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Journal of Pathology

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https://www.readbyqxmd.com/read/28727149/aortic-microcalcification-associates-with-elastin-fragmentation-in-marfan-syndrome
#1
Shaynah A Wanga, Stijntje Hibender, Yanto Ridwan, Cindy van Roomen, Mariska Vos, Ingeborg van der Made, Nicole van Vliet, Romy Franken, Luigi Amjg van Riel, Maarten Groenink, Aeilko H Zwinderman, Barbara Jm Mulder, Carlie Jm de Vries, Jeroen Essers, Vivian de Waard
Marfan syndrome (MFS) is a connective tissue disorder, in which aortic rupture is the major cause of death. MFS patients with an aortic diameter below the advised limit for prophylactic surgery (<5cm) may unexpectedly experience an aortic dissection or rupture, despite yearly monitoring. Hence, there is a clear need for improved prognostic markers to predict such aortic events. We hypothesize that elastin fragments play a causal role in aortic calcification in MFS and that microcalcification serves as a marker for aortic disease severity...
July 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28727142/genomic-and-transcriptomic-heterogeneity-of-colorectal-tumors-arising-in-lynch-syndrome
#2
Hans Binder, Lydia Hopp, Michal R Schweiger, Steve Hoffmann, Frank Jühling, Martin Kerick, Bernd Timmermann, Susann Siebert, Christina Grimm, Lilit Nersisyan, Arsen Arakelyan, Maria Herberg, Peter Buske, Henry Loeffler-Wirth, Maciej Rosolowski, Christoph Engel, Jens Przybilla, Martin Peifer, Nicolaus Friedrichs, Gabriela Moeslein, Margarete Odenthal, Michelle Hussong, Sophia Peters, Stefanie Holzapfel, Jacob Nattermann, Robert Hueneburg, Wolff Schmiegel, Brigitte Royer-Pokora, Stefan Aretz, Michael Kloth, Matthias Kloor, Reinhard Buettner, Jörg Galle, Markus Loeffler
Colorectal cancer (CRC) arising in Lynch Syndrome (LS) comprises tumors with constitutional mutations in DNA mismatch-repair genes. Whole-genome and transcriptome studies of LS-CRC are still missing to address questions about similarities and differences of mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch-repair in LS colonic mucosa and the possible role of immune editing...
July 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28722204/loss-of-the-tumor-suppressor-gene-aip-mediates-the-browning-of-human-brown-fat-tumors
#3
Linda Magnusson, Nils Hansen, Karim H Saba, Jenny Nilsson, Thoas Fioretos, Pehr Rissler, Karolin H Nord
Human brown fat tumors (hibernomas) display concomitant loss of the tumor suppressor genes MEN1 and AIP. In the present study, we hypothesized that the brown fat phenotype is attributed to these mutations. Accordingly, we demonstrate that silencing of AIP in human brown preadipocytic and white fat cell lines results in the induction of the brown fat marker UCP1. In human adipocytic tumors, loss of MEN1 was found both in white (one out of 51 lipomas) and brown fat tumors. In contrast, concurrent loss of AIP was always accompanied by a brown fat morphology...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28722124/pancreatic-undifferentiated-carcinoma-with-osteoclast-like-giant-cells-is-genetically-similar-to-but-clinically-distinct-from-conventional-ductal-adenocarcinoma
#4
Claudio Luchini, Antonio Pea, Gemma Lionheart, Andrea Mafficini, Alessia Nottegar, Nicola Veronese, Peter Chianchiano, Lodewijk A A Brosens, Michaël Noë, G Johan A Offerhaus, Raluca Yonescu, Yi Ning, Giuseppe Malleo, Giulio Riva, Paola Piccoli, Ivana Cataldo, Paola Capelli, Giuseppe Zamboni, Aldo Scarpa, Laura D Wood
Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGC, including the whole exome sequencing of 8 UCOGC. We observed that 60% of the UCOGC contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28722118/at2-r-deficiency-mediated-podocyte-loss-via-activation-of-ectopic-hedgehog-interacting-protein-hhip-gene-expression
#5
Min-Chun Liao, Xin-Ping Zhao, Shiao-Ying Chang, Chao-Sheng Lo, Isabelle Chenier, Tomoko Takano, Julie R Ingelfinger, Shao-Ling Zhang
Angiotensin II type 2 receptor (AT2 R) deficiency in AT2 R knockout (KO) mice has been linked to congenital abnormalities of the kidney and urinary tract; however, the mechanisms by which this occurs are poorly understood. In this study, we examined whether AT2 R deficiency impaired glomerulogenesis and mediated podocyte loss/dysfunction in vivo and in vitro. Nephrin-cyan fluorescent protein (CFP)-transgenic (Tg) and Nephrin/AT2 RKO mice were used to assess glomerulogenesis, while wild-type and AT2 RKO mice were used to evaluate maturation of podocyte morphology/function...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28722111/monoamine-oxidase-a-is-highly-expressed-in-classical-hodgkin-lymphoma
#6
Pei Chuan Li, Imran N Siddiqi, Anja Mottok, Eric Y Loo, Chieh Hsi Wu, Wendy Cozen, Christian Steidl, Jean Chen Shih
Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines and produces H2 O2. It facilitates the progression of gliomas and prostate cancer, but its expression and functional relevance have not been studied in lymphoma. Here, we evaluated MAOA in 427 cases of Hodgkin and non-Hodgkin lymphoma and in a spectrum of reactive lymphoid tissues by immunohistochemistry on formalin-fixed paraffin-embedded specimens. MAOA was expressed by Hodgkin Reed-Sternberg (HRS) cells in the majority of classical Hodgkin lymphomas (cHL) (181/241; 75%), with 34...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28722109/genomic-signatures-of-adenosquamous-carcinoma-of-the-pancreas-pasc
#7
Yuan Fang, Zhe Su, Jing Xie, Ruidong Xue, Qi Ma, Yanmeng Li, Yifan Zhao, Zeshi Song, Xiongxiong Lu, Hongwei Li, Chenghong Peng, Bai Fan, Baiyong Shen
In pancreatic cancer (PC), adenosquamous carcinoma of the pancreas (PASC) containing both ductal adenocarcinoma and squamous carcinoma in the same tumor represents ~ 4% of the total incidence. To date, the genomic features of this mixed tumor are still unknown. We analyzed genomes of 17 PASCs and 34 ductal adenocarcinomas (PDACs), showing that PASC carried highly enriched TP53 mutations and 3p loss compared to PDAC. Furthermore, we uncovered that adenomatous and squamous components of PASC harbored comparable genomic alterations, suggesting that two cellular components are developed from the same progenitor cancer cells...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28722107/the-peritoneum-healing-immunity-and-diseases
#8
REVIEW
Annalisa Capobianco, Lucia Cottone, Antonella Monno, Angelo A Manfredi, Patrizia Rovere-Querini
The peritoneum defines a confined microenvironment, which is stable under normal conditions, but is exposed to the damaging effect of infections, surgical injuries, and other neoplastic and non-neoplastic events. Its response to damage includes the recruitment, proliferation and activation of a variety of haematopoietic and stromal cells. In physiologic conditions, effective responses to injuries are organized, inflammatory triggers are eliminated, inflammation quickly abates, and the normal tissue architecture is restored...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28718916/the-genetic-landscape-of-endometrial-clear-cell-carcinomas
#9
Deborah F DeLair, Kathleen A Burke, Pier Selenica, Raymond S Lim, Sasinya N Scott, Sumit Middha, Abhinita S Mohanty, Donavan T Cheng, Michael F Berger, Robert A Soslow, Britta Weigelt
Clear cell carcinoma of the endometrium is a rare type of endometrial cancer generally associated with an aggressive clinical behavior. Here we sought to define the repertoire of somatic genetic alterations in endometrial clear cell carcinomas (ECCs) and whether ECCs could be classified into the molecular subtypes described for endometrial endometrioid and serous carcinomas. We performed a rigorous histopathological review, immunohistochemical analysis and massively parallel sequencing targeting 300 cancer-related genes of 32 pure ECCs...
July 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28707808/cytotoxic-necrotizing-factor-1-promotes-prostate-cancer-progression-through-activating-the-cdc42-pak1-axis
#10
Yaxiu Guo, Zhisong Zhang, Huiting Wei, Jingyu Wang, Junqiang Lv, Kai Zhang, Evan T Keller, Zhi Yao, Quan Wang
Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections and plays a role in prostatic carcinogenesis and prostate cancer (PCa) progression. However, the mechanisms through which UPEC promotes PCa development and progression are unclear. Cytotoxic necrotizing factor 1 (CNF1) is one of the most important UPEC toxins and its role in PCa progression has never been studied. We found that UPEC-secreted CNF1 promoted the migration and invasion of PCa cells and PCa metastasis. In vitro studies showed that CNF1 promotes pro-migratory and pro-invasive activity through entering PCa cells and activating Cdc42, which subsequently induced PAK1 phosphorylation and upregulation of MMP-9 expression...
July 14, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28707729/sox11-promotes-invasive-growth-and-dcis-progression
#11
Erik Oliemuller, Naoko Kogata, Philip Bland, Divya Kriplani, Frances Daley, Syed Haider, Vandna Shah, Elinor J Sawyer, Beatrice A Howard
Here, we show that SOX11, an embryonic mammary marker, normally silent in postnatal breast cells, is expressed in many ER-negative (ER-) preinvasive DCIS lesions. Mature mammary epithelial cells engineered to express SOX11 displayed alterations in progenitor cell populations, including an expanded basal-like population with increased ALDH activity, and increased mammosphere-forming capacity. DCIS.com cells engineered to express SOX11 displayed increased ALDH activity, a feature of cancer stem cells. The CD44+/CD24-/ALDH+ cell population was increased in DCIS...
July 14, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28696069/hcc-associated-single-nucleotide-variants-and-deletions-identified-using-genome-wide-high-throughput-analysis-of-hbv
#12
Wen-Chun Liu, I-Chin Wu, Yen-Chien Lee, Chih-Peng Lin, Ji-Hong Cheng, Yih-Jyh Lin, Chia-Jui Yen, Pin-Nan Cheng, Pei-Fu Li, Yi-Ting Cheng, Pei-Wen Cheng, Koun-Tem Sun, Shu-Ling Yan, Jia-Jhen Lin, Jui-Chu Yang, Kung-Chao Chang, Cheng-Hsun Ho, Vincent S Tseng, Bill Chia-Han Chang, Jaw-Ching Wu, Ting-Tsung Chang
This study investigated hepatitis B virus (HBV) single nucleotide variants (SNVs) and deletion mutations linked with hepatocellular carcinoma (HCC). Ninety-three HCC patients and 108 non-HCC patients were enrolled for HBV genome-wide next-generation sequencing (NGS) analysis. Systemic literature review and meta-analysis were performed to validate NGS-defined HCC-associated SNVs and deletions. The experimental results identified 60 NGS-defined HCC-associated SNVs, including 41 novel SNVs, and their pathogenic frequencies...
July 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28682481/significant-association-between-tnfaip3-inactivation-and-biased-ighv4-34-usage-in-malt-lymphoma
#13
Sarah Moody, Leire Escudero-Ibarz, Ming Wang, Alexandra Clipson, Eguzkine Ochoa Ruiz, Deborah Dunn-Walters, Xuemin Xue, Naiyan Zeng, Alistair Robson, Shih-Sung Chuang, Sergio Cogliatti, Hongxiang Liu, John Goodlad, Margaret Ashton-Key, Markus Raderer, Yingwen Bi, Ming-Qing Du
Both antigenic drive and genetic change play a critical role in the development of mucosa-associated lymphoid tissue (MALT) lymphoma [EdQ please check change], but neither alone is sufficient for malignant transformation, and lymphoma development critically depends on their cooperation. However, which of these different events concur and how they cooperate in MALT lymphomagenesis is totally unknown. To explore this, we investigated somatic mutations of 17 genes and immunoglobulin heavy chain variable region (IGHV) [EdQ please check change]usage in 179 MALT lymphomas from various sites...
July 6, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28678427/clear-cell-and-endometrioid-carcinomas-are-their-differences-attributable-to-distinct-cells-of-origin
#14
Dawn R Cochrane, Basile Tessier-Cloutier, Katherine M Lawrence, Tayyebeh Nazeran, Anthony N Karnezis, Clara Salamanca, Angela S Cheng, Jessica N McAlpine, Lien N Hoang, C Blake Gilks, David G Huntsman
Endometrial epithelium is the presumed tissue of origin for both eutopic and endometriosis-derived clear cell and endometrioid carcinomas. We had previously hypothesized that the morphological, biological and clinical differences between these carcinomas are due to histotype-specific mutations. Although some mutations and genomic landscape features are more likely to be found in one of these histotypes, we were not able to identify a single class of mutations that was exclusively present in one histotype and not the other...
July 5, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28678391/interferon-lambda1-il-29-and-inorganic-polyphosphate-are-novel-regulators-of-neutrophil-driven-thromboinflammation
#15
Akrivi Chrysanthopoulou, Konstantinos Kambas, Dimitrios Stakos, Ioannis Mitroulis, Alexandros Mitsios, Veroniki Vidali, Iliana Angelidou, Magdalena Bochenek, Stella Arelaki, Athanasios Arampatzioglou, Ioanna-Evdokia Galani, Panagiotis Skendros, Elias A Couladouros, Stavros Konstantinides, Evangelos Andreakos, Katrin Schäfer, Konstantinos Ritis
Neutrophils and neutrophil-released meshwork structures termed neutrophil extracellular traps (NETs) are major mediators of thromboinflammation and emerging targets for therapy, yet the mechanisms and pathways that control the role of neutrophils in thromboinflammation remain poorly understood. Here, we explored the role of IFN-λ1/IL-29, a major antiviral cytokine recently shown to suppress the neutrophil migratory capacity, in prothrombotic and proNETotic functions of neutrophils. In an ex vivo human experimental setting of acute ST-segment elevation myocardial infarction (STEMI), we show that IFN-λ1/IL-29 hinders NET release and diminishes the amount of cytoplasmic TF in neutrophils...
July 5, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28678347/trap1-controls-cell-cycle-g2-m-transition-through-the-regulation-of-cdk1-and-mad2-expression-ubiquitination
#16
Lorenza Sisinni, Francesca Maddalena, Valentina Condelli, Giuseppe Pannone, Vittorio Simeon, Valeria Li Bergolis, Elvira Lopes, Annamaria Piscazzi, Danilo Swann Matassa, Carmela Mazzoccoli, Filomena Nozza, Giacomo Lettini, Maria Rosaria Amoroso, Pantaleo Bufo, Franca Esposito, Matteo Landriscina
Regulation of tumor cell proliferation by molecular chaperones is still a complex issue. Here, the role of the HSP90 molecular chaperone TRAP1 in cell cycle regulation was investigated in a wide range of human breast, colorectal and lung carcinoma cell lines and tumor specimens. TRAP1 modulates the expression and/or the ubiquitination of key cell cycle regulators through a dual mechanism: i) a transcriptional regulation of CDK1, CYCLIN B1 and MAD2, as suggested by a gene expression profiling of TRAP1-silenced breast carcinoma cells, and ii) a post-transcriptional quality control of CDK1 and MAD2, being the ubiquitination of these two proteins enhanced upon TRAP1 downregulation...
July 5, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28671736/overexpression-of-pcdhb9-promotes-peritoneal-metastasis-and-correlates-with-poor-prognosis-in-patients-with-gastric-cancer
#17
Shoichiro Mukai, Naohide Oue, Takashi Oshima, Takeharu Imai, Yohei Sekino, Ririno Honma, Naoya Sakamoto, Kazuhiro Sentani, Hiroki Kuniyasu, Hiroyuki Egi, Kazuaki Tanabe, Kazuhiro Yoshida, Hideki Ohdan, Wataru Yasui
Gastric cancer (GC) is one of the most common human cancers. Genes expressed only in cancer tissue, especially on the cell membrane, may be useful biomarkers for cancer diagnosis and therapeutics. In the present study, we focused on the PCDHB9 gene, which encodes transmembrane protein protocadherin B9. Immunohistochemical analysis revealed that 62 (36%) of 173 GC cases were positive for protocadherin B9. Protocadherin B9 staining was mainly observed on GC cell membrane. Expression of protocadherin B9 was frequently found in intestinal type GC and correlated with poor prognosis in patients with intestinal type GC...
July 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28671728/clonality-analysis-of-synchronous-gastroesophageal-junction-carcinoma-and-distal-gastric-cancer-by-whole-exome-sequencing
#18
Xiaofang Xing, Shuqin Jia, Jianmin Wu, Qin Feng, Bin Dong, Bo Li, Yongning Jia, Fei Shan, Ying'ai Li, Yan Zhang, Ying Hu, Xiaodong Wang, Xiangtao Liu, Shiwei Yu, Lianhai Zhang, Zhaode Bu, Aiwen Wu, Ziyu Li, Jiafu Ji
Gastroesophageal junction (GEJ) carcinoma and distal gastric cancer (GC) have distinct epidemiology and clinical features and their relationship is uncertain. Synchronous multiple gastric cancers located mostly at proximal and distal sites provide rare specimens for investigating the comprehensive genomic relationships among these cancers in the context of identical genetic circumstances. Formalin-fixed, paraffin-embedded (FFPE) samples from 12 patients with synchronous GEJ carcinoma and distal GC were collected in this study...
July 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28657664/conditional-abrogation-of-transforming-growth-factor-beta-receptor-1-in-pten-inactivated-endometrium-promotes-endometrial-cancer-progression-in-mice
#19
Yang Gao, Pengfei Lin, John P Lydon, Qinglei Li
Although a putative role for TGF beta (TGFB) signaling in the pathogenesis of human endometrial cancer has long been proposed, the precise function of TGFB signaling in the development and progression of endometrial cancer remains elusive. Depletion of PTEN in the mouse uterus causes endometrial cancer. To identify the potential role of TGFB signaling in endometrial cancer, we simultaneously deleted TGFB receptor 1 (Tgfbr1) and Pten in the mouse uterus using Cre-recombinase driven by the progesterone receptor (termed Pten(d/d) ; Tgfbr1(d/d) )...
June 28, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28657654/quantitative-proteomics-identifies-altered-o-glcnacylation-of-structural-synaptic-and-memory-associated-proteins-in-alzheimer-s-disease
#20
Sheng Wang, Feng Yang, Vladislav A Petyuk, Anil K Shukla, Matthew E Monroe, Marina A Gritsenko, Karin D Rodland, Richard D Smith, Wei-Jun Qian, Cheng-Xin Gong, Tao Liu
Protein modification by O-linked beta-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer's disease, however detailed molecular characterization of this important protein posttranslational modification at proteome level has been highly challenging, due to its low stoichiometry and labile nature. Herein we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in post-mortem human brain tissues with and without Alzheimer's disease using isobaric tandem mass tags labeling, chemoenzymatic photocleavage enrichment and liquid chromatography coupled to mass spectrometry...
June 28, 2017: Journal of Pathology
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