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Cancer multidrug resistance

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https://www.readbyqxmd.com/read/28101198/elevated-expression-of-nrf2-mediates-multidrug-resistance-in-cd133-head-and-neck-squamous-cell-carcinoma-stem-cells
#1
Bao-Cai Lu, Jing Li, Wen-Fa Yu, Guo-Zheng Zhang, Hui-Min Wang, Hui-Min Ma
Enhanced expression of the ATP-binding cassette (ABC) transporter protein ABC sub-family G member 2 (ABCG2) in cancer stem cells (CSCs) plays a major role in chemotherapeutic drug efflux, which results in therapy failure and tumor relapse. In addition to downregulating apoptosis in CSCs, it has been reported that the transcriptional upregulation of the redox sensing factor Nrf2 is involved in the upregulation of ABCG2 expression and consequent chemoresistance. The current study investigated the presence of cancer stem-like side population (SP) cells from head and neck squamous cell carcinoma (HNSCC) samples, and evaluated the Nrf2 expression profile and multidrug resistance properties of HNSCC stem cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100110/mortality-in-patients-with-septic-shock-by-multidrug-resistant-bacteria
#2
Stefano Busani, Giulia Serafini, Elena Mantovani, Claudia Venturelli, Maddalena Giannella, Pierluigi Viale, Cristina Mussini, Andrea Cossarizza, Massimo Girardis
BACKGROUND: Patients with septic shock by multidrug resistant (MDR) microorganism maybe considered a specific population of critical patients at very high risk of death in whom the effects of standard sepsis treatment has never been assessed. The objective of this retrospective analysis was to evaluate the risk factors for 30-day mortality and the impact of sepsis management in patients with septic shock caused by MDR bacteria. METHODS: Patients with septic shock by MDR bacteria admitted to the mixed intensive care unit (ICU) of Modena University Hospital during a 6-year period were studied...
January 1, 2017: Journal of Intensive Care Medicine
https://www.readbyqxmd.com/read/28099443/inhibition-of-human-drug-transporter-activities-by-the-pyrethroid-pesticides-allethrin-and-tetramethrin
#3
Lisa Chedik, Arnaud Bruyere, Marc Le Vee, Bruno Stieger, Claire Denizot, Yannick Parmentier, Sophie Potin, Olivier Fardel
Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulatory effects of these pesticides towards activities of main ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, using transporter-overexpressing cells...
2017: PloS One
https://www.readbyqxmd.com/read/28098863/effect-and-mechanism-of-resveratrol-on-drug-resistance-in-human-bladder-cancer-cells
#4
Shanshan Wang, Qian Meng, Qing Xie, Man Zhang
Multidrug resistance (MDR) is a significant barrier to the effective treatment of bladder cancer. In order to improve the management of bladder cancer, it is crucial to identify strategies that may reverse MDR. The effects of three herbal medicines, ginsenoside Rh2, (‑)‑epigallocatechin gallate (EGCG) and resveratrol (RES) on bladder cancer were determined. The effect of these three herbal medicines against the drug resistance in adriamycin (ADM)‑resistant pumc‑91 cells (pumc‑91/ADM) was assessed using the Cell Counting Kit‑8 cell proliferation assay system...
January 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28098816/estrogen-enhances-the-expression-of-the-multidrug-transporter-gene-abcg2-increasing-drug-resistance-of-breast-cancer-cells-through-estrogen-receptors
#5
Fung-Wei Chang, Hueng-Chuen Fan, Jui-Ming Liu, Tai-Ping Fan, Jin Jing, Chia-Ling Yang, Ren-Jun Hsu
BACKGROUND: Multidrug resistance is a major obstacle in the successful therapy of breast cancer. Studies have proved that this kind of drug resistance happens in both human cancers and cultured cancer cell lines. Understanding the molecular mechanisms of drug resistance is important for the reasonable design and use of new treatment strategies to effectively confront cancers. RESULTS: In our study, ATP-binding cassette sub-family G member 2 (ABCG2), adenosine triphosphate (ATP) synthase and cytochrome c oxidase subunit VIc (COX6C) were over-expressed more in the MCF-7/MX cell line than in the normal MCF7 cell line...
January 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28095178/current-trends-in-multidrug-optimization
#6
Andrea Weiss, Patrycja Nowak-Sliwinska
The identification of effective and long-lasting cancer therapies still remains elusive, partially due to patient and tumor heterogeneity, acquired drug resistance, and single-drug dose-limiting toxicities. The use of drug combinations may help to overcome some limitations of current cancer therapies by challenging the robustness and redundancy of biological processes. However, effective drug combination optimization requires the careful consideration of numerous parameters. The complexity of this optimization problem is clearly nontrivial and likely requires the assistance of advanced heuristic optimization techniques...
December 1, 2016: Journal of Laboratory Automation
https://www.readbyqxmd.com/read/28093974/anticancer-properties-of-traditional-chinese-medicine
#7
Zhaokun Yan, Zijun Lai, Jiumao Lin
Cancer is a systemic disease. Cancer occurrence is associated with several factors, including cell proliferation, apoptosis, metastasis, tumor microenvironment and immune system. Traditional Chinese medicine (TCM) has been widely used for thousands of years in China for its anti-cancer therapeutic effect. The advantage of using TCM is related to its action on multiple signaling pathways and molecular targets related to cancer, whilst causing few adverse effects. TCM exerts its anticancer effects through multiple mechanisms, including apoptosis induction, proliferation inhibition, metastasis suppression, multidrug resistance reversal and immune function regulation...
January 16, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28088112/a-current-perspective-on-the-oncopreventive-and-oncolytic-properties-of-selective-serotonin-reuptake-inhibitors
#8
REVIEW
Daniel P Radin, Parth Patel
Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers...
January 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28087910/-progress-on-anti-tumor-molecular-mechanisms-of-dihydroartemisinin
#9
Peng Cao, Dongjin Leng, Ying Li, Ziwei Zhang, Lei Liu, Xiaoyan Li
Artemisinin is an anti-malarial drug with poor water solubility and oral absorption; so a variety of derivatives based on the parent nucleus have been developed. Compared with artemisinin, dihydroartemisinin (DHA) has a stronger anti-malaria activity, and has the advantages of high metabolic rate and better water solubility. Recent studies have discovered that DHA has a good inhibitory effect on tumor cells, which is closely related to the peroxide bridge in its molecular structure. Since tumor cells need more Fe(3+) than normal cells, there are a large number of transferrin receptors on the tumor cell membrane...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28077793/integrated-proteomic-and-n-glycoproteomic-analyses-of-doxorubicin-sensitive-and-resistant-ovarian-cancer-cells-reveal-glycoprotein-alteration-in-protein-abundance-and-glycosylation
#10
Yanlong Ji, Shasha Wei, Junjie Hou, Chengqian Zhang, Peng Xue, Jifeng Wang, Xiulan Chen, Xiaojing Guo, Fuquan Yang
Ovarian cancer is one of the most common cancer among women in the world, and chemotherapy remains the principal treatment for patients. However, drug resistance is a major obstacle to the effective treatment of ovarian cancers and the underlying mechanism is not clear. An increased understanding of the mechanisms that underline the pathogenesis of drug resistance is therefore needed to develop novel therapeutics and diagnostic. Herein, we report the comparative analysis of the doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI/ADR-RES cells using integrated global proteomics and N-glycoproteomics...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075474/isomahanine-induces-endoplasmic-reticulum-stress-and-simultaneously-triggers-p38%C3%A2-mapk-mediated-apoptosis-and-autophagy-in-multidrug-resistant-human-oral-squamous-cell-carcinoma-cells
#11
Tanyarath Utaipan, Anan Athipornchai, Apichart Suksamrarn, Surasak Chunsrivirot, Warangkana Chunglok
Advanced oral squamous cell carcinoma (OSCC) is typically aggressive and closely correlated with disease recurrence and poor survival. Multidrug resistance (MDR) is the most critical problem leading to therapeutic failure. Investigation of novel anticancer candidates targeting multidrug-resistant OSCC cells may provide a basis for developing effective strategies for OSCC treatment. In the present study, we investigated the cytotoxic mechanism of a carbazole alkaloid, namely isomahanine, in a multidrug‑resistant OSCC cell line CLS-354/DX...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28072526/type-i-dna-topoisomerases
#12
Giovanni Capranico, Jessica Marinello, Giovanni Chillemi
DNA topoisomerases constitute a large family of essential enzymes in all domains of life. Even though they share the general reaction chemistry and the ability to govern DNA topology and resolve strand entanglements during fundamental molecular processes, they are characterized by differences in structural organization, modes of enzymatic catalysis and biological functions. Moreover, hundreds of compounds are known to interfere with bacterial and/or eukaryotic enzymes, and some of them are effective drugs for the treatment of infectious diseases and cancers...
January 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28070974/stimulus-responsive-short-peptide-nanogels-for-controlled-intracellular-drug-release-and-overcome-tumor-resistance
#13
Bengang Xing, Linna Lyu, Fang Liu, Xiaoyong Wang, Ming Hu, Jing Mu, Haolun Cheong, Gang Liu
Multidrug resistance (MDR) places a major burden against cancer treatment. As one important factor contributing to MDR, over-expression of P-glycoprotein (P-gp), results in the reduced intracellular drug accumulation. Hence, the ability to effectively block the efflux protein and accumulate the therapeutics in cancer cells is of great significance in clinical practice. In this work, we successfully developed a smart stimulus-responsive short peptide assembled system, termed as PD/VER nanogels, which synergistically combined the acid activatable Doxorubicin (Dox) antitumor prodrug with the P-gp inhibitor (Verapamil, VER) for reversing MDR...
January 9, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28069938/crystal-structure-and-mechanistic-basis-of-a-functional-homolog-of-the-antigen-transporter-tap
#14
Anne Nöll, Christoph Thomas, Valentina Herbring, Tina Zollmann, Katja Barth, Ahmad Reza Mehdipour, Thomas M Tomasiak, Stefan Brüchert, Benesh Joseph, Rupert Abele, Vincent Oliéric, Meitian Wang, Kay Diederichs, Gerhard Hummer, Robert M Stroud, Klaas M Pos, Robert Tampé
ABC transporters form one of the largest protein superfamilies in all domains of life, catalyzing the movement of diverse substrates across membranes. In this key position, ABC transporters can mediate multidrug resistance in cancer therapy and their dysfunction is linked to various diseases. Here, we describe the 2.7-Å X-ray structure of heterodimeric Thermus thermophilus multidrug resistance proteins A and B (TmrAB), which not only shares structural homology with the antigen translocation complex TAP, but is also able to restore antigen processing in human TAP-deficient cells...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069328/antimicrobial-activity-of-ceftazidime-avibactam-and-comparator-agents-when-tested-against-bacterial-isolates-causing-infection-in-cancer-patients-2013-2014
#15
Helio S Sader, Mariana Castanheira, Ronald N Jones, Robert K Flamm
We evaluated the antimicrobial susceptibility of 623 Gram-negative organisms causing infection in patients with cancer in 52 United States hospitals (2013-2014) as part of the International Network for Optimal Resistance Monitoring (INFORM) program. Isolates were tested for susceptibility by broth microdilution method. β-lactamase encoding genes were evaluated for all Escherichia coli and Klebsiella spp. with an extended-spectrum β-lactamase (ESBL) phenotype by microarray-based assay. ESBL-phenotype was observed among 17...
November 29, 2016: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28068430/molecular-mimics-of-classic-p-glycoprotein-inhibitors-as-multidrug-resistance-suppressors-and-their-synergistic-effect-on-paclitaxel
#16
Moustafa E El-Araby, Abdelsattar M Omar, Maan T Khayat, Hanan A Assiri, Ahmed M Al-Abd
P-glycoprotein (Pgp) is a membrane bound efflux pump spread in a variety of tumor cells and considered as a main component of multidrug resistance (MDR) to chemotherapies. In this work, three groups of compounds (imidazolone, oxazolone and vinyl dipeptide derivatives) were synthesized aiming to develop a molecular framework that effectively suppresses MDR. When tested for their influence on Pgp activity, four compounds coded Cur1-01, Cur1-12V, Curox-1 and Curox-3 significantly decreased remaining ATP concentration indicating Pgp substrate site blocking...
2017: PloS One
https://www.readbyqxmd.com/read/28067173/marine-derived-anticancer-drugs-targeting-microtubule
#17
Oindrila De, Biswa Prasun Chatterji
BACKGROUND: Microtubule dynamics play a vital role in regulating crucial cellular functions and are one of the most attractive anticancer drug targets. Microtubule targeting agents (MTAs) such as the vinca alkaloids or taxanes, although are effective for cancer therapy, have adverse side effects. Another hindrance in their development is multiple drug resistance in tumor cells. These drawbacks have urged the need to develop novel MTAs from alternative sources, with better therapeutic efficacy...
January 9, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28065245/research-advances-in-the-mechanisms-of-gastric-cancer-multidrug-resistance
#18
Hao Huang, Xing-Jiu Yang, Ran Gao
Gastric cancer is one of the most common human malignancies and the third cause of death from cancer in China and worldwide. Chemotherapy is still one of the major treatment options for advanced gastric cancer. However,the efficacy of chemotherapy for gastric cancer remains poor due to its insensitivity and the development of multidrug resistance (MDR). While many molecules and mechanisms have been found to be associated with the development of gastric cancer MDR,the specific mechanisms remains unclear. In our current article,we reviews the identification of MDR-related molecules and mechanisms,with an attempt to a better understand the specific mechanisms of gastric cancer MDR and thus provide new insights into the fight against gastric cancer MDR...
December 20, 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28064519/three-new-antitumor-annonaceous-acetogenins-from-the-seeds-of-annona-squamosa
#19
Chengyao Ma, Qiwen Wang, Yeye Shi, Yue Li, Xunan Wang, Xiang Li, Yong Chen, Jianwei Chen
Two new annonaceous acetogenins squamocin P (2) and annosquatin III (3) and one new ACG precursor dieporeticenin B (1) along with five known precursors (4-8) were isolated from the seeds of Annona squamosa. Their structures were ascertained by chemical methods and various spectral evidences. These compounds showed inhibitory effects against three multidrug-resistant (MDR) cancer cell lines. Compound 2 and 3 displayed selective cytotoxicity against SMMC 7721/T (IC50 0.435 and 1.79 μM) and MCF-7/ADR (IC50 values 3...
January 9, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28062543/multiple-slc-and-abc-transporters-contribute-to-the-placental-transfer-of-entecavir
#20
Zhiyuan Ma, Xi Yang, Ting Jiang, Mengru Bai, Caihong Zheng, Su Zeng, Dongli Sun, Huidi Jiang
Entecavir (ETV), a nucleoside analogue with high efficacy against hepatitis B virus, is recommended as a first-line antiviral drug for the treatment of chronic hepatitis B. However, scant information is available on the use of ETV in pregnancy. To better understand the safety of ETV in pregnant women, we aimed to demonstrate whether ETV could permeate placental barrier and the underlying mechanism. Our study showed that small amount of ETV could permeate across placenta in mice. ETV accumulation in activated or non-activated BeWo cells (treated with or without forskolin) was sharply reduced in the presence of 100 μM of adenosine, cytidine and in Na+ free medium, indicating that nucleoside transporters possibly mediate the uptake of ETV...
January 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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