scholarly journals Comparison of Effects of Aminosalicylic Acid, Glucocorticoids and Immunosuppressive Agents On The Expression of Multidrug-Resistant Genes in Ucerative Colitis

2021 ◽  
Author(s):  
Yan Chen ◽  
Ping Wang ◽  
Yin Zhang ◽  
Xiao-Yu Du ◽  
Ying-Jian Zhang
Keyword(s):  
Multidrug Resistance ◽  
Immunosuppressive Agents ◽  
Multidrug Resistant ◽  
Aminosalicylic Acid ◽  
Multidrug Resistance Gene ◽  
Expression Levels ◽  
Treatment And Prevention ◽  
Resistant Genes ◽  
Mucosal Tissues ◽  
Mdr1 Mrna

Abstract Objective: To compare the effects of aminosalicylic acid, glucocorticoids and immunosuppressive agents on the expression levels of multidrug-resistant genes in ucerative colitis (UC) patients, aiming to provide theoretical and therapeutic basis for the diagnosis, treatment and prevention of UC.Methods: Fresh specimen of colon mucosal tissues pathological mucosal tissues under endoscopy or postoperative pathological biopsy tissues were collected from 148 UC patients and then prepared for subsequent experiment.Immunohistochemical staining was conducted to detect the distribution site and pattern of P-glycoprotein （P-gp）. The effects of ASA glucocorticoids and immunosupresive agents on P-gp were statistically compared.The expression levels of Multidrug resistance gene （MDR1）mRNA before and after corresponding treatment were quantitatively measured by using RT-PCR. In addition, the effects of three agents upon MDR1 mRNA were also comparatively analyzed.Results: Administration of 5-aminosalicylic acid (5-ASA) drugs were not correlated with the expression of multidrug resistance genes in UC, whereas delivery of glucocorticoids and immunosuppressant drugs was positively correlated with the expression profile. The expression levels of MDR1 gene and its product P-gp were significantly up-regulated in patients who were nonresponsive to glucocorticoids and immunosuppressant agents.Conclusions: Overall, the findings in the present study demonstrate that 5-ASA exerts no effect upon the expression levels of MDR1 and its product P-gp in patients diagnosed with UC. Nevertheless, administration of glucocorticoids and immunosuppressant drugs can up-regulate the expression levels of MDR1.

Expression of multidrug resistance gene mdr1 mRNA in a subset of normal bone marrow cells

1992 ◽  
Vol 81 (2) ◽  
pp. 145-152 ◽  
Author(s):  
Jean-Pierre Marie ◽  
Nathalie A. Brophy ◽  
Mohamed N. Ehsan ◽  
Yukoh Aihara ◽  
Named A. Mohamed ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multidrug Resistance ◽  
Resistance Gene ◽  
Bone Marrow Cells ◽  
Normal Bone Marrow ◽  
Multidrug Resistance Gene ◽  
Normal Bone ◽  
Mdr1 Mrna ◽  
Marrow Cells

Prognostic Significance of Multidrug Resistance Gene 1 (MDR1), Multidrug Resistance-Related Protein (MRP) and Lung Resistance Protein (LRP) mRNA Expression in Acute Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4418-4418
Author(s):  
Hee Jin Huh ◽  
Chan-Jeoung Park ◽  
Seongsoo Jang ◽  
Eul-Ju Seo ◽  
Hyun-Sook Chi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multidrug Resistance ◽  
Acute Leukemia ◽  
Mrna Expression ◽  
Prognostic Significance ◽  
Multidrug Resistance Gene ◽  
Lung Resistance Protein ◽  
Mdr1 Mrna ◽  
Resistance Protein ◽  
Multidrug Resistance Related Protein

Abstract The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (AML 39, ALL 32) using nested reverse transcription polymerase chain reaction (RT-PCR). The expression of each of these genes was then expressed as a ratio in relation to ß-actin gene expression, and the three genes were categorized as being either not expressed (0), weakly expressed (1+), moderately expressed (2+) or strongly expressed (3+). MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1%, respectively, of acute leukemia patients. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion of these patients, compared to LRP-negative patients (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-year survival (P=0.049 and p=0.04, respectively) compared to MRP-negative and non-high MDR1 mRNA-expressing patients, respectively. Patients expressing both MRP and LRP mRNA had poorer outcomes in response to induction chemotherapy and had worse 2-year survival compared to patients not expressing both genes. The present data suggest that MDR gene expression affects CR and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.

scholarly journals JNK1/2 Activation by an Extract from the Roots ofMorus albaL. Reduces the Viability of Multidrug-Resistant MCF-7/Dox Cells by Inhibiting YB-1-Dependent MDR1 Expression

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Youn Kyung Choi ◽  
Sung-Gook Cho ◽  
Hyeong Sim Choi ◽  
Sang-Mi Woo ◽  
Yee Jin Yun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Multidrug Resistant ◽  
Morus Alba ◽  
Root Extract ◽  
Multidrug Resistance Gene ◽  
Mdr1 Expression ◽  
Mcf 7

Cancer cells acquire anticancer drug resistance during chemotherapy, which aggravates cancer disease. MDR1 encoded from multidrug resistance gene 1 mainly causes multidrug resistance phenotypes of different cancer cells. In this study, we demonstrate that JNK1/2 activation by an extract from the root ofMorus albaL. (White mulberry) reduces doxorubicin-resistant MCF-7/Dox cell viability by inhibiting YB-1 regulation ofMDR1gene expression. When MCF-7 or MCF-7/Dox cells, where MDR1 is highly expressed were treated with an extract from roots or leaves ofMorus albaL., respectively, the root extract from the mulberry (REM) but not the leaf extract (LEM) reduced cell viabilities of both MCF-7 and MCF-7/Dox cells, which was enhanced by cotreatment with doxorubicin. REM but not LEM further inhibited YB-1 nuclear translocation and its regulation ofMDR1gene expression. Moreover, REM promoted phosphorylation of c-Jun NH2-terminal kinase 1/2 (JNK1/2) and JNK1/2 inhibitor, SP600125 and rescued REM inhibition of both MDR1 expression and viabilities in MCF-7/Dox cells. Consistently, overexpression of JNK1, c-Jun, or c-Fos inhibited YB-1-dependent MDR1 expression and reduced viabilities in MCF-7/Dox cells. In conclusion, our data indicate that REM-activated JNK-cJun/c-Fos pathway decreases the viability of MCF-7/Dox cells by inhibiting YB-1-dependentMDR1gene expression. Thus, we suggest that REM may be useful for treating multidrug-resistant cancer cells.

scholarly journals Tracking of antibiotic resistance transfer and rapid plasmid evolution in a hospital setting by Nanopore sequencing

2019 ◽  
Author(s):  
Silke Peter ◽  
Mattia Bosio ◽  
Caspar Gross ◽  
Daniela Bezdan ◽  
Javier Gutierrez ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Multidrug Resistance ◽  
Rapid Evolution ◽  
Hospital Setting ◽  
Gene Cassette ◽  
Multidrug Resistant ◽  
Nanopore Sequencing ◽  
Multidrug Resistance Gene ◽  
Plasmid Evolution ◽  
Resistance Gene Cassette

AbstractBackgroundInfection of patients with multidrug-resistant (MDR) bacteria often leave very limited or no treatment options. The transfer of antimicrobial resistance genes (ARG) carrying plasmids between bacterial species by horizontal gene transfer represents an important mode of expansion of ARGs. Here, we evaluated the application of Nanopore sequencing technology in a hospital setting for monitoring the transfer and rapid evolution of antibiotic resistance plasmids within and across multiple species.ResultsIn 2009 we experienced an outbreak with an extensively multidrug resistant P. aeruginosa harboring the carbapenemase enzyme blaIMP-8, and in 2012 the first Citrobacter freundii and Citrobacter werkmanii harboring the same enzyme were detected. Using Nanopore and Illumina sequencing we conducted a comparative analysis of all blaIMP-8 bacteria isolated in our hospital over a 6-year period (n = 54). We developed the computational platforms pathoLogic and plasmIDent for Nanopore-based characterization of clinical isolates and monitoring of ARG transfer, comprising de-novo assembly of genomes and plasmids, polishing, QC, plasmid circularization, ARG annotation, comparative genome analysis of multiple isolates and visualization of results. Using plasmIDent we identified a 40 kb plasmid carrying blaIMP-8 in P. aeruginosa and C. freundii, verifying that plasmid transfer had occurred. Within C. freundii the plasmid underwent further evolution and plasmid fusion, resulting in a 164 kb mega-plasmid, which was transferred to C. werkmanii. Moreover, multiple rearrangements of the multidrug resistance gene cassette were detected in P. aeruginosa, including deletions and translocations of complete ARGs.ConclusionPlasmid transfer, plasmid fusion and rearrangement of the multidrug resistance gene cassette mediated the rapid evolution of opportunistic pathogens in our hospital. We demonstrated the feasibility of tracking plasmid evolution dynamics and ARG transfer in clinical settings in a timely manner. The approach will allow for successful countermeasures to contain not only clonal, but also plasmid mediated outbreaks.

scholarly journals Enhancing the Therapeutic Efficacy of Daunorubicin and Mitoxantrone with Bavachinin, Candidone, and Tephrosin

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Sina Darzi ◽  
Seyed Abbas Mirzaei ◽  
Fatemeh Elahian ◽  
Sadegh Shirian ◽  
Amir Peymani ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Treatment ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell Line ◽  
Multidrug Resistant ◽  
Resistant Cell ◽  
Dependent Manner ◽  
Expression Levels ◽  
Treatment Research

The capability of flavonoids in sensitizing cancer cells was demonstrated in numerous works to chemotherapy and converse multidrug resistance by modulating efflux pumps and apoptosis mechanisms. Three flavonoids, namely, bavachinin, tephrosin, and candidone, have been recently introduced to cancer treatment research presenting various activities, such as antibacterial, immunomodulatory, cell death, and anticancer. Less information exists regarding the therapeutic significance of these flavonoids in cancer treatment, especially in overcoming multidrug resistance (MDR). Here, we tempted to investigate the potency of these agents in reversing MDR by analyzing their effects as chemosensitizers on cell cytotoxicity, P-gp and ABCG2 protein expression levels, and their function on two multidrug-resistant cell lines, P-gp-overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB) and ABCG2-overexpressing human epithelial breast cancer cell line (MCF7/MX). The inhibitory concentration of 10% (IC10) of bavachinin, tephrosin, and candidone in EPG85.257RDB cells was 1588.7 ± 202.2, 264.8 ± 86.15, and 1338.6 ± 114.11 nM, respectively. Moreover, these values in MCF7/MX cell were 2406.4 ± 257.63, 38.8 ± 4.28, and 27.9 ± 5.59 nM, respectively. Expression levels of ABCG2 and P-gp were not significantly downregulated by these flavonoids. Maximum levels of daunorubicin and mitoxantrone accumulations and minimum rates of drug efflux in both cell lines were detected 48 hrs posttreatment with tephrosin and bavachinin, respectively. Chemosensitization to mitoxantrone and daunorubicin treatments was, respectively, achieved in MCF7/MX and EPG85.257RDB cells in response to IC10 of bavachinin and tephrosin, independently. These effects did not follow time-dependent manner, and each flavonoid had its cell-dependent patterns. Overall, bavachinin, tephrosin, and candidone showed potency to sensitize MDR cells to daunorubicin and mitoxantrone and could be considered as attractive MDR modulators for cancer treatment. However, their action was time and cell specific.

scholarly journals Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA.

1987 ◽  
Vol 7 (12) ◽  
pp. 4549-4552 ◽  
Author(s):  
Y Sugimoto ◽  
I B Roninson ◽  
T Tsuruo
Keyword(s):  
Multidrug Resistance ◽  
Cell Lines ◽  
Multidrug Resistant ◽  
Human Tumors ◽  
Myelogenous Leukemia ◽  
Mdr1 Gene ◽  
Mdr1 Mrna

Amplification and increased expression of the mdr1 gene associated with multidrug resistance in human tumors were found in multidrug-resistant sublines of human myelogenous leukemia K562 selected with vincristine (K562/VCR) or adriamycin (K562/ADM). In two revertant cell lines of K562/ADM, amplification of the mdr1 gene was maintained at the same level as in K562/ADM, but expression of the 4.5-kilobase mdr1 mRNA was greatly decreased, indicating that amplified genes may be inactivated at the level of transcription without a corresponding loss of amplified DNA.

Modulation of Multidrug Resistance Gene (mdr-1) with Antisense Oligodeoxynucleotides

1996 ◽  
Vol 91 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Chao Liu ◽  
Imran Ahmad Qureshi ◽  
Xun-Jie Ding ◽  
Yi-Fei Shan ◽  
Yi-Wei Huang ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Multidrug Resistant ◽  
Polymerase Chain Reaction Method ◽  
Antisense Oligodeoxynucleotides ◽  
Multidrug Resistance Gene ◽  
Glycoprotein Synthesis ◽  
P Glycoprotein ◽  
Anti Cancer ◽  
Initiator Codon ◽  
Mdr 1

1. Multidrug resistance is the major obstacle to successful cancer chemotherapy. Circumventing multidrug resistance therefore represents a high priority for clinical anti-cancer treatment. Among many reversal strategies, antisense oligodeoxynucleotides may offer a molecular targeting tool for overcoming cellular multidrug resistance. 2. Two 17-mer phosphorothioate antisense oligomers, complementary to the 5′ end of the ATG initiator codon-containing region and loop-forming site (located at nucleotides 991–1007 from the first ATG codon) in mdr-1 cDNA sequence, were synthesized. The purpose was to study their effects on the function and expression of P-glycoprotein and mdr-1 gene. 3. The results showed that 10 μmol/l antisense oligomers could significantly inhibit the growth of multidrug resistant K562/Adm cells cultured in adriamycin-containing medium. No such effect was observed for parental (sensitive) K562/S cells. Intracellular daunorubicin accumulation increased greatly in the K562/Adm cells after they were treated with oligomers for 48 h and P-glycoprotein synthesis was strikingly reduced. 4. Further investigation with [α-32P]dCTP incorporation by the reverse transcriptase—polymerase chain reaction method revealed that antisense oligomers could result in a reduction in the level of mdr-1 mRNA, probably through hindering mdr-1 gene transcription. 5. The high reversal efficiency and specificity of antisense oligomers in regulating mdr-1 gene expression suggest a potential clinical application in gene therapy for drug resistant malignancies.

Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA

1987 ◽  
Vol 7 (12) ◽  
pp. 4549-4552
Author(s):  
Y Sugimoto ◽  
I B Roninson ◽  
T Tsuruo
Keyword(s):  
Multidrug Resistance ◽  
Cell Lines ◽  
Multidrug Resistant ◽  
Human Tumors ◽  
Myelogenous Leukemia ◽  
Mdr1 Gene ◽  
Mdr1 Mrna

Amplification and increased expression of the mdr1 gene associated with multidrug resistance in human tumors were found in multidrug-resistant sublines of human myelogenous leukemia K562 selected with vincristine (K562/VCR) or adriamycin (K562/ADM). In two revertant cell lines of K562/ADM, amplification of the mdr1 gene was maintained at the same level as in K562/ADM, but expression of the 4.5-kilobase mdr1 mRNA was greatly decreased, indicating that amplified genes may be inactivated at the level of transcription without a corresponding loss of amplified DNA.

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