Cell Reports Medicine最新文献_第4页

The expanding benefits of GLP-1 medicines. GLP-1药物的益处越来越大。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-07-15 DOI: 10.1016/j.xcrm.2025.102214

Maria J Gonzalez-Rellan, Daniel J Drucker

引用次数: 0

Targeting synthetic lethality between non-homologous end joining and radiation in very-high-risk medulloblastoma. 针对高危髓母细胞瘤非同源末端连接与放疗之间的合成致死率。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-07-15 Epub Date: 2025-06-24 DOI: 10.1016/j.xcrm.2025.102202

Alexandria DeCarlo, Graham MacLeod, Carolina Fernandes da Silva, Li Qing Shen, Julija Povilaikaite, Madeline Deane, Lucas Aragao, Mariska Sie, Deborah Termini, Jonathan Magee, Brian Gudenas, Sneha Sukumaran, Frederic Charron, Richard Marcellus, Rima Al-Awar, Ahmed Aman, Denis Reynaud, Amarine Trolat, Leanne Wybenga-Groot, Uri Tabori, Carolina Nör, Shane M Harding, Michael F Moran, Paul A Northcott, Peter Dirks, Stephane Angers, Vijay Ramaswamy

{"title":"Targeting synthetic lethality between non-homologous end joining and radiation in very-high-risk medulloblastoma.","authors":"Alexandria DeCarlo, Graham MacLeod, Carolina Fernandes da Silva, Li Qing Shen, Julija Povilaikaite, Madeline Deane, Lucas Aragao, Mariska Sie, Deborah Termini, Jonathan Magee, Brian Gudenas, Sneha Sukumaran, Frederic Charron, Richard Marcellus, Rima Al-Awar, Ahmed Aman, Denis Reynaud, Amarine Trolat, Leanne Wybenga-Groot, Uri Tabori, Carolina Nör, Shane M Harding, Michael F Moran, Paul A Northcott, Peter Dirks, Stephane Angers, Vijay Ramaswamy","doi":"10.1016/j.xcrm.2025.102202","DOIUrl":"10.1016/j.xcrm.2025.102202","url":null,"abstract":"Specific and biologically informed treatments for medulloblastoma, especially for the highly lethal TP53-mutant SHH subgroup, remain elusive, where radiotherapy is the primary treatment modality. Leveraging genome-wide CRISPR-Cas9 dropout screening in combination with lethal doses of radiotherapy, we identify loss of p53 as the main driver of radiation resistance in SHH medulloblastoma. A negative-selection CRISPR-Cas9 screen across multiple models of Trp53-deficient SHH medulloblastoma reveals a strong synthetic lethal interaction between components of the non-homologous end-joining pathway and radiation, particularly DNA-dependent protein kinase (DNA-PK) and its binding partners. Both genetic and pharmacological perturbation of DNA-PK enhance radiosensitivity in TP53-deficient SHH medulloblastoma, leading to cell death. In vivo treatment of both somatic and germline TP53-mutant SHH medulloblastoma models with peposertib, a small-molecule inhibitor of DNA-PK, significantly improves survival when combined with radiotherapy, strongly supporting further clinical investigation.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102202"},"PeriodicalIF":11.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overcoming multidrug resistance in gastrointestinal cancers with a CDH17-targeted ADC conjugated to a DNA topoisomerase inhibitor. 利用cdh17靶向ADC偶联DNA拓扑异构酶抑制剂克服胃肠道癌症的多药耐药。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-07-15 Epub Date: 2025-07-01 DOI: 10.1016/j.xcrm.2025.102213

Rui Wang, Peng Fang, Xi Chen, Jiali Ji, Dongan Yu, Fei Mei, Zhenzhen Wang, Wei Zhou, Wenjing Peng, Rongjuan Wang, Jian Wang, Cuicui Guo, Hai Wu, Datao Liu, Xiaoding Tan, Xun Gui

{"title":"Overcoming multidrug resistance in gastrointestinal cancers with a CDH17-targeted ADC conjugated to a DNA topoisomerase inhibitor.","authors":"Rui Wang, Peng Fang, Xi Chen, Jiali Ji, Dongan Yu, Fei Mei, Zhenzhen Wang, Wei Zhou, Wenjing Peng, Rongjuan Wang, Jian Wang, Cuicui Guo, Hai Wu, Datao Liu, Xiaoding Tan, Xun Gui","doi":"10.1016/j.xcrm.2025.102213","DOIUrl":"10.1016/j.xcrm.2025.102213","url":null,"abstract":"Cadherin 17 (CDH17) has emerged as a promising target for gastrointestinal (GI) cancers, which are often complicated by multidrug resistance (MDR) and recurrence. In this study, we developed 7MW4911, a CDH17-targeted antibody-drug conjugate (ADC) that incorporates a topoisomerase inhibitor MF-6 (Topi MF-6) payload linked via a cleavable linker, designed specifically to address MDR in GI cancers. 7MW4911 exhibited high specificity for CDH17-expressing cancer cells and potent cytotoxicity in vitro. In preclinical models, including patient-derived xenografts (PDXs) with distinct mutations, 7MW4911 achieved tumor growth inhibition ranging from 71% to 99%. Remarkably, 7MW4911 outperformed monomethyl auristatin E (MMAE)-based and Deruxtecan (DXd)-based ADCs in MDR models, highlighting its effectiveness against drug-resistant cancer phenotypes. Additionally, 7MW4911 showed favorable pharmacokinetics and a highest non-severely toxic dose (HNSTD) exceeding 20 mg/kg in cynomolgus monkeys, underscoring its promising safety profile. Together, these findings position 7MW4911 as a promising ADC candidate capable of enhancing therapeutic outcomes in GI cancers.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102213"},"PeriodicalIF":11.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elucidating the heterogeneity of prediabetes through subphenotyping with a two-dimensional tree structure. 通过二维树状结构的亚表型来阐明糖尿病前期的异质性。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-07-15 Epub Date: 2025-07-02 DOI: 10.1016/j.xcrm.2025.102212

Hong Lin, Yilan Ding, Xiaojing Jia, Xuejiang Gu, Shuangyuan Wang, Mian Li, Yu Xu, Min Xu, Yiming Mu, Lulu Chen, Tianshu Zeng, Lixin Shi, Qing Su, Yuhong Chen, Xuefeng Yu, Li Yan, Guijun Qin, Qin Wan, Gang Chen, Xulei Tang, Zhengnan Gao, Feixia Shen, Ruying Hu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Guixia Wang, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Feiyue Huang, Xingkun Xu, Huapeng Wei, Jie Zheng, Tiange Wang, Zhiyun Zhao, Jiajun Zhao, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu

{"title":"Elucidating the heterogeneity of prediabetes through subphenotyping with a two-dimensional tree structure.","authors":"Hong Lin, Yilan Ding, Xiaojing Jia, Xuejiang Gu, Shuangyuan Wang, Mian Li, Yu Xu, Min Xu, Yiming Mu, Lulu Chen, Tianshu Zeng, Lixin Shi, Qing Su, Yuhong Chen, Xuefeng Yu, Li Yan, Guijun Qin, Qin Wan, Gang Chen, Xulei Tang, Zhengnan Gao, Feixia Shen, Ruying Hu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Guixia Wang, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Feiyue Huang, Xingkun Xu, Huapeng Wei, Jie Zheng, Tiange Wang, Zhiyun Zhao, Jiajun Zhao, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu","doi":"10.1016/j.xcrm.2025.102212","DOIUrl":"10.1016/j.xcrm.2025.102212","url":null,"abstract":"Prediabetes, an intermediate stage of developing diabetes, exhibits considerable phenotypic heterogeneity. Here, we apply the Discriminative Dimensionality Reduction Tree (DDRTree) algorithm to explore prediabetes heterogeneity in 55,777 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) study. Based on 12 clinically available variables, we identify four distinct phenotypes and observe differential risks of type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and cardiovascular disease (CVD). Phenotype 4, characterized by hyperglycemia, insulin resistance, obesity, elevated triglycerides, and liver enzymes, has the highest T2DM risk, while phenotype 3, predominantly driven by obesity, insulin resistance, hyperglycemia, and dyslipidemia, has the highest CKD risk. Phenotypes 3 and 4 show higher CVD risk, with distinct distributions of CVD subtypes. These findings are validated in the external cohort SN_2009-2021, and a user-friendly online tool is provided for individual risk prediction. Overall, our study elucidates the intricate dynamics of prediabetes progression, aiding in personalized management for prediabetes care.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102212"},"PeriodicalIF":11.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetic profiling identifies markers of endocrine resistance and therapeutic options for metastatic castration-resistant prostate cancer. 表观遗传学分析确定内分泌抵抗和治疗选择转移性去势抵抗前列腺癌的标志物。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-07-15 Epub Date: 2025-07-02 DOI: 10.1016/j.xcrm.2025.102215

Tesa M Severson, Emma Minnee, Yanyun Zhu, Karianne Schuurman, Holly M Nguyen, Lisha G Brown, Sini Hakkola, Renee Menezes, Sebastian Gregoricchio, Yongsoo Kim, Jeroen Kneppers, Simon Linder, Suzan Stelloo, Cor Lieftink, Michiel S van der Heijden, Matti Nykter, Vincent van der Noort, Joyce Sanders, Ben Morris, Guido Jenster, Geert Jlh van Leenders, Mark Pomerantz, Matthew L Freedman, Roderick L Beijersbergen, Alfonso Urbanucci, Lodewyk Wessels, Peter S Nelson, Eva Corey, Stefan Prekovic, Wilbert Zwart, Andries M Bergman

{"title":"Epigenetic profiling identifies markers of endocrine resistance and therapeutic options for metastatic castration-resistant prostate cancer.","authors":"Tesa M Severson, Emma Minnee, Yanyun Zhu, Karianne Schuurman, Holly M Nguyen, Lisha G Brown, Sini Hakkola, Renee Menezes, Sebastian Gregoricchio, Yongsoo Kim, Jeroen Kneppers, Simon Linder, Suzan Stelloo, Cor Lieftink, Michiel S van der Heijden, Matti Nykter, Vincent van der Noort, Joyce Sanders, Ben Morris, Guido Jenster, Geert Jlh van Leenders, Mark Pomerantz, Matthew L Freedman, Roderick L Beijersbergen, Alfonso Urbanucci, Lodewyk Wessels, Peter S Nelson, Eva Corey, Stefan Prekovic, Wilbert Zwart, Andries M Bergman","doi":"10.1016/j.xcrm.2025.102215","DOIUrl":"10.1016/j.xcrm.2025.102215","url":null,"abstract":"Androgen receptor (AR) signaling inhibitors, including enzalutamide, are treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), but resistance inevitably develops. Using metastatic samples from a prospective phase 2 clinical trial, we epigenetically profile enhancer/promoter activities with acetylation of lysine residue 27 on histone 3 (H3K27ac) chromatin immunoprecipitation followed by sequencing, before and after AR-targeted therapy. We identify a distinct subset of H3K27ac-differentially marked regions that are associated with treatment responsiveness, which we successfully validate in mCRPC patient-derived xenograft (PDX) models. In silico analyses reveal histone deacetylase (HDAC)3 to critically drive resistance to hormonal interventions, which we validate in vitro. Critically, we identify the pan-HDAC inhibitor vorinostat to be effective in decreasing tumor cell proliferation, both in vitro and in vivo. Moreover, we uncover evidence for HDAC3 working together with glucocorticoid receptor (GR) as a potential mechanism for this therapeutic effect. These findings demonstrate the rationale for therapeutic strategies including HDAC inhibitors to improve patient outcome in advanced stages of mCRPC.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102215"},"PeriodicalIF":11.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immune targeting of triple-negative breast cancer through a clinically actionable STING agonist-CAR T cell platform. 通过临床可操作的STING激动剂- car - T细胞平台免疫靶向三阴性乳腺癌。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-07-15 Epub Date: 2025-06-20 DOI: 10.1016/j.xcrm.2025.102198

Yuqing Zhang, Zehua Li, Jessica Ritter, Elliott J Brea, Navin R Mahadevan, Deborah A Dillon, Sung-Rye Park, Eric Minwei Liu, Michael Y Tolstorukov, William E McGourty, Patrick Lizotte, Elena V Ivanova, Caroline Fahey, Koji Haratani, Tran C Thai, Kara M Soroko, Sophie Kivlehan, Eric L Smith, Prafulla C Gokhale, Cloud P Paweletz, David A Barbie, Thanh U Barbie

{"title":"Immune targeting of triple-negative breast cancer through a clinically actionable STING agonist-CAR T cell platform.","authors":"Yuqing Zhang, Zehua Li, Jessica Ritter, Elliott J Brea, Navin R Mahadevan, Deborah A Dillon, Sung-Rye Park, Eric Minwei Liu, Michael Y Tolstorukov, William E McGourty, Patrick Lizotte, Elena V Ivanova, Caroline Fahey, Koji Haratani, Tran C Thai, Kara M Soroko, Sophie Kivlehan, Eric L Smith, Prafulla C Gokhale, Cloud P Paweletz, David A Barbie, Thanh U Barbie","doi":"10.1016/j.xcrm.2025.102198","DOIUrl":"10.1016/j.xcrm.2025.102198","url":null,"abstract":"Stimulator of interferon genes (STING) has emerged as a critical cancer immunotherapy target. However, no STING agonist has advanced beyond phase I/II clinical trials, as obstacles center around applying STING agonism to the appropriate clinical context, retaining it in the tumor microenvironment (TME), and limiting its T cell toxicity. Using triple-negative breast cancer (TNBC), we identify defective STING turnover as a cancer state promoting hypersensitivity to STING agonism. We also repurpose a US Food and Drug Administration (FDA)-approved polyethylene glycol (PEG) biopsy marker to deliver STING agonists in a controlled release fashion into the TME. However, STING agonist-induced T cell toxicity limits robust endogenous clonal T cell response, which can be overcome by sequential co-delivery of the STING agonists with CAR T cell therapy using the same PEG marker, eradicating orthotopic TNBC in mouse models while also controlling distant disease. These findings identify a highly translatable platform to combine STING agonists with CAR T cell therapy locally for TNBC and potentially other solid cancers.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102198"},"PeriodicalIF":11.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CAR-T cell therapy and reconstructive oncologic surgery in peripheral solid tumors-A narrative review. 外周实体瘤的CAR-T细胞治疗和肿瘤重建手术——综述。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-07-08 DOI: 10.1016/j.xcrm.2025.102240

Leonard Knoedler, Konstantin Herfeld, Daniel A Schaefer, Fortunay Diatta, James Clune, Brogan Evans, Michelle Seu, Bong-Sung Kim, Michael Alfertshofer, Thomas Schaschinger, Jasper Iske, Samuel Knoedler, Alexandre G Lellouch, Maxime Jeljeli, Alberto Carturan, Marco Ruella, Max Heiland, Hendrik Poeck, Markus Perl, Bohdan Pomahac, Martin Kauke-Navarro

{"title":"CAR-T cell therapy and reconstructive oncologic surgery in peripheral solid tumors-A narrative review.","authors":"Leonard Knoedler, Konstantin Herfeld, Daniel A Schaefer, Fortunay Diatta, James Clune, Brogan Evans, Michelle Seu, Bong-Sung Kim, Michael Alfertshofer, Thomas Schaschinger, Jasper Iske, Samuel Knoedler, Alexandre G Lellouch, Maxime Jeljeli, Alberto Carturan, Marco Ruella, Max Heiland, Hendrik Poeck, Markus Perl, Bohdan Pomahac, Martin Kauke-Navarro","doi":"10.1016/j.xcrm.2025.102240","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102240","url":null,"abstract":"This review addresses the integration of chimeric antigen receptor (CAR)-T cell therapy with reconstructive oncologic surgery in treating peripheral solid tumors, including melanoma, sarcomas, breast cancer, and head and neck cancers. While CAR-T cells have demonstrated effectiveness in blood cancers, their efficacy in solid tumors has been limited due to tumor heterogeneity, immune suppression, and poor cellular infiltration. Emerging approaches involving localized CAR-T cell delivery, improved CAR design, and targeted antigen selection (such as HER2, MUC1, GD2, and B7-H3) are discussed as promising strategies to enhance therapeutic outcomes. Clinical studies highlighted in this review indicate improved local tumor control and potential to optimize surgical resections. Additionally, combining CAR-T therapy with surgery may reduce tumor recurrence and positively influence reconstructive outcomes. Overall, this review underscores CAR-T cell therapy as a potential adjunctive treatment in oncologic surgery, emphasizing the importance of interdisciplinary approaches to improve patient outcomes in solid tumor management.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102240"},"PeriodicalIF":11.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Benmelstobart plus anlotinib and chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: A phase 2 study. Benmelstobart + anlotinib和化疗治疗her2阴性晚期胃或胃食管交界处腺癌：一项2期研究

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-06-17 Epub Date: 2025-05-22 DOI: 10.1016/j.xcrm.2025.102145

Liangyu Bie, Chen Wei, Suxia Luo, Shuailei Dong, Zhiwei Gu, Yijie Ma, Qingxin Xia, He Zhang, Jing Li, Wenying Deng, Ning Li

{"title":"Benmelstobart plus anlotinib and chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: A phase 2 study.","authors":"Liangyu Bie, Chen Wei, Suxia Luo, Shuailei Dong, Zhiwei Gu, Yijie Ma, Qingxin Xia, He Zhang, Jing Li, Wenying Deng, Ning Li","doi":"10.1016/j.xcrm.2025.102145","DOIUrl":"10.1016/j.xcrm.2025.102145","url":null,"abstract":"This phase 2 study investigates first-line benmelstobart plus anlotinib and chemotherapy in human epidermal growth factor receptor 2 (HER2)-negative unresectable locally advanced/metastatic gastric or gastroesophageal junction (G/GEJ) cancer. Twenty-five eligible patients receive benmelstobart plus anlotinib and chemotherapy for 6 cycles, followed by benmelstobart and anlotinib maintenance. Of 24 patients with post-treatment imaging, objective response rate (ORR) is 75.0% (95% confidence interval [CI], 53.3%-90.2%; partial response [PR], 18 [75.0%]), and disease control rate (DCR) is 100.0%. The median duration of response (DoR) is 10.9 months. By the date cutoff, the median follow-up is 15.8 months. Median progression-free survival (PFS) and overall survival (OS) among all 25 patients are 10.3 and 18.2 months, respectively. Survival outcomes are not associated with programmed death-ligand 1 (PD-L1) expression. Lymphocytes, T cells, and CD3+CD8+ T cells are enriched in patients with long-term response (PFS > 12 months). Most common grade ≥3 treatment-related adverse event (TRAE) is neutrophil count decreased (12%). This study shows promising efficacy and safety, representing a potential first-line option in patients with HER2-negative advanced G/GEJ cancer, regardless of PD-L1 expressions. The study was registered at ClinicalTrials.gov (NCT04891900).","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102145"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AI-powered digital probing improves periodontal disease diagnosis. 人工智能数字探诊提高了牙周病的诊断。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-06-17 DOI: 10.1016/j.xcrm.2025.102185

Jiamin Wu, James Kit Hon Tsoi

引用次数: 0

Safety and efficacy of perioperative dual PD-1 and HER2 blockade in HER2-positive gastric cancer. 围手术期双重PD-1和HER2阻断治疗HER2阳性胃癌的安全性和有效性。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-06-17 DOI: 10.1016/j.xcrm.2025.102190

Run-Cong Nie, Xiao-Jiang Chen, Cheng-Cai Liang, Bai-Wei Zhao, Wei Wang, Fei-Yang Zhang, Mu-Yan Cai, Hai-Bo Qiu, Zhi-Cheng Xue, Guo-Ming Chen, Zhi-Min Liu, Jun Chi, Jin-Ling Duan, Dong-Sheng Zhang, Ying-Bo Chen, Zhi-Wei Zhou, Yong-Ming Chen, Shu-Qiang Yuan, Yuan-Fang Li

{"title":"Safety and efficacy of perioperative dual PD-1 and HER2 blockade in HER2-positive gastric cancer.","authors":"Run-Cong Nie, Xiao-Jiang Chen, Cheng-Cai Liang, Bai-Wei Zhao, Wei Wang, Fei-Yang Zhang, Mu-Yan Cai, Hai-Bo Qiu, Zhi-Cheng Xue, Guo-Ming Chen, Zhi-Min Liu, Jun Chi, Jin-Ling Duan, Dong-Sheng Zhang, Ying-Bo Chen, Zhi-Wei Zhou, Yong-Ming Chen, Shu-Qiang Yuan, Yuan-Fang Li","doi":"10.1016/j.xcrm.2025.102190","DOIUrl":"10.1016/j.xcrm.2025.102190","url":null,"abstract":"The use of trastuzumab and programmed death-1 (PD-1) inhibitor is effective in patients with HER2-positive advanced gastric or gastro-esophageal junction cancer; however, their use has not been investigated in patients with localized disease. This phase 2 trial evaluates the safety and efficacy of dual PD-1 (sintilimab) and HER2 blockade with chemotherapy in patients with resectable HER2-positive gastric and gastro-esophageal junction adenocarcinoma. 22 patients are enrolled, and 20 patients undergo surgery. The primary endpoint is achieved; 12 (55%, 95% confidence interval [CI]: 32-76) of 22 patients have a major pathological response, and 11 (50%, 95% CI: 28-72) of 22 patients achieve pathological complete response. The most common grade 3 treatment-related adverse events are neutropenia and thrombocytopenia. No treatment-related deaths occur. Transcriptomic analysis, bioinformatics analysis, and immunofluorescence staining demonstrate that regulatory T cells are associated with possibility of drug resistance. This study was registered at the Chinese Clinical Trial Registry (identifier: ChiCTR2200058732).","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 6","pages":"102190"},"PeriodicalIF":11.7,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0