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https://www.readbyqxmd.com/read/29149196/easy-xeno-free-and-feeder-free-method-for-isolating-and-growing-limbal-stromal-and-epithelial-stem-cells-of-the-human-cornea
#1
Djida Ghoubay-Benallaoua, Céline de Sousa, Raphaël Martos, Gaël Latour, Marie-Claire Schanne-Klein, Elisabeth Dupin, Vincent Borderie
Epithelial and stromal stem cells are required to maintain corneal transparency. The aim of the study was to develop a new method to isolate and grow both corneal stromal (SSC) and epithelial limbal (LSC) stem cells from small human limbal biopsies under culture conditions in accordance with safety requirements mandatory for clinical use in humans. Superficial limbal explants were retrieved from human donor corneo-scleral rims. Human limbal cells were dissociated by digestion with collagenase A, either after epithelial scraping or with no scraping...
2017: PloS One
https://www.readbyqxmd.com/read/29147815/atp-binding-cassette-transporters-limit-the-brain-penetration-of-wee1-inhibitors
#2
Mark C de Gooijer, Levi C M Buil, Jos H Beijnen, Olaf van Tellingen
Introduction Wee1 is an important kinase involved in the G2 cell cycle checkpoint and frequently upregulated in intracranial neoplasms such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG). Two small molecules are available that target Wee1, AZD1775 and PD0166285, and clinical trials with AZD1775 have already been started. Since GBM and DIPG are highly invasive brain tumors, they are at least to some extent protected by the blood-brain barrier (BBB) and its ATP-binding cassette (ABC) efflux transporters...
November 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29138424/structure-function-relationships-in-abcg2-insights-from-molecular-dynamics-simulations-and-molecular-docking-studies
#3
Ricardo J Ferreira, Cátia A Bonito, M Natália D S Cordeiro, Maria-José U Ferreira, Daniel J V A Dos Santos
Efflux pumps of the ATP-binding cassette transporters superfamily (ABC transporters) are frequently involved in the multidrug-resistance (MDR) phenomenon in cancer cells. Herein, we describe a new atomistic model for the MDR-related ABCG2 efflux pump, also named breast cancer resistance protein (BCRP), based on the recently published crystallographic structure of the ABCG5/G8 heterodimer sterol transporter, a member of the ABCG family involved in cholesterol homeostasis. By means of molecular dynamics simulations and molecular docking, a far-reaching characterization of the ABCG2 homodimer was obtained...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29134945/drug-drug-interaction-potential-of-the-hepatitis-b-and-hepatitis-d-virus-entry-inhibitor-myrcludex-b-assessed-in-vitro
#4
Antje Blank, Katrin Meier, Stephan Urban, Walter Emil Haefeli, Johanna Weiss
BACKGROUND: Myrcludex B is a first-in-class virus entry inhibitor for patients with chronic hepatitis B or B/D infections. In patients it will be co-administered with drugs needed for the disease or comorbidities. We aimed to define the risk of drug-drug interactions by characterizing the influence of myrcludex B on relevant drug transporting and metabolizing enzymes in vitro. METHODS: Inhibition of P-glycoprotein (P-gp, ABCB1), breast cancer resistance protein (BCRP/ABCG2), and the organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1/SLCO1B1 and OATP1B3/SLCO1B3) was measured in cells over-expressing the respective transporter using fluorogenic substrates...
November 14, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/29133573/the-rars-mad1l1-fusion-gene-induces-cancer-stem-cell-like-properties-and-therapeutic-resistance-in-nasopharyngeal-carcinoma
#5
Qian Zhong, Zhihua Liu, Zhi-Rui Lin, Ze-Dong Hu, Li Yuan, Yan-Min Liu, Ai-Jun Zhou, Li-Hua Xu, Li-Juan Hu, Zi-Feng Wang, Xin Yuan Guan, Jia-Jie Hao, Vivian Wai Yan Lui, Ling Guo, Hai-Qiang Mai, Ming-Yuan Chen, Fei Han, Yun-Fei Xia, Jennifer R Grandis, Xing Zhang, Mu-Sheng Zeng
PURPOSE: Nasopharyngeal carcinoma (NPC) is most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC. EXPERIMENTAL DESIGN: RNA-seq was applied to look for interchromosome translocation in NPC. PCR, FISH and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies...
November 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29127331/divergent-effects-of-wnt-%C3%AE-catenin-signaling-modifiers-on-the-preservation-of-human-limbal-epithelial-progenitors-according-to-culture-condition
#6
Hyun Jung Lee, J Mario Wolosin, So-Hyang Chung
Wnt signaling plays an important role in the regulation of self-renewal in stem cells. Here we investigated the effect of CHIR99021, the primary transducer of the Wnt signaling canonical pathway, and IWP2, a wide action Wnt signal blocker, on the growth and differentiation of the limbal epithelial progenitor cells when these cells are cultured in two different, common culture approaches, outgrowth from limbal biopsy explants and isolated cell seeded in low calcium medium. Consistent with their expected effects, irrespective of the culture system, IWP2 decreased total β-catenin while CHIR99021 increased it in nuclear localization...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121857/meta-analysis-of-sequence-based-association-studies-across-three-cattle-breeds-reveals-25-qtl-for-fat-and-protein-percentages-in-milk-at-nucleotide-resolution
#7
Hubert Pausch, Reiner Emmerling, Birgit Gredler-Grandl, Ruedi Fries, Hans D Daetwyler, Michael E Goddard
BACKGROUND: Genotyping and whole-genome sequencing data have been generated for hundreds of thousands of cattle. International consortia used these data to compile imputation reference panels that facilitate the imputation of sequence variant genotypes for animals that have been genotyped using dense microarrays. Association studies with imputed sequence variant genotypes allow for the characterization of quantitative trait loci (QTL) at nucleotide resolution particularly when individuals from several breeds are included in the mapping populations...
November 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29111349/the-developmental-transcription-factor-irf6-attenuates-abcg2-gene-expression-and-distinctively-reverses-stemness-phenotype-in-nasoparyngeal-carcinoma
#8
Liang Xu, Tie-Jun Huang, Hao Hu, Meng-Yao Wang, Si-Mei Shi, Qin Yang, Fen Lin, Yuan-Yuan Qiang, Yan Mei, Yan-Hong Lang, Chang-Zhi Li, Li-Xia Peng, Li-Sheng Zheng, Jia-Ling Huang, Xin-Jian Li, Shi-Jun Zhang, Chao-Nan Qian, Bi-Jun Huang
Nasopharyngeal carcinoma (NPC), which originates from the nasopharynx, is highly prevalent in Southern China and Southeast Asia, and more than 90% of all NPCs are non-keratinizing undifferentiated cells or poorly differentiated squamous cells. Cancer stem cells (CSCs) are capable of self-renewal and have differentiation potential. These properties form the basis of cancer initiation, development, and radiochemoresistance. However, the molecular mechanisms underlying NPC CSC maintenance remain poorly understood...
October 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29106709/a-new-genetic-background-for-the-jr-a-blood-group-phenotype-caused-by-the-abcg2-439t-allele-encoding-a-p-arg147trp-change
#9
Carola Wieckhusen, Gabi Rink, Erwin A Scharberg, Sina Rothenberger, Annette Stürtzel, Ekkehard Richter, Peter Bugert
No abstract text is available yet for this article.
November 6, 2017: Transfusion
https://www.readbyqxmd.com/read/29103027/inhibition-of-mir-155-a-therapeutic-target-for-breast-cancer-prevented-in-cancer-stem-cell-formation
#10
Jiangcheng Zuo, Yalan Yu, Man Zhu, Wei Jing, Mingxia Yu, Hongyan Chai, Chunzi Liang, Jiancheng Tu
BACKGROUND: Breast cancer is a common cancer in women of worldwide. Cancer cells with stem-like properties played important roles in breast cancer, such as relapse, metastasis and treatment resistance. Micro-RNA-155 (miR-155) is a well-known oncogenic miRNA overexpressed in many human cancers. METHODS: The expression levels of miR-155 in 38 pairs of cancer tissues and adjacent normal tissues from breast cancer patients were detected using quantitative real-time PCR...
October 27, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29101532/the-phytoestrogens-daidzein-and-equol-inhibit-the-drug-transporter-bcrp-abcg2-in-breast-cancer-cells-potential-chemosensitizing-effect
#11
Juan Pablo Rigalli, Paul Niklas Scholz, Guillermo Nicolás Tocchetti, María Laura Ruiz, Johanna Weiss
PURPOSE: The soy isoflavone genistein has been described to up-regulate breast cancer resistance protein (BCRP) and, thus, enhance chemoresistance in breast cancer cells. The aim of this work was to assess the effect of long- and short-term incubation with daidzein, the second most abundant soy isoflavone and its metabolite equol on the expression and activity of P-glycoprotein, multidrug resistance-associated proteins 1 and 2 (MRP1 and MRP2) and BCRP in breast cancer cells. METHODS: MCF-7 and MDA-MB-231 cells were treated with phytoestrogen concentrations within the range achieved in individuals with a high isoflavone intake...
November 3, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/29096246/isolation-of-stem-like-cancer-cells-in-primary-endometrial-cancer-using-cell-surface-markers-cd133-and-cxcr4
#12
Yi Sun, Toshiko Yoshida, Motonori Okabe, Kaixuan Zhou, Fang Wang, Chika Soko, Sigeru Saito, Toshio Nikaido
Endometrial cancer (EC) is the most common familiar gynecologic malignant tumor identified in the female reproductive system and has been increasing yearly. In this study, we will identify the surface markers and stem cell markers related with cancer stem cells (CSCs) of EC. Tissue samples were obtained from endometrial cancer patients during surgical procedures. Single cells were isolated from the tissues for culturing, transfection into nude mice, and histopathology analysis. RT-PCR demonstrated that the cultured cells strongly expressed stemness-related genes, such as c-Myc, Sox-2, Nanog, Oct 4A, ABCG2, BMI-1, CK-18, Nestin and β-actin...
December 2017: Translational Oncology
https://www.readbyqxmd.com/read/29090664/pharmacogenetics-of-metabolic-genes-of-anthracyclines-in-acute-myeloid-leukemia
#13
Juan Eduardo Megias-Vericat, David Martinez-Cuadron, Maria Jose Herrero, Salvador F Alino, Jose Luis Poveda, Miguel Angel Sanz, Pau Montesinos
BACKGROUND: Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of patients will show initial resistance or will relapse after initial complete remission. Genetic variability in genes involved in anthracyclines metabolic pathway could be one of the causes of the interindividual differences in clinical outcomes. METHODS: A systematic review of published studies in AML cohorts was carried out in order to analyze the influence of polymorphisms in genes of anthracycline metabolism on efficacy and toxicity...
November 1, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29064386/the-role-of-pxr-genotype-and-transporter-expression-in-the-placental-transport-of-lopinavir-in-mice
#14
Sarabjit S Gahir, Micheline Piquette-Miller
Lopinavir (LPV), an antiretroviral protease inhibitor frequently prescribed in HIV-positive pregnancies, is a substrate of Abcb1 and Abcc2. As differences in placental expression of these transporters were seen in Pregnane X Receptor (PXR) -/- mice, we examined the impact of placental transporter expression and fetal PXR genotype on the fetal accumulation of LPV. PXR +/- dams bearing PXR +/+, PXR +/-, and PXR -/- fetuses were generated by mating PXR +/- female mice with PXR +/- males. On gestational day 17, dams were administered 10 mg/kg LPV (i...
October 24, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29061978/the-structure-of-the-human-abc-transporter-abcg2-reveals-a-novel-mechanism-for-drug-extrusion
#15
Narakorn Khunweeraphong, Thomas Stockner, Karl Kuchler
The human ABC transporter ABCG2 (Breast Cancer Resistance Protein, BCRP) is implicated in anticancer resistance, in detoxification across barriers and linked to gout. Here, we generate a novel atomic model of ABCG2 using the crystal structure of ABCG5/G8. Extensive mutagenesis verifies the structure, disclosing hitherto unrecognized essential residues and domains in the homodimeric ABCG2 transporter. The elbow helix, the first intracellular loop (ICL1) and the nucleotide-binding domain (NBD) constitute pivotal elements of the architecture building the transmission interface that borders a central cavity which acts as a drug trap...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29061583/bioengineered-nrf2-sirna-is-effective-to-interfere-with-nrf2-pathways-and-improve-chemosensitivity-of-human-cancer-cells
#16
Peng-Cheng Li, Mei-Juan Tu, Pui Yan Ho, Joseph L Jilek, Zhijiang Duan, Qian-Yu Zhang, Ai-Xi Yu, Ai-Ming Yu
The nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a transcription factor in the regulation of many oxidative enzymes and efflux transporters critical for oxidative stress and cellular defense against xenobiotics. NRF2 is dysregulated in patient osteosarcoma (OS) tissues and correlates with therapeutic outcomes. Nevertheless, research on the NRF2 regulatory pathways and its potential as a therapeutic target is limited to the use of synthetic small interfering RNA (siRNA) carrying extensive artificial modifications...
October 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29048645/establishment-and-characterization-of-human-osteosarcoma-cells-resistant-to-pyropheophorbide-%C3%AE-methyl-ester-mediated-photodynamic-therapy
#17
Yong Tao, Yunsheng Ou, Hang Yin, Yanyang Chen, Shenxi Zhong, Yongjian Gao, Zenghui Zhao, Bin He, Qiu Huang, Qianxing Deng
The present study was performed to establish and characterize new human osteosarcoma cell lines resistant to pyropheophorbide-α methyl ester‑mediated photodynamic therapy (MPPa-PDT). MPPa-PDT-resistant cells are isolated from the human osteosarcoma MG63 and HOS cell lines and two resistant populations were finally acquired, including MG63/PDT and HOS/PDT. Cell Counting Kit-8 (CCK-8) assay was used to determine the MPPa-PDT, cisplatin (CDDP) resistance and proliferation of MG63, MG63/PDT, HOS and HOS/PDT cells...
September 27, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29039601/vasohibin2-promotes-adriamycin-resistance-of-breast-cancer-cells-through-regulating-abcg2-via-akt-signaling-pathway
#18
Deliang Ma, Liang Wu, Shuangjie Li, Zhigang Sun, Kai Wang
As a well‑known angiogenic factor in different histology and pathological conditions, the pro‑progressive role of vasohibin2 (VASH2) has been reported in various types of tumors. However, its role in drug resistance of breast cancer has not been reported so far. The present study demonstrated that MCF‑7 cells with increased expression of VASH2 demonstrate stronger adriamycin (ADM) resistance compared with MDA‑MB‑231 cells with decreased expression of VASH2. Overexpression of VASH2 in MDA‑MB‑231 cells increased ADM resistance and silencing VASH2 in MCF‑7 cells inhibited ADM resistance...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29031817/bcrp-abcg2-and-high-alert-medications-biochemical-pharmacokinetic-pharmacogenetic-and-clinical-implications
#19
REVIEW
Daiki Hira, Tomohiro Terada
The human breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette efflux transporter that uses ATP hydrolysis to expel xenobiotics from cells, including anti-cancer medications. It is expressed in the gastrointestinal tract, liver, kidney, and brain endothelium. Thus, ABCG2 functions as a tissue barrier to drug transport that strongly influences the pharmacokinetics of substrate medications. Genetic polymorphisms of ABCG2 are closely related to inter-individual variations in therapeutic performance...
October 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29023674/reverse-translational-research-of-abcg2-bcrp-in-human-disease-and-drug-response
#20
Deanna J Brackman, Kathleen M Giacomini
Reverse translational research takes a bedside to bench approach, using sophisticated basic research to explain the biological mechanisms behind observed clinical data. For transporters, which play a role in human disease and drug response, this approach offers a distinct advantage over the typical translational research, which often falters due to inadequate in vitro and preclinical animal models. Research on ABCG2, which encodes the Breast Cancer Resistance Protein (BCRP), has benefited immensely from a reverse translational approach due to its broad implications to disease susceptibility and both therapeutic and adverse drug response...
October 12, 2017: Clinical Pharmacology and Therapeutics
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