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Cancer multidrug resistance

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https://www.readbyqxmd.com/read/29456815/crispr-cas9-a-new-approach-to-successful-knockdown-of-abcb1-p-glycoprotein-and-reversal-of-chemosensitivity-in-human-epithelial-ovarian-cancer-cell-line
#1
Leyla Norouzi-Barough, Mohammadreza Sarookhani, Rasoul Salehi, Mohammadreza Sharifi, Sahar Moghbelinejad
Objectives: Multidrug resistance (MDR) is a major obstacle in the successful chemotherapy of ovarian cancer. Inhibition of P-glycoprotein (P-gp), a member of ATP-binding cassette (ABC) transporters, is a well-known strategy to overcome MDR in cancer. The aim of this study was to investigate the efficiency and ability of CRISPR/Cas9 genome editing technology to knockdown ABCB1 gene expression in adriamycin resistant (A2780/ADR) ovarian cancer cell line and evaluate the sensitivity changes to doxorubicin...
February 2018: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29455646/tyrosine-kinase-inhibitors-enhanced-the-efficacy-of-conventional-chemotherapeutic-agent-in-multidrug-resistant-cancer-cells
#2
REVIEW
Shaocong Wu, Liwu Fu
Multidrug resistance (MDR) triggered by ATP binding cassette (ABC) transporter such as ABCB1, ABCC1, ABCG2 limited successful cancer chemotherapy. Unfortunately, no commercial available MDR modulator approved by FDA was used in clinic. Tyrosine kinase inhibitors (TKIs) have been administrated to fight against cancer for decades. Almost TKI was used alone in clinic. However, drug combinations acting synergistically to kill cancer cells have become increasingly important in cancer chemotherapy as an approach for the recurrent resistant disease...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29453043/understanding-of-human-atp-binding-cassette-superfamily-and-novel-multidrug-resistance-modulators-to-overcome-mdr
#3
REVIEW
Imran Shair Mohammad, Wei He, Lifang Yin
Indeed, multi-drug resistance (MDR) is a significant obstacle to effective chemotherapy. The overexpression of ATP-binding cassette (ABC) membrane transporters is a principal cause of enhanced cytotoxic drug efflux and treatment failure in various types of cancers. At cellular level, the pumps of ABC family regulate the transportation of numerous substances including drugs in and out of the cells. In past, the overexpression of ABC pumps suggested a well-known mechanism of drug resistance in cancers as well as infectious diseases...
February 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29451962/nucleopeptide-assemblies-selectively-sequester-atp-in-cells
#4
Huaimin Wang, Zhaoqianqi Feng, Yanan Qin, Jiaqing Wang, Bing Xu
Here we report that assemblies of nucleopeptides selectively sequestrate ATP in complex conditions (e.g., serum and cytosol). We develop assemblies of nucleopeptides that selectively sequester ATP over ADP. Counteracting enzymes interconvert ATP and ADP to modulate the nanostructures formed by the nucleopeptides and the nucleotides. The nucleopeptides, sequestering ATP effectively in cells, slow down efflux pumps in multidrug resistance cancer cells, thus boosting the efficacy of an anticancer drug. Examining additional 11 nucleopeptides (including D- and L-enantiomers) yields five more nucleopeptides that differentiate ATP and ADP via either precipitation or gelation...
February 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29450946/down-regulation-of-lrig1-by-microrna-20a-modulates-gastric-cancer-multidrug-resistance
#5
Lin Zhou, Xiaowei Li, Fan Zhou, Zhi'an Jin, Di Chen, Pin Wang, Shu Zhang, Yuzheng Zhuge, Yulong Shang, Xiaoping Zou
Multidrug resistance (MDR) significantly restricts the clinical efficacy of gastric cancer (GC) chemotherapy, and it is critical to search novel targets to predict and overcome MDR. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been proved to be correlated with drug resistance in several cancers. The present study revealed that LRIG1 was overexpressed in chemo-sensitive GC tissues and decreased expression of LRIG1 predicted poor survival in GC patients. We observed that up-regulation of LRIG1 enhanced chemo-sensitivity in GC cells...
February 16, 2018: Cancer Science
https://www.readbyqxmd.com/read/29448055/proteomic-characterization-of-withaferin-a-targeted-protein-networks-for-the-treatment-of-monoclonal-myeloma-gammopathies
#6
Martin Dom, Fritz Offner, Wim Vanden Berghe, Xaveer Van Ostade
Withaferin A (WA), a natural steroid lactone from the plant Withania somnifera, is often studied because of its antitumor properties. Although many in vitro and in vivo studies have been performed, the identification of Withaferin A protein targets and its mechanism of antitumor action remain incomplete. We used quantitative chemoproteomics and differential protein expression analysis to characterize the WA antitumor effects on a multiple myeloma cell model. Identified relevant targets were further validated by Ingenuity Pathway Analysis and Western blot and indicate that WA targets protein networks that are specific for monoclonal gammopathy of undetermined significance (MGUS) and other closely related disorders, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM)...
February 12, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29446732/biomedical-potentialities-of-taraxacum-officinale-based-nanoparticles-biosynthesized-using-methanolic-leaf-extract
#7
Tahir Rasheed, Muhammad Bilal, Chuanlong Li, Hafiz M N Iqbal
BACKGROUND: In the present study, the potential of methanolic leaf extract of Taraxacum officinale plant as a function of bio-inspired green synthesis for the fabrication of silver nanoparticles (AgNPs) has been explored. METHODS: The bio-reduction of aqueous silver nitrate (AgNO3) solution was confirmed by visually detecting the color change from pale yellow to blackish-brown. Maximum absorbance was observed at 420 nm due to the presence of characteristic surface Plasmon resonance of nano silver by UV-visible spectroscopy...
February 14, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29445340/inhibition-of-glucose-6-phosphate-dehydrogenase-reverses-cisplatin-resistance-in-lung-cancer-cells-via-the-redox-system
#8
Weipeng Hong, Peiheng Cai, Chuncao Xu, Di Cao, Weibang Yu, Zhongxiang Zhao, Min Huang, Jing Jin
The pentose phosphate pathway (PPP), which branches from glycolysis, is correlated with cancer cell proliferation, survival and senescence. In this study, differences in the metabolic profile of the PPP and the redox status of human lung carcinoma A549 cells and cisplatin-induced multidrug-resistant A549/DDP cells were analyzed and evaluated. The results showed that A549/DDP cells exhibited differential PPP-derived metabolic features and redox-related molecules. A549/DDP cells exhibited increased expression and enzymatic activity of PPP enzyme glucose-6-phosphate dehydrogenase (G6PD)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29445170/brm270-inhibits-cancer-stem-cell-maintenance-via-microrna-regulation-in-chemoresistant-a549-lung-adenocarcinoma-cells
#9
Taeho Kwon, Nisansala Chandimali, Do Luong Huynh, Jiao Jiao Zhang, Nameun Kim, Yesol Bak, Do-Young Yoon, Dae-Yeul Yu, Jae Cheol Lee, Meeta Gera, Mrinmoy Ghosh, Yang Ho Park, Dong Kee Jeong
Chemotherapy is a standard treatment for non-small-cell lung cancer (NSCLC). However, the dose-limiting toxicity of drugs and the development of chemoresistance are major clinical challenges to successful management of NSCLC. Asian traditional medicine is gaining global attention as a non-toxic alternative to chemotherapy. BRM270 is an extract formulated from seven Asian medicinal plants that has been shown to inhibit tumor cell proliferation in diverse cancer types. We previously demonstrated that BRM270 suppresses tumorigenesis by negatively regulating nuclear factor-κB signaling in multidrug-resistant cancer stem cells (CSCs)...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445149/let-7c-inhibits-cholangiocarcinoma-growth-but-promotes-tumor-cell-invasion-and-growth-at-extrahepatic-sites
#10
Yu Xie, Hang Zhang, Xing-Jun Guo, Ye-Chen Feng, Rui-Zhi He, Xu Li, Shuo Yu, Yan Zhao, Ming Shen, Feng Zhu, Xin Wang, Min Wang, Asha Balakrishnan, Michael Ott, Feng Peng, Ren-Yi Qin
Cholangiocarcinoma (CCA) is a cancer type with high postoperative relapse rates and poor long-term survival largely due to tumor invasion, distant metastasis, and multidrug resistance. Deregulated microRNAs (miRNAs) are implicated in several cancer types including CCA. The specific roles of the miRNA let-7c in cholangiocarcinoma are not known and need to be further elucidated. In our translational study we show that microRNA let-7c expression was significantly downregulated in human cholangiocarcinoma tissues when compared to adjacent tissues of the same patient...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29439258/bone-marrow-cell-therapy-on-1-2-dimethylhydrazine-dmh-induced-colon-cancer-in-rats
#11
Manal F El-Khadragy, Heba M Nabil, Basmaa N Hassan, Amany A Tohamy, Hanaa F Waaer, Hany M Yehia, Afra M Alharbi, Ahmed Esmat Abdel Moneim
BACKGROUND/AIMS: Stem cell based therapies are being under focus due to their possible role in treatment of various tumors. Bone marrow stem cells believed to have anticancer potential and are preferred for their activities by stimulating the immune system, migration to the site of tumor and ability for inducting apoptosis in cancer cells. The current study was aimed to investigate the tumor suppressive effects of bone marrow cells (BMCs) in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats...
February 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29437858/coarse-grained-molecular-dynamics-simulations-reveal-lipid-access-pathways-in-p-glycoprotein
#12
Estefania Barreto-Ojeda, Valentina Corradi, Ruo-Xu Gu, D Peter Tieleman
P-glycoprotein (P-gp) exports a broad range of dissimilar compounds, including drugs, lipids, and lipid-like molecules. Because of its substrate promiscuity, P-gp is a key player in the development of cancer multidrug resistance. Although P-gp is one of the most studied ABC transporters, the mechanism by which its substrates access the cavity remains unclear. In this study, we perform coarse-grained molecular dynamics simulations to explore possible lipid access pathways in the inward-facing conformation of P-gp embedded in bilayers of different lipid compositions...
February 6, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29436100/lupeol-alters-er-stress-signaling-pathway-by-downregulating-abcg2-expression-to-induce-oxaliplatin-resistant-lovo-colorectal-cancer-cell-apoptosis
#13
Ming-Cheng Chen, Hsi-Hsien Hsu, Yuan-Yuan Chu, Sue-Fei Cheng, Chia-Yao Shen, Yi-Jiun Lin, Ray-Jade Chen, Vijaya Padma Viswanadha, Yueh-Min Lin, Chih-Yang Huang
Colorectal cancer (CRC) is one of the most common cancers and causes of cancer-related death. There are several first-line chemotherapeutic drugs used to treat CRC. Oxaliplatin (OXA) is an alkylating cytotoxic agent that is usually combined with other chemotherapeutic drugs to treat stage II and stage III CRC. However, cancer cells commonly acquire multidrug resistance (MDR), which is a major obstruction to cancer treatment. Recent studies have shown that natural components from traditional Chinese medicine or foods that have many biological functions may be new adjuvant therapies in clinical trials...
February 13, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29433753/a-glutathione-responsive-sulfur-dioxide-polymer-prodrug-as-a-nanocarrier-for-combating-drug-resistance-in-cancer-chemotherapy
#14
Wei Shen, Wanguo Liu, Huailin Yang, Peng Zhang, Chunsheng Xiao, Xuesi Chen
Multidrug resistance (MDR) in cancer remains a significant challenge for curing cancer by chemotherapy. In this work, a kind of glutathione (GSH)-responsive polymer prodrug of SO2 was designed and synthesized, which presented synergistic effect with doxorubicin (DOX) for combating MCF-7 ADR human breast cancer cell. Firstly, a small molecular prodrug of SO2, N-(3-azidopropyl)-2,4-dinitrobenzenesulfonamide (AP-DNs), was chemically conjugated onto the side chain of methoxy poly (ethylene glycol)-block-poly (γ-propargyl-l-glutamate) (mPEG-PPLG) block copolymer to generate an amphiphilic polymer prodrug of SO2, mPEG-PLG (DNs)...
February 3, 2018: Biomaterials
https://www.readbyqxmd.com/read/29427708/tribromophenol-affects-the-metabolism-proliferation-migration-and-multidrug-resistance-transporters-activity-of-murine-melanoma-cells-b16f1
#15
Yvanna Carla S de Salgado, Marianna Boia Ferreira, Jessica Zablocki da Luz, Francisco Filipak Neto, Ciro Alberto de Oliveira Ribeiro
Murine melanoma cells B16F1 were exposed to the flame retardant and wood preservative chemical 2,4,6-tribromophenol (TBP) during 24 and 48 h, at the concentrations found in human diet. TBP-exposed cells had increased MTT and Alamar blue® metabolism and ABCB5 mRNA levels (qPCR), but the cells had decreased proliferation (crystal violet assay), migration (scratch assay), and drug-effux transporters activity (rhodamine B efflux assay). Exposure to TBP did not affect the cell viability (neutral red and annexin V-PI assays), colony formation (colony number, clonogenic assay), and the levels of reactive oxygen species (DCF probe) or P53 mRNA (qPCR)...
February 7, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29426932/quantitative-analysis-of-receptor-mediated-uptake-and-pro-apoptotic-activity-of-mistletoe-lectin-1-by-high-content-imaging
#16
N Beztsinna, M B C de Matos, J Walther, C Heyder, E Hildebrandt, G Leneweit, E Mastrobattista, R J Kok
Ribosome inactivating proteins (RIPs) are highly potent cytotoxins that have potential as anticancer therapeutics. Mistletoe lectin 1 (ML1) is a heterodimeric cytotoxic protein isolated from European Mistletoe and belongs to RIP class II. The aim of this project was to systematically study ML1 cell binding, endocytosis pathway(s), subcellular processing and apoptosis activation. For this purpose, state of the art cell imaging equipment and automated image analysis algorithms were used. ML1 displayed very fast binding to sugar residues on the membrane and energy-dependent uptake in CT26 cells...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29425587/reversal-of-multidrug-resistance-by-icaritin-in-doxorubicin-resistant-human-osteosarcoma-cells
#17
Zhen-Dong Wang, Rui-Zhi Wang, Yuan-Zheng Xia, Ling-Yi Kong, Lei Yang
Multidrug resistance (MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant (MG-63/DOX) cells. It is reported that icariin is usually metabolized to icariside II and icaritin. Herein, we investigated the effects of icariin, icariside II, and icaritin (ICT) on reversing MDR in MG-63/DOX cells. Among these compounds, ICT exhibited strongest effect and showed no obvious cytotoxicity effect on both MG-63 and MG-63/DOX cells ranging from 1 to 10 μmol·L-1...
January 2018: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29424355/cytotoxicity-of-propolis-nanopreparations-in-cancer-cell-monolayers-multimode-of-action-including-apoptotsis-and-nitric-oxide-production
#18
Mahmoud S Sherif, Taha A Rehab, Zayed A Hamdia, Vladmir P Torchilin
Natural products are invaluable resource of anticancer drug discovery. They generally viewed as safe but weak, within the framework of nanotechnology, they can serve as template for potent anticancer drugs. We first evaluated the cytotoxic activity of different propolis extracts (water, 70% ethanol, absolute ethanol and hexane) in many cancer cell lines, then the solid nanoparticles from the organic solvent extracts were prepared and their cytotoxicity was evaluated as well. Finally, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes were prepared from the most cytotoxic organic solvent extract and their cytotoxicity was also evaluated...
January 2018: General Physiology and Biophysics
https://www.readbyqxmd.com/read/29423046/vitexin-induces-apoptosis-by-suppressing-autophagy-in-multi-drug-resistant-colorectal-cancer-cells
#19
Monika Bhardwaj, Hee Jun Cho, Souren Paul, Rekha Jakhar, Imran Khan, Seon-Jin Lee, Bo-Yeon Kim, Manigandan Krishnan, Tejinder Pal Khaket, Hee Gu Lee, Sun Chul Kang
Cancer treatment is limited due to the diverse multidrug resistance acquired by cancer cells and the collateral damage caused to adjacent normal cells by chemotherapy. The flavonoid compound vitexin exhibits anti-oxidative, anti-inflammatory and anti-tumor activity. This study elucidated the antitumor effects of vitexin and its underlying mechanisms in a multi-drug resistant human colon cancer cell line (HCT-116 DR ), which exhibits higher levels of multidrug-resistant protein 1 (MDR1) expression as compared with its parental cell line (HCT-116)...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29423015/interaction-between-cd133-and-pi3k-p85-promotes-chemoresistance-in-gastric-cancer-cells
#20
Shuzheng Song, Guoqing Pei, Yaqiong Du, Jugang Wu, Xiaochun Ni, Shoulian Wang, Bojian Jiang, Meng Luo, Jiwei Yu
Chemoresistance in gastric cancer is the leading cause of tumor recurrence and poses a substantial therapeutic challenge. The stem cell biomarker CD133 has been implicated in drug resistance of tumor-initiating cells in a number of cancers including gastric cancer. Therefore, we investigated the molecular mechanism of CD133-associated multidrug resistance in gastric cancer cells. Using CD133 overexpressing and knockdown gastric cancer cell lines, we demonstrated that loss of CD133 significantly increased the growth inhibition of chemotherapeutic agents; whereas, overexpression significantly reduced growth inhibition...
2018: American Journal of Translational Research
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