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Qifei Zou, Ying Hou, Haibo Wang, Kui Wang, Xianglei Xing, Yong Xia, Xuying Wan, Jun Li, Binghua Jiao, Jingfeng Liu, Aimin Huang, Dong Wu, Hongjun Xiang, Timothy M Pawlik, Hongyang Wang, Wan Yee Lau, Yizheng Wang, Feng Shen
Over-expression of aspartyl (asparagynal)-β-hydroxylase (ASPH) contributes to hepatocellular carcinoma (HCC) invasiveness, but the role of ASPH hydroxylase activity in this process remains to be defined. As such, the current study investigated the role of ASPH hydroxylase activity in downstream signalling of HCC tumorgenesis and, specifically, metastasis development. Over-expression of wild-type ASPH, but not a hydroxylase mutant, promoted HCC cell migration in vitro, as well as intrahepatic and distant metastases in vivo...
May 12, 2018: EBioMedicine
Chuan Li, Hong-Jiang Li, Qu Chen, Xue-Mei Zhang, Chang-Long Li
OBJECTIVE: To investigate the expression of mRNA of aspartyl/asparaginyl beta-hydroxylase (ASPH) gene in invasive breast cancer (IBC) and the relationship between methylation of gene promoter and clinicopathological parameters. METHODS: In 91 cases of breast cancer tissues and matched normal tissues (MNT),mRNA expression of the ASPH gene was detected by reverse transcription of real-time fluorescence quantification PCR and the methylation status of CpG island in the ASPH gene promoter region was detected by methylation specific PCR (MSP)...
January 2018: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
Wei-Feng Yao, Jun-Wei Liu, Dong-Sheng Huang
The primary objective of this study was to investigate the role of miR-200a in cell proliferation and epithelial-mesenchymal transition (EMT) through regulating targeting aspartate-β-hydroxylase (ASPH), which may further affect the activation of ERK/PI3K/Akt pathway. Liver cancer and adjacent tissues were collected from 72 cases of liver cancer patients with surgery in our hospital. In this study, the mRNA expression level of miR-200a was significantly decreased by real-time PCR (RT-PCR) detection. ASPH expressions, however, had an opposite tendency compared to that of miR-200a...
2018: American Journal of Translational Research
Chiung-Kuei Huang, Yoshifumi Iwagami, Jing Zou, Sarah Casulli, Shaolei Lu, Katsuya Nagaoka, Chengcheng Ji, Kousuke Ogawa, Kevin Y Cao, Jin-Song Gao, Rolf I Carlson, Jack R Wands
Cholangiocarcinoma (CCA) is a highly lethal and aggressive disease. Recently, IDH1/2 mutations have been identified in approximately 20% of CCAs which suggests an involvement of 2-oxoglutarate (2-OG) -dependent dioxygenases in oncogenesis. We investigated if the 2-OG dependent dioxygenase, aspartate beta-hydroxylase (ASPH) was important in tumor development and growth. Immunoassays were used to clarify how ASPH modulates CCA progression by promoting phosphorylation of the retinoblastoma protein (RB1). A xenograft model was employed to determine the role of ASPH on CCA growth...
May 4, 2018: Cancer Letters
Senu Apewokin, Jeannette Y Lee, Julia A Goodwin, Kent D McKelvey, Owen W Stephens, Daohong Zhou, Elizabeth Ann Coleman
BACKGROUND: Clostridium difficile infection (CDI) is the most common hospital-acquired infection. Unfortunately, genes that identify CDI-susceptible patients have not been well described. We performed a genome-wide association study (GWAS) to determine genetic variants associated with the development of CDI. METHODS: A cohort study of Caucasian patients undergoing autologous stem cell transplantation for multiple myeloma was performed. Patients were genotyped using Illumina® Whole Genome Genotyping Infinium chemistry...
March 28, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Ming Tong, Howard Gonzalez-Navarrete, Tyler Kirchberg, Billy Gotama, Emine B Yalcin, Jared Kay, Suzanne M de la Monte
Alcohol-induced white matter (WM) degeneration is linked to cognitive-motor deficits and impairs insulin/insulin-like growth factor (IGF) and Notch networks regulating oligodendrocyte function. Ethanol downregulates Aspartyl-Asparaginyl- β -Hydroxylase (ASPH) which drives Notch. These experiments determined if alcohol-related WM degeneration was linked to inhibition of ASPH and Notch. Adult Long Evans rats were fed for 3, 6 or 8 weeks with liquid diets containing 26% ethanol (caloric) and in the last two weeks prior to each endpoint they were binged with 2 g/kg ethanol, 3 × /week...
2017: Journal of Drug and Alcohol Research
Christina N Banti, Constantina Papatriantafyllopoulou, Anastasios J Tasiopoulos, Sotiris K Hadjikakou
The non steroidal anti-inflammatory drugs (NSAID's)-silver(I) metallodrugs of aspirin (aspH), salicylic acid (salH2 ), naproxen (napH) acid or p-hydrobenzoic acid (pHbzaH) and the mitochondriotropic triphenylarsine (tpAs) with the formulae [Ag(asp)(tpAs)3 ] (1), [Ag(salH)(tpAs)3 ] (2), [Ag(nap)(tpAs)3 ] (3) and {[Ag(pHbza)(tpAs)3 ]∙(dmf)} (4) and [Ag(tpAs)3 (NO3 )] (5) have been synthesized and characterized by m.p., FT-IR, UV-vis and1 H NMR, spectroscopic techniques and X-ray crystallography. The in vitro cytotoxic activity of 1-5 against human breast adenocarcinoma cancer cells: MCF-7 (positive to estrogen receptors (ERs)) and MDA-MB-231 (negative to estrogen receptors (ERs)) was evaluated...
January 1, 2018: European Journal of Medicinal Chemistry
Masafumi Shimoda, Ami Hori, Jack R Wands, Ryo Tsunashima, Yasuto Naoi, Tomohiro Miyake, Tomonori Tanei, Naofumi Kagara, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi
Although prognostic markers for early estrogen receptor (ER)-positive breast cancer have been extensively developed, predictive markers for adjuvant endocrine therapy are still lacking. Focusing on the mechanisms underlying endocrine resistance, we investigated whether the endocrine sensitivity of ER-positive breast cancer cells was correlated with the expression of aspartate-β-hydroxylase (ASPH), which is involved in the development of hepatocellular carcinoma. ASPH expression in ER-positive and tamoxifen-resistant breast cancer cells was upregulated by the MAPK and phosphoinositide-3 kinase (PI3K) pathways, which both play pivotal roles in endocrine resistance...
December 2017: Cancer Science
Yoshifumi Iwagami, Sarah Casulli, Katsuya Nagaoka, Miran Kim, Rolf I Carlson, Kosuke Ogawa, Michael S Lebowitz, Steve Fuller, Biswajit Biswas, Solomon Stewart, Xiaoqun Dong, Hossein Ghanbari, Jack R Wands
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a difficult to treat tumor with a poor prognosis. Aspartate β-hydroxylase (ASPH) is a highly conserved enzyme overexpressed on the cell surface of both murine and human HCC cells. METHODS: We evaluated therapeutic effects of nanoparticle lambda (λ) phage vaccine constructs against ASPH expressing murine liver tumors. Mice were immunized before and after subcutaneous implantation of a syngeneic BNL HCC cell line...
September 2017: Heliyon
C Tang, Y Hou, H Wang, K Wang, H Xiang, X Wan, Y Xia, J Li, W Wei, S Xu, Z Lei, T M Pawlik, H Wang, M Wu, F Shen
The mechanism of aberrant mitochondrial genome and function in hepatocellular carcinoma (HCC) remains largely unknown. Our previous study demonstrated an increased expression of aspartate β-hydroxylase (ASPH) in HCC tissues, which was associated with tumor invasiveness and a worse prognosis. Currently, we unexpectedly observed the presence of ASPH in purified mitochondrial protein fraction. In addition, immunostaining of both exogenously and endogenously expressed ASPH showed a colocalization with mitochondrial biomarkers...
July 17, 2017: Oncogenesis
Reka Nagy, Thibaud S Boutin, Jonathan Marten, Jennifer E Huffman, Shona M Kerr, Archie Campbell, Louise Evenden, Jude Gibson, Carmen Amador, David M Howard, Pau Navarro, Andrew Morris, Ian J Deary, Lynne J Hocking, Sandosh Padmanabhan, Blair H Smith, Peter Joshi, James F Wilson, Nicholas D Hastie, Alan F Wright, Andrew M McIntosh, David J Porteous, Chris S Haley, Veronique Vitart, Caroline Hayward
BACKGROUND: The Generation Scotland: Scottish Family Health Study (GS:SFHS) is a family-based population cohort with DNA, biological samples, socio-demographic, psychological and clinical data from approximately 24,000 adult volunteers across Scotland. Although data collection was cross-sectional, GS:SFHS became a prospective cohort due to of the ability to link to routine Electronic Health Record (EHR) data. Over 20,000 participants were selected for genotyping using a large genome-wide array...
March 7, 2017: Genome Medicine
Lisa-Marie Sturla, Ming Tong, Nick Hebda, Jinsong Gao, John-Michael Thomas, Mark Olsen, Suzanne M de la Monte
BACKGROUND: Despite therapeutic advances, survival with glioblastoma multiforme (GBM) remains below 15 months from diagnosis due to GBM's highly infiltrative nature which precludes complete surgical resection. Patient outcomes could potentially be improved by targeting genes and pathways that drive neoplastic cell motility and invasiveness, including hypoxia-inducible factor-1 (HIF-1α), NOTCH, and aspartate-β-hydroxylase (ASPH). METHODS: Human astrocytoma biopsy specimens (n = 37), WHO Grades II-IV, were analyzed for levels and distributions of ASPH and HIF-1α immunoreactivity by immunohistochemical staining, and ASPH, Notch, JAG, HES1, HEY1 and HIF1α mRNA expression by quantigene multiplex analysis...
December 2016: Heliyon
Niclas Eriksson, Lars Wallentin, Lars Berglund, Tomas Axelsson, Stuart Connolly, John Eikelboom, Michael Ezekowitz, Jonas Oldgren, Guillaume Paré, Paul Reilly, Agneta Siegbahn, Ann-Christine Syvanen, Claes Wadelius, Salim Yusuf, Mia Wadelius
AIMS: We investigated associations between genetic variation in candidate genes and on a genome-wide scale with warfarin maintenance dose, time in therapeutic range (TTR), and risk of major bleeding. MATERIALS & METHODS: In total, 982 warfarin-treated patients from the RE-LY trial were studied. RESULTS: After adjusting for SNPs in VKORC1 and CYP2C9, SNPs in DDHD1 (rs17126068) and NEDD4 (rs2288344) were associated with dose. Adding these SNPs and CYP4F2 (rs2108622) to a base model increased R(2) by 2...
August 2016: Pharmacogenomics
Asaf Vivante, Daw-Yang Hwang, Stefan Kohl, Jing Chen, Shirlee Shril, Julian Schulz, Amelie van der Ven, Ghaleb Daouk, Neveen A Soliman, Aravind Selvin Kumar, Prabha Senguttuvan, Elijah O Kehinde, Velibor Tasic, Friedhelm Hildebrandt
Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%)...
January 2017: Journal of the American Society of Nephrology: JASN
Chiung-Kuei Huang, Yoshifumi Iwagami, Arihiro Aihara, Waihong Chung, Suzanne de la Monte, John-Michael Thomas, Mark Olsen, Rolf Carlson, Tunan Yu, Xiaoqun Dong, Jack Wands
Cholangiocarcinoma (CCA) has a poor prognosis due to widespread intrahepatic spread. Aspartate β-hydroxylase (ASPH) is a transmembrane protein and catalyzes the hydroxylation of aspartyl and asparaginyl residues in calcium binding epidermal growth factor (cbEGF)-like domains of various proteins, including Notch receptors and ligands. ASPH is highly overexpressed (>95%) in human CCA tumors. We explored the molecular mechanisms by which ASPH mediated the CCA malignant phenotype and evaluated the potential of ASPH as a therapeutic target for CCA...
2016: PloS One
Ting Huyan, Ruihua Tang, Jing Li, Qi Li, Xiaoping Xue, Hui Yang
BACKGROUND: The humbug gene is a truncated isoform of Aspartyl β-hydroxylase (ASPH) gene that is overexpressed in many human malignancies. In recent years, since humbug has received increasing attention, it is considered as a potential therapeutic molecular target. Therefore, it is necessary for preparing humbug protein and its monoclonal antibody to investigate its structure and function. METHOD: The optimized humbug gene, synthesized by Genscript in Nanjing, China on December 21st 2013, was expressed in Pichia pastoris cells that were cultured in a 10-L bioreactor...
December 2015: Iranian Journal of Public Health
Lisanne J M Kempkes, Jonathan K Martens, Josipa Grzetic, Giel Berden, Jos Oomens
RATIONALE: Deamidation of Asn and Gln residues is a primary route for spontaneous post-translational protein modification. Several structures have been proposed for the deamidation products of the protonated amino acids. Here we verify these structures by ion spectroscopy, as well as the structures of parallel and sequential fragmentation products. METHODS: Infrared ion spectroscopy using the free electron laser FELIX has been applied to the reaction products from deamidation of protonated glutamine and asparagine in a tandem mass spectrometer...
February 28, 2016: Rapid Communications in Mass Spectrometry: RCM
Yoshifumi Iwagami, Chiung-Kuei Huang, Mark J Olsen, John-Michael Thomas, Grace Jang, Miran Kim, Qiushi Lin, Rolf I Carlson, Carl E Wagner, Xiaoqun Dong, Jack R Wands
UNLABELLED: Aspartate β-hydroxylase (ASPH) is an enzyme overexpressed in human hepatocellular carcinoma (HCC) tumors that participates in the malignant transformation process. We determined if ASPH was a therapeutic target by exerting effects on cellular senescence to retard HCC progression. ASPH knockdown or knockout was achieved by short hairpin RNAs or the CRISPR/Cas9 system, respectively, whereas enzymatic inhibition was rendered by a potent second-generation small molecule inhibitor of ASPH...
April 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Chetram Deochand, Ming Tong, Amit R Agarwal, Enrique Cadenas, Suzanne M de la Monte
BACKGROUND: Human studies suggest tobacco smoking is a risk factor for cognitive impairment and neurodegeneration, including Alzheimer's disease (AD). However, experimental data linking tobacco smoke exposures to underlying mediators of neurodegeneration, including impairments in brain insulin and insulin-like growth factor (IGF) signaling in AD are lacking. OBJECTIVE: This study tests the hypothesis that cigarette smoke (CS) exposures can impair brain insulin/IGF signaling and alter expression of AD-associated proteins...
2016: Journal of Alzheimer's Disease: JAD
Daniele Guido, Nicolas Demaurex, Paula Nunes
Local intracellular Ca(2+) elevations increase the efficiency of phagocytosis, a process that is essential for innate and adaptive immunity. These local Ca(2+) elevations are generated in part by the store-operated Ca(2+) entry (SOCE) sensor STIM1, which recruits endoplasmic reticulum (ER) cisternae to phagosomes and opens phagosomal Ca(2+) channels at ER-phagosome junctions. However, residual ER-phagosome contacts and periphagosomal Ca(2+) hotspots remain in Stim1(-/-) cells. Here, we tested whether junctate (also called ASPH isoform 8), a molecule that targets STIM1 to ER-plasma-membrane contacts upon Ca(2+)-store depletion, cooperates with STIM1 at phagosome junctions...
November 15, 2015: Journal of Cell Science
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