262 results match your criteria Annual review of pathology[Journal]


Malformations of Cerebral Cortex Development: Molecules and Mechanisms.

Annu Rev Pathol 2019 Jan;14:293-318

Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195, USA; email: ,

Malformations of cortical development encompass heterogeneous groups of structural brain anomalies associated with complex neurodevelopmental disorders and diverse genetic and nongenetic etiologies. Recent progress in understanding the genetic basis of brain malformations has been driven by extraordinary advances in DNA sequencing technologies. For example, somatic mosaic mutations that activate mammalian target of rapamycin signaling in cortical progenitor cells during development are now recognized as the cause of hemimegalencephaly and some types of focal cortical dysplasia. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012927DOI Listing
January 2019
1 Read

Systems-Wide Approaches in Induced Pluripotent Stem Cell Models.

Annu Rev Pathol 2019 Jan 31;14:395-419. Epub 2018 Oct 31.

Stanford Cardiovascular Institute, and Department of Medicine, Division of Cardiology, Stanford University, Stanford, California 94305, USA; email:

Human induced pluripotent stem cells (iPSCs) provide a renewable supply of patient-specific and tissue-specific cells for cellular and molecular studies of disease mechanisms. Combined with advances in various omics technologies, iPSC models can be used to profile the expression of genes, transcripts, proteins, and metabolites in relevant tissues. In the past 2 years, large panels of iPSC lines have been derived from hundreds of genetically heterogeneous individuals, further enabling genome-wide mapping to identify coexpression networks and elucidate gene regulatory networks. Read More

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-pathmechdi
Publisher Site
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-013046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450651PMC
January 2019
2 Reads

Molecular Pathogenesis of the Tauopathies.

Annu Rev Pathol 2019 Jan 24;14:239-261. Epub 2018 Oct 24.

Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, St. Lucia Campus, Brisbane, Queensland 4072, Australia; email:

The tauopathies constitute a group of diseases that have Tau inclusions in neurons or glia as their common denominator. In this review, we describe the biochemical and histological differences in Tau pathology that are characteristic of the spectrum of frontotemporal lobar degeneration as primary tauopathies and of Alzheimer's disease as a secondary tauopathy, as well as the commonalities and differences between the familial and sporadic forms. Furthermore, we discuss selected advances in transgenic animal models in delineating the different pathomechanisms of Tau. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012936DOI Listing
January 2019

Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection.

Annu Rev Pathol 2019 Jan 24;14:319-338. Epub 2018 Oct 24.

Department of Laboratory Medicine, University of California, San Francisco, California 94107, USA; email:

Nearly all infectious agents contain DNA or RNA genomes, making sequencing an attractive approach for pathogen detection. The cost of high-throughput or next-generation sequencing has been reduced by several orders of magnitude since its advent in 2004, and it has emerged as an enabling technological platform for the detection and taxonomic characterization of microorganisms in clinical samples from patients. This review focuses on the application of untargeted metagenomic next-generation sequencing to the clinical diagnosis of infectious diseases, particularly in areas in which conventional diagnostic approaches have limitations. Read More

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-pathmechdi
Publisher Site
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345613PMC
January 2019
19 Reads

Modeling Disease with Human Inducible Pluripotent Stem Cells.

Annu Rev Pathol 2019 Jan 24;14:449-468. Epub 2018 Oct 24.

Wellcome and MRC Cambridge Stem Cell Institute, Anne McLaren Laboratory, University of Cambridge, Cambridge CB2 0SZ, United Kingdom; email:

Understanding the physiopathology of disease remains an essential step in developing novel therapeutics. Although animal models have certainly contributed to advancing this enterprise, their limitation in modeling all the aspects of complex human disorders is one of the major challenges faced by the biomedical research field. Human induced pluripotent stem cells (hiPSCs) derived from patients represent a great opportunity to overcome this deficiency because these cells cover the genetic diversity needed to fully model human diseases. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-043634DOI Listing
January 2019

Pathology and Pathogenesis of Chagas Heart Disease.

Annu Rev Pathol 2019 Jan 24;14:421-447. Epub 2018 Oct 24.

Department of Pathology and Laboratory Medicine and Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA; email: , ,

Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of people infected with the protozoan parasite Trypanosoma cruzi. One way T. cruzi is transmitted to people is through contact with infected kissing bugs, which are found in much of the Western Hemisphere, including in vast areas of the United States. Read More

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-pathol-020
Publisher Site
http://dx.doi.org/10.1146/annurev-pathol-020117-043711DOI Listing
January 2019
15 Reads

RNA Binding Proteins and the Pathogenesis of Frontotemporal Lobar Degeneration.

Annu Rev Pathol 2019 Jan 24;14:469-495. Epub 2018 Oct 24.

Department of Pathology, University of California, San Francisco, California 94143, USA; email:

Frontotemporal dementia is a group of early onset dementia syndromes linked to underlying frontotemporal lobar degeneration (FTLD) pathology that can be classified based on the formation of abnormal protein aggregates involving tau and two RNA binding proteins, TDP-43 and FUS. Although elucidation of the mechanisms leading to FTLD pathology is in progress, recent advances in genetics and neuropathology indicate that a majority of FTLD cases with proteinopathy involving RNA binding proteins show highly congruent genotype-phenotype correlations. Specifically, recent studies have uncovered the unique properties of the low-complexity domains in RNA binding proteins that can facilitate liquid-liquid phase separation in the formation of membraneless organelles. Read More

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-pathmechdi
Publisher Site
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012955DOI Listing
January 2019
5 Reads

Cellular and Molecular Mechanisms of Prion Disease.

Annu Rev Pathol 2019 Jan 24;14:497-516. Epub 2018 Oct 24.

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.

Prion diseases are rapidly progressive, incurable neurodegenerative disorders caused by misfolded, aggregated proteins known as prions, which are uniquely infectious. Remarkably, these infectious proteins have been responsible for widespread disease epidemics, including kuru in humans, bovine spongiform encephalopathy in cattle, and chronic wasting disease in cervids, the latter of which has spread across North America and recently appeared in Norway and Finland. The hallmark histopathological features include widespread spongiform encephalopathy, neuronal loss, gliosis, and deposits of variably sized aggregated prion protein, ranging from small, soluble oligomers to long, thin, unbranched fibrils, depending on the disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-013109DOI Listing
January 2019
1 Read

Molecular Genetics of Endometrial Carcinoma.

Annu Rev Pathol 2019 Jan 17;14:339-367. Epub 2018 Oct 17.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine/New York Presbyterian Hospital, New York, New York 10065, USA; email:

Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Endometrioid endometrial carcinomas constitute approximately 85% of newly diagnosed cases; serous carcinomas represent approximately 3-10% of diagnoses; clear cell carcinoma accounts for <5% of diagnoses; and uterine carcinosarcomas are rare, biphasic tumors. Longstanding molecular observations implicate PTEN inactivation as a major driver of endometrioid carcinomas; TP53 inactivation as a major driver of most serous carcinomas, some high-grade endometrioid carcinomas, and many uterine carcinosarcomas; and inactivation of either gene as drivers of some clear cell carcinomas. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-043609DOI Listing
January 2019
2 Reads

Pathophysiology of Sickle Cell Disease.

Annu Rev Pathol 2019 Jan 17;14:263-292. Epub 2018 Oct 17.

Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.

Since the discovery of sickle cell disease (SCD) in 1910, enormous strides have been made in the elucidation of the pathogenesis of its protean complications, which has inspired recent advances in targeted molecular therapies. In SCD, a single amino acid substitution in the β-globin chain leads to polymerization of mutant hemoglobin S, impairing erythrocyte rheology and survival. Clinically, erythrocyte abnormalities in SCD manifest in hemolytic anemia and cycles of microvascular vaso-occlusion leading to end-organ ischemia-reperfusion injury and infarction. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012838DOI Listing
January 2019
7 Reads

Opportunities for microRNAs in the Crowded Field of Cardiovascular Biomarkers.

Annu Rev Pathol 2019 Jan 17;14:211-238. Epub 2018 Oct 17.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; email:

Cardiovascular diseases exist across all developed countries. Biomarkers that can predict or diagnose diseases early in their pathogeneses can reduce their morbidity and mortality in afflicted individuals. microRNAs are small regulatory RNAs that modulate translation and have been identified as potential fluid-based biomarkers across numerous maladies. Read More

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-pathmechdi
Publisher Site
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442682PMC
January 2019
3 Reads
18.750 Impact Factor

Type I Interferons in Autoimmune Disease.

Annu Rev Pathol 2019 Jan 17;14:369-393. Epub 2018 Oct 17.

Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York, New York 10021, USA; email:

Type I interferons, which make up the first cytokine family to be described and are the essential mediators of antivirus host defense, have emerged as central elements in the immunopathology of systemic autoimmune diseases, with systemic lupus erythematosus as the prototype. Lessons from investigation of interferon regulation following virus infection can be applied to lupus, with the conclusion that sustained production of type I interferon shifts nearly all components of the immune system toward pathologic functions that result in tissue damage and disease. We review recent data, mainly from studies of patients with systemic lupus erythematosus, that provide new insights into the mechanisms of induction and the immunologic consequences of chronic activation of the type I interferon pathway. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-043952DOI Listing
January 2019
4 Reads

Innate Immune Signaling in Nonalcoholic Fatty Liver Disease and Cardiovascular Diseases.

Annu Rev Pathol 2019 Jan 19;14:153-184. Epub 2018 Sep 19.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; email:

The physiological significance of innate immune signaling lies primarily in its role in host defense against invading pathogens. It is becoming increasingly clear that innate immune signaling also modulates the development of metabolic diseases, especially nonalcoholic fatty liver disease and cardiovascular diseases, which are characterized by chronic, low-grade inflammation due to a disarrangement of innate immune signaling. Notably, recent studies indicate that in addition to regulating canonical innate immune-mediated inflammatory responses (or immune-dependent signaling-induced responses), molecules of the innate immune system regulate pathophysiological responses in multiple organs during metabolic disturbances (termed immune-independent signaling-induced responses), including the disruption of metabolic homeostasis, tissue repair, and cell survival. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-013003DOI Listing
January 2019
3 Reads
18.750 Impact Factor

Immunological Basis for Recurrent Fetal Loss and Pregnancy Complications.

Annu Rev Pathol 2019 Jan 5;14:185-210. Epub 2018 Sep 5.

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.

Pregnancy stimulates an elaborate assortment of dynamic changes, allowing intimate approximation of genetically discordant maternal and fetal tissues. Although the cellular and molecular details about how this works remain largely undefined, important clues arise from evaluating how a prior pregnancy influences the outcome of a future pregnancy. The risk of complications is consistently increased when complications occurred in a prior pregnancy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012743DOI Listing
January 2019
2 Reads

Pathogenesis of Rickettsial Diseases: Pathogenic and Immune Mechanisms of an Endotheliotropic Infection.

Annu Rev Pathol 2019 Jan 27;14:127-152. Epub 2018 Aug 27.

The University of Texas Medical Branch at Galveston, Galveston, Texas 77555-0609, USA; email: , , ,

Obligately intracytosolic rickettsiae that cycle between arthropod and vertebrate hosts cause human diseases with a spectrum of severity, primarily by targeting microvascular endothelial cells, resulting in endothelial dysfunction. Endothelial cells and mononuclear phagocytes have important roles in the intracellular killing of rickettsiae upon activation by the effector molecules of innate and adaptive immunity. In overwhelming infection, immunosuppressive effects contribute to the severity of illness. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012800DOI Listing
January 2019
1 Read

Pathological Issues in Dystrophinopathy in the Age of Genetic Therapies.

Annu Rev Pathol 2019 Jan 27;14:105-126. Epub 2018 Aug 27.

Department of Pathology and Laboratory Medicine, and Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA; email: , ,

Dystrophinopathy is a class of genetic skeletal muscle disease characterized by myofiber degeneration and regeneration due to insufficient levels or functioning of dystrophin. Pathological evaluation for dystrophinopathy includes the identification of dystrophic skeletal muscle pathology and the immunohistochemical evaluation of dystrophin epitopes, but biopsies have become rare in recent years. However, the evaluation of dystrophin expression in the research setting has become critically important due to recent advances in genetic therapies, including exon skipping and gene therapy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012945DOI Listing
January 2019
1 Read

Insights into Pathogenic Interactions Among Environment, Host, and Tumor at the Crossroads of Molecular Pathology and Epidemiology.

Annu Rev Pathol 2019 Jan 20;14:83-103. Epub 2018 Aug 20.

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02215, USA; email: , ,

Evidence indicates that diet, nutrition, lifestyle, the environment, the microbiome, and other exogenous factors have pathogenic roles and also influence the genome, epigenome, transcriptome, proteome, and metabolome of tumor and nonneoplastic cells, including immune cells. With the need for big-data research, pathology must transform to integrate data science fields, including epidemiology, biostatistics, and bioinformatics. The research framework of molecular pathological epidemiology (MPE) demonstrates the strengths of such an interdisciplinary integration, having been used to study breast, lung, prostate, and colorectal cancers. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345592PMC
January 2019
1 Read

Epstein-Barr Virus and Cancer.

Authors:
Paul J Farrell

Annu Rev Pathol 2019 Jan 20;14:29-53. Epub 2018 Aug 20.

Section of Virology, Imperial College Faculty of Medicine, London W2 1PG, United Kingdom; email:

Epstein-Barr virus (EBV) contributes to about 1.5% of all cases of human cancer worldwide, and viral genes are expressed in the malignant cells. EBV also very efficiently causes the proliferation of infected human B lymphocytes. Read More

View Article

Download full-text PDF

Source
https://www.annualreviews.org/doi/10.1146/annurev-pathmechdi
Publisher Site
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-013023DOI Listing
January 2019
4 Reads

Exposure to Ultraviolet Radiation in the Modulation of Human Diseases.

Annu Rev Pathol 2019 Jan 20;14:55-81. Epub 2018 Aug 20.

Centre for Dermatology Research, Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, and Faculty of Biology, Medicine, and Health, The University of Manchester and Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9PL, United Kingdom; email:

This review focuses primarily on the beneficial effects for human health of exposure to ultraviolet radiation (UVR). UVR stimulates anti-inflammatory and immunosuppressive pathways in skin that modulate psoriasis, atopic dermatitis, and vitiligo; suppresses cutaneous lesions of graft-versus-host disease; and regulates some infection and vaccination outcomes. While polymorphic light eruption and the cutaneous photosensitivity of systemic lupus erythematosus are triggered by UVR, polymorphic light eruption also frequently benefits from UVR-induced immunomodulation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012809DOI Listing
January 2019
28 Reads

Polyglutamine Repeats in Neurodegenerative Diseases.

Annu Rev Pathol 2019 Jan 8;14:1-27. Epub 2018 Aug 8.

Department of Neurology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA; email: ,

Among the age-dependent protein aggregation disorders, nine neurodegenerative diseases are caused by expansions of CAG repeats encoding polyglutamine (polyQ) tracts. We review the clinical, pathological, and biological features of these inherited disorders. We discuss insights into pathogenesis gleaned from studies of model systems and patients, highlighting work that informs efforts to develop effective therapies. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387631PMC
January 2019
20 Reads

Pathogenesis of Peripheral T Cell Lymphoma.

Annu Rev Pathol 2018 01;13:293-320

Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, NY 10021, USA; email:

Peripheral T cell lymphomas (PTCLs) are highly heterogeneous tumors, displaying distinct clinical and biological features. The pathogenesis and normal counterpart of such entities have been elusive for decades. Recent studies have, however, disclosed key mechanisms of peripheral T cell transformation, including (a) the deregulation of signaling pathways controlling T cell development, differentiation, and maturation; (b) the remodeling of the peritumor microenvironment; and (c) the virus-mediated rewiring of T cell biology. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-043821DOI Listing
January 2018
3 Reads

Desmosomes in Human Disease.

Authors:
Nicole A Najor

Annu Rev Pathol 2018 01;13:51-70

Department of Biology, University of Detroit Mercy, Detroit, Michigan 48221; email:

Tissue integrity is crucial for maintaining the homeostasis of living organisms. Abnormalities that affect sites of cell-cell contact can cause a variety of debilitating disorders. The desmosome is an essential cell-cell junctional protein complex in tissues that undergo stress, and it orchestrates intracellular signal transduction. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-044030DOI Listing
January 2018
1 Read

Recent Insights into the Pathogenesis of Nonalcoholic Fatty Liver Disease.

Annu Rev Pathol 2018 01;13:321-350

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna A-1090, Austria; email:

Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic and cardiometabolic mortality. The rapidly increasing prevalence of this disease and of its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches based on a profound understanding of its pathogenesis to halt disease progression to advanced fibrosis or cirrhosis and cancer. The pathogenesis of NAFLD involves a complex interaction among environmental factors (i. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-043617DOI Listing
January 2018
4 Reads

Epithelial Mesenchymal Transition in Tumor Metastasis.

Authors:
Vivek Mittal

Annu Rev Pathol 2018 01;13:395-412

Department of Cardiothoracic Surgery, Department of Cell and Developmental Biology, and Neuberger Berman Foundation Lung Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA; email:

Metastasis is the major cause of cancer-related deaths; therefore, the prevention and treatment of metastasis are fundamental to improving clinical outcomes. Epithelial mesenchymal transition (EMT), an evolutionarily conserved developmental program, has been implicated in carcinogenesis and confers metastatic properties upon cancer cells by enhancing mobility, invasion, and resistance to apoptotic stimuli. Furthermore, EMT-derived tumor cells acquire stem cell properties and exhibit marked therapeutic resistance. Read More

View Article

Download full-text PDF

Source
http://www.annualreviews.org/doi/10.1146/annurev-pathol-0201
Publisher Site
http://dx.doi.org/10.1146/annurev-pathol-020117-043854DOI Listing
January 2018
3 Reads

Intrinsic Neuronal Stress Response Pathways in Injury and Disease.

Annu Rev Pathol 2018 01;13:93-116

Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030; email:

From injury to disease to aging, neurons, like all cells, may face various insults that can impact their function and survival. Although the consequences are substantially dictated by the type, context, and severity of insult, distressed neurons are far from passive. Activation of cellular stress responses aids in the preservation or restoration of nervous system function. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-012414-040354DOI Listing
January 2018

Perspectives from a Pathologist: My Journey on the Path to Women's Health Research, Sex and Gender Policy, and Practice Implications.

Authors:
Vivian W Pinn

Annu Rev Pathol 2018 01;13:1-25

Former Director (Retired), Office of Research on Women's Health, National Institutes of Health, Bethesda, Maryland 20892; email:

These words reflect my recollections of major transition points in my life and career: as I first became dedicated to becoming a physician, being introduced to the field of pathology and research, and then transitioning to a somewhat different career focus by becoming the first director of the National Institutes of Health Office of Research on Women's Health. Many of the experiences that I gained during my years in pathology served me well as I made efforts to establish women's health research and sex and gender based studies as scientific endeavors. Participating in research and teaching as an academic pathologist, setting funding priorities, and supporting and encouraging research careers through governmental office programs have been the essence of my more than 50 years as a pathologist and physician. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-044020DOI Listing
January 2018

The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future.

Annu Rev Pathol 2018 01;13:379-394

Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA; email: ,

The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Read More

View Article

Download full-text PDF

Source
http://www.annualreviews.org/doi/10.1146/annurev-pathol-0512
Publisher Site
http://dx.doi.org/10.1146/annurev-pathol-051217-111018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803388PMC
January 2018
9 Reads

New Insights into Lymphoma Pathogenesis.

Annu Rev Pathol 2018 01 15;13:193-217. Epub 2017 Nov 15.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email: ,

Lymphomas represent clonal proliferations of lymphocytes that are broadly classified based upon their maturity (peripheral or mature versus precursor) and lineage (B cell, T cell, and natural killer cell). Insights into the pathogenetic mechanisms involved in lymphoma impact the classification of lymphoma and have significant implications for the diagnosis and clinical management of patients. Serial scientific and technologic advances over the last 30 years in immunology, cytogenetics, molecular biology, gene expression profiling, mass spectrometry-based proteomics, and, more recently, next-generation sequencing have contributed to greatly enhance our understanding of the pathogenetic mechanisms in lymphoma. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-043803DOI Listing
January 2018
12 Reads

Cellular and Molecular Mechanisms of Autoimmune Hepatitis.

Annu Rev Pathol 2018 01;13:247-292

Division of Rheumatology, Allergy, and Clinical Immunology, School of Medicine, University of California, Davis, California 95817, USA; email:

Autoimmune hepatitis is an uncommon idiopathic syndrome of immune-mediated destruction of hepatocytes, typically associated with autoantibodies. The disease etiology is incompletely understood but includes a clear association with human leukocyte antigen (HLA) variants and other non-HLA gene variants, female sex, and the environment. Pathologically, there is a CD4+ T cell-rich lymphocytic inflammatory infiltrate with variable hepatocyte necrosis and subsequent hepatic fibrosis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-043534DOI Listing
January 2018

Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology.

Annu Rev Pathol 2018 01 10;13:351-378. Epub 2017 Nov 10.

Division of Experimental Pathology, Department of Pathology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261, USA.

The liver is an organ that performs a multitude of functions, and its health is pertinent and indispensable to survival. Thus, the cellular and molecular machinery driving hepatic functions is of utmost relevance. The Wnt signaling pathway is one such signaling cascade that enables hepatic homeostasis and contributes to unique hepatic attributes such as metabolic zonation and regeneration. Read More

View Article

Download full-text PDF

Source
http://www.annualreviews.org/doi/10.1146/annurev-pathol-0201
Publisher Site
http://dx.doi.org/10.1146/annurev-pathol-020117-044010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927358PMC
January 2018
4 Reads

Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems.

Annu Rev Pathol 2018 01 3;13:163-191. Epub 2017 Nov 3.

Department of Pediatrics, Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; email:

Multisystem metabolic disorders caused by defects in oxidative phosphorylation (OXPHOS) are severe, often lethal, conditions. Inborn errors of OXPHOS function are termed primary mitochondrial disorders (PMDs), and the use of nutritional interventions is routine in their supportive management. However, detailed mechanistic understanding and evidence for efficacy and safety of these interventions are limited. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-043644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911915PMC
January 2018
8 Reads

New Insights into Graft-Versus-Host Disease and Graft Rejection.

Annu Rev Pathol 2018 01 3;13:219-245. Epub 2017 Nov 3.

Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA; email:

Allogeneic transplantation of foreign organs or tissues has lifesaving potential, but can lead to serious complications. After solid organ transplantation, immune-mediated rejection mandates the use of prolonged global immunosuppression and limits the life span of transplanted allografts. After bone marrow transplantation, donor-derived immune cells can trigger life-threatening graft-versus-host disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-043720DOI Listing
January 2018
6 Reads

Genomic Hallmarks of Thyroid Neoplasia.

Annu Rev Pathol 2018 01 30;13:141-162. Epub 2017 Oct 30.

Departments of Pathology and Internal Medicine, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA; email:

The genomic landscape of thyroid cancers that are derived from follicular cells has been substantially elucidated through the coordinated application of high-throughput genomic technologies. Here, I review the common genetic alterations across the spectrum of thyroid neoplasia and present the resulting model of thyroid cancer initiation and progression. This model illustrates the striking correlation between tumor differentiation and overall somatic mutational burden, which also likely explains the highly variable clinical behavior and outcome of patients with thyroid cancers. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-121808-102139DOI Listing
January 2018
5 Reads

Cancer Metastasis: A Reappraisal of Its Underlying Mechanisms and Their Relevance to Treatment.

Annu Rev Pathol 2018 01 25;13:117-140. Epub 2017 Oct 25.

Experimental Pathology Service, Centre Hospitalier Universitaire Vaudois, University of Lausanne, CH-1005 Lausanne, Switzerland; email:

Metastases are responsible for the vast majority of cancer-related deaths, but, despite intense efforts to understand their underlying mechanisms with the goal of uncovering effective therapeutic targets, treatment of metastatic cancer has progressed minimally. In this review, we examine the biological programs currently proposed to be key drivers of metastasis. On the basis of evidence from a growing body of research, we discuss to what extent the cellular and molecular mechanisms that are suggested to underlie cancer cell dissemination are specific to the metastatic process, as opposed to representing natural primary tumor progression. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-044127DOI Listing
January 2018
2 Reads

Stem Cell Pathology.

Annu Rev Pathol 2018 01 20;13:71-92. Epub 2017 Oct 20.

Department of Biomedical Sciences and Cornell Stem Cell Program, Cornell University, Ithaca, New York 14853, USA; email:

Rapid advances in stem cell biology and regenerative medicine have opened new opportunities for better understanding disease pathogenesis and the development of new diagnostic, prognostic, and treatment approaches. Many stem cell niches are well defined anatomically, thereby allowing their routine pathological evaluation during disease initiation and progression. Evaluation of the consequences of genetic manipulations in stem cells and investigation of the roles of stem cells in regenerative medicine and pathogenesis of various diseases such as cancer require significant expertise in pathology for accurate interpretation of novel findings. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-043935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857951PMC
January 2018
7 Reads

Hemophagocytic Lymphohistiocytosis.

Annu Rev Pathol 2018 01 13;13:27-49. Epub 2017 Sep 13.

Brigham & Women's Hospital, Boston, Massachusetts 02115; email:

Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages resulting in hypercytokinemia and immune-mediated injury of multiple organ systems. It is seen in both children and adults and is recognized as primary (driven by underlying genetic mutations that abolish critical proteins required for normal function of cytotoxic T cells and NK cells) or secondary (resulting from a malignant, infectious, or autoimmune stimulus without an identifiable underlying genetic trigger). Clinical and laboratory manifestations include fever, splenomegaly, neurologic dysfunction, coagulopathy, liver dysfunction, cytopenias, hypertriglyceridemia, hyperferritinemia, hemophagocytosis, and diminished NK cell activity. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-020117-043625DOI Listing
January 2018
1 Read

Dissecting Clinical Heterogeneity in Neurofibromatosis Type 1.

Annu Rev Pathol 2017 01;12:53-74

Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110; email:

Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder in which affected children and adults are predisposed to the development of benign and malignant nervous system tumors. Caused by a germline mutation in the NF1 tumor suppressor gene, individuals with NF1 are prone to optic gliomas, malignant gliomas, neurofibromas, and malignant peripheral nerve sheath tumors, as well as behavioral, cognitive, motor, bone, cardiac, and pigmentary abnormalities. Although NF1 is a classic monogenic syndrome, the clinical features of the disorder and their impact on patient morbidity are variable, even within individuals who bear the same germline NF1 gene mutation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100228DOI Listing
January 2017
4 Reads

Disorders of Astrocytes: Alexander Disease as a Model.

Annu Rev Pathol 2017 Jan;12:131-152

Department of Pathology and Cell Biology, Columbia University, New York, NY 10032; email: ,

Astrocytes undergo important phenotypic changes in many neurological disorders, including strokes, trauma, inflammatory diseases, infectious diseases, and neurodegenerative diseases. We have been studying the astrocytes of Alexander disease (AxD), which is caused by heterozygous mutations in the GFAP gene, which is the gene that encodes the major astrocyte intermediate filament protein. AxD is a primary astrocyte disease because GFAP expression is specific to astrocytes in the central nervous system (CNS). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100218DOI Listing
January 2017
33 Reads

Pathogenesis and Pathology of Mastocytosis.

Annu Rev Pathol 2017 Jan;12:487-514

Tel Hai College, Upper Galilee, 1220800 Israel; email:

Systemic mastocytosis is a clonal disorder of mast cells that may variably present with characteristic skin lesions, episodes of mast cell mediator release, and disturbances of hematopoiesis. No curative therapy presently exists. Conventional management has relied on agents that antagonize mediators released by mast cells, inhibit mediator secretion, or modulate mast cell proliferation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100312DOI Listing
January 2017
24 Reads

Circulating Tumor Cells: Fluid Surrogates of Solid Tumors.

Annu Rev Pathol 2017 Jan;12:419-447

Bridge Institute, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California 90089; email:

Evaluation of circulating tumor cells (CTCs) has demonstrated clinical validity as a prognostic tool based on enumeration, but since the introduction of this tool to the clinic in 2004, further clinical utility and widespread adoption have been limited. However, immense efforts have been undertaken to further the understanding of the mechanisms behind the biology and kinetics of these rare cells, and progress continues toward better applicability in the clinic. This review describes recent advances within the field, with a particular focus on understanding the biological significance of CTCs, and summarizes emerging methods for identifying, isolating, and interrogating the cells that may provide technical advantages allowing for the discovery of more specific clinical applications. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100256DOI Listing
January 2017
2 Reads

Focal Cortical Dysplasia: Gene Mutations, Cell Signaling, and Therapeutic Implications.

Annu Rev Pathol 2017 Jan;12:547-571

Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland 21201; email:

Focal cortical dysplasias (FCDs) are malformations of cortical development (MCDs) that are highly associated with medication-resistant epilepsy and are the most common cause of neocortical epilepsy in children. FCDs are a heterogeneous group of developmental disorders caused by germline or somatic mutations that occur in genes regulating the PI3K/Akt/mTOR pathway-a key pathway in neuronal growth and migration. Accordingly, FCDs are characterized by abnormal cortical lamination, cell morphology (e. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100138DOI Listing
January 2017
3 Reads

Hydatidiform Moles: Genetic Basis and Precision Diagnosis.

Annu Rev Pathol 2017 Jan;12:449-485

Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231.

Hydatidiform moles are intriguing pathologic entities representing abnormal placental villous tissue with unique genetic profiles and a wide spectrum of morphologic features, which makes accurate diagnosis challenging. Overrepresentation of the paternal genome in sporadic hydatidiform moles (purely androgenetic in complete hydatidiform moles and diandric triploid in partial hydatidiform moles) is a fundamental genetic event leading to global alteration of imprinting gene expression in the molar trophoblast. Rare familial biparental hydatidiform moles (due to NLRP7 or KHDC3L mutations) share such global imprinting alterations, implying a common end point of pathogenesis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100237DOI Listing
January 2017
15 Reads

Immunity to Commensal Fungi: Detente and Disease.

Annu Rev Pathol 2017 Jan 21;12:359-385. Epub 2016 Dec 21.

F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048; email: , ,

Fungi are ubiquitous in our environment, and a healthy immune system is essential to maintain adequate protection from fungal infections. When this protection breaks down, superficial and invasive fungal infections cause diseases that range from irritating to life-threatening. Millions of people worldwide develop invasive infections during their lives, and mortality for these infections often exceeds 50%. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100342DOI Listing
January 2017
21 Reads

Metabolic Reprogramming in Brain Tumors.

Annu Rev Pathol 2017 Jan 21;12:515-545. Epub 2016 Dec 21.

Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065; email:

Next-generation sequencing has substantially enhanced our understanding of the genetics of primary brain tumors by uncovering several novel driver genetic alterations. How many of these genetic modifications contribute to the pathogenesis of brain tumors is not well understood. An exciting paradigm emerging in cancer biology is that oncogenes actively reprogram cellular metabolism to enable tumors to survive and proliferate. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-012615-044329DOI Listing
January 2017
11 Reads

Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis.

Annu Rev Pathol 2017 Jan 5;12:331-357. Epub 2016 Dec 5.

Department of Medicine, Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611; email:

Chronic rhinosinusitis (CRS) is a troublesome, chronic inflammatory disease that affects over 10% of the adult population, causing decreased quality of life, lost productivity, and lost time at work and leading to more than a million surgical interventions annually worldwide. The nose, paranasal sinuses, and associated lymphoid tissues play important roles in homeostasis and immunity, and CRS significantly impairs these normal functions. Pathogenic mechanisms of CRS have recently become the focus of intense investigations worldwide, and significant progress has been made. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514544PMC
January 2017
12 Reads

Amyloidosis: Insights from Proteomics.

Authors:
Ahmet Dogan

Annu Rev Pathol 2017 Jan 5;12:277-304. Epub 2016 Dec 5.

Departments of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065; email:

Amyloidoses are a spectrum of disorders caused by abnormal folding and extracellular deposition of proteins. The deposits lead to tissue damage and organ dysfunction, particularly in the heart, kidneys, and nerves. There are at least 30 different proteins that can cause amyloidosis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100200DOI Listing
January 2017
6 Reads

The Varied Roles of Notch in Cancer.

Annu Rev Pathol 2017 Jan 5;12:245-275. Epub 2016 Dec 5.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.

Notch receptors influence cellular behavior by participating in a seemingly simple signaling pathway, but outcomes produced by Notch signaling are remarkably varied depending on signal dose and cell context. Here, after briefly reviewing new insights into physiologic mechanisms of Notch signaling in healthy tissues and defects in Notch signaling that contribute to congenital disorders and viral infection, we discuss the varied roles of Notch in cancer, focusing on cell autonomous activities that may be either oncogenic or tumor suppressive. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933931PMC
January 2017
7 Reads

Emerging Concepts and Technologies for the Discovery of Microorganisms Involved in Human Disease.

Annu Rev Pathol 2017 Jan 5;12:217-244. Epub 2016 Dec 5.

Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215; email:

Established infectious agents continue to be a major cause of human morbidity and mortality worldwide. However, the causative agent remains unknown for a wide range of diseases; many of these are suspected to be attributable to yet undiscovered microorganisms. The advent of unbiased high-throughput sequencing and bioinformatics has enabled rapid identification and molecular characterization of known and novel infectious agents in human disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-012615-044305DOI Listing
January 2017
26 Reads

Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials.

Annu Rev Pathol 2017 Jan 5;12:305-330. Epub 2016 Dec 5.

Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94158-2517; email:

Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557092PMC
January 2017
5 Reads

The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer.

Annu Rev Pathol 2017 01 5;12:153-186. Epub 2016 Dec 5.

Department of Medicine, Columbia University, New York, NY 10032; email:

Liver cancer is the second leading cause of cancer mortality worldwide, causing more than 700,000 deaths annually. Because of the wide landscape of genomic alterations and limited therapeutic success of targeting tumor cells, a recent focus has been on better understanding and possibly targeting the microenvironment in which liver tumors develop. A unique feature of liver cancer is its close association with liver fibrosis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-pathol-052016-100322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720358PMC
January 2017
10 Reads