L-Histidinol in experimental cancer chemotherapy: improving the selectivity and efficacy of anticancer drugs, eliminating metastatic disease and reversing the multidrug-resistant phenotype

1992 ◽  
Vol 70 (5) ◽  
pp. 365-375 ◽  
Author(s):  
R. C. Warrington
Keyword(s):  
Multidrug Resistance ◽  
Anticancer Drugs ◽  
Cancer Chemotherapy ◽  
Antineoplastic Agents ◽  
Human Cancer ◽  
Protein Biosynthesis ◽  
Multidrug Resistant ◽  
Human Leukemia ◽  
Drug Resistant ◽  
Experimental Cancer

Human cancer chemotherapy is limited by two major problems: the failure of commonly used anticancer drugs to act against tumor cells in a specific manner and the ability of malignant cells to resist killing by antineoplastic agents. Experimentally, both of these problems can be solved by using L-histidinol in combination with conventional anticancer drugs. A structural analogue of the essential amino acid L-histidine and an inhibitor of protein biosynthesis. L-histidinol improves the selectivity and the efficacy of a variety of cancer drugs in several transplantable murine tumors. Furthermore, L-histidinol circumvents the drug-resistant traits of a variety of cancer cells, including those showing multidrug resistance. This review will summarize these properties of L-histidinol, present new evidence on its ability to increase the vulnerability of both drug-sensitive and drug-resistant human leukemia cells to various anticancer drugs, and show that, in addition to inhibiting protein synthesis, L-histidinol acts as an intracellular histamine antagonist. The establishment of a connection between the latter mechanism and the capacity to modulate anticancer drug action has resulted in a clinical trial in the treatment of human cancer.Key words: L-histidinol, antineoplastic agents, transplantable tumors, metastasis, multidrug resistance.

LDH-doped electrospun short fibers enable dual drug loading and multistage release for chemotherapy of drug-resistant cancer cells

2021 ◽  
Author(s):  
Yupei Ma ◽  
Du Li ◽  
Yunchao Xiao ◽  
Zhijun OuYang ◽  
Mingwu Shen ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Cancer Chemotherapy ◽  
Side Effect ◽  
Drug Loading ◽  
Adverse Side Effect ◽  
Drug Resistant ◽  
Short Fibers ◽  
Dual Drug

Conventional cancer chemotherapy is facing difficulties in improving the bioavailability, overcoming the severe adverse side effect of chemotherapeutics and reversing the multidrug resistance of cancer cells. To address these challenges,...

scholarly journals Overcoming multidrug-resistance in vitro and in vivo using the novel P-glycoprotein inhibitor 1416

2012 ◽  
Vol 32 (6) ◽  
pp. 559-566 ◽  
Author(s):  
Yan Xu ◽  
Feng Zhi ◽  
Guangming Xu ◽  
Xiaolei Tang ◽  
Sheng Lu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Chemotherapy ◽  
Antitumour Activity ◽  
Multidrug Resistant ◽  
The Novel ◽  
Mice Model ◽  
P Glycoprotein ◽  
Channel Currents

MDR (multidrug-resistance) represents a major obstacle to successful cancer chemotherapy and is usually accomplished by overexpression of P-gp (P-glycoprotein). Much effort has been devoted to developing P-gp inhibitors to modulate MDR. However, none of the inhibitors on the market have been successful. 1416 [1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane hydrochloride (phenoprolamine hydrochloride)] is a new VER (verapamil) analogue with a higher IC50 for blocking calcium channel currents than VER. In the present paper, we examined the inhibition effect of 1416 on P-gp both in vitro and in vivo. 1416 significantly enhanced cytotoxicity of VBL (vinblastine) in P-gp-overexpressed human multidrug-resistant K562/ADM (adriamycin) and KBV cells, but had no such effect on the parent K562 and KB cells. The MDR-modulating function of 1416 was further confirmed by increasing intracellular Rh123 (rhodanmine123) content in MDR cells. Human K562/ADM xenograft-nude mice model verified that 1416 potentiates the antitumour activity of VBL in vivo. RT-PCR (reverse transcriptase-PCR) and FACS analysis demonstrated that the expression of MDR1/P-gp was not affected by 1416 treatment. All these observations suggest that 1416 could be a promising agent for overcoming MDR in cancer chemotherapy.

scholarly journals Explaining risk factors for drug-resistant tuberculosis in England and Wales: contribution of primary and secondary drug resistance

2004 ◽  
Vol 132 (6) ◽  
pp. 1099-1108 ◽  
Author(s):  
S. J. CONATY ◽  
A. C. HAYWARD ◽  
A. STORY ◽  
J. R. GLYNN ◽  
F. A. DROBNIEWSKI ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multidrug Resistance ◽  
Hiv Infection ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Isoniazid Resistance ◽  
Drug Resistant Tuberculosis ◽  
England And Wales ◽  
Resistance Risk ◽  
Resistant Tuberculosis

Drug-resistant tuberculosis can be transmitted (primary) or develop during the course of treatment (secondary). We investigated risk factors for each type of resistance. We compared all patients in England and Wales with isoniazid- and multidrug-resistant tuberculosis in two time-periods (1993–1994 and 1998–2000) with patients with fully sensitive tuberculosis, examining separately patients without and with previous tuberculosis (a proxy for primary and secondary drug-resistant tuberculosis). Patients with previous tuberculosis smear positivity and arrival in the United Kingdom <5 years were strongly associated with multidrug resistance and isoniazid resistance. In patients with no previous tuberculosis HIV infection, residence in London and foreign birth were risk factors for multidrug resistance, and non-white ethnicity, residence in London and HIV infection for isoniazid resistance. Risk factors for each type of resistance differ. Elevated risks associated with London residence, HIV positivity, and ethnicity were mainly seen in those without previous tuberculosis (presumed transmission).

Chalcone derivatives and their activities against drug-resistant cancers: An overview

2020 ◽  
Vol 20 ◽  
Author(s):  
Jiaqi Xiao ◽  
Meixiang Gao ◽  
Qiang Diao ◽  
Feng Gao
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Rational Design ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Chalcone Derivatives ◽  
Potential Activity ◽  
Defensive Mechanisms

: Drug resistance including multidrug resistance resulting from different defensive mechanisms in cancer cells is the leading cause of the failure about the cancer therapy, making it an urgent need to develop more effective anticancer agents. Chalcones, widely distributed in nature, could act on diverse enzymes and receptors in cancer cells. Accordingly, chalcone derivatives possess potential activity against various cancers including drug-resistant even multidrug-resistant cancer. This review outlines the recent development of chalcone derivatives with potential activity against drug-resistant cancers covering articles published between 2010 and 2020, so as to facilitate further rational design of more effective candidate.

Alterations of ionic membrane permeabilities in multidrug-resistant neuroblastoma x glioma hybrid cells.

1998 ◽  
Vol 201 (1) ◽  
pp. 21-31
Author(s):  
V Gérard ◽  
B Rouzaire-Dubois ◽  
P Dilda ◽  
J M Dubois
Keyword(s):  
Multidrug Resistance ◽  
Membrane Potential ◽  
Current Density ◽  
Neuroblastoma Cells ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Resting Membrane Potential ◽  
Drug Resistant ◽  
Membrane Permeabilities ◽  
Resistant Cells

A population of NG108-15 neuroblastoma cells resistant to doxorubicin (NG/DOXR) was established. The cells exhibited a multidrug resistance phenotype with cross-resistance to vinblastin and colchicine, overexpression of a 170 kDa membrane protein identified as P-glycoprotein and reversal of resistance by verapamil and quinine. Compared with NG108-15 cells, NG/DOXR cells showed an increase in Na+ current density and a decrease in cyclic-AMP-activated Cl- current density with no change in K+- and volume-sensitive Cl- current densities. As previously observed in NG108-15 cells, the vacuolar-type H+-ATPase inhibitors bafilomycin A1 and nitrate induced membrane depolarizations in NG/DOXR cells. The resting potentials of sensitive and resistant cells were not significantly different, but the depolarizations evoked by these agents were significantly larger in NG/DOXR than in NG108-15 cells. The resting membrane potential of NG/DOXR cells, but not that of NG108-15 cells, was depolarized by verapamil, and this effect was abolished by bafilomycin. The volume-sensitive Cl- currents of drug-sensitive and drug-resistant cells were inhibited by a decrease in intracellular pH from 7.3 to 6.8. Whereas bafilomycin prevents activation of Cl- currents in both drug-sensitive and drug-resistant cells, verapamil inhibited the Cl- current only in NG/DOXR cells. The results are discussed in terms of the roles of cytoplasmic pH and membrane potential in multidrug resistance.

scholarly journals High Prevalence of Multidrug-Resistant and Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: A Cross-Sectional Study at Arsho Advanced Medical Laboratory, Addis Ababa, Ethiopia

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Adane Bitew ◽  
Estifanos Tsige
Keyword(s):  
Multidrug Resistance ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Medical Laboratory ◽  
Beta Lactamase ◽  
Drug Resistant ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum ◽  
High Prevalence ◽  
Vitek 2

Background. Multidrug-resistant Enterobacteriaceae particularly extended-spectrum beta-lactamase producers have become a major public health threat. Despite efforts to limit their spread, rates of multidrug-resistance members of the Enterobacteriaceae continue to increase throughout the world causing increased morbidity and mortality and raised costs for medical care. Objective. The aim of this study was to determine the prevalence of multidrug resistance and extended-spectrum β-lactamase-producing Enterobacteriaceae. Methods. Four hundred forty Enterobacteriaceae isolates from outpatients referred to Arsho Advanced Medical Laboratory were identified and assessed for their antimicrobial resistance pattern by using the automated VITEK 2 compact system. Extended-spectrum β-lactamase production was determined by the VITEK 2 automated compact system using the extended-spectrum β-lactamase test panel as per the instruction of the manufacturer. Results. The overall resistance rates of Enterobacteriaceae against cephalosporins, aminoglycosides, and fluoroquinolones were high. Nitrofurantoin with a resistance rate of 14.3% and piperacillin/tazobactam combination with a resistance rate of 17.3% were better active against this group of Gram-negative bacteria. Out of 440 isolates of Enterobacteriaceae, 42.1% were multidrug-resistant of which 34.3% and 8.95% were extensively drug-resistant and pan-drug resistant, respectively. Among 185 multidrug-resistant Enterobacteriaceae, 63.9% of the isolates produced extended-spectrum β-lactamase of which 75.4%, 19.5%, 1.7%, 2.5%, and 0.8% were E. coli, K. pneumoniae, C. freundii, E. cloacae, and P. mirabilis, respectively. Conclusions. The present study demonstrated high prevalence rates of multidrug-resistant and extended-spectrum-beta-lactamase-producing Enterobacteriaceae. In order to combat these problems, infection control strategy and proper antibiotic policies should be formulated.

scholarly journals Whole genomic sequencing based genotyping reveals a specific X3 sublineage restricted to Mexico and related with multidrug resistance

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Cristina Jiménez-Ruano ◽  
Carlos Francisco Madrazo-Moya ◽  
Irving Cancino-Muñoz ◽  
Paulina M. Mejía-Ponce ◽  
Cuauhtémoc Licona-Cassani ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Multidrug Resistant ◽  
Genomic Sequencing ◽  
Whole Genome ◽  
Drug Resistant ◽  
The Past ◽  
High Prevalence ◽  
Genomic Cluster

AbstractWhole genome sequencing (WGS) has been shown to be superior to traditional procedures of genotyping in tuberculosis (TB), nevertheless, reports of its use in drug resistant TB (DR-TB) isolates circulating in Mexico, are practically unknown. Considering the above the main of this work was to identify and characterize the lineages and genomic transmission clusters present in 67 DR-TB isolates circulating in southeastern Mexico. The results show the presence of three major lineages: L1 (3%), L2 (3%) and L4 (94%), the last one included 16 sublineages. Sublineage 4.1.1.3 (X3) was predominant in 18 (27%) of the isolates, including one genomic cluster, formed by eleven multidrug resistant isolates and sharing the SIT 3278, which seems to be restricted to Mexico. By the use of WGS, it was possible to identify the high prevalence of L4 and a high number of sublineages circulating in the region, also was recognized the presence of a novel X3 sublineage, formed exclusively by multidrug resistant isolates and with restrictive circulation in Mexico for at least the past 17 years.

scholarly journals Metformin Derivative HL156A Reverses Multidrug Resistance by Inhibiting HOXC6/ERK1/2 Signaling in Multidrug-Resistant Human Cancer Cells

2020 ◽  
Vol 13 (9) ◽  
pp. 218
Author(s):  
Yun Soo Jeong ◽  
Thuy Giang Lam ◽  
Seho Jeong ◽  
Sang-Gun Ahn
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Human Cancer ◽  
Chorioallantoic Membrane ◽  
Multidrug Resistant ◽  
Therapeutic Modality ◽  
Phase Cell ◽  
Closure Rate ◽  
Human Cancer Cells ◽  
Cellular Expression

Multidrug resistance is a significant clinical crisis in cancer treatment and has been linked to the cellular expression of multidrug efflux transporters. The aim of this study was to examine the effects and mechanisms of the metformin derivative HL156A on human multidrug resistance (MDR) cancer cells. Here, HL156A significantly suppressed cell growth and colony formation through G2/M phase cell cycle arrest in MDR cancer cells. HL156A also reduced the wound closure rate and cell migration and induced caspase-3-dependent apoptosis. We found that HL156A inhibited the expression of MDR1 by inhibiting the HOXC6-mediated ERK1/2 signaling pathway and increased the sensitivity to paclitaxel or doxorubicin in MDR cells. Furthermore, HL156A significantly inhibited angiogenesis in a chicken chorioallantoic membrane (CAM) assay. These results suggest the potential of the metformin derivative HL156A as a candidate therapeutic modality for the treatment of human multidrug-resistant cancers.

scholarly journals pfmdr1 Amplification and Fixation of pfcrt Chloroquine Resistance Alleles in Plasmodium falciparum in Venezuela

2010 ◽  
Vol 54 (4) ◽  
pp. 1572-1579 ◽  
Author(s):  
Sean Griffing ◽  
Luke Syphard ◽  
Sankar Sridaran ◽  
Andrea M. McCollum ◽  
Tonya Mixson-Hayden ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Evolutionary History ◽  
Selective Pressure ◽  
Multidrug Resistant ◽  
Chloroquine Resistance ◽  
Drug Resistant ◽  
Molecular Tools ◽  
Drug Policies ◽  
Number Variation

ABSTRACT Molecular tools are valuable for determining evolutionary history and the prevalence of drug-resistant malaria parasites. These tools have helped to predict decreased sensitivity to antimalarials and fixation of multidrug resistance genotypes in some regions. In order to assess how historical drug policies impacted Plasmodium falciparum in Venezuela, we examined molecular changes in genes associated with drug resistance. We examined pfmdr1 and pfcrt in samples from Sifontes, Venezuela, and integrated our findings with earlier work describing dhfr and dhps in these samples. We characterized pfmdr1 genotypes and copy number variation, pfcrt genotypes, and proximal microsatellites in 93 samples originating from surveillance from 2003 to 2004. Multicopy pfmdr1 was found in 12% of the samples. Two pfmdr1 alleles, Y184F/N1042D/D1246Y (37%) and Y184F/S1034C/N1042D/D1246Y (63%), were found. These alleles share ancestry, and no evidence of strong selective pressure on mutations was found. pfcrt chloroquine resistance alleles are fixed with two alleles: S tctVMNT (91%) and S agtVMNT (9%). These alleles are associated with strong selection. There was also an association between pfcrt, pfmdr1, dhfr, and dhps genotypes/haplotypes. Duplication of pfmdr1 suggests a potential shift in mefloquine sensitivity in this region, which warrants further study. A bottleneck occurred in P. falciparum in Sifontes, Venezuela, and multidrug resistance genotypes are present. This population could be targeted for malaria elimination programs to prevent the possible spread of multidrug-resistant parasites.

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