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https://www.readbyqxmd.com/read/28345785/nanog-overexpression-and-its-correlation-with-stem-cell-and-differentiation-markers-in-meningiomas-of-different-who-grades
#1
Diana Freitag, Aaron Lawson McLean, Michèle Simon, Arend Koch, Susanne Grube, Jan Walter, Rolf Kalff, Christian Ewald
NANOG, as a key regulator of pluripotency and acting synergistically with other factors, has been described as a crucial transcription factor in various types of cancer. In meningiomas the expression of this marker has not yet been described. With our study, we aimed to identify and localize Nanog and other possible markers of pluripotency, stem cell properties and differentiation in meningioma tissue, to elucidate a possible effect on tumorigenesis. The gene expression levels of NANOG (NANOG1 and NANOGP8), SOX2, OCT4, KLF4, ABCG2, CMYC, MSI1, CD44, NOTCH1, NES, SALL4B, TP53 and EPAS1 were quantitatively examined using RT-qPCR in 33 surgical specimens of low- (WHO grade I) as well as in atypical and anaplastic (WHO grade II/III) meningiomas with dural tissue as reference...
March 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28342201/expression-of-oxysterol-pathway-genes-in-estrogen-positive-breast-carcinomas
#2
Alzbeta Kloudova, Veronika Brynychova, Radka Vaclavikova, David Vrana, Jiri Gatek, Marcela Mrhalova, Roman Kodet, Pavel Soucek
OBJECTIVE: The present study investigated whether gene expression levels of key modulators of the oxysterol signaling pathway modify the prognosis of patients with estrogen receptor positive (ER+) breast carcinomas via interaction with endocrine therapy. CONTEXT: The prognosis of ER+ breast carcinoma patients depends on several factors. Previous studies have suggested that some oxygenated forms of cholesterol (oxysterols) bind to estrogen receptor and antiestrogen binding site which may deregulate cholesterol homeostasis and influence effect of therapy...
March 25, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28341962/tumour-suppressor-ep300-a-modulator-of-paclitaxel-resistance-and-stemness-is-downregulated-in-metaplastic-breast-cancer
#3
Muhammad Asaduzzaman, Stephanie Constantinou, Haoxiang Min, John Gallon, Meng-Lay Lin, Poonam Singh, Selina Raguz, Simak Ali, Sami Shousha, R Charles Coombes, Eric W-F Lam, Yunhui Hu, Ernesto Yagüe
PURPOSE: We have previously described a novel pathway controlling drug resistance, epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer cells. Upstream in the pathway, three miRs (miR-106b, miR-93 and miR-25) target EP300, a transcriptional activator of E-cadherin. Upregulation of these miRs leads to the downregulation of EP300 and E-cadherin with initiation of an EMT. However, miRs regulate the expression of many genes, and the contribution to EMT by miR targets other than EP300 cannot be ruled out...
March 24, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28340578/abcb1-and-abcg2-drug-transporters-are-differentially-expressed-in-non-small-cell-lung-cancers-nsclc-and-expression-is-modified-by-cisplatin-treatment-via-altered-wnt-signaling
#4
M Vesel, J Rapp, D Feller, E Kiss, L Jaromi, M Meggyes, G Miskei, B Duga, G Smuk, T Laszlo, I Karner, J E Pongracz
BACKGROUND: Lung cancer (LC) is still the most common cause of cancer related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all LC cases but is not a single entity. It is now accepted that, apart from the characteristic driver mutations, the unique molecular signatures of adeno- (AC) and squamous cell carcinomas (SCC), the two most common NSCLC subtypes should be taken into consideration for their management. Therapeutic interventions, however, frequently lead to chemotherapy resistance highlighting the need for in-depth analysis of regulatory mechanisms of multidrug resistance to increase therapeutic efficiency...
March 24, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28335742/characteristics-of-early-onset-hematotoxicity-of-sunitinib-in-japanese-patients-with-renal-cell-carcinoma
#5
Renpei Kato, Yoichiro Kato, Tomohiko Matsuura, Mitsugu Kanehira, Ryo Takata, Wataru Obara
BACKGROUND: A high incidence of severe hematological adverse events during sunitinib treatment complicates decision making on dose and treatment cycle. We identified the characteristics of early-onset hematotoxicity of sunitinib in Japanese patients with renal cell carcinoma (RCC). METHODS: Seventy-nine patients were treated with sunitinib as 6-week cycles of "4-week on 2-week off" schedule. To evaluate early-onset hematotoxicity, we compared patients with dose reduction during the first cycle (dose-reduced group, n = 57) and those who maintained the initial dose (dose-maintained group, n = 22)...
March 23, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28335376/genetic-polymorphisms-contribute-to-the-individual-variations-of-imatinib-mesylate-plasma-levels-and-adverse-reactions-in-chinese-gist-patients
#6
Jing Liu, Zhiyu Chen, Hanmei Chen, Yingyong Hou, Weiqi Lu, Junyi He, Hanxing Tong, Yuhong Zhou, Weimin Cai
Imatinib mesylate (IM) has dramatically improved the outcomes of gastrointestinal stromal tumor (GIST) patients. However, the clinical responses of IM may considerably vary among single individuals. This study aimed to investigate the influences of genetic polymorphisms of drug-metabolizing enzyme (CYP3A4), transporters (ABCB1, ABCG2), and nuclear receptor (Pregnane X Receptor (PXR, encoded by NR1I2)) on IM plasma levels and related adverse reactions in Chinese GIST patients. A total of 68 Chinese GIST patients who have received IM 300-600 mg/day were genotyped for six single nucleotide polymorphisms (SNPs) (CYP3A4 rs2242480; ABCB1 rs1045642; ABCG2 rs2231137; NRI12 rs3814055, rs6785049, rs2276706), and the steady-state IM trough plasma concentrations were measured by a validated HPLC method...
March 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28329446/in-vitro-intrinsic-permeability-a-transporter-independent-measure-of-caco-2-cell-permeability-in-drug-design-and-development
#7
Linda Fredlund, Susanne Winiwarter, Constanze Hilgendorf
In-vitro permeability data have a central place in absorption risk assessments in drug discovery and development. For compounds where active efflux impacts permeability in vitro, the inherent passive membrane permeability ("intrinsic permeability"), gives a concentration-independent measure of the compound's permeability. This work describes the validation of an in-vitro intrinsic permeability assay and application of the data in a predictive in-silico model. Apparent intrinsic permeability (Papp) across Caco-2 cell monolayers is determined in presence of an optimized cocktail of chemical inhibitors towards the three major efflux transporters ABCB1, ABCC2, and ABCG2...
March 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28323029/the-dopamine-d3-receptor-antagonists-pg01037-ngb2904-sb277011a-and-u99194-reverse-abcg2-transporter-mediated-drug%C3%A2-resistance-in-cancer-cell-lines
#8
Noor Hussein, Haneen Amawi, Chandrabose Karthikeyan, F Scott Hall, Roopali Mittal, Piyush Trivedi, Charles R Ashby, Amit K Tiwari
The ATP - binding cassette (ABC) family G2 (ABCG2) transporters are known to produce multidrug resistance (MDR) in cancer, thereby limiting the clinical response to chemotherapy. Molecular modeling data indicated that certain dopamine (DA) D3 receptor antagonists had a significant binding affinity for ABCG2 transporter. Therefore, in this in vitro study, we determined the effect of the D3 receptor antagonists PG01037, NGB2904, SB277011A, and U99194 on MDR resulting from the overexpression of ABCG2 transporters...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28322941/small-dosing-clinical-study-pharmacokinetic-pharmacogenomic-slco2b1-and-abcg2-and-interaction-atorvastatin-and-grapefruit-juice-profiles-of-five-probes-for-oatp2b1-and-bcrp
#9
Yushi Kashihara, Ichiro Ieiri, Takashi Yoshikado, Maeda Kazuya, Masato Fukae, Miyuki Kimura, Takeshi Hirota, Shunji Matsuki, Shin Irie, Noritomo Izumi, Hiroyuki Kusuhara, Yuichi Sugiyama
The aims of this study were (1) to investigate the effects of atorvastatin (10 mg, therapeutic dose) and grapefruit juice (GFJ), inhibitors of OATP2B1, on the pharmacokinetics of substrates for OATP2B1 and BCRP under oral small-dosing conditions (300 μg sulfasalazine, 250 μg rosuvastatin, 300 μg glibenclamide, 1200 μg celiprolol, and 600 μg sumatriptan), and (2) to evaluate the contribution of SLCO2B1*3 and ABCG2 c.421C>A polymorphisms to the pharmacokinetics of the five test drugs in 23 healthy volunteers...
March 17, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28316087/influence-of-abcc2-cyp2c8-and-cyp2j2-polymorphisms-on-tacrolimus-and-mycophenolate-sodium-based-treatment-in-brazilian-kidney-transplant-recipients
#10
Fabiana D V Genvigir, Alvaro M Nishikawa, Claudia R Felipe, Helio Tedesco-Silva, Nagilla Oliveira, Antony B C Salazar, Jose O Medina-Pestana, Sonia Q Doi, Mario H Hirata, Rosario D C Hirata
STUDY OBJECTIVE: To investigate the influence of single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP2C8, CYP2J2, and UGT2B7) and transporters (ABCC2 and ABCG2) on dose and/or dose-adjusted trough blood concentrations (C/D ratio), clinical outcomes, and occurrence of adverse events of tacrolimus and mycophenolate sodium in Brazilian kidney transplant recipients. DESIGN: Pharmacogenetic analysis of patients enrolled in a previously published study...
March 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28303028/alectinib-ch5424802-antagonizes-abcb1-and-abcg2-mediated-multidrug-resistance-in-vitro-in-vivo-and-ex-vivo
#11
Ke Yang, Yifan Chen, Kenneth Kin Wah To, Fang Wang, Delan Li, Likun Chen, Liwu Fu
Alectinib, an inhibitor of anaplastic lymphoma kinase (ALK), was approved by the Food and Drug Administration (FDA) for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC). Here we investigated the reversal effect of alectinib on multidrug resistance (MDR) induced by ATP-binding cassette (ABC) transporters, which is the primary cause of chemotherapy failure. We provide the first evidence that alectinib increases the sensitivity of ABCB1- and ABCG2-overexpressing cells to chemotherapeutic agents in vitro and in vivo...
March 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28300564/contrasting-roles-of-the-abcg2-q141k-variant-in-prostate-cancer
#12
Kathryn M Sobek, Jessica L Cummings, Dean J Bacich, Denise S O'Keefe
ABCG2 is a membrane transport protein that effluxes growth-promoting molecules, such as folates and dihydrotestosterone, as well as chemotherapeutic agents. Therefore it is important to determine how variants of ABCG2 affect the transporter function in order to determine whether modified treatment regimens may be necessary for patients harboring ABCG2 variants. Previous studies have demonstrated an association between the ABCG2 Q141K variant and overall survival after a prostate cancer diagnosis. We report here that in patients with recurrent prostate cancer, those who carry the ABCG2 Q141K variant had a significantly shorter time to PSA recurrence post-prostatectomy than patients homozygous for wild-type ABCG2 (P=0...
March 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28297580/a-human-corneal-epithelial-cell-line-model-for-limbal-stem-cell-biology-and-limbal-immunobiology
#13
Bakiah Shaharuddin, Sajjad Ahmad, Nani Md Latar, Simi Ali, Annette Meeson
Limbal stem cell (LSC) deficiency is a visually debilitating condition caused by abnormal maintenance of LSCs. It is treated by transplantation of donor-derived limbal epithelial cells (LECs), the success of which depends on the presence and quality of LSCs within the transplant. Understanding the immunobiological responses of these cells within the transplants could improve cell engraftment and survival. However, human corneal rings used as a source of LSCs are not always readily available for research purposes...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28293855/growth-hormone-receptor-knockdown-sensitizes-human-melanoma-cells-to-chemotherapy-by-attenuating-expression-of-abc-drug-efflux-pumps
#14
Reetobrata Basu, Nicholas Baumgaertel, Shiyong Wu, John J Kopchick
Melanoma remains one of the most therapy-resistant forms of human cancer despite recent introductions of highly efficacious targeted therapies. The intrinsic therapy resistance of human melanoma is largely due to abundant expression of a repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) transporter family. Here, we report that GH action is a key mediator of chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly associated with melanoma drug resistance in different human melanoma cells and tested the efficacy of five different anti-cancer compounds (cisplatin, doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action...
March 14, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28292469/down-regulation-of-the-placental-bcrp-abcg2-transporter-in-response-to-hypoxia-signaling
#15
Lissa N Francois, Ludwik Gorczyca, Jianyao Du, Kristin M Bircsak, Elizabeth Yen, Xia Wen, Mei-Juan Tu, Ai-Ming Yu, Nicholas P Illsley, Stacy Zamudio, Lauren M Aleksunes
INTRODUCTION: The BCRP/ABCG2 efflux transporter protects the developing fetus by limiting the transplacental transfer of drugs and chemicals and prevents the apoptosis of trophoblasts. The purpose of this study was to determine whether hypoxia-related signaling alters placental BCRP expression and function in vitro and in human pregnancies. METHODS: Human BeWo choriocarcinoma cells were treated with the hypoxia mimetic, cobalt chloride (CoCl2), or 3% oxygen for 24-48 h...
March 2017: Placenta
https://www.readbyqxmd.com/read/28289864/correlation-between-clinical-response-to-sorafenib-in-hepatocellular-carcinoma-treatment-and-polymorphisms-of-p-glycoprotein-abcb1-and-of-breast-cancer-resistance-protein-abcg2-monocentric-study
#16
Mahamadou Tandia, Asma Mhiri, Bernard Paule, Raphaël Saffroy, Valérie Cailliez, Gaëlle Noé, Robert Farinotti, Laurence Bonhomme-Faivre
OBJECTIVES: We studied the relation between the polymorphism of P-glycoprotein (P-gp) and of breast cancer resistance protein (BCRP), encoded by ABCB1 and ABCG2 genes, respectively, and the pharmacokinetic variability and clinical response during the treatment with sorafenib of hepatocellular carcinoma. METHODS: At the Paul Brousse Hospital in Villejuif, France, 47 consecutive patients with advanced HCC treated with a single agent sorafenib, were enrolled. Sorafenib exposure was measured by its plasma concentration 3 h after oral administration of 400 mg (bid) by liquid chromatography...
March 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28288939/breast-cancer-resistance-protein-bcrp-abcg2-and-p-glycoprotein-p-gp-abcb1-transport-afatinib-and-restrict-its-oral-availability-and-brain-accumulation
#17
Stéphanie van Hoppe, Rolf W Sparidans, Els Wagenaar, Jos H Beijnen, Alfred H Schinkel
Afatinib is a highly selective, irreversible inhibitor of EGFR and HER-2. It is orally administered for the treatment of patients with EGFR mutation-positive types of metastatic NSCLC. We investigated whether afatinib is a substrate for the multidrug efflux transporters ABCB1 and ABCG2 and whether these transporters influence oral availability and brain and other tissue accumulation of afatinib. We used in vitro transport assays to assess human (h)ABCB1-, hABCG2- or murine (m)Abcg2-mediated transport of afatinib...
March 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28283692/pharmacokinetics-and-pharmacogenetics-of-the-mek1-2-inhibitor-selumetinib-in-asian-and-western-healthy-subjects-a-pooled-analysis
#18
Angela W Dymond, Cathy Elks, Paul Martin, David J Carlile, Gabriella Mariani, Susan Lovick, Yifan Huang, Ulrike Lorch, Helen Brown, Karen So
PURPOSE: Emerging data on selumetinib, a MEK1/2 inhibitor in clinical development, suggest a possible difference in pharmacokinetics (PK) between Japanese and Western patients. This pooled analysis sought to assess the effect of ethnicity on selumetinib exposure in healthy Western and Asian subjects, and to identify any association between genetic variants in the UGT1A1, CYP2C19 and ABCG2 genes and observed differences in selumetinib PK. METHODS: A pooled analysis of data from ten Phase I studies, one in Asian subjects (encompassing Japanese, non-Japanese Asian and Indian Asian subjects) and nine in Western subjects, was conducted...
March 10, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28281205/transmembrane-domain-single-nucleotide-polymorphisms-impair-expression-and-transport-activity-of-abc-transporter-abcg2
#19
Noora Sjöstedt, Jeroen J M W van den Heuvel, Jan B Koenderink, Heidi Kidron
PURPOSE: To study the function and expression of nine naturally occurring single-nucleotide polymorphisms (G406R, F431L, S441N, P480L, F489L, M515R, L525R, A528T and T542A) that are predicted to reside in the transmembrane regions of the ABC transporter ABCG2. METHODS: The transport activity of the variants was tested in inside-out membrane vesicles from Sf9 insect and human derived HEK293 cells overexpressing ABCG2. Lucifer Yellow and estrone sulfate were used as probe substrates of activity...
March 9, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28280847/neuronal-differentiation-capability-of-nasal-polyps-of-chronic-rhinosinusitis
#20
Michael Koennecke, Robert Böscke, Ann-Christin Pfannerstill, Stefan Reers, Martina Elsner, Benjamin Fell, Anja Richter, Karl-Ludwig Bruchhage, Sandra Schumann, Ralph Pries, Ludger Klimek, Barbara Wollenberg
Chronic rhinosinusitis with nasal polyps is considered a subgroup of chronic rhinosinusitis and a significant health problem, but the pathogenesis remains unclear to date. Therefore, we investigated the stemness to determine the role of stem cells in nasal polyps, with additional analysis of the neuronal differentiation potential of nasal polyp cells. We determined gene and protein expression profiles of stem cells in nasal polyp tissues, using whole genome microarray, quantitative real-time PCR (qPCR), immunohistochemistry, and flow cytometry...
March 9, 2017: Archivum Immunologiae et Therapiae Experimentalis
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