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Mehrdad Khajavi, Yi Zhou, Amy E Birsner, Lauren Bazinet, Amanda Rosa Di Sant, Alex J Schiffer, Michael S Rogers, Subrahmanian Tarakkad Krishnaji, Bella Hu, Vy Nguyen, Leonard Zon, Robert J D'Amato
Recent findings indicate that growth factor-driven angiogenesis is markedly influenced by genetic variation. This variation in angiogenic responsiveness may alter the susceptibility to a number of angiogenesis-dependent diseases. Here, we utilized the genetic diversity available in common inbred mouse strains to identify the loci and candidate genes responsible for differences in angiogenic response. The corneal micropocket neovascularization assay was performed on 42 different inbred mouse strains using basic fibroblast growth factor (bFGF) pellets...
June 2017: PLoS Genetics
Sachi Horibata, Katherine E Rogers, David Sadegh, Lynne J Anguish, John L McElwee, Pragya Shah, Paul R Thompson, Scott A Coonrod
BACKGROUND: Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process. METHODS: For our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes in cell migration and cell morphology...
May 26, 2017: BMC Cancer
Ryo Funayama, Hajime Taniguchi, Masamichi Mizuma, Fumiyoshi Fujishima, Minoru Kobayashi, Shinobu Ohnuma, Michiaki Unno, Keiko Nakayama
Expression of the gene for protein-arginine deiminase 2 (PADI2) has been shown to be downregulated in colon cancer, with such downregulation being indicative of a poor prognosis in individuals with this disease. We have now examined the expression of PADI2 in matched colon cancer and normal colon tissue specimens as well as in colon cancer cell lines. We found that isoform 1 of PADI2 is the predominant isoform in colon tissue and is downregulated during colon carcinogenesis. Immunohistochemical analysis showed that PADI2 is expressed in normal colonic epithelial cells...
April 2017: Cancer Science
Wei Guo, Yabing Zheng, Bing Xu, Fang Ma, Chang Li, Xiaoqian Zhang, Yao Wang, Xiaotian Chang
BACKGROUND: Peptidylarginine deiminase (PAD) catalyzes the conversion of arginine residues to citrulline residues, termed citrullination. Recent studies have suggested that PAD isoform 2 (PADI2) plays an important role in tumors, although its tumorigenic effect and mechanism are largely unknown. MATERIALS AND METHODS: Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to investigate the expression level of PADI2 in various tumor tissues and patient blood samples, respectively...
2017: OncoTargets and Therapy
Wei-Chuan Shangkuan, Hung-Che Lin, Yu-Tien Chang, Chen-En Jian, Hueng-Chuen Fan, Kang-Hua Chen, Ya-Fang Liu, Huan-Ming Hsu, Hsiu-Ling Chou, Chung-Tay Yao, Chi-Ming Chu, Sui-Lung Su, Chi-Wen Chang
BACKGROUND: Colorectal cancer (CRC) is one of the leading cancers worldwide. Several studies have performed microarray data analyses for cancer classification and prognostic analyses. Microarray assays also enable the identification of gene signatures for molecular characterization and treatment prediction. OBJECTIVE: Microarray gene expression data from the online Gene Expression Omnibus (GEO) database were used to to distinguish colorectal cancer from normal colon tissue samples...
2017: PeerJ
A S Hoekstra, B van den Ende, X P Julià, L van Breemen, K Scheurwater, C M Tops, A Malinoc, P Devilee, H P H Neumann, J-P Bayley
Germline mutations in genes encoding subunits of succinate dehydrogenase (SDH) are associated with hereditary paraganglioma and pheochromocytoma. Although most mutations in SDHB, SDHC and SDHD are intraexonic variants, large germline deletions may represent up to 10% of all variants but are rarely characterized at the DNA sequence level. Additional phenotypic effects resulting from deletions that affect neighboring genes are also not understood. We performed multiplex ligation-dependent probe amplification, followed by a simple long-range PCR 'chromosome walking' protocol to characterize breakpoints in 20 SDHx-linked paraganglioma-pheochromocytoma patients...
April 2017: Clinical Genetics
Huifeng Wang, Bing Xu, Xiaoqian Zhang, Yabing Zheng, Yan Zhao, Xiaotian Chang
BACKGROUND: Peptidylarginine deiminase (PAD) post-translationally converts arginine residues to citrulline residues. Recent studies have suggested that PADI2 (PAD isoform 2), a member of the PAD family, is involved in the tumorigenic process of some tumors, especially breast cancer. However, little is known about the mechanisms of PADI2 in tumorigenesis. This study aimed to elucidate the tumorigenic role and regulatory pathway of PADI2 in breast tumors. METHODS: The Sequenom MassARRAY and TaqMan genotyping methods were used to investigate the correlation between PADI2 gene SNPs and various tumor risks...
2016: Cancer Cell International
Sanjay Tanday
No abstract text is available yet for this article.
August 2016: Lancet Oncology
G McNee, K L Eales, W Wei, D S Williams, A Barkhuizen, D B Bartlett, S Essex, S Anandram, A Filer, P A H Moss, G Pratt, S Basu, C C Davies, D A Tennant
Multiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow. This microenvironment facilitates crucial interactions between the cancer cells and stromal cell types that permit the tumour to survive and proliferate. There is increasing evidence that the bone marrow mesenchymal stem cell (BMMSC) is stably altered in patients with MM-a phenotype also postulated to exist in patients with monoclonal gammopathy of undetermined significance (MGUS) a benign condition that precedes MM...
February 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Neus Cantariño, Eva Musulén, Vanesa Valero, Miquel Angel Peinado, Manuel Perucho, Victor Moreno, Sònia-Vanina Forcales, Julien Douet, Marcus Buschbeck
UNLABELLED: Peptidyl arginine deiminases (PADI) are a family of enzymes that catalyze the poorly understood posttranslational modification converting arginine residues into citrullines. In this study, the role of PADIs in the pathogenesis of colorectal cancer was investigated. Specifically, RNA expression was analyzed and its association with survival in a cohort of 98 colorectal cancer patient specimens with matched adjacent mucosa and 50 controls from donors without cancer. Key results were validated in an independent collection of tumors with matched adjacent mucosa and by mining of a publicly available expression data set...
September 2016: Molecular Cancer Research: MCR
Akari Suzuki, Yuta Kochi, Hirofumi Shoda, Yu Seri, Keishi Fujio, Tetsuji Sawada, Ryo Yamada, Kazuhiko Yamamoto
BACKGROUND: Peptidylarginine deiminase type 4 (PADI4) has been identified as a susceptibility gene for rheumatoid arthritis (RA) by genome-wide association studies. PADI4 is highly expressed in the bone marrow, macrophages, neutrophils, and monocytes. Peptidyl citrulline is an interesting molecule in RA because it is a target antigen for anti-citrullinated peptide antibodies, and only PADs (translated proteins from PADI genes) can provide peptidyl citrulline via the modification of protein substrates...
2016: BMC Musculoskeletal Disorders
Neus Cantariño, M Teresa Fernández-Figueras, Vanesa Valero, Eva Musulén, Roberto Malinverni, Isabel Granada, Stephen J Goldie, Juan Martín-Caballero, Julien Douet, Sonia-Vanina Forcales, Marcus Buschbeck
Squamous cell carcinomas have a range of histopathological manifestations. The parameters that determine this clinically observed heterogeneity are not fully understood. Here, we report the generation of a cell culture model that reflects part of this heterogeneity. We have used the catalytic subunit of human telomerase hTERT and large T to immortalize primary UV-unexposed keratinocytes. Then, mutant HRAS G12V has been introduced to transform these immortal keratinocytes. When injected into immunosuppressed mice, transformed cells grew as xenografts with distinct histopathological characteristics...
September 1, 2016: International Journal of Cancer. Journal International du Cancer
Fei Wang, Fang-Fang Chen, Wen-Bo Gao, Hai-Yong Wang, Ning-Wei Zhao, Min Xu, De-Yu Gao, Wei Yu, Xiao-Ling Yan, Jian-Ning Zhao, Xiao-Jun Li
The objective of the study is to investigate potential citrullinated autoantigens as targets of anti-citrullinated protein antibodies (ACPAs) response in synovial fluids (SFs) of patients with rheumatoid arthritis (RA). SFs from six RA patients and six osteoarthritis (OA) patients as controls were collected. The citrullinated proteins in SFs were extracted by immunoprecipitation with rabbit anti-citrulline antibodies. Matrix-assisted laser desorption/ionization time of flight mass spectrometry/time of flight mass spectrometry (MALDI-TOF/TOF) mass spectrometry was subsequently performed to discover a characteristic neutral loss to finally determine citrullinated autoantigens...
September 2016: Clinical Rheumatology
Yukinori Okada, Tomoki Muramatsu, Naomasa Suita, Masahiro Kanai, Eiryo Kawakami, Valentina Iotchkova, Nicole Soranzo, Johji Inazawa, Toshihiro Tanaka
The impact of microRNA (miRNA) on the genetics of human complex traits, especially in the context of miRNA-target gene networks, has not been fully assessed. Here, we developed a novel analytical method, MIGWAS, to comprehensively evaluate enrichment of genome-wide association study (GWAS) signals in miRNA-target gene networks. We applied the method to the GWAS results of the 18 human complex traits from >1.75 million subjects, and identified significant enrichment in rheumatoid arthritis (RA), kidney function, and adult height (P < 0...
March 1, 2016: Scientific Reports
Yuan Lu, Jilong Li, Jianlin Cheng, Dennis B Lubahn
BACKGROUND: Orphan nuclear receptor estrogen related receptor β (Esrrb or ERRβ) is well known in stem cells and early embryonic development. However, little is known about its function in cancer. METHOD: We investigated the mRNA profile alterations induced by Esrrb expression and its synthetic ligand DY131 in human prostate cancer DU145 cells via RNA-Seq analysis. RESULTS: We distinguished 67 mRNAs differentially expressed by Esrrb alone...
December 1, 2015: BMC Molecular Biology
Elizabeth Olivares-Martínez, Diego F Hernández-Ramírez, Carlos A Núñez-Álvarez, Antonio R Cabral, Luis Llorente
The objective of this study was to determine the relationship between citrullinated proteins in synovial tissue with peripheral anti-citrullinated peptides autoantibodies (ACPA) and peptidylarginine deiminase (PADI) PADI2, PADI3, and PADI4 messenger RNA (mRNA) expressions in synovial tissue and fibroblast-like synoviocytes in rheumatoid arthritis (RA) patients. Eleven RA and 12 osteoarthritis (OA) patients who underwent knee replacement surgery were studied. We detected citrullinated proteins in synovial tissue homogenates by western blot and serum ACPA by ELISA to anti-cyclic citrullinated peptide (anti-CCP) antibodies, and PADI2, PADI3, and PADI4 mRNA expressions in synovial tissue and in fibroblast-like synoviocytes...
January 2016: Clinical Rheumatology
Sachi Horibata, Tommy V Vo, Venkataraman Subramanian, Paul R Thompson, Scott A Coonrod
Given the inherent difficulties in investigating the mechanisms of tumor progression in vivo, cell-based assays such as the soft agar colony formation assay (hereafter called soft agar assay), which measures the ability of cells to proliferate in semi-solid matrices, remain a hallmark of cancer research. A key advantage of this technique over conventional 2D monolayer or 3D spheroid cell culture assays is the close mimicry of the 3D cellular environment to that seen in vivo. Importantly, the soft agar assay also provides an ideal tool to rigorously test the effects of novel compounds or treatment conditions on cell proliferation and migration...
2015: Journal of Visualized Experiments: JoVE
John L McElwee, Sunish Mohanan, Sachi Horibata, Kelly L Sams, Lynne J Anguish, Dalton McLean, Iva Cvitaš, Joseph J Wakshlag, Scott A Coonrod
Peptidylarginine deiminase 2 (PAD2/PADI2) has been implicated in various inflammatory diseases and, more recently, cancer. The goal of this study was to test the hypothesis that PAD2 promotes oncogenesis using a transgenic mouse model. We found that about 37% of transgenic mice overexpressing human FLAG-PAD2 downstream of the MMTV-LTR promoter develop spontaneous neoplastic skin lesions. Molecular and histopathologic analyses of the resulting lesions find that they contain increased levels of markers for invasion, inflammation, and epithelial-to-mesenchymal transition (EMT) and that a subset of the lesions progress to invasive squamous cell carcinoma (SCC)...
November 1, 2014: Cancer Research
Pei-Chen Hsu, Ya-Fan Liao, Chin-Li Lin, Wen-Hao Lin, Guang-Yaw Liu, Hui-Chih Hung
Peptidylarginine deiminase type 2 (PADI2) deiminates (or citrullinates) arginine residues in protein to citrulline residues in a Ca2+-dependent manner, and is found in lymphocytes and macrophages. Vimentin is an intermediate filament protein and a well-known substrate of PADI2. Citrullinated vimentin is found in ionomycin-induced macrophage apoptosis. Citrullinated vimentin is the target of anti-Sa antibodies, which are specific to rheumatoid arthritis, and play a critical role in the pathogenesis of the disease...
May 2014: Molecules and Cells
Xiaotian Chang, Yifang Xia, Jihong Pan, Qingsong Meng, Yan Zhao, Xinfeng Yan
Citrullination, a posttranslational modification of peptidyl arginine to citrulline, plays an essential role in rheumatoid arthritis (RA). Citrullination is catalyzed by a group of peptidylarginine deiminases (PADs) including PADI 1, 2, 3, 4 and 6. Many studies have indicated that the gene encoding PADI4 is a factor in susceptibility to RA. Some studies have detected PADI2 expression in RA synovial tissues, suggesting that PADI2 also plays an important role in the disease. This study evaluated the possible association between the PADI2-encoding gene and RA...
2013: PloS One
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