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Hui-Min Niu, Ping Yang, Huan-Huan Chen, Ruo-Han Hao, Shan-Shan Dong, Shi Yao, Xiao-Feng Chen, Han Yan, Yu-Jie Zhang, Yi-Xiao Chen, Feng Jiang, Tie-Lin Yang, Yan Guo
Nearly 95% of susceptibility SNPs identified by genome-wide association studies (GWASs) are located in non-coding regions, which causes a lot of difficulty in deciphering their biological functions on disease pathogenesis. Here, we aimed to conduct a comprehensive functional annotation for all the schizophrenia susceptibility loci obtained from GWASs. Considering varieties of epigenomic regulatory elements, we annotated all 22,688 acquired susceptibility SNPs according to their genomic positions to obtain functional SNPs...
January 31, 2019: Translational Psychiatry
Nádia P Castro, Maria C Rangel, Anand S Merchant, Gabriel M MacKinnon, Frank Cuttitta, David S Salomon, Young S Kim
Triple-negative breast cancer (TNBC) represents the poorest prognosis among all of breast cancer subtypes with no currently available effective therapy. In this study, we hypothesized that sulforaphane (SFN), a dietary component abundant in broccoli and its sprouts, can inhibit malignant cell proliferation and tumor sphere formation of cancer stem-like cells (CSCs) in TNBC. CSC population was isolated using fluorescently activated cell sorting (FACS) analysis with the combined stem cell surface markers, CD44+/CD24-/CD49f+...
January 24, 2019: Cancer Prevention Research
Yichao Wang, Ruixue Yang, Xiaolin Wang, Hongfei Ci, Lei Zhou, Bo Zhu, Shiwu Wu, Danna Wang
Vasculogenic mimicry (VM) is a new blood supply style in tumors and has long been treated as a useful factor in malignant tumor metastasis and prognosis. Notch4 (a marker of Notch signaling pathway receptors), DLL4 (a marker of Notch signaling pathway ligands) and KAI1/CD82 (a suppressor gene of tumor metastasis) are all effective predictive factors for tumor metastasis. In this study, we analyzed correlations among VM, Notch4, DLL4, and KAI1/CD82 in non-small cell lung cancer (NSCLC), and their respective associations with patients' clinicopathological parameters and survival rate in NSCLC...
December 2018: Medicine (Baltimore)
Paul Takam Kamga, Giada Dal Collo, Martina Midolo, Annalisa Adamo, Pietro Delfino, Angela Mercuri, Simone Cesaro, Elda Mimiola, Massimiliano Bonifacio, Angelo Andreini, Marco Chilosi, Mauro Krampera
Notch3 and Notch4 support survival of primary B cell acute lymphoblastic leukemia (B-ALL) cells, suggesting a role for Notch signaling in drug response. Here we used in vitro, in silico, and in vivo mouse xenograft model-based approaches to define the role of the Notch pathway in B-ALL chemosensitivity. We observed significant Notch receptor and ligand expression in B-ALL primary cells and cell lines. Primary leukemia cells from high-risk patients overexpressed Notch3, Notch4, and Jagged2 while displaying a reduction in expression levels of Notch1-4 following chemotherapy...
December 18, 2018: Cancer Research
Yingchang Lu, Sun-Seog Kweon, Chizu Tanikawa, Wei-Hua Jia, Yong-Bing Xiang, Qiuyin Cai, Chenjie Zeng, Stephanie L Schmit, Aesun Shin, Keitaro Matsuo, Sun Ha Jee, Dong-Hyun Kim, Jeongseon Kim, Wanqing Wen, Jiajun Shi, Xingyi Guo, Bingshan Li, Nan Wang, Ben Zhang, Xinxiang Li, Min-Ho Shin, Hong-Lan Li, Zefang Ren, Jae Hwan Oh, Isao Oze, Yoon-Ok Ahn, Keum Ji Jung, David V Conti, Fredrick R Schumacher, Gad Rennert, Mark A Jenkins, Peter T Campbell, Michael Hoffmeister, Graham Casey, Stephen B Gruber, Jing Gao, Yu-Tang Gao, Zhi-Zhong Pan, Yoichiro Kamatani, Yi-Xin Zeng, Xiao-Ou Shu, Jirong Long, Koichi Matsuda, Wei Zheng
BACKGROUND & AIMS: Genome-wide association studies (GWASs) have associated approximately 50 loci with risk of colorectal cancer (CRC)-nearly one-third of these loci were initially associated with CRC in studies conducted in East Asian populations. We conducted a GWAS of East Asians to identify CRC risk loci and evaluate the generalizability of findings from GWAS of European populations to Asian populations METHODS: We analyzed genetic data from 22,775 patients with CRC (cases) and 47,731 individuals without cancer (controls) from 14 studies in the Asia Colorectal Cancer Consortium...
December 6, 2018: Gastroenterology
Xiaodong Zhou, Hongye Li, Shicheng Guo, Jiucun Wang, Chunhua Shi, Maribel Espitia, Xinjian Guo, Qingwen Wang, Mengyuan Liu, Shervin Assassi, John D Reveille, Maureen D Mayes
OBJECTIVE: Findings from previous genome-wide association studies indicated an association of the NOTCH4 gene with systemic sclerosis (SSc). This is a followup study to fine-map exonic variants of NOTCH4 in SSc. METHODS: All exons of NOTCH4 were sequenced and analyzed in a total of 1006 patients with SSc and 1004 controls of US white ancestry with the Ion Torrent system. Identified SSc-associated variants were confirmed with Sanger sequencing, and then examined in a Chinese Han cohort consisting of 576 patients with SSc and 574 controls...
November 15, 2018: Journal of Rheumatology
Heju Zhong, Peng Wang, Yumo Song, Xiaoling Zhang, Lianqiang Che, Bin Feng, Yan Lin, Shengyu Xu, Jian Li, De Wu, Qiaofeng Wu, Zhengfeng Fang
Background: Persistent lactation, as the result of mammary cellular anabolism and secreting function, is dependent on substantial mobilization or catabolism of body reserves under nutritional deficiency. However, little is known about the biochemical mechanisms for nutrition-restricted lactating animals to simultaneously maintain the anabolism of mammary cells while catabolism of body reserves. In present study, lactating sows with restricted feed allowance (RFA) ( n  = 6), 24% feed restriction compared with the control (CON) group ( n  = 6), were used as the nutrition-restricted model...
2018: Journal of Animal Science and Biotechnology
Julien Chabanais, François Labrousse, Alain Chaunavel, Agnès Germot, Abderrahman Maftah
BACKGROUND: While protein O -fucosyltransferase 1 ( POFUT1 ) overexpression has been recently proposed as a potential biomarker for different cancer types, no study was carried out on POFUT1 implication in colorectal cancer (CRC). METHODS: Data from 626 tumors and 51 non-tumor adjacent tissues available in FireBrowse had been used in this study. Statistical analyses on POFUT1 expression and gene copy number, NOTCH receptors (main targets of POFUT1 enzymatic activity) expression and association of POFUT1 and NOTCH1 expressions with clinical parameters were investigated...
October 30, 2018: Cancers
D M Tian, Y M Liang, Y Q Zhang
Objective: To evaluate the effects of endothelial cell-targeted soluble Notch ligand hD1R protein on the proliferation of acute myeloid leukemia (AML) cells. Methods: The expression levels of Notch1, Notch2, Notch3, Notch4, Hes1 in bone marrow CD34(+) cells from 24 cases of untreated AML (AML group) and 9 healthy controls (control group) were determined by real time quantitative polymerase chain reaction (PCR) . Recombinant hD1R protein was first induced and purified. Bone marrow CD34(+) cells were co-cultured on human umbilical vein endothelial cells (HUVEC) supplemented with a cocktail containing 5 types of human cytokines (5GF) and soluble hD1R...
October 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Ming Cui, Ya Hu, Yalan Bi, Weiwei Wang, Mengyi Wang, Xiang Zhang, Ronghua Zhang, Peipei Wang, Zhe Su, Xiang Gao, Jiali Wang, Qing Li, Quan Liao, Yupei Zhao
Parathyroid carcinoma (PC) is a rare endocrine malignancy. Surgical resection is curative for local lesions, while effective therapies are lacking for recurrent or metastatic PCs. To study whether targeted therapies could be applied in recurrent or metastatic PCs, potential therapeutic targets were identified with next-generation sequencing (NGS). DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections from 19 recurrent or metastatic PC samples. A panel of 560 genes was sequenced with NGS to identify genomic alterations at an average sequencing depth of 581×...
October 26, 2018: International Journal of Cancer. Journal International du Cancer
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...
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...
October 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
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