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Krzysztof Drews, Agata Różycka, Magdalena Barlik, Andrzej Klejewski, Grażyna Kurzawińska, Hubert Wolski, Marian Majchrzycki, Agnieszka Gryszczyńska, Adam Kamiński, Agnieszka Seremak-Mrozikiewicz
OBJECTIVES: Choline and folate metabolism disturbances may be involved in the occurrence of intrauterine fetal death (IUFD). The proper activity of this metabolism could be determined by genetic variants involved in choline pathway e.g. CHKA (gene encoding choline kinase α), PCYT1A (gene encoding CCTα) and CHDH (gene encoding choline dehydrogenase). Our study aimed at determining the genotype and allele frequencies of CHKA rs7928739, PCYT1A rs712012, PCYT1A rs7639752, CHDH rs893363 and CHDH rs2289205 polymorphisms in mothers with IUFD occurrence...
2017: Ginekologia Polska
Ariel B Ganz, Vanessa V Cohen, Camille C Swersky, Julie Stover, Gerardo A Vitiello, Jessica Lovesky, Jasmine C Chuang, Kelsey Shields, Vladislav G Fomin, Yusnier S Lopez, Sanjay Mohan, Anita Ganti, Bradley Carrier, Olga V Malysheva, Marie A Caudill
Single nucleotide polymorphisms (SNPs) in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations...
January 26, 2017: International Journal of Molecular Sciences
Xi-Meng Lin, Liang Hu, Jin Gu, Ruo-Yu Wang, Liang Li, Jing Tang, Bao-Hua Zhang, Xing-Zhou Yan, Yan-Jing Zhu, Cong-Li Hu, Wei-Ping Zhou, Shao Li, Jing-Feng Liu, Frank J Gonzalez, Meng-Chao Wu, Hong-Yang Wang, Lei Chen
BACKGROUND & AIMS: Choline kinase α (CHKA) catalyzes conversion of choline to phosphocholine and can contribute to carcinogenesis. Little is known about the role of CHKA in the pathogenesis of hepatocellular carcinoma (HCC). METHODS: We performed whole-exome and transcriptome sequence analyses of 9 paired HCC and non-tumor-adjacent tissues. We performed tissue chip analyses of 120 primary HCC and non-tumor-adjacent tissues from patients who received surgery in Shanghai, China from January 2006 through December 2009; 48 sets of specimens (HCC and non-tumor-adjacent tissues) were also analyzed...
April 2017: Gastroenterology
Xianhu Zheng, Youyi Kuang, Weihua Lv, Dingchen Cao, Zhipeng Sun, Xiaowen Sun
Muscle fat content is an important phenotypic trait in fish, as it affects the nutritional, technical and sensory qualities of flesh. To identify loci and candidate genes associated with muscle fat content and abdominal fat traits, we performed a genome-wide association study (GWAS) using the common carp 250 K SNP assay in a common carp F2 resource population. A total of 18 loci surpassing the genome-wide suggestive significance level were detected for 4 traits: fat content in dorsal muscle (MFdo), fat content in abdominal muscle (MFab), abdominal fat weight (AbFW), and AbFW as a percentage of eviscerated weight (AbFP)...
2016: PloS One
Zhong-Ze Fang, Naoki Tanaka, Dan Lu, Chang-Tao Jiang, Wei-Hua Zhang, Chunze Zhang, Zuo Du, Zhi-Wei Fu, Peng Gao, Yun-Feng Cao, Hong-Zhi Sun, Zhi-Tu Zhu, Yan Cai, Kristopher W Krausz, Zhi Yao, Frank J Gonzalez
Alpha-naphthyl isothiocyanate (ANIT)-induced liver damage is regarded as a useful model to study drug-induced cholestatic hepatitis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based metabolomics revealed clues to the mechanism of ANIT-induced liver injury, which facilitates the elucidation of drug-induced liver toxicity. 1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:0) and 1-oleoyl-2-hydroxy-sn-glycero-3-phosphocholine (LPC 18:1) were significantly increased in serum from ANIT-treated mice, and this increase resulted from altered expression of genes encoding the lipid metabolism enzymes Chka and Scd1...
November 16, 2016: Archives of Toxicology
Xi Chen, Heng Qiu, Chao Wang, Yu Yuan, Jennifer Tickner, Jiake Xu, Jun Zou
Choline, a hydrophilic cation, has versatile physiological roles throughout the body, including cholinergic neurotransmission, memory consolidation and membrane biosynthesis and metabolism. Choline kinases possess enzyme activity that catalyses the conversion of choline to phosphocholine, which is further converted to cytidine diphosphate-coline (CDP-choline) in the biosynthesis of phosphatidylcholine (PC). PC is a major constituent of the phospholipid bilayer which constitutes the eukaryotic cell membrane, and regulates cell signal transduction...
February 2017: Cytokine & Growth Factor Reviews
Li Zhang, Ping Chen, Shen Yang, Guodong Li, Wentao Bao, Peng Wu, Shujuan Jiang
Choline kinase α (CHKA), the enzyme that converts choline to phosphocholine, has been studied in human carcinogenesis widely. However, the expression and underlying clinicopathological characteristics of CHKA in lung adenocarcinoma remains elusive. In the present study, a tissue microarray of 119 pairs of lung adenocarcinoma samples and corresponding adjacent normal mucosae was used to analysis CHKA expression by immunohistochemistry, and CHKA was observed to exhibit enhanced expression in lung adenocarcinoma tissues...
September 2016: Oncology Letters
Shaffer R S Mok, Sachin Mohan, Navjot Grewal, Adam B Elfant, Thomas A Judge
BACKGROUND: Biphenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC) is an uncommon primary liver neoplasm. Due to limitations in radiologic imaging for the diagnosis of this condition, biopsy is a common method for diagnosis, which is invasive and holds potential complications. To identify alternative means for obtaining the diagnosis and assessing the prognosis of this condition, we evaluated biomarkers for biphenotypic HCC-CC using a genetic database. METHODS: To evaluate the genetic associations with each variable we utilized GeneCards(®), The Human Gene Compendium (http://www...
August 2016: Journal of Gastrointestinal Oncology
Liang Hu, Ruo-Yu Wang, Jian Cai, Dan Feng, Guang-Zhen Yang, Qing-Guo Xu, Yan-Xia Zhai, Yu Zhang, Wei-Ping Zhou, Qing-Ping Cai
Aberrant expression of choline kinase alpha (CHKA) has been reported in a variety of human malignancies including colorectal carcinoma (CRC). However, the role of CHKA in the progression and prognosis of CRC remains unknown. In this study, we found that CHKA was frequently upregulated in CRC clinical samples and CRC-derived cell lines and was significantly correlated with lymph node metastasis (p = 0.028), TNM stage (p = 0.009), disease recurrence (p = 0.004) and death (p < 0.001). Survival analyses indicated that patients with higher CHKA expression had a significantly shorter disease-free survival (DFS) and disease-specific survival (DSS) than those with lower CHKA expression...
October 11, 2016: Oncotarget
Benjamin L King, Viravuth P Yin
BACKGROUND: Although regenerative capacity is evident throughout the animal kingdom, it is not equally distributed throughout evolution. For instance, complex limb/appendage regeneration is muted in mammals but enhanced in amphibians and teleosts. The defining characteristic of limb/appendage regenerative systems is the formation of a dedifferentiated tissue, termed blastema, which serves as the progenitor reservoir for regenerating tissues. In order to identify a genetic signature that accompanies blastema formation, we employ next-generation sequencing to identify shared, differentially regulated mRNAs and noncoding RNAs in three different, highly regenerative animal systems: zebrafish caudal fins, bichir pectoral fins and axolotl forelimbs...
2016: PloS One
Mohammad Asim, Charlie E Massie, David E Neal
To identify clinically relevant downstream effectors of androgen signaling, the androgen-regulated kinome was defined in prostate cancer (PCa). Within this study, choline kinase α (CHKA) was identified as an androgen receptor chaperone that is both a biomarker of progression and a potential therapeutic target for PCa.
May 2016: Molecular & Cellular Oncology
Sebastian Trousil, Maciej Kaliszczak, Zachary Schug, Quang-De Nguyen, Giampaolo Tomasi, Rosy Favicchio, Diana Brickute, Robin Fortt, Frazer J Twyman, Laurence Carroll, Andrew Kalusa, Naveenan Navaratnam, Thomas Adejumo, David Carling, Eyal Gottlieb, Eric O Aboagye
The glycerophospholipid phosphatidylcholine is the most abundant phospholipid species of eukaryotic membranes and essential for structural integrity and signaling function of cell membranes required for cancer cell growth. Inhibition of choline kinase alpha (CHKA), the first committed step to phosphatidylcholine synthesis, by the selective small-molecule ICL-CCIC-0019, potently suppressed growth of a panel of 60 cancer cell lines with median GI50 of 1.12 μM and inhibited tumor xenograft growth in mice. ICL-CCIC-0019 decreased phosphocholine levels and the fraction of labeled choline in lipids, and induced G1 arrest, endoplasmic reticulum stress and apoptosis...
June 14, 2016: Oncotarget
Weihuan Huang, Yeyin Liang, Jiajian Wang, Guoqiang Li, Guocai Wang, Yaolan Li, Hau Yin Chung
BACKGROUND: Wedelia chinensis is a traditional medicinal herb used in Asia and it has been reported to possess various bioactivities including anti-inflammatory and anticancer effects. However, its anti-angiogenic activity has never been reported. PURPOSE: To determine the most potent anti-angiogenic component in W. chinensis and its molecular mechanism of action. STUDY DESIGN: Initially, the active fraction of the plant was studied. Then, we determined the active components of the fraction and explored the mechanism of the most active compound...
March 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Mohammad Asim, Charles E Massie, Folake Orafidiya, Nelma Pértega-Gomes, Anne Y Warren, Mohsen Esmaeili, Luke A Selth, Heather I Zecchini, Katarina Luko, Arham Qureshi, Ajoeb Baridi, Suraj Menon, Basetti Madhu, Carlos Escriu, Scott Lyons, Sarah L Vowler, Vincent R Zecchini, Greg Shaw, Wiebke Hessenkemper, Roslin Russell, Hisham Mohammed, Niki Stefanos, Andy G Lynch, Elena Grigorenko, Clive D'Santos, Chris Taylor, Alastair Lamb, Rouchelle Sriranjan, Jiali Yang, Rory Stark, Scott M Dehm, Paul S Rennie, Jason S Carroll, John R Griffiths, Simon Tavaré, Ian G Mills, Iain J McEwan, Aria Baniahmad, Wayne D Tilley, David E Neal
BACKGROUND: The androgen receptor (AR) is a major drug target in prostate cancer (PCa). We profiled the AR-regulated kinome to identify clinically relevant and druggable effectors of AR signaling. METHODS: Using genome-wide approaches, we interrogated all AR regulated kinases. Among these, choline kinase alpha (CHKA) expression was evaluated in benign (n = 195), prostatic intraepithelial neoplasia (PIN) (n = 153) and prostate cancer (PCa) lesions (n = 359). We interrogated how CHKA regulates AR signaling using biochemical assays and investigated androgen regulation of CHKA expression in men with PCa, both untreated (n = 20) and treated with an androgen biosynthesis inhibitor degarelix (n = 27)...
May 2016: Journal of the National Cancer Institute
Lionel Mignion, Pierre Danhier, Julie Magat, Paolo E Porporato, Julien Masquelier, Vincent Gregoire, Giulio G Muccioli, Pierre Sonveaux, Bernard Gallez, Bénédicte F Jordan
The cholinic phenotype, characterized by elevated phosphocholine and a high production of total-choline (tCho)-containing metabolites, is a metabolic hallmark of cancer. It can be exploited for targeted therapy. Non-invasive imaging biomarkers are required to evaluate an individual's response to targeted anticancer agents that usually do not rapidly cause tumor shrinkage. Because metabolic changes can manifest at earlier stages of therapy than changes in tumor size, the aim of the current study was to evaluate (1)H-MRS and diffusion-weighted MRI (DW-MRI) as markers of tumor response to the modulation of the choline pathway in mammary tumor xenografts...
April 15, 2016: International Journal of Cancer. Journal International du Cancer
Kelsey Caetano-Anolles, Minseok Seo, Sandra Rodriguez-Zas, Jae-Don Oh, Jae Yong Han, Kichoon Lee, Tae Sub Park, Sangsu Shin, Zhang Jiao Jiao, Mrinmoy Ghosh, Dong Kee Jeong, Seoae Cho, Heebal Kim, Ki-Duk Song, Hak-Kyo Lee
Japanese quail (Coturnix coturnix japonica) reach sexual maturity earlier, breed rapidly and successfully, and cost less and require less space than other birds raised commercially. Given the value of this species for food production and experimental use, more studies are necessary to determine chromosomal regions and genes associated with gender and breed-differentiation. This study employed Trinity and edgeR for transcriptome analysis of next-generation RNA-seq data, which included 4 tissues obtained from 3 different breeding lines of Japanese quail (random bred control, heavy weight, low weight)...
2015: PloS One
Amarnath Challapalli, Sebastian Trousil, Steve Hazell, Kasia Kozlowski, Mihir Gudi, Eric O Aboagye, Stephen Mangar
AIMS: Malignant transformation results in overexpression of choline-kinase (CHK) and altered choline metabolism, which is potentially detectable by immunohistochemistry (IHC). We investigated the utility of CHK-alpha (CHKA) IHC as a complement to current diagnostic investigation of prostate cancer by analysing expression patterns in normal (no evidence of malignancy) and malignant human prostate tissue samples. METHODS: As an initial validation, paraffin-embedded prostatectomy specimen blocks with both normal and malignant prostate tissue were analysed for CHKA protein and mRNA expression by western blot and quantitative reverse transcriptase PCR (qRT-PCR), respectively...
September 2015: Journal of Clinical Pathology
Elena López-Knowles, Paul M Wilkerson, Ricardo Ribas, Helen Anderson, Alan Mackay, Zara Ghazoui, Aradhana Rani, Peter Osin, Ash Nerurkar, Lorna Renshaw, Alexey Larionov, William R Miller, J Michael Dixon, Jorge S Reis-Filho, Anita K Dunbier, Lesley-Ann Martin, Mitch Dowsett
INTRODUCTION: Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach...
2015: Breast Cancer Research: BCR
Anna Granata, Roberta Nicoletti, Paola Perego, Egidio Iorio, Balaji Krishnamachary, Fabio Benigni, Alessandro Ricci, Franca Podo, Zaver M Bhujwalla, Silvana Canevari, Marina Bagnoli, Delia Mezzanzanica
Epithelial Ovarian Cancer (EOC) "cholinic phenotype", characterized by increased intracellular phosphocholine content sustained by over-expression/activity of choline kinase-alpha (ChoKα/CHKA), is a metabolic cellular reprogramming involved in chemoresistance with still unknown mechanisms.By stable CHKA silencing and global metabolic profiling here we demonstrate that CHKA knockdown hampers growth capability of EOC cell lines both in vitro and in xenotransplant in vivo models. It also affected antioxidant cellular defenses, decreasing glutathione and cysteine content while increasing intracellular levels of reactive oxygen species, overall sensitizing EOC cells to current chemotherapeutic regimens...
May 10, 2015: Oncotarget
Hongde Li, Wandi Zhu, Leike Zhang, Hehua Lei, Xiangyu Wu, Lin Guo, Xinwen Chen, Yulan Wang, Huiru Tang
Chronic infection caused by the hepatitis B virus (HBV), is strongly associated with hepatitis, fatty liver and hepatocellular carcinoma. To investigate the underlying mechanisms, we characterize the metabolic features of host cells infected with the virus using systems biological approach. The results show that HBV replication induces systematic metabolic alterations in host cells. HBV infection up-regulates the biosynthesis of hexosamine and phosphatidylcholine by activating glutamine-fructose-6-phosphate amidotransferase 1 (GFAT1) and choline kinase alpha (CHKA) respectively, which were reported for the first time for HBV infection...
2015: Scientific Reports
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