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Annual Review of Pathology-Mechanisms of Disease最新文献

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Extrachromosomal Circular DNA in Pathobiology: Current State 染色体外环状DNA在病理生物学中的研究现状
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2026-10-01 DOI: 10.1146/annurev-pathmechdis-032125-105611
Saba Tufail,Anindya Dutta
{"title":"Extrachromosomal Circular DNA in Pathobiology: Current State","authors":"Saba Tufail,Anindya Dutta","doi":"10.1146/annurev-pathmechdis-032125-105611","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-032125-105611","url":null,"abstract":"With advances in sequencing technologies and molecular tools, extrachromosomal circular DNA (eccDNA), once considered a mere by-product of genomic instability, is now recognized as playing important roles in genome plasticity, gene regulation, and cancer. In this review, we provide a comprehensive overview of eccDNA from its historical origins to the current state of the field. We distinguish between small eccDNAs and large eccDNAs. Small eccDNAs are usually too small to encode full genes and arise through DNA repair and replication-associated processes, while large eccDNAs carry full genes that drive oncogene amplification and tumor evolution. We summarize the current understanding of their mechanisms of biogenesis, functions, and emerging diagnostic and therapeutic applications. In addition, we discuss the broad spectrum of diseases associated with eccDNA, including cancer and aging-related diseases, as well as recent advances in engineering platforms and computational tools that are transforming our ability to study eccDNA structure and biology.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"93 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089009","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
Proteomics for Precision Oncology: Lessons from Liver Cancer 精确肿瘤学的蛋白质组学：来自肝癌的教训
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2026-09-25 DOI: 10.1146/annurev-pathmechdis-042424-123909
Amanda Smythers,Shelby Ruiz,Benjamin C. Orsburn
{"title":"Proteomics for Precision Oncology: Lessons from Liver Cancer","authors":"Amanda Smythers,Shelby Ruiz,Benjamin C. Orsburn","doi":"10.1146/annurev-pathmechdis-042424-123909","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042424-123909","url":null,"abstract":"It is an exciting time for the field of proteomics, which has finally demonstrated the capabilities the term has long suggested. Today it is possible to deeply analyze the proteomes of up to 100 human samples at depth on a single instrument in a single day. Recent advances now make it possible to analyze previously impossible samples such as single human cells and body fluids at depths of thousands of proteins per sample. With mature technologies it is time to finally apply these tools to large cohort studies. This review aims to provide a summary of the current technologies and their capabilities and how they may be applied to precision oncology.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"28 7 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149049098","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
Integration and Intersection of Cancer Metabolism with Epigenetic Pathways in Gliomas. 胶质瘤中肿瘤代谢与表观遗传通路的整合与交叉。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-11-18 DOI: 10.1146/annurev-pathmechdis-111523-023424
Siva Kumar Natarajan,Matthew Pun,James Haggerty-Skeans,Sriram Venneti
{"title":"Integration and Intersection of Cancer Metabolism with Epigenetic Pathways in Gliomas.","authors":"Siva Kumar Natarajan,Matthew Pun,James Haggerty-Skeans,Sriram Venneti","doi":"10.1146/annurev-pathmechdis-111523-023424","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023424","url":null,"abstract":"The interplay between metabolomics and epigenetics is a key glioma driver. Both tumor-intrinsic and microenvironmental metabolic cues can shape chromatin. Epigenetic methylation and demethylation are metabolically regulated by S-adenosyl methionine (SAM) (via methionine metabolism) and the TCA-cycle-related metabolite α-ketoglutarate (α-KG), respectively. Additionally, glycolysis and the TCA cycle modulate histone acetylation and lactylation. Gliomas in both adults and children hijack these pathways. Adult isocitrate dehydrogenase (IDH)-wild-type tumors enhance glycolysis via epidermal growth factor receptor to alter chromatin. IDH-mutant gliomas generate D-2-hydroxyglutarate (D-2HG), which inhibits α-KG demethylases to create epigenetic hypermethylation. Pediatric gliomas, including gliomas with lysine-to-methionine mutations at residue 27 of histone H3 and posterior fossa group A ependymomas, can also rewire metabolism to regulate chromatin. These pathways can be targeted for therapeutic development. Inhibiting IDH mutations with vorasidenib lowers D-2HG and is beneficial to patients. Other drugs like ONC201 and metformin can metabolically suppress oncogenic chromatin states in pediatric gliomas. This dynamic cross talk between metabolism and epigenetics not only underpins tumor biology but also presents opportunities for innovative therapeutic strategies.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"154 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545228","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
The Role of Fibroblasts Across Inflammation and Immunity 成纤维细胞在炎症和免疫中的作用
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-29 DOI: 10.1146/annurev-pathmechdis-080624-105114
Max J.B. Cowan, Sarah Davidson, Mark Coles, Christopher D. Buckley
{"title":"The Role of Fibroblasts Across Inflammation and Immunity","authors":"Max J.B. Cowan, Sarah Davidson, Mark Coles, Christopher D. Buckley","doi":"10.1146/annurev-pathmechdis-080624-105114","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-080624-105114","url":null,"abstract":"Fibroblasts have been canonically considered as extracellular matrix organizing cells but are now recognized as active participants in immune regulation and tissue homeostasis. In the context of fibrosis, fibroblasts are a well-understood contributor to global morbidity and mortality across cardiac, pulmonary, renal, and hepatic tissue. Beyond this, the fibroblast is a key contributor to barrier immunity and stem cell niche formation and a determinant of vascular permeability, yet it is also capable of lymphocyte homeostasis in the context of lymphoid tissue regulation. Here, we explore the role of fibroblasts across acute and chronic inflammation and their relationship to innate and adaptive immune elements, through the lens of immune-mediated inflammatory diseases. Together, the diversity of fibroblast functions presents a therapeutic challenge, but one with the potential to restore inflamed tissue to health. We discuss novel approaches driven by technological developments that now make immunotherapeutic interventions targeting fibroblasts increasingly possible.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"85 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397490","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
Pathology of the Coronary Arteries and Myocardium in Kawasaki Disease. 川崎病冠状动脉和心肌的病理。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-28 DOI: 10.1146/annurev-pathmechdis-111523-023453
Chisato Shimizu,José María Pérez Pomares,Conor J Loy,Iwijn De Vlaminck,Adriana H Tremoulet,Adrián Ruiz-Villalba,Jane C Burns
{"title":"Pathology of the Coronary Arteries and Myocardium in Kawasaki Disease.","authors":"Chisato Shimizu,José María Pérez Pomares,Conor J Loy,Iwijn De Vlaminck,Adriana H Tremoulet,Adrián Ruiz-Villalba,Jane C Burns","doi":"10.1146/annurev-pathmechdis-111523-023453","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023453","url":null,"abstract":"Kawasaki disease (KD) has replaced rheumatic fever as the most common cause of pediatric acquired heart disease across the globe. The acute illness, characterized by fever and associated mucocutaneous features, is associated with a coronary artery arteritis and myocarditis. The destruction of the arterial wall leads to aneurysm formation in 25% of untreated children. Myocardial inflammation accompanies the vasculitis, and the long-term consequences of this acute inflammation are still being defined. Our incomplete understanding of the pathology stems in part from the unknown etiology of this vasculitis. We review here the current understanding of the pathology of KD and the animal models used to elucidate KD pathogenesis and define new therapeutic targets. Improved imaging techniques and cell-free RNA studies are critically contributing to our understanding of KD pathology, but much remains to be learned before we gain more complete knowledge of this complex and important condition.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"51 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380828","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
Role of Immune Cells in Hepatitis B Virus and Associated Sequelae. 免疫细胞在乙型肝炎病毒及其相关后遗症中的作用
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-28 DOI: 10.1146/annurev-pathmechdis-042524-030646
Jonah Lin,Adam J Gehring
{"title":"Role of Immune Cells in Hepatitis B Virus and Associated Sequelae.","authors":"Jonah Lin,Adam J Gehring","doi":"10.1146/annurev-pathmechdis-042524-030646","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042524-030646","url":null,"abstract":"Hepatitis B virus (HBV) chronically infects 250 million people worldwide, making it a primary risk factor for progressive liver disease. The virus itself is not responsible for liver damage. HBV can replicate at very high levels and produces large amounts of viral antigen, but this does not lead to hepatocyte death or liver inflammation. Instead, pathogenesis of chronic hepatitis B (CHB) is driven by the interaction between the host immune system and the virus. In chronically infected individuals, the HBV-specific immune response is dysfunctional and not able to clear the infection. This inability to clear the virus leads to aberrant immune activation in the liver, causing hepatocellular damage that, over time, leads to fibrosis, cirrhosis, and liver cancer. This review covers two aspects of sequalae associated with CHB: (a) mechanisms of tissue damage leading to fibrosis and (b) dysfunctional features of HBV-specific immunity.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"57 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380826","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
The Role of MicroRNAs in Viral and Bacterial Infections. microrna在病毒和细菌感染中的作用。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-28 DOI: 10.1146/annurev-pathmechdis-042424-114814
Laura Groeger,Eckart Meese,Andreas Keller
{"title":"The Role of MicroRNAs in Viral and Bacterial Infections.","authors":"Laura Groeger,Eckart Meese,Andreas Keller","doi":"10.1146/annurev-pathmechdis-042424-114814","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042424-114814","url":null,"abstract":"In 2024, the Nobel Prize committee recognized the groundbreaking discovery of microRNAs (miRNAs), highlighting their fundamental role in gene regulation. Since their identification, extensive research has established that miRNAs are critical for maintaining cellular homeostasis, with their dysregulation contributing to various diseases, including cancer, neurological disorders, and cardiovascular diseases. While much of the focus has been on miRNAs in cancer, growing evidence suggests that they also play a pivotal role in viral and bacterial infections. In this review, we examine both the host miRNA response to infection and pathogen-derived small regulatory RNAs, highlighting key players such as miR-21, miR-146a, and miR-155. Finally, we discuss future research directions, emphasizing the need for functional studies, deeper exploration of bacterial and viral small RNAs, and the investigation of cross-kingdom RNA exchange.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"103 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380829","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
Mechanisms of Norovirus Immunity: Implications for Vaccine Design. 诺如病毒免疫机制：对疫苗设计的启示。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-16 DOI: 10.1146/annurev-pathmechdis-042524-021922
Arya B Ökten,Joseph E Craft,Craig B Wilen
{"title":"Mechanisms of Norovirus Immunity: Implications for Vaccine Design.","authors":"Arya B Ökten,Joseph E Craft,Craig B Wilen","doi":"10.1146/annurev-pathmechdis-042524-021922","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042524-021922","url":null,"abstract":"Human noroviruses are the predominant cause of acute gastroenteritis globally, causing significant morbidity and mortality especially in low- and middle-income countries. Despite this immense public health burden, there are no commercially available vaccines or antiviral drugs, highlighting a critical unmet medical need. Norovirus vaccine development faces several challenges including extensive viral diversity and limited mechanistic understanding of protective immunity. While several vaccine candidates-including virus-like particle, adenovirus-vector, and mRNA-lipid nanoparticle vaccines-are in clinical trials, none have achieved complete protection in adults or demonstrated efficacy in young children. Understanding the mechanisms underlying norovirus immunity and the relative importance of mucosal responses remains crucial for vaccine optimization. Continued research addressing these basic questions, along with strategic antigen selection and platform optimization, are essential to overcome current limitations to the development of broadly protective norovirus vaccines.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"356 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305628","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
Genomic Taxonomy of Aggressive B-Cell Lymphoid Neoplasms. 侵袭性b细胞淋巴样肿瘤的基因组分类学。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-16 DOI: 10.1146/annurev-pathmechdis-111523-023413
Laura K Hilton,Brett Collinge,David W Scott
{"title":"Genomic Taxonomy of Aggressive B-Cell Lymphoid Neoplasms.","authors":"Laura K Hilton,Brett Collinge,David W Scott","doi":"10.1146/annurev-pathmechdis-111523-023413","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-111523-023413","url":null,"abstract":"Aggressive B-cell lymphomas are a heterogeneous group of neoplasms, organized in the current classifications into more than 20 categories on the basis of morphology, immunophenotype, clinical presentation, and limited molecular features. Over the past 25 years, there has been an exponential accumulation of detailed genomic characterizations of these lymphomas. Many defined categories have been confirmed as relatively homogeneous, fulfilling the classification ideal of sharing core biological hallmarks. However, the largest group, diffuse large B-cell lymphoma, not otherwise specified, which makes up 70-74% of the patients, has been revealed to be remarkably heterogeneous at a genomic and biological level. In this review, we summarize the current state of knowledge and then propose an evolution of the classification of aggressive B-cell lymphomas to a genomics-informed taxonomy based around normal B-cell development and the different modes by which lymphomas achieve key hallmarks of cancer-hallmarks that can inform on patient management.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"104 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305333","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
Molecular Mechanisms of Respiratory Syncytial Virus Pathogenesis. 呼吸道合胞病毒发病机制的分子机制。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-16 DOI: 10.1146/annurev-pathmechdis-042424-114052
Madison J Granoski,Aleksandra Stojic,Stephen Z Lee,David J Marchant
{"title":"Molecular Mechanisms of Respiratory Syncytial Virus Pathogenesis.","authors":"Madison J Granoski,Aleksandra Stojic,Stephen Z Lee,David J Marchant","doi":"10.1146/annurev-pathmechdis-042424-114052","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-042424-114052","url":null,"abstract":"Respiratory syncytial virus (RSV) is one of the leading causes of infant hospitalization and mortality worldwide. RSV pathogenesis is a result of various virus-host interactions. While significant work has been done to elucidate mechanisms of RSV pathogenesis at a systemic level from the host perspective, here we examine how RSV pathogenesis occurs on a molecular level. While each RSV protein plays an essential role in establishing and advancing disease, each one also executes multifaceted strategies for evasion of host detection. In this review, we outline how each component of the RSV replication cycle works to co-opt host cell proteins and modulate host immune responses during entry, transcription, replication, translation, assembly, and egress. We examine the latest literature regarding RSV protein function and discuss outstanding questions in the field.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"33 1","pages":""},"PeriodicalIF":36.2,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305334","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
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