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https://www.readbyqxmd.com/read/28537559/enforcement-of-developmental-lineage-specificity-by-transcription-factor-oct1
#1
Zuolian Shen, Jinsuk Kang, Arvind Shakya, Marcin Tabaka, Elke A Jarboe, Aviv Regev, Dean Tantin
Embryonic stem cells co-express Oct4 and Oct1, a related protein with similar DNA binding specificity. To study the role of Oct1 in ESC pluripotency and transcriptional control, we constructed germline and inducible-conditional Oct1 deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal and growth, but manifest defects upon differentiation. They fail to form beating cardiomyocytes, generate neurons poorly, form small, poorly differentiated teratomas, and cannot generate chimeric mice. Upon RA-mediated differentiation, Oct1 deficient cells induce lineage-appropriate developmentally poised genes poorly while lineage-inappropriate genes, including extra-embryonic genes, are inappropriately expressed...
May 24, 2017: ELife
https://www.readbyqxmd.com/read/28499878/possible-role-of-organic-cation-transporters-in-the-distribution-of-11-c-sulpiride-a-dopamine-d2-receptor-antagonist
#2
Harumasa Takano, Sumito Ito, Xuan Zhang, Hiroshi Ito, Ming-Rong Zhang, Hiroshi Suzuki, Kazuya Maeda, Hiroyuki Kusuhara, Tetsuya Suhara, Yuichi Sugiyama
We synthesized [(11)C]sulpiride as a positron emission tomography (PET) probe for investigating the drug distribution in the human body. [(11)C]Sulpiride was injected to healthy male subjects in either tracer dose of [(11)C]sulpiride (ca 222 MBq) or with therapeutic dose of sulpiride (500 mg, po) 3 hours prior to the injection in a crossover fashion. Whole body PET imaging demonstrated that [(11)C]sulpiride accumulated exceedingly in the bladder, followed by liver, gall bladder and kidney respectively; at 30 minutes after the injection, whereas scarcely in the brain...
May 9, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28479364/involvement-of-organic-cation-transporters-in-the-kinetics-of-trimethylamine-n-oxide
#3
Takeshi Miyake, Tadahaya Mizuno, Tatsuki Mochizuki, Miyuki Kimura, Shunji Matsuki, Shin Irie, Ichiro Ieiri, Maeda Kazuya, Hiroyuki Kusuhara
Recent studies suggest that trimethylamine N-oxide (TMAO) is associated with the development of chronic kidney disease and heart failure. In this study, we investigated the importance of organic cation transporters (OCTs) in the clearance and tissue distribution of TMAO. The low affinity and high capacity transport of TMAO by mouse and human OCT1 and OCT2 was observed. Uptake and efflux of TMAO by the mouse hepatocytes as well as TMAO uptake into mouse kidney slices were significantly decreased by the addition of tetraethylammonium or Oct1/2 double knockout (dKO)...
May 4, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28470102/oct1-genetic-variants-are-associated-with-postoperative-morphine-related-adverse-effects-in-children
#4
Rajiv Balyan, Xue Zhang, Vidya Chidambaran, Lisa J Martin, Tomoyuki Mizuno, Tsuyoshi Fukuda, Alexander A Vinks, Senthilkumar Sadhasivam
AIM: Large interindividual variability in morphine pharmacokinetics (PK) could contribute to variability in morphine analgesia and adverse events. Respiratory depression (RD) and postoperative nausea and vomiting (PONV) are significant adverse drug response of intravenous morphine in the perioperative setting limiting its efficacy in achieving adequate surgical pain relief. OCT1 is a transporter in the liver that transports morphine from the bloodstream into hepatocytes. Earlier we reported association of genetic polymorphisms in OCT1 with morphine PK, and lower morphine clearance in Caucasian children as compared with African-American (AA) children...
May 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28463838/engineering-the-rapid-adenovirus-production-and-amplification-rapa-cell-line-to-expedite-the-generation-of-recombinant-adenoviruses
#5
Qiang Wei, Jiaming Fan, Junyi Liao, Yulong Zou, Dongzhe Song, Jianxiang Liu, Jing Cui, Feng Liu, Chao Ma, Xue Hu, Li Li, Yichun Yu, Xiangyang Qu, Liqun Chen, Xinyi Yu, Zhicai Zhang, Chen Zhao, Zongyue Zeng, Ruyi Zhang, Shujuan Yan, Xingye Wu, Yi Shu, Russell R Reid, Michael J Lee, Jennifer Moritis Wolf, Tong-Chuan He
BACKGROUND/AIMS: While recombinant adenoviruses are among the most widely-used gene delivery vectors and usually propagated in HEK-293 cells, generating recombinant adenoviruses remains time-consuming and labor-intense. We sought to develop a rapid adenovirus production and amplification (RAPA) line by assessing human Ad5 genes (E1A, E1B19K/55K, pTP, DBP, and DNA Pol) and OCT1 for their contributions to adenovirus production. METHODS: Stable transgene expression in 293T cells was accomplished by using piggyBac system...
May 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28456419/choroidal-imaging-with-swept-source-optical-coherence-tomography-in-patients-with-birdshot-chorioretinopathy-choroidal-reflectivity-and-thickness
#6
Anna I Dastiridou, Elodie Bousquet, Laura Kuehlewein, Tudor Tepelus, Dominique Monnet, Sawsen Salah, Antoine Brezin, Srinivas R Sadda
PURPOSE: To characterize choroidal thickness and choroidal reflectivity in the eyes of patients with birdshot chorioretinopathy (BSCR). DESIGN: Cross-sectional observational study. PARTICIPANTS: Two hundred twenty BSCR patients and 59 healthy controls. METHODS: Patients with BSCR and healthy controls underwent imaging of the macula in both eyes with a swept-source optical coherence tomography device (DRI-OCT1 Atlantis; Topcon)...
April 26, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28380657/genetic-polymorphisms-in-organic-cation-transporter-1-attenuates-hepatic-metformin-exposure-in-humans
#7
Elias Immanuel Ordell Sundelin, Lars Christian Gormsen, Jonas Brorson Jensen, Mikkel Holm Vendelbo, Steen Jakobsen, Ole Lajord Munk, Mette Marie Hougaard Christensen, Kim Brøsen, Jørgen Frøkiaer, Niels Jessen
Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed non-invasive (11) C-metformin PET/CT to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1...
April 5, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28364304/inter-subject-variability-in-oct1-activity-in-27-batches-of-cryopreserved-human-hepatocytes-and-association-with-oct1-mrna-expression-and-genotype
#8
Sarinj Fattah, Abhijit Babaji Shinde, Maja Matic, Myriam Baes, Ron H N van Schaik, Karel Allegaert, Celine Parmentier, Lysiane Richert, Patrick Augustijns, Pieter Annaert
PURPOSE: OCT1/3 (Organic Cation Transporter-1 and -3; SLC22A1/3) are transmembrane proteins localized at the basolateral membrane of hepatocytes. They mediate the uptake of cationic endogenous compounds and/or xenobiotics. The present study was set up to verify whether the previously observed variability in OCT activity in hepatocytes may be explained by inter-individual differences in OCT1/3 mRNA levels or OCT1 genotype. METHODS: Twenty-seven batches of cryopreserved human hepatocytes (male and female, age 24-88 y) were characterized for OCT activity, normalized OCT1/3 mRNA expression, and OCT1 genetic mutation...
June 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28363126/interaction-between-the-zebrafish-danio-rerio-organic-cation-transporter-1-oct1-and-endo-and-xenobiotics
#9
Ivan Mihaljević, Marta Popović, Roko Žaja, Nikola Maraković, Goran Šinko, Tvrtko Smital
Organic cation transporters (OCTs) serve as uptake transporters of numerous endo- and xenobiotics. They have been in the focus of medical toxicological research for more than a decade due to their key role in absorption, distribution, metabolism and excretion due to their expression on basolateral membranes of various barrier tissues. OCTs belong to the SLC22A family within the SLC (Solute carrier) protein superfamily, with three co-orthologs identified in humans (OCT1, 2 and 3), and two Oct orthologs in zebrafish (Oct1 and Oct2)...
June 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28362799/organic-cation-transporter-1-oct1-is-involved-in-pentamidine-transport-at-the-human-and-mouse-blood-brain-barrier-bbb
#10
Gayathri N Sekhar, Ana R Georgian, Lisa Sanderson, Gema Vizcay-Barrena, Rachel C Brown, Paula Muresan, Roland A Fleck, Sarah A Thomas
Pentamidine is an effective trypanocidal drug used against stage 1 Human African Trypanosomiasis (HAT). At the blood-brain barrier (BBB), it accumulates inside the endothelial cells but has limited entry into the brain. This study examined transporters involved in pentamidine transport at the human and mouse BBB using hCMEC/D3 and bEnd.3 cell lines, respectively. Results revealed that both cell lines expressed the organic cation transporters (OCT1, OCT2 and OCT3), however, P-gp was only expressed in hCMEC/D3 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28353455/pharmacogenomic-influence-on-sepsis-outcome-in-critically-ill-patients
#11
Sarah Allegra, Giovanna Fatiguso, Lorena Baietto, Silvia Corcione, Fabio Favata, Alessandra Ariaudo, Nicole Pagani, Vito Marco Ranieri, Francesco Giuseppe De Rosa, Giovanni Di Perri, Antonio D'Avolio
In infectious and inflammatory diseases, pharmacogenetics affects treatment efficacy and toxicity. Moreover, recent studies suggest its important role in predicting the clinical outcome of sepsis. Our aim was to investigate the influence of single nucleotide polymorphisms (SNPs) in genes which we supposed to be involved in linezolid elimination upon sepsis outcome. Fourteen ICU-admitted patients in therapy with intravenous linezolid (600mg q12h) were enrolled and classified into three groups: group 0 for sepsis, 1 for severe sepsis and 2 for septic shock...
March 1, 2017: Le Infezioni in Medicina
https://www.readbyqxmd.com/read/28337145/dioscin-protects-anit-induced-intrahepatic-cholestasis-through-regulating-transporters-apoptosis-and-oxidative-stress
#12
Hong Yao, Youwei Xu, Lianhong Yin, Xufeng Tao, Lina Xu, Yan Qi, Xu Han, Pengyuan Sun, Kexin Liu, Jinyong Peng
Intrahepatic cholestasis, a clinical syndrome, is caused by excessive accumulation of bile acids in body and liver. Proper regulation of bile acids in liver cells is critical for liver injury. We previously reported the effects of dioscin against α-naphthylisothio- cyanate (ANIT)-induced cholestasis in rats. However, the pharmacological and mechanism data are limited. In our work, the animals of rats and mice, and Sandwich-cultured hepatocytes (SCHs) were caused by ANIT, and dioscin was used for the treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28286932/hoct1-gene-expression-predict-for-optimal-response-to-imatinib-in-tunisian-patients-with-chronic-myeloid-leukemia
#13
Islem Ben Hassine, Hanene Gharbi, Ismail Soltani, Mouheb Teber, Ahlem Farrah, Hind Ben Hadj Othman, Hassiba Amouri, Hatem Bellaaj, Rayhane Ben Lakhal, Neila Ben Romdhane, Salem Abbes, Samia Menif
PURPOSE: Imatinib mesylate (IM) is considered as a highly effective therapy for chronic myeloid leukemia (CML) patients. However, a minority of patients fail to achieve optimal response due to impaired bioavailability of IM. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in IM uptake into CML cells. Genetic variants and/or hOCT1 expression changes may influence IM response. In this study, we aimed to investigate the impact of both hOCT1 polymorphisms located in exon 7 and hOCT1 mRNA levels on the clinical outcome in CML patients...
March 12, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28281384/transport-properties-of-valsartan-sacubitril-and-its-active-metabolite-lbq657-as-determinants-of-disposition
#14
Imad Hanna, Natalya Alexander, Matthew H Crouthamel, John Davis, Adrienne Natrillo, Phi Tran, Arpine Vapurcuyan, Bing Zhu
1. The potential for drug-drug interactions of LCZ696 (a novel, crystalline complex comprising sacubitril and valsartan) was investigated in vitro. 2. Sacubitril was shown to be a highly permeable P-glycoprotein (P-gp) substrate and was hydrolyzed to the active anionic metabolite LBQ657 by human carboxylesterase 1 (CES1b and 1c). The multidrug resistance-associated protein 2 (MRP2) was shown to be capable of LBQ657 and valsartan transport that contributes to the elimination of either compound. 3. LBQ657 and valsartan were transported by OAT1, OAT3, OATP1B1 and OATP1B3, whereas no OAT- or OATP-mediated sacubitril transport was observed...
March 10, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28264478/crosstalk-of-the-androgen-receptor-with-transcriptional-collaborators-potential-therapeutic-targets-for-castration-resistant-prostate-cancer
#15
REVIEW
Daisuke Obinata, Kenichi Takayama, Satoru Takahashi, Satoshi Inoue
Prostate cancer is the second leading cause of death from cancer among males in Western countries. It is also the most commonly diagnosed male cancer in Japan. The progression of prostate cancer is mainly influenced by androgens and the androgen receptor (AR). Androgen deprivation therapy is an established therapy for advanced prostate cancer; however, prostate cancers frequently develop resistance to low testosterone levels and progress to the fatal stage called castration-resistant prostate cancer (CRPC)...
February 28, 2017: Cancers
https://www.readbyqxmd.com/read/28230985/discovery-of-competitive-and-noncompetitive-ligands-of-the-organic-cation-transporter-1-oct1-slc22a1
#16
Eugene C Chen, Natalia Khuri, Xiaomin Liang, Adrian Stecula, Huan-Chieh Chien, Sook Wah Yee, Yong Huang, Andrej Sali, Kathleen M Giacomini
Organic cation transporter 1 (OCT1) plays a critical role in the hepatocellular uptake of structurally diverse endogenous compounds and xenobiotics. Here we identified competitive and noncompetitive OCT1-interacting ligands in a library of 1780 prescription drugs by combining in silico and in vitro methods. Ligands were predicted by docking against a comparative model based on a eukaryotic homologue. In parallel, high-throughput screening (HTS) was conducted using the fluorescent probe substrate ASP(+) in cells overexpressing human OCT1...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28228010/selective-fusion-of-heterogeneous-classifiers-for-predicting-substrates-of-membrane-transporters
#17
Naeem Shaikh, Mahesh Sharma, Prabha Garg
Membrane transporters play a crucial role in determining fate of administered drugs in a biological system. Early identification of plausible transporters for a drug molecule can provide insights into its therapeutic, pharmacokinetic, and toxicological profiles. In the present study, predictive models for classifying small molecules into substrates and nonsubstrates of various pharmaceutically important membrane transporters were developed using quantitative structure-activity relationship (QSAR) and proteochemometric (PCM) approaches...
March 6, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28223391/evaluation-of-para-aminosalicylic-acid-as-a-substrate-of-multiple-solute-carrier-uptake-transporters-and-possible-drug-interactions-with-nonsteroidal-anti-inflammatory-drugs-in-vitro
#18
M Masud Parvez, Ho Jung Shin, Jin Ah Jung, Jae-Gook Shin
para-Aminosalicylic acid (PAS) is a second-line antituberculosis drug that has been used to treat multidrug-resistant and extensively drug-resistant tuberculosis for more than 60 years. Renal secretion and glomerular filtration are the major pathways for the elimination of PAS. We comprehensively studied PAS transport by using cell lines that overexpressed various transporters and found that PAS acts as a novel substrate of an organic anionic polypeptide (OATP1B1), organic cationic transporters (OCT1 and OCT2), and organic anion transporters (OAT1 and OAT3) but is not a substrate of any ATP-binding cassette (ABC) transporters...
May 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28199941/effect-directed-analysis-reveals-inhibition-of-zebrafish-uptake-transporter-oatp1d1-by-caulerpenyne-a-major-secondary-metabolite-from-the-invasive-marine-alga-caulerpa-taxifolia
#19
P Marić, M Ahel, I Senta, S Terzić, I Mikac, A Žuljević, T Smital
Caulerpa taxifolia is a marine alga of tropical and subtropical distribution and a well-known invasive species in several temperate regions. Its invasiveness mainly stems from the production of secondary metabolites, some of which are toxic or repellent substances. In this study we investigated the possible inhibitory effects of C. taxifolia secondary metabolites on the activity of two zebrafish (Danio rerio) uptake transporters that transport organic anions (Oatp1d1) and cations (Oct1). Both transporters were transiently transfected and overexpressed in human embryonic kidney HEK293T cells...
May 2017: Chemosphere
https://www.readbyqxmd.com/read/28178663/the-lack-of-the-organic-cation-transporter-oct1-at-the-plasma-membrane-of-tumor-cells-precludes-a-positive-response-to-sorafenib-in-patients-with-hepatocellular-carcinoma
#20
Andreas Geier, Rocio I R Macias, Dominik Bettinger, Johannes Weiss, Heike Bantel, Daniel Jahn, Ruba Al-Abdulla, Jose J G Marin
BACKGROUND: Sorafenib is the drug of choice in the treatment of advanced hepatocellular carcinoma (HCC). Beneficial effects are limited by mechanisms of chemoresistance, which include downregulation and/or impaired function of plasma membrane transporters accounting for drug uptake. The organic cation transporter 1 (OCT1) plays a major role in sorafenib uptake and decreased expression in HCC has been associated with poorer response. METHODS: The multicenter retrospective TRANSFER study involved tumor biopsies from 39 patients with advanced HCC and sorafenib therapy for ≥4 wk...
February 28, 2017: Oncotarget
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