Search results for "Multiple Drug Resistance"
showing 10 items of 113 documents
Inhibition of ATP-Binding Cassette Transporters by Chinese Herbs and Phytochemicals
2012
The gene family of ATP-binding cassette (ABC) transporters is widely distributed over the evolutionary tree of life from bacteria to man. In cancer, several ABC transporters are involved in the transport of anticancer drugs. This leads to the development of resistance to a broad spectrum of anticancer agents, termed multidrug resistance. An attractive strategy to overcome multidrug resistance is to block the transport function of ABC transporters leading to lethal intracellular concentrations of anticancer drugs. Efforts to identify transport inhibitors lead to a huge amount of chemical substances, none of which successfully passed clinical trials in cancer patients because of high toxicity…
Liver and gastrointestinal cancers
2020
Abstract One important limitation in the treatment of liver and gastrointestinal cancers is their poor response to available chemotherapy, which is due in part to efficient mechanisms of defense against antitumor drugs. An important role in chemoresistance is played by ATP-binding cassette (ABC) proteins, normally involved in barrier/secretory functions of the digestive apparatus. ABC pumps, often up-regulated in cancers derived from these organs, actively export antitumor agents from cancer cells, thereby reducing the pharmacological effect of these drugs. Among the ABC proteins with the highest impact on the multidrug resistance (MDR) phenotype of many cancer types is MDR1 or P-glycoprote…
Molecular epidemiology of Acinetobacter baumannii in Iran: endemic and epidemic spread of multiresistant isolates
2014
Objectives We examined the molecular epidemiology of Acinetobacter baumannii clinical isolates from two cities (Tehran and Tabriz) of Iran. Methods DiversiLab repetitive extragenic palindromic PCR (rep-PCR), multilocus sequence typing and sequence group multiplex PCR were performed. The presence of resistance mechanisms including metallo-β-lactamases, extended-spectrum β-lactamases, OXA carbapenemases, aminoglycoside-modifying enzymes and RNA methylases was also investigated. Results DiversiLab rep-PCR identified 11 clusters and 11 singleton isolates. Twelve sequence types (STs), including six novel types, were identified. Sequence groups (SGs) 1-3 as well as five additional banding pattern…
Genomic analysis of the emergence and evolution of multidrug resistance during a Klebsiella pneumoniae outbreak including carbapenem and colistin res…
2014
et al.
Modulation of P-Glycoprotein-Mediated Multidrug Resistance by Synthetic and Phytochemical Small Molecules, Monoclonal Antibodies, and Therapeutic Nuc…
2014
Multidrug resistance of malignant tumors severely hampers their successful treatment frequently leading to fatal consequences for affected patients. During the past three decades, many efforts have been spent to develop strategies to overcome multidrug resistance. Many chemical compounds have been shown to inhibit the drug efflux of the multidrug-resistance-mediating P-glycoprotein. Chemical P-glycoprotein inhibitors are from the classes of calcium channel antagonists, calmodulin inhibitors, cyclosporins, antiarrhythmics, hormones, antimalarials, antibiotics, detergents, beta-blockers, antidepressants, blood pressure lowering indol alkaloids, aerobic glycolysis inhibitors, HIV-protease inhi…
Curcumin as a possible lead compound against hormone-independent, multidrug-resistant breast cancer
2009
We examine the possible evidence that the phytochemical curcumin may overcome resistance to hormonal and cytotoxic agents in breast cancer. We present our observations on MCF-7R, a multidrug-resistant (MDR) variant of the MCF-7 breast cancer cell line. In contrast to MCF-7, MCF-7R lacks aromatase and estrogen receptor alpha (ERalpha) and overexpresses the multidrug transporter ABCB1 and the products of different genes implicated in cell proliferation and survival, like c-IAP-1, NAIP, survivin, and COX-2. Nevertheless, in cytotoxicity and cell death induction assays, we found that the antitumor activity of curcumin is substantial both in MCF-7 and in MCF-7R. We elaborated the diketone system…
Cytotoxicity of medicinal plants of the West-Canadian Gwich׳in Native Americans towards sensitive and multidrug-resistant cancer cells
2015
Abstract Ethnopharmacological relevance Traditional medicine of the Native Americans has a long tradition of medicinal plants, which also influenced modern oncology. For instance, podophyllotoxin the active ingredient of Podophyllum peltatum L. (Berberidaceae) used by Native Americans to treat warts led to the development of etoposide and teniposide. In the present investigation, we studied 10 medicinal plants used by the Gwich׳in First Nation of West-Canada, which have been used against diverse diseases including cancer. Material and methods Sensitive and multidrug-resistant (MDR) tumor cell lines expressing various ATP-binding cassette (ABC) transporters (P-glycoprotein/ ABCB1/MDR1 , MRP1…
Laurus nobilis L. Seed Extract Reveals Collateral Sensitivity in Multidrug-Resistant P-Glycoprotein-Expressing Tumor Cells.
2015
The frequent failure of standard cancer chemotherapy requires the development of novel drugs capable of killing otherwise drug-resistant tumors. Here, we have investigated a chloroform extract of Laurus nobilis seeds. Fatty acids and 23 constituents of the volatile fraction were identified by gas chromotography/flame ionization detection (GC/FID) and gas chromatography/mass spectrometry (GC/MS), in good agreement with (1)H NMR (nuclear magnetic resonance) spectrum. Multidrug-resistant P-glycoprotein-expressing CEM/ADR5000 leukemia cells were hypersensitive (collaterally sensitive) toward this extract compared to drug-sensitive CCRF-CEM cells, whereas CEM/ADR5000 cells were 2586-fold resista…
Comparative activity of idarubicin and idarubicinol in combination with cyclosporin A in multidrug-resistant leukemia cells
1996
4-Demethoxydaunorubicin (idarubicin, IDA) is an anthracycline that has shown good cytotoxic activity in vitro against tumor cell lines displaying the multidrug-resistant (MDR) phenotype. IDA is converted in the liver into idarubicinol (2HIDA) and, in this form, seems to exert its antitumoral activity in vivo. Recent studies have shown that 2HIDA has tumoricidal activity similar to that of the parent drug when tested in vitro in sensitive neoplastic cells. In this work we compared in vitro the effects of IDA and 2HIDA used alone and in combination with 2 microM cyclosporin A (CyA) in the MDR leukemic cell lines FLCR and K562R and in their sensitive parent cell lines FLC and K562. IDA and 2HI…
Selective induction of apoptosis in multidrug resistant HL60R cells by the thiazolobenzoimidazole derivative 1-(2,6-difluorophenyl)-1H,3H-thiazolo [3…
1999
We investigated the antitumour effects of 1-(2,6-difluorophenyl)-1H,3H-thiazolo [3,4-a]benzimidazole (TBZ) a new anti-HIV-1 agent, on human promyelocytic HL60 leukaemia, both a parental and a multidrug resistant form (HL60R). HL60R overexpresses P-glycoprotein and, like HL60, lacks p53 protein expression. HL60 and HL60R show similar levels of Bcl-2 protein. In contrast to the conventional chemotherapeutic agents daunorubicin, etoposide and mitoxantrone, TBZ caused equal or even greater cytotoxicity in HL60R than in HL60, and this result was associated with a more marked induction of apoptosis in the drug resistant cells. The antitumour activity of TBZ occurred in the range of concentrations…