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Undraga Schagdarsurengin, Angela Lammert, Natalie Schunk, Diana Sheridan, Stefan Gattenloehner, Klaus Steger, Florian Wagenlehner, Temuujin Dansranjavin
BACKGROUND: Human cancer cells often exhibit impaired IGF2 expression and the underlying mechanisms are multifaceted and complex. Besides the well-known imprinting control region IGF2/H19-ICR, the involvement of a differentially methylated region in the promoter P0 of IGF2 gene (IGF2-DMR0) has been suggested. Here, we evaluate several mechanisms potentially leading to up- and/or down-regulation of IGF2 expression in prostate cancer and present a novel role of Kruppel-like factor 4 (KLF4) as a transcriptional regulator of IGF2 binding in IGF2-DMR0...
October 10, 2017: Cell Communication and Signaling: CCS
Mojgan Naghitorabi, Hamid Mir Mohammad Sadeghi, Javad Mohammadi Asl, Mohammad Rabbani, Abbas Jafarian-Dehkordi
Promoter methylation is one of the main epigenetic mechanisms that leads to the inactivation of tumor suppressor genes during carcinogenesis. Due to the reversible nature of DNA methylation, many studies have been performed to correct theses epigenetic defects by inhibiting DNA methyltransferases (DNMTs). In this case novel therapeutics especially siRNA oligonucleotides have been used to specifically knock down the DNMTs at mRNA level. Also many studies have focused on transcriptional gene silencing in mammalian cells via siRNA mediated promoter methylation...
2017: Iranian Journal of Pharmaceutical Research: IJPR
Guanglei Chen, Hao Zhang, Lisha Sun, Yanlin Jiang, Zhen Xu, Huizi Gu, Hong Xu, Jie Yang, Yining Wang, Tiantian Xu, Yingchao Zhang, Caigang Liu
BACKGROUND: Previous studies showed that glutathione S-transferase Pi 1 (GSTP1) is a critical metabolic driver that is heightened specifically in triple negative breast cancer (TNBC) and drives breast cancer pathogenicity. This study focuses on investigating the relationship between the expression of the GSTP1 protein and TNBC metastasis and prognosis in China. RESULTS: Chi-square and Fisher's exact tests showed that tumor size (P=0.023) and clinical stage (P=0...
September 15, 2017: Oncotarget
Konda Kumaraswami, Shiva Krishna Katkam, Amita Aggarwal, Aman Sharma, Ramesh Manthri, Vijay Kumar Kutala, Liza Rajasekhar
AIM: To investigate the impact of genetic variants in CYP2C9, CYP2C19, CYP3A4, GSTT1, GSTM1 and GSTP1 on the efficacy of cyclophosphamide (CYC) therapy in patients with lupus nephritis. MATERIALS & METHODS: Lupus nephritis patients (n = 220) treated with CYC were included in the study. RESULTS: Logistic regression analysis identified CYP2C19*2 as an independent predictor of CYC therapeutic failure (odds ratio [OR]: 2.69; p = 0.0043). Bivariate and trivariate analysis showed the subjects harboring CYP2C19*2 and GSTP1 (OR: 3...
October 4, 2017: Pharmacogenomics
Elizabeth Smyth, Shenli Zhang, David Cunningham, Andrew Wotherspoon, Richie Soong, Clare Peckitt, Nicola Valeri, Matteo Fassan, Massimo Rugge, Alicia Fc Okines, William Allum, Sally Stenning, Matthew Nankivell, Ruth E Langley, Patrick Tan
PURPOSE: Germline polymorphisms may affect chemotherapy efficacy and toxicity. We examined the effect of polymorphisms in drug metabolism and DNA repair genes on pathological response rates, survival, and toxicity for patients randomised to surgery alone or perioperative ECF chemotherapy in the MRC MAGIC trial. EXPERIMENTAL DESIGN: DNA was extracted from non-tumor resection FFPE blocks. ERCC1, ERCC2, XRCC1, DYPD, and OPRT SNPs were evaluated using Sequenom, GSTP1, GSTT1 deletion and TYMS (TS) 5' 2R/3R using multiplex PCR...
October 2, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Xueyan Dong, Qiang Hou, Yueming Chen, Xianjun Wang
This study sought to evaluate the diagnostic value of the methylation of multiple gene promoters in serum in hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). A total of 343 participants were enrolled, including 98 patients with HCC, 75 patients with liver cirrhosis (LC), 90 patients with chronic hepatitis B (CHB), and 80 healthy individuals. RASSF1A, APC, BVES, TIMP3, GSTP1, and HOXA9 were selected as the candidate genes. The MethyLight method was used to assay promoter methylation statuses...
2017: Disease Markers
Siti Maziras Makhtar, Azlan Husin, Abdul Aziz Baba, Ravindran Ankathil
The detoxifying activity of glutathione S-transferases (GST) enzymes not only protect cells from the adverse effects of xenobiotics, but also alters the effectiveness of drugs in cancer cells, resulting in toxicity or drug resistance. In this study, we aimed to evaluate the association of GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms with treatment response among Malaysian chronic myeloid leukaemia (CML) patients who everyday undergo 400 mg of imatinib mesylate (IM) therapy. Multiplex polymerase chain reaction (multiplex-PCR) was performed to detect GSTM1 and GSTT1 polymorphisms simultaneously and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was conducted to detect the GSTP1 Ile195Val polymorphism...
September 2017: Journal of Genetics
Guilherme Ribeiro Romualdo, Tony Fernando Grassi, Renata Leme Goto, Mariana Baptista Tablas, Lucas Tadeu Bidinotto, Ana Angélica Henrique Fernandes, Bruno Cogliati, Luís Fernando Barbisan
This study aimed the integrative characterization of morphological, biochemical and molecular features of chemically-induced cirrhosis-associated hepatocarcinogenesis. Thus, male Wistar rats were submitted to a diethylnitrosamine (DEN)/thioacetamide (TAA)-induced model. Liver tissue was processed for global gene expression, histopathological and collagen evaluations; as well as immunohistochemical and oxidative stress analysis. Gene Ontology and functional analysis showed the upregulation of extracellular matrix deposition genes, such as collagen type I alpha 1 and 2 (Col1α1 and Col1α2) and tissue inhibitor of metalloproteinase 1 and 2 genes (Timp1 and Timp2)...
September 21, 2017: Toxicology Letters
Sreemanta Pramanik, Depanwita Saha
Fluorosis, caused by ingestion of excess fluoride, is endemic in at least 25 countries across the globe, China and India being the worst affected among them. Dental, skeletal and non-skeletal are the major types of fluorosis affecting millions of people in these countries. A number of genetic epidemiological studies carried out by investigators have shown the evidence for association between genetic polymorphisms in candidate genes and differences in the susceptibility pattern of different types of fluorosis among individuals living in the same community and having the same environmental exposure...
September 15, 2017: Environmental Toxicology and Pharmacology
Rance Nault, Kelly A Fader, Jack R Harkema, Tim Zacharewski
The aryl hydrocarbon receptor (AhR) is a highly conserved transcription factor that mediates a broad spectrum of species-, strain-, sex-, age-, tissue-, and cell-specific responses elicited by structurally diverse ligands including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dose-dependent effects on liver-specific and sexually dimorphic gene expression were examined in male and female mice gavaged with TCDD every 4 days for 28 or 92 days. RNA-seq data revealed the coordinated repression of 181 genes predominately expressed in the liver including albumin (3...
2017: PloS One
Youjin Kim, Alex G Wu, Asha Jaja-Chimedza, Brittany L Graf, Carrie Waterman, Michael P Verzi, Ilya Raskin
Moringa (Moringa oleifera Lam.) seed extract (MSE) has anti-inflammatory and antioxidant activities. We investigated the effects of MSE enriched in moringa isothiocyanate-1 (MIC-1), its putative bioactive, on ulcerative colitis (UC) and its anti-inflammatory/antioxidant mechanism likely mediated through Nrf2-signaling pathway. Dextran sulfate sodium (DSS)-induced acute (n = 8/group; 3% DSS for 5 d) and chronic (n = 6/group; cyclic rotations of 2.5% DSS/water for 30 d) UC was induced in mice that were assigned to 4 experimental groups: healthy control (water/vehicle), disease control (DSS/vehicle), MSE treatment (DSS/MSE), or 5-aminosalicyic acid (5-ASA) treatment (positive control; DSS/5-ASA)...
2017: PloS One
Duojia Wu, Jie Ni, Julia Beretov, Paul Cozzi, Mark Willcox, Valerie Wasinger, Bradley Walsh, Peter Graham, Yong Li
Prostate cancer (CaP) is the most common cancer in men and the second leading cause of cancer deaths in males in Australia. Although serum prostate-specific antigen (PSA) has been the most widely used biomarker in CaP detection for decades, PSA screening has limitations such as low specificity and potential association with over-diagnosis. Current biomarkers used in the clinic are not useful for the early detection of CaP, or monitoring its progression, and have limited value in predicting response to treatment...
October 2017: Critical Reviews in Oncology/hematology
Siddhartha Deb, Kylie L Gorringe, Jia-Min B Pang, David J Byrne, Elena A Takano, kConFab Investigators, Alexander Dobrovic, Stephen B Fox
BACKGROUND: Male breast cancer (MBC) represents a poorly characterised group of tumours, the management of which is largely based on practices established for female breast cancer. However, recent studies demonstrate biological and molecular differences likely to impact on tumour behaviour and therefore patient outcome. The aim of this study was to investigate methylation of a panel of commonly methylated breast cancer genes in familial MBCs. METHODS: 60 tumours from 3 BRCA1 and 25 BRCA2 male mutation carriers and 32 males from BRCAX families were assessed for promoter methylation by methylation-sensitive high resolution melting in a panel of 10 genes (RASSF1A, TWIST1, APC, WIF1, MAL, RARβ, CDH1, RUNX3, FOXC1 and GSTP1)...
September 11, 2017: BMC Cancer
Huijie Gao, Chao Liu, Sijia Song, Chuanqiang Zhang, Qun Ma, Xiao Li, Luo Xu
Increasing lines of evidence show that oxidative stress plays a role in the pathophysiological mechanisms of schizophrenia (SCZ). Polymorphic variants of oxidative stress-related candidate genes GPX1 and GST1 can affect the antioxidant activities of their encoded enzymes. Therefore, this study aimed to explore the association between the single nucleotide polymorphisms (SNPs) of GPX1 and GSTP1 and susceptibility to schizophrenia in the Chinese Han population. DNA from 323 healthy controls and 210 schizophrenic patients was genotyped for SNPs rs1050450 in GPX1 and rs1695 in GSTP1 using a predesigned TaqMan SNP genotyping assay...
September 1, 2017: Neuroreport
Tomohiko Sakabe, Junya Azumi, Yoshihisa Umekita, Kan Toriguchi, Etsuro Hatano, Yasuaki Hirooka, Goshi Shiota
BACKGROUND/AIM: Cancer stem cells (CSCs) are associated with prognosis of hepatocellular carcinoma (HCC). In our previous study, we created cDNA microarray databases on the CSC population of human HuH7 cells. In the present study, we identified genes that might serve as prognostic markers of HCC by employing existing databases. MATERIALS AND METHODS: Expressions of glutathione S-transferase pi 1 (GSTP1), lysozyme (LYZ), C-X-C motif chemokine ligand 5 (CXCL5), interleukin-8 (IL8) and dickkopf WNT signaling pathway inhibitor 1 (DKK1), the five most highly expressed genes in the CSC cDNA microarray databases, were examined in 99 patients with HCC by real-time polymerase chain reaction (qRT-PCR), and their clinical significance was analyzed...
September 2017: Anticancer Research
Asmaa Abo-Bakr, Ghada Mossallam, Nevin El Azhary, Hanafy Hafez, Ragia Badawy
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The interindividual genetic variations in drug metabolizing enzymes and DNA repair genes influence the efficacy and toxicity of numerous chemotherapeutic drugs affecting the treatment outcome. AIM OF THE WORK: The aim of the study was to investigate the impact of drug metabolizing CYP1, GSTP1 and DNA repair (XRCC1) genes polymorphisms on the toxicity and response to chemotherapy in childhood ALL...
August 22, 2017: Journal of the Egyptian National Cancer Institute
Fangming Kan, Lei Ye, Tao Yan, Jiaqi Cao, Jianhua Zheng, Wuping Li
BACKGROUND: Human hepatitis B virus (HBV) infection is an important public health issue in the Asia-Pacific region and is associated with chronic hepatitis, liver fibrosis, cirrhosis and even liver cancer. However, the underlying mechanisms of HBV-associated liver fibrosis remain incompletely understood. RESULTS: In the present study, proteomic and transcriptomic approaches as well as biological network analyses were performed to investigate the differentially expressed molecular signature and key regulatory networks that were associated with HBV-mediated liver fibrosis...
August 22, 2017: BMC Genomics
B S Chagas, A P A D Gurgel, S S L Paiva Júnior, R C P Lima, M N Cordeiro, R R Moura, A V C Coelho, K C G Nascimento, J C Silva Neto, S Crovella, A C Freitas
Human papillomavirus (HPV) infection is considered a risk factor for cervical cancer. Even if the high-risk HPV (HR-HPV) infection is necessary, environmental co-factors and genetic susceptibility also play an important role in cervical cancer development. In this study, a possible association of rs1695 GSTP1 polymorphisms, HR-HPV infection, and oral contraceptive use with cancer lesion development in women was investigated. The study population comprised 441 Brazilian women from the Northeast region including 98 HPV-infected women with high-grade squamous intraepithelial lesions, 77 HPV-infected women with low-grade squamous intraepithelial lesions, and 266 HPV-negative women with no lesion, used as a control...
August 17, 2017: Genetics and Molecular Research: GMR
Hie-Won Hann, Surbhi Jain, Grace Park, Jamin D Steffen, Wei Song, Ying-Hsiu Su
AIM: This study aimed to explore the potential of detecting hepatocellular carcinoma (HCC)-associated DNA markers, TP53 249T mutations and aberrant methylation of RASSF1A and GSTP1 genes, for monitoring HCC recurrence. HCC remains a leading cause of death worldwide, with one of the fastest growing incidence rates in the US. While treatment options are available and new ones emerging, there remains a poor prognosis of this disease mostly due to its late diagnosis and high recurrence rate...
2017: Hepatoma Research
Asha Jaja-Chimedza, Brittany L Graf, Charlotte Simmler, Youjin Kim, Peter Kuhn, Guido F Pauli, Ilya Raskin
Moringa oleifera Lam. is a tropical plant, used for centuries as food and traditional medicine. The aim of this study was to develop, validate and biochemically characterize an isothiocyanate-enriched moringa seed extract (MSE), and to compare the anti-inflammatory effects of MSE-containing moringa isothiocyanate-1 (MIC-1) with a curcuminoid-enriched turmeric extract (CTE), and a material further enriched in its primary phytochemical, curcumin (curcumin-enriched material; CEM). MSE was prepared by incubating ground moringa seeds with water to allow myrosinase-catalyzed enzymatic formation of bioactive MIC-1, the predominant isothiocyanate in moringa seeds...
2017: PloS One
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