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https://www.readbyqxmd.com/read/27933604/chemoresistant-lung-cancer-stem-cells-display-high-dna-repair-capability-to-remove-cisplatin-dna-damage
#1
Wai-Kin Yu, Zhigang Wang, Chi-Chun Fong, Dandan Liu, Tak-Chun Yip, Siu-Kie Au, Guangyu Zhu, Mengsu Yang
BACKGROUND AND PURPOSE: The persistence of lung cancer stem cells (LCSCs) has been proposed to be the main factor of lung cancer recurrence due to their high resistance to conventional chemotherapy. The underlying mechanisms, however, have not been fully addressed. EXPERIMENTAL APPROACH: In this study, we examined the cellular response of a human lung cancer stem cell line upon treatment with cisplatin, a DNA-damaging anticancer drug that is extensively applied in clinics...
December 9, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27933340/enhancement-of-pharmacological-effects-of-uricosuric-agents-by-concomitant-treatment-with-pyrazinamide-in-rats
#2
Tetsuya Taniguchi, Naoki Ashizawa, Koji Matsumoto, Takashi Iwanaga
Our goal was to establish a model for the evaluation of the effects of uricosuric agents and to clarify the underlying mechanism(s). The effects of a uricosuric agent co-treated with pyrazinamide, an anti-tubercular agent, on urate handling were examined in rats. Furthermore, the effects of uricosuric agents on urate uptake were evaluated using the vesicles of rat renal brush-border membrane. Treatment with probenecid, at a dose of 100 mg/kg, significantly increased the urinary urate to creatinine ratio (UUA/UCRE) in pyrazinamide-treated rats although the same treatment did not produce any uricosuric effects in intact rats...
December 8, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27932985/pregnane-x-receptor-pxr-mediated-gene-repression-and-cross-talk-of-pxr-with-other-nuclear-receptors-via-coactivator-interactions
#3
REVIEW
Petr Pavek
Pregnane X receptor is a ligand-activated nuclear receptor (NR) that mainly controls inducible expression of xenobiotics handling genes including biotransformation enzymes and drug transporters. Nowadays it is clear that PXR is also involved in regulation of intermediate metabolism through trans-activation and trans-repression of genes controlling glucose, lipid, cholesterol, bile acid, and bilirubin homeostasis. In these processes PXR cross-talks with other NRs. Accumulating evidence suggests that the cross-talk is often mediated by competing for common coactivators or by disruption of coactivation and activity of other transcription factors by the ligand-activated PXR...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27932882/sustained-release-liquisolid-compact-tablets-containing-artemether-lumefantrine-as-alternate-day-regimen-for-malaria-treatment-to-improve-patient-compliance
#4
Petra Obioma Nnamani, Agatha Adaora Ugwu, Emmanuel Chinedu Ibezim, Franklin Chimaobi Kenechukwu, Paul Achile Akpa, John-Dike Nwabueze Ogbonna, Nicholas Chinedu Obitte, Amelia Ngozi Odo, Maike Windbergs, Claus-Michael Lehr, Anthony Amaechi Attama
The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether-lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol(®) ATO 5/Transcutol(®) HP and tallow fat/Transcutol(®) HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27932669/annals-express-quantification-of-the-steady-state-plasma-concentrations-of-clozapine-and-n-desmethylclozapine-in-japanese-patients-with-schizophrenia-using-a-novel-hplc-method-and-the-effects-of-cyps-and-abc-transporters-polymorphisms
#5
Yumiko Akamine, Yuka Sugawara-Kikuchi, Tsukasa Uno, Tetsuo Shimizu, Masatomo Miura
BACKGROUND: This study developed a novel high-performance liquid chromatography (HPLC) method for the simultaneous quantification of clozapine and its active metabolite, N-desmethylclozapine, in human plasma and investigated the effects of various factors, including genetic polymorphisms in cytochrome P450 (CYP) 2D6, CYP3A5, ABCB1, and ABCG2, on the steady-state plasma trough concentrations (C0) of clozapine and N-desmethylclozapine in Japanese patients with schizophrenia. METHODS: Forty-five patients had been receiving fixed doses of clozapine for at least 4 weeks...
December 8, 2016: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/27931922/qualitative-analysis-of-the-risks-and-practices-associated-with-the-spread-of-african-swine-fever-within-the-smallholder-pig-value-chains-in-uganda
#6
Michel Dione, Emily Ouma, Felix Opio, Brian Kawuma, Danilo Pezo
A study was undertaken between September 2014 and December 2014 to assess the perceptions of smallholder pig value chain actors of the risks and practices associated with the spread of African swine fever (ASF) disease within the pig value chains. Data was collected from 136 value chain actors and 36 key informants through 17 group discussions and two key informant interview (KII) sessions respectively using Participatory Rural Appraisal (PRA) tools. Results from this study revealed that according to value chain actors and stakeholders, the transporting, slaughtering, and collecting/bulking nodes represent the highest risk, followed by the inputs and services (feeds and drugs) supply nodes...
December 1, 2016: Preventive Veterinary Medicine
https://www.readbyqxmd.com/read/27931149/chrysosplenetin-inhibits-artemisinin-efflux-in-p-gp-over-expressing-caco-2-cells-and-reverses-p-gp-mdr1-mrna-up-regulated-expression-induced-by-artemisinin-in-mouse-small-intestine
#7
Liping Ma, Shijie Wei, Bei Yang, Wei Ma, Xiuli Wu, Hongyan Ji, Hong Sui, Jing Chen
CONTEXT: CYP3A4 and P-gp together form a highly efficient barrier for orally absorbed drugs and always share the same substrates. Our previous work revealed that chrysosplenetin (CHR) significantly augmented the rat plasma level and anti-malarial efficacy of artemisinin (ART), partially due to the uncompetitive inhibition effect of CHR on rat CYP3A. But the impact of CHR on P-gp is still unknown. OBJECTIVE: The present study investigates whether CHR interferes with P-gp-mediated efflux of ART and elucidates the underlying mechanism...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27930637/the-use-of-drug-transporters-as-therapeutic-targets
#8
Kathleen M Giacomini
No abstract text is available yet for this article.
November 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27929465/using-multi-fluorinated-bile-acids-and-in-vivo-magnetic-resonance-imaging-to-measure-bile-acid-transport
#9
Jessica Felton, Kunrong Cheng, Anan Said, Aaron C Shang, Su Xu, Diana Vivian, Melissa Metry, James E Polli, Jean-Pierre Raufman
Along with their traditional role as detergents that facilitate fat absorption, emerging literature indicates that bile acids are potent signaling molecules that affect multiple organs; they modulate gut motility and hormone production, and alter vascular tone, glucose metabolism, lipid metabolism, and energy utilization. Changes in fecal bile acids may alter the gut microbiome and promote colon pathology including cholerrheic diarrhea and colon cancer. Key regulators of fecal bile acid composition are the small intestinal Apical Sodium-dependent Bile Acid Transporter (ASBT) and fibroblast growth factor-19 (FGF19)...
November 27, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27929454/thermostabilization-expression-purification-and-crystallization-of-the-human-serotonin-transporter-bound-to-s-citalopram
#10
Jonathan A Coleman, Evan M Green, Eric Gouaux
The serotonin transporter is a sodium and chloride-coupled transporter that "pumps" extracellular serotonin into cells. S-citalopram is a drug used to treat depression and anxiety by binding to the serotonin transporter with high-affinity, blocking serotonin reuptake. Here we report an efficient procedure and a set of tools to stabilize, express, purify, and crystallize serotonin transporter-antibody complexes bound to S-citalopram and other antidepressants. Mutations which stabilize the serotonin transporter were identified using an S-citalopram binding assay...
November 27, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27928109/na-ca-2-exchanger-contributes-to-stool-transport-in-mice-with-experimental-diarrhea
#11
Kazuhiro Nishiyama, Kohta Tanioka, Yasu-Taka Azuma, Satomi Hayashi, Yasuyuki Fujimoto, Natsuho Yoshida, Satomi Kita, Sho Suzuki, Hidemitsu Nakajima, Takahiro Iwamoto, Tadayoshi Takeuchi
The Na(+)/Ca(2+) exchanger (NCX) is a bidirectional transporter that is controlled by membrane potential and transmembrane gradients of Na(+) and Ca(2+). To reveal the functional role of NCX on gastrointestinal motility, we have previously used NCX1 and NCX2 heterozygote knockout mice (HET). We found that NCX1 and NCX2 play important roles in the motility of the gastric fundus, ileum and distal colon. Therefore, we believed that NCX1 and NCX2 play an important role in transport of intestinal contents. Here, we investigated the role of NCX in a mouse model of drug-induced diarrhea...
December 8, 2016: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/27926596/donor-genotype-and-intragraft-expression-of-cyp3a5-reflect-the-response-to-steroid-treatment-during-acute-renal-allograft-rejection
#12
N V Rekers, T M Flaig, M J K Mallat, M J Spruyt-Gerritse, M Zandbergen, J D H Anholts, I M Bajema, M C Clahsen-van Groningen, J Yang, J W de Fijter, F H J Claas, S Brakemeier, N Lachmann, R Kreutz, E de Heer, K Budde, J Bolbrinker, M Eikmans
BACKGROUND: Glucocorticoid-refractory acute rejection is a risk factor for inferior renal allograft outcome. We investigated genetic predisposition to the response to steroid treatment of acute allograft rejection. METHODS: Single nucleotide polymorphisms of genes involved in glucocorticoid signaling (GR, GLCCI1) and drug metabolism and transport (CYP3A5, ABCB1, and PXR) were analyzed in kidney transplant recipients (1995-2005, Leiden cohort, n=153) treated with methylprednisolone...
December 6, 2016: Transplantation
https://www.readbyqxmd.com/read/27926506/disruption-of-the-association-between-drug-transporter-and-actin-cytoskeleton-abolishes-drug-resistance-in-hypertrophic-scar
#13
Linlin Su, Lanqing Fu, Yan Li, Fangfang Yang, Min Zhang, Dahai Hu
Hypertrophic scar is characterized by the overgrowth of fibroblasts and often considered as a kind of benign skin tumor, thus chemotherapeutic drugs have been used to treat scars. In view of the similarity, this study aims to investigate whether drug resistance in cancer that contributes to the failure of chemotherapy also exists in hypertrophic scar, and what is the possible mechanism. Fibroblasts derived from hypertrophic scar and normal skin tissues were first compared for their resistance to verapamil and etoposide phosphate...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925473/the-role-of-cancer-stem-cells-in-tumor-heterogeneity-and-resistance-to-therapy
#14
Christina Valbirk Konrad, Reshma Murali, Binitha Anu Varghese, Radhika Nair
Cancer is a heterogenous disease displaying marked inter- and intra-tumoral diversity. The existence of cancer stem cells (CSCs) has been experimentally demonstrated in a number of cancer types as a subpopulation of tumor cells that drives the tumorigenic and metastatic properties of the entire cancer. Thus, eradication of the CSC population is critical for the complete ablation of a tumor. This is, however, confounded by the inherent resistance of CSCs to standard anticancer therapies, eventually leading to the outgrowth of resistant tumor cells and relapse in patients...
September 3, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27925256/pharmacokinetic-drug-drug-interactions-of-tyrosine-kinase-inhibitors-a-focus-on-cytochrome-p450-transporters-and-acid-suppression-therapy
#15
REVIEW
Caroline Gay, Delphine Toulet, Pascal Le Corre
The extensive use of tyrosine kinase inhibitors (TKI's) in hematology and oncology has shown that these drugs have a significant potential for drug-drug interactions. Since these drugs have a rather low therapeutic window, some drug interactions are of particular clinical relevance either on drug toxicity or on patient's response. Significant interactions occur with concomitant use of acid-suppressive therapy leading to a decreased oral bioavailability. However, such interactions are drug dependent according to their solubility pattern and to the duration of action of acid-suppressive therapy, which is coprescribed...
December 7, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27925230/role-of-abc-transporters-in-trans-epithelial-transport-of-vitamin-k-antagonists
#16
Bernadette Espana, Solange Couturier, Caroline Prouillac
Vitamin K antagonists remain (VKAs) the oral anticoagulant of choice of venous thromboembolic disease. These drugs are characterized by a large inter-individual variability requiring frequent dose tailoring. Genetic polymorphisms for cytochrome CYP2C9 and VKORC1 explain some of the variability, especially in warfarin and acenocoumarol responses. The aim of this study is to assess on cell models the role of ABC transporters in the intestinal transfer of the main coumarin derivatives (warfarin, acenocoumarol) and indanedione derivatives (phenindione, fluindione)...
December 7, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27925179/hepatoma-cell-functions-modulated-by-nek2-are-associated-with-liver-cancer-progression
#17
Sheng-Ming Wu, Syuan-Ling Lin, Kang-Yun Lee, Hsiao-Chi Chuang, Po-Hao Feng, Wan-Li Cheng, Chia-Jung Liao, Hsiang-Cheng Chi, Yang-Hsiang Lin, Chung-Ying Tsai, Wei-Jan Chen, Chau-Ting Yeh, Kwang-Huei Lin
NEK2 (NIMA-related expressed kinase 2) is a serine/threonine centrosomal kinase that acts as a critical regulator of centrosome structure and function. Aberrant NEK2 activities lead to failure in regulating centrosome duplication. NEK2 overexpression promotes tumorigenesis and is associated with poor prognosis in several cancers. Increased NEK2 expression during the late pathological stage has been detected in the Oncomine liver dataset and hepatocellular carcinoma (HCC) specimens. Elevated NEK2 protein is associated with poor overall survival in patients with HCC...
December 7, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27924725/anticancer-drug-targets-of-salvia-phytometabolites-chemistry-biology-and-omics
#18
Da-Cheng Hao, Guang-Bo Ge, Pei-Gen Xiao
Salvia displays diverse anticancer properties, which are attributable to their diterpene and phenolic contents. There is no comprehensive review on the anticancer diversity and molecular targets of Salvia components. We investigate the diversity and molecular targets of Salvia phytometabolites responsible for the prevention and treatment of cancer and sarcoma. Traditional therapeutic knowledge suggests that Salvia species can be used to develop anticancer drugs. Lots of concerns have been raised for tanshinone (Tan) IIA and cryptotanshinone...
December 7, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27924724/delivery-systems-for-antimicrobial-peptides-and-proteins-towards-optimization-of-bioavailability-and-targeting
#19
Joana R Costa, Nádia C Silva, Bruno Sarmento, Manuela Pintado
Antimicrobial peptides (AMPs) and proteins are produced by a wide range of organisms as important elements of their defense mechanisms, forming a large number of antimicrobial compounds that can be used to treat several human infections. The potential for the use of AMPs and antimicrobial proteins in therapeutics is growing, but their application is often limited, due to their poor physical and/or chemical properties. In recent years, several drug delivery systems have been proposed to carry such molecules, in an attempt to overcome the difficulties regarding their properties...
December 7, 2016: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/27924312/protein-ligand-interaction-detection-with-a-novel-method-of-transient-induced-molecular-electronic-spectroscopy-times-experimental-and-theoretical-studies
#20
Tiantian Zhang, Tao Wei, Yuanyuan Han, Heng Ma, Mohammadreza Samieegohar, Ping-Wei Chen, Ian Lian, Yu-Hwa Lo
Protein-ligand interaction detection without disturbances (e.g., surface immobilization, fluorescent labeling, and crystallization) presents a key question in protein chemistry and drug discovery. The emergent technology of transient induced molecular electronic spectroscopy (TIMES), which incorporates a unique design of microfluidic platform and integrated sensing electrodes, is designed to operate in a label-free and immobilization-free manner to provide crucial information for protein-ligand interactions in relevant physiological conditions...
November 23, 2016: ACS Central Science
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