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Journal of Pathology

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https://www.readbyqxmd.com/read/28816351/recent-advances-in-genomic-profiling-of-adenosquamous-carcinoma-of-the-pancreas
#1
Rebecca Marcus, Anirban Maitra, Jason Roszik
Adenosquamous carcinoma of the pancreas (ASCP) is a mixed tumor type which contains squamous cell carcinoma and also ductal adenocarcinoma components. Due to the rarity of this malignancy, only very limited genomic profiling has been performed. A recent paper by Fang et al. published in The Journal of Pathology contributed to our knowledge of genomic alterations by performing whole genome and exome sequencing of 17 ASCP tumors. They found major genomic similarities to pancreatic ductal adenocarcinoma; however, the p53 pathway was altered in a greater proportion of cases, while a high frequency of 3p loss was a distinct copy number alteration pattern observed in ASCP...
August 17, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28815607/a-3d-tri-culture-system-reveals-that-activin-receptor-like-kinase-5-and-connective-tissue-growth-factor-drive-human-glomerulosclerosis
#2
John P Waters, Yvonne C Richards, Jeremy N Skepper, Mark Southwood, Paul D Upton, Nicholas W Morrell, Jordan S Pober, John R Bradley
Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GEC), podocytes and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFβ, which has been implicated as an important mediator of glomerulosclerosis...
August 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28805995/germline-pms2-and-somatic-poleexo-mutations-cause-hypermutability-of-the-leading-dna-strand-in-biallelic-mismatch-repair-deficiency-syndrome-brain-tumors
#3
Andrianova Maria, Ghati Kasturirangan Chetan, Madathan Kandi Sibin, Thomas Mckee, Doron Merkler, Rao Kvl Narasinga, Pascale Ribaux, Jean-Louis Blouin, Periklis Makrythanasis, Vladimir B Seplyarskiy, Stylianos E Antonarakis, Sergey I Nikolaev
Biallelic Mismatch Repair Deficiency (bMMRD) in tumors is frequently associated with somatic mutations in the exonuclease domains of DNA polymerases POLE or POLD1 and results to a characteristic mutational profile. In this study we describe the genetic basis of ultramutated high grade brain tumors in the context of bMMRD. We performed exome sequencing of two second-cousin patients from a large consanguineous family of Indian origin with early onset of high grade glioblastoma and astrocytoma. We identified a germline homozygous nonsense variant R802X in the PMS2 gene...
August 14, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28802057/hmgb1-released-by-autophagic-cancer-associated-fibroblasts-maintains-the-stemness-of-luminal-breast-cancer-cells
#4
Xi-Long Zhao, Yong Lin, Jun Jiang, Zhuo Tang, Shuai Yang, Lu Lu, Yan Liang, Xue Liu, Jiao Tan, Xu-Gang Hu, Qin Niu, Wen-Juan Fu, Ze-Xuan Yan, De-Yu Guo, Yi-Fang Ping, Ji Ming Wang, Xia Zhang, Hsiang-Fu Kung, Xiu-Wu Bian, Xiao-Hong Yao
Cancer stem/initiating cells (CSCs/CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer associated fibroblasts (CAFs) are major components of the niche of breast cancer initiating cells (BCICs) and their interactions may profoundly affect breast cancer progression. Autophagy has been considered as a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance remains elusive...
August 12, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28799208/ccr2-monocytic-myeloid-derived-immunosuppressive-cells-m-mdsc-inhibit-collagen-degradation-and-promote-lung-fibrosis-by-producing-tgf-%C3%AE-1
#5
Astrid Lebrun, Sandra Lo Re, Mathilde Chantry, Xavier Izquierdo Carerra, Francine Uwambayinema, Doriana Ricci, Raynal Devosse, Saloua Ibouraadaten, Lisa Brombin, Mihaly Palmai-Pallag, Yousof Yakoub, Manolis Pasparakis, Dominique Lison, François Huaux
Monocytes infiltrating scar tissue are predominantly viewed as progenitor cells. Here, we show that tissue CCR2(+) monocytes possess specific immunosuppressive and pro-fibrotic functions. CCR2(+) monocytic cells are acutely recruited to the lung before the onset of silica-induced fibrosis in mice. These tissue monocytes are defined as monocytic-Myeloid-Derived Suppressor Cells (M-MDSC) because they significantly suppress T lymphocyte proliferation in vitro. M-MDSC collected from silica-treated mice also express TGF-β1, which stimulates lung fibroblasts to release TIMP-1, an inhibitor of metalloproteinase collagenolytic activity...
August 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28791728/smoking-is-associated-with-hypermethylation-of-the-apc-1a-promoter-in-colorectal-cancer-the-colocare-study
#6
Timothy M Barrow, Hagen Klett, Reka Toth, Jürgen Böhm, Biljana Gigic, Nina Habermann, Dominique Scherer, Petra Schrotz-King, Stephanie Skender, Clare Abbenhardt-Martin, Lin Zielske, Martin Schneider, Alexis Ulrich, Peter Schirmacher, Esther Herpel, Hermann Brenner, Hauke Busch, Melanie Boerries, Cornelia M Ulrich, Karin B Michels
Smoking tobacco is a known risk factor for the development of colorectal cancer, and for mortality associated with the disease. Smoking has been reported to be associated with changes in DNA methylation in blood and in lung tumour tissues, although there has been scant investigation of how epigenetic factors may be implicated in the increased risk of developing colorectal cancer. To identify epigenetic changes associated with smoking behaviours, we performed epigenome-wide analysis of DNA methylation in colorectal tumours from 36 never smokers, 47 former smokers and 13 active smokers, and adjacent mucosa from 49 never smokers, 64 former smokers and 18 active smokers...
August 9, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28791720/infectivity-in-bone-marrow-from-sporadic-cjd-patients
#7
Alvina Huor, Jean Yves Douet, Caroline Lacroux, Séverine Lugan, Cécile Tillier, Naima Aron, Hervé Cassard, Mark Arnold, Juan Maria Torres, James W Ironside, Olivier Andréoletti
Prion infectivity was recently identified in the blood of both sporadic and variant Creutzfeldt-Jakob disease (CJD) patients. In variant CJD (vCJD) the widespread distribution of prions in peripheral tissues of both asymptomatic and symptomatic patients is likely to explain the occurrence of the observed prionaemia. However, in sporadic CJD (sCJD) prion infectivity is described to be located principally in the central nervous system. In this study, we investigated the presence of prion infectivity in bone marrow collected after death in patients affected with different sCJD agents...
August 9, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28771750/comprehensive-t-cell-immunophenotyping-and-next-generation-sequencing-from-hpv-positive-and-negative-head-and-neck-squamous-cell-carcinomas
#8
Kate Poropatich, Joel Fontanarosa, Suchitra Swaminathan, Dave Dittmann, Siqi Chen, Sandeep Samant, Bin Zhang
The success of PD-1 inhibition in achieving a clinical response in a subset of HNSCC patients emphasizes the need to better understand the immunobiology of head and neck squamous cell carcinomas (HNSCC). Immunophenotyping was performed on 30 patients with HNSCC (16 HPV-positive, 14 HPV-negative) from matched tissue from the primary tumor site, locally metastatic cervical lymph nodes (LN), uninvolved local cervical LN and peripheral blood. CD4(+) and CD8(+) T cell lymphocytes obtained from tissue were analyzed for expression levels of inhibitory receptors PD-1, TIM-3 and CTLA-4...
August 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28771744/loss-of-sorting-nexin-5-stabilizes-internalized-growth-factor-receptors-to-promote-thyroid-cancer-progression
#9
Sumito Jitsukawa, Ryuta Kamekura, Koji Kawata, Fumie Ito, Akinori Sato, Hiroshi Matsumiya, Tomonori Nagaya, Keiji Yamashita, Terufumi Kubo, Tomoki Kikuchi, Noriyuki Sato, Tadashi Hasegawa, Hiroshi Kiyonari, Yoshiko Mukumoto, Ken-Ichi Takano, Tetsuo Himi, Shingo Ichimiya
Thyroid carcinoma is the most common endocrine malignancy and its prevalence has recently been increasing worldwide. We previously reported that the level of sorting nexin 5 (Snx5), an endosomal translocator, is preferentially decreased during the progression of well-differentiated thyroid carcinoma into poorly differentiated carcinoma. To address the functional role of Snx5 in the development and progression of thyroid carcinoma, we established Snx5-deficient (Snx5(-/-) ) mice. In comparison to wild-type (Snx5(+/+) ) mice, Snx5(-/-) mice exhibited enlarged thyroid glands that consisted of thyrocytes with large irregular-shaped vacuoles...
August 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28771739/endostatin-sensitizes-p53-deficient-non-small-cell-lung-cancer-to-genotoxic-chemotherapy-by-targeting-dna-pkcs
#10
Lin Jia, Xin-An Lu, Guanghua Liu, Shan Wang, Min Xu, Yang Tian, Shaosen Zhang, Yan Fu, Yongzhang Luo
Endostatin was discovered as an endogenous angiogenesis inhibitor with broad-spectrum antitumor activities. Although clinical efficacy was observed when combining endostatin with standard chemotherapy for non-small cell lung cancer (NSCLC), as well as other cancer types, the specific mechanisms underlying the benefit of endostatin are not completely understood. Extensive investigations suggest that endostatin is a multifunctional protein possessing more than anti-angiogenic activity. Here, we identified that endostatin exerts a direct chemosensitizing effect on p53-deficient tumor cells...
August 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28741662/molecular-breakdown-a-comprehensive-view-of-anaplastic-lymphoma-kinase-alk-rearranged-non-small-cell-lung-cancer
#11
Ka-Won Noh, Mi-Sook Lee, Seung Eun Lee, Ji-Young Song, Hyun-Tae Shin, Yu Jin Kim, Doo Yi Oh, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Young Mog Shim, Jae Ill Zo, Jhingook Kim, Woong-Yang Park, Se-Hoon Lee, Yoon-La Choi
Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how Echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors...
July 25, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28727149/aortic-microcalcification-associates-with-elastin-fragmentation-in-marfan-syndrome
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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