This study was aimed to investigate the distribution and implication of tap1 (transporter associated with antigen processing) and tap2 loci allelic and genotypic frequencies. The distribution of tap1 and tap2 loci allelic and genotypic frequencies in 339 random samples of healthy Chinese Hans was analyzed by TaqMan PCR. Several genetic information about power of discrimination, cumulative DP, polymorphism information content, expected heterozygosity and observed heterozygosity were calculated. The results indicated that 5 tap1 alleles (tap1*0101, 020101, 020102, 0301 and 0401) and 4 tap2 alleles (tap2*0101, 0102, 0103 and 0201) were detected in all samples. 8 tap1 genotypes were found which account for 53.3% of the theoretic genotype and 6 tap2 genotypes were found which account for 60% of the theoretic genotype. The genotyping results of tap1 and tap2 both conform to the Hardy-Weinberg expectations (p > 0.05). Tap1*0101 (79.79%) and tap2*0101 (82.74%) are the most common alleles in Chinese Hans. It is concluded that tap1*0101 and tap2*0101 are most common alleles in Chinese Hans, tap1 and tap2 loci carry some power of individual discrimination and polymorphism information content. These two locl can be used for the research in the fields of human genetics, linkage analysis of genetic disease genes, paternity test and individual identification and so on.
ATP-Binding Cassette Sub-Family B Member 2 ; ATP-Binding Cassette Transporters ; genetics ; ATP-Binding Cassette, Sub-Family B, Member 3 ; Alleles ; Asian Continental Ancestry Group ; genetics ; Gene Frequency ; Genotype ; Haplotypes ; Humans

<b>OBJECTIVEb>To investigate the expression of multidrug resistance gene ABCB1 and ABCG2 in FaDu cells (human hypopharyngeal carcinoma cell line) and the multidrug resistance (MDR) cell lines FaDu/T transformed from FaDu cells by taxol and underlying mechanisms of MDR.

<b>METHODSb>The multidrug resistance sensitivities of FaDu and FaDu/T to cisplatin (DDP), 5-fluorouracil (5-FU), doxorubicin (Dox), and vincristine (VCR) were examined by methyl-thiazolyl-tetrazolium (MTT) assay. The mRNA and protein expressions of multidrug resistance genes ABCB1 and ABCG2 were analysed with RT-PCR, Western blot and laser confocal microscopy. JNK signal proteins were detected through Western blot.

<b>RESULTSb>The multidrug resistance of FaDu/T cells to Taxol, DDP, 5-FU, ADM and VCR was more than that of FaDu cells. The expression of ABCB1 in FaDu/T cells was significantly higher than that in FaDu cells (t = 22.42, P < 0.05), but the expression of ABCG2 in FaDu/T cells was significantly lower than that in FaDu cells (t = 10.06, P < 0.05). JNK signal was inhibited in FaDu or FaDu/T cells and the inhibited JNK was reactivated by taxol or anisomycin (an activator for MAPK signal transduction pathways). Anisomycin down-regulated the expression of ABCB1 (F = 33.72, P < 0.05) and up-regulated the expression of ABCG2 (F = 220.16, P < 0.05) in FaDu/T cells, but not in FaDu/T cells pretreated by JNK inhibitor SP600125 (P > 0.05).

<b>CONCLUSIONb>The overexpression of ABCB1 and the down-regulation of ABCG2 in FaDu/T cells were the main features of MDR in hypopharyngeal carcinomas, in which JNK signal transduction pathways could play an important role.

ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette Sub-Family B Member 2 ; ATP-Binding Cassette Transporters ; genetics ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Cell Line, Tumor ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Humans ; Hypopharyngeal Neoplasms ; genetics

<b>OBJECTIVEb>To compare the expression differences of breast cancer resistance protein(BCRP/ABCG2) and P-glycoprotein(P-gp) in breast cancer tissue before chemotherapy and in residual breast cancer tissue, and to explore its correlation with breast cancer stem cells.

<b>METHODSb>Immunohistochemistry was used to detect the expression of ABCG2, P-gp, and breast cancer stem cells(BCSCs) markers(CD44 and CD24) in breast cancer tissue before chemotherapy and residual breast cancer tissue after chemotherapy. Immunofluorescence was applied for determination of the CD44 and CD24 protein expressions of BCSCs microspheres cells. The monoclone-forming ability of BCSCs microspheres cells was detected by limited dilution assay. The expressions of ABCG2, P-gp, CD44, and CD24 proteins were detected by Western blot.

<b>RESULTSb>Compared with those in breast cancer tissue before chemotherapy, the expression levels of ABCG2 and P-gp were positively correlated with the expression level of CD44 protein(Χ(2)=41.34, r=0.83;Χ(2)=22.81, r=0.61) in residual breast cancer tissue after chemotherapy;meanwhile, they were negatively correlated with the expression of CD24 protein(Χ(2)=-21.25, r=0.72;Χ(2)=-17.26, r=0.65) (all P<0.05) .The diameter of BCSCs microspheres were increased significantly after chemotherapy.The content of BCSCs increased by about 2.5 times after chemotherapy.The expressions of ABCG2, P-gp and CD44 proteins significantly increased and that of CD24 protein significantly declined(P<0.05) .

<b>CONCLUSIONb>Chemotherapy endows residual breast cancer tissue with cancer stem cells-like features, leading to multidrug resistance of breast cancer.

ATP Binding Cassette Transporter, Sub-Family B ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adult ; Aged ; Breast Neoplasms ; drug therapy ; metabolism ; CD24 Antigen ; metabolism ; Cell Culture Techniques ; Drug Resistance, Neoplasm ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neoplasm, Residual ; Neoplastic Stem Cells ; cytology ; metabolism

<b>OBJECTIVEb>To investigate the correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer (CRC).

<b>METHODSb>Clinical data of CRC patients treated with irinotecan-based chemotherapy in the Peking University Cancer Hospital between January 1996 and December 2011 were collected, and their blood samples were collected accordingly. Genomic DNA was extracted from blood samples. The following SNP detection of MDR1 and ABCG2 genes was conducted by direct sequencing method. The correlation of genetic SNPs with efficacy and toxicity of irinotecan treatment was further analyzed.

<b>RESULTSb>Allele frequencies of MDR1 2677 G>T/A, ABCG2 421 C>A, 34 G>A, 376 C>T were comparable with previous studies. Genetic SNPs results from peripheral blood samples and tumor tissues were highly consistent. Patients carrying MDR1 2677 wild type had higher clinical benefit than those carrying mutant genotype, while the differences were not significant. The progression-free survival (PFS) was longer in wild-type patients as compared to mutant-type patients in second-line chemotherapy (P=0.012). There were no significant correlations between ABCG2 421 C>A, 34 G>A, 376 C>T and chemotherapy efficacy. No significant correlations were observed between MDR1 2677 G>T/A, ABCG2 421 C>A, ABCG2 34 G>A, ABCG2 376 C>T and irinotecan-related grade 3 and 4 neutropenia or diarrhea.

<b>CONCLUSIONb>MDR1 2677 G>T/A may be served as a biomarker in predicting the efficacy of irinotecan chemotherapy in patients with colorectal cancer.

ATP Binding Cassette Transporter, Sub-Family B ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; genetics ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Adult ; Aged ; Camptothecin ; analogs & derivatives ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; genetics ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Proteins ; genetics ; Polymorphism, Single Nucleotide ; Retrospective Studies ; Treatment Outcome ; Young Adult

This study was aimed to investigate the effect of Docetaxel on drug-resistant leukemia cell line HL-60/ADR and its influence on expression of P-pg, BCL-2 and BAX proteins so as to provide a new strategy and theoretical basis for clinical solution of leukemia drug-resistance. The morphological changes of HL-60/ADR were observed by light and transmission electron microscopes; the cell apoptosis was detected by flow cytometry with Annexin V FITC/PI double labeling; the expressions of P-gp, BCL-2 and BAX were determined by immunohistochemical technique and computer image analysis system. The results showed that the HL-60/ADR cells treated with Docetaxel displayed typical apoptotic morphological changes; the Docetaxel significantly inhibited the growth of HL-60/ADR cells in concentration-and time-dependent manners (r=0.853, r=0.989) and induced the apoptosis of HL-60/ADR cells, but apoptosis rate did not showed the increase trend along with concentration change of drug. The HL-60/ADR cells highly expressed P-gp, there were no significant differences between each groups; the expression of BCL-2 and BAX in HL-60/ADR cells decreased and increased respectively. It is concluded that the Docetaxel induces apoptosis of HL-60/ADR cells, decreases the expression of BCL-2 protein and increases the expression of BAX protein.
ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Apoptosis ; drug effects ; HL-60 Cells ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Taxoids ; pharmacology ; bcl-2-Associated X Protein ; metabolism

To study the effect of Siwu decoction on the function and expression of P-glycoprotein (P-gp) in Caco-2 cells. The Real-time quantitative poly-merase chain reaction (Q-PCR) was used to analyze the mRNA expression of MDR1 gene in Caco-2 cells. Flow cytometer was used to study the effect of Siwu decoction on the uptake of Rhodamine 123 in Caco-2 cells, in order to evaluate the efflux function of P-gp. Western blotting method was used to detect the effect of Siwu decoction on the P-gp protein expression of Caco-2 cells. Compared with the blank control group, after Caco-2 incubation with Siwu decoction at concentrations of 3.3, 5.0, 10.0 g x L(-1) for 24, 48, 72 h, the mRNA expression of MDR1 was up-regulated, suggesting the effect of Siwu decoction in inducing the expression of MDR1. After the administration with Siwu decoction in Caco-2 cells for 48 h, the uptake of Rhodamine 123 in Caco-2 cells decreased by respectively 16.6%, 22.1% (P < 0.05) and 45.4% (P < 0.01), indicating that the long-term administration of Siwu decoction can enhance the P-gp efflux function of Caco-2 cells. After the incubation of Caco-2 cells with Siwu decoction for 48 h, the P-gp protein expression on Caco-2 cell emebranes, demonstrating the effect of Siwu decoction in inducing the protein expression of P-gp.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Caco-2 Cells ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Up-Regulation ; drug effects

Drug metabolism will change significantly during inflammation, including the reduction of expression and activity of many drug metabolizing enzymes and transporters. Body would release a series of inflammatory cytokines which can regulate drug metabolizing enzymes. Recent studies have revealed that drug transporters are also regulated by the cytokines with obvious species difference. Mechanism studies show that several transcription factors play important roles during the signal pathways of regulation. This review focuses on the progress in the regulation of drug transporters during inflammation.
ATP Binding Cassette Subfamily B Member 11 ; ATP Binding Cassette Transporter, Sub-Family B ; metabolism ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; Animals ; Biological Transport ; Humans ; Inflammation ; metabolism ; Membrane Transport Proteins ; metabolism ; Multidrug Resistance-Associated Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; Organic Anion Transporters ; metabolism ; Organic Cation Transport Proteins ; metabolism ; Signal Transduction

<b>OBJECTIVEb>To study the influence and mechanism of HBV core region mutation on HLA-I expression.

<b>METHODSb>Eukaryotic expression vectors of HBV core region mutations L97, G87 and V60 were constructed and transfected into HepG2 cells. Then the expressions of HLA-I were detected by RT-PCR and Western blot. The mRNA of antigen-presentation-associated genes, including LMP2, TAP1 and tapasin, were measured using RT-PCR.

<b>RESULTSb>Different levels of HBsAg in the supernatants of transfected cells were detected by ELISA. The HBsAg of the mutated groups was markedly higher than that of the wild ones. All the transfected cells expressed HLA-I molecules, especially the L97 group. It was also found that the mRNA of TAP1 gene was up-regulated, while the mRNA of LMP and tapasin genes had no changes.

<b>CONCLUSIONb>The core region mutation of HBV can lower the expression of HBsAg; mutated groups and wild ones both can increase the expression of HLA-I molecules. The up-regulation of TAP1 gene expression might be the cause of these changes.

ATP-Binding Cassette Sub-Family B Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; Gene Expression Regulation, Viral ; Hep G2 Cells ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B virus ; genetics ; Histocompatibility Antigens Class I ; genetics ; metabolism ; Humans ; Mutation

<b>OBJECTIVEb>To study the relationship between TAP (transporter associated with antigen processing) gene promoter regional methylation level and cervical lesions with HPV infection in Uyghur women.

<b>METHODSb>A specialized software was used to design specific primers of CpG island fragments of TAP1 and TAP2 gene promoter for PCR amplification, bisulfitemodified SiHa cancer cell DNA for PCR amplification, cloning and sequencing analysis to obtain the relevant information on the gene base sequence methylation of CpG sites. Seventy-eight fresh cervical tissue samples from Uyghur women with cervicitis (number = 15), cervical intraepithelial neoplasia (CIN, number = 30) and cervical squamous cell carcinoma (number = 33) were collected. The methylation level of TAP1 and TAP2 gene promoter regions was detected using MassArray DNA technology. HPV infection status was determined by HPV gene chips. The relationship between CpG-island methylation of gene promoter regions and HPV infection was then analyzed.

<b>RESULTSb>Each TAP1 and TAP2 gene corresponding target fragment contained 23 and 8 CpG sites. There were 5 and 8 CpG sites methylation occurred in SiHa cervical cancer cells genomic DNA respectively. The TAP1 methylation level increased steadily with the severity of cervical lesions. The methylation levels in cervical squamous cell carcinoma and CIN (0.048 ± 0.039 and 0.037 ± 0.026, respectively) were higher than that of normal cervical tissue (0.035 ± 0.029, P < 0.05). Although TAP2 gene methylation level also demonstrated similar changes, the difference however was not statistically significant (P > 0.05). HPV gene chip detected 13 HPV genotypes, with HPV16 infection rate being 66.7% (52/78). The methylated proportion of TAP1 positively correlated with HPV16 infection (χ(2) = 6.08, P = 0.039).

<b>CONCLUSIONb>TAP1 methylation is a remarkable phenomenon occurring in a range of cervical lesions and significantly associated with cervical HPV infection.

ATP-Binding Cassette Sub-Family B Member 2 ; ATP-Binding Cassette Transporters ; genetics ; ATP-Binding Cassette, Sub-Family B, Member 3 ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Carcinoma, Squamous Cell ; genetics ; virology ; Cervical Intraepithelial Neoplasia ; genetics ; virology ; CpG Islands ; genetics ; DNA Methylation ; Female ; Human papillomavirus 16 ; Humans ; Middle Aged ; Papillomavirus Infections ; Promoter Regions, Genetic ; Uterine Cervical Neoplasms ; genetics ; virology ; Uterine Cervicitis ; genetics ; virology

ATP-Binding Cassette Sub-Family B Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 3 ; Calnexin ; metabolism ; Calreticulin ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; virology ; Cysteine Endopeptidases ; metabolism ; Female ; HLA-A Antigens ; metabolism ; Human papillomavirus 16 ; isolation & purification ; Humans ; Lymphatic Metastasis ; Papillomavirus Infections ; Proteasome Endopeptidase Complex ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; virology