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https://www.readbyqxmd.com/read/28101198/elevated-expression-of-nrf2-mediates-multidrug-resistance-in-cd133-head-and-neck-squamous-cell-carcinoma-stem-cells
#1
Bao-Cai Lu, Jing Li, Wen-Fa Yu, Guo-Zheng Zhang, Hui-Min Wang, Hui-Min Ma
Enhanced expression of the ATP-binding cassette (ABC) transporter protein ABC sub-family G member 2 (ABCG2) in cancer stem cells (CSCs) plays a major role in chemotherapeutic drug efflux, which results in therapy failure and tumor relapse. In addition to downregulating apoptosis in CSCs, it has been reported that the transcriptional upregulation of the redox sensing factor Nrf2 is involved in the upregulation of ABCG2 expression and consequent chemoresistance. The current study investigated the presence of cancer stem-like side population (SP) cells from head and neck squamous cell carcinoma (HNSCC) samples, and evaluated the Nrf2 expression profile and multidrug resistance properties of HNSCC stem cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100911/variants-on-chromosome-4q21-near-pkd2-and-siblings-are-associated-with-dental-caries
#2
Scott Eckert, Eleanor Feingold, Margaret Cooper, Michael M Vanyukov, Brion S Maher, Rebecca L Slayton, Marcia C Willing, Steven E Reis, Daniel W McNeil, Richard J Crout, Robert J Weyant, Steven M Levy, Alexandre R Vieira, Mary L Marazita, John R Shaffer
A recent genome-wide association study (GWAS) for dental caries nominated the chromosomal region 4q21 near ABCG2, PKD2 and the SIBLING (small integrin-binding ligand N-linked glycoprotein) gene family. In this investigation, we followed up and fine-mapped this region using a tag-SNP (single-nucleotide polymorphism) approach in 13 age- and race-stratified samples from 6 independent studies (N=4089). Participants were assessed for dental caries via intraoral examination and 49 tag-SNPs were genotyped capturing much of the variation in the 4q21 locus...
January 19, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28098816/estrogen-enhances-the-expression-of-the-multidrug-transporter-gene-abcg2-increasing-drug-resistance-of-breast-cancer-cells-through-estrogen-receptors
#3
Fung-Wei Chang, Hueng-Chuen Fan, Jui-Ming Liu, Tai-Ping Fan, Jin Jing, Chia-Ling Yang, Ren-Jun Hsu
BACKGROUND: Multidrug resistance is a major obstacle in the successful therapy of breast cancer. Studies have proved that this kind of drug resistance happens in both human cancers and cultured cancer cell lines. Understanding the molecular mechanisms of drug resistance is important for the reasonable design and use of new treatment strategies to effectively confront cancers. RESULTS: In our study, ATP-binding cassette sub-family G member 2 (ABCG2), adenosine triphosphate (ATP) synthase and cytochrome c oxidase subunit VIc (COX6C) were over-expressed more in the MCF-7/MX cell line than in the normal MCF7 cell line...
January 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28092857/universal-efavirenz-determination-in-transport-study-rat-placenta-perfusion-and-placenta-lysate-by-hplc-uv
#4
Lucie Zelena, Josef Reznicek, Martina Ceckova, Hana Sklenarova
Efavirenz is an antiretroviral drug used in the treatment of HIV-positive patients. A simple, fast and sensitive high-performance liquid chromatography (HPLC) method was developed in order to determine efavirenz in three types of samples provided from pharmacokinetic studies. The analysis took 5min and was performed using a C18 analytical column (Discovery HS C18, 150×4.6mm, particle size of 5μm) in isocratic mode with a mobile phase containing acetonitrile and water (65:35, v/v), a flow rate of 1.6mLmin(-1), a sample volume of 10μL and UV detection at 245nm...
January 11, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28090290/shared-gene-expression-patterns-in-mesenchymal-progenitors-derived-from-lung-and-epidermis-in-pulmonary-arterial-hypertension-identifying-key-pathways-in-pulmonary-vascular-disease
#5
Christa Gaskill, Shennea Marriott, Sidd Pratap, Swapna Menon, Lora K Hedges, Joshua P Fessel, Jonathan A Kropski, DeWayne Ames, Lisa Wheeler, James E Loyd, Anna R Hemnes, Dennis R Roop, Dwight J Klemm, Eric D Austin, Susan M Majka
Rapid access to lung-derived cells from stable subjects is a major challenge in the pulmonary hypertension field, given the relative contraindication of lung biopsy. In these studies, we sought to demonstrate the importance of evaluating a cell type that actively participates in disease processes, as well as the potential to translate these findings to vascular beds in other nonlung tissues, in this instance perivascular skin mesenchymal cells (MCs). We utilized posttransplant or autopsy lung explant-derived cells (ABCG2-expressing mesenchymal progenitor cells [MPCs], fibroblasts) and skin-derived MCs to test the hypothesis that perivascular ABCG2 MPCs derived from pulmonary arterial hypertension (PAH) patient lung and skin would express a gene profile reflective of ongoing vascular dysfunction...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28059154/abcg2-overexpressing-h460-mx20-cell-xenografts-in-athymic-nude-mice-maintained-original-biochemical-and-cytological-characteristics
#6
Wei Zhang, Zhen Chen, Likun Chen, Fang Wang, Furong Li, Xiaokun Wang, Liwu Fu
H460/MX20 are derived from large cell lung cancer H460 cell line and then transformed into ABCG2-overexpressing cells by mitoxantrone's induction, which are widely used in study of multidrug resistance (MDR) in vitro. To establish and spread the model of H460/MX20 cell xenografts, we investigated whether cell biological characteristics and the MDR phenotype were maintained in vivo model. Our results demonstrated that the cell proliferation, cell cycle, and ABCG2 expression level in xH460/MX20 cells isolated from H460/MX20 cell xenografts were similar to H460/MX20 cells in vitro...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28054657/rapamycin-prolongs-the-survival-of-corneal-epithelial-cells-in-culture
#7
Sanaz Gidfar, Farnoud Y Milani, Behrad Y Milani, Xiang Shen, Medi Eslani, Ilham Putra, Michael J Huvard, Hossein Sagha, Ali R Djalilian
Rapamycin has previously been shown to have anti-aging effects in cells and organisms. These studies were undertaken to investigate the effects of rapamycin on primary human corneal epithelial cells in vitro. Cell growth and viability were evaluated by bright field microscopy. Cell proliferation and cycle were evaluated by flow cytometry. The expression of differentiation markers was evaluated by quantitative PCR and Western blot. Senescence was evaluated by senescence-associated β-Galactosidase staining and by Western blot analysis of p16...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28049953/cobalt-chloride-induces-expression-and-function-of-breast-cancer-resistance-protein-bcrp-abcg2-in-human-renal-proximal-tubular-epithelial-cell-line-hk-2
#8
Katsuki Nishihashi, Kei Kawashima, Takami Nomura, Yumiko Urakami-Takebayashi, Makoto Miyazaki, Mikihisa Takano, Junya Nagai
The human breast cancer resistance protein (BCRP/ABCG2), a member of the ATP-binding cassette transporter family, is a drug transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. The cis-regulatory elements in the BCRP promoter include a hypoxia response element, i.e., the DNA binding site for hypoxia-inducible factor-1 (HIF-1). In this study, we investigated the effect of cobalt chloride, a chemical inducer of HIF-1α, on the expression and function of BCRP in human renal proximal tubular cell line HK-2...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28043125/inhibition-of-breast-cancer-resistance-protein-and-multidrug-resistance-associated-protein-2-by-natural-compounds-and-their-derivatives
#9
Noora Sjöstedt, Kira Holvikari, Päivi Tammela, Heidi Kidron
The food and dietary supplements we consume contain a wide variety of plant secondary metabolites and other compounds, which, like drugs, can be absorbed, metabolized, distributed, and excreted from the body. In the intestine, these compounds can interact with transport proteins such as the multidrug resistance associated protein 2 (MRP2, ABCC2) and the breast cancer resistance protein (BCRP, ABCG2) that regulate the absorption of drugs and other compounds. Inhibition of these transporters by dietary components could lead to increased exposure and adverse effects of concomitantly administered drugs...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28042952/uncoupling-protein-2-downregulation-by-hypoxia-through-repression-of-peroxisome-proliferator-activated-receptor-%C3%AE-promotes-chemoresistance-of-non-small-cell-lung-cancer
#10
Mingxing Wang, Guoyin Li, Zhiwei Yang, Lei Wang, Lei Zhang, Ting Wang, Yimeng Zhang, Shengli Zhang, Yong Han, Lintao Jia
Hypoxic microenvironment is critically involved in the response of non-small cell lung cancer (NSCLC) to chemotherapy, the mechanisms of which remain largely unknown. Here, we found that NSCLC patients exhibited increased chemotherapeutic resistance when complicated by chronic obstructive pulmonary disease (COPD), a critical cause of chronic hypoxemia. The downregulation of uncoupling protein 2 (UCP2), which is attributed to hypoxia-inducible factor 1 (HIF-1)-mediated suppression of the transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ), was involved in NSCLC chemoresistance, and predicted a poor survival rate of patients receiving routine chemotherapy...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032597/elevation-of-%C3%AE-galactoside-%C3%AE-2-6-sialyltransferase-1-in-a-fructoseresponsive-manner-promotes-pancreatic-cancer-metastasis
#11
Chi-Che Hsieh, Yi-Ming Shyr, Wen-Ying Liao, Tien-Hua Chen, Shin-E Wang, Peir-Chuen Lu, Pei-Yu Lin, Yan-Bo Chen, Wan-Yu Mao, Hsin-Ying Han, Michael Hsiao, Wen-Bin Yang, Wen-Shan Li, Yuh-Pyng Sher, Chia-Ning Shen
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of pancreatic cancer with clinical characteristics of local invasion and early metastasis. Recent cohort studies indicate high fructose intake is associated with an increase in pancreatic cancer risk. However, the mechanisms by which fructose promotes pancreatic tumorigenesis remain unclear. Herein, Kras+/LSLG12D mice were crossed with Elas-CreER transgenic mice to determine whether fructose intake directly contributes to tumor formation. Orthotopic tumor-xenograft experiments were performed to determine whether fructose substitution enhances the metastatic potential of PDAC cells...
December 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/28030534/single-nucleotide-polymorphism-of-cyp3a5-impacts-the-exposure-to-tacrolimus-in-pediatric-renal-transplant-recipients-a-pharmacogenetic-substudy-of-the-twist-trial
#12
Heiko Billing, Britta Höcker, Alexander Fichtner, Rita van Damme-Lombaerts, Styrbjorn Friman, Jenö Jaray, Karel Vondrak, Eniko Sarvary, Luca Dello Strologo, Michael Oellerich, Nicolas von Ahsen, Burkhard Tönshoff
BACKGROUND: The pharmacokinetics (PK) of tacrolimus (TAC) and mycophenolic acid (MPA) are highly variable. An impact of single-nucleotide polymorphisms (SNPs) of the genes coding for enzymes and transporters involved in the PK of TAC and/or MPA is intuitively conceivable. Accordingly, we sought to analyze the influence of different SNPs on TAC and MPA exposure in pediatric renal transplant recipients. METHODS: A subpopulation of 37 patients (median age: 12.8 years, range 2...
November 24, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28029654/abcg2-confers-promotion-in-gastric-cancer-through-modulating-downstream-crkl-in-vitro-combining-with-biostatistics-mining
#13
Junqing Wang, Zhou Yunyun, Lu Wang, Xuehua Chen, Zhenggang Zhu
ABCG2, member of ATP-binding cassette (ABC) transporter family, is known as crucial regulator related to multi-drug resistance in human tumors and has recently been putatively studied as human carcinoma cell biomarker. While, effects of ABCG2 on human gastric cancer (GC) has not been illustrated thoroughly. In this study, by applying biostatistics mining methods, we observed that ABCG2 is frequently aberrantly expressed in GC patients through exploring dataset of GSE19826 in NCBI GEO database. Contemporary, extreme up-regulation of ABCG2 was discovered in both GC specimens and cell lines of our center, from which we observed high level of ABCG2 associated with GC clinicopathologic features and poor outcomes...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/28008607/microrna-320a-and-4496-attenuate-helicobacter-pylori-caga-induced-cancer-initiating-potential-and-chemo-resistance-by-targeting-%C3%AE-catenin-and-abcg2
#14
Dong Woo Kang, Eun Sun Yang, Yu Na Noh, Won Chan Hwang, Se-Young Jo, Young-Ah Suh, Won Sang Park, Kang-Yell Choi, Do Sik Min
Infection by Helicobacter pylori (H. pylori) is closely linked to increased risk of gastric cancer. Although CagA, a major virulence factor of H. pylori, is known to be a causal factor of gastric carcinogenesis, the molecular link between CagA and gastric cancer-initiating cell (CIC)-like properties remains elusive. Here, we demonstrate that CagA is required for increased expression of β-catenin and its target CIC markers via downregulation of microRNA (miR)-320a and miR-4496. CagA promotes gastric CIC properties and is responsible for chemo-resistance...
December 23, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28005280/abcg2-bcrp-specific-and-nonspecific-modulators
#15
REVIEW
Diana Peña-Solórzano, Simone Alexandra Stark, Burkhard König, Cesar Augusto Sierra, Cristian Ochoa-Puentes
Multidrug resistance (MDR) in cancer cells is the development of resistance to a variety of structurally and functionally nonrelated anticancer drugs. This phenomenon has become a major obstacle to cancer chemotherapy seriously affecting the clinical outcome. MDR is associated with increased drug efflux from cells mediated by an energy-dependent mechanism involving the ATP-binding cassette (ABC) transporters, mainly P-glycoprotein (ABCB1), the MDR-associated protein-1 (ABCC1), and the breast cancer resistance protein (ABCG2)...
December 22, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27991849/trough-concentration-and-abcg2-polymorphism-are-better-to-predict-imatinib-response-in-chronic-myeloid-leukemia-a-meta-analysis
#16
Zhi-Ping Jiang, Xie-Lan Zhao, Naoto Takahashi, Sabrina Angelini, Biswajit Dubashi, Li Sun, Ping Xu
AIM: The present study aimed to conduct a series of meta-analyses to investigate the influence of imatinib trough concentration (C0), as well as ABCB1 and ABCG2 polymorphisms, on the clinical response in patients with chronic myeloid leukemia (CML). METHODS: A literature search was conducted using the PubMed and Cochrane electronic databases to locate relevant papers from 2003 onward. Then, an initial meta-analysis of 14 studies involving 2184 patients was conducted to understand the effect of imatinib mesylate (IM) C0 on clinical outcome in CML patients...
January 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/27988213/down-regulation-of-abcg2-a-urate-exporter-by-parathyroid-hormone-enhances-urate-accumulation-in-secondary-hyperparathyroidism
#17
Ryusei Sugimoto, Hiroshi Watanabe, Komei Ikegami, Yuki Enoki, Tadashi Imafuku, Yoshiaki Sakaguchi, Michiya Murata, Kento Nishida, Shigeyuki Miyamura, Yu Ishima, Motoko Tanaka, Kazutaka Matsushita, Hirotaka Komaba, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which the serum parathyroid hormone (PTH) affects serum urate levels remains unknown. This was studied in uremic rats with secondary hyperparathyroidism where serum urate levels were found to be increased and urate excretion in the intestine and kidney decreased, presumably due to down-regulation of the expression of the urate exporter ABCG2 in intestinal and renal epithelial membranes...
December 14, 2016: Kidney International
https://www.readbyqxmd.com/read/27977217/identification-and-characterization-of-trimethylamine-n-oxide-uptake-and-efflux-transporters
#18
Wendy A Teft, Bridget L Morse, Brenda F Leake, Aze Wilson, Sara E Mansell, Robert A Hegele, Richard H Ho, Richard B Kim
Trimethylamine-N-oxide (TMAO) is a recently identified predictor of cardiovascular and chronic kidney disease. TMAO is primarily generated through gut-microbiome mediated conversion of dietary choline and carnitine to TMA, which is converted to TMAO by hepatic flavin monooxygenase 3 (FMO3) and subsequently undergoes renal elimination. We investigated the role of uptake and efflux drug transporters in TMAO disposition in vitro and in vivo. After screening a large array of uptake transporters, we show organic cation transporter 2 (OCT2) is the key transporter for TMAO cellular uptake...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27974484/buprenorphine-norbuprenorphine-r-methadone-and-s-methadone-upregulate-bcrp-abcg2-expression-by-activating-aryl-hydrocarbon-receptor-in-human-placental-trophoblasts
#19
Naveen K Neradugomma, Michael Z Liao, Qingcheng Mao
Opioid dependence during pregnancy is a rising concern. Maintaining addicted pregnant women on long-acting opioid receptor agonist is the most common strategy to manage pregnancy drug abuse. Methadone (MET) and Buprenorphine (BUP) are widely prescribed for opiate-maintenance therapy. Norbuprenorphine (NBUP) is the primary active metabolite of BUP. These medications can cross the placenta to the fetus, leading to postpartum neonatal abstinence syndrome. Despite their use during pregnancy, little is known about the cellular changes brought about by these drugs in the placenta...
December 14, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27967318/effect-of-polymorphisms-in-cyp3a4-ppara-nr1i2-nfkb1-abcg2-and-slco1b1-on-the-pharmacokinetics-of-lovastatin-in-healthy-chinese-volunteers
#20
Guilian Zhao, Mei Liu, Xiujun Wu, Guofei Li, Feng Qiu, Jingkai Gu, Limei Zhao
AIM: This study examined whether gene polymorphisms (CYP3A4, ABCG2, SLCO1B1, NR1I2, PPARA and NFKB1) influenced the pharmacokinetics of lovastatin in Chinese healthy subjects. PATIENTS & METHOD: Plasma concentrations of lovastatin and lovastatin acid were quantified using LC/MS/MS. RESULTS: PPARA c.208+3819 G allele carriers had approximately twofold higher AUC0-∞ and Cmax of lovastatin than wild-type (PPARA c.208+3819 AA) subjects. After adjustment for the PPARA variants, subjects with the SLCO1B1 521TT genotype had approximately 50% lower AUC0-∞ of lovastatin acid than those with 521TC/CC genotypes, while the AUC0-∞ of lovastatin lactone in NFKB1-94 DD wild-type carriers was twofold higher than in mutant homozygotes carriers...
January 2017: Pharmacogenomics
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