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https://www.readbyqxmd.com/read/29343829/targeted-inhibitors-of-p-glycoprotein-increase-chemotherapeutic-induced-mortality-of-multidrug-resistant-tumor-cells
#1
Amila K Nanayakkara, Courtney A Follit, Gang Chen, Noelle S Williams, Pia D Vogel, John G Wise
Overexpression of ATP-binding cassette (ABC) transporters is often linked to multidrug resistance (MDR) in cancer chemotherapies. P-glycoprotein (P-gp) is one of the best studied drug transporters associated with MDR. There are currently no approved drugs available for clinical use in cancer chemotherapies to reverse MDR by inhibiting P-glycoprotein. Using computational studies, we previously identified several compounds that inhibit P-gp by targeting its nucleotide binding domain and avoiding its drug binding domains...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29342419/investigation-of-the-transport-of-xanthine-dehydrogenase-inhibitors-by-the-urate-transporter-abcg2
#2
Makiko Nakamura, Kyoko Fujita, Yu Toyoda, Tappei Takada, Hiroshi Hasegawa, Kimiyoshi Ichida
Hyperuricemia induces gout and kidney stones and accelerates the progression of renal and cardiovascular diseases. Adenosine 5'-triphosphate-binding cassette subfamily G member 2 (ABCG2) is a urate transporter, and common dysfunctional variants of ABCG2, non-functional Q126X (rs72552713) and semi-functional Q141K (rs2231142), are risk factors for hyperuricemia and gout. A recent genome wide association study suggested that allopurinol, a serum uric acid-lowering drug that inhibits xanthine dehydrogenase, is a potent substrate of ABCG2...
November 22, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29342288/association-between-abcg2-rs2231142-and-poor-response-to-allopurinol-replication-and-meta-analysis
#3
Mary C Wallace, Rebecca L Roberts, Payal Nanavati, Jeffrey N Miner, Nicola Dalbeth, Ruth Topless, Tony R Merriman, Lisa K Stamp
Objective: ABCG2 rs2231142 (Q141K) has been reported to be associated with poor response to allopurinol, while there are conflicting data on the association between the genetically independent ABCG2 rs10011796 variant and allopurinol response. The aim of this study was to replicate the association of ABCG2 rs2231142 and rs10011796 with allopurinol response and perform a meta-analysis. Methods: Participants in the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) (n = 299) were studied...
January 12, 2018: Rheumatology
https://www.readbyqxmd.com/read/29342177/a-new-fluorescent-dye-accumulation-assay-for-parallel-measurements-of-the-abcg2-abcb1-and-abcc1-multidrug-transporter-functions
#4
Edit Szabó, Dóra Türk, Ágnes Telbisz, Nóra Kucsma, Tamás Horváth, Gergely Szakács, László Homolya, Balázs Sarkadi, György Várady
ABC multidrug transporters are key players in cancer multidrug resistance and in general xenobiotic elimination, thus their functional assays provide important tools for research and diagnostic applications. In this study we have examined the potential interactions of three key human ABC multidrug transporters with PhenGreen diacetate (PGD), a cell permeable fluorescent metal ion indicator. The non-fluorescent, hydrophobic PGD rapidly enters the cells and, after cleavage by cellular esterases, in the absence of quenching metal ions, PhenGreen (PG) becomes highly fluorescent...
2018: PloS One
https://www.readbyqxmd.com/read/29341237/the-impact-of-diuretic-use-and-abcg2-genotype-on-the-predictive-performance-of-a-published-allopurinol-dosing-tool
#5
Daniel F B Wright, Nicola Dalbeth, Amanda J Phipps-Green, Tony R Merriman, Murray L Barclay, Jill Drake, Paul Tan, Anne Horne, Lisa K Stamp
This research aims to evaluate the predictive performance of a published allopurinol dosing tool. Allopurinol dose predictions were compared to the actual dose required to achieve serum urate (SU) <0.36 mmol L-1 using mean prediction error. The influence of patient factors on dose predictions was explored using multilinear regression. Allopurinol doses were over-predicted by the dosing tool, however, this was minimal in patients without diuretic therapy (MPE 63mg day-1 , 95%CI 40-87) compared to those receiving diuretics (MPE 295mg day-1 , 95%CI 260-330, p<0...
January 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29340035/abcb1-3435tt-and-abcg2-421cc-genotypes-were-significantly-associated-with-longer-progression-free-survival-in-chinese-breast-cancer-patients
#6
Wanjun Li, Dan Zhang, Fen Du, Xuemei Xing, Ying Wu, Dong Xiao, Ming Liang, Zhigang Fan, Peng Zhao, Tao Liu, Guoyin Li
Objective: To investigate the distribution of ABCB1 C3435T and ABCG2 C421A gene polymorphisms in Chinese Han population and their influences on the susceptibility and prognosis of breast carcinoma. Methods: A total of 200 female subjects were enrolled in this study, comprising 100 breast cancer patients and 100 healthy controls. Carcinoma and para-carcinoma tissues were collected from the breast cancer patients, while peripheral blood was collected from healthy controls...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29334793/controlled-synthesis-and-size-effects-of-multifunctional-mesoporous-silica-nanosystem-for-precise-cancer-therapy
#7
Bin Ma, Lizhen He, Yuanyuan You, Jianbin Mo, Tianfeng Chen
Nanomaterials-based drug delivery systems display potent applications in cancer therapy, owing to the enhanced permeability and retention effect and diversified chemical modification. In this study, we have tailored and synthesized different sized mesoporous silica nanoparticles (MSNs) through reactant control to investigate the relevancy of nanoparticle size toward anticancer efficacy and suppressing cancer multidrug resistance. The different sized MSNs loaded with anticancer ruthenium complex (RuPOP) and conjugated with folate acid (FA) to enhance the selectivity between cancer and normal cells...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29331420/dacomitinib-antagonizes-multidrug-resistance-mdr-in-cancer-cells-by-inhibiting-the-efflux-activity-of-abcb1-and-abcg2-transporters
#8
Ying-Fang Fan, Wei Zhang, Leli Zeng, Zi-Ning Lei, Chao-Yun Cai, Pranav Gupta, Dong-Hua Yang, Qingbin Cui, Zuo-Dong Qin, Zhe-Sheng Chen, Louis D Trombetta
The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Numerous mechanisms have been recognized that cause MDR, but one of the most important mechanisms is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters, through which the efflux of various anticancer drugs against their concentration gradients is powered by ATP. In recent years, small molecular tyrosine kinase inhibitors (TKIs) have been developed for treatment in various human cancers overexpressing epidermal growth factor receptor (EGFR)...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29331377/%C3%AE-cellulin-promotes-the-proliferation-of-corneal-epithelial-stem-cells-through-the-phosphorylation-of-erk1-2
#9
Won-Yong Jeong, Hye-Young Yoo, Chan-Wha Kim
The proliferation of corneal epithelial stem cells (CESCs) is a very important process in the recovery of corneal wounds. Recent studies have shown that β-cellulin (BC) is effective in the repair of other tissues. However, its mechanism of action in corneal wound healing is not yet clear. The purpose of this study was to investigate how BC accelerates wound healing of the cornea. Here, we confirmed that the proliferation of CESCs was induced at a specific concentration (0.2, 2 and 20 ng/mL) by treatment with BC...
January 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29330434/targeting-melanoma-stem-cells-with-the-vitamin-e-derivative-%C3%AE-tocotrienol
#10
Monica Marzagalli, Roberta Manuela Moretti, Elio Messi, Marina Montagnani Marelli, Fabrizio Fontana, Alessia Anastasia, Maria Rosa Bani, Giangiacomo Beretta, Patrizia Limonta
The prognosis of metastatic melanoma is very poor, due to the development of drug resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism, contributing to disease relapse. We first characterized CSCs in melanoma cell lines. We observed that A375 (but not BLM) cells are able to form melanospheres and show CSCs traits: expression of the pluripotency markers SOX2 and KLF4, higher invasiveness and tumor formation capability in vivo with respect to parental adherent cells. We also showed that a subpopulation of autofluorescent cells expressing the ABCG2 stem cell marker is present in the A375 spheroid culture...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29327946/posttranscriptional-regulation-of-human-antigen-r-by-mir-133b-enhances-docetaxel-cytotoxicity-through-the-inhibition-of-atp-binding-cassette-subfamily-g-member-2-in-prostate-cancer-cells
#11
Hui Liu, Xiaolong Song, Junqing Hou, Zhenhua Zhao, Junkai Chang
Docetaxel (DTX)-based chemotherapy is a first-line therapy in patients with castration-resistant prostate cancer. However, development of DTX resistance remains a challenge in cancer treatment. miRNAs have been shown to be involved in drug resistance in tumors. Nevertheless, little is known about the function and detailed molecular mechanism of miR-133b in DTX resistance of prostate cancer cells. The current study showed that miR-133b was downregulated, while human antigen R (HuR) was upregulated in prostate cancer cells...
January 12, 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29317200/hyperuricemia-enhances-intracellular-urate-accumulation-via-down-regulation-of-cell-surface-bcrp-abcg2-expression-in-vascular-endothelial-cells
#12
Hisakazu Komori, Kazuyuki Yamada, Ikumi Tamai
Hyperuricemia has been recognized as an independent risk factor for cardiovascular disease. Urate stimulates NADPH oxidase and induces production of reactive oxygen species (ROS); consequently, intracellular urate accumulation can induce oxidative stress leading to endothelial dysfunction. Here, we studied the mechanism involved, using human umbilical vascular endothelial cells (HUVEC) as a model. Pretreatment with 15mg/dL unlabeled uric acid (corresponding to hyperuricemia) resulted in increased uptake of [14C]uric acid at steady-state by HUVEC, whereas pretreatment with 5mg/dL uric acid (in the normal serum concentration range) did not...
January 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29311482/population-pharmacokinetics-and-adverse-events-of-erlotinib-in-japanese-patients-with-non-small-cell-lung-cancer-impact-of-genetic-polymorphisms-in-metabolizing-enzymes-and-transporters
#13
Chihiro Endo-Tsukude, Ji-Ichiro Sasaki, Sho Saeki, Norihiro Iwamoto, Megumi Inaba, Sunao Ushijima, Hiroto Kishi, Shinji Fujii, Hiroshi Semba, Kosuke Kashiwabara, Yukari Tsubata, Mitsuhiro Hayashi, Yuki Kai, Hideyuki Saito, Takeshi Isobe, Hirotsugu Kohrogi, Akinobu Hamada
Determinants of interindividual variability in erlotinib pharmacokinetics (PK) and adverse events remain to be elucidated. This study with 50 Japanese non-small-cell lung cancer patients treated with oral erlotinib at a standard dose of 150 mg aimed to investigate whether genetic polymorphisms affect erlotinib PK and adverse events. Single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP1A1, CYP1A2, CYP2D6, CYP3A4, CYP3A5, UGT1A1, UGT2B7, GSTM1, and GSTT1) or efflux transporters (ABCB1, and ABCG2) were analyzed as covariates in a population PK model...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29307774/liaison-between-heme-metabolism-and-bioenergetics-pathways-a-multimodal-elucidation-for-early-diagnosis-of-oral-cancer
#14
Ripon Sarkar, Kabita Chaterjee, Durbadal Ojha, Bijurica Chakraborty, Sanghamitra Sengupta, Debprasad Chattopadhyay, Chirasree RoyChaudhuri, Ananya Barui
Metabolic alterations of oral epithelial cells under oxidative stress are important signatures for early diagnosis of oral cancer. Amongst different metabolic alterations, non-invasive photo-diagnostic methods have been extensively used for determining cellular heme metabolism and accumulation of protoporphyrin IX (PpIX) under administration of suitable photosensitizer. In this study, we report these metabolic alterations by direct analysis of oral exfoliated cells obtained from individuals with prolonged smoking habit without the exogenous administration of any photosensitizer...
January 4, 2018: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/29304406/multixenobiotic-resistance-in-mytilus-edulis-molecular-and-functional-characterization-of-an-abcg2-type-transporter-in-hemocytes-and-gills
#15
Yosra Ben Cheikh, Benoit Xuereb, Céline Boulangé-Lecomte, Frank Le Foll
Among the cellular protection arsenal, ABC transporters play an important role in xenobiotic efflux in marine organisms. Two pumps belonging to B and C subfamily has been identified in Mytilus edulis. In this study, we investigated the presence of the third major subtype ABCG2/BCRP protein in mussel tissues. Transcript was expressed in hemocytes and with higher level in gills. Molecular characterization revealed that mussel ABCG2 transporter shares the sequence and organizational structure with mammalian and molluscan orthologs...
December 28, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29303075/abc-transporters-regulation-and-association-with-multidrug-resistance-in-hepatocellular-carcinoma-and-colorectal-carcinoma
#16
Maria Paula Ceballos Mancini, Juan Pablo Rigalli, Lucila Ines Cere, Mariana Semeniuk, Viviana Alicia Catania, Maria Laura Ruiz
For most cancers, the treatment of choice is still being chemotherapy despite of its severe adverse effects, systemic toxicity and limited efficacy due to the development of multidrug resistance (MDR). MDR leads to chemotherapy failure generally associated with a decrease in drug concentration inside cancer cells, frequently due to an overexpression of ABC transporters such as P-glycoprotein (P-gp/MDR1/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP/ABCG2) that limit the efficacy of chemotherapeutic drugs...
January 4, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29296553/effect-of-air-lifting-on-the-stemness-junctional-protein-formation-and-cytokeratin-expression-of-in-vitro-cultivated-limbal-epithelial-cell-sheets
#17
Lily Wei Chen, Yan-Ming Chen, Chia-Ju Lu, Mei-Yun Chen, Szu-Yuan Lin, Fung-Rong Hu, Wei-Li Chen
PURPOSE: The aim of this study is to evaluate the effects of air-lifting on the stemness, junctional protein formation, and cytokeratin expression of rabbit limbal stem cells cultivated in vitro, and to find out the proper timing of air-lifting before transplantation as limbal epithelial cell sheets for the treatment of limbal insufficiency. MATERIALS AND METHODS: Limbal epithelial cells were isolated from the limbus of New Zealand white rabbits and cultivated in vitro...
October 2017: Taiwan Journal of Ophthalmology
https://www.readbyqxmd.com/read/29291022/nfe2l2-nrf2-silencing-inducible-mir-206-targets-c-met-egfr-and-suppresses-bcrp-abcg2-in-cancer-cells
#18
Bo-Hyun Choi, Da Young Ryu, In-Geun Ryoo, Mi-Kyoung Kwak
The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2/NRF2) plays a critical role in the expression of multiple antioxidant and detoxifying enzymes. Herein, we provide evidence of the molecular links between NRF2 and oncogenic signaling hepatocyte growth factor receptor (HGFR/c-MET) and epidermal growth factor receptor (EGFR). Interfering RNA-induced stable inhibition of NRF2 in ovarian carcinoma SKOV3 and renal carcinoma A498 reduced the levels of c-MET and EGFR. MicroRNA-206 (miR-206) that was increased in both NRF2-silenced cells was predicted as a dual regulator of c-MET and EGFR...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29286612/unexpected-lower-expression-of-oncoprotein-gankyrin-in-drug-resistant-abcg2-overexpressing-breast-cancer-cell-lines
#19
Taheri Taheri, Khadijeh Jamialahmadi, Fatemeh Khadijeh
Background: Development of a multidrug resistance (MDR) phenotype to chemotherapy remains a major barrier in the treatment of cancer. Gankyrin (p28, p28GANK or PSMD10) is an oncoprotein overexpressed in different carcinoma cell lines. The aim of this study was to compare Gankyrin expression level in MDR cells (MCF-7/ADR and MCF-7/ MX) and non-MDR counterparts (MCF-7). Methods: Gankyrin, MDR1 (also known as ABCB1; the ATP-binding cassette sub-family B member 1) and ABCG2 (also known as BCRP; the human breast cancer resistance protein) mRNA levels were analyzed by real-time RT-PCR...
December 29, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29276047/overcoming-resistance-to-the-thz-series-of-covalent-transcriptional-cdk-inhibitors
#20
Yang Gao, Tinghu Zhang, Hideki Terai, Scott B Ficarro, Nicholas Kwiatkowski, Ming-Feng Hao, Bandana Sharma, Camilla L Christensen, Edmond Chipumuro, Kwok-Kin Wong, Jarrod A Marto, Peter S Hammerman, Nathanael S Gray, Rani E George
Irreversible inhibition of transcriptional cyclin-dependent kinases (CDKs) provides a therapeutic strategy for cancers that rely on aberrant transcription; however, lack of understanding of resistance mechanisms to these agents will likely impede their clinical evolution. Here, we demonstrate upregulation of multidrug transporters ABCB1 and ABCG2 as a major mode of resistance to THZ1, a covalent inhibitor of CDKs 7, 12, and 13 in neuroblastoma and lung cancer. To counter this obstacle, we developed a CDK inhibitor, E9, that is not a substrate for ABC transporters, and by selecting for resistance, determined that it exerts its cytotoxic effects through covalent modification of cysteine 1039 of CDK12...
December 15, 2017: Cell Chemical Biology
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