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Journal of Pathology

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https://www.readbyqxmd.com/read/29023722/prevalence-and-clonality-of-synchronous-primary-carcinomas-in-the-bladder-and-prostate
#1
Ying Jing, Ruiyun Zhang, Pengfei Ma, Mei-Chun Cai, Guanglei Zhuang, Haige Chen
Incidental prostate adenocarcinoma (IPCa) has been frequently discovered during postoperative histopathological evaluation of radical cystoprostatectomy specimens in patients with bladder cancer (BCa). However, there is currently no conclusive study addressing the clinical significance of IPCa and the clonal relatedness of IPCa and BCa. Here, we performed a retrospective single-center review of 919 BCa cases and an additional meta-analysis including a total of 19,868 individuals who underwent radical cystectomy for bladder cancer...
October 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28991374/synaptopodin-2-suppresses-metastasis-of-triple-negative-breast-cancer-via-inhibition-of-yap-taz-activity
#2
Junling Liu, Liping Ye, Qingyuan Li, Xianqiu Wu, Bin Wang, Ying Ouyang, Zhongyu Yuan, Jun Li, Chuyong Lin
Triple negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer with a high incidence of distant metastasis; however, the underlying mechanism for this frequent recurrence remains unclear. Herein, we find that Synaptopodin 2, a putative tumor suppressor in aggressive cancer, is frequently downregulated in TNBC by methylation of the promoter of SYNPO2. Low expression levels of SYNPO2 correlated significantly with 5-year metastatic relapse, and predicted poorer prognosis in breast cancer patients...
October 9, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28991373/novel-enriched-pathways-in-superficial-malignant-peripheral-nerve-sheath-tumors-mpnst-and-spindle-desmoplastic-melanomas-sdm
#3
George Jour, Nicole K Andeen, Rami Al -Rohil, Phyu P Aung, Meenakshi Mehrotra, Dzifa Duose, Benjamin Hoch, Zolt Argenyi, Rajyalakshmi Luthra, Ignacio I Wistuba, Victor G Prieto
Superficial malignant peripheral nerve sheath tumor (MPNST) is a rare, soft tissue neoplasm that shares morphological features and some molecular events with spindle and desmoplastic melanoma (SDM). Herein we sought to identify molecular targets for therapy using targeted RNA/DNA sequencing and gene expression of key immunological players. DNA and RNA from formalin-fixed, paraffin-embedded (FFPE) tissue were extracted and processed. Massive high-throughput deep parallel sequencing was performed using the Oncomine comprehensive panel enabling detection of relevant SNVs, CNVs, gene fusions, and indels from 143 unique genes on the Ion torrent sequencer for clinical trial research programs...
October 9, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28991363/microrna-495-3p-functions-as-a-tumour-suppressor-by-regulating-multiple-epigenetic-modifiers-in-gastric-carcinogenesis
#4
Jung Woo Eun, Hyung Seok Kim, Qingyu Shen, Hee Doo Yang, Sang Yean Kim, Jung Hwan Yoon, Won Sang Park, Jung Young Lee, Suk Woo Nam
MicroRNAs (miRNAs) engage in complex interactions with the machinery that controls the transcriptome and concurrently target multiple mRNAs. Here we demonstrate that microRNA-495-3p (miR-495-3p) functions as a potent tumour suppressor by governing ten oncogenic epigenetic modifiers (EMs) in gastric carcinogenesis. From the large cohort transcriptome datasets of gastric cancer (GC) patients available from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), we were able to recapitulate fifteen EMs as significantly overexpressed in GC among the 51 EMs that were previously reported to be involved in cancer progression...
October 9, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28981147/reduced-cerebral-vascularisation-in-experimental-neuronopathic-gaucher-disease
#5
Nicholas J C Smith, Maria Fuller, Jennifer T Saville, Timothy M Cox
The glycosphingolipidosis of Gaucher disease, in which a range of neurological manifestations occur, results from a deficiency of acid β-glucocerebrosidase, with subsequent accumulation of β-glucocerebroside, its upstream substrates and the non-acylated congener, β-glucosylsphingosine. However, the mechanisms by which end-organ dysfunction arise are poorly understood. Here we report strikingly diminished cerebral microvascular density in a murine model of disease and provide a detailed analysis of the accompanying cerebral glycosphingolipidome in these animals, with marked elevations of β-glucosylsphingosine...
October 5, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28944962/hpv-e6-protein-enriches-the-cd55-population-in-cervical-cancer-cells-promoting-radio-resistance-and-cancer-aggressiveness
#6
Thomas Ho-Yin Leung, Hermit Wai-Man Tang, Michelle Kwan-Yee Siu, David Wai Chan, Karen Kar-Loen Chan, Annie Nga-Yin Cheung, Hextan Yuen-Sheung Ngan
Accumulating evidence indicates that the human papilloma virus (HPV) E6 protein plays a crucial role in the development of cervical cancer. Sub-populations of cells that reside within tumors are responsible for tumor resistance to cancer therapy and recurrence. However, the identity of such cells residing in cervical cancer and their relationship with the HPV-E6 protein have not been identified. Here, we isolated sphere-forming cells, which exhibited self-renewal ability, from primary cervical tumors. Gene expression profiling revealed that CD55 was upregulated in primary cervical cancer sphere cells...
September 25, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28940516/analysis-of-clonal-expansions-through-the-normal-and-premalignant-human-breast-epithelium-reveals-the-presence-of-luminal-stem-cells
#7
Biancastella Cereser, Marnix Jansen, Emily Austin, George Elia, Taneisha McFarlane, Carolien Hm van Deurzen, Anieta M Sieuwerts, Maria G Daidone, Paul J Tadrous, Nicholas A Wright, Louise Jones, Stuart Ac McDonald
It is widely accepted that the cell of origin of breast cancer is the adult mammary epithelial stem cell, however demonstrating the presence and location of tissue stem cells in the human breast has proved difficult. Furthermore, we do not know the clonal architecture of the normal and premalignant mammary epithelium or its cellular hierarchy. Here we use deficiency in the mitochondrial enzyme cytochrome c oxidase (CCO), typically caused by somatic mutations in the mitochondrial genome, as a means to perform lineage tracing in the human mammary epithelium...
September 22, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28940209/chronic-psychological-stress-promotes-lung-metastatic-colonization-of-circulating-breast-cancer-cells-by-decorating-a-pre-metastatic-niche-through-activating-%C3%AE-adrenergic-signaling
#8
Hongyu Chen, Dan Liu, Liang Guo, Xiang Cheng, Ning Guo, Ming Shi
Numerous studies have indicated that primary tumors induce formation of a pre-metastatic niche in distant organs by secreting tumor-derived factors. The present study shows that pre-exposure to chronic stress enhanced lung colonization efficiency by circulating tumor cells, suggesting that chronic stress critically influences pre-metastatic lungs before arrival of disseminated tumor cells. Ablation of the sympathetic nerve function by 6-OHDA or blockage of the β-adrenergic signaling by propranolol remarkably suppressed stress-induced lung metastasis...
September 22, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28940538/androgenic-to-estrogenic-switch-in-human-adult-prostate-gland-is-regulated-by-epigenetic-silencing-of-steroid-5%C3%AE-reductase-2
#9
Zongwei Wang, Libing Hu, Keyan Salari, Seth Bechis, Rongbin Ge, Shulin Wu, Cyrus Rassoulian, Jonathan Pham, Chin-Lee Wu, Shahin Tabatabaei, Strand W Douglas, Aria F Olumi
Benign prostatic hyperplasia (BPH) is the most common proliferative abnormality of the prostate. While all men experience some prostate growth as they age, the rate of growth varies among individuals. Steroid 5α-reductase 2 (SRD5A2) is a critical enzyme for prostatic development and growth. Previous work indicates that one-third of adult prostate samples do not express SRD5A2, secondary to epigenetic modifications. Here we show that estradiol is dramatically elevated, concomitant with significantly upregulated estrogen response genes, in prostate samples that are methylated at the SRD5A2 promoter...
September 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28940253/pbrm1-restricts-the-basal-activity-of-innate-immune-system-through-repressing-rig-i-like-receptor-signaling-and-is-a-potential-prognostic-biomarker-for-colon-cancer
#10
Xing-Sheng Shu, Yingying Zhao, Yanmei Sun, Lan Zhong, Yingduan Cheng, Yixiang Zhang, Kaile Ning, Qian Tao, Yejun Wang, Ying Ying
It has long been known that patients suffering from inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). The innate immune system of host cells provides a first-line defence against pathogenic infection, whereas uncontrolled inflammatory response under homeostatic conditions usually leads to pathological consequences, as exemplified by the chronic inflammation of IBD. The key molecules and pathways keeping innate immunity in check are still poorly defined. Here, we report that chromatin remodeler polybromo-1 (PBRM1) is a repressor of innate immune signaling mediated by RIG-I-like receptors (RLRs)...
September 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28940194/a-new-model-system-identifies-egfr-her2-and-her2-her3-heterodimers-as-potent-inducers-of-oesophageal-epithelial-cell-invasion
#11
Christiane Daniela Fichter, Camilla Maria Przypadlo, Achim Buck, Nicola Herbener, Bianca Riedel, Luisa Schäfer, Hiroshi Nakagawa, Axel Walch, Thomas Reinheckel, Martin Werner, Silke Lassmann
Oesophageal squamous cell carcinomas and oesophageal adenocarcinomas display distinct patterns of ErbB expression and dimers. The functional effects of specific ErbB homo- or heterodimers on oesophageal (cancer) cell behaviour, particularly invasion of early carcinogenesis remains unknown. Here, a new cellular model system for controlled activation of EGFR or HER2 and EGFR/HER2 or HER2/HER3 homo- and heterodimers was studied in non-neoplastic squamous oesophageal epithelial Het-1A cells. EGFR, HER2 and HER3 intracellular domains (ICDs) were fused to dimerization domains (DmrA / DmrA and DmrC), and transduced into Het-1A cells lacking ErbB expression...
September 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28892161/a-gene-is-known-by-the-company-it-keeps-enrichment-of%C3%A2-tnfaip3%C3%A2-gene-aberrations-in-malt-lymphomas-expressing-ighv4-34-antigen-receptors
#12
Andreas Agathangelidis, Aliki Xochelli, Kostas Stamatopoulos
Associations between immunoglobulin (IG) receptors with distinctive immunogenetic features and particular gene mutations is a recurring theme in mature B cell lymphomas. Relevant observations have been made in chronic lymphocytic leukemia (CLL), where gene mutations are distributed asymmetrically in cases bearing or not somatic hypermutations within the clonotypic immunoglobulin heavy chain variable region (IGHV) genes (e.g. TP53 mutations predominate in IG-unmutated CLL, whereas the opposite is seen for MYD88 mutations, enriched in IG-mutated CLL) and in subsets of cases with stereotyped IG (enrichment for SF3B1 mutations in CLL subset #2)...
September 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28892150/hepatic-inflammation-caused-by-dysregulated-bile-acid-synthesis-is-reversible-by-butyrate-supplementation
#13
Lili Sheng, Prasant Kumar Jena, Ying Hu, Hui-Xin Liu, Nidhi Nagar, Karen M Kalanetra, Samuel William French, Samuel Wheeler French, David A Mills, Yu-Jui Yvonne Wan
Dysregulated bile acid (BA) synthesis or reduced farnesoid x receptor (FXR) levels are found in patients having metabolic diseases, autoimmune hepatitis, and liver cirrhosis or cancer. The objective of this study was to establish the relationship between butyrate and dysregulated BA synthesis-induced hepatitis as well as the effect of butyrate in reversing the liver pathology. Wild type (WT) and FXR knockout (KO) male mice were placed on control (CD) or Western diet (WD) for 15 months. In the presence or absence of butyrate supplementation, feces obtained from 15-month-old WD-fed FXR KO mice, which had severe hepatitis and liver tumors, were transplanted to 7-month-old WD-fed FXR KO for 3 months...
September 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28888050/significance-of-perivascular-tumour-cells-defined-by-cd109-expression-in-progression-of-glioma
#14
Yukihiro Shiraki, Shinji Mii, Atsushi Enomoto, Hiroyuki Momota, Yi-Peng Han, Takuya Kato, Kaori Ushida, Akira Kato, Naoya Asai, Yoshiki Murakumo, Kosuke Aoki, Hiromichi Suzuki, Fumiharu Ohka, Toshihiko Wakabayashi, Tomoki Todo, Seishi Ogawa, Atsushi Natsume, Masahide Takahashi
In the progression of glioma, tumour cells often exploit the perivascular microenvironment to promote their survival and resistance to conventional therapies. Some of these cells are considered to be brain tumour stem cells (BTSCs); however, the molecular nature of perivascular tumour cells has not been specifically clarified because of the complexity of glioma. Here, we identified CD109, a glycosylphosphatidylinositol- anchored protein and regulator of multiple signalling pathways, as a critical regulator of the progression of lower-grade glioma (World Health Organization grade II/III) by clinicopathological and whole genome sequencing analysis of tissues from human glioma...
September 9, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28888037/myc-drives-overexpression-of-telomerase-rna-htr-terc-in-prostate-cancer
#15
Javier A Baena-Del Valle, Qizhi Zheng, David M Esopi, Michael Rubenstein, Gretchen K Hubbard, Maria C Moncaliano, Andrew Hruszkewycz, Ajay Vaghasia, Srinivasan Yegnasubramanian, Sarah J Wheelan, Alan K Meeker, Christopher M Heaphy, Mindy K Graham, Angelo M De Marzo
Telomerase consists of at least two essential elements, an RNA component hTR or TERC that contains the template for telomere DNA addition, and a catalytic reverse transcriptase (TERT). While expression of TERT has been considered the key rate limiting component for telomerase activity, increasing evidence suggests an important role for the regulation of TERC in telomere maintenance and perhaps other functions in human cancer. By using three orthogonal methods including RNAseq, RT-qPCR, and an analytically validated chromogenic RNA in situ hybridization assay, we report consistent overexpression of TERC in prostate cancer...
September 9, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28862768/airway-remodelling-and-inflammation-in-asthma-are-dependent-on-the-extracellular-matrix-protein-fibulin-1c
#16
Gang Liu, Marion A Cooley, Prema M Nair, Chantal Donovan, Alan C Hsu, Andrew G Jarnicki, Tatt Jhong Haw, Nicole G Hansbro, Qi Ge, Alexandra C Brown, Hock Tay, Paul S Foster, Peter A Wark, Jay C Horvat, Jane E Bourke, Chris L Grainge, W Scott Argraves, Brian G Oliver, Darryl A Knight, Janette K Burgess, Philip M Hansbro
Asthma is a chronic inflammatory disease of the airways. It is characterised by allergic airway inflammation, remodelling and hyperresponsiveness (AHR). Asthma patients, in particular those with chronic or severe asthma, have airway remodelling that is associated with the accumulation of extracellular matrix (ECM) proteins, such as collagens. Fibulin-1 (Fbln1) is an important ECM protein that stabilises collagen and other ECM proteins. Fbln1c, one of the four Fbln1 variants, which predominates in both humans and mice, is increased in the serum and airways fluids in asthma but its function is unclear...
September 1, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28862766/genomic-profiles-of-lung-cancer-associated-with-idiopathic-pulmonary-fibrosis
#17
Ji An Hwang, Deokhoon Kim, Sung-Min Chun, SooHyun Bae, Joon Seon Song, Mi Young Kim, Hyun Jung Koo, Jin Woo Song, Woo Sung Kim, Jae Cheol Lee, Hyeong Ryul Kim, Chang-Min Choi, Se Jin Jang
Little is known on the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis-associated lung cancer (IPF-LC). This study was performed to investigate the genomic profiles of IPF-LC and to explore the possibility of defining potential therapeutic targets in IPF-LC. We assessed genomic profiles of IPF-LC using targeted exome sequencing (OncoPanel version 2) in 35 matched tumor/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed using GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively...
September 1, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28862757/ctcf-foxm1-axis-regulates-tumor-growth-and-metastasis-in-hepatocellular-carcinoma
#18
Bin Zhang, Yajing Zhang, Xiaoping Zou, Anthony W H Chan, Rui Zhang, Terence Kin-Wah Lee, Hang Liu, Eunice Yuen-Ting Lau, Nicole Pui-Yu Ho, Paul B S Lai, Yue-Sun Cheung, Ka-Fai To, Hoi Kin Wong, Kwong Wai Choy, Vincent W Keng, Larry M C Chow, Kenrick K Y Chan, Alfred S Cheng, Ben C B Ko
CCCTC-binding factor (CTCF) is a DNA-binding protein that interacts with a large number of highly divergent target sequences throughout the genome. It is implicated in a variety of functions, including chromatin organization and transcriptional control. The functional role of CTCF in tumor pathogenesis remains elusive. We showed that CTCF is frequently upregulated in a subset of primary hepatocellular carcinoma (HCC) compared with non-tumoral liver. Overexpression of CTCF was associated with shorter disease-free survival of patients...
September 1, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28833123/telomere-length-variation-in-tumor-cells-and-cancer-associated-fibroblasts-potential-biomarker-for-hepatocellular-carcinoma
#19
Li-Jie Ma, Xiao-Ying Wang, Meng Duan, Long-Zi Liu, Jie-Yi Shi, Liang-Qing Dong, Liu-Xiao Yang, Zhi-Chao Wang, Zhen-Bin Ding, Ai-Wu Ke, Ya Cao, Xiao-Ming Zhang, Jian Zhou, Jia Fan, Qiang Gao
The role of telomere dysfunction and aberrant telomerase activities in hepatocellular carcinoma (HCC) has been overlooked for many years. This study aimed to delineate the variation and prognostic value of telomere length in HCC. Telomere-specific fluorescence in situ hybridization (FISH) and qPCR were used to evaluate telomere length in HCC cell lines, tumor tissues and isolated non-tumor cells within the tumor. Significant telomere attrition was found in tumor cells and cancer-associated fibroblasts (CAFs) compared to their normal counterparts, but not in intratumor leukocytes or bile duct epithelial cells...
August 21, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28816351/recent-advances-in-genomic-profiling-of-adenosquamous-carcinoma-of-the-pancreas
#20
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
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