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Cancer multidrug resistance

Chaoyu Liang, Heping Wang, Min Zhang, Wei Cheng, Zihuang Li, Junpeng Nie, Gan Liu, Daizheng Lian, Zhenhua Xie, Laiqiang Huang, Xiaowei Zeng
Oxaliplatin is a promising antitumor drug, but its effectiveness is limited by its side effects in vivo. In this study, we introduced an Oxaliplatin prodrug (Oxa(IV)) self-controlled release strategy, in which Oxa(IV) is encapsulated by TPGS functionalized mesoporous silica nanoparticles (MSNs), and its release is controlled by biological stimuli, such as acidic environments in tumor tissue and high concentrations of reductants in cancer cells. Despite the lack of auxiliary "gatekeepers" to MSNs, this simplified model of Oxa(IV)-MSNs-TPGS could fine-tune the movements of the drug release...
April 16, 2018: Journal of Colloid and Interface Science
Santosh Kumar Singh, James W Lillard, Rajesh Singh
The folate receptor (FR) is a valued target that is highly expressed in various cancers, which will expedite the development of ligand-receptor binding based cancer therapeutics. In the present investigation, through tissue microarray analysis, we report higher levels of folate receptor expression in prostate cancer (PCa) tissue derived from patients, which were minimal in normal tissue. For folate-receptor based targeted therapy of PCa, we generated novel planetary ball milled (PBM) nanoparticles (NPs) encapsulated with resveratrol (RES), and in combination with docetaxel (DTX) and conjugated with folic acid (FA) on the surface...
April 17, 2018: Cancer Letters
Raphael Silveira Vidal, Julia Quarti, Franklin D Rumjanek, Vivian M Rumjanek
Cancer outcome has improved since introduction of target therapy. However, treatment success is still impaired by the same drug resistance mechanism of classical chemotherapy, known as multidrug resistance (MDR) phenotype. This phenotype promotes resistance to drugs with different structures and mechanism of action. Recent reports have shown that resistance acquisition is coupled to metabolic reprogramming. High-gene expression, increase of active transport, and conservation of redox status are one of the few examples that increase energy and substrate demands...
2018: Frontiers in Oncology
Ales Sorf, Jakub Hofman, Radim Kučera, Frantisek Staud, Martina Ceckova
Ribociclib is a novel cyclin-dependent kinase (CDK) 4 and 6 selective inhibitor that recently gained breakthrough therapy status and global approval for advanced breast cancer treatment. ATP-binding cassette (ABC) transporters may become a site of severe drug interactions and a mechanism of multidrug resistance (MDR) development. With respect to rapid progress of ribociclib in the clinical field, we aimed to identify its interactions with ABC transporters and cytochrome P450 (CYP) isoenzymes and evaluate its potential to overcome transporter-mediated MDR using established in vitro methods...
April 16, 2018: Biochemical Pharmacology
Seyed Abbas Mirzaei, Mansureh Safari Kavishahi, Zhila Keshavarz, Fatemeh Elahian
The search for new chemotherapeutics unaffected by efflux pumps would significantly increase life expectancy in patients with malignant cancers. In this study, butylcycloheptylprodigiosin and undecylprodigiosin were HPLC-purified and verified, using nuclear magnetic resonance spectroscopy. Cell cytotoxicity and transportation kinetics on multiple-drug resistance (MDR) cells were evaluated. Daunorubicin and butylcycloheptylprodigiosin were less toxic in the MDR1 overexpressing line, but undecylprodigiosin revealed potent toxicity toward MDR1 and BCRP expressing malignant cells...
April 19, 2018: DNA and Cell Biology
Vahid Shafiei-Irannejad, Nasser Samadi, Roya Salehi, Bahman Yousefi, Mahdi Rahimi, Abolfazl Akbarzadeh, Nosratollah Zarghami
PURPOSE: P-glycoprotein (P-gp) mediated multidrug resistance (MDR) has been recognized as the main obstacle against successful cancer treatment. To address this problem, co-encapsulated doxorubicin (DOX) and metformin (Met) in a biodegradable polymer composed of poly(lactide-co-glycolide) (PLGA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared. We reported in our previous study that Met inhibits P-gp in DOX resistant breast cancer (MCF-7/DOX) cells. TPGS is a bioactive compound which has also been shown to inhibit P-gp, further to its pharmaceutical advantages...
April 18, 2018: Pharmaceutical Research
Xue Jiang, Ting Lei, Man Zhang
OBJECTIVE: To explore the correlation of formyl peptide receptor 1 expression with drug resistance and the functions of formyl peptide receptor 1 in drug-resistant bladder cancer. METHODS: Expression of formyl peptide receptor 1 in T24 and T24/DDP cisplatin-resistant bladder cancer cell lines was tested by quantitative real-time Polymerase Chain Reaction and Western blotting. After incubation of T24/DDP with N-formyl-Met-Leu-Phe, the phosphor proteins were tested by Western blot analysis...
January 1, 2018: Technology in Cancer Research & Treatment
Yanli Li, Xiaonan Gao, Zhengze Yu, Bo Liu, Wei Pan, Na Li, Bo Tang
Multidrug resistance (MDR), as one of the main problems in clinical breast cancer chemotherapy, is closely related with the overexpression of drug efflux transporter P-glycoprotein (P-gp). In this study, a novel drug-loaded nanosystem was developed for inhibiting the P-gp expression and reversing multidrug resistance by multiplexed gene silencing, which composes of graphene oxide (GO) modified with two molecular beacons (MBs) and Doxorubicin (Dox). When the nanosystem was uptaken by the MDR breast cancer cells, Dox was released in the acidic endosomes and MBs were hybridized with target sequences...
April 17, 2018: ACS Applied Materials & Interfaces
Qingyu Luo, Xiaowei Wu, Yiping Zhang, Tong Shu, Fang Ding, Hongyan Chen, Pengfei Zhao, Wan Chang, Xiaolin Zhu, Zhihua Liu
Multiple Drug Resistance (MDR) of ovarian cancer is a severe trouble for clinical treatment and always attributes to a bad prognosis. AT-rich interaction domain 1 A (ARID1A) has been recognized as a bona fide tumor suppressor gene in recent years, with the highest mutation rate in ovarian cancer. Previous study illustrated that ARID1A expression is negatively correlated with chemoresistance of ovarian cancer cases. However, the specific role of ARID1A in chemoresistance of ovarian cancer remains elusive. In this study, we showed that ARID1A knockdown in ovarian cancer cells significantly reduced their apoptosis rate and led to MDR, while ectopic expression of ARID1A showed opposite effects...
April 13, 2018: Cancer Letters
Clemencia Chaves-López, Donatella Usai, Matthew Gavino Donadu, Annalisa Serio, Robert Tulio González-Mina, Maria Chiara Simeoni, Paola Molicotti, Stefania Zanetti, Antonio Pinna, Antonello Paparella
Borojó (Borojoa patinoi Cuatrec.) is a fruit used in Colombian traditional medicine with supposed antihypertensive, antitumoral, diuretic, healing, immunological, anti-inflammatory and aphrodisiac effects. To explore the relative merits in terms of biological activities of borojó aqueous extract (BAE), we investigated in vitro its antimicrobial activity on nosocomial pathogenic and multidrug resistant (MDR) strains of Pseudomonas aeruginosa (6), Staphylococcus aureus (1) and Candida species (6), as well as its cytotoxicity on human conjunctive Wong-Kilbourne derivative (WKD) cells and Caco-2 cells from heterogeneous human epithelial colorectal adenocarcinoma...
April 16, 2018: Food & Function
Fozia A Adem, Victor Kuete, Armelle T Mbaveng, Matthias Heydenreich, Andreas Koch, Albert Ndakala, Beatrice Irungu, Abiy Yenesew, Thomas Efferth
A new isoflavone, 4'-prenyloxyvigvexin A (1) and a new pterocarpan, (6aR,11aR)-3,8-dimethoxybitucarpin B (2) were isolated from the leaves of Lonchocarpus bussei and the stem bark of Lonchocarpus eriocalyx, respectively. The extract of L. bussei also gave four known isoflavones, maximaisoflavone H, 7,2'-dimethoxy-3',4'-methylenedioxyisoflavone, 6,7,3'-trimethoxy-4',5'-methylenedioxyisoflavone, durmillone; a chalcone, 4-hydroxylonchocarpin; a geranylated phenylpropanol, colenemol; and two known pterocarpans, (6aR,11aR)-maackiain and (6aR,11aR)-edunol...
April 16, 2018: Natural Product Research
Ya-Sheng Li, Dong-Sheng Zhao, Xing-Yu Liu, Yi-Xian Liao, Hong-Wei Jin, Gao-Peng Song, Zi-Ning Cui
Multidrug resistance (MDR) is a tendency in which cells become resistant to structurally and mechanistically unrelated drugs, which is mediated by P-glycoprotein (P-gp). It is one of the noteworthy problems in cancer therapy. As one of the most important drugs in cancer therapy, doxorubicin has not good effectiveness if used independently. So targeting the P-gp protein is one of the key points to solve the MDR. Three series of furan derivatives containing tetrahydroquinoline or tetrahydroisoquinoline were designed and synthesized as P-gp inhibitors in this paper...
April 5, 2018: European Journal of Medicinal Chemistry
Jia Pan, Dong Miao, Li Chen
Multidrug resistance (MDR) usually causes chemotherapy failure of chronic myelogenous leukemia (CML). Germacrone is a terpenoid compound and has been reported to reverse MDR in breast cancer cells. However, the effect of germacrone on MDR in CML cells was unknown. The aim of the present study was to evaluate the effect of germacrone on MDR in adriamycin resistance of CML cells. Treatment with a combination of germacrone and adriamycin synergistically inhibited the viability and increased LDH release in K562/ADM cells...
April 12, 2018: Chemico-biological Interactions
Beda Islas-Muñoz, Patricia Volkow-Fernández, Cynthia Ibanes-Gutiérrez, Alberto Villamar-Ramírez, Diana Vilar-Compte, Patricia Cornejo-Juárez
OBJECTIVE: The aim of this study was to evaluate the clinical characteristics and risk factors associated with mortality in cancer patients with bloodstream infections (BSI), analyzing multidrug resistant bacteria (MDRB). METHODS: We conducted a prospective observational study at a cancer referral center from August 2016 to July 2017, which included all BSI. RESULTS: 4,220 patients were tested with blood cultures; 496 were included. Mean age was 48 years...
April 9, 2018: International Journal of Infectious Diseases: IJID
Xiaoqin Chen, Yajun Tang, Amin Liu, Yuda Zhu, Dong Gao, You Yang, Jing Sun, Hongsong Fan, Xingdong Zhang
Lanthanide-doped upconversion nanoparticles (UCNPs), especially the 808 nm activated UCNPs, are promising imaging agents for biological applications due to their minimal tissue overheating effects and low autofluorescence background. Optimizing the emission peaks located in the "biological window (600 nm-1100 nm)" is of vital importance to obtain maximum penetration depth and intense deep tissue imaging. On the other hand, because of the widely existed multi-drug resistance (MDR) of tumor cells, traditional tumor chemotherapy is often unable to reach the desired effect...
April 12, 2018: ACS Applied Materials & Interfaces
Robert W Robey, Kristen M Pluchino, Matthew D Hall, Antonio T Fojo, Susan E Bates, Michael M Gottesman
Most patients who die of cancer have disseminated disease that has become resistant to multiple therapeutic modalities. Ample evidence suggests that the expression of ATP-binding cassette (ABC) transporters, especially the multidrug resistance protein 1 (MDR1, also known as P-glycoprotein or P-gp), which is encoded by ABC subfamily B member 1 (ABCB1), can confer resistance to cytotoxic and targeted chemotherapy. However, the development of MDR1 as a therapeutic target has been unsuccessful. At the time of its discovery, appropriate tools for the characterization and clinical development of MDR1 as a therapeutic target were lacking...
April 11, 2018: Nature Reviews. Cancer
Lisa Gruber, Sara Abdelfatah, Tony Fröhlich, Christoph Reiter, Volker Klein, Svetlana B Tsogoeva, Thomas Efferth
Two major obstacles for successful cancer treatment are the toxicity of cytostatics and the development of drug resistance in cancer cells during chemotherapy. Acquired or intrinsic drug resistance is responsible for almost 90% of treatment failure. For this reason, there is an urgent need for new anticancer drugs with improved efficacy against cancer cells, and with less toxicity on normal cells. There are impressive examples demonstrating the success of natural plant compounds to fight cancer, such as Vinca alkaloids, taxanes, and anthracyclines...
April 6, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Suradet Buttachon, Alice A Ramos, Ângela Inácio, Tida Dethoup, Luís Gales, Michael Lee, Paulo M Costa, Artur M S Silva, Nazim Sekeroglu, Eduardo Rocha, Madalena M M Pinto, José A Pereira, Anake Kijjoa
A previously unreported bis -indolyl benzenoid, candidusin D ( 2e ) and a new hydroxypyrrolidine alkaloid, preussin C ( 5b ) were isolated together with fourteen previously described compounds: palmitic acid, clionasterol, ergosterol 5,8-endoperoxides, chrysophanic acid ( 1a ), emodin ( 1b ), six bis -indolyl benzenoids including asterriquinol D dimethyl ether ( 2a ), petromurin C ( 2b ), kumbicin B ( 2c ), kumbicin A ( 2d ), 2″-oxoasterriquinol D methyl ether ( 3 ), kumbicin D ( 4 ), the hydroxypyrrolidine alkaloid preussin ( 5a ), (3 S , 6 S )-3,6-dibenzylpiperazine-2,5-dione ( 6 ) and 4-(acetylamino) benzoic acid ( 7 ), from the cultures of the marine sponge-associated fungus Aspergillus candidus KUFA 0062...
April 6, 2018: Marine Drugs
Anna L Luss, Pavel P Kulikov, Sven B Romme, Camilla L Andersen, Cristian P Pennisi, Anca O Docea, Andrey N Kuskov, Kelly Velonia, Yaroslav O Mezhuev, Mikhail I Shtilman, Aristidis M Tsatsakis, Leonid Gurevich
AIM: Ability to deliver drugs into the cell nuclei can significantly increase the efficacy of cancer therapies, in particular in the case of multidrug-resistant cancer Results: Polymer nanocarriers based on amphiphilic thiooctadecyl-terminated poly-N-vinyl-2-pyrrolidone were produced and loaded with a model hydrophobic drug, curcumin. Two commonly used loading approaches - emulsification and ultrasonic dispersion - were found to lead to two different size distributions with distinctively different biological effect...
April 9, 2018: Nanomedicine
Atsushi Kainuma, Kyoko Momiyama, Takeshi Kimura, Koichi Akiyama, Keita Inoue, Yoshifumi Naito, Mao Kinoshita, Masaru Shimizu, Hideya Kato, Nobuaki Shime, Naohisa Fujita, Teiji Sawa
Antimicrobial-resistant isolates of Pseudomonas aeruginosa collected from 2005 to 2014 in a university hospital in Kyoto, Japan, were retrospectively analyzed by multilocus sequence typing (MLST), exoenzyme genotype determination, integron characterization, and clinical associations. During the study, 1573 P. aeruginosa isolates were detected, and 41 of these were resistant to more than two classes of antimicrobial agents. Twenty-five (61.0%) isolates were collected from urine. All isolates were resistant to ciprofloxacin, 8 (19...
April 5, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
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