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https://www.readbyqxmd.com/read/27898169/cross-sectional-analysis-of-progressive-familial-intrahepatic-cholestasis-in-puerto-rican-children
#1
Dellys M Soler, Antonio I Del Valle, David Fernandez-Lube, Benjamin L Shneider
OBJECTIVE: Specific inherited disorders may be more common in island communities. Prior case reports suggest that cholestatic liver diseases may constitute a group of these inherited disorders in Puerto Rico. A cross-sectional survey of liver diseases in children was conducted to assess this hypothesis. METHODS: A cross-sectional analysis was performed in patients with chronic cholestasis at "Hospital Pediátrico Universitario" in San Juan, Puerto Rico. Ten potential participants with high gamma-glutamyl transpeptidase (GGTP) cholestasis were identified...
December 2016: Puerto Rico Health Sciences Journal
https://www.readbyqxmd.com/read/27895309/hepatocyte-specific-expression-of-an-oncogenic-variant-of-%C3%AE-catenin-results-in-cholestatic-liver-disease
#2
Ursula J Lemberger, Claudia Fuchs, Matthias Karer, Stefanie Haas, Tatjana Stojakovic, Christian Schöfer, Hanns-Ulrich Marschall, Fritz Wrba, Makoto M Taketo, Gerda Egger, Michael Trauner, Christoph H Österreicher
BACKGROUND: The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, tissue homeostasis, wound healing and malignant transformation in different organs including the liver. The consequences of continuous β-catenin signaling in hepatocytes remain elusive. RESULTS: Livers of Ctnnb1CA hep mice were characterized by disturbed liver architecture, proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile acid levels were significantly increased in Ctnnb1CA hep mice...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27883295/identification-of-novel-snps-associated-with-risk-and-prognosis-in-patients-with-castration-resistant-prostate-cancer
#3
Tristan M Sissung, John Deeken, Crystal R Leibrand, Douglas K Price, Sheryl Ehrlich, Seth M Steinberg, David J Liewehr, William Dahut, William D Figg
AIM: Metabolism and transport play major roles in life-long exposure to endogenous and exogenous carcinogens. We therefore explored associations between polymorphisms in absorption, distribution, metabolism and elimination genes and the risk and prognosis of castration-resistant prostate cancer (CRPC). MATERIALS & METHODS: A total of 634 genotypes were tested in 74 patients using the Affymetrix DMETv1.0 platform. RESULTS: No relation to risk was found...
November 24, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27825922/ursodeoxycholic-acid-therapy-in-intrahepatic-cholestasis-of-pregnancy-results-in-real-world-conditions-and-factors-predictive-of-response-to-treatment
#4
Yannick Bacq, Matthieu le Besco, Anne-Isabelle Lecuyer, Chantal Gendrot, Jérôme Potin, Christian R Andres, Alexandre Aubourg
BACKGROUND: Ursodeoxycholic acid (UDCA) therapy is commonly used in intrahepatic cholestasis of pregnancy (ICP). AIM: To evaluate the efficacy and tolerance of UDCA in real-world conditions and to search for factors predictive of response to treatment. METHODS: This observational study included 98 consecutive patients suffering from pruritus during pregnancy associated with increased ALT levels or total bile acid (TBA) concentrations, without other causes of cholestasis...
October 20, 2016: Digestive and Liver Disease
https://www.readbyqxmd.com/read/27810576/effects-of-pharmaceuticals-and-personal-care-products-ppcps-on-multixenobiotic-resistance-mxr-related-efflux-transporter-activity-in-zebrafish-danio-rerio-embryos
#5
V Cunha, K Burkhardt-Medicke, P Wellner, M M Santos, P Moradas-Ferreira, T Luckenbach, M Ferreira
Certain ATP binding cassette (ABC) transporter proteins, such as zebrafish Abcb4, are efflux pumps acting as a cellular defence against a wide range of different, potentially toxic chemical compounds thus mediating so called multixenobiotic resistance (MXR). Certain chemicals target MXR proteins and, as so called chemosensitisers, inhibit the activity of these proteins thus increasing the toxicity of other chemicals that would normally be effluxed. In this study 14 pharmaceuticals and personal care products (PPCPs) that are being increasingly detected in aquatic systems, were assessed for interference with the MXR system of zebrafish (Danio rerio)...
October 28, 2016: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/27788395/in-silico-investigation-of-the-impact-of-synonymous-variants-in-abcb4-gene-on-mrna-stability-structure-splicing-accuracy-and-codon-usage-potential-contribution-to-pfic3-disease
#6
Boudour Khabou, Olfa Siala-Sahnoun, Lamia Gargouri, Emna Mkaouar-Rebai, Leila Keskes, Mongia Hachicha, Faiza Fakhfakh
Progressive Familial Intrahepatic Cholestasis type 3 (PFIC3) is an autosomal-recessive liver disease due to mutations in the ABCB4 gene encoding for the MDR3 protein. In the present study, we performed molecular and bioinformatic analyses in PFIC3 patients in order to understand the molecular basis of the disease. The three studied patients with PFIC3 were screened by PCR amplification followed by direct sequencing of the 27 coding exons of ABCB4. In silico analysis was performed by bioinformatic programs. We revealed three synonymous polymorphisms c...
October 22, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/27664577/characterization-of-acquired-paclitaxel-resistance-of-breast-cancer-cells-and-involvement-of-abc-transporters
#7
Vlasta Němcová-Fürstová, Dana Kopperová, Kamila Balušíková, Marie Ehrlichová, Veronika Brynychová, Radka Václavíková, Petr Daniel, Pavel Souček, Jan Kovář
Development of taxane resistance has become clinically very important issue. The molecular mechanisms underlying the resistance are still unclear. To address this issue, we established paclitaxel-resistant sublines of the SK-BR-3 and MCF-7 breast cancer cell lines that are capable of long-term proliferation in 100nM and 300nM paclitaxel, respectively. Application of these concentrations leads to cell death in the original counterpart cells. Both sublines are cross-resistant to doxorubicin, indicating the presence of the MDR phenotype...
November 1, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27513977/danio-rerio-embryos-on-prozac-effects-on-the-detoxification-mechanism-and-embryo-development
#8
V Cunha, P Rodrigues, M M Santos, P Moradas-Ferreira, M Ferreira
In the past decade the presence of psychopharmaceuticals, including fluoxetine (FLU), in the aquatic environment has been associated with the increasing trend in human consumption of these substances. Aquatic organisms are usually exposed to chronic low doses and, therefore, risk assessments should evaluate the effects of these compounds in non-target organisms. Teleost fish possess an array of active defence mechanisms to cope with the deleterious effects of xenobiotics. These include ABC transporters, phase I and II of cellular detoxification and oxidative stress enzymes...
September 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27391331/tlr4-deficiency-protects-against-hepatic-fibrosis-and-diethylnitrosamine-induced-pre-carcinogenic-liver-injury-in-fibrotic-liver
#9
Susanne Nicole Weber, Annika Bohner, Dianne H Dapito, Robert F Schwabe, Frank Lammert
BACKGROUND: The development of hepatocellular carcinoma (HCC) is a common consequence of advanced liver fibrosis but the interactions between fibrogenesis and carcinogenesis are still poorly understood. Recently it has been shown that HCC promotion depends on Toll-like receptor (TLR) 4. Pre-cancerogenous events can be modelled in mice by the administration of a single dose of diethylnitrosamine (DEN), with HCC formation depending amongst others on interleukin (IL) 6 production. Mice lacking the hepatocanalicular phosphatidylcholine transporter ABCB4 develop liver fibrosis spontaneously, resemble patients with sclerosing cholangitis due to mutations of the orthologous human gene, and represent a valid model to study tumour formation in pre-injured cholestatic liver...
2016: PloS One
https://www.readbyqxmd.com/read/27277198/the-stepwise-evolution-of-the-exome-during-acquisition-of-docetaxel-resistance-in-breast-cancer-cells
#10
Stine Ninel Hansen, Natasja Spring Ehlers, Shida Zhu, Mathilde Borg Houlberg Thomsen, Rikke Linnemann Nielsen, Dongbing Liu, Guangbiao Wang, Yong Hou, Xiuqing Zhang, Xun Xu, Lars Bolund, Huanming Yang, Jun Wang, Jose Moreira, Henrik J Ditzel, Nils Brünner, Anne-Sofie Schrohl, Jan Stenvang, Ramneek Gupta
BACKGROUND: Resistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic alterations, evolving across evolutionary stages during the acquisition of docetaxel resistance in breast cancer cell lines. RESULTS: Two human breast cancer in vitro models (MCF-7 and MDA-MB-231) of the step-wise acquisition of docetaxel resistance were developed by exposing cells to 18 gradually increasing concentrations of docetaxel...
2016: BMC Genomics
https://www.readbyqxmd.com/read/27256251/functional-characterization-of-abcb4-mutations-found-in-progressive-familial-intrahepatic-cholestasis-type-3
#11
Hyo Jin Park, Tae Hee Kim, So Won Kim, Shin Hye Noh, Kyeong Jee Cho, Choe Choi, Eun Young Kwon, Yang Ji Choi, Heon Yung Gee, Ji Ha Choi
Multidrug resistance 3 (MDR3), encoded by the ATP-binding cassette, subfamily B, member 4 gene (ABCB4), localizes to the canalicular membrane of hepatocytes and translocates phosphatidylcholine from the inner leaflet to the outer leaflet of the canalicular membrane. Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare hepatic disease caused by genetic mutations of ABCB4. In this study, we characterized 8 ABCB4 mutations found in PFIC3 patients, using in vitro molecular assays. First, we examined the transport activity of each mutant by measuring its ATPase activity using paclitaxel or phosphatidylcholine...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27203216/down-regulation-of-abcg2-and-abcb4-transporters-in-the-placenta-of-rats-exposed-to-cadmium
#12
Lili Liu, Liang Zhou, Shuiwang Hu, Shanyu Zhou, Yingyu Deng, Ming Dong, Jianxun Huang, Yuli Zeng, Xiaoyan Chen, Na Zhao, Hongling Li, Zhenhua Ding
As a maternal and developmental toxicant, cadmium (Cd) possesses weak penetrability through the placental barrier. However, the underlying mechanism remains unclear. To gain insight into the protein molecules associated with Cd toxicity in placenta and explore their roles in Cd transportation, a reproductive animal experiment was carried out using Sprague-Dawley rats. We performed proteomic analysis of the placenta by Difference Gel Electrophoresis (DIGE) combined with Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Tandem Mass Spectroscopy (MALDI-TOF/TOF MS)...
May 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27197003/recommendations-for-genetic-testing-to-reduce-the-incidence-of-anthracycline-induced-cardiotoxicity
#13
REVIEW
Folefac Aminkeng, Colin J D Ross, Shahrad R Rassekh, Soomi Hwang, Michael J Rieder, Amit P Bhavsar, Anne Smith, Shubhayan Sanatani, Karen A Gelmon, Daniel Bernstein, Michael R Hayden, Ursula Amstutz, Bruce C Carleton
AIMS: Anthracycline-induced cardiotoxicity (ACT) occurs in 57% of treated patients and remains an important limitation of anthracycline-based chemotherapy. In various genetic association studies, potential genetic risk markers for ACT have been identified. Therefore, we developed evidence-based clinical practice recommendations for pharmacogenomic testing to further individualize therapy based on ACT risk. METHODS: We followed a standard guideline development process, including a systematic literature search, evidence synthesis and critical appraisal, and the development of clinical practice recommendations with an international expert group...
September 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27158408/prevalence-of-abcb4-polymorphisms-in-gallstone-disease-in-han-chinese-population
#14
Lei Zhan, Yao-Zhen Pan, Ling Chen, Hao Zhang, Hong Zhang, Jian Song, Chi-Meng Tzeng, Cheng-Yi Sun
ATP Binding Cassette Transporter A4 (ABCB4) is a sterol export pump that regulates excretion of biliary cholesterol. We tested association between ABCB4 polymorphisms and gallstone disease using meta-analysis. In a cross-sectional study, 296 subjects were recruited from a hospital-based population. Total of 171 subjects were diagnosed as gallstone disease by abdominal ultrasonography from three cohort studies. We evaluated prevalence of ABCG8 rs11887534 (D19H) as a positive control, and the ABCB4 rs1202283 and rs2230028 polymorphisms on Chinese population were screened by meta-analysis and genotyped using TaqMan® SNP assay...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27075526/molecular-characterization-of-exons-6-8-and-9-of-abcb4-gene-in-children-with-progressive-familial-intrahepatic-cholestasis-type-3
#15
Mona Fathy, Manal Kamal, Marwa Al-Sharkawy, Hanaa Al-Karaksy, Nora Hassan
AIM OF WORK: To estimate the frequency of mutations involving exons 6, 8 and 9 of Adenosine triphosphate-binding cassette, subfamily B, member 4 (ABCB4) gene among children with progressive intrahepatic cholestasis with high γ-GT activity (PFIC3). SUBJECTS AND METHODS: Cross sectional study was conducted on 30 children with PFIC3. Genotyping was performed by sequencing analysis of exons 6, 8 and exon 9 of ABCB4 gene. RESULTS: Heterozygous synonymous polymorphic variant was detected in exon 6 (rs 1202283) and in exon 8 (rs 2109505)...
November 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/27062773/-effect-of-doxorubicin-on-abcb4-gene-expression-in-zebrafish-danio-rerio-embryos
#16
Cong-jie Sun, Zhi-xu He, Li-ping Shu, Rong-ying Hu, Si-jia He
OBJECTIVE: To determine the effect of doxorubicin (DOX) on abcb4 gene expression and the role of abcb4 gene in multidrug-resistance. METHODS: Zebrafish embryos were treated with 2 mL/L DMSO, 10 μmol/L DOX and 2 mL/L DMSO+10 μmol/L DOX, respectively. The zebrafish embryos treated with Eggwater served as controls. Exposures started at 4 to 16 cell stage of the embryos and terminated 120 hours post fertilization (hpf). The expression of abcb4 gene in zebrafish embryos was examined on 48, 72, 96, and 120 hpf with whole-mount in situ hybridization (WISH) and quantitative real-time PCR (qPCR)...
January 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/27040680/simvastatin-effects-on-detoxification-mechanisms-in-danio-rerio-embryos
#17
V Cunha, M M Santos, P Moradas-Ferreira, M Ferreira
The transcription and protein activity of defence mechanisms such as ABC transporters, phase I and II of cellular detoxification and antioxidant enzymes can be altered in the presence of emerging contaminants such as pharmaceuticals impacting the overall detoxification mechanism. The present work aimed to characterise the effects of simvastatin on the detoxification mechanisms of embryonic stages of Danio rerio. In a first approach, constitutive transcription of key genes involved in detoxification was determined...
June 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/27004088/role-of-interleukin-1-and-its-antagonism-of-hepatic-stellate-cell-proliferation-and-liver-fibrosis-in-the-abcb4-mouse-model
#18
Florian P Reiter, Ralf Wimmer, Lena Wottke, Renate Artmann, Jutta M Nagel, Manuel O Carranza, Doris Mayr, Christian Rust, Peter Fickert, Michael Trauner, Alexander L Gerbes, Simon Hohenester, Gerald U Denk
AIM: To study the interleukin-1 (IL-1) pathway as a therapeutic target for liver fibrosis in vitro and in vivo using the ATP-binding cassette transporter b4(-/-) (Abcb4(-/-)) mouse model. METHODS: Female and male Abcb4(-/-) mice from 6 to 13 mo of age were analysed for the degree of cholestasis (liver serum tests), extent of liver fibrosis (hydroxyproline content and Sirius red staining) and tissue-specific activation of signalling pathways such as the IL-1 pathway [quantitative polymerase chain reaction (qPCR)]...
March 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/26900700/functional-rescue-of-trafficking-impaired-abcb4-mutants-by-chemical-chaperones
#19
Raquel Gordo-Gilart, Sara Andueza, Loreto Hierro, Paloma Jara, Luis Alvarez
Multidrug resistance protein 3 (MDR3, ABCB4) is a hepatocellular membrane protein that mediates biliary secretion of phosphatidylcholine. Null mutations in ABCB4 gene give rise to severe early-onset cholestatic liver disease. We have previously shown that the disease-associated mutations p.G68R, p.G228R, p.D459H, and p.A934T resulted in retention of ABCB4 in the endoplasmic reticulum, thus failing to target the plasma membrane. In the present study, we tested the ability of two compounds with chaperone-like activity, 4-phenylbutyrate and curcumin, to rescue these ABCB4 mutants by assessing their effects on subcellular localization, protein maturation, and phospholipid efflux capability...
2016: PloS One
https://www.readbyqxmd.com/read/26812075/gene-expression-profiling-in-human-precision-cut-liver-slices-in-response-to-the-fxr-agonist-obeticholic-acid
#20
Noortje Ijssennagger, Aafke W F Janssen, Alexandra Milona, José M Ramos Pittol, Danielle A A Hollman, Michal Mokry, Bark Betzel, Frits J Berends, Ignace M Janssen, Saskia W C van Mil, Sander Kersten
BACKGROUND & AIMS: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA alters hepatic expression of many genes. However, no data are available on the effects of OCA in the human liver. Here we generated gene expression profiles in human precision cut liver slices (hPCLS) after treatment with OCA...
May 2016: Journal of Hepatology
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