severe coronavirus infection-induced pneumonia. Treatment with interleukin-37 (IL-37), an anti-inflammatory factor, has unique anti-inflammatory and antiviral effects on infections caused by various pathogens. In this study, we investigated the effect of IL-37 treatment on the SARS-CoV-2 Omicron-infection induced inflammatory response and its molecular mechanism. Our results demonstrated that IL-37 treatment effectively alleviated symptoms, reduced viral loads, suppressed the production of proinflammatory cytokines and chemokines both systemically (in serum) and locally (in the lungs), and attenuated lung lesions and inflammatory cell infiltration in Omicron-infected mice. The suppressed proinflammatory factors were macrophage-related, particularly CCL3 and CCL4, which were significantly inhibited. Furthermore, treatment with IL-37 significantly reduced the proportion of M1-type macrophages in lungs of Omicron-infected mice. In addition, we found that IL-37 targeted M1 macrophages through modulation of the NF-κB signaling pathway to suppress the production of proinflammtory factors during Omicron infection. This study elucidated the anti-inflammatory effect of IL-37 treatment on the Omicron-induced inflammatory response while identifying its specific target site, thereby providing fundamental insights for exploring potential clinical therapeutic interventions.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70229","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy and Safety of Neoadjuvant Immunotherapy plus Chemotherapy versus Neoadjuvant Chemotherapy in Non-Small Cell Lung Cancer Treatment: A Mixed Method Meta-Analysis Based on Global Randomized Controlled Trials 新辅助免疫治疗加化疗与新辅助化疗治疗非小细胞肺癌的疗效和安全性：基于全球随机对照试验的混合方法荟萃分析

IF 10.7

MedComm Pub Date : 2025-05-31 DOI: 10.1002/mco2.70211

Shen Li, Chenhao Xu, Yuanling Meng, Yiyang Li, Jiaqing Yang, Junxuan Du, Fan Zhang, Hu Liao, Xuelei Ma

{"title":"Efficacy and Safety of Neoadjuvant Immunotherapy plus Chemotherapy versus Neoadjuvant Chemotherapy in Non-Small Cell Lung Cancer Treatment: A Mixed Method Meta-Analysis Based on Global Randomized Controlled Trials","authors":"Shen Li, Chenhao Xu, Yuanling Meng, Yiyang Li, Jiaqing Yang, Junxuan Du, Fan Zhang, Hu Liao, Xuelei Ma","doi":"10.1002/mco2.70211","DOIUrl":"https://doi.org/10.1002/mco2.70211","url":null,"abstract":"This study explores the efficacy and safety of combining immunotherapy with chemotherapy for neoadjuvant non-small cell lung cancer (NSCLC) treatment. Despite the rapid advancement of immunotherapy, direct evidence comparing it with chemotherapy alone is limited. Following PRISMA guidelines, we analyzed global phase II and III randomized controlled trials data. Our meta-analysis included nine trials with 3431 participants, showing that combined treatment significantly improved event-free survival, pathological complete response, major pathological response, surgical acceptance, and R0 resection rates in NSCLC compared with chemotherapy alone. Safety analysis revealed similar all adverse event incidences between treatments, while Grade ≥3 adverse events were higher than those in neoadjuvant chemotherapy. Network meta-analysis confirmed the benefits of different immunotherapeutic drugs and efficacy in different subgroups. The study's high-quality evidence suggests that neoadjuvant immunotherapy plus chemotherapy should be considered in clinical practice for NSCLC, with further research needed to optimize treatment strategies and improve patient outcomes.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myeloid-Derived Suppressor Cells in Cancer: Mechanistic Insights and Targeted Therapeutic Innovations 骨髓源性抑制细胞在癌症中的作用：机制见解和靶向治疗创新

IF 10.7

MedComm Pub Date : 2025-05-31 DOI: 10.1002/mco2.70231

Tianying Hu, Jianxue Zhai, Zhanda Yang, Jiajia Peng, Chuxuan Wang, Xinyao Liu, Yawen Li, Jiaqi Yao, Fengxi Chen, Haixia Li, Taixue An, Zongcai Liu, Haifang Wang

{"title":"Myeloid-Derived Suppressor Cells in Cancer: Mechanistic Insights and Targeted Therapeutic Innovations","authors":"Tianying Hu, Jianxue Zhai, Zhanda Yang, Jiajia Peng, Chuxuan Wang, Xinyao Liu, Yawen Li, Jiaqi Yao, Fengxi Chen, Haixia Li, Taixue An, Zongcai Liu, Haifang Wang","doi":"10.1002/mco2.70231","DOIUrl":"https://doi.org/10.1002/mco2.70231","url":null,"abstract":"Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that expand aberrantly in cancer and exhibit potent immunosuppressive properties. They contribute to tumor progression through both immunological and nonimmunological mechanisms. Immunologically, MDSCs suppress antitumor responses by inhibiting effector cells such as T cells and NK cells, facilitating immune evasion. Nonimmunologically, they promote tumor growth and metastasis through processes such as the epithelial‒mesenchymal transition, angiogenesis, and premetastatic niche formation. MDSC accumulation is closely linked to accelerated tumor progression, including resistance to both immunotherapies and conventional treatments, making these cells critical therapeutic targets. Clinical studies have demonstrated the potential of MDSC-targeted strategies to improve treatment efficacy. However, challenges remain in achieving specificity and effectiveness in MDSC-targeted therapies, emphasizing the need for a deeper understanding of their biology. This review summarizes the origin, classification, and biological characteristics of MDSCs, their dual roles in tumor progression, and their clinical significance. We also discuss recent advances in clinical and preclinical studies, including both traditional targeted therapies and emerging innovative strategies. By integrating current findings, we aim to provide a comprehensive perspective on the role of MDSCs in cancer and valuable insights for advancing cancer treatment and drug development.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prevalence, Risk Factors, Lung Function, and Associated Comorbidities of Adult Preserved Ratio Impaired Spirometry: A Meta-Analysis 成人保留比例肺功能受损的患病率、危险因素、肺功能和相关合并症：荟萃分析

IF 10.7

MedComm Pub Date : 2025-05-31 DOI: 10.1002/mco2.70235

Haoyu Wang, Ruiyuan Yang, Dan Liu, Weimin Li

{"title":"Prevalence, Risk Factors, Lung Function, and Associated Comorbidities of Adult Preserved Ratio Impaired Spirometry: A Meta-Analysis","authors":"Haoyu Wang, Ruiyuan Yang, Dan Liu, Weimin Li","doi":"10.1002/mco2.70235","DOIUrl":"https://doi.org/10.1002/mco2.70235","url":null,"abstract":"It is demonstrated that preserved ratio impaired spirometry (PRISm) is associated with chronic obstructive pulmonary disease development and mortality. However, comprehensive evidence on its prevalence, risk factors, lung function, and comorbidities is ambiguous. We searched for relevant studies from Medline, Web of Science, Embase, and Scopus up to March 26, 2024, and conducted a meta-analysis based on PRISMA 2020 to merge the results of eligible studies to reveal the prevalence, risk factors, lung function, and associated comorbidities in PRISm population. Thirty-two studies involving 1,196,856 participants were included. The prevalence of PRISm was 11% (95%CI: 10–13%), with decreased forced vital capacity (FVC) (L) (MD: −0.78, 95%CI: −0.90 to −0.66) and FVC% predicted (MD: −24.74, 95%CI: −26.33 to −23.16). Older age, high body mass index, current or ever smoking, and low education were positively associated with PRISm, while cardiovascular and endocrine comorbidities were common in patients with PRISm. The prevalence of PRISm is high in general population, with multiple risk factors, reduced lung function, and increased comorbidities. Therefore, clinicians should raise more concerns regarding this population to benefit them.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144185897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition Peroxiredoxin-2 by Capsaicin Ameliorates Rheumatoid Arthritis via ROS-Mediated Apoptosis in Fibroblast-Like Synoviocytes 辣椒素抑制过氧化物还毒素2通过ros介导的纤维母细胞样滑膜细胞凋亡改善类风湿关节炎

IF 10.7

MedComm Pub Date : 2025-05-29 DOI: 10.1002/mco2.70209

Hengkai He, Mingjing Hao, Piao Luo, Junhui Chen, Yehai An, Jingnan Huang, Ruiyi He, Qingfeng Du, Qian Zhang, Jigang Wang

{"title":"Inhibition Peroxiredoxin-2 by Capsaicin Ameliorates Rheumatoid Arthritis via ROS-Mediated Apoptosis in Fibroblast-Like Synoviocytes","authors":"Hengkai He, Mingjing Hao, Piao Luo, Junhui Chen, Yehai An, Jingnan Huang, Ruiyi He, Qingfeng Du, Qian Zhang, Jigang Wang","doi":"10.1002/mco2.70209","DOIUrl":"https://doi.org/10.1002/mco2.70209","url":null,"abstract":"Rheumatoid arthritis (RA), a prevalent and incurable autoimmune disease globally, is characterized by the immune system attacking the body's own tissues, leading to joint inflammation and damage. Capsaicin (CAP), from Capsicum annuum L., is known for its burning sensation-inducing property and has shown various pharmacological effects, yet its specific mechanisms and targets in RA treatment remain largely unclear. This study aimed to investigate the role of CAP in RA by synthesizing CAP probes and using activity-based protein profiling. We found that CAP reduced joint swelling in arthritic mice and exerted anti-inflammatory and antiproliferative effects on fibroblast-like synoviocytes. We identified that CAP binds to PRDX2, inhibiting its antioxidant function and inducing oxidative stress and apoptosis, contributing to the antiarthritic effects. These results suggest that PRDX2 is a potential target for CAP in RA treatment, providing new insights into the molecular mechanisms and potential therapeutic strategies for RA.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies 乳酸化：从体内平衡到病理意义和治疗策略

IF 10.7

MedComm Pub Date : 2025-05-29 DOI: 10.1002/mco2.70226

Xi Chen, Yixiao Yuan, Fan Zhou, Lihua Li, Jun Pu, Yong Zeng, Xiulin Jiang

{"title":"Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies","authors":"Xi Chen, Yixiao Yuan, Fan Zhou, Lihua Li, Jun Pu, Yong Zeng, Xiulin Jiang","doi":"10.1002/mco2.70226","DOIUrl":"https://doi.org/10.1002/mco2.70226","url":null,"abstract":"Lactylation, a recently identified post-translational modification, represents a groundbreaking addition to the epigenetic landscape, revealing its pivotal role in gene regulation and metabolic adaptation. Unlike traditional modifications, lactylation directly links metabolic intermediates, such as lactate, to protein function and cellular behavior. Emerging evidence highlights the critical involvement of lactylation in diverse biological processes, including immune response modulation, cellular differentiation, and tumor progression. However, its regulatory mechanisms, biological implications, and disease associations remain poorly understood. This review systematically explores the enzymatic and nonenzymatic mechanisms underlying protein lactylation, shedding light on the interplay between cellular metabolism and epigenetic control. We comprehensively analyze its biological functions in normal physiology, such as immune homeostasis and tissue repair, and its dysregulation in pathological contexts, including cancer, inflammation, and metabolic disorders. Moreover, we discuss advanced detection technologies and potential therapeutic interventions targeting lactylation pathways. By integrating these insights, this review aims to bridge critical knowledge gaps and propose future directions for research. Highlighting lactylation's multifaceted roles in health and disease, this review provides a timely resource for understanding its clinical implications, particularly as a novel target for precision medicine in metabolic and oncological therapies.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell Death and Senescence-Based Molecular Classification and an Individualized Prediction Model for Lung Adenocarcinoma 基于细胞死亡和衰老的分子分类和肺腺癌的个体化预测模型

IF 10.7

MedComm Pub Date : 2025-05-29 DOI: 10.1002/mco2.70237

Pan Wang, Chaoqi Zhang, Peng Wu, Zhihong Zhao, Nan Sun, Qi Xue, Shugeng Gao, Jie He

{"title":"Cell Death and Senescence-Based Molecular Classification and an Individualized Prediction Model for Lung Adenocarcinoma","authors":"Pan Wang, Chaoqi Zhang, Peng Wu, Zhihong Zhao, Nan Sun, Qi Xue, Shugeng Gao, Jie He","doi":"10.1002/mco2.70237","DOIUrl":"https://doi.org/10.1002/mco2.70237","url":null,"abstract":"The exploration of cell death and cellular senescence (CDS) in cancer has been an area of interest, yet a systematic evaluation of CDS features and their interactions in lung adenocarcinoma (LUAD) to understand tumor heterogeneity, tumor microenvironment (TME) characteristics, and patient clinical outcomes is previously uncharted. Our study characterized the activities and interconnections of 21 CDS features in 1788 LUAD cases across 15 cohorts, employing unsupervised clustering to categorize patients into three CDS subtypes with distinct TME profiles. The CDS index (CDSI), derived from principal component analysis, was developed to assess individual tumor CDS regulation patterns. Twelve CDSI core genes, enriched in proliferating T cells within the TME as per single-cell analysis, were identified and their functional roles and prognostic significance were validated. High CDSI correlated with improved overall survival in discovery cohort, four independent validation cohorts, and subgroup analysis. CDSI-low patients exhibited a favorable clinical response to immunotherapy and potential sensitivity to mitosis pathway drugs, while CDSI-high patients might benefit from drugs targeting ERK/MAPK and MDM2–p53 pathways. The clinical utility of CDSI was further validated using 9185 pan-cancer samples, demonstrating the broad relevance of our prediction model across various cancer types and its potential clinical implications for cancer management.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phase II Trial of Hypofractionated Radiotherapy and Immunochemotherapy in Primary Refractory Diffuse Large B-Cell Lymphoma: Preliminary Results and Insights from Digital Spatial Profiling 低分割放疗和免疫化疗治疗原发性难治性弥漫性大b细胞淋巴瘤的II期试验：初步结果和数字空间分析的见解

IF 10.7

MedComm Pub Date : 2025-05-25 DOI: 10.1002/mco2.70225

Yong Yang, Jing Yu, Xiao-Mei Hu, Si-Lin Chen, Rui-Zhi Zhao, Cheng Huang, Jiang-Rui Guo, Tian-Lan Tang, Cheng Chen, Yu-Ping Lin, Ying Wang, Tian-Xiu Liu, Hao Zheng, Si-Qin Liao, Jin-Hua Chen, Hai-Ying Fu, Ting-Bo Liu

{"title":"Phase II Trial of Hypofractionated Radiotherapy and Immunochemotherapy in Primary Refractory Diffuse Large B-Cell Lymphoma: Preliminary Results and Insights from Digital Spatial Profiling","authors":"Yong Yang, Jing Yu, Xiao-Mei Hu, Si-Lin Chen, Rui-Zhi Zhao, Cheng Huang, Jiang-Rui Guo, Tian-Lan Tang, Cheng Chen, Yu-Ping Lin, Ying Wang, Tian-Xiu Liu, Hao Zheng, Si-Qin Liao, Jin-Hua Chen, Hai-Ying Fu, Ting-Bo Liu","doi":"10.1002/mco2.70225","DOIUrl":"https://doi.org/10.1002/mco2.70225","url":null,"abstract":"This open-label, single-arm phase II study assessed the safety and efficacy of sequential hypofractionated radiotherapy (RT) followed by zimberelimab and R-GemOx (rituximab, gemcitabine, oxaliplatin) in patients with primary refractory diffuse large B-cell lymphoma (DLBCL). Fourteen patients were enrolled between June 2022 and December 2023, with 13 included in the analysis. RT doses of 36 and 24 Gy were delivered to the gross and target volumes in 12 fractions, followed by zimberelimab and R-GemOx. The overall response rate within the irradiated field was 92.3%, and a complete response (CR) was achieved by 61.5% of patients; however, 38.5% experienced disease progression. Treatment-related toxicities were manageable, primarily comprising mild leukocytopenia. Digital spatial profiling revealed 53 differentially expressed genes in CD20-rich lymphoma regions and 93 in CD3-rich T cell regions in non-CR patients. Reactome analysis identified key immune system pathways. T cell infiltration correlated with treatment efficacy, and multiplex immunohistochemistry validated immune pathways as potential therapeutic targets. This study demonstrated the promising role of RT combined with immunochemotherapy in refractory DLBCL and suggests immune pathways as critical targets to improve treatment outcomes.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70225","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Incidence of Metastasis in the Central Nervous System in Advanced Breast Cancer Treated With CDK 4/6 Inhibitors: A Multicenter, Retrospective Study cdk4 /6抑制剂治疗晚期乳腺癌中枢神经系统转移的发生率：一项多中心回顾性研究

IF 10.7

MedComm Pub Date : 2025-05-24 DOI: 10.1002/mco2.70221

Yan-Ling Wen, Xi-Wen Bi, Xue-Wen Zhang, Si-Fen Wang, Chang Jiang, Li Wang, Yong-Yi Zhong, Yuan-Yuan Huang, Jian-Li Zhao, Qian-Jun Chen, Cong Xue, Zhong-Yu Yuan

{"title":"Incidence of Metastasis in the Central Nervous System in Advanced Breast Cancer Treated With CDK 4/6 Inhibitors: A Multicenter, Retrospective Study","authors":"Yan-Ling Wen, Xi-Wen Bi, Xue-Wen Zhang, Si-Fen Wang, Chang Jiang, Li Wang, Yong-Yi Zhong, Yuan-Yuan Huang, Jian-Li Zhao, Qian-Jun Chen, Cong Xue, Zhong-Yu Yuan","doi":"10.1002/mco2.70221","DOIUrl":"https://doi.org/10.1002/mco2.70221","url":null,"abstract":"Central nervous system (CNS) metastasis remains a major cause of mortality in advanced breast cancer (ABC). While cyclin-dependent kinase 4/6 inhibitors (CDKIs) combined with endocrine therapy (ET) delay resistance in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative ABC, their impact on CNS metastasis development has not been fully elucidated. This retrospective study analyzed 435 ABC patients without baseline CNS metastases who received first-line ET with or without CDKIs across three Chinese hospitals (August 2018–July 2022). Primary end points included CNS as the first metastatic site, CNS metastasis-free survival (CNSM-FS), and CNS metastasis incidence over time. Secondary end points were progression-free survival (PFS) and overall survival (OS). The results indicated that the addition of CDKIs to ET significantly reduced the incidence of CNS as the first site of metastasis (3.7% vs. 9.5% with ET alone; p = 0.0015) and extended CNSM-FS (71.6 months vs. 63.6 months, respectively; hazard ratio [HR], 0.53; 95% CI, 0.31–0.92). Overall, CNS metastasis incidence was lower with ET + CDKIs (7.9% vs. 15.5%, p = 0.014), and improvements were observed in both PFS and OS. These findings suggest that ET + CDKIs as first-line therapy in ABC may reduce CNS metastasis risk and extend CNSM-FS, offering a potential strategy for preventing CNS metastases.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting LIF With Cyclovirobuxine D to Suppress Tumor Progression via LIF/p38MAPK/p62-Modulated Mitophagy in Hepatocellular Carcinoma 环维黄素D靶向LIF通过LIF/p38MAPK/p62调控的肝癌细胞自噬抑制肿瘤进展

IF 10.7

MedComm Pub Date : 2025-05-24 DOI: 10.1002/mco2.70227

Yingying Shao, Di Lu, Wenke Jin, Sibao Chen, Lifeng Han, Tao Wang, Leilei Fu, Haiyang Yu

{"title":"Targeting LIF With Cyclovirobuxine D to Suppress Tumor Progression via LIF/p38MAPK/p62-Modulated Mitophagy in Hepatocellular Carcinoma","authors":"Yingying Shao, Di Lu, Wenke Jin, Sibao Chen, Lifeng Han, Tao Wang, Leilei Fu, Haiyang Yu","doi":"10.1002/mco2.70227","DOIUrl":"https://doi.org/10.1002/mco2.70227","url":null,"abstract":"Leukemia inhibitory factor (LIF) exerts an oncogenic function in several types of cancer, including hepatocellular carcinoma (HCC). However, small-molecule inhibitors of LIF haven't been established. Here, we identified that LIF was remarkably overexpressed in HCC by multi-omics approaches, indicating that inhibition of LIF would be a promising therapeutic strategy. Inhibiting LIF could suppress proliferation and metastasis by activating p38MAPK/p62-modulated mitophagy. Interestingly, we found that the natural small-molecule Cyclovirobuxine-D (CVB-D), was a new inhibitor of cytoplasmic LIF in HCC. We further validated LIF as a potential target of CVB-D through biotin-modified CVB-D-Probe utilizing mass spectrometry. Mechanistically, we showed that CVB-D could bind to LIF at Val145, thereby inducing mitophagy, accompanied by cell cycle arrest and inhibition of invasion and migration. Moreover, we demonstrated that CVB-D had a therapeutic potential by targeting LIF-modulated mitophagy in patient-derived xenograft (PDX) models, which would elucidate LIF as a druggable target and regulatory mechanisms and exploit CVB-D as the novel small-molecule inhibitor of LIF for future HCC drug discovery.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 6","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0