Astragalus polysaccharides affects multidrug resistance gene 1 and P-glycoprotein 170 in adriamycin nephropathy rats via regulating microRNA-16/NF-κB axis / 中南大学学报(医学版)

OBJECTIVES@#Nephrotic syndrome is a common disease of the urinary system. The aim of this study is to explore the effect of astragalus polysaccharides (APS) on multidrug resistance gene 1 (MDR1) and P-glycoprotein 170 (P-gp170) in adriamycin nephropathy rats and the underlying mechanisms.@*METHODS@#A total of 72 male Wistar rats were divided into a control group, a model group, an APS low-dose group, an APS high-dose group, an APS+micro RNA (miR)-16 antagomir group and an APS+miR-16 antagomir control group, with 12 rats in each group. Urine protein (UP) was detected by urine analyzer, and serum cholesterol (CHOL), albumin (ALB), blood urea nitrogen (BUN), and creatinine (SCr) were detected by automatic biochemical analyzer; serum interleukin-6 (IL-6), IL-1β, tumor necrosis factor α (TNF-α) levels were detected by ELISA kit; the morphological changes of kidney tissues were observed by HE staining; the levels of miR-16 and MDR1 mRNA in kidney tissues were detected by real-time RT-PCR; the expression levels of NF-κB p65, p-NF-κB p65, and P-gp170 protein in kidney tissues were detected by Western blotting; and dual luciferase was used to verify the relationship between miR-16 and NF-κB.@*RESULTS@#The renal tissue structure of rats in the control group was normal without inflammatory cell infiltration. The renal glomeruli of rats in the model group were mildly congested, capillary stenosis or occlusion, and inflammatory cell infiltration was obvious. The rats in the low-dose and high-dose APS groups had no obvious glomerular congestion, the proliferation of mesangial cells was significantly reduced, and the inflammatory cells were reduced. Compared with the high-dose APS group and the APS+miR-16 antagomir control group, there were more severe renal tissue structure damages in the APS + miR-16 antagomir group. Compared with the control group, the levels of UP, CHOL, BUN, SCr, IL-6, IL-1β, TNF-α, and MDR1 mRNA, and the protein levels of p-NF-κB p65 and P-gp170 in the model group were significantly increased (all P<0.05); the levels of ALB and miR-16 were significantly decreased (both P<0.05). Compared with the model group, the levels of UP, CHOL, BUN, SCr, IL-6, IL-1β, TNF-α, and MDR1 mRNA, and the protein levels of pNF-κB p65 and P-gp170 in the low-dose and high-dose APS groups were significant decreased (all P<0.05); and the levels of ALB and miR-16 were significantly increased (both P<0.05). Compared with APS+miR-16 antagomir control group, the UP, CHOL, BUN, SCr, IL-6, IL-1β, and TNF-α levels, MDR1 mRNA, and the protein levels of p-NF-κB p65 and P-gp170 were significantly increased (all P<0.05). The levels of ALB and miR-16 were significantly decreased in the APS+miR-16 antagomir group compared with the APS+miR-16 antagomir control group (both P<0.05).@*CONCLUSIONS@#APS can regulate the miR-16/NF-κB signaling pathway, thereby affecting the levels of MDR1 and P-gp170, and reducing the inflammation in the kidney tissues in the adriamycin nephropathy rats.

High Expression of Multidrug Resistance Gene-1 Can Aggravate Resistance to Methotrexate in Rheumatoid Arthritis Patients / 中国医学科学院学报

Objective To explore the role of multidrug resistance gene-1(MDR1)gene in methotrexate(MTX)resistance in patients with rheumatoid arthritis(RA).Methods Fibroblast-like synoviocytes(FLS)from RA patients were infected with recombinant adenovirus Ad-EGFP-MDR1 to obtain MDR1 over-expressed RA FLS.The transcription level of MDR1 gene and the expression level of its coding product P-glycoprotein(P-gp) rotein were detected by real-time PCR and Western blot analysis.The efflux function was verified by rhodamine 123 efflux assay.The resistance to MTX was detected by MTT assay.Results RA FLS were infected with recombinant adenovirus Ad-EGFP-MDR1;72 hours later,the particles size in MDR1 over-expressed RA FLS increased,the cell volume became larger,and the growth rate decreased.The transcription level of MDR1(1.4325±0.3924 0.0650±0.0070;=6.035,=0.004),the expression level of P-gp protein(1.8667±0.2857 0.9367±0.0551;=5.536,=0.005),and the ability of extracellular rhodamine 123(979.43±196.81 1680.06±147.04;=-4.940,=0.008) in MDR1 over-expressed RA FLS were significantly higher than those of negative virus control RA-FLS,and the survival rate of MDR1 over-expressed RA FLS was significantly increased at each concentration of MTX(<0.05).Conclusion The high expression of MDR1 can affect the efflux ability to MTX by up-regulating the expression of P-gp,thus enhancing the drug resistance to MTX in RA FLS.

Establishment of allele-specific PCR for the detection of CYP3A5 and MDR-1 gene polymorphisms and its clinical application / 临床检验杂志

Objective To establish an allele-specific PCR method for the detection of cytochrome P-450 CYP3A5 (A6986G) and multiding resistance gene MDR-1 (C3435T) polymorphisms,and investigate the correlations of their polymorphisms with blood tacrolimus (Tac) concentration/dose (C/D) ratio in renal transplant recipients.Methods The allele-specific PCR primers were designed according to the polymorphism sites of CYP3A5 (A6986G) and MDR-1 (C3435T) genes.Then,their polymorphisms in the genomic DNA of peripheral blood samples from 72 renal transplant recipients were analyzed,and the results were validated by DNA sequencing.The blood Tac concentration was determined by the chemiluminescence microparticle immunoassay and the differences of concentration,dose and C/D ratio of blood Tac in renal transplant recipients with different genotypes were compared at 1 month after transplantation.Results The coincidence rate between the established allele-specific PCR and DNA sequencing was 100％.The frequencies of CYP3A5 * 1/* 1,* 1/* 3 and * 3/* 3 genotypes in 72 renal transplant recipients were 18.1％,31.9％ and 50.0％,respectively,and those of MDR-1 C/C,C/T and T/T genotypes were 27.8％,58.3％ and 13.9％,respectively.There were significant differences in blood Tac concentration (P =0.014) and Tac C/D ratio (P =0.019) between different CYP3A5 genotypes of renal transplant recipients.Further analysis found that the Tac C/D ratio of CYP3A5 * 3/* 3 genotype was significantly higher than that of CYP3A5 * 1/* 1 and * 1/* 3 genotypes (P ＜ 0.05).Conclusion The allele-specific PCR method for the detection of CYP3A5 and MDR-1 polymorphisms is successfully established and the polymorphism of CYP3A5 * 3 gene in renal transplant recipients is obviously correlated with the pharmacokinetics of Tac.

HMGB1 upregulates P-glycoprotein expression in the brain microvascular endothelial cells of the mouse / 医学研究生学报

[Abstract ] Objective High-mobility group box-1 (HMGB1) is abundantly released in the epileptogenic brain tissue , but few reports are seen about the effect of HMGB 1 on the expression of P-glycoprotein ( P-gp) in the vascular endothelial cells of the epi-leptogenic tissue .This study is to explore whether HMGB 1 can regulate P-gp expression in the brain microvascular endothelial cells of the mouse in vitro . Methods Immortalized brain microvascular endothelial bEnd .3 cells of the mouse were cultured in vitro and al-located to different concentration groups ( treated with culture medium containing 10 , 100 , 500 , and 1000 ng/mL HMGB1 for 8 hours), treatment duration groups (treated with culture medium containing 100 ng/mL HMGB1 for 4, 8, 16, 24, and 32 hours), and a control group ( treated with culture medium without HMGB 1 ) .The mRNA expression of P-gp-encoding gene-multidrug resistance gene 1a (mdr1a) was detected by real-time qPCR, and its protein expression determined by Western blot and immunocytochemistry . Results The results of qPCR manifested that the expressions of mdr 1a mRNA were 1.646 ±0.176, 1.777 ±0.135, 1.617 ±0.043, and 1.398 ±0.182 in the 10, 100, 500, and 1000 ng/mL HMGB1 groups, respectively, significantly higher than 1.030 ±0.284 in the control group (P<0.05), and so were those in the 4, 8, 16, 24 h, and 32 h groups (2.655 ±0.112, 2.168 ±0.212, 1.823 ± 0.232, 1.418 ±0.376, and 1.445 ±0.123) than in the control (1.010 ±0.164) (P <0.05).Western blot showed a significant increase in the P-gp protein expression in all the concentration groups (P<0.05) as well as in the 8 h and 16 h treatment duration groups as compared with the control group (P<0.05).Immunocytochemis-try also revealed a higher P-gp expression in the HMGB1-treated than in the control cells (P<0.01). Conclusion HMGB1 can upregu-late the expressions of mdr1a mRNA and P-gp protein in the brain microvascular endothelial cells of the mouse , which may associated with drug resistance of central nervous system diseases , especially that of epilepsy .

Advances in AEG-1 mediated drug resistance / 实用肿瘤学杂志

It has been demonstrated that astrocyte elevated gene 1 ( AEG-1 ) can promote tumor initia-tion and progression .Over expression of AEG -1 is correlated with tumor angiogenesis ,metastasis and chemother-apy resistance of tumor cells of different origins .The present article is a review on the mechanism of AEG -1 me-diated drug resistance .Studies have shown that AEG -1 participates in carcinogenesis through Ha -ras,myc,NF-κB and PI3K/Akt signalling pathways .AEG-1 can also promote autophagy through activating AMP Kinase . Other researchers demonstrate that AEG -1 promotes MDR1 protein translation by up-regulating MDR1 mRNA expression ,and thus increases polyribosome .It is testified that AEG-1 can influence drug susceptibility and ex-pression of MDR gene as a RNA binding protein .Multiple functions of AEG -1 in drug resistance in multiple cancers demonstrate that AEG -1 can be used as a novel target for antitumor drugs .

Inlfuence of transport protein gene polymorphisms on the effects and toxicity of high-dose methotrexate in child-hood acute lymphoblastic leukemia / 临床儿科杂志

Objectives To investigate the inlfuence of polymorphisms of SLC19A1 80G>A, MDR1 exon26C>T and MDR1 exon21G>T/A on curative effect and adverse reaction of high-dose methotrexate in patients with acute lymphoblastic leukemia. Methods MALDI-TOF-MS technique was used to detect the polymorphisms of SLC19A1 80G>A, MDR1 exon 26C>T and MDR1 exon21G>T/A in 108 patients with acute lymphoblastic leukemia (ALL). The relationship of genetic polymorphism, survival rate and toxicity was analyzed. Results The 36-month event-free survival was not related to any polymorphisms of MDR1 and SLC19A1. Patients with mutant types of MDR1 exon26C>T and MDR1 exon21G>T/A showed a much higher MTX plasma levels at 24 hours and higher incidence of hepatic injury (PT, MDR1 exon21G>T/A has a large inlfuence on hepatic toxicity and plasma concentra-tions of MTX.

Reversal effects of short hairpin RNA interference and tetrandrine on multidrug resistance of human colorectal cancer cell line LoVo/5-fluorouracil / 中华消化外科杂志

Objective To compare the reversal effects of short hairpin RNA (shRNA) interference and tetrandrine on multidrug resistance (MDR) of human colorectal cancer cell line LoVo/5-fluorouracil(5-FU ).Methods An eukaryotic expression plasmid of shRNA targeting MDR1 was constructed and transfected into human colorectal cancer cell line LoVo/5-FU (transfection group).LoVo/5-FU was also pretreated with tetrandrine (tetrandrine group).Drug sensitivity was detected by methyl thiazolyltetrazolium colorimetric method.Cell cycle,apoptosis of cells and positive expression rate of P-glycoprotein (P-gp) were determined by flow cytometry assay.The expressions of MDR1 mRNA and P-gp were detected by real-time polymerase chain reaction and Western blot,respectively.All data were analyzed by analysis of variance and SNK-q test.Results (1)Drug sensitivity:the 50％ concentration of inhibition(IC50)of the control group,tetrandrine group and transfection group were (7.3 ± 0.3),(4.4 ±0.7) and (2.4 ±0.4) mmol/L,respectively,a significant difference between the 3 groups was found(F =65.27,P ＜ 0.05 ).There was a significant difference in the IC50 between the tetrandrine group and the transfection group (q =6.67,P ＜ 0.05 ).(2) Changes of cell cycle:the proportion of cells in the G1 phase and S phase of the control group,tetrandrine group and transfection group were 38.13％ ± 3.75％,51.36％ ± 2.76％,59.24％±4.31％ and 20.46％±2.23％,14.32％± 1.91％,9.40％± 1.65％,respectively,a significant difference between the 3 groups was found(F =25.23,24.37,P ＜ 0.05 ).There were significant differences in the proportion of cells in the G1 phase and S phase between the tetrandrine group and the transfection group(q =3.67,4.35,P ＜ 0.05 ).(3) Cell apoptosis:the cell apoptotic rates of the control group,tetrandrine group and transfection group were 1.32％ ± 0.47％,3.24％ ± 0.26％,5.88％ ±- 0.44％,respectively,a significant difference between the 3 groups was found(F =99.26,P ＜ 0.05 ).There was a significant difference in the cell apoptotic rate between the tetrandrine group and transfection group(q =11.48,P ＜ 0.05 ).(4)The expression of P-gp:the positive expression rates of P-gp of the control group,tetrandrine group and transfection group were 96.9％ ± 2.3％,61.6％ ± 4.9％,76.6％ ± 3.6％,respectively,a significant difference between the 3 groups was found(F =67.83,P ＜ 0.05 ).There was a significant difference in the positive expression rate of P-gp between the tetrandrine group and transfection group (q =6.97,P ＜ 0.05 ).(5)The mRNA expression of MDR1:the mRNA expressions of MDR1 of the control group,tetrandrine group and transfection group were 1462 ±161,570 ±85,233 ± 81,respectively,a significant difference between the 3 groups was found(F =90.59,P ＜ 0.05 ).There was a significant difference in the mRNA expression of MDR1 between the tetrandrine group and transfection group (q =5.12,P ＜ 0.05 ).Conclusions MDR1 shRNA and tetrandrine could reverse M DR1 gene-mediated m.ultidrug resistance in human colon cancer cell line LoVo/5-FU,but the effect of MDR1 shRNA is better than that of tetrandrine.MDR1 shRNA and tetrandrine might take effect by inhibiting P-gp expression and down-regulating mRNA expression of MDR1.

Enhancive Effect of TNF-a on Transfection Efficiency of Ad-mediated Multidrug Resistance Gene1 (MDR1) in Mononuclear Cells of Mouse / 中国肿瘤临床

Objective: To investigate the enhancive effect of TNF-α on transfection efficiency of adenovi-rus in mononuclear cells of mouse and the enhancive capability of protection of bone marrow by MDR1. Meth-ods: Before the mononuclear cells of mouse were infected by recombinant adenovirus encoding human MDR1 gene, they had been pretreated by TNF-α. Transfection efficiency of adenovirus was monitored by fluo-rescence microscopy, immunohistochemistry and flow cytometry (FCM). mRNA and protein levels of MDR1 in the mononuclear cells of mouse were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot before and after treatment of TNF-α. Results: After treatment of TNF-α, tansfection rates of adenovirus were obviously increased in the treated group (26.26%) compared with the untreated group (11.96%). mRNA levels and protein levels of MDR1 were obviously increased in the treated group compared with the untreated group. Conclusion: TNF-α could enhance transfection efficiency of adenovirus in mononu-clear cells of mouse and enhance capability of protection of bone marrow by MDR1.

Impact of high dose X-ray irradiation on the expression of multidrug resistance gene CNE1 cells / 中华放射肿瘤学杂志

Objective To invstigate the effect of high dose X-ray irradiation on the expression of multidrug resistance-1 (MDR1), Bcl-2, MMP7 genes. Methods A nasopharyngeal carcinoma cell line,CNE1, were irradiated with a total dose of 50 Gy. The resistance to the cisplatin of CNE1 cells and the irradiated CNE1 (CNE1 R) cells was detected by MTT. mRNAs expression of MDR1 , Bcl-2 and MMP7 was measured by quantitative RT-PCR. Results The expression of MDR1 increased in CNE1 R cells. The semiquantitative A value of MDR1 mRNA was 0.47 ±0.04, and the value of CNE1R cells (1st, 7th, 21st,28th, 35th, 42nd and 49th days after irradiation) were 0.67 ± 0. 06 (t = -5.44, P = 0. 003) ,0.70 ± 0. 01(t=-5.90,P=0. 002),0.73±0. 01(t= -6. 45,P=0. 001) ,0. 67 ± 0. 03 (t= -3.97,P=0.011),0.65 ±0.01(t = -4.43,P=0. 007),0. 62±0. 05(t= -2. 64,P=0.046) and 0.62 ±0.02(t = -3.34,P=0.021), respectively. Bcl-2 mRNA expression were 0.55 ±0.02 and 1.05 ±0.04(t = -9.93,P=0. 000) and MMP7 mRNA expression were 0.51 ±0.01 and 0.82 ±0.02(t = -8.51,P=0.000) in CNE1and CNE1 R cells. Conclusions The MDR1 expression was increased after a total dose of50 Gy irradiation,which may be related to the synchronous change of Bcl-2 and MMP7 genes.

The expression and significance of multidrug resistance gene in children with refractory epilepsy / 临床儿科杂志

Objective To study the expression and significance of multidrug resistance gene (MDR1) in children with refractory epilepsy (RE). Methods Children with RE (n = 30), non-RE (n = 30) and healthy children (n=30) were collected. The expression of MDR1-mRNA in peripheral blood was analyzed by fluorescence quantitative PCR. The relationship of MDRI-mRNA with epileptic frequency and numbers of antiepileptic drugs (AEDs) were observed. Results The expression of MDR1 in RE group obviously increased when compared with that of non-RE group and healthy group (P < 0.01, P < 0.01) ; MDR1 expression was more among patients with high frequent epilepsy than patients with low frequent epilepsy (P < 0.01) ; more in patients administered with four kinds of AEDs than those with two or three kinds of AEDs (P < 0.01). Concinsions MDR1 overexpression in blood of children with RE may be linked to drug-resistant mechanism of RE. It might be used as a clinical indicator of RE.

Differences of tacrolimus' dosage and concentration of individuals in morning periods after renal transplantation / 中华泌尿外科杂志

Objective To study the influential factors of tacrolimus'dosage and concentration differences between individuals in morning periods after renal transplantation.Methods The clinical data consisted of 118 receptors in morning periods after renal transplantation,whose immune suppressions were tacrolimus,mycophenolate and hormone.At 3,7,14 and 30 d after operation,all the receptors'weight,dosage of tacrolimus,dosage of hormone,diarrhea,blood fat,liver function,renal function,albumn and erythrocrit were recorded respectively,and at the same time their concentrations of tacrolimus and genetic polymorphisms of CYP3A5,MDRl 3435,MDR1 2677 and MDRl 1236 weredetected.Multiple linear regressions were performed.Results The fitting degrees of stepwise regression equations were low.At 3,7,14 and 30 d after operation,the adjusted R2was 0.284,0.267,0.417 and 0.324,respectively.From the aspect of pharmacogenomics,the main factors rela-ted to the differences of tacrolimus'dosage and concentration included MDR1 2677,MDRl 1236 and MDR13435,which varied intensively.Age,albumn,renal function,blood fat and liver function were important factors too.Conclusions The main reasons of the differences of tacrolimus'dosage and concentration between individuals in morning periods after renal transplantation are medicines and changes of internal environment after operation.The genetic polymorphisms of MDR1,age,albumn,renal runetion.blood fat and liver function are important factors too.

Construction of lentiviral vector of RNA interference and its effect on A549 and A549/DDP cells / 中国癌症杂志

Background and purpose: Multidrug resistance (MDR) of tumor cell is the main reason for clinical chemotherapy failure as well as cancer recurrence and metastasis. This study was to construct a lentiveral vector of RNA interference of MDR1 gene and observe its inhibitive role on the expression of MDR1 in A549 and A549/DDP cells. Methods: Oligos of base pairs for hairpin RNA targeting MDR1 were chemically synthesized. Via annealing and inserting them into the down-stream of H1 promoter of linearized pSUPER, we obtained the siRNA constructs for MDR1, which were afterwards transfected into A549, a human lung cancer cell line expressing high level MDR1, the impact of constructs was observed on the expression and interference efficiency of siRNA against MDR1. The effective sequence of siRNA targeting MDR1 gene was confirmed. Both sense and antisence oligo DNA of the targeting sequence was designed, synthesized and cloned into the PTM vector, containing a promoter and a green fluorescent protein (GFP). The resulting lentiviral vector containing MDR1 siRNA was named PTM-siMDR1 and then transfected into A549 and A549/DDP cells after being confirmed by PCR and sequencing. Results: Restriction digestion and DNA sequencing showed that the siRNA constructs for MDR1 were successfully produced and the expressed siRNA could effectively down-regnlate the expression of MDRI. PCR demonstrated that the lentivirus RNAi vector of MDR1 producing PTM-siMDR1 was constructed successfully. The chemosensitivity of A549/DDP cells to cisplatin were enhanced obviously after trartsfection. Conclusion: The lentivirus RNAi vector of MDR1 can significantly revise the resistance ofA549/ DDP cells with eisplatin after infection.

Expressions and clinical significance of HIF-1? and multidrug resistance genes in human colorectal adenocarcinoma / 中国癌症杂志

Background and purpose:Micro-environmental hypoxia is a common phenomenon in most human solid tumors,and this investigation is done to observe the expression of HIF-1? and chemo-resistance-associated genes in human colon cancer cell line under hypoxic micro-environment in vitro,and study the influence of micro-environmental hypoxia on chemo-resistance and the possible mechanisms in human colon cancer.Methods:Human colon cancer cell line SW620 was cultured under hypoxia for 12,24,48 hr,with normoxia as control.Then the expression of HIF-1? and chemo-resistance-associated genes mdr1/P-Gp、LRP were investigated by RT-PCR and western-blot.Results:With prolongation of the hypoxic time,the mRNA expressions of HIF-1? and LRP remained at the same level,but the mRNA expressions of mdr1 showed a time-dependent increase(P

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

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 (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to beta-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1 %, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission 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.

The Expression and Significance of Multidrug Resistant Gene mdr1 in Hepatocellular Carcinoma / 中国普外基础与临床杂志

Objective To explore the relationship between mdr1 gene expression of hepatocellular carcinoma (HCC) and pathological characteristics,chemotherapy and prognosis. Methods The mdr1 gene expression of HCC in 56 patients with the methods of immunohistochemistry was studied. The results were analysed with the pathological data by statistic methods. Results The positive expression of mdr1 gene in cancer tissues and pericancerous tissues of HCC were 30/56(53.6%) and 19/56 (33.9%) respectively. The difference was statistically significant (? 2=4.39, P

Advances in Overcoming Multidrug Resistance of Tumors Caused by mdr1 Gene / 中国普外基础与临床杂志

Objective To review the advances in overcoming multidrug resistance of tumors caused by mdr1 gene. Methods Different ways of overcoming multidrug resistance of tumors caused by mdr1 gene in the literatures were reviewed. Results One of the important reasons causing multidrug resistance was due to the overexpression of mdr1 gene and its product P-glycoprotein. There were two ways to overcome multidrug resistance of tumors through mdr1 genes mRNA and its product P-glycoprotein effectively.Conclusion The clinical test of the unitary way to overcome multidrug resistance of tumors is unsatisfactory, combining different ways to overcome multidrug resistance of tumors will be the hot spot of tumors research in the future.

The relationship between the single nucleotide polymorphisms of multidrug resistance gene 1,brain derived neurotrophic factor gene and childhood drug resistance epilepsy / 中国药理学通报

Aim To explore the relationship of the single nucleotide polymorphisms of multidrug resistance gene 1 and brain derived neurotrophic factor(BDNF) gene to childhood drug resistance epilepsy.Methods Two single nucleotide polymorphisms,T-129C polymorphism in multidrug resistance gene 1 and C270T polymorphism in BDNF gene,were conducted with PCR-restriction fragment length polymorphism analysis.The distribution of genotypes and allele frequencies of two single nucleotide polymorphisms in childhood drug resistance epilepsy were compared to those in drug respond epilepsy and controls.Results The distribution of TT genotype and T allele frequencies of multidrug resistance gene 1 in drug resistance epilepsy differed significantly from those in drug respond epilepsy and controls(P0.05).Conclusions The findings suggested that the T-129C polymorphism of multidrug resistance gene 1 maybe associated with childhood drug resistance epilepsy and played some role in the etiology of drug resistance epilepsy,but C270T polymorphism of BDNF gene was not confirmed to relate to childhood drug resistance epilepsy.

Functional expression and temporality of MDR1 gene in bone marrow of rabbits after autologous transplantation with the gene modification to mononuclear cells / 第三军医大学学报

Objective To explore the functional expression and temporality of MDR1 gene in bone marrow of rabbits after autologous bone marrow transplantation with MDR1 transferred bone marrow mononuclear cells. Methods The supernatant of the amphotropic virus producer cell line PA317-HaMDR1/A was collected and concentrated to cocultivate with the bone marrow mononuclear cells of the rabbits. After large dose of chemotherapy with cyclophosphamide,the transferred cells were autotransplanted into the bone marrow. The integration,transfection rate and physiological function of MDR1 gene were tested by PCR,SP immunohistochemical method and daunorubicin (DNR) extrusion test respectively. Results After autologous bone marrow transplantation had been executed for 1-4 months,the integration of MDR1 gene in genome of bone marrow mononuclear cells was detected by PCR,and the expression rates of P-gp in cells tested by SP immunohistochemical method were 9.5%,8.5%,6.0% and 3.5% respectively. The physiological function of MDR1 gene in bone marrow cells was proved by DNR extrusion test. Conclusion After the autotransplantation with bone marrow mononuclear cells transferred by MDR1 gene,the MDR1 gene can implant into the bone marrow of rabbits and has expressed functionally for 4 months,which has provided a basis for further research on chemoprotection experiment of the MDR1 gene transferred into the bone marrow cells.

Coexpression of multidrug resistance in non-small cell lung cancer and its clinical significance / 中国实用内科杂志

Objective To investigate the expression and clinical significance of multidrug resistance gene(MDR1),multidrug-resistance-associated protein (MRP),lung resistance protein (LRP),glutathione S-transferase-?(GST-?)mRNA in non-small cell lung cancer. Methods From Oct.1996 to Oct.2001,RT-PCR was used to investigate the mRNA expression of the above four genes.We followed up the survival time one by one and calculated the probability of survival. Results The total positive rate of the four multidrug resistance gene was 53.1%,65.3%,67.3%,83.3%.There was a significant difference between the coexpression and the single positive rate( P 0.05).With the increasing expression of the MDR the curves moved to left,the survival time and probability reduced. Conclusion The coexpression of the MRG results in the MDR and affects the prognosis directly.It can be used as a criterion to evaluate the prognosis.

Expression of Multidrug Resistance Gene of the Malignant Lymphoma at Nasalcavity or Pharynx Nasalis:A Clinical Study / 中国药房

OBJECTIVE:To discuss the clinical significance of the expression of P- glycoprotein(P-gp),the multidrug resistance gene - 1(MDR - 1) expression product in the malignant lymphoma of nasalcavity and pharynx nasalis.METHODS: The expression of P - gp in the malignancy lymphoma of nasalcavity and pharynx nasalis of 37 cases was detected by S - P Immunohistochemical staining,and its correlations with patents' first visit,return visit,original sites,pathological type, immunohistochemical typing and prognosis were analyzed.RESULTS:Positive P- gp expression appeared in 87.5%(7/8) of the patients for return visit vs.34.5%(10/29) for first visit and 70.0%(7/10) with malignant lymphoma at pharynx nasalis vs.37.0%(10/27) with malignant lymphoma at nasal cavity,all showing significant differences.There were also significant differences in drug resistance between the patients with positive P- gp expression and those with negative P- gp expression (88.2%(15/17) vs.10.0%(2/20)).CONCLUSION:Positive P-gp expression serves as scientific basis for clinicians in predicating drug resistance and selecting drugs and establishing schemes.