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ABCG2

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https://www.readbyqxmd.com/read/28938556/abcg2-and-ncf4-polymorphisms-are-associated-with-clinical-outcomes-in-diffuse-large-b-cell-lymphoma-patients-treated-with-r-chop
#1
Duo Liu, Nan Wu, Haiming Sun, Mei Dong, Tianzhu Guo, Peng Chi, Guofu Li, Donglin Sun, Yan Jin
The impact of pharmacogenetics on predicting survival in diffuse large B-cell lymphoma (DLBCL) remains unclear. We tested 337 DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 9 single nucleotide polymorphisms from 6 genes (CD20, FCGR2A, NAD(P)H, ABCC2, ABCG2 and CYP3A5). Patients who carried the NCF4 rs1883112 GG genotype showed significantly shorter progression-free survival (PFS) (P = 0.023) and event-free survival (EFS) (P < 0.001) comparing with A allele...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28935760/ultrasound-reverses-chemo-resistance-in-breast-cancer-stem-cell-like-cells-by-altering-abcg2%C3%A2-expression
#2
Lijuan Guo, Pengfei Zheng, Huijun Fan, Haiyan Wang, Wenzhong Xu, Wenyan Zhou
Doxorubicin (DOX)-resistance in breast cancer largely results from the breast cancer stem cell-like cells (BCSCs) which could be targeted to improve the efficacy of chemotherapy. Cell permeabilization using microbubbles (MB) and ultrasound (US) have the potential for delivering molecules into the cytoplasm. We aim to evaluate a new methodology of US on BCSCs. First, our findings indicated that ALDHA1(+) spheres which were derived from fresh primary breast cancer samples displayed stem cell-like features and were resistant to DOX...
September 21, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28930109/abcg2-regulatory-single-nucleotide-polymorphisms-alter-in-vivo-enhancer-activity-and-expression
#3
Rachel J Eclov, Mee J Kim, Aparna Chhibber, Robin P Smith, Nadav Ahituv, Deanna L Kroetz
OBJECTIVES: The expression and activity of the breast cancer resistance protein (ABCG2) contributes toward the pharmacokinetics of endogenous and xenobiotic substrates. The effect of genetic variation on the activity of cis-regulatory elements and nuclear response elements in the ABCG2 locus and their contribution toward ABCG2 expression have not been investigated systematically. In this study, the effect of genetic variation on the in-vitro and in-vivo enhancer activity of six previously identified liver enhancers in the ABCG2 locus was examined...
September 18, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28928160/quantitative-and-mechanistic-understanding-of-azd1775-penetration-across-human-blood-brain-barrier-in-glioblastoma-patients-using-an-ivive-pbpk-modeling-approach
#4
Jing Li, Jianmei Wu, Xun Bao, Norissa Honea, Youming Xie, Seongho Kim, Alex Sparreboom, Nader Sanai
PURPOSE: AZD1775, a first-in-class, small molecule inhibitor of the Wee1 tyrosine kinase, is under evaluation as a potential chemo- and radio-sensitizer for treating glioblastoma. This study was to prospectively, quantitatively, and mechanistically investigate the penetration of AZD1775 across human blood-brain barrier (BBB). EXPERIMENTAL DESIGN: AZD1775 plasma and tumor pharmacokinetics were evaluated in 20 glioblastoma patients. The drug metabolism, transcellular passive permeability, and interactions with efflux and uptake transporters were determined using human derived in vitro systems...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28927112/non-small-cell-lung-cancer-pc-9-cells-exhibit-increased-sensitivity-to-gemcitabine-and-vinorelbine-upon-acquiring-resistance-to-egfr-tyrosine-kinase-inhibitors
#5
Junko Hamamoto, Hiroyuki Yasuda, Kaito Aizawa, Makoto Nishino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Tomoko Betsuyaku, Kenzo Soejima
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of non-small cell lung cancers (NSCLCs) harboring EGFR-activating mutations. However, lung cancer cells inevitably acquire resistance to these EGFR-TKIs. The majority of patients whose lung cancer acquires resistance to EGFR-TKIs are subjected to treatment using cytotoxic agents. The present study aimed to determine if lung cancer cells acquiring resistance to EGFR-TKIs also develop altered sensitivity to cytotoxic agents...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927110/characteristics-of-primary-side-population-cervical-cancer-cells
#6
Zhen-Tong Wei, Xiao-Wei Yu, Jia-Xue He, Yan Liu, Song-Ling Zhang
The aim of the present study was to identify and characterize side population (SP) cells in primary cervical cancer. A primary culture was successfully established, and the SP cells were isolated via fluorescence-activated cell sorting. Subsequently, in vitro analysis of clonogenic capacity by soft agar assay and in vivo analysis of tumorigenicity were performed. The isolated SP cells accounted for ~4.73% of the total primary culture cells. The SP cells had a decreased proliferation rate and an increased distribution in G0/G1 compared with non-SP (NSP) cells...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923017/within-breed-and-multi-breed-gwas-on-imputed-whole-genome-sequence-variants-reveal-candidate-mutations-affecting-milk-protein-composition-in-dairy-cattle
#7
Marie-Pierre Sanchez, Armelle Govignon-Gion, Pascal Croiseau, Sébastien Fritz, Chris Hozé, Guy Miranda, Patrice Martin, Anne Barbat-Leterrier, Rabia Letaïef, Dominique Rocha, Mickaël Brochard, Mekki Boussaha, Didier Boichard
BACKGROUND: Genome-wide association studies (GWAS) were performed at the sequence level to identify candidate mutations that affect the expression of six major milk proteins in Montbéliarde (MON), Normande (NOR), and Holstein (HOL) dairy cattle. Whey protein (α-lactalbumin and β-lactoglobulin) and casein (αs1, αs2, β, and κ) contents were estimated by mid-infrared (MIR) spectrometry, with medium to high accuracy (0.59 ≤ R(2) ≤ 0.92), for 848,068 test-day milk samples from 156,660 cows in the first three lactations...
September 18, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28921565/the-impact-of-p-glycoprotein-and-breast-cancer-resistance-protein-on-the-brain-pharmacokinetics-and-pharmacodynamics-of-a-panel-of-mek-inhibitors
#8
Mark C de Gooijer, Ping Zhang, Ruud Weijer, Levi C M Buil, Jos H Beijnen, Olaf van Tellingen
Mitogen/extracellular signal-regulated kinase (MEK) inhibitors have been tested in clinical trials for treatment of intracranial neoplasms, including glioblastoma (GBM), but efficacy of these drugs has not yet been demonstrated. The blood-brain barrier (BBB) is a major impediment to adequate delivery of drugs into the brain and may thereby also limit the successful implementation of MEK inhibitors against intracranial malignancies. The BBB is equipped with a range of ATP-dependent efflux transport proteins, of which P-gp (ABCB1) and BCRP (ABCG2) are the two most dominant for drug efflux from the brain...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28920531/role-of-kr%C3%A3-ppel-like-factor-4-in-the-maintenance-of-chemoresistance-of-anaplastic-thyroid-cancer
#9
Su In Lee, Dae Kyoung Kim, Eun Jin Seo, Eun Jung Choi, Yang Woo Kwon, Il Ho Jang, Jin Choon Lee, Hyun Yul Kim, Minho Shong, Jae Ho Kim, Seong-Jang Kim
BACKGROUND: Anaplastic thyroid cancer (ATC) has a very poor prognosis due to its aggressive nature and resistance to conventional treatment. Radiotherapy and chemotherapy are not fully effective because of the undifferentiated phenotype and enhanced drug resistance of ATC. The objective of this study was to evaluate the involvement of Krüppel-like factor 4 (KLF4), a stemness-associated transcription factor, in the undifferentiated phenotype and drug resistance of ATC. METHODS: ATC cells were compared with papillary thyroid cancer cells in drug resistance and gene expression...
September 16, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28919747/ge11-peptide-conjugated-nanoliposomes-to-enhance-the-combinational-therapeutic-efficacy-of-docetaxel-and-sirna-in-laryngeal-cancers
#10
Wei-Wei Xu, Da-Yu Liu, Ying-Chun Cao, Xiang-Yun Wang
In this study, dual therapeutic-loaded GE11 peptide-conjugated liposomes were developed and applied to enhance therapeutic efficacies of standard-of-care regimens for the treatment of laryngeal cancer. The therapeutic strategy used here was a combination treatment with the chemotherapeutic docetaxel (DTX) and siRNA against the ABCG2 gene that regulates multidrug resistance in many tumor types. Liposome-encapsulated DTX/ABCG2-siRNA molecules were targeted to recognize tumor cells of squamous morphology by conjugation to the EGFR-targeting ligand, GE11...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28916341/design-synthesis-and-biological-evaluation-of-benzamide-and-phenyltetrazole-derivatives-with-amide-and-urea-linkers-as-bcrp-inhibitors
#11
Nehaben A Gujarati, Leli Zeng, Pranav Gupta, Zhe-Sheng Chen, Vijaya L Korlipara
Breast cancer resistant protein (BCRP/ABCG2), a 72kDa plasma membrane transporter protein is a member of ABC transporter superfamily. Increased expression of BCRP causes increased efflux and therefore, reduced intracellular accumulation of many unrelated chemotherapeutic agents leading to multidrug resistance (MDR). A series of 31 benzamide and phenyltetrazole derivatives with amide and urea linkers has been synthesized to serve as potential BCRP inhibitors in order to overcome BCRP-mediated MDR. The target derivatives were tested for their cytotoxicity and reversal effects in human non-small cell lung cancer cell line H460 and mitoxantrone resistant cell line H460/MX20 using the MTT assay...
September 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28915692/biomarker-analysis-of-the-phase-3-torch-trial-for-first-line-erlotinib-versus-chemotherapy-in-advanced-non-small-cell-lung-cancer-patients
#12
Lucia Kim, Mauro Saieg, Massimo Di Maio, Ciro Gallo, Charles Butts, Fortunato Ciardiello, Ronald Feld, Dengxiao Cheng, Vittorio Gebbia, Marco Angelo Burgio, Yasmin Alam, Simona Signoriello, Antonio Rossi, Natasha Leighl, Paolo Maione, Alessandro Morabito, Geoffrey Liu, Ming-Sound Tsao, Francesco Perrone, Cesare Gridelli
BACKGROUND: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. METHODS: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912477/brain-barriers-and-functional-interfaces-with-sequential-appearance-of-abc-efflux-transporters-during-human-development
#13
Kjeld Møllgård, Katarzyna M Dziegielewska, Camilla B Holst, Mark D Habgood, Norman R Saunders
Adult brain is protected from entry of drugs and toxins by specific mechanisms such as ABC (ATP-binding Cassette) efflux transporters. Little is known when these appear in human brain during development. Cellular distribution of three main ABC transporters (ABCC1, ABCG2, ABCB1) was determined at blood-brain barriers and interfaces in human embryos and fetuses in first half of gestation. Antibodies against claudin-5 and -11 and antibodies to α-fetoprotein were used to describe morphological and functional aspects of brain barriers...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912036/dual-effects-of-the-pi3k-inhibitor-zstk474-on-multidrug-efflux-pumps-in-resistant-cancer-cells
#14
Divya Muthiah, Richard Callaghan
ZSTK474 is a potent phosphoinositide 3-kinase (PI3K) inhibitor that reduces cell proliferation via G1-arrest. However, there is little information on the susceptibility of this anticancer drug to resistance conferred by the multidrug pumps P-glycoprotein (ABCB1) and ABCG2. We have demonstrated that ZSTK474 generated cytotoxicity in cells over-expressing either pump with potency similar to that in drug sensitive cells. In addition, the co-administration of ZSTK474 with the cytotoxic anti-cancer drugs vinblastine and mitoxantrone caused a potentiated cytotoxic effect in both drug sensitive and efflux pump expressing cells...
September 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28904007/synthetic-analogs-of-curcumin-modulate-the-function-of-multidrug-resistance-linked-abc-transporter-abcg2
#15
Megumi Murakami, Shinobu Ohnuma, Michihiro Fukuda, Eduardo E Chufan, Katsuyoshi Kudoh, Keigo Kanehara, Norihiko Sugisawa, Masaharu Ishida, Takeshi Naitoh, Hiroyuki Shibata, Yoshiharu Iwabuchi, Suresh V Ambudkar, Michiaki Unno
Multidrug resistance (MDR) caused by the overexpression of ATP-binding cassette (ABC) transporters in cancer cells is a major obstacle in cancer chemotherapy. Previous studies have shown that curcumin, a natural product and a dietary constituent of turmeric, inhibits the function of MDR-related ABC transporters, including ABCB1, ABCC1, and especially ABCG2. However, the limited bioavailability of curcumin prevents its use for modulation of the function of these transporters in the clinical setting. In this study, we investigated the effects of twenty-four synthetic curcumin analogs with increased bioavailability on the transport function of ABCG2...
September 13, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28894469/ex-vivo-expansion-of-human-limbal-epithelial-cells-using-human-placenta-derived-and-umbilical-cord-derived-mesenchymal-stem-cells
#16
Sang Min Nam, Yong-Sun Maeng, Eung Kweon Kim, Kyoung Yul Seo, Helen Lew
Ex vivo culture of human limbal epithelial cells (LECs) is used to treat limbal stem cell (LSC) deficiency, a vision loss condition, and suitable culture systems using feeder cells or serum without animal elements have been developed. This study evaluated the use of human umbilical cord or placenta mesenchymal stem cells (C-MSCs or P-MSCs, resp.) as feeder cells in an animal/serum-free coculture system with human LECs. C-/P-MSCs stimulated LEC colony formation of the stem cell markers (p63, ABCG2) and secreted known LEC clonal growth factors (keratinocyte growth factor, β-nerve growth factor)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28893612/tyrphostin-rg14620-selectively-reverses-abcg2-mediated-multidrug-resistance-in-cancer-cell-lines
#17
Chung-Pu Wu, Sung-Han Hsiao, Megumi Murakami, Ming-Jie Lu, Yan-Qing Li, Chia-Hung Hsieh, Suresh V Ambudkar, Yu-Shan Wu
The multidrug resistance (MDR) phenotype associated with the overexpression of ATP-binding cassette (ABC) drug transporters ABCB1, ABCC1 and ABCG2 is a major obstacle in cancer chemotherapy. Numerous epidermal growth factor receptor (EGFR) inhibitors have previously been shown capable of reversing MDR in ABCG2-overexpressing cancer cells. However, most of them are not transporter-specific due to the substantial overlapping substrate specificity among the transporters. In this study, we investigated the interaction between ABCG2 and tyrphostin RG14620, an EGFR inhibitor of the tyrphostin family, in multidrug-resistant cancer cell lines...
September 8, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28881812/a-combination-of-valproic-acid-sodium-salt-chir99021-e-616452-tranylcypromine-and-3-deazaneplanocin-a-causes-stem-cell-like-characteristics-in-cancer-cells
#18
Shuang Sha, Yuanfen Zhai, Chengzhao Lin, Heyong Wang, Qing Chang, Shuang Song, Mingqiang Ren, Gentao Liu
Many studies are based on the hypothesis that recurrence and drug resistance in lung carcinoma are due to a subpopulation of cancer stem-like cells (CSLCs) in solid tumors. Therefore it is crucial to screen for and recognize lung CSLCs. In this study, we stimulated non-small cell lung cancer (NSCLC) A549 cells to display stem cell-like characteristics using a combination of five small molecule compounds. The putative A549 stem cells activated an important CSLC marker, CD133 protein, as well multiple CSLC-related genes including ATP-binding cassette transporter G2 (ABCG2), C-X-C chemokine receptor type 4 (CXCR4), NESTIN, and BMI1...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880970/optimization-of-western-blotting-analysis-for-the-isolation-and-detection-of-membrane-xenobiotic-transporter-abcg2
#19
Małgorzata Szczygieł, Marcin Markiewicz, Milena Szafraniec, Roxana Zuziak, Krystyna Urbańska, Leszek Fiedor
All organisms are exposed to numerous stress factors, which include harmful xenobiotics. The diversity of these compounds is enormous, thus in the course of evolution diverse biological defense mechanisms at various levels of organization have developed. One of them engages an evolutionarily conserved family of transporters from the ABC superfamily, found in most species - from bacteria to humans. An important example of such a transporter is the breast cancer resistance protein (BCRP/ABCG2), a typical integral membrane protein...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28880238/implications-of-abcg2-expression-on-irinotecan-treatment-of-colorectal-cancer-patients-a-review
#20
REVIEW
Dorte Lisbet Nielsen, Jesper Andreas Palshof, Nils Brünner, Jan Stenvang, Birgitte Martine Viuff
BACKGROUND: One of the main chemotherapeutic drugs used on a routine basis in patients with metastatic colorectal cancer ((m)CRC) is the topoisomerase-1 inhibitor, irinotecan. However, its usefulness is limited by the pre-existing or inevitable development of resistance. The ATP-binding cassette (ABC) transporter ABCG2/breast cancer resistance protein (BRCP) through its function in xenobiotic clearance might play an important role in irinotecan resistance. With a goal to evaluate the clinical significance of ABCG2 measurements, we here review the current literature on ABCG2 in relation to irinotecan treatment in CRC patients...
September 7, 2017: International Journal of Molecular Sciences
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