Reduced lysosomal clearance of autophagosomes promotes survival and colonization of Helicobacter pylori
The Journal of Pathology,Volume 244, Issue 4, Page 432-444, April 2018. (Source: The Journal of Pathology)
Source: The Journal of Pathology - January 12, 2018 Category: Pathology Source Type: research
Podocytes are new cellular targets of haemoglobin ‐mediated renal damage
In conclusion, podocytes take up Hb both in vitro and during intravascular haemolysis, promoting oxidative stress, podocyte dysfunction, and apoptosis. Nrf2 may be a potential therapeutic target to prevent loss of renal function in patients with intravascular haemolysis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. (Source: The Journal of Pathology)
Source: The Journal of Pathology - January 10, 2018 Category: Pathology Authors: Alfonso Rubio ‐Navarro, Maria Dolores Sanchez‐Niño, Melania Guerrero‐Hue, Cristina García‐Caballero, Eduardo Gutiérrez, Claudia Yuste, Ángel Sevillano, Manuel Praga, Javier Egea, Elena Román, Pablo Cannata, Rosa Ortega, Isabel Cortegano, Bel Tags: Original Paper Source Type: research
Targeting early PKC θ‐dependent T‐cell infiltration of dystrophic muscle reduces disease severity in a mouse model of muscular dystrophy
Abstract
Chronic muscle inflammation is a critical feature of Duchenne muscular dystrophy and contributes to muscle fibre injury and disease progression. Although previous studies have implicated T cells in the development of muscle fibrosis, little is known about their role during the early stages of muscular dystrophy. Here, we show that T cells are among the first cells to infiltrate mdx mouse dystrophic muscle, prior to the onset of necrosis, suggesting an important role in early disease pathogenesis. Based on our comprehensive analysis of the kinetics of the immune response, we further identify the early pre‐necroti...
Source: The Journal of Pathology - January 9, 2018 Category: Pathology Authors: Biliana Lozanoska ‐Ochser, Anna Benedetti, Giuseppe Rizzo, Valeria Marrocco, Rosanna Di Maggio, Piera Fiore, Marina Bouche Tags: Original Paper Source Type: research
Anti ‐oncostatin M antibody inhibits the pro‐malignant effects of oncostatin M receptor overexpression in squamous cell carcinoma
Abstract
The oncostatin M (OSM) receptor (OSMR) shows frequent gene copy number gains and overexpression in cervical squamous cell carcinomas (SCCs), associated with adverse clinical outcomes. In SCC cells that overexpress OSMR, the major ligand OSM induces multiple pro‐malignant effects, including invasion, secretion of angiogenic factors, and metastasis. Here, we demonstrate, for the first time, that OSMR overexpression in SCC cells activates cell‐autonomous feed‐forward signalling, via further expression of OSMR and OSM and sustained STAT3 activation, despite expression of the negative regulator suppressor of cyto...
Source: The Journal of Pathology - January 9, 2018 Category: Pathology Authors: Justyna A Kucia ‐Tran, Valtteri Tulkki, Cinzia G Scarpini, Stephen Smith, Maja Wallberg, Marta Paez‐Ribes, Angela M Araujo, Jan Botthoff, Maria Feeney, Katherine Hughes, Maria M Caffarel, Nicholas Coleman Tags: Original Paper Source Type: research
The emerging significance of secondary germline testing in cancer genomics
The Journal of Pathology,Volume 244, Issue 5, Page 610-615, April 2018. (Source: The Journal of Pathology)
Source: The Journal of Pathology - January 2, 2018 Category: Pathology Source Type: research
Translational control of aberrant stress responses as a hallmark of cancer
The Journal of Pathology,Volume 244, Issue 5, Page 650-666, April 2018. (Source: The Journal of Pathology)
Source: The Journal of Pathology - January 2, 2018 Category: Pathology Source Type: research
Translational control of aberrant stress responses as a novel hallmark of cancer
ABSTRACT
Altered mRNA translational control is emerging as a critical factor in cancer development and progression. Targeting specific elements of the translational machinery, such as mTORC1 or eIF4E, is emerging as a new strategy for innovative cancer therapy. While translation of most mRNAs takes place through cap‐dependent mechanisms, a sub‐population of cellular mRNA species, particularly stress‐inducible mRNAs with highly structured 5'‐UTR regions, are primarily translated through cap‐independent mechanisms. Intriguingly, many of these mRNAs encode proteins that are involved in tumour cell adaptation to micr...
Source: The Journal of Pathology - January 2, 2018 Category: Pathology Authors: Amal M El ‐Naggar, Poul H Sorensen Tags: Invited Review Source Type: research
Reduced lysosomal clearance of autophagosomes promotes survival and colonization of Helicobacter pylori
Abstract
Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection. Autophagy was assayed in H. pylori‐infected human gastric epithelium and the functional role of autophagy was determined via genetic or pharmacologic ablation of autophagy in mouse and cell line models of H. pylori infection. Here we showed that H. pylori inhibited lysosomal function and the...
Source: The Journal of Pathology - January 1, 2018 Category: Pathology Authors: Lin Zhang, Wei Hu, Chi H. Cho, Francis K. L. Chan, Jun Yu, J. Ross Fitzgerald, Cynthia K. Y. Cheung, Zhan G. Xiao, Jing Shen, Long F. Li, Ming X. Li, Justin C. Y. Wu, Thomas K. W. Ling, Jason Y. K. Chan, Ko Ho, Gary Tse, Siew C. Ng, Sidney Yu, Maggie H. T Tags: Original Paper Source Type: research
Role of Wnt Signalling in Advanced Prostate Cancer
Abstract
Recent next‐generation‐sequencing studies demonstrate that multiple pathways are often deregulated in advanced and metastatic prostate cancer (PC). In a recent issue of The Journal of Pathology, an elegant study by Jefferies et al used in vivo modelling to demonstrate how activation of the PI3K, WNT and MAPK pathway converges on mTORC1 signalling to drive aggressive disease. The study also highlights that approaches to target advanced PC require intelligent combination of agents to target single/multiple signalling pathways in combination with androgen receptor (AR) blockade. (Source: The Journal of Pathology)
Source: The Journal of Pathology - January 1, 2018 Category: Pathology Authors: Imran Ahmad, Owen J Sansom Tags: Invited Commentary Source Type: research
The emerging significance of secondary germline testing in cancer genomics
Abstract
Many clinical laboratories now sequence the tumors from advanced cancer patients to identify oncogenic drivers and guide targeted therapies and clinical trials. One limitation of tumor sequencing is that it cannot distinguish between tumor‐specific somatic (acquired) mutations and patients’ germline (constitutional) variants. To definitively identify somatic variants, some clinical labs sequence both a normal sample from a patient alongside their tumor to subtract the germline variants from the somatic variants. Having a paired normal sample also allows for the identification of secondary germline mutations in...
Source: The Journal of Pathology - January 1, 2018 Category: Pathology Authors: Diana Mandelker, Liying Zhang Tags: Invited Review Source Type: research
Pan ‐cancer insights from The Cancer Genome Atlas: the pathologist's perspective
ABSTRACT
The Cancer Genome Atlas (TCGA) represents one of several international consortia dedicated to performing comprehensive genomic and epigenomic analyses of selected tumor types to advance understanding of disease and provide an open‐access resource for worldwide cancer research. Thirty‐three tumor types (selected by histology or tissue of origin, to include both common and rare diseases), comprising over 11,000 specimens were subjected to DNA sequencing, copy number and methylation analysis, and transcriptomic, proteomic, and histologic evaluation. Each cancer type was analyzed individually to identify tissue‐...
Source: The Journal of Pathology - December 30, 2017 Category: Pathology Authors: Lee A.D. Cooper, Elizabeth G. Demicco, Joel H. Saltz, Reid T. Powell, Arvind Rao, Alexander J. Lazar Tags: Invited Review Source Type: research
PanCancer insights from The Cancer Genome Atlas: the pathologist's perspective
The Journal of Pathology,Volume 244, Issue 5, Page 512-524, April 2018. (Source: The Journal of Pathology)
Source: The Journal of Pathology - December 30, 2017 Category: Pathology Source Type: research
From Bad to Worse: When Lung Cancer Complicates Idiopathic Pulmonary Fibrosis
Abstract
Patients with idiopathic pulmonary fibrosis have a significantly increased risk for the development of lung cancer. The morbidity and mortality of this disease combination is substantial, and unfortunately, there is currently little data to help guide clinicians in its diagnosis and treatment. In a recent issue of this Journal, Hwang et al. present one of the first studies to evaluate lung cancer in idiopathic pulmonary fibrosis at the molecular level. They demonstrate variants in regulators of the cell cycle, which are known to be important in malignant transformation and may also be important in the pathogenesis...
Source: The Journal of Pathology - December 28, 2017 Category: Pathology Authors: Stephen B. Strock, Jonathan K. Alder, Daniel J. Kass Tags: Invited Commentary Source Type: research
MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB –NFIB fusion gene
In conclusion, we demonstrate that MYBL1 rearrangements and MYB amplification probably constitute alternative genetic drivers of breast AdCCs, functioning through MYBL1 or MYB overexpression. These observations emphasize that breast AdCCs probably constitute a convergent phenotype, whereby activation of MYB and MYBL1 and their downstream targets can be driven by the MYB–NFIB fusion gene, MYBL1 rearrangements, MYB amplification, or other yet to be identified mechanisms. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. (Source: The Journal of Pathology)
Source: The Journal of Pathology - December 28, 2017 Category: Pathology Authors: Jisun Kim, Felipe C Geyer, Luciano G Martelotto, Charlotte KY Ng, Raymond S Lim, Pier Selenica, Anqi Li, Fresia Pareja, Nicola Fusco, Marcia Edelweiss, Rahul Kumar, Rodrigo Gularte ‐Merida, Andre N Forbes, Ekta Khurana, Odette Mariani, Sunil Badve, Anne Tags: Brief Definitive Report Source Type: research
From bad to worse: when lung cancer complicates idiopathic pulmonary fibrosis
The Journal of Pathology,Volume 244, Issue 4, Page 383-385, April 2018. (Source: The Journal of Pathology)
Source: The Journal of Pathology - December 27, 2017 Category: Pathology Source Type: research
