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Journal of Pathology

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https://www.readbyqxmd.com/read/28097660/in-brief-myeloid-derived-suppressor-cells-in-cancer
#1
S Solito, L Pinton, S Mandruzzato
The role of myeloid-derived suppressor cells (MDSCs) in cancer development has become clear over recent years and MDSC targeting is an emerging opportunity for enhancing the effectiveness of current anti-cancer therapies. Since MDSCs are not only able to limit anti-tumour T cell responses, but also promote tumour angiogenesis and invasion, their monitoring has prognostic and predictive value. Herein we review the key features of MDSCs in cancer promotion.
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28097652/mdm4-is-a-rational-target-for-treating-breast-cancers-with-mutant-p53
#2
Panimaya Jeffreena Miranda, Daniel Buckley, Dinesh Raghu, Jia-Min B Pang, Elena A Takano, Reshma Vijayakumaran, Amina F A S Teunisse, Atara Posner, Tahlia Procter, Marco J Herold, Cristina Gamell, Jean-Christophe Marine, Stephen B Fox, Aart Jochemsen, Sue Haupt, Ygal Haupt
Mutation of the key tumour suppressor p53 defines a transition in the progression toward aggressive and metastatic breast cancer (BC) with the poorest outcome. Specifically, p53 mutation frequency exceeds 50% in Triple Negative BC (TNBC). Key regulators of mutant p53 that facilitate its oncogenic functions are potential therapeutic targets. We report here that the MDM4 protein is frequently abundant in the context of mutant p53 in basal-like BC samples. Importantly, we show that MDM4 plays a critical role in the proliferation of these BC cells...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28097645/bacterial-subversion-of-camp-signalling-inhibits-cathelicidin-expression-which-is-required-for-innate-resistance-to-mycobacterium-tuberculosis
#3
Shashank Gupta, Kathryn Winglee, Richard Gallo, William R Bishai
Antimicrobial peptides such as cathelicidins are an important component of innate immune defence against inhaled microorganisms and have demonstrated antimicrobial activity against Mycobacterium tuberculosis with in vitro models. Despite this, little is known about the regulation and expression of cathelicidin during tuberculosis in vivo. We sought to determine whether the cathelicidin-related antimicrobial peptide (Cramp) gene, the murine functional homologue of the human cathelicidin gene (CAMP or LL-37), is required for regulating protective immunity during M...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28054715/tubal-origin-of-ovarian-cancer-the-double-edged-sword-of-haemoglobin
#4
Shiou-Fu Lin, Emily Gerry, Ie-Ming Shih
Ovarian high-grade serous carcinoma (HGSC) is the most malignant neoplasm of the gynaecologic tract. While the origins of many human malignant neoplasms are clear, the origin of HGSC remains poorly understood. This lack of knowledge limits our understanding of its pathogenesis and compromises efforts devoted to develop better early detection tools and effective preventative intervention. The tubal origin of HGSC has been put forward since the initial report of dysplastic lesions (now known as serous tubal intraepithelial carcinomas, or STICs) that morphologically resemble HGSC in the fallopian tube...
January 5, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28054337/combined-mirna-profiling-and-proteomics-demonstrates-that-different-mirnas-target-a-common-set-of-proteins-to-promote-colorectal-cancer-metastasis
#5
Sofía Torres, Irene Garcia-Palmero, Rubén A Bartolomé, María Jesús Fernandez-Aceñero, Elena Molina, Eva Calviño, Miguel F Segura, J Ignacio Casal
The process of liver colonisation in colorectal cancer remains poorly characterised. Here, we addressed the role of microRNA (miRNA) dysregulation in metastasis. We first compared miRNA expression profiles between colorectal cancer cell lines with different metastatic properties and then identified target proteins of the dysregulated miRNAs to establish their functions and prognostic value. We found that 38 miRNAs were differentially expressed between highly metastatic (KM12SM/SW620) and poorly metastatic (KM12C/SW480) cancer cell lines...
January 5, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28039859/cholesterol-crystallisation-in-human-atherosclerosis-is-triggered-in-smooth-muscle-cells-during-the-transition-from-fatty-streak-to-fibroatheroma
#6
Benoît Ho-Tin-Noé, Sophie Vo, Richard Bayles, Stephen Ferrière, Hayette Ladjal, Sondes Toumi, Catherine Deschildre, Véronique Ollivier, Jean-Baptiste Michel
Recent studies have shown that in addition to being major constituents of the atheromatous core, solid cholesterol crystals (CCs) promote atherosclerotic lesion development and rupture by causing mechanical damage and exerting cytotoxic and pro-inflammatory effects. These findings suggest that targeting CCs might represent a therapeutic strategy for plaque stabilisation. However, little is known about how cholesterol crystallisation is initiated in human atherothrombotic disease. Here, we investigated these mechanisms...
December 31, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28035683/nuclear-inclusion-bodies-of-mutant-and-wild-type-p53-in-cancer-a-hallmark-of-p53-inactivation-and-proteostasis-remodeling-by-p53-aggregation
#7
Frederik De Smet, Mirian Saiz Rubio, Daphne Hompes, Evelyne Naus, Greet De Baets, Tobias Langenberg, Mark S Hipp, Bert Houben, Filip Claes, Sarah Charbonneau, Javier Delgado Blanco, Stephane Plaisance, Shakti Ramkissoon, Lori Ramkissoon, Colinda Simons, Piet van den Brandt, Matty Weijenberg, Manon Van England, Sandrina Lambrechts, Frederic Amant, André D'Hoore, Keith L Ligon, Xavier Sagaert, Joost Schymkowitz, Frederic Rousseau
Although p53 protein aggregates have been observed in cancer cell lines and tumour tissue, their impact in cancer remains largely unknown. Here, we extensively screened for p53 aggregation phenotypes in tumour biopsies and identified nuclear inclusion bodies (nIBs) of transcriptionally inactive mutant or wild-type p53 as the most frequent aggregation-like phenotype across six different cancer types. p53-positive nIBs co-stained with nuclear aggregation markers and shared molecular hallmarks of nIBs commonly found in neurodegenerative disorders...
December 30, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28035672/molecular-insights-into-tumour-metastasis-tracing-the-dominant-events
#8
REVIEW
Ke Jin, Tong Li, Hans van Dam, Fangfang Zhou, Long Zhang
Metastasis of malignant cells to vital organs remains the major cause of mortality in many types of cancers. The tumour invasion-metastasis cascade is a stepwise and multistage process whereby tumour cells disseminate from primary sites and spread to colonise distant sites through the systemic haematogenous or lymphatic circulations. The general steps of metastasis may be similar in almost all tumour types, but metastasis to different tissues seems to require distinct sets of regulators and/or an "educated" microenvironment which may facilitate the infiltration and colonisation of tumour cells to specific tissues...
December 30, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28026875/the-evidence-for-and-against-different-modes-of-tumour-cell-extravasation-in-the-lung-diapedesis-capillary-destruction-necroptosis-and-endothelialisation
#9
Sandor Paku, Viktoria Laszlo, Katalin Dezso, Peter Nagy, Mir Alireza Hoda, Walter Klepetko, Ferenc Renyi-Vamos, Jozsef Timar, Andrew R Reynolds, Balazs Dome
The development of lung metastasis is a significant negative prognostic factor for cancer patients. The extravasation phase of lung metastasis involves interactions of tumour cells with the pulmonary endothelium. These interactions may have broad biological and medical significance, with potential clinical implications ranging from the discovery of lung metastasis biomarkers to the identification of targets for intervention in preventing lung metastases. Because of the potential significance, the mechanisms of tumour cell extravasation require cautious, systematic studies...
December 27, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28026024/loss-of-dual-specificity-phosphatase-2-promotes-angiogenesis-and-metastasis-via-upregulation-of-interleukin-8-in-colon-cancer
#10
Shih-Chieh Lin, Kuei-Yang Hsiao, Ning Chang, Pei-Chi Hou, Shaw-Jenq Tsai
Dual-specificity phosphatase 2 (DUSP2) is a negative regulator of mitogen-activated protein kinases. Our previous study showed that DUSP2 expression is downregulated in many human cancers and loss of DUSP2 promotes cancer progression; however, the underlying mechanism remains largely uncharacterized. Herein, we found that loss of DUSP2 induces angiogenesis while forced expression of DUSP2 inhibits microvessel formation in xenografted mouse tumours. Genome-wide screening of expression profiles, and meta-analysis of clinical data, identified that the level of interleukin-8 (IL-8) correlated negatively with that of DUSP2, suggesting it may be a downstream target of DUSP2...
December 27, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28026023/effects-of-long-term-ethanol-consumption-and-aldh1b1-depletion-on-intestinal-tumourigenesis-in-mice
#11
Mike F Müller, Ying Zhou, David J Adams, Mark J Arends
Ethanol and its metabolite acetaldehyde have been classified as carcinogens for the upper aerodigestive tract, liver, breast and colorectum. Whereas mechanisms related to oxidative stress and Cyp2e1 induction seem to prevail in the liver, and acetaldehyde has been proposed to play a crucial role in the upper aerodigestive tract, pathological mechanisms in the colorectum have not yet been clarified. Moreover, all evidence for a pro-carcinogenic role of ethanol in colorectal cancer is derived from correlations observed in epidemiological studies or from rodent studies with additional carcinogen application or tumour suppressor gene inactivation...
December 27, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28026019/activating-the-akt2-nf%C3%AE%C2%BAb-lcn-2-axis-elicits-an-inflammatory-response-in-age-related-macular-degeneration
#12
Sayan Ghosh, Peng Shang, Meysam Yazdankhah, Imran Bhutto, Stacey Hose, Sandra R Montezuma, Tianqi Luo, Sreya Chattopadhyay, Jiang Qian, Gerard A Lutty, Deborah A Ferrington, J Samuel Zigler, Debasish Sinha
Age-related macular degeneration (AMD) is a complex and progressive degenerative eye disease resulting in severe loss of central vision. Recent evidence indicates that immune system dysregulation could contribute to the development of AMD. We hypothesize that defective lysosome-mediated clearance causes accumulation of waste products in the retinal pigmented epithelium (RPE), activating the immune system and leading to retinal tissue injury and AMD. We have generated unique genetically engineered mice in which lysosome-mediated clearance (both by phagocytosis and autophagy) in RPE cells is compromised, causing development of features of early AMD...
December 27, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28008607/microrna-320a-and-4496-attenuate-helicobacter-pylori-caga-induced-cancer-initiating-potential-and-chemo-resistance-by-targeting-%C3%AE-catenin-and-abcg2
#13
Dong Woo Kang, Eun Sun Yang, Yu Na Noh, Won Chan Hwang, Se-Young Jo, Young-Ah Suh, Won Sang Park, Kang-Yell Choi, Do Sik Min
Infection by Helicobacter pylori (H. pylori) is closely linked to increased risk of gastric cancer. Although CagA, a major virulence factor of H. pylori, is known to be a causal factor of gastric carcinogenesis, the molecular link between CagA and gastric cancer-initiating cell (CIC)-like properties remains elusive. Here, we demonstrate that CagA is required for increased expression of β-catenin and its target CIC markers via downregulation of microRNA (miR)-320a and miR-4496. CagA promotes gastric CIC properties and is responsible for chemo-resistance...
December 23, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28008606/derivation-of-marker-gene-signatures-from-human-skin-and-their-use-in-the-interpretation-trancriptional-changes-associated-with-dermatological-disorders
#14
Barbara Bo-Ju Shih, Ajit Johnson Nirmal, Denis John Headon, Arne Nalpon Akbar, Neil Andrew Mabbott, Tom Charles Freeman
Numerous studies have explored the altered transcriptional landscape associated with skin diseases to understand the nature of these disorders. However, data interpretation represents a significant challenge due to a lack of good maker sets for many of the specialised cell types that make up this tissue, whose composition may fundamentally alter during disease. Here we have sought to derive expression signatures that define the various cell types and structures that make up human skin, and demonstrate how they can be used to aid the interpretation of transcriptomic data derived from this organ...
December 23, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27990646/controversial-role-of-the-possible-oxyntic-stem-cell-marker-aspm-in-gastric-cancer
#15
LETTER
Fan Wang, Jin Li, Jing Liu, Qiu Zhao
We read with great interest the article by Vange et al in the December 2015 issue of The Journal of Pathology, as well as the subsequent commentary by Zhu et al in the January 2016 issue of The Journal of Pathology. We found the results of the study were controversial.
December 19, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27990644/author-reply-to-letter-to-the-editor-entitled-controversial-role-of-the-possible-oxyntic-stem-cell-marker-aspm-in-gastric-cancer-manuscript-id-16-892
#16
LETTER
Pål Vange, Torunn Bruland, Ingunn Bakke
No abstract text is available yet for this article.
December 19, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27981571/haematopoietic-prolyl-hydroxylase-1-deficiency-promotes-m2-macrophage-polarization-and-is-both-necessary-and-sufficient-to-protect-against-experimental-colitis
#17
Sophie Van Welden, Martine De Vos, Ben Wielockx, Simon J Tavernier, Melissa Dullaers, Sara Neyt, Benedicte Descamps, Lindsey Devisscher, Sarah Devriese, Lien Van den Bossche, Tom Holvoet, Ann Baeyens, Carmen Correale, Silvia D'Alessio, Christian Vanhove, Filip De Vos, Bruno Verhasselt, Georg Breier, Bart N Lambrecht, Sophie Janssens, Peter Carmeliet, Silvio Danese, Dirk Elewaut, Debby Laukens, Pieter Hindryckx
Prolyl hydroxylase domain-containing proteins (PHD) regulate the adaptation of cells to hypoxia. Pan-hydroxylase inhibition is protective in experimental colitis in which PHD1 plays a prominent role. However, it is currently unknown how PHD1 targeting regulates this protection and which cell type(s) are involved. Here we demonstrated that Phd1 deletion in endothelial and haematopoietic cells (Phd1(f/)(f) Tie2:cre) protected mice from dextran sulphate sodium (DSS)-induced colitis with reduced epithelial erosions, immune cell infiltration and colonic microvascular dysfunction, whereas the response of Phd2(f/+) Tie2:cre and Phd3(f/)(f) Tie2:cre mice to DSS was similar to their littermate controls...
December 16, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27976373/tumor-associated-macrophage-mediated-survival-of-myeloma-cells-through-stat3-activation
#18
Nathan De Beule, Kim De Veirman, Ken Maes, Elke De Bruyne, Eline Menu, Karine Breckpot, Hendrik De Raeve, Rian Van Rampelbergh, Jo A Van Ginderachter, Rik Schots, Els Van Valckenborgh, Karin Vanderkerken
Overcoming drug resistance is one of the greatest challenges in the treatment of multiple myeloma (MM). The interaction of myeloma cells with the bone marrow (BM) micro-environment is a major contributing factor to drug resistance. Tumor-associated macrophages or TAMs with different polarization states are an important component of this micro-environment. Previous studies revealed a role of TAMs in MM survival and drug resistance; however, the impact of macrophage polarization (anti-tumoral "M1" versus pro-tumoral "M2"-like phenotype) in this process is not yet described...
December 15, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27976371/apolipoprotein-c-i-plays-a-role-in-the-pathogenesis-of-glomerulosclerosis
#19
Pascal Bus, Louise Pierneef, Rosalie Bor, Ron Wolterbeek, Leendert A van Es, Patrick C N Rensen, Emile de Heer, Louis M Havekes, Jan A Bruijn, Jimmy F Berbée, Hans J Baelde
Diabetic nephropathy is the leading cause of end-stage renal disease. Diabetic patients have increased plasma concentrations of apolipoprotein C-I (apoCI), and meta-analyses found that a polymorphism in APOC1 is associated with an increased risk of developing nephropathy. To investigate whether overexpressing apoCI contributes to the development of kidney damage, we studied renal tissue and peritoneal macrophages from APOC1 transgenic (APOC1-tg) mice and wild-type littermates. In addition, we examined renal autopsy material from diabetic patients with and without diabetic nephropathy and from control subjects...
December 15, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27976366/proteomic-signatures-reveal-a-dualistic-and-clinically-relevant-classification-of-anal-canal-carcinoma
#20
Michael Herfs, Rémi Longuespée, Charles M Quick, Patrick Roncarati, Meggy Suarez-Carmona, Pascale Hubert, Alizée Lebeau, Diane Bruyere, Gabriel Mazzucchelli, Nicolas Smargiasso, Dominique Baiwir, Keith Lai, Andrew Dunn, Fabiola Obregon, Eric J Yang, Edwin De Pauw, Christopher P Crum, Philippe Delvenne
Etiologically linked to HPV infection, malignancies of the anal canal have substantially increased in incidence over the last 20 years. Although most anal squamous cell carcinomas (SCC) respond well to chemoradiotherapy, about 30% of patients experience a poor outcome, for undetermined reasons. Despite cumulative efforts for discovering independent predictors of overall survival, both nodal status and tumour size are still the only reliable factors predicting patient outcome. Recent efforts have revealed that the biology of HPV-related lesions in the cervix is strongly linked to the originally infected cell population...
December 15, 2016: Journal of Pathology
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