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Yongzhong Mao, Shaotao Tang, Li Yang, Kang Li
BACKGROUND/AIMS: Viral infections, especially with rotavirus, are often considered an initiator of the pathogenesis of biliary atresia (BA). However, the mechanism by which rotavirus induces BA is still unclear. METHODS: A BA mouse model was induced in newborn mice by i.p. inoculation with rhesus rotavirus within 6 h of birth. The expression of Notch pathway-associated molecules (JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, DII1, DII3, and DII4) was measured by quantitative PCR and western blot analysis...
September 7, 2018: Cellular Physiology and Biochemistry
Marie-Eve Bergeron, Anguel Stefanov, Christina K Haston
Susceptibility to fibrotic lung disease differs among people and among inbred strains of mice exposed to bleomycin where C57BL/6J mice are susceptible and C3H/HeJ mice are spared fibrotic disease. Genetic mapping studies completed in offspring derived from these inbred strains revealed the inheritance of C57BL/6J alleles at loci, including the major locus on chromosome 17, called Blmpf1 bleomycin-induced pulmonary fibrosis 1, to be linked to pulmonary fibrosis in treated mice. In the present study, to reduce the interval of Blmpf1, we bred and phenotyped a panel of subcongenic mice with C3H/HeJ alleles in a C57BL/6J background...
September 1, 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
B Gutiérrez-Gil, C Esteban-Blanco, A Suarez-Vega, J J Arranz
This study presents a scan of the ovine genome to identify quantitative trait loci (QTL) influencing the somatic cell score (SCS), a classical indicator of subclinical mastitis in sheep, and a subsequent high-resolution analysis of one of the identified QTL regions based on the analysis of whole-genome sequence data sets. A half-sib commercial population of Churra sheep genotyped with a 50K SNP-Chip was analyzed using linkage analysis (LA) and combined linkage and linkage disequilibrium analysis (LDLA). By LA, 2 5% chromosome-wide significant QTL on OAR5 and OAR25 and one 5% genome-wide significant QTL on ovine chromosome 20 (OAR20) were detected, whereas 22 significant associations were identified by LDLA...
August 9, 2018: Journal of Dairy Science
Xu Liang, Sophie Vacher, Anais Boulai, Virginie Bernard, Sylvain Baulande, Mylene Bohec, Ivan Bièche, Florence Lerebours, Céline Callens
BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. Using a custom-made breast cancer gene sequencing panel, we investigated somatic mutations in IBC to better understand the genomic differences compared with non-IBC and to consider new targeted therapy in IBC patients. METHODS: Targeted next-generation sequencing (NGS) of 91 candidate breast cancer-associated genes was performed on 156 fresh-frozen breast tumor tissues from IBC patients...
August 7, 2018: Breast Cancer Research: BCR
Guiyang Wu, Zaiping Chen, Jing Li, Fubo Ye, Guoping Chen, Qinghao Fan, Hao Dong, Shichao Yuan, Xiongwen Zhu
Notch family plays vital role in carcinogenesis and progression of various cancer, however, its clinical significance and prognostic value in colorectal cancer isn't fully investigated. In present study, we first investigated the NOTCH4 expression in The Cancer Genome Atlas (TCGA) (n=361) and GSE39582 (n=474) database and then validated with our own database (n=248). The transcriptional and protein levels of NOTCH4 were evaluated by RT-PCR and immunohistochemistry study, respectively. Univariate and multivariate survival analyses were performed to explore the relationship between various prognostic factors and survival outcomes...
2018: Journal of Cancer
Q P Xu, R D Xiao, W M Xiong, F He, L Cai
Objective: To analyze the relationship between single nucleotide polymorphisms (SNP) of Notch signaling pathway and susceptibility to lung cancer. Methods: The present study was a hospital-based case-control study. All 1 121 patients of lung cancer diagnosed by histopathology three hospitals in Fujian and Nanjing were selected as cases from January 2006 to December 2012. At the same time, 1 121 healthy population from other departments of the hospital to visit patients or community, excluding those with tumor, chronic disease, and immediate family members of lung cancer, were enrolled in control group...
March 6, 2018: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
Lijiao Pei, Xiaoqian He, Shuman Li, Ran Sun, Qin Xiang, Guosheng Ren, Tingxiu Xiang
Several studies have recently reported that KRAB zinc finger protein 382 (ZNF382) is downregulated in multiple carcinoma types due to promoter methylation. The exact role of ZNF382 in gastric carcinogenesis, however, remains elusive. In this study, we investigated the alterations and functions of ZNF382 in the pathogenesis of gastric cancer (GC). Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), quantitative (real-time) PCR (qPCR) and immunohistochemistry were carried out to detect the expression patterns of ZNF382 in GC cell lines and gastric tissue samples...
September 2018: International Journal of Oncology
Michael Lattanzi, Yesung Lee, Danny Simpson, Una Moran, Farbod Darvishian, Randie H Kim, Eva Hernando, David Polsky, Doug Hanniford, Richard Shapiro, Russell Berman, Anna C Pavlick, Melissa A Wilson, Tomas Kirchhoff, Jeffrey S Weber, Judy Zhong, Iman Osman
Background: Two primary histologic subtypes, superficial spreading melanoma (SSM) and nodular melanoma (NM), comprise the majority of all cutaneous melanomas. NM is associated with worse outcomes, which have been attributed to increased thickness at presentation, and it is widely expected that NM and SSM would exhibit similar behavior once metastasized. Herein, we tested the hypothesis that primary histologic subtype is an independent predictor of survival and may impact response to treatment in the metastatic setting...
June 15, 2018: Journal of the National Cancer Institute
Hai-Yan Song, Ying Wang, Hong Lan, Yu-Xiang Zhang
Pancreatic cancer is the fourth leading cause of cancer-associated mortality in developed countries. Pancreatic ductal adenocarcinoma (PDAC) accounts for ~90% of all pancreatic cancer cases. The Notch signaling pathway serves a crucial role in embryonic development, as well as during the tumorigenesis of different types of cancer. However, Notch signaling serves either oncogenic or tumor suppressor roles depending on the tissue type. There are four Notch receptors (Notch1-4) and five ligands [Jagged1, Jagged2, δ-like ligand protein (DLL)1, DLL3 and DLL4]; therefore, it has been suggested that the different Notch receptors serve distinct roles in the same type of tissue...
July 2018: Experimental and Therapeutic Medicine
Monika A Jarzabek, William R Proctor, Jennifer Vogt, Rupal Desai, Patrick Dicker, Gary Cain, Rajiv Raja, Jens Brodbeck, Dale Stevens, Eric P van der Stok, John W M Martens, Cornelis Verhoef, Priti S Hegde, Annette T Byrne, Jacqueline M Tarrant
Drug-related sinusoidal dilatation (SD) is a common form of hepatotoxicity associated with oxaliplatin-based chemotherapy used prior to resection of colorectal liver metastases (CRLM). Recently, hepatic SD has also been associated with anti-delta like 4 (DLL4) cancer therapies targeting the NOTCH pathway. To investigate the hypothesis that NOTCH signaling plays an important role in drug-induced SD, gene expression changes were examined in livers from anti-DLL4 and oxaliplatin-induced SD in non-human primate (NHP) and patients, respectively...
2018: PloS One
Mian Xie, Shenhai Wei, Xiaojun Wu, Xiaoxiang Li, You You, Chaosheng He
INTRODUCTION: Adenoid cystic carcinoma (ACC) of the trachea lacks of well-characterized molecular markers. There is currently no specific treatment for metastatic ACC of the trachea. This study aimed to identify genomic mutations of Notch pathway and investigate the efficacy of NOTCH inhibitor in ACC of the trachea. METHODS: 73 Patients with ACC of the trachea at four institutions from 2008 to 2016 were identified. Analysis of hotspot mutations in cancer-related genes of Notch pathway was performed using next generation sequencing...
July 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Zhe-Yu Hu, Ning Xie, Can Tian, Xiaohong Yang, Liping Liu, Jing Li, Huawu Xiao, Hui Wu, Jun Lu, Jianxiang Gao, Xuming Hu, Min Cao, Zhengrong Shui, Mengjia Xiao, Yu Tang, Qiongzhi He, Lianpeng Chang, Xuefeng Xia, Xin Yi, Qianjin Liao, Quchang Ouyang
PURPOSE: In cancer patients, tumor gene mutations contribute to drug resistance and treatment failure. In patients with metastatic breast cancer (MBC), these mutations increase after multiline treatment, thereby decreasing treatment efficiency. The aim of this study was to evaluate gene mutation patterns in MBC patients to predict drug resistance and disease progression. METHOD: A total of 68 MBC patients who had received multiline treatment were recruited. Circulating tumor DNA (ctDNA) mutations were evaluated and compared among hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) subgroups...
June 2018: EBioMedicine
Jing-Wei Wang, Xiao-Long Wei, Xiao-Wei Dou, Wen-He Huang, Cai-Wen Du, Guo-Jun Zhang
Notch4, a family member of the Notch signaling pathway, has important roles in cellular developmental pathways, including proliferation, differentiation and apoptosis. The present study aimed to investigate the association between Notch4 expression and clinical outcomes with immunohistochemistry. Notch4 was expressed in 55.6% of triple-negative breast cancer (TNBC), 45.8% of Her-2-overexpressing and 25.5% of luminal breast cancer cases, with significantly higher expression occurring in TNBC (P<0.05). Furthermore, Notch4 expression was inversely associated with estrogen receptor (ER) and/or progesterone receptor positivity, and positively associated with larger tumor size, more lymph node involvement, and more advanced tumor node metastasis stage (P<0...
June 2018: Oncology Letters
Hyun Lee, Je-Gun Joung, Hyun-Tae Shin, Duk-Hwan Kim, Yujin Kim, Hojoong Kim, O Jung Kwon, Young Mog Shim, Ho Yun Lee, Kyung Soo Lee, Yoon-La Choi, Woong-Yang Park, D Neil Hayes, Sang-Won Um
In-depth molecular pathogenesis of ground-glass nodular lung adenocarcinoma has not been well understood. The objectives of this study were to identify genomic alterations in ground-glass nodular lung adenocarcinomas and to investigate whether viral transcripts were detected in these tumors. Nine patients with pure (n = 4) and part-solid (n = 5) ground-glass nodular adenocarcinomas were included. Six were females with a median age of 58 years. We performed targeted exon sequencing and RNA sequencing...
May 16, 2018: Scientific Reports
J A N Meester, A Verstraeten, M Alaerts, D Schepers, L Van Laer, B L Loeys
The NOTCH signalling pathway is an essential pathway, involved in many cellular processes, including cell fate decision, cell proliferation, and cell death and important in the development of most organs. Mutations in genes encoding components of the NOTCH signalling pathway lead to a spectrum of congenital disorders. Over the past decades, mutations in human NOTCH signalling genes have been identified in several diseases with cardiovascular involvement. NOTCH1 mutations have been described in bicuspid aortic valve disease, left-sided congenital heart disease, and Adams-Oliver syndrome...
May 16, 2018: Clinical Genetics
Sukrutha Chettimada, David R Lorenz, Vikas Misra, Simon T Dillon, R Keith Reeves, Cordelia Manickam, Susan Morgello, Gregory D Kirk, Shruti H Mehta, Dana Gabuzda
Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics...
May 8, 2018: Scientific Reports
L Gelsomino, S Panza, C Giordano, I Barone, G Gu, E Spina, S Catalano, S Fuqua, S Andò
The detection of recurrent mutations affecting the hormone binding domain (HBD) of estrogen receptor alpha (ERα/ESR1) in endocrine therapy-resistant and metastatic breast cancers has prompted interest in functional characterization of these genetic alterations. Here, we explored the role of HBD-ESR1 mutations in influencing the behavior of breast cancer stem cells (BCSCs), using various BC cell lines stably expressing wild-type or mutant (Y537 N, Y537S, D538G) ERα. Compared to WT-ERα clones, mutant cells showed increased CD44+ /CD24- ratio, mRNA levels of stemness genes, Mammosphere Forming Efficiency (MFE), Self-Renewal and migratory capabilities...
August 1, 2018: Cancer Letters
Zixi Zhang, Xin Bu, Jingyi Yang, Shaojun Zhu, Shuixiang He, Jianyong Zheng, Weizhong Wang, Dake Chu
Notch signal has complex roles in human malignancies, which might be attributed to the diversity of Notch receptors. Here, we set out to identify the association of NOTCH4 with colorectal cancer (CRC). In the hospital-based study cohort, we investigated NOTCH4 mRNA levels in primary CRC, as well as its association with clinicopathologic characteristics. Besides, NOTCH4 cDNA and siRNA was transfected into colorectal cancer cell line to elucidate its impact on tumor cell proliferation and migration. Results revealed a statistically significant lower expression of NOTCH4 mRNA in tumor specimens compared with that in control...
October 2018: Journal of Cellular Physiology
Mingcan Xia, Hani Harb, Arian Saffari, Constantinos Sioutas, Talal A Chatila
BACKGROUND: Exposure to traffic-related particulate matter promotes asthma and allergic diseases. However, the precise cellular and molecular mechanisms by which particulate matter exposure acts to mediate these effects remain unclear. OBJECTIVE: We sought to elucidate the cellular targets and signaling pathways critical for augmentation of allergic airway inflammation induced by ambient ultrafine particles (UFP). METHODS: We used in vitro cell-culture assays with lung-derived antigen-presenting cells and allergen-specific T cells and in vivo mouse models of allergic airway inflammation with myeloid lineage-specific gene deletions, cellular reconstitution approaches, and antibody inhibition studies...
April 5, 2018: Journal of Allergy and Clinical Immunology
Sigal Kfir, Raghavendra Basavaraja, Noa Wigoda, Shifra Ben-Dor, Irit Orr, Rina Meidan
To unveil novel global changes associated with corpus luteum (CL) maturation, we analyzed transcriptome data for the bovine CL on days 4 and 11, representing the developing vs. mature gland. Our analyses revealed 681 differentially expressed genes (363 and 318 on day 4 and 11, respectively), with ≥2 fold change and FDR of <5%. Different gene ontology (GO) categories were represented prominently in transcriptome data at these stages (e.g. days 4: cell cycle, chromosome, DNA metabolic process and replication and on day 11: immune response; lipid metabolic process and complement activation)...
2018: PloS One
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