AIM：To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein（BCRP）,lung resistance protein（LRP）,and multidrug resistance protein 1（MDR1） at the inner blood...AIM：To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein（BCRP）,lung resistance protein（LRP）,and multidrug resistance protein 1（MDR1） at the inner blood-retinal barrier（BRB） during the development of early diabetic retinopathy（DR） and/or aging in mice.METHODS：Relative m RNA and protein expression profiles of these three efflux transporters in the retina during the development of early DR and/or aging in mice were examined.The differing expression profiles of Zonula occludens 1（ ZO-1） and vascular endothelial growth factor-A（ VEGFA） in the retina as well as the perfusion characterization of fluorescein isothiocyanate（FITC）-dextran and Evans blue were examined to evaluate the integrity of the inner BRB.RESULTS：There were significant alterations in these three efflux transporters＇ expression profiles in the m RNA and protein levels of the retina during the development of diabetes mellitus and/or aging.The development of early DR was confirmed by the expression profiles of ZO-1 and VEGFA in the retina as well as the compromised integrity of the inner BRB.CONCLUSION：The expression profiles of some efflux transporters such as BCRP,LRP,and MDR1 in mice retina during diabetic and/or aging conditions are tested,and the attenuated expression of BCRP,LRP,and MDR1 along with the breakdown of the inner BRB is found,which may be linked to the pathogenesis of early DR.展开更多
BACKGROUND:Sulfonylurea receptor 1(SUR1)and multidrug resistance protein 1(MRP1)are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate ...BACKGROUND:Sulfonylurea receptor 1(SUR1)and multidrug resistance protein 1(MRP1)are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion. METHODS:Fasting glucose,insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma patients.Insulin content,SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence. RESULTS:Insulinoma patients presented the typical demons-trations of Whipple’s triad.Fasting glucose of each insulinoma patient was lower than 2.8 mmol/L,and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high glucose.Immunohistochemistry and immunofluorescence staining showed that SUR1 increased,but MRP1 decreased in insulinoma compared with the adjacent islets. CONCLUSIONS:The hypersecretion of insulin in insulinomas might be,at least partially,due to the enrichment of SUR1. In contrast,MRP1,which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.展开更多
Objective: To investigate the relationship between the expression of multidrug resistance-associated protein (MRP) and clinicopathological factors and prognosis. Methods: The expression of MRP in 62 cases with non-sma...Objective: To investigate the relationship between the expression of multidrug resistance-associated protein (MRP) and clinicopathological factors and prognosis. Methods: The expression of MRP in 62 cases with non-small cell lung cancer (NSCLC) was detected using immunohistochemistry method. The expression of MRP in 30 cases of NSCLC and corresponding normal lung tissues were detected using immunohistochemistry and Western Blot. Results: this study of tumor tissues confirmed the plasma membrane and/or cytoplasm locations of MRP. There was apparent difference between normal lung tissues and NSCLC in MRP. The survival analysis of 62 NSCLC showed that the mean survival time of the patients with negative MRP expression was 69.8117.41 months and that of patients with positive MRP expression, 25.384.46 months. Log-rank test suggested that the difference between them was significant (P=0.0156). It was also found that in squamous cell lung cancer the statistically significant difference between the mean survival time of patients with positive MRP expression and those with negative MRP expression (P=0.0153). Multivariate Cox model analysis suggested that the survival time was significantly related to expression of MRP (P=0.035) and lymphatic metastasis (P=0.038). Conclusion: MRP expression in NSCLC is significantly higher compared with normal lung tissues. The mean survival time of patients with negative MRP was relative longer and expression of MRP was an independent factor for prognosis.展开更多
AIM:To investigate the effect of the G-1666A polymorphism in the multidrug resistance related protein-1 (MRP1) on outcome of hepatocellular carcinoma (HCC). METHODS:A cohort of 162 patients with surgically resected HC...AIM:To investigate the effect of the G-1666A polymorphism in the multidrug resistance related protein-1 (MRP1) on outcome of hepatocellular carcinoma (HCC). METHODS:A cohort of 162 patients with surgically resected HCC who received no postsurgical treatment until relapse was studied. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. Electrophoretic mobility shift assay (EMSA) was used to evaluate the influence of the G-1666A polymorphism on the binding affinity of the MRP1 promoter with its putative transcription factors. RESULTS:Kaplan-Meier analysis showed that patients with GG homologues had a reduced 4-year disease-free survival compared with those carrying at least one A allele (P = 0.011). Multivariate Cox regression analysis indicated that the-1666GG genotype represented an independent predictor of poorer disease-free survival [hazard ratio (HR) = 3.067,95% confidence interval (CI):1.587-5.952,P = 0.001],and this trend became worse in men (HR = 3.154,95% CI:1.604-6.201,P = 0.001). A similar association was also observed between 4-year overall survival and the polymorphism in men (HR = 3.342,95% CI:1.474-7.576,P = 0.004). Moreover,EMSA suggested that the G allele had a stronger binding affinity to nuclear proteins. CONCLUSION:The MRP1-1666GG genotype predicted a worse outcome and was an independent predictor of poor survival in patients with HCC from Southeast China.展开更多
Our previous study demonstrated that BM-cyclin 1, a traditional anti-mycoplasma drug, could effectively reverse the multidrug resistance （MDR） of C-A120 cells. The present study aims to explore the reversal effect o...Our previous study demonstrated that BM-cyclin 1, a traditional anti-mycoplasma drug, could effectively reverse the multidrug resistance （MDR） of C-A120 cells. The present study aims to explore the reversal effect of BM-cyclin 1 on MDR and its mechanisms in BALB/C nude mice bearing C-A120 cells. Irnmunoblotting analysis and reverse transcription-polymerase chain reaction （RT-PCR） were used to study the change in multidrug resistance-associated protein 2 （MRP2） induced by BM-cyclin 1. We found that the expression levels of MRP2 protein and mRNA in C-A120 cells treated with BM-cyclin 1 were reduced significantly. Chemical colorimetry revealed no significant change in the level of glutathione （GSH）. In the xenografl model, the inhibitory rate of C-A120 cells growth in BM-cyclin 1 plus adriamycin （ADM） group was 52%, which was significantly higher than in control group （P〈0.01）. The immunoblotting and RT-PCR results conclusively demonstrated that BM-cycin 1 could significantly reduce the expression of MRP2 in transplanted tumor. In conclusion, BM-cyclin 1 could effectively reverse the MDR of C-A 120 cells in vivo by suppressing the expression of MRP2.展开更多
目的:探讨参慈胶囊对人肺腺癌A549/DDP裸鼠体内多药耐药相关基因的影响。方法:将50只C57BL/6小鼠接种人肺腺癌细胞A549/DDP细胞悬液建立实体瘤模型,随机分为对照组、参慈胶囊组、参慈胶囊+顺铂组、顺铂组,各10只。对照组予等量生理盐水...目的:探讨参慈胶囊对人肺腺癌A549/DDP裸鼠体内多药耐药相关基因的影响。方法:将50只C57BL/6小鼠接种人肺腺癌细胞A549/DDP细胞悬液建立实体瘤模型,随机分为对照组、参慈胶囊组、参慈胶囊+顺铂组、顺铂组,各10只。对照组予等量生理盐水,其余各组荷瘤小鼠均用药21 d,断颈处死取肿瘤组织,采用FQ-PCR技术检测人肺腺癌A549/DDP肺癌组织MDR1、MRP1、LRP m RNA的表达情况。结果:MDR1 m RNA、MRP1 m RNA、LRP1 m RNA在各组均有表达,各治疗组的MDR1m RNA、MRP1 m RNA、LRP1 m RNA均低于对照组,差异均有统计学意义(P<0.01);参慈胶囊+顺铂组的MDR1 m RNA、MRP1 m RNA、LRP1 m RNA的表达均明显低于参慈胶囊组和顺铂组,差异均有统计学意义(P<0.01)。结论:通过降低MDR1、MRP1、LRP多药耐药相关基因的表达,可能是参慈胶囊逆转人肺腺癌A549/DDP裸鼠体内多药耐药的作用机制之一。展开更多
基金Supported by the National Natural Science Foundation of China(No.81271036No.81500751)+1 种基金the Key Research Project of Shandong Province,China(No.2015GSF118121)the Natural Science Foundation of Shandong Province,China(No.ZR2015PH062)
文摘AIM：To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein（BCRP）,lung resistance protein（LRP）,and multidrug resistance protein 1（MDR1） at the inner blood-retinal barrier（BRB） during the development of early diabetic retinopathy（DR） and/or aging in mice.METHODS：Relative m RNA and protein expression profiles of these three efflux transporters in the retina during the development of early DR and/or aging in mice were examined.The differing expression profiles of Zonula occludens 1（ ZO-1） and vascular endothelial growth factor-A（ VEGFA） in the retina as well as the perfusion characterization of fluorescein isothiocyanate（FITC）-dextran and Evans blue were examined to evaluate the integrity of the inner BRB.RESULTS：There were significant alterations in these three efflux transporters＇ expression profiles in the m RNA and protein levels of the retina during the development of diabetes mellitus and/or aging.The development of early DR was confirmed by the expression profiles of ZO-1 and VEGFA in the retina as well as the compromised integrity of the inner BRB.CONCLUSION：The expression profiles of some efflux transporters such as BCRP,LRP,and MDR1 in mice retina during diabetic and/or aging conditions are tested,and the attenuated expression of BCRP,LRP,and MDR1 along with the breakdown of the inner BRB is found,which may be linked to the pathogenesis of early DR.
文摘BACKGROUND:Sulfonylurea receptor 1(SUR1)and multidrug resistance protein 1(MRP1)are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion. METHODS:Fasting glucose,insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma patients.Insulin content,SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence. RESULTS:Insulinoma patients presented the typical demons-trations of Whipple’s triad.Fasting glucose of each insulinoma patient was lower than 2.8 mmol/L,and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high glucose.Immunohistochemistry and immunofluorescence staining showed that SUR1 increased,but MRP1 decreased in insulinoma compared with the adjacent islets. CONCLUSIONS:The hypersecretion of insulin in insulinomas might be,at least partially,due to the enrichment of SUR1. In contrast,MRP1,which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.
文摘Objective: To investigate the relationship between the expression of multidrug resistance-associated protein (MRP) and clinicopathological factors and prognosis. Methods: The expression of MRP in 62 cases with non-small cell lung cancer (NSCLC) was detected using immunohistochemistry method. The expression of MRP in 30 cases of NSCLC and corresponding normal lung tissues were detected using immunohistochemistry and Western Blot. Results: this study of tumor tissues confirmed the plasma membrane and/or cytoplasm locations of MRP. There was apparent difference between normal lung tissues and NSCLC in MRP. The survival analysis of 62 NSCLC showed that the mean survival time of the patients with negative MRP expression was 69.8117.41 months and that of patients with positive MRP expression, 25.384.46 months. Log-rank test suggested that the difference between them was significant (P=0.0156). It was also found that in squamous cell lung cancer the statistically significant difference between the mean survival time of patients with positive MRP expression and those with negative MRP expression (P=0.0153). Multivariate Cox model analysis suggested that the survival time was significantly related to expression of MRP (P=0.035) and lymphatic metastasis (P=0.038). Conclusion: MRP expression in NSCLC is significantly higher compared with normal lung tissues. The mean survival time of patients with negative MRP was relative longer and expression of MRP was an independent factor for prognosis.
基金Supported by The Scientific and Technological Program of Guangdong Province, China, No. 2003B30102
文摘AIM:To investigate the effect of the G-1666A polymorphism in the multidrug resistance related protein-1 (MRP1) on outcome of hepatocellular carcinoma (HCC). METHODS:A cohort of 162 patients with surgically resected HCC who received no postsurgical treatment until relapse was studied. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. Electrophoretic mobility shift assay (EMSA) was used to evaluate the influence of the G-1666A polymorphism on the binding affinity of the MRP1 promoter with its putative transcription factors. RESULTS:Kaplan-Meier analysis showed that patients with GG homologues had a reduced 4-year disease-free survival compared with those carrying at least one A allele (P = 0.011). Multivariate Cox regression analysis indicated that the-1666GG genotype represented an independent predictor of poorer disease-free survival [hazard ratio (HR) = 3.067,95% confidence interval (CI):1.587-5.952,P = 0.001],and this trend became worse in men (HR = 3.154,95% CI:1.604-6.201,P = 0.001). A similar association was also observed between 4-year overall survival and the polymorphism in men (HR = 3.342,95% CI:1.474-7.576,P = 0.004). Moreover,EMSA suggested that the G allele had a stronger binding affinity to nuclear proteins. CONCLUSION:The MRP1-1666GG genotype predicted a worse outcome and was an independent predictor of poor survival in patients with HCC from Southeast China.
基金supported by grants from Guangdong Provincial Natural Science Foundation of China(No.S2012010008792)Fundamental Research Funds for the Central Universities of China(No.10ykpy05)
文摘Our previous study demonstrated that BM-cyclin 1, a traditional anti-mycoplasma drug, could effectively reverse the multidrug resistance （MDR） of C-A120 cells. The present study aims to explore the reversal effect of BM-cyclin 1 on MDR and its mechanisms in BALB/C nude mice bearing C-A120 cells. Irnmunoblotting analysis and reverse transcription-polymerase chain reaction （RT-PCR） were used to study the change in multidrug resistance-associated protein 2 （MRP2） induced by BM-cyclin 1. We found that the expression levels of MRP2 protein and mRNA in C-A120 cells treated with BM-cyclin 1 were reduced significantly. Chemical colorimetry revealed no significant change in the level of glutathione （GSH）. In the xenografl model, the inhibitory rate of C-A120 cells growth in BM-cyclin 1 plus adriamycin （ADM） group was 52%, which was significantly higher than in control group （P〈0.01）. The immunoblotting and RT-PCR results conclusively demonstrated that BM-cycin 1 could significantly reduce the expression of MRP2 in transplanted tumor. In conclusion, BM-cyclin 1 could effectively reverse the MDR of C-A 120 cells in vivo by suppressing the expression of MRP2.
基金supported by a grant from NIH(R01 CA120221)China Scholarship Council and Scholarship Award for Excellent Doctoral Student granted by Ministry of Education of China
文摘目的:探讨参慈胶囊对人肺腺癌A549/DDP裸鼠体内多药耐药相关基因的影响。方法:将50只C57BL/6小鼠接种人肺腺癌细胞A549/DDP细胞悬液建立实体瘤模型,随机分为对照组、参慈胶囊组、参慈胶囊+顺铂组、顺铂组,各10只。对照组予等量生理盐水,其余各组荷瘤小鼠均用药21 d,断颈处死取肿瘤组织,采用FQ-PCR技术检测人肺腺癌A549/DDP肺癌组织MDR1、MRP1、LRP m RNA的表达情况。结果:MDR1 m RNA、MRP1 m RNA、LRP1 m RNA在各组均有表达,各治疗组的MDR1m RNA、MRP1 m RNA、LRP1 m RNA均低于对照组,差异均有统计学意义(P<0.01);参慈胶囊+顺铂组的MDR1 m RNA、MRP1 m RNA、LRP1 m RNA的表达均明显低于参慈胶囊组和顺铂组,差异均有统计学意义(P<0.01)。结论:通过降低MDR1、MRP1、LRP多药耐药相关基因的表达,可能是参慈胶囊逆转人肺腺癌A549/DDP裸鼠体内多药耐药的作用机制之一。
