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https://www.readbyqxmd.com/read/29786110/multi%C3%A2-layered-prevention-and-treatment-of-chronic-inflammation-organ-fibrosis-and-cancer-associated-with-canonical-wnt-%C3%AE-%C3%A2-catenin-signaling-activation-review
#1
Masaru Katoh
β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulators (BCL9, BCL9L, CREBBP/CBP, EP300/p300, FOXM1, MED12, SMARCA4/BRG1 and TCF/LEF). Gain‑of‑function CTTNB1 mutations are detected in bladder cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer and uterine cancer, whereas loss‑of‑function CTNNB1 mutations are also detected in human cancer...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29781244/oprm1-influence-on-and-effectiveness-of-an-individualized-treatment-plan-for-prescription-opioid-use-disorder-patients
#2
Javier Muriel, César Margarit, Beatriz Planelles, María J Serralta, Carmen Puga, María-Del-Mar Inda, Esperanza Cutillas, Domingo Morales, José F Horga, Ana M Peiró
Screening for opioid use disorder should be considered in chronic non-cancer pain (CNCP) patients with long-term use of opioids. The aim of our study was to assess the effectiveness of an individualized treatment plan (ITP) for prescription opioid dependence that included screening of pharmacogenetic markers. An observational prospective study was performed using prescription opioid-dependent CNCP outpatients (n = 88). Patients were divided into nonresponders, responders, or high responders according to their response to the ITP...
May 20, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29780320/cloning-and-transcriptional-activity-analysis-of-the-porcine-abcb1-gene-promoter-transcription-factor-sp1-regulates-the-expression-of-porcine-abcb1
#3
Tingting Guo, Jinhu Huang, Changchao Huan, Fang He, Yujuan Zhang, Zohaib A Bhutto, Liping Wang
P-Glycoprotein (P-gp, Abcb1) plays a crucial role in drug disposition and functions by hydrolyzing ATP. However, little is known about the regulatory elements governing the transcription of the porcine Abcb1 gene. In this study, the transcription start site of the pig Abcb1 gene was identified by 5'-RACE. A 1.9-kb fragment of the 5'-flanking region of the Abcb1 gene was cloned from pig genomic DNA and sequenced. The region critical for its promoter activity was investigated via progressive deletions. Further, using mutation assays, two proximal Sp1 binding sites within the 5'-flanking region of Abcb1 were proven to be important cis- regulatory elements involved in regulating the constitutive expression of porcine Abcb1 ...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29777711/uca1-confers-paclitaxel-resistance-to-ovarian-cancer-through-mir-129-abcb1-axis
#4
Junrong Wang, Cong Ye, Junbao Liu, Yubo Hu
Increasing evidence has demonstrated the involvement of dysregulated long non-coding RNAs (lncRNAs) in chemoresistance acting as potential oncogenes or tumor suppressors in various cancers. Nevertheless, the profound molecular mechanisms of lncRNAs in ovarian cancer (OC) chemoresistance is not well elucidated. The objective of this work was to investigate the role and molecular mechanisms of urothelial carcinoma associated 1 (UCA1) in paclitaxel (PTX) resistance in OC. Our results indicated that UCA1 was significantly up-regulated in PTX-resistant OC cells (SKOV3/PTX and HeyA-8/PTX) compared with their parental cells (SKOV3 and HeyA-8)...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777510/clopidogrel-pharmacogenetics-in-iranian-patients-undergoing-percutaneous-coronary-intervention
#5
Nejat Mahdieh, Ahmad Rabbani, Ata Firouzi, Ali Zahedmehr, Maryam Hoseinimoghaddam, Sedigheh Saeidi, Hamidreza Sanati, Hosseinali Basiri, Feridoun Noohi, Bahareh Rabbani, Majid Maleki
Clopidogrel is used in patients with coronary syndromes and at risk of thrombotic events or receiving percutaneous coronary intervention (PCI) for reducing heart attack and stroke. Here we present genotype and phenotype study of Iranian patients undergoing PCI treated with clopidogrel during a 6-month period of follow-up; common variants of CYP2C19, CYP3A5, CYP3A4, and ABCB1 genes were determined as well as the patients' cardiovascular outcomes to find out the effect of these variants individually and in combination...
May 18, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29775201/tacrolimus-population-pharmacokinetics-and-multiple-cyp3a5-genotypes-in-black-and-white-renal-transplant-recipients
#6
Olivia Campagne, Donald E Mager, Daniel Brazeau, Rocco C Venuto, Kathleen M Tornatore
Tacrolimus exhibits inter-patient pharmacokinetic variability attributed to CYP3A5 isoenzymes and the efflux transporter, P-glycoprotein. Most black renal transplant recipients require higher tacrolimus doses compared to whites to achieve similar troughs when race-adjusted recommendations are used. An established guideline provides tacrolimus genotype dosing recommendations based on CYP3A5*1(W/T) and loss of protein function variants: CYP3A5*3 (rs776746), CYP3A5*6 (rs10264272), CYP3A5*7 (rs41303343) and may provide more comprehensive race-adjusted dosing recommendations...
May 18, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29768303/post-mortem-analysis-of-suicide-victims-shows-abcb1-haplotype-1236t-2677t-3435t-as-a-candidate-predisposing-factor-behind-adverse-drug-reactions-in-females-erratum
#7
(no author information available yet)
No abstract text is available yet for this article.
June 2018: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/29765522/establishment-of-preclinical-chemotherapy-models-for-gastroenteropancreatic-neuroendocrine-carcinoma
#8
Akihiro Ohmoto, Masami Suzuki, Erina Takai, Hirofumi Rokutan, Yuko Fujiwara, Chigusa Morizane, Kazuyoshi Yanagihara, Tatsuhiro Shibata, Shinichi Yachida
Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a rare and devastating malignancy, and preclinical studies are needed to evaluate potential therapeutic regimens. Here, we examined the antitumor effects of cisplatin (CDDP), etoposide (ETP) and irinotecan (CPT-11) and their combinations on GEP-NEC using three small-cell GEP-NEC cell lines (pancreatic NEC, A99; esophageal NEC, TYUC-1; duodenum NEC, TCC-NECT-2). In vitro studies were conducted using cell viability assays. In vivo experiments were conducted in mice inoculated with A99 or TCC-NECT-2 and treated with no agent, CDDP, CDDP+ETP (EP) or CDDP+CPT-11 (IP)...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29754150/does-g2677t-polymorphism-of-the-mdr1-gene-make-a-difference-in-the-therapeutic-response-to-paroxetine-in-depressed-patients-in-a-slovakian-population
#9
Zuzana Vancova, Martina Cizmarikova, Jozef Dragasek, Silvia Zofcakova, Peter Kolarcik, Jan Mojzis
BACKGROUND The role of multidrug resistance 1 gene (MDR1 or ABCB1) polymorphism G2677T was studied in relation to paroxetine therapeutic efficacy and its side effects, as well as its association with selected demographic and clinical characteristics of patients with depressive disorder. MATERIAL AND METHODS To evaluate therapeutic efficacy, all patients (n=61) were rated at week 0, 2, 4, and 6 using the Hamilton Rating Scale for Depression (HAMD-21). They were labelled as "responders" (a decrease in HAMD ≥50%) and "nonresponders"...
May 13, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29748235/p-glycoprotein-abcb1-inhibits-the-influx-and-increases-the-efflux-of-11-c-metoclopramide-across-the-blood-brain-barrier-a-pet-study-on-non-human-primates
#10
Sylvain Auvity, Fabien Caillé, Solène Marie, Catriona Wimberley, Martin Bauer, Oliver Langer, Irène Buvat, Sébastien Goutal, Nicolas Tournier
Rationale : PET imaging using radiolabeled high-affinity substrates of P-glycoprotein (ABCB1) has convincingly revealed the role of this major efflux transporter in limiting the influx of its substrates from blood into the brain across the blood-brain barrier (BBB). Many drugs, such as metoclopramide, are weak ABCB1 substrates and distribute into the brain even when ABCB1 is fully functional. In this study, we used kinetic modeling and validated simplified methods to highlight and quantify the impact of ABCB1 on the BBB influx and efflux of 11 C-metoclopramide, as a model weak ABCB1 substrate, in non-human primates...
May 10, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29747752/reversal-effect-of-quercetin-on-multidrug-resistance-via-fzd7-%C3%AE-catenin-pathway-in-hepatocellular-carcinoma-cells
#11
Zhaolin Chen, Cheng Huang, Taotao Ma, Ling Jiang, Liqin Tang, Tianlu Shi, Shantang Zhang, Lei Zhang, Pengli Zhu, Jun Li, Aizong Shen
BACKGROUND: Chemotherapy has been widely used to treat cancer, but the appearance of multidrug resistance (MDR) is the biggest obstacle to successful chemotherapy. One of the conventional mechanisms of MDR is overexpression of ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated proteins (MRPs/ABCCs) that limits the prolonged and efficient use of chemotherapeutic drugs. To enhance the chemosensitivity of tumor cells, attentions have been focused on effective MDR modulators...
April 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29744867/p-glycoprotein-mdr1-abcb1-restricts-brain-accumulation-and-cytochrome-p450-3a-cyp3a-limits-oral-availability-of-the-novel-alk-ros1-inhibitor-lorlatinib
#12
Wenlong Li, Rolf W Sparidans, Yaogeng Wang, Maria C Lebre, Els Wagenaar, Jos H Beijnen, Alfred H Schinkel
Lorlatinib (PF-06463922) is a promising oral anaplastic lymphoma kinase (ALK) and ROS1 inhibitor currently in Phase III clinical trials for treatment of non-small cell lung cancer (NSCLC) containing an ALK rearrangement. With therapy-resistant brain metastases a major concern in NSCLC, lorlatinib was designed to have high membrane and blood-brain barrier permeability. We investigated the roles of the multidrug efflux transporters ABCB1 and ABCG2, and the multispecific drug-metabolizing enzyme CYP3A in plasma pharmacokinetics and tissue distribution of lorlatinib using genetically modified mouse strains...
May 9, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29742496/ceritinib-enhances-the-efficacy-of-substrate-chemotherapeutic-agent-in-human-abcb1-overexpressing-leukemia-cells-in-vitro-in-vivo-and-ex-vivo
#13
Li Yang, Manjun Li, Fang Wang, Chen Zhen, Min Luo, Xiaona Fang, Hong Zhang, Jianye Zhang, Qingshan Li, Liwu Fu
BACKGROUND/AIMS: Multidrug resistance (MDR) triggered by ATP binding cassette (ABC) transporters, such as ABCB1, ABCC1, and ABCG2, is a key obstacle for successful cancer chemotherapy. There is currently no FDA-approved MDR modulator that can be used in clinic. Ceritinib, a selective ALK inhibitor, has been approved as the second-line treatment for ALK-positive non-small cell lung cancer. Here, we examined the role of ceritinib in leukemia associated MDR in therapy. METHODS: The cell proliferation was detected by MTT assay...
May 5, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29740849/atorvastatin-modulates-drug-transporters-and-ameliorates-nicotine-induced-testicular-toxicity
#14
S Syam Das, S S Nair, M Indira
We studied the changes in mRNA expressions of influx and efflux transporters, blood-testis-barrier proteins (BTB) and key apoptotic genes in the testis of rats coadministered with nicotine and atorvastatin. Rats were divided into four groups: (i) control, (ii) atorvastatin (10 mg/kg b.wt), (iii) nicotine (0.6 mg/kg b.wt) and (iv) atorvastatin (10 mg/kg b.wt) + nicotine (0.6 mg/kg b.wt). Atorvastatin was given by oral intubation and nicotine by intraperitoneal injection. After 60 days of treatment, expressions of key apoptotic genes involved in both intrinsic and extrinsic pathways; solute carrier influx transporters SLCOB1, SLC22A1 and efflux transporter ABCB1 associated with transport of atorvastatin and nicotine, and proteins of BTB were assayed...
May 8, 2018: Andrologia
https://www.readbyqxmd.com/read/29736778/effects-of-polymorphisms-in-nr1i2-cyp3a4-and-abc-transporters-on-the-steady-state-plasma-trough-concentrations-of-bosutinib-in-japanese-patient-with-chronic-myeloid-leukemia
#15
Maiko Abumiya, Akiko Mita, Saori Takahashi, Tomoko Yoshioka, Yoshihiro Kameoka, Naoto Takahashi, Masatomo Miura
We investigated the effects of polymorphisms in NR1I2 (7635A>G, 8055C>T), CYP3A4 (20230G>A), ABCB1 (1199G>A, 1236C>T, 2677G>T/A, 3435C>T), and ABCG2 (421C>A) on the mean plasma trough concentrations (C0 ) of bosutinib at the steady-state in 30 Japanese patients with chronic myeloid leukemia. Bosutinib C0 values were monitored using high-performance liquid chromatography. The median coefficient of variation (CV) value of the bosutinib C0 for one patient (intrapatient) during bosutinib therapy was 25...
May 7, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29734517/rosuvastatin-induced-rhabdomyolysis-possible-role-of-ticagrelor-and-patients-pharmacogenetic-profile
#16
Majda Vrkić Kirhmajer, Viola Macolić Šarinić, Livija Šimičević, Iva Ladić, Krešimir Putarek, Ljiljana Banfić, Nada Božina
Up to the beginning of 2018, a total of eight cases describing rare but clinically important drug interactions between rosuvastatin and ticagrelor which resulted in rhabdomyolysis have been noted in the Global World Health Organization (WHO) adverse drug reaction (ADR) database (VigiBase) as well as in available literature. There are several possible factors which could contribute to the onset of rhabdomyolysis: old age, initially excessive rosuvastatin dose, drug-drug interactions (DDI) on metabolic enzymes (CYPs and UGTs) and drug transporter levels (ABCB1, ABCG2, OATP1B1) and pharmacogenetic predisposition...
May 7, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29725907/genetic-factors-associated-with-postoperative-nausea-and-vomiting-a-systematic-review
#17
Pedro López-Morales, Diego Flores-Funes, Elena González Sánchez-Migallón, Ramón José Lirón-Ruiz, José Luis Aguayo-Albasini
BACKGROUND: In previous studies, there seems to be a relationship between different genetic polymorphisms and postoperative nausea and vomiting (PONV). We perform a systematic review of the current literature about the relationship between genetic polymorphisms and the presence of PONV. METHODS: Two bibliographic searches were carried out in three databases (PubMed, Web of Science, and Scopus) of studies, preferably prospective, about PONV following abdominal surgery...
May 3, 2018: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/29725709/using-the-lentiviral-vector-system-to-stably-express-chicken-p-gp-and-bcrp-in-mdck-cells-for-screening-the-substrates-and-studying-the-interplay-of-both-transporters
#18
Yujuan Zhang, Jinhu Huang, Yang Liu, Tingting Guo, Liping Wang
Transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are known to influence the pharmacokinetics and toxicity of substrate drugs. However, no detailed information is as yet available about functional activity and substrate spectra of chicken P-gp and BCRP. In this study, BCRP single and BCRP/P-gp double-transfected MDCK cell lines (named MDCK-chAbcg2 and MDCK-chAbcg2/Abcb1, respectively) were generated using lentiviral vector system to develop reliable systems for screening the substrates for these two transporters and study the interplay between them...
May 3, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29723984/triorganotin-derivatives-induce-cell-death-effects-on-l1210-leukemia-cells-at-submicromolar-concentrations-independently-of-p-glycoprotein-expression
#19
Viera Bohacova, Mario Seres, Lucia Pavlikova, Szilvia Kontar, Martin Cagala, Pavel Bobal, Jan Otevrel, Julius Brtko, Zdena Sulova, Albert Breier
The acceleration of drug efflux activity realized by plasma membrane transporters in neoplastic cells, particularly by P-glycoprotein (P-gp, ABCB1 member of the ABC transporter family), represents a frequently observed molecular cause of multidrug resistance (MDR). This multiple resistance represents a real obstacle in the effective chemotherapy of neoplastic diseases. Therefore, identifying cytotoxic substances that are also effective in P-gp overexpressing cells may be useful for the rational design of substances for the treatment of malignancies with developed MDR...
May 1, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29723928/effect-of-abcb1-c3435t-polymorphism-on-pharmacokinetics-of-antipsychotics-and-antidepressants
#20
Miriam Saiz-Rodríguez, Carmen Belmonte, Manuel Román, Dolores Ochoa, Carolina Jiang-Zheng, Dora Koller, Gina Mejía, Pablo Zubiaur, Aneta Wojnicz, Francisco Abad-Santos
P-glycoprotein, encoded by ABCB1, is an ATP-dependent drug efflux pump which exports substances outside the cell. Some studies described connections between C3435T polymorphism T allele and lower P-glycoprotein expression; therefore homozygous T/T could show higher plasma levels. Our aim was to evaluate the effect of C3435T on pharmacokinetics of 4 antipsychotics (olanzapine, quetiapine, risperidone and aripiprazole) and 4 antidepressants (trazodone, sertraline, agomelatine and citalopram). The study included 473 healthy volunteers receiving a single oral dose of one of these drugs, genotyped by real-time PCR...
May 3, 2018: Basic & Clinical Pharmacology & Toxicology
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