Cell Reports Medicine最新文献_第8页

CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches. CTC 衍生的胰腺癌模型可作为研究工具，适用于精准医疗方法。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-08-19 DOI: 10.1016/j.xcrm.2024.101692

Jiajia Tang, Quan Zheng, Qi Wang, Yaru Zhao, Preeta Ananthanarayanan, Chiara Reina, Berina Šabanović, Ke Jiang, Ming-Hsin Yang, Clara Csilla Meny, Huimin Wang, Mette Ø Agerbaek, Thomas Mandel Clausen, Tobias Gustavsson, Chenlei Wen, Felice Borghi, Alfredo Mellano, Elisabetta Fenocchio, Vanesa Gregorc, Anna Sapino, Thor G Theander, Da Fu, Alexandra Aicher, Ali Salanti, Baiyong Shen, Christopher Heeschen

{"title":"CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches.","authors":"Jiajia Tang, Quan Zheng, Qi Wang, Yaru Zhao, Preeta Ananthanarayanan, Chiara Reina, Berina Šabanović, Ke Jiang, Ming-Hsin Yang, Clara Csilla Meny, Huimin Wang, Mette Ø Agerbaek, Thomas Mandel Clausen, Tobias Gustavsson, Chenlei Wen, Felice Borghi, Alfredo Mellano, Elisabetta Fenocchio, Vanesa Gregorc, Anna Sapino, Thor G Theander, Da Fu, Alexandra Aicher, Ali Salanti, Baiyong Shen, Christopher Heeschen","doi":"10.1016/j.xcrm.2024.101692","DOIUrl":"10.1016/j.xcrm.2024.101692","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a \"liquid biopsy\" that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4+ CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008312","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

The impact of multi-omics in medicine 多组学对医学的影响

IF 14.3 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 DOI: 10.1016/j.xcrm.2024.101742

Linghua Wang, Jing Qu, Oscar Harari, Justin A. Boddey, Zhang Wang, Suvi Linna-Kuosmanen

引用次数: 0

Decoupling HIV-1 antiretroviral drug inhibition from plasma antibody activity to evaluate broadly neutralizing antibody therapeutics and vaccines. 将 HIV-1 抗逆转录病毒药物抑制与血浆抗体活性解耦，以评估广谱中和抗体疗法和疫苗。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-08-30 DOI: 10.1016/j.xcrm.2024.101702

Magdalena Schwarzmüller, Cristina Lozano, Merle Schanz, Irene A Abela, Silvan Grosse-Holz, Selina Epp, Martina Curcio, Jule Greshake, Peter Rusert, Michael Huber, Roger D Kouyos, Huldrych F Günthard, Alexandra Trkola

{"title":"Decoupling HIV-1 antiretroviral drug inhibition from plasma antibody activity to evaluate broadly neutralizing antibody therapeutics and vaccines.","authors":"Magdalena Schwarzmüller, Cristina Lozano, Merle Schanz, Irene A Abela, Silvan Grosse-Holz, Selina Epp, Martina Curcio, Jule Greshake, Peter Rusert, Michael Huber, Roger D Kouyos, Huldrych F Günthard, Alexandra Trkola","doi":"10.1016/j.xcrm.2024.101702","DOIUrl":"10.1016/j.xcrm.2024.101702","url":null,"abstract":"The development of broadly neutralizing antibody (bnAb)-based therapeutic HIV-1 vaccines and cure concepts depends on monitoring bnAb plasma activity in people with HIV (PWH) on suppressive antiretroviral therapy (ART). To enable this, analytical strategies must be defined to reliably distinguish antibody-based neutralization from drug inhibition. Here, we explore strategies that either utilize drug-resistant viruses or remove drugs from plasma. We develop ART-DEX (ART dissociation and size exclusion), an approach which quantitatively separates drugs from plasma proteins following pH-triggered release allowing accurate definition of antibody-based neutralization. We demonstrate that ART-DEX, alone or combined with ART-resistant viruses, provides a highly effective and scalable means of assessing antibody neutralization during ART. Implementation of ART-DEX in standard neutralization protocols should be considered to enhance the analytical capabilities of studies evaluating bnAb therapeutics and therapeutic vaccines, furthering the development of advanced ART and HIV-1 cure strategies.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104784","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

CMG901, a Claudin18.2-specific antibody-drug conjugate, for the treatment of solid tumors. 用于治疗实体瘤的 Claudin18.2 特异性抗体-药物共轭物 CMG901。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-09-03 DOI: 10.1016/j.xcrm.2024.101710

Gang Xu, Wei Liu, Ying Wang, Xiaoli Wei, Furong Liu, Yanyun He, Libo Zhang, Qin Song, Zhiyao Li, Changyu Wang, Ruihua Xu, Bo Chen

{"title":"CMG901, a Claudin18.2-specific antibody-drug conjugate, for the treatment of solid tumors.","authors":"Gang Xu, Wei Liu, Ying Wang, Xiaoli Wei, Furong Liu, Yanyun He, Libo Zhang, Qin Song, Zhiyao Li, Changyu Wang, Ruihua Xu, Bo Chen","doi":"10.1016/j.xcrm.2024.101710","DOIUrl":"10.1016/j.xcrm.2024.101710","url":null,"abstract":"Claudin18.2 has been recently recognized as a potential therapeutic target for gastric/gastroesophageal junction or pancreatic cancer. Here, we develop a Claudin18.2-directed antibody-drug conjugate (ADC), CMG901, with a potent microtubule-targeting agent MMAE (monomethyl auristatin E) and evaluate its preclinical profiles. In vitro studies show that CMG901 binds specifically to Claudin18.2 on the cell surface and kills tumor cells through direct cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and bystander killing activity. In vivo pharmacological studies show significant antitumor activity in patient-derived xenograft (PDX) models. Toxicity studies show that the major adverse effects related to CMG901 are reversible hematopoietic changes attributed to MMAE. The highest non-severely toxic dose (HNSTD) is 6 mg/kg in cynomolgus monkeys and 10 mg/kg in rats once every 3 weeks. CMG901's favorable preclinical profile supports its entry into the human clinical study. CMG901 is currently under phase 3 investigation in patients with advanced gastric/gastroesophageal junction adenocarcinoma expressing Claudin18.2 (NCT06346392).","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131952","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

Radiomics in breast cancer: Current advances and future directions 乳腺癌放射组学：当前进展与未来方向

IF 14.3 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 DOI: 10.1016/j.xcrm.2024.101719

Ying-Jia Qi, Guan-Hua Su, Chao You, Xu Zhang, Yi Xiao, Yi-Zhou Jiang, Zhi-Ming Shao

引用次数: 0

Next-generation lung cancer pathology: Development and validation of diagnostic and prognostic algorithms. 新一代肺癌病理学：诊断和预后算法的开发与验证。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-08-22 DOI: 10.1016/j.xcrm.2024.101697

Carina Kludt, Yuan Wang, Waleed Ahmad, Andrey Bychkov, Junya Fukuoka, Nadine Gaisa, Mark Kühnel, Danny Jonigk, Alexey Pryalukhin, Fabian Mairinger, Franziska Klein, Anne Maria Schultheis, Alexander Seper, Wolfgang Hulla, Johannes Brägelmann, Sebastian Michels, Sebastian Klein, Alexander Quaas, Reinhard Büttner, Yuri Tolkach

{"title":"Next-generation lung cancer pathology: Development and validation of diagnostic and prognostic algorithms.","authors":"Carina Kludt, Yuan Wang, Waleed Ahmad, Andrey Bychkov, Junya Fukuoka, Nadine Gaisa, Mark Kühnel, Danny Jonigk, Alexey Pryalukhin, Fabian Mairinger, Franziska Klein, Anne Maria Schultheis, Alexander Seper, Wolfgang Hulla, Johannes Brägelmann, Sebastian Michels, Sebastian Klein, Alexander Quaas, Reinhard Büttner, Yuri Tolkach","doi":"10.1016/j.xcrm.2024.101697","DOIUrl":"10.1016/j.xcrm.2024.101697","url":null,"abstract":"Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors. In this study, we develop a clinically useful computational pathology platform for NSCLC that can be a foundation for multiple downstream applications and provide immediate value for patient care optimization and individualization. We train the primary multi-class tissue segmentation algorithm on a substantial, high-quality, manually annotated dataset of whole-slide images with lung adenocarcinoma and squamous cell carcinomas. We investigate two downstream applications. NSCLC subtyping algorithm is trained and validated using a large, multi-institutional (n = 6), multi-scanner (n = 5), international cohort of NSCLC cases (slides/patients 4,097/1,527). Moreover, we develop four AI-derived, fully explainable, quantitative, prognostic parameters (based on tertiary lymphoid structure and necrosis assessment) and validate them for different clinical endpoints. The computational platform enables the high-precision, quantitative analysis of H&E-stained slides. The developed prognostic parameters facilitate robust and independent risk stratification of patients with NSCLC.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046435","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

Loss of p53 and SMAD4 induces adenosquamous subtype pancreatic cancer in the absence of an oncogenic KRAS mutation. 在没有致癌 KRAS 突变的情况下，p53 和 SMAD4 的缺失会诱发腺鳞癌亚型胰腺癌。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-09-03 DOI: 10.1016/j.xcrm.2024.101711

Daowei Yang, Xinlei Sun, Rohan Moniruzzaman, Hua Wang, Citu Citu, Zhongming Zhao, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen

{"title":"Loss of p53 and SMAD4 induces adenosquamous subtype pancreatic cancer in the absence of an oncogenic KRAS mutation.","authors":"Daowei Yang, Xinlei Sun, Rohan Moniruzzaman, Hua Wang, Citu Citu, Zhongming Zhao, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen","doi":"10.1016/j.xcrm.2024.101711","DOIUrl":"10.1016/j.xcrm.2024.101711","url":null,"abstract":"Pancreatic cancer is associated with an oncogenic KRAS mutation in approximately 90% of cases. However, a non-negligible proportion of pancreatic cancer cases harbor wild-type KRAS (KRAS-WT). This study establishes genetically engineered mouse models that develop spontaneous pancreatic cancer in the context of KRAS-WT. The Trp53loxP/loxP;Smad4loxP/loxP;Pdx1-Cre (PPSSC) mouse model harbors KRAS-WT and loss of Trp53/Smad4. The Trp53loxP/loxP;Tgfbr2loxP/loxP;Pdx1-Cre (PPTTC) mouse model harbors KRAS-WT and loss of Trp53/Tgfbr2. We identify that either Trp53/Smad4 loss or Trp53/Tgfbr2 loss can induce spontaneous pancreatic tumor formation in the absence of an oncogenic KRAS mutation. The Trp53/Smad4 loss and Trp53/Tgfbr2 loss mouse models exhibit distinct pancreatic tumor histological features, as compared to oncogenic KRAS-driven mouse models. Furthermore, KRAS-WT pancreatic tumors with Trp53/Smad4 loss reveal unique histological features of pancreatic adenosquamous carcinoma (PASC). Single-cell RNA sequencing (scRNA-seq) analysis reveals the distinct tumor immune microenvironment landscape of KRAS-WT (PPSSC) pancreatic tumors as compared with that of oncogenic KRAS-driven pancreatic tumors.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131953","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

TNFR1 signaling promotes pancreatic tumor growth by limiting dendritic cell number and function. TNFR1 信号通过限制树突状细胞的数量和功能促进胰腺肿瘤的生长。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-08-22 DOI: 10.1016/j.xcrm.2024.101696

Muhammad S Alam, Matthias M Gaida, Hagen R Witzel, Shizuka Otsuka, Aamna Abbasi, Theresa Guerin, Abdalla Abdelmaksoud, Nathan Wong, Margaret C Cam, Serguei Kozlov, Jonathan D Ashwell

{"title":"TNFR1 signaling promotes pancreatic tumor growth by limiting dendritic cell number and function.","authors":"Muhammad S Alam, Matthias M Gaida, Hagen R Witzel, Shizuka Otsuka, Aamna Abbasi, Theresa Guerin, Abdalla Abdelmaksoud, Nathan Wong, Margaret C Cam, Serguei Kozlov, Jonathan D Ashwell","doi":"10.1016/j.xcrm.2024.101696","DOIUrl":"10.1016/j.xcrm.2024.101696","url":null,"abstract":"Pancreatic adenocarcinoma (PDAC) is one the most intractable cancers, in part due to its highly inflammatory microenvironment and paucity of infiltrating dendritic cells (DCs). Here, we find that genetic ablation or antibody blockade of tumor necrosis factor receptor 1 (TNFR1) enhanced intratumor T cell activation and slowed PDAC growth. While anti-PD-1 checkpoint inhibition alone had little effect, it further enhanced intratumor T cell activation in combination with anti-TNFR1. The major cellular alteration in the tumor microenvironment in the absence of TNFR1 signaling was a large increase in DC number and immunostimulatory phenotype. This may reflect a direct effect on DCs, because TNF induced TNFR1-dependent apoptosis of bone-marrow-derived DCs. The therapeutic response to anti-TNFR1 alone was superior to the combination of DC-activating agonistic anti-CD40 and Flt3 ligand (Flt3L). These observations suggest that targeting TNFR1, perhaps in concert with other strategies that promote DC generation and mobilization, may have therapeutic benefits.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046436","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

Prof. Serena Nik-Zainal. Serena Nik-Zainal 教授。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 DOI: 10.1016/j.xcrm.2024.101739

Serena Nik-Zainal

引用次数: 0

Robust SARS-CoV-2-neutralizing antibodies sustained through 6 months post XBB.1.5 mRNA vaccine booster. 在注射 XBB.1.5 mRNA 疫苗强化剂后的 6 个月内，SARS-CoV-2 中和抗体一直保持稳定。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2024-09-17 Epub Date: 2024-08-28 DOI: 10.1016/j.xcrm.2024.101701

Qian Wang, Ian A Mellis, Yicheng Guo, Carmen Gherasim, Riccardo Valdez, Aubree Gordon, David D Ho, Lihong Liu

{"title":"Robust SARS-CoV-2-neutralizing antibodies sustained through 6 months post XBB.1.5 mRNA vaccine booster.","authors":"Qian Wang, Ian A Mellis, Yicheng Guo, Carmen Gherasim, Riccardo Valdez, Aubree Gordon, David D Ho, Lihong Liu","doi":"10.1016/j.xcrm.2024.101701","DOIUrl":"10.1016/j.xcrm.2024.101701","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies are substantially expanded 1 month after a shot of XBB.1.5 monovalent mRNA vaccine (XBB.1.5 MV) booster, but the durability of this response remains unknown. Here, we address this question by performing neutralization assays on four viral variants (D614G, BA.5, XBB.1.5, and JN.1) using sera from participants obtained at ∼1 month, ∼3 months, and ∼6 months post an XBB.1.5 MV booster. Our findings indicate that the resulting neutralizing antibody titers are robust and generally remain at stable levels for the study period, similar to those following XBB infection. Importantly, this durability of neutralizing antibody titers contrasts with the decline observed after a booster of the original monovalent or BA.5 bivalent mRNA vaccine. Our results are in line with the recent national data from the Centers for Disease Control and Prevention, showing that the efficacy against symptomatic SARS-CoV-2 infection is sustained for up to 4 months after an XBB.1.5 MV booster.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104790","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