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https://www.readbyqxmd.com/read/29777275/overexpression-of-abcb4-contributes-to-acquired-doxorubicin-resistance-in-breast-cancer-cells-in-vitro
#1
Jia-Feng Huang, Chun-Jie Wen, Guo-Zhi Zhao, Yi Dai, Ying Li, Lan-Xiang Wu, Hong-Hao Zhou
PURPOSE: Doxorubicin is one of the most active agents in the first-line therapy for metastatic breast cancer, but its utility is partially limited by the frequent emergence of doxorubicin resistance. In this study, we aimed to investigate the role of ATP-binding cassette sub-family B, member 4 (ABCB4) in acquired doxorubicin resistance in breast cancer cells, as well as its potential mechanism. METHODS: In doxorubicin-sensitive and -resistant breast cancer cell lines MCF-7 and MDA-MB-231, the expression levels of ABCB4 were detected using real-time quantitative PCR and Western blot analysis, the DNA methylation and histone acetylation status of ABCB4 gene were investigated by bisulfite-sequencing PCR (BSP) and chromatin immunoprecipitation (ChIP) assays, and the doxorubicin sensitivity and intracellular doxorubicin accumulation were observed using cell cytotoxicity assay and flow cytometry...
May 18, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29761167/phenotypic-spectrum-and-diagnostic-pitfalls-of-abcb4-deficiency-depending-on-age-of-onset
#2
Stephanie Barbara Schatz, Christoph Jüngst, Verena Keitel-Anselmo, Ralf Kubitz, Christina Becker, Patrick Gerner, Eva-Doreen Pfister, Imeke Goldschmidt, Norman Junge, Daniel Wenning, Stephan Gehring, Stefan Arens, Dirk Bretschneider, Dirk Grothues, Guido Engelmann, Frank Lammert, Ulrich Baumann
Genetic variants in the adenosine triphosphate-binding cassette subfamily B member 4 ( ABCB4 ) gene, which encodes hepatocanalicular phosphatidylcholine floppase, can lead to different phenotypes, such as progressive familial intrahepatic cholestasis (PFIC) type 3, low phospholipid-associated cholelithiasis, and intrahepatic cholestasis of pregnancy. The aim of this multicenter project was to collect information on onset and progression of this entity in different age groups and to assess the relevance of this disease for the differential diagnosis of chronic liver disease...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29751877/pathologic-features-of-hereditary-cholestatic-diseases
#3
REVIEW
Andrew D Clouston
The inherited diseases causing conjugated hyperbilirubinemia are diverse, with variability in clinical severity, histologic appearance, and time of onset. The liver biopsy appearances can also vary depending on whether the initial presentation is in the neonatal period or later. Although many of the disorders have specific histologic features in fully developed and classic cases, biopsies taken early in the disease course may be nonspecific, showing either cholestatic hepatitis or an obstructive pattern of injury requiring close correlation with the laboratory and clinical findings to reach the correct diagnosis...
June 2018: Surgical Pathology Clinics
https://www.readbyqxmd.com/read/29743122/spin1-negatively-regulated-by-mir-148-152-enhances-adriamycin-resistance-via-upregulating-drug-metabolizing-enzymes-and-transporter-in-breast-cancer
#4
Xu Chen, Ya-Wen Wang, Peng Gao
BACKGROUND: Spindlin1 (SPIN1), a protein highly expressed in several human cancers, has been correlated with tumorigenesis and development. Alterations of drug metabolizing enzymes and drug transporters are major determinants of chemoresistance in tumor cells. However, whether the metabolizing enzymes and transporters are under the control of SPIN1 in breast cancer chemoresistance has not yet been defined. METHODS: SPIN1 expression in breast cancer cells and tissues was detected by quantitative real-time PCR (qRT-PCR) and immunohistochemistry...
May 9, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29709678/lysyl-oxidase-like-protein-2-loxl2-modules-barrier-function-in-cholangiocytes-in-cholestasis
#5
Marion J Pollheimer, Silvia Racedo, Amanda Mikels-Vigdal, Derek Marshall, Christopher Bowlus, Carolin Lackner, Tobias Madl, Tom H Karlsen, Johannes R Hov, Susan K Lyman, Joanne Adamkewicz, Victoria Smith, Emmanuel Moreau, Gernot Zollner, Tor Jacob Eide, Tatjana Stojakovic, Hubert Scharnagl, Hans-Jürgen Gruber, Rudolf E Stauber, Michael Trauner, Peter Fickert
BACKGROUND: The lysyl oxidase-like protein 2 (LOXL2) promotes stabilization of the extracellular matrix, chemotaxis, cell growth and cell mobility. We aimed to (i) identify stimuli of LOXL2 in cholangiopathies, (ii) characterize the effects of LOXL2 on biliary epithelial cells' (BECs) barrier function, (iii) compare LOXL2 expression in PSC, PBC, and disease controls, and (iv) to determine LOXL2 expression and cellular sources in 4 mouse models for cholangiopathies. METHODS: Cultured murine BECs were challenged with well-known triggers of cellular senescence, hypoxia, phospholipid-deficient Abcb4-/- mouse bile and chenodeoxycholic acid (CDCA) and investigated for LOXL2, SNAIL1 and E-cadherin expression and transepithelial electrical resistance (TEER) with and without LOX-inhibition...
April 27, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29643204/l1-retrotransposition-is-a-common-feature-of-mammalian-hepatocarcinogenesis
#6
Stephanie N Schauer, Patricia E Carreira, Ruchi Shukla, Daniel J Gerhardt, Patricia Gerdes, Francisco J Sanchez-Luque, Paola Nicoli, Michaela Kindlova, Serena Ghisletti, Alexandre Dos Santos, Delphine Rapoud, Didier Samuel, Jamila Faivre, Adam D Ewing, Sandra R Richardson, Geoffrey J Faulkner
The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) is a continuing source of germline and somatic mutagenesis in mammals. Deregulated L1 activity is a hallmark of cancer, and L1 mutagenesis has been described in numerous human malignancies. We previously employed retrotransposon capture sequencing (RC-seq) to analyze hepatocellular carcinoma (HCC) samples from patients infected with hepatitis B or hepatitis C virus and identified L1 variants responsible for activating oncogenic pathways. Here, we have applied RC-seq and whole-genome sequencing (WGS) to an Abcb4 (Mdr2) -/- mouse model of hepatic carcinogenesis and demonstrated for the first time that L1 mobilization occurs in murine tumors...
April 11, 2018: Genome Research
https://www.readbyqxmd.com/read/29616130/co-expression-of-atp-binding-cassette-transporters-is-associated-with-poor-prognosis-in-acute-myeloid-leukemia
#7
Bei Liu, Li-Jun Li, Xia Gong, Wei Zhang, Hui Zhang, Li Zhao
Chemotherapy failure remains a challenge when treating patients with acute myeloid leukemia (AML), who often suffer from persistent or relapsed disease. The multidrug resistance (MDR) mediated by efflux transporters of the ATP binding cassette (ABC) superfamily is a major obstacle for successful chemotherapy. The present study aimed to elucidate whether the expression of ABC transporters was associated with prognostic factors and responses to chemotherapy in patients with AML, with particular focus on whether co-expression of multiple ABC transporters resulted in a worse prognosis...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29572910/ntcp-inhibition-has-hepatoprotective-effects-in-cholestasis-in-mice
#8
Davor Slijepcevic, Reinout L P Roscam Abbing, Claudia D Fuchs, Lizette C M Haazen, Ulrich Beuers, Michael Trauner, Ronald P J Oude Elferink, Stan F J van de Graaf
Accumulation of bile salts during cholestasis leads to hepatic and biliary injury, driving inflammatory and fibrotic processes. The Na+ -Taurocholate Cotransporting Polypeptide (NTCP) is the major hepatic uptake transporter of bile salts, and can be specifically inhibited by myrcludex B. We hypothesized that inhibition of NTCP dampens cholestatic liver injury. Acute cholestasis was induced in mice by a 3.5-diethoxycarbonyl-1.4-dihydrocollidine (DDC) diet or by bile duct ligation (BDL). Chronic cholestasis was investigated in Atp8b1-G308V and Abcb4/Mdr2 deficient mice...
March 24, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29454797/alterations-in-intestinal-microbiota-lead-to-production-of-interleukin-17-by-intrahepatic-%C3%AE-%C3%AE-t-cell-receptor-positive-cells-and-pathogenesis-of-cholestatic-liver-disease
#9
Dana Tedesco, Manoj Thapa, Chui-Yoke Chin, Yong Ge, Minghao Gong, Jing Li, Sanjeev Gumber, Patrick Speck, Elizabeth J Elrod, Eileen M Burd, William H Kitchens, Joseph F Magliocca, Andrew B Adams, David S Weiss, Mansour Mohamadzadeh, Arash Grakoui
BACKGROUND & AIMS: Variants at the ABCB4 or MDR2 locus, which encodes a biliary transport protein, are associated with a spectrum of cholestatic liver diseases. Exacerbation of liver disease has been linked to increased hepatic levels of interleukin (IL) 17, yet the mechanisms of this increase are not understood. We studied mice with disruption of Mdr2 to determine how defects in liver and alteration in the microbiota contribute to production of IL17 by intrahepatic γδ T cells. METHODS: We performed studies with Mdr2-/- and littermate FVB/NJ (control) mice...
February 15, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29390323/liver-transplantation-for-decompensated-liver-cirrhosis-caused-by-progressive-familial-intrahepatic-cholestasis-type-3-a-case-report
#10
Deng Xiang, Jiannan He, Hongmei Wang, Fangfang Xiong, Hao Cheng, Junhua Ai, Renfeng Shan, Renhua Wan, Lunli Zhang, Jun Shi
RATIONALE: Progressive familial intrahepatic cholestasis (PFIC) type 3, characterized by high gamma glutamyl transferase (GGT), is an autosomal recessive genetic disease. It often occurs in patients' first years of age. However, high GGT type PFIC is still rare. PATIENT CONCERNS: The present study reports a case of liver transplantation for decompensated liver cirrhosis caused by PFIC type 3. An 18-year-old male presented with a history of abdominal distension and jaundice for 2 months...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29371412/loss-of-abcb4-attenuates-the-caspase-dependent-apoptosis-regulating-resistance-to-5-fu-in-colorectal-cancer
#11
Hanqing Hu, Meng Wang, Xu Guan, Ziming Yuan, Zheng Liu, Chaoxia Zou, Guiyu Wang, Xu Gao, Xishan Wang
The adenosine triphosphate-binding cassette (ABC) is a large group of proteins involved in material transportation, cellular homeostasis, and closely associated with chemoresistance. ATP-binding cassette protein B4 (ABCB4) is a member of ABCs which has a similar structure to ABCB1, but fewer researches were performed. The present study is aimed to investigate the putative mechanism of ABCB4 in 5-fluorouracil (5-Fu) resistance. Then, we found that ABCB4 was significantly down-regulated in the 5-Fu resistant HCT8 cell lines by polymerase chain reaction (PCR) and Western blot...
February 28, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29356312/cenicriviroc-a-cytokine-receptor-antagonist-potentiates-all-trans-retinoic-acid-in-reducing-liver-injury-in-cholestatic-rodents
#12
Dongke Yu, Shi-Ying Cai, Albert Mennone, Pamela Vig, James L Boyer
BACKGROUND & AIMS: Cholestatic liver injury is mediated by bile acid-induced inflammatory responses. We hypothesized that superior therapeutic effects might be achieved by combining treatments that reduce the bile acid pool size with one that blocks inflammation. METHODS: Bile duct-ligated (BDL) rats and Mdr2(Abcb4)-/- mice were treated with all-trans retinoic acid (atRA), a potent inhibitor of bile acid synthesis, 5 mg/kg/d by gavage, or Cenicriviroc (CVC), a known antagonist of CCR2 and CCR5, 50 mg/kg/d alone or in combination for 14 days and 1 month respectively...
January 22, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29304564/unexplained-cholestasis-in-adults-and-adolescents-diagnostic-benefit-of-genetic-examination
#13
Luise Aamann, Nikolaj Ørntoft, Ida Vogel, Henning Grønbaek, Naja Becher, Hendrik Vilstrup, Peter Ott, Dorte Launholt Lildballe
OBJECTIVES: A few adult and adolescent patients with even severe cholestatic liver disease remain unexplained after standard diagnostic work-up. We studied the value of genetic examination in such patients and developed a panel of eight genes with known cholestatic associations. MATERIALS AND METHODS: Thirty-three patients with unexplained cholestasis despite a thorough clinical work-up were examined for sequence variations in the coding regions of the ABCB4, ABCB11, ABCC2, ABCG5, ATP8B1, JAG1, NOTCH2, and UGT1A1 genes and the promoter region of UGT1A1 by massive parallel sequencing of DNA extracted from whole blood...
March 2018: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/29285212/tumor-suppressive-effect-of-s-adenosylmethionine-supplementation-in-a-murine-model-of-inflammation-mediated-hepatocarcinogenesis-is-dependent-on-treatment-longevity
#14
Evgeniy Stoyanov, Lina Mizrahi, Devorah Olam, Temima Schnitzer-Perlman, Eithan Galun, Daniel S Goldenberg
Chronic inflammation precedes the majority of hepatocellular carcinoma (HCC) cases. We investigated the chemopreventive potential of S-adenosylmethionine (SAM), an essential donor for all methylation reactions in the cell, at the late precancerous stage of HCC development using the Mdr2-knockout (Mdr2-KO, Abcb4-/- ) mice, a model of inflammation-mediated hepatocarcinogenesis. Previously, we revealed down-regulation of the genes regulating SAM metabolism in the liver of these mice at the precancerous stages...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29238877/cryptogenic-cholestasis-in-young-and-adults-atp8b1-abcb11-abcb4-and-tjp2-gene-variants-analysis-by-high-throughput-sequencing
#15
Giovanni Vitale, Stefano Gitto, Francesco Raimondi, Alessandro Mattiaccio, Vilma Mantovani, Ranka Vukotic, Antonietta D'Errico, Marco Seri, Robert B Russell, Pietro Andreone
BACKGROUND: Mutations in ATP-transporters ATPB81, ABCB11, and ABCB4 are responsible for progressive familial intrahepatic cholestasis (PFIC) 1, 2 and 3, and recently the gene for tight junction protein-2 (TJP2) has been linked to PFIC4. AIM: As these four genes have been poorly studied in young people and adults, we investigated them in this context here. METHODS: In patients with cryptogenic cholestasis, we analyzed the presence of mutations by high-throughput sequencing...
December 13, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/29219179/multidrug-resistant-lncrna-profile-in-chemotherapeutic-sensitive-and-resistant-ovarian-cancer-cells
#16
Juan Xu, Jiacong Wu, Chenyang Fu, Fang Teng, Siyu Liu, Chencheng Dai, Rong Shen, Xuemei Jia
Most ovarian cancer patients are chemosensitive initially, but finally relapse with acquired chemoresistance. Multidrug-resistance is the extremely terrible situation. The mechanism for the acquired chemoresistance of ovarian cancer patients is still not clear. LncRNAs have been recognized as the important regulator of a variety of biological processes, including the multidrug-resistant process. Here, we carried out the lncRNA sequencing of the ovarian cancer cell line A2780 and the paxitaxel resistant cell line A2780/PTX which is also cross resistant to the cisplatin and epirubicin...
June 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29145976/not-only-p-glycoprotein-amplification-of-the-abcb1-containing-chromosome-region-7q21-confers-multidrug-resistance-upon-cancer-cells-by-coordinated-overexpression-of-an-assortment-of-resistance-related-proteins
#17
Ilaria Genovese, Andrea Ilari, Yehuda G Assaraf, Francesco Fazi, Gianni Colotti
The development of drug resistance continues to be a dominant hindrance toward curative cancer treatment. Overexpression of a wide-spectrum of ATP-dependent efflux pumps, and in particular of ABCB1 (P-glycoprotein or MDR1) is a well-known resistance mechanism for a plethora of cancer chemotherapeutics including for example taxenes, anthracyclines, Vinca alkaloids, and epipodopyllotoxins, demonstrated by a large array of published papers, both in tumor cell lines and in a variety of tumors, including various solid tumors and hematological malignancies...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/28924228/an-expanded-role-for-heterozygous-mutations-of-abcb4-abcb11-atp8b1-abcc2-and-tjp2-in-intrahepatic-cholestasis-of-pregnancy
#18
Peter H Dixon, Melissa Sambrotta, Jennifer Chambers, Pamela Taylor-Harris, Argyro Syngelaki, Kypros Nicolaides, A S Knisely, Richard J Thompson, Catherine Williamson
Intrahepatic cholestasis of pregnancy (ICP) affects 1/140 UK pregnancies; with pruritus, hepatic impairment and elevated serum bile acids. Severe disease is complicated by spontaneous preterm delivery and stillbirth. Previous studies have reported mutations in hepatocellular transporters (ABCB4, ABCB11). High throughput sequencing in 147 patients was performed in the transporters ABCB4, ABCB11, ATP8B1, ABCC2 and tight junction protein 2 (TJP2). Twenty-six potentially damaging variants were identified with the following predicted protein changes: Twelve ABCB4 mutations - Arg47Gln, Met113Val, Glu161Gly, Thr175Ala, Glu528Glyfs*6, Arg590Gln, Ala601Ser, Glu884Ter, Gly722Ala, Tyr775Met (x2), Trp854Ter...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28902970/a-genetic-screen-in-rodent-malaria-parasites-identifies-five-new-apicoplast-putative-membrane-transporters-one-of-which-is-essential-in-human-malaria-parasites
#19
Claire P Sayers, Vanessa Mollard, Hayley D Buchanan, Geoffrey I McFadden, Christopher D Goodman
The malaria-causing parasite, Plasmodium, contains a unique non-photosynthetic plastid known as the apicoplast. The apicoplast is an essential organelle bound by four membranes. Although membrane transporters are attractive drug targets, only two transporters have been characterised in the malaria parasite apicoplast membranes. We selected 27 candidate apicoplast membrane proteins, 20 of which are annotated as putative membrane transporters, and performed a genetic screen in Plasmodium berghei to determine blood stage essentiality and subcellular localisation...
January 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/28894223/long-term-administration-of-nuclear-bile-acid-receptor-fxr-agonist-prevents-spontaneous-hepatocarcinogenesis-in-abcb4-mice
#20
Marica Cariello, Claudia Peres, Roberta Zerlotin, Emanuele Porru, Carlo Sabbà, Aldo Roda, Antonio Moschetta
Altered bile acid (BA) signaling is associated with hepatotoxicity. The farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally regulates BA homeostasis. Mice with FXR ablation present hepatocarcinoma (HCC) due to high toxic BA levels. Mice with Abcb4 ablation accumulate toxic BA within the bile ducts and present HCC. We have previously shown that intestinal specific activation of FXR by transgenic VP16-FXR chimera is able to reduce BA pool size and prevent HCC. Here we tested chemical FXR activation by administering for 15 months the dual FXR/ membrane G protein-coupled receptor (TGR5) agonist INT-767 (6α-ethyl-3α,7α,23-trihydroxy-24-nor-5β-cholan-23-sulphate) to Fxr(-/-) and Abcb4(-/-) mice...
September 11, 2017: Scientific Reports
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