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Journal of Pathology

Luciana H Osaki, Kevin A Bockerstett, Chun Fung Wong, Eric L Ford, Blair B Madison, Richard J DiPaolo, Jason C Mills
Chronic inflammation of the gastric mucosa, often caused by autoimmune gastritis and/or infection with Helicobacter pylori, can lead to atrophy of acid-secreting parietal cells with metaplasia of remaining cells. The histological pattern marks a critical step in the progression from chronic gastritis to gastric cancer, yet underlying mechanism(s) of inflammation-induced cell death of gastric epithelial cells are poorly understood. We investigated direct effects of a type 1 cytokine associated with autoimmunity and infection, interferon-γ (IFN-γ), on gastric epithelial cells...
December 3, 2018: Journal of Pathology
Roy Rabbie, Peter Ferguson, Christian Molina-Aguilar, David J Adams, Carla Daniela Robles-Espinoza
Melanoma is characterised by its ability to metastasise at early stages of tumour development. Current clinico-pathologic staging based on the American Joint Committee on Cancer criteria is used to guide surveillance and management in early-stage disease, but its ability to predict clinical outcome has limitations. Herein we review the genomics of melanoma subtypes including cutaneous, acral, uveal and mucosal, with a focus on the prognostic and predictive significance of key molecular aberrations.
December 3, 2018: Journal of Pathology
Kartika R Pertiwi, Onno J de Boer, Claire Mackaaij, Dara R Pabittei, Robbert J de Winter, Xiaofei Li, Allard C van der Wal
Extracellular traps generated by neutrophils contribute to thrombus progression in coronary atherosclerotic plaques. It is not known whether other inflammatory cell types in coronary atherosclerotic plaque or thrombus also release extracellular traps. We investigated their formation by macrophages, mast cells and eosinophils in human coronary atherosclerosis, and in relation to the age of thrombus of myocardial infarction patients. Coronary arteries with thrombosed or intact plaques were retrieved from patients who died from myocardial infarction...
December 2, 2018: Journal of Pathology
Svenja Loering, Guy J M Cameron, Malcolm R Starkey, Philip M Hansbro
Lung development is a complex process mediated through the interaction of multiple cell types, factors and mediators. In mice, it starts as early as embryonic day 9 and continues into early adulthood. The process can be separated into five different developmental stages: embryonic, pseudoglandular, canalicular, saccular and alveolar. Whilst lung bud formation and branching morphogenesis have been studied extensively, the mechanisms of alveolarization are incompletely understood. Aberrant lung development can lead to deleterious consequences for respiratory health such as bronchopulmonary dysplasia, a disease primarily affecting preterm neonates, which is characterized by increased pulmonary inflammation and disturbed alveolarization...
December 2, 2018: Journal of Pathology
Aliki Xochelli, Vasilis Bikos, Eleftheria Polychronidou, Chrysi Galigalidou, Andreas Agathangelidis, Frédéric Charlotte, Panagiotis Moschonas, Zadie Davis, Monica Colombo, Maria Roumelioti, Lesley-Ann Sutton, Patricia Groenen, Michiel van den Brand, Myriam Boudjoghra, Patricia Algara, Alexandra Traverse-Glehen, Ana Ferrer, Evangelia Stalika, Maria Karypidou, George Kanellis, Christina Kalpadakis, Manuella Mollejo, Gerasimos Pangalis, Panayiotis Vlamos, Rose-Marie Amini, Sarka Pospisilova, David Gonzalez, Maurilio Ponzoni, Achilles Anagnostopoulos, Véronique Giudicelli, Marie-Paule Lefranc, Blanca Espinet, Panagiotis Panagiotidis, Miguel Angel Piris, Ming-Qing Du, Richard Rosenquist, Theodora Papadaki, Chrysoula Belessi, Manlio Ferrarini, David Oscier, Dimitrios Tzovaras, Paolo Ghia, Frederic Davi, Anastasia Hadzidimitriou, Kostas Stamatopoulos
The B cell receptor immunoglobulin (BcR IG) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n=488) i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL) as well as provisional entities (n=76) according to the World Health Organization classification. The most striking IG gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different IG gene distributions depending on the primary site of involvement...
November 28, 2018: Journal of Pathology
Jie Liu, Caihong Wang, Xuhui Ma, Yang Tian, Chunying Wang, Yan Fu, Yongzhang Luo
Chemokine receptors are highly expressed in various cancers and play crucial roles in tumor progression. However, their expression patterns and functions in melanoma are unclear. The present study aimed to identify the chemokine receptors that play critical roles in melanoma progression and unravel the underlying molecular mechanisms. We found that the C-C chemokine receptor 5 (CCR5) was more abundant in melanoma cells than normal cells and was positively associated with tumor malignancy in clinical patients...
November 26, 2018: Journal of Pathology
Hirofumi Rokutan, Hiroyuki Abe, Hiromi Nakamura, Tetsuo Ushiku, Erika Arakawa, Fumie Hosoda, Shinichi Yachida, Yosuke Tsuji, Mitsuhiro Fujishiro, Kazuhiko Koike, Yasushi Totoki, Masashi Fukayama, Tatsuhiro Shibata
Gastric cancer (GC) is one of the most common and life-threatening malignancies. The course of disease and tumor aggressiveness vary among GCs, although how early fate is determined and by what factors remains elusive. To solve this question, we collected 43 gastric intramucosal neoplasias (GINs), comprising dysplasia/intraepithelial neoplasia (D/IEN; a premalignant lesion) and minute GC (miGC; ≤10 mm) of intestinal histotype, and performed targeted deep DNA sequencing of 67 GC-related genes derived from large-scale data...
November 26, 2018: Journal of Pathology
Juan Díaz-Martín, Michele Biscuola, Jonathan Benoit, David Marcilla, Gema Civantos, Enrique de Álava
This commentary addresses the issue of the classification of sarcomas in the article written by Watson and colleagues published recently in this journal. That article delves into the molecular characterization and distinct phenotypes of some recently described entities (e.g. BCOR-rearranged sarcomas, CIC-fused sarcomas), and describes new groups with common characteristics. This commentary focuses on several questions raised in the article, such as what makes a group of sarcomas become a clinical entity, which should be the main driver of sarcoma classification, how the classification of small round cell sarcomas is expected to evolve and how high-throughput techniques could be applied to sarcoma diagnosis in the short term...
November 25, 2018: Journal of Pathology
Suzanne A B M Aarts, Tom T P Seijkens, Pascal J H Kusters, Claudia M van Tiel, Myrthe E Reiche, Myrthe den Toom, Linda Beckers, Cindy P A A van Roomen, Menno P J de Winther, Gijs Kooij, Esther Lutgens
The co-stimulatory CD40L-CD40 dyad plays a major role in multiple sclerosis (MS). CD40 is highly expressed on MHCII+ B cells, dendritic cells and macrophages in human MS lesions. Here we investigated the role of the CD40 downstream signaling intermediates TRAF2 and TRAF6 in MHCII+ cells in experimental autoimmune encephalomyelitis (EAE). Both MHCII-CD40-Traf2-/- and MHCII-CD40-Traf6-/- mice showed a reduction in clinical signs of EAE and prevented demyelination. However, only MHCII-CD40-Traf6-/- mice displayed a decrease in myeloid and lymphoid cell infiltration into the central nervous system (CNS) that was accompanied by reduced levels of TNF-α, IL-6, and IFN-γ...
November 24, 2018: Journal of Pathology
Katharina Jandl, Helene Thekkekara Puthenparampil, Leigh M Marsh, Julia Hoffmann, Jochen Wilhelm, Christine Veith, Katharina Sinn, Walter Klepetko, Horst Olschewski, Andrea Olschewski, Matthias Brock, Grazyna Kwapiszewska
In idiopathic pulmonary arterial hypertension (IPAH), global transcriptional changes induce a smooth muscle cell phenotype characterized by excessive proliferation, migration and apoptosis resistance. Long non-coding RNAs (lncRNAs) are key regulators of cellular function. Using a compartment-specific transcriptional profiling approach, we sought to investigate the link between transcriptional reprogramming by lncRNAs and the maladaptive smooth muscle cell phenotype in IPAH. Transcriptional profiling of small remodelled arteries from 18 IPAH patients and 17 controls revealed global perturbations in metabolic, neuronal, proliferative and immunological processes...
November 18, 2018: Journal of Pathology
Yuko Kuboki, Catherine G Fischer, Violeta Beleva Guthrie, Wenjie Huang, Jun Yu, Peter Chianchiano, Waki Hosoda, Hao Zhang, Lily Zheng, Xiaoshan Shao, Elizabeth D Thompson, Kevin Waters, Justin Poling, Jin He, Matthew J Weiss, Christopher L Wolfgang, Michael G Goggins, Ralph H Hruban, Nicholas J Roberts, Rachel Karchin, Laura D Wood
Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer; however, little is known about genetic heterogeneity in these lesions. The objective of this study was to characterize genetic heterogeneity in IPMNs at the single-cell level. We isolated single cells from fresh tissue from ten IPMNs, followed by whole genome amplification and targeted next generation sequencing of pancreatic driver genes. We then determined single-cell genotypes using a novel multi-sample mutation calling algorithm...
November 14, 2018: Journal of Pathology
Maryse Fiche, Valentina Scabia, Patrick Aouad, Laura Battista, Assia Treboux, Athina Stravodimou, Khalil Zaman, Valerian Dormoy, Ayyakkannu Ayyanan, George Sflomos, Cathrin Brisken
Estrogen receptor α positive (ER+ ) or "luminal" breast cancers (BC) were notoriously difficult to establish as patient-derived xenografts (PDXs). We and others recently demonstrated that the microenvironment is critical for ER+ tumor cells; when grafted as single cells into milk ducts of NOD Scid gamma (NSG) females >90% of ER+ tumors can be established as xenografts and recapitulate many features of the human disease in vivo. This intra-ductal (ID) approach holds promise for personalized medicine, yet human and murine stroma are organized differently and this and other species specificities may limit the value of this model...
November 14, 2018: Journal of Pathology
Gonzalo Sánchez-Duffhues, Amaya García de Vinuesa, Vera van de Pol, Marlieke E Geerts, Margreet R de Vries, Stef G T Janson, Hans van Dam, Jan Lindeman, Marie-José Goumans, Peter Ten Dijke
Endothelial-to-mesenchymal transition (EndMT) has been unveiled as a common cause for a multitude of human pathologies, including cancer and cardiovascular disease. Vascular calcification is a risk factor for ischemic vascular disorders and slowing calcification may reduce mortality in affected patients. The absence of early biomarkers hampers the identification of patients at risk. EndMT and vascular calcification are induced upon cooperation between distinct stimuli, including inflammatory cytokines and transforming growth factor beta (TGF-β) family members...
November 14, 2018: Journal of Pathology
Hiroaki Iwata, Mayumi Kamaguchi, Hideyuki Ujiie, Inkin Ujiie, Ken Natsuga, Wataru Nishie, Hiroshi Shimizu
Immunoglobulins consist of two antigen-binding regions (Fab) and one constant region (Fc). Protein A and protein G are bacterial proteins used for the purification of IgG by virtue of their high affinities for Fc fragment. Rheumatoid factors are autoantibodies against IgG Fc fragments, which are present in the body under physiological conditions. Little is known about the influence of Fc-binding proteins on the pathogenicity of antibody-induced autoimmune diseases. Pemphigoid diseases are a group of autoimmune sub-epidermal blistering disorders that includes bullous pemphigoid and mucous membrane pemphigoid...
November 14, 2018: Journal of Pathology
Chen Ni, Pan Ma, Ruirui Wang, Xiaohan Lou, Xiaomeng Liu, Yue Qin, Rui Xue, Ingolf Blasig, Ulrike Erben, Zhihai Qin
Immune responses contribute to a large extent to heart diseases. However, it is still not clear how the key inflammatory mediator Interferon-γ (IFNγ) plays a role in doxorubicin (DOX)-induced cardiomyopathy. We report here that DOX-induced heart dysfunction involves IFNγ signaling in mice. The IFNγ receptor was found to be highly expressed on cardiomyocytes, and its downstream signaling was activated in heart tissues upon DOX treatment. In vitro, IFNγ strongly aggravated the injury of cardiomyocytes exposed to DOX...
November 14, 2018: Journal of Pathology
Jules A Westbrook, Steven L Wood, David A Cairns, Kathryn McMahon, Renu Gahlaut, Helene Thygesen, Mike Shires, Stephanie Roberts, Helen Marshall, Maria R Oliva, Mark J Dunning, Andrew M Hanby, Peter J Selby, Valerie Speirs, Georgia Mavria, Robert E Coleman, Janet E Brown
Skeletal metastasis occurs in around 75% of advanced breast cancers, with the disease incurable once cancer cells disseminate to bone, but there remains an unmet need for biomarkers to identify patients at high risk of bone recurrence. This study aimed to identify such a biomarker and to assess its utility in predicting response to adjuvant zoledronic acid. We used quantitative proteomics (SILAC-MS), to compare protein expression in a bone-homed variant (BM1) of the human breast cancer cell line MDA-MB-231 with parental non-bone-homing cells to identify novel biomarkers for risk of subsequent bone metastasis in early breast cancer...
November 14, 2018: Journal of Pathology
Nan Qin, Ting Cai, Qingqing Ke, Qi Yuan, Jing Luo, Xiaoming Mao, Lei Jiang, Hongdi Cao, Ping Wen, Ke Zen, Yang Zhou, Junwei Yang
Acute kidney injury (AKI) is a public health concern with high morbidity and mortality rates in hospitalized patients and because survivors have increased risk of progression to chronic kidney disease. Mitochondrial damage is the critical driver of AKI-associated dysfunction and loss of tubular epithelial cells; however, the pathways that mediate these events are poorly defined. Here, in murine ischemia/reperfusion-induced (I/R-induced) AKI, we determined that mitochondrial damage is associated with the level of renal uncoupling protein 2 (UCP2)...
November 14, 2018: Journal of Pathology
Amy E McCart Reed, Priyakshi Kalita-de Croft, Jamie Kutasovic, Jodi M Saunus, Sunil R Lakhani
During the last decade, the genomics revolution has driven critical advances in molecular oncology and pathology, and a deeper appreciation of heterogeneity that is beginning to reshape our thinking around diagnostic classification. Recent developments have seen existing classification systems modified and improved where possible, gene-based diagnostics implemented and tumour-immune interactions modulated. We present a detailed discussion of this progress, including the advances in understanding of breast tumour classification, for example mixed ductal-lobular tumours and the spectrum of triple-negative breast cancer...
November 14, 2018: Journal of Pathology
Jessica Gagné-Sansfacon, Ariane Langlois, Marie-Josée Langlois, Geneviève Coulombe, Sarah Tremblay, Vanessa Vaillancourt-Lavigueur, Cheng-Kui Qu, Alfredo Menendez, Nathalie Rivard
The Src homology-2 domain-containing tyrosine phosphatase 2 (SHP-2) regulates many cellular processes including proliferation, differentiation and survival. Polymorphisms in the gene encoding SHP-2 are associated with an increased susceptibility to develop ulcerative colitis. We recently reported that intestinal epithelial cell (IEC)-specific deletion of Shp-2 in mice (Shp-2IEC-KO ) leads to chronic colitis and colitis-associated cancer (CAC). This suggests that SHP-2-dependent signaling protects the colonic epithelium against inflammation and CAC development...
October 30, 2018: Journal of Pathology
Peyman Ghorbani, Tyler K T Smith, Morgan D Fullerton
Non-alcoholic fatty liver disease (NAFLD) often develops in concert with related metabolic diseases like obesity, dyslipidemia and insulin resistance. Prolonged lipid accumulation and inflammation can progress to non-alcoholic steatohepatitis (NASH). Although factors associated with the development of NAFLD are known, the triggers for the progression of NAFLD to NASH are poorly understood. Recent findings published in The Journal of Pathology reveal the possible regulation of NASH progression by metabolites of the mevalonate pathway...
October 30, 2018: Journal of Pathology
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