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Annual Review of Pathology-Mechanisms of Disease最新文献

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The Accidental Pathologist: A Curiosity-Driven Journey from Plant Evolution to Innate Immunity. 意外病理学家:从植物进化到先天免疫的好奇心驱动之旅。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2021-01-24 DOI: 10.1146/annurev-pathmechdis-012419-032855
Vinay Kumar
{"title":"The Accidental Pathologist: A Curiosity-Driven Journey from Plant Evolution to Innate Immunity.","authors":"Vinay Kumar","doi":"10.1146/annurev-pathmechdis-012419-032855","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-012419-032855","url":null,"abstract":"<p><p>I have had the singular opportunity to perform research and to participate in medical education. Not unexpectedly, people have asked me which of the two was more important to me. My answer has always been and remains that I am equally passionate about research and teaching. My research has been curiosity driven and not purposeful; hence, I was willing to take risks. That my research led to the discovery of natural killer cells and the unraveling of the molecular basis of a human disease was an unexpected reward. By contrast, my interest in medical education was purposeful, with the goal of improving healthcare by teaching pathology as the scientific foundation of medicine. It started with participation in Robbins pathology texts but progressed toward development of technology-based tools for medical education. This was driven by the belief that technology, by providing equal access to knowledge across the world, can be a powerful democratizing force.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"16 ","pages":"1-22"},"PeriodicalIF":36.2,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38861090","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
Monocytes in the Tumor Microenvironment. 肿瘤微环境中的单核细胞。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2021-01-24 DOI: 10.1146/annurev-pathmechdis-012418-013058
Stefano Ugel, Stefania Canè, Francesco De Sanctis, Vincenzo Bronte
{"title":"Monocytes in the Tumor Microenvironment.","authors":"Stefano Ugel,&nbsp;Stefania Canè,&nbsp;Francesco De Sanctis,&nbsp;Vincenzo Bronte","doi":"10.1146/annurev-pathmechdis-012418-013058","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-012418-013058","url":null,"abstract":"<p><p>Immunotherapy has revolutionized cancer treatment over the past decade. Nonetheless, prolonged survival is limited to relatively few patients. Cancers enforce a multifaceted immune-suppressive network whose nature is progressively shaped by systemic and local cues during tumor development. Monocytes bridge innate and adaptive immune responses and can affect the tumor microenvironment through various mechanisms that induce immune tolerance, angiogenesis, and increased dissemination of tumor cells. Yet monocytes can also give rise to antitumor effectors and activate antigen-presenting cells. This yin-yang activity relies on the plasticity of monocytes in response to environmental stimuli. In this review, we summarize current knowledge of the ontogeny, heterogeneity, and functions of monocytes and monocyte-derived cells in cancer, pinpointing the main pathways that are important for modeling the immunosuppressive tumor microenvironment.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"16 ","pages":"93-122"},"PeriodicalIF":36.2,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38866729","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: 99
Genetic Disease and Therapy. 遗传疾病和治疗。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2021-01-24 DOI: 10.1146/annurev-pathmechdis-012419-032626
Theodore L Roth, Alexander Marson
{"title":"Genetic Disease and Therapy.","authors":"Theodore L Roth,&nbsp;Alexander Marson","doi":"10.1146/annurev-pathmechdis-012419-032626","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-012419-032626","url":null,"abstract":"Genetic diseases cause numerous complex and intractable pathologies. DNA sequences encoding each human's complexity and many disease risks are contained in the mitochondrial genome, nuclear genome, and microbial metagenome. Diagnosis of these diseases has unified around applications of next-generation DNA sequencing. However, translating specific genetic diagnoses into targeted genetic therapies remains a central goal. To date, genetic therapies have fallen into three broad categories: bulk replacement of affected genetic compartments with a new exogenous genome, nontargeted addition of exogenous genetic material to compensate for genetic errors, and most recently, direct correction of causative genetic alterations using gene editing. Generalized methods of diagnosis, therapy, and reagent delivery into each genetic compartment will accelerate the next generations of curative genetic therapies. We discuss the structure and variability of the mitochondrial, nuclear, and microbial metagenomic compartments, as well as the historical development and current practice of genetic diagnostics and gene therapies targeting each compartment.","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"16 ","pages":"145-166"},"PeriodicalIF":36.2,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9704033/pdf/nihms-1850350.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38866730","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: 17
Pathogenesis of Cholangiocarcinoma. 胆管癌的发病机制。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2021-01-24 Epub Date: 2020-12-02 DOI: 10.1146/annurev-pathol-030220-020455
Pedro M Rodrigues, Paula Olaizola, Nuno A Paiva, Irene Olaizola, Alona Agirre-Lizaso, Ana Landa, Luis Bujanda, Maria J Perugorria, Jesus M Banales
{"title":"Pathogenesis of Cholangiocarcinoma.","authors":"Pedro M Rodrigues,&nbsp;Paula Olaizola,&nbsp;Nuno A Paiva,&nbsp;Irene Olaizola,&nbsp;Alona Agirre-Lizaso,&nbsp;Ana Landa,&nbsp;Luis Bujanda,&nbsp;Maria J Perugorria,&nbsp;Jesus M Banales","doi":"10.1146/annurev-pathol-030220-020455","DOIUrl":"https://doi.org/10.1146/annurev-pathol-030220-020455","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) encompasses a group of malignancies that can arise at any point in the biliary tree. Although considered a rare cancer, the incidence of CCA is increasing globally. The silent and asymptomatic nature of these tumors, particularly in their early stages, in combination with their high aggressiveness, intra- and intertumor heterogeneity, and chemoresistance, significantly compromises the efficacy of current therapeutic options, contributing to a dismal prognosis. During the last few years, increasing efforts have been made to unveil the etiologies and pathogenesis of these tumors and to develop more effective therapies. In this review, we summarize current findings in the field of CCA, mainly focusing on the mechanisms of pathogenesis, cells of origin, genomic and epigenetic abnormalities, molecular alterations, chemoresistance, and therapies.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"16 ","pages":"433-463"},"PeriodicalIF":36.2,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-pathol-030220-020455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38667506","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: 55
Detection and Diagnostic Utilization of Cellular and Cell-Free Tumor DNA. 细胞和非细胞肿瘤DNA的检测和诊断应用。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2021-01-24 Epub Date: 2020-11-23 DOI: 10.1146/annurev-pathmechdis-012419-032604
Jonathan C Dudley, Maximilian Diehn
{"title":"Detection and Diagnostic Utilization of Cellular and Cell-Free Tumor DNA.","authors":"Jonathan C Dudley,&nbsp;Maximilian Diehn","doi":"10.1146/annurev-pathmechdis-012419-032604","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-012419-032604","url":null,"abstract":"<p><p>Because cancer is caused by an accumulation of genetic mutations, mutant DNA released by tumors can be used as a highly specific biomarker for cancer. Although this principle was described decades ago, the advent and falling costs of next-generation sequencing have made the use of tumor DNA as a biomarker increasingly practical. This review surveys the use of cellular and cell-free DNA for the detection of cancer, with a focus on recent technological developments and applications to solid tumors. It covers (<i>a</i>) key principles and technology enabling the highly sensitive detection of tumor DNA; (<i>b</i>) assessment of tumor DNA in plasma, including for genotyping, minimal residual disease detection, and early detection of localized cancer; (<i>c</i>) detection of tumor DNA in body cavity fluids, such as urine or cerebrospinal fluid; and (<i>d</i>) challenges posed to the use of tumor DNA as a biomarker by the phenomenon of benign clonal expansions.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"16 ","pages":"199-222"},"PeriodicalIF":36.2,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-pathmechdis-012419-032604","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38635056","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: 14
Complement in Neurologic Disease. 神经系统疾病中的补体。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2021-01-24 Epub Date: 2020-11-24 DOI: 10.1146/annurev-pathol-031620-113409
Nicholas E Propson, Manasee Gedam, Hui Zheng
{"title":"Complement in Neurologic Disease.","authors":"Nicholas E Propson,&nbsp;Manasee Gedam,&nbsp;Hui Zheng","doi":"10.1146/annurev-pathol-031620-113409","DOIUrl":"https://doi.org/10.1146/annurev-pathol-031620-113409","url":null,"abstract":"<p><p>Classic innate immune signaling pathways provide most of the immune response in the brain. This response activates many of the canonical signaling mechanisms identified in peripheral immune cells, despite their relative absence in this immune-privileged tissue. Studies over the past decade have strongly linked complement protein production and activation to age-related functional changes and neurodegeneration. The reactivation of the complement signaling pathway in aging and disease has opened new avenues for understanding brain aging and neurological disease pathogenesis and has implicated cell types such as astrocytes, microglia, endothelial cells, oligodendrocytes, neurons, and even peripheral immune cells in these processes. In this review, we aim to unravel the past decade of research related to complement activation and its numerous consequences in aging and neurological disease.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"16 ","pages":"277-298"},"PeriodicalIF":36.2,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-pathol-031620-113409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38639866","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: 20
The Complex Clinical and Genetic Landscape of Hereditary Peripheral Neuropathy. 遗传性周围神经病变的复杂临床和遗传景观。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2021-01-24 DOI: 10.1146/annurev-pathol-030320-100822
Soumitra Ghosh, Warren G Tourtellotte
{"title":"The Complex Clinical and Genetic Landscape of Hereditary Peripheral Neuropathy.","authors":"Soumitra Ghosh,&nbsp;Warren G Tourtellotte","doi":"10.1146/annurev-pathol-030320-100822","DOIUrl":"https://doi.org/10.1146/annurev-pathol-030320-100822","url":null,"abstract":"<p><p>Hereditary peripheral neuropathy (HPN) is a complex group of neurological disorders caused by mutations in genes expressed by neurons and Schwann cells. The inheritance of a single mutation or multiple mutations in several genes leads to disease phenotype. Patients exhibit symptoms during development, at an early age or later in adulthood. Most of the mechanistic understanding about these neuropathies comes from animal models and histopathological analyses of postmortem human tissues. Diagnosis is often very complex due to the heterogeneity and overlap in symptoms and the frequent overlap between various genes and different mutations they possess. Some symptoms in HPN are common through different subtypes such as axonal degeneration, demyelination, and loss of motor and sensory neurons, leading to similar physiologic abnormalities. Recent advances in gene-targeted therapies, genetic engineering, and next-generation sequencing have augmented our understanding of the underlying pathogenetic mechanisms of HPN.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"16 ","pages":"487-509"},"PeriodicalIF":36.2,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38861087","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: 2
Animal Models and Their Role in Understanding the Pathophysiology of Cystic Fibrosis-Associated Gastrointestinal Lesions. 动物模型及其在理解囊性纤维化相关胃肠道病变病理生理学中的作用。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2021-01-24 DOI: 10.1146/annurev-pathol-022420-105133
Katherine N Gibson-Corley, John F Engelhardt
{"title":"Animal Models and Their Role in Understanding the Pathophysiology of Cystic Fibrosis-Associated Gastrointestinal Lesions.","authors":"Katherine N Gibson-Corley,&nbsp;John F Engelhardt","doi":"10.1146/annurev-pathol-022420-105133","DOIUrl":"https://doi.org/10.1146/annurev-pathol-022420-105133","url":null,"abstract":"<p><p>The life expectancy of cystic fibrosis (CF) patients has greatly increased over the past decade, and researchers and clinicians must now navigate complex disease manifestations that were not a concern prior to the development of modern therapies. Explosive growth in the number of CF animal models has also occurred over this time span, clarifying CF disease pathophysiology and creating opportunities to understand more complex disease processes associated with an aging CF population. This review focuses on the CF-associated pathologies of the gastrointestinal system and how animal models have increased our understanding of this complex multisystemic disease. Although CF is primarily recognized as a pulmonary disease, gastrointestinal pathology occurs very commonly and can affect the quality of life for these patients. Furthermore, we discuss how next-generation genetic engineering of larger animal models will impact the field's understanding of CF disease pathophysiology and the development of novel therapeutic strategies.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"16 ","pages":"51-67"},"PeriodicalIF":36.2,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38866731","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: 5
When a House Is Not a Home: A Survey of Antimetastatic Niches and Potential Mechanisms of Disseminated Tumor Cell Suppression. 当一个房子不是一个家:抗转移龛和播散性肿瘤细胞抑制的潜在机制的调查。
IF 36.2 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2021-01-24 Epub Date: 2020-12-04 DOI: 10.1146/annurev-pathmechdis-012419-032647
Sarah B Crist, Cyrus M Ghajar
{"title":"When a House Is Not a Home: A Survey of Antimetastatic Niches and Potential Mechanisms of Disseminated Tumor Cell Suppression.","authors":"Sarah B Crist,&nbsp;Cyrus M Ghajar","doi":"10.1146/annurev-pathmechdis-012419-032647","DOIUrl":"https://doi.org/10.1146/annurev-pathmechdis-012419-032647","url":null,"abstract":"<p><p>Over the last four decades, the cancer biology field has concentrated on cellular and microenvironmental drivers of metastasis. Despite this focus, mortality rates upon diagnosis of metastatic disease remain essentially unchanged. Would a small change in perspective help? Knowing what constitutes an inhospitable, rather than hospitable, microenvironment could provide the inspiration necessary to develop better therapies and preventative strategies. In this review, we canvas the literature for hints about what characteristics four common antimetastatic niches-skeletal muscle, spleen, thyroid, and yellow bone marrow-have in common. We posit that thorough molecular and mechanistic characterization of antimetastatic tissues may inspire reimagined therapies that inhibit metastatic development and/or progression in an enduring manner.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"16 ","pages":"409-432"},"PeriodicalIF":36.2,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-pathmechdis-012419-032647","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38674499","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: 11
Genetic Insights into Alzheimer's Disease. 阿尔茨海默病的遗传学启示
IF 28.4 1区 医学
Annual Review of Pathology-Mechanisms of Disease Pub Date : 2021-01-24 DOI: 10.1146/annurev-pathmechdis-012419-032551
Caitlin S Latimer, Katherine L Lucot, C Dirk Keene, Brenna Cholerton, Thomas J Montine
{"title":"Genetic Insights into Alzheimer's Disease.","authors":"Caitlin S Latimer, Katherine L Lucot, C Dirk Keene, Brenna Cholerton, Thomas J Montine","doi":"10.1146/annurev-pathmechdis-012419-032551","DOIUrl":"10.1146/annurev-pathmechdis-012419-032551","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a pervasive, relentlessly progressive neurodegenerative disorder that includes both hereditary and sporadic forms linked by common underlying neuropathologic changes and neuropsychological manifestations. While a clinical diagnosis is often made on the basis of initial memory dysfunction that progresses to involve multiple cognitive domains, definitive diagnosis requires autopsy examination of the brain to identify amyloid plaques and neurofibrillary degeneration. Over the past 100 years, there has been remarkable progress in our understanding of the underlying pathophysiologic processes, pathologic changes, and clinical phenotypes of AD, largely because genetic pathways that include but expand beyond amyloid processing have been uncovered. This review discusses the current state of understanding of the genetics of AD with a focus on how these advances are both shaping our understanding of the disease and informing novel avenues and approaches for development of potential therapeutic targets.</p>","PeriodicalId":50753,"journal":{"name":"Annual Review of Pathology-Mechanisms of Disease","volume":"16 ","pages":"351-376"},"PeriodicalIF":28.4,"publicationDate":"2021-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8664069/pdf/nihms-1759189.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38866733","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
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