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Journal of Pathology

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https://read.qxmd.com/read/30746716/ulcer-associated-cell-lineage-expresses-genes-involved-in-regeneration-and-is-hallmarked-by-high-neutrophil-gelatinase-associated-lipocalin-ngal-levels
#1
Silje Thorsvik, Atle van Beelen Granlund, Tarjei Dahl Svendsen, Ingunn Bakke, Elin Synnøve Røyset, Trude Helen Flo, Jan Kristian Damås, Ann Elisabet Østvik, Torunn Bruland, Arne Kristian Sandvik
Neutrophil gelatinase associated lipocalin (NGAL), also known as Lipocalin 2, is an antimicrobial protein, encoded by the gene LCN2, strongly upregulated in inflammatory bowel disease (IBD) and a promising biomarker for IBD. Here we demonstrate that NGAL is highly expressed in all parts of pyloric metaplasia, also known as the ulcer-associated cell lineage (UACL), a metaplastic cell lineage suggested to play a role in wound healing in Crohn's disease (CD). We further show NGAL expression in regenerative intestinal crypts and in undifferentiated patient-derived colonoids...
February 11, 2019: Journal of Pathology
https://read.qxmd.com/read/30746706/molecular-comparison-of-interval-and-screen-detected-breast-cancers
#2
Dane Cheasley, Na Li, Simone M Rowley, Kenneth Elder, G Bruce Mann, Sherene Loi, Peter Savas, David L Goode, Tanjina Kader, Magnus Zethoven, Tim Semple, Stephen B Fox, Jia-Min Pang, David Byrne, Lisa Devereux, Carolyn Nickson, Pietro Procopio, Grant Lee, Siobhan Hughes, Hugo Saunders, Kenji M Fujihara, Keilly Kuykhoven, Jacquie Connaughton, Paul A James, Kylie L Gorringe, Ian G Campbell
Breast cancer (BC) diagnosed after a negative mammogram but prior to the next screening episode is termed an "interval breast cancer" (IBC). Understanding the molecular differences between IBC and screen-detected breast cancers (SDBC) could improve mammographic screening and management options. Therefore, we assessed both germline and somatic genomic aberrations in a prospective cohort. Utilizing the Lifepool cohort of >54,000 women attending mammographic screening programs, 930 BC cases with screening status were identified (726 SDBC and 204 IBC)...
February 11, 2019: Journal of Pathology
https://read.qxmd.com/read/30737779/androgen-receptor-variant-12-promotes-migration-and-invasion-by-regulating-mylk-in-gastric-cancer
#3
Nan Xia, Jiantao Cui, Min Zhu, Rui Xing, Youyong Lu
Androgen receptor (AR) and its variants (AR-Vs) promote tumorigenesis and metastasis in many hormone-related cancers, such as breast, prostate and hepatocellular cancers. However, the expression patterns and underlying molecular mechanisms of AR in gastric cancer (GC) are not fully understood. This study aimed to detect the expression of AR-Vs in GC and explored their role in metastasis of GC. Here, the AR expression form was identified in GC cell lines and tissues by RT-PCR and qPCR. Transwell assays and experimental lung metastasis animal models were used to assess the function of AR in cell migration and invasion...
February 8, 2019: Journal of Pathology
https://read.qxmd.com/read/30734924/n-homocysteinylation-of-tau-and-map1-is-increased-in-autopsy-specimens-of-alzheimer-s-disease-and-vascular-dementia
#4
Carine Bossenmeyer-Pourié, A David Smith, Sylvain Lehmann, Vincent Deramecourt, Bernard Sablonnière, Jean-Michel Camadro, Grégory Pourié, Racha Kerek, Deborah Helle, Remy Umoret, Rosa-Maria Guéant-Rodriguez, Valérie Rigau, Audrey Gabelle, Jeffrey M Sequeira, Edward V Quadros, Jean-Luc Daval, Jean-Louis Guéant
The pathomechanisms that associate a deficit in folate and/or vitamin B12 and the subsequent hyperhomocysteinemia with pathological brain ageing are unclear. We investigated the homocysteinylation of microtubule-associated proteins (MAPs) in brains of patients with Alzheimer's disease or vascular dementia, and in rats depleted in folate and vitamin B12, Cd320 KO mice with selective B12 brain deficiency and H19-7 neuroprogenitors lacking folate. Compared with controls, N-homocysteinylated tau and MAP1 were increased and accumulated in protein aggregates and tangles in the cortex, hippocampus and cerebellum of patients and animals...
February 8, 2019: Journal of Pathology
https://read.qxmd.com/read/30734304/recent-advances-in-pathology-the-2019-annual-review-issue-of-the-journal-of-pathology
#5
EDITORIAL
C Simon Herrington, Richard Poulsom, Philip J Coates
In this Annual Review Issue of The Journal of Pathology, we present 15 invited reviews on topical aspects of pathology, ranging from the impacts of the microbiome in human disease through mechanisms of cell death and autophagy to recent advances in immunity and the uses of genomics for understanding, classifying and treating human cancers. Each of the reviews is authored by experts in their fields and our intention is to provide comprehensive updates in specific areas of pathology in which there has been considerable recent progress...
February 8, 2019: Journal of Pathology
https://read.qxmd.com/read/30734298/l-pgds-derived-pgd-2-attenuates-acute-lung-injury-by-enhancing-endothelial-barrier-formation
#6
Daiki Horikami, Naoki Toya, Koji Kobayashi, Keisuke Omori, Nanae Nagata, Takahisa Murata
Acute lung injury (ALI) is caused by various stimuli such as acid aspiration and infection, resulting in severe clinical outcomes with high mortality. Prostaglandin D2 (PGD2 ) is a lipid mediator produced in the lungs of patients with ALI. There are two prostaglandin D synthase (PGDS), namely, lipocalin-type PGDS (L-PGDS) and hematopoietic PGDS (H-PGDS). We previously reported the anti-inflammatory role of H-PGDS-derived PGD2 in an endotoxin-induced murine ALI model. Therefore, in this study, we investigated the role of L-PGDS-derived PGD2 in ALI in comparison to H-PGDS-derived PGD2 ...
February 8, 2019: Journal of Pathology
https://read.qxmd.com/read/30719704/multiregion-human-bladder-cancer-sequencing-reveals-tumour-evolution-bladder-cancer-phenotypes-and-implications-for-targeted-therapy
#7
Timon Heide, Angela Maurer, Monika Eipel, Katrin Knoll, Mirja Geelvink, Juergen Veeck, Ruth Knuechel, Julius van Essen, Robert Stoehr, Arndt Hartmann, Janine Altmueller, Trevor A Graham, Nadine T Gaisa
We present an evolutionary analysis of the relative time of genetic events underlying tumorigenesis in human bladder cancers from ten whole cystectomy specimens using multiregional whole exome sequencing. We timed bladder cancer drivers, mutational signatures, ploidy and copy number alterations, provided evidence for kataegis and correlated alterations with tumour areas and histological phenotypes. We found that: i) heterogeneous tumour areas/phenotypes had distinct driver mutations, ii) papillary-invasive tumours divided early into two parallel evolving branches, and iii) parallel evolution of subclonal driver mutations occurred...
February 4, 2019: Journal of Pathology
https://read.qxmd.com/read/30714168/f-box-protein-fbxo16-functions-as-a-tumor-suppressor-by-attenuating-nuclear-%C3%AE-catenin-function
#8
Debasish Paul, Sehbanul Islam, Rajesh Kumar Manne, U S Dinesh, Sunil K Malonia, Biswanath Maity, Ramanamurthy Boppana, Srikanth Rapole, Pravin Shetty, Manas Kumar Santra
Aberrant activation of β-catenin has been implicated in a variety of human diseases including cancer. In spite of significant progress, the regulation of active Wnt/β-catenin signaling pathway is still poorly understood. In this study, we show that F-box protein 16 (FBXO16) is a putative tumor suppressor. It is a component of SCF (SKP1-Cullin1-F-box protein) complex, which targets nuclear β-catenin protein for facilitating proteasomal degradation through the 26S proteasome. FBXO16 interacts physically with the C-terminal domain of β-catenin and promotes its lysine 48 linked polyubiquitination...
February 4, 2019: Journal of Pathology
https://read.qxmd.com/read/30714146/local-hyperthyroidism-promotes-pancreatic-acinar-cell-proliferation-during-acute-pancreatitis
#9
Ermanno Malagola, Rong Chen, Marta Bombardo, Enrica Saponara, Monica Dentice, Domenico Salvatore, Theresia Reding, Stephen Myers, Andrew P Hills, Rolf Graf, Sabrina Sonda
Proliferation of pancreatic acinar cells is a critical process in the pathophysiology of pancreatic diseases, because limited or defective proliferation is associated with organ dysfunction and patient morbidity. In this context, elucidating the signalling pathways that trigger and sustain acinar proliferation is pivotal to develop therapeutic interventions promoting the regenerative process of the organ. In this study we used genetic and pharmacological approaches to manipulate both local and systemic levels of thyroid hormones to elucidate their role in acinar proliferation following caerulein-mediated acute pancreatitis in mice...
February 4, 2019: Journal of Pathology
https://read.qxmd.com/read/30714167/plasma-epstein-barr-virus-dna-as-an-archetypal-circulating-tumour-dna-marker
#10
REVIEW
Wai Kei Jacky Lam, Kwan Chee Allen Chan, Yuk Ming Dennis Lo
Analysis of circulating tumour DNA (ctDNA), as one type of 'liquid biopsy', has recently attracted great attention. Researchers are exploring many potential applications of liquid biopsy in many different types of cancers. In particular, it is of biological interest and clinical relevance to study the molecular characteristics of ctDNA. For such purposes, plasma Epstein-Barr virus (EBV) DNA from patients with nasopharyngeal carcinoma (NPC) would provide a good model to understand the biological properties and clinical applications of ctDNA in general...
February 3, 2019: Journal of Pathology
https://read.qxmd.com/read/30714150/rn181-is-a-tumour-suppressor-in-gastric-cancer-by-regulation-of-the-erk-mapk-cyclin-d1-cdk4-pathway
#11
Suihai Wang, Xiaobo Wang, Yanjun Gao, Yingxia Peng, Ningning Dong, Qian Xie, Xian Zhang, Yingsong Wu, Ming Li, Ji-Liang Li
RN181, a RING finger domain-containing protein, is an E3 ubiquitin ligase. However, its biological function and clinical significance in cancer biology are obscure. Here, we report that RN181 expression is significantly down-regulated in 165 tumour tissues of gastric carcinoma (GC) versus adjacent non-tumour tissues, and inversely-associated with tumour differentiation, tumour size, clinical stage and patient's overall survival. Alterations of RN181 expression in GC cells by retrovirus-transduced up-regulation and down-regulation demonstrated that RN181 functions as a tumour suppressor to inhibit growth of GC in both in vitro culture and in vivo animal models by decreasing tumour cell proliferation and increasing tumour cell apoptosis...
February 3, 2019: Journal of Pathology
https://read.qxmd.com/read/30714148/the-pathological-features-of-regulated-necrosis
#12
REVIEW
Wulf Tonnus, Claudia Meyer, Alexander Paliege, Alexia Belavgeni, Anne von Mässenhausen, Stefan R Bornstein, Christian Hugo, Jan Ulrich Becker, Andreas Linkermann
Necrosis of a cell is defined by the loss of its plasma membrane integrity. Morphologically, necrosis occurs in several forms such as coagulative necrosis, colliquative necrosis, caseating necrosis, fibrinoid necrosis and others. Biochemically, necrosis was demonstrated to represent a number of genetically determined signalling pathways. These include i) kinase-mediated necroptosis, which depends on receptor interacting protein kinase 3 (RIPK3)-mediated phosphorylation of the pseudokinase mixed lineage kinase domain like (MLKL); ii) gasdermin-mediated necrosis downstream of inflammasomes, also referred to as pyroptosis; and iii) an iron-catalysed mechanism of highly specific lipid peroxidation named ferroptosis...
February 3, 2019: Journal of Pathology
https://read.qxmd.com/read/30697731/tbx3-promotes-progression-of-pre-invasive-breast-cancer-cells-by-inducing-emt-and-directly-up-regulating-slug
#13
Milica Krstic, Bart Kolendowski, Matthew J Cecchini, Carl O Postenka, Haider M Hassan, Joseph Andrews, Connor D MacMillan, Karla Williams, Hon S Leong, Muriel Brackstone, Joseph Torchia, Ann F Chambers, Alan B Tuck
The acquisition of cellular invasiveness by breast epithelial cells and subsequent transition from ductal carcinoma in situ (DCIS) to invasive breast cancer is a critical step in breast cancer progression. Little is known about the molecular dynamics governing this transition. We have previously shown that overexpression of the transcriptional regulator TBX3 in DCIS-like cells increases survival, growth and invasiveness. To explore this mechanism further and assess direct transcriptional targets of TBX3 in a high-resolution, isoform-specific context, we conducted genome-wide chromatin-immunoprecipitation arrays coupled with transcriptomic analysis...
January 29, 2019: Journal of Pathology
https://read.qxmd.com/read/30690729/genomic-profiling-of-combined-hepatocellular-cholangiocarcinoma-reveals-similar-genetics-to-hepatocellular-carcinoma
#14
Nancy M Joseph, Christos G Tsokos, Sarah E Umetsu, A Hunter Shain, Robin K Kelley, Courtney Onodera, Sarah Bowman, Eric Talevich, Linda D Ferrell, Sanjay Kakar, Gregor Krings
Combined hepatocellular-cholangiocarcinomas (CHC) are mixed tumours with both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) components. CHC prognosis is similar to intrahepatic cholangiocarcinoma (ICC) and worse than HCC, and staging and treatment generally follow ICC algorithms. However, the molecular biology of CHC remains poorly characterized. We performed capture-based next generation sequencing of 20 CHC and for comparison, 10 ICC arising in cirrhosis. Intratumour heterogeneity was assessed by separately sequencing the HCC and CC components of nine CHC...
January 28, 2019: Journal of Pathology
https://read.qxmd.com/read/30689202/bmi1-marks-gastric-stem-cells-located-in-the-isthmus-in-mice
#15
Takuto Yoshioka, Akihisa Fukuda, Osamu Araki, Satoshi Ogawa, Yuta Hanyu, Yoshihide Matsumoto, Yuichi Yamaga, Yuki Nakanishi, Kenji Kawada, Yoshiharu Sakai, Tsutomu Chiba, Hiroshi Seno
In the mammalian stomach, the isthmus has been considered as a stem cell zone. However, various locations and proliferative activities of gastric stem cells have been reported. We focused here on the stem cell marker Bmi1, a polycomb group protein, aiming to elucidate the characteristics of Bmi1-expressing cells in the stomach and to examine their stem cell potential. We investigated the Bmi1-expressing cell lineage in Bmi1-CreERT; Rosa26-YFP, LacZ, or Rosa26-Confetti mice. We examined the in vivo and ex vivo effects of Bmi1-expressing cell ablation by using Bmi1-CreERT; Rosa26-iDTR mice...
January 28, 2019: Journal of Pathology
https://read.qxmd.com/read/30684265/emerging-therapeutic-potential-of-group-2-innate-lymphoid-cells-in-acute-kidney-injury
#16
REVIEW
Guy J M Cameron, Simon H Jiang, Svenja Loering, Aniruddh V Deshpande, Philip M Hansbro, Malcolm R Starkey
Acute kidney injury remains a global challenge and, despite the availability of dialysis and transplantation, can be fatal. Those that survive an acute kidney injury are at increased risk of developing chronic kidney disease and end stage renal failure. Understanding the fundamental mechanisms underpinning the pathophysiology of acute kidney injury is critical for developing novel strategies for diagnosis and treatment. A growing body of evidence indicates that amplifying type 2 immunity may have therapeutic potential in kidney injury and disease...
January 25, 2019: Journal of Pathology
https://read.qxmd.com/read/30680732/the-innate-immune-architecture-of-lung-tumors-and-its-implication-in-disease-progression
#17
REVIEW
Simon Milette, Pierre O Fiset, Logan A Walsh, Jonathan D Spicer, Daniela F Quail
Lung malignancies are the leading cause of cancer-related mortality. By virtue of its unique physiological function, the lung microenvironment is highly dynamic and constantly subjected to mechanical, chemical and pathogenic stimuli. Thus, the airways rely on highly organized innate defense mechanisms to rapidly protect against pathogens and maintain pulmonary homeostasis. However, in the context of lung malignancy, these defenses often provide collateral inflammatory insults that can foster tumor progression...
January 25, 2019: Journal of Pathology
https://read.qxmd.com/read/30680725/hepatitis-c-virus-infection-induces-endoplasmic-reticulum-stress-and-apoptosis-in-human-fetal-liver-stem-cells
#18
Xuan Guo, Wei-Li Liu, Dong Yang, Zhi-Qiang Shen, Zhi-Gang Qiu, Min Jin, Jun-Wen Li
The cellular mechanisms by which Hepatitis C Virus (HCV) replication might mediate cytopathic effects are controversial and not entirely clear. In this study, we found that blood-borne HCV (bbHCV) infection could lead to endoplasmic reticulum (ER)-stress and mitochondria-related/caspase-dependent apoptosis at the early stages of infection based on use of the highly efficient blood-borne HCV (bbHCV) cell culture model established previously. Sections of bbHCV-infected human fetal liver stem cells (hFLSCs) revealed convolution and non-linear ER, cell vacuolization, swelling of mitochondria, and numerous double membrane vesicles (DMVs)...
January 24, 2019: Journal of Pathology
https://read.qxmd.com/read/30666658/regulation-of-s1pr2-by-the-ebv-oncogene-lmp1-in-aggressive-abc-subtype-diffuse-large-b-cell-lymphoma
#19
Martina Vockerodt, Katerina Vrzalikova, Maha Ibrahim, Eszter Nagy, Sandra Margielewska, Robert Hollows, Lauren Lupino, Reuben Tooze, Matthew Care, William Simmons, Alexandra Schrader, Tracey Perry, Maizaton Abdullah, Stephen Foster, Gary Reynolds, Alexander Dowell, Zbigniew Rudski, Daniel Krappmann, Dieter Kube, Ciaran Woodman, Wenbin Wei, Graham Taylor, Paul G Murray
The Epstein-Barr virus (EBV) is found almost exclusively in the activated B cell (ABC) subtype of diffuse large B cell lymphoma (DLBCL), yet its contribution to this tumour remains poorly understood. We have focussed on the EBV-encoded latent membrane protein-1 (LMP1), a constitutively activated CD40 homologue expressed in almost all EBV-positive DLBCL and which can disrupt germinal centre (GC) formation and drive lymphomagenesis in mice. Comparison of the transcriptional changes that follow LMP1 expression with those that follow transient CD40 signalling in human GC B cells enabled us to define pathogenic targets of LMP1 aberrantly expressed in ABC-DLBCL...
January 21, 2019: Journal of Pathology
https://read.qxmd.com/read/30666650/nsd2-circular-rna-promotes-metastasis-of-colorectal-cancer-by-targeting-mir-199b-5p-mediated-ddr1-and-jag1-signalling
#20
Liang-Yan Chen, Zheng Zhi, Lian Wang, Yuan-Yuan Zhao, Min Deng, Yu-Hong Liu, Yan Qin, Meng-Meng Tian, Yao Liu, Tong Shen, Li-Na Sun, Jian-Ming Li
Liver metastasis is the main cause of death in patients with colorectal cancer (CRC). Here, we searched for CRC metastasis associated circular RNA, in a mouse model of liver metastasis of CRC by using RNA (transcriptome)-sequencing. We identified a novel and conserved circular RNA, circ-NSD2, functioning as a promoter of CRC metastasis. Circ-NSD2 expression was elevated in CRC tissues, and was markedly increased in advanced stages or metastatic tumour of CRC patients. Gain-of-function and loss-of-function experiments demonstrated that circ-NSD2 promoted migration and metastasis of CRC in vitro and in vivo...
January 21, 2019: Journal of Pathology
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