ABSTRACT
<p><b>OBJECTIVE</b>To study the changes of expression of Survivin mRNA, BCRP mRNA and HER-2 mRNA in breast cancer after TE regimen neoadjuvant chemotherapy, and to find biological markers to predict the efficiency of TE regimen neoadjuvant chemotherapy.</p><p><b>METHODS</b>The gene expressions were detected by RT-PCR from 56 breast cancer patients before and after TE regimen neoadjuvant chemotherapy (docetaxel and epirubicin). The relationships between these gene expressions and chemotherapy responses were analyzed.</p><p><b>RESULTS</b>The overall response rate to neoadjuvant chemotherapy was 71.4%, including 8.9% (5/56) with complete response and 62.5% (35/56) with partial response. Pathological complete response was found in 4 cases (7.1%). Stable disease and progression of disease were 23.2% (13/56) and 5.4% (3/56), respectively. The expression of Survivin mRNA after neoadjuvant chemotherapy was 35.7% (20/56), significantly lower than 60.7% (34/56) before neoadjuvant chemotherapy (P = 0.008). The expression of BCRP mRNA after neoadjuvant chemotherapy was 19.6%, significantly lower than 37.5% before neoadjuvant chemotherapy (P = 0.036). The positive rate of HER-2 mRNA expression was 41.1% before the chemotherapy, and reduced to 21.4% after the chemotherapy (P = 0.025). The effective rates of the single positive expression of Survivin mRNA or BCRP mRNA were both lower than that of negative expression (P < 0.05). The level of HER-2 mRNA expression alone was not significantly associated with the effective rate of chemotherapy (P = 0.144). When the expression of all Survivin mRNA, BCRP mRNA and HER-2 mRNA were negative, the effective rate of neoadjuvant chemotherapy was higher than that in patients with positive expression (P = 0.003). The level of Survivin mRNA expression was not significantly associated with BCRP mRNA and HER-2 mRNA (P > 0.05).</p><p><b>CONCLUSION</b>The expression of Survivin in combination with BCRP and HER-2 is associated with clinical response to TE neoadjuvant chemotherapy in breast cancer, and can be used as predictive biomarkers for chemosensitivity of TE regimen neoadjuvant chemotherapy for breast cancer.</p>
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , ATP Binding Cassette Transporter, Subfamily G, Member 2 , ATP-Binding Cassette Transporters , Genetics , Metabolism , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Breast Neoplasms , Drug Therapy , Metabolism , General Surgery , Carcinoma, Ductal, Breast , Drug Therapy , Metabolism , General Surgery , Carcinoma, Lobular , Drug Therapy , Metabolism , General Surgery , Disease Progression , Epirubicin , Inhibitor of Apoptosis Proteins , Genetics , Metabolism , Mastectomy, Radical , Methods , Neoadjuvant Therapy , Neoplasm Proteins , Genetics , Metabolism , RNA, Messenger , Metabolism , Receptor, ErbB-2 , Genetics , Metabolism , Remission Induction , TaxoidsABSTRACT
<p><b>OBJECTIVE</b>To investigate the distribution of Hepatitis B virus genotypes and subgenotypes among patients with chronic hepatitis B in Xinjiang Uighur.</p><p><b>METHODS</b>The HBV genotypes and subgenotypes were analyzed by PCR-restriction fragment length polymorphism in 109 patients with chronic hepatitis B.</p><p><b>RESULTS</b>Two HBV genotypes, genotype C (45.9%) and genotype C/D (29.4%) were prevalent, genotype B (8.3%) and genotype D (16.5%) were also found in Xinjiang Uighur. Genotype C had two subgenotypes, C1 (54%) and C2 (46%). Genotype B had only one subgenotype, i.e. Ba. The subgenotype C2 was associated with cirrhosis and hepatocellular carcinoma.</p><p><b>CONCLUSION</b>In Uygurs, the most common HBV genotypes were C and C/D, and the subgenotype C2 was associated with cirrhosis and hepatocellular carcinoma.</p>
Subject(s)
Humans , Carcinoma, Hepatocellular , Virology , Genotype , Hepatitis B virus , Genetics , Hepatitis B, Chronic , Virology , Liver Neoplasms , VirologyABSTRACT
<p><b>OBJECTIVE</b>To observe the changes of replication and antigen expressions of lamivudine-resistant hepatitis B virus (HBV) with polymerase gene mutation.</p><p><b>METHODS</b>With site-directed mutagenesis, we constructed 3 HBV plasmids with polymerase gene mutation based on the template P3.8II. All the plasmids were transfected into HepG2 cells, in which the replication and expression of the virus were analyzed.</p><p><b>RESULTS</b>The 3 polymerase gene mutant HBVs were successfully constructed. HBsAg and HBeAg expressions were detected in the supernatants of HepG2 cells transfected with these plasmids. The replication of the 3 mutant plasmids with rtG172E, rtG174C and rtG172E/rtG174C mutation decreased significantly in comparison with the wild-type virus.</p><p><b>CONCLUSION</b>The 3 polymerase gene mutant HBVs shows depressed capacity for viral replication, and in vitro drug sensitivity study is needed to establish the relationship between these mutations and nucleoside analogue resistance.</p>
Subject(s)
Humans , Base Sequence , Drug Resistance, Viral , Genetics , Gene Expression , Genetic Engineering , Methods , Genome, Viral , Genetics , Hep G2 Cells , Hepatitis B Surface Antigens , Genetics , Hepatitis B e Antigens , Genetics , Hepatitis B virus , Genetics , Allergy and Immunology , Physiology , Lamivudine , Pharmacology , Mutation , Plasmids , Genetics , Transfection , Virus Replication , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the association between the C311S polymorphism of paraoxonase 2 (PON2) gene and ischemic stroke in Chinese type 2 diabetes mellitus (T2DM) patients.</p><p><b>METHODS</b>A case-control study of 279 Chinese subjects (including 162 T2DM with or without ischemic stroke and 117 non-diabetic control) was performed. Genotype frequencies of C311S polymorphism were studied by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) analysis with DdeI digestion.</p><p><b>RESULTS</b>C311S polymorphism of PON2 gene was detected in Chinese with the C/S allele frequencies 0.145 and 0.855. The frequency distribution showed significant difference between Chinese and Asian Indian. Furthermore, the genotype distribution (SS, CS and CC) of the PON2 C311S gene polymorphism exhibited a significant difference between T2DM patients complicated with ischemic stroke and T2DM without ischemic stroke, the former had a significantly higher C allele frequency(P<0.05).</p><p><b>CONCLUSION</b>The above data indicate that the polymorphism at codon 311(Cys --> Ser)in the PON2 gene is associated with ischemic morbidity in Chinese T2DM patients and C allele might be a risk factor.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Aryldialkylphosphatase , Genetics , Asian People , Genetics , Diabetes Mellitus, Type 2 , Genetics , Polymorphism, Genetic , Stroke , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To study the heterogeneity of polymerase gene (P gene) within hepatitis B virus (HBV) genotypes based on a systematic analysis of 202 HBV P genes, providing some useful references for further studies on the relationship among HBV genotypes, P gene mutations, replication and nucleoside analogues drug-resistance.</p><p><b>METHODS</b>202 HBV complete sequences containing P genes were obtained from GenBank and were analysed using computer softwares.</p><p><b>RESULTS</b>There were some genotype-related characteristics of HBV P genes. As reverse transcriptase domain was concerned, there were more amino acid divergences in genotype C and D compared with these in genotype A. There were also amino acid substitutions in the A-F conserved regions of the reverse transcriptase domain within and between HBV genotypes.</p><p><b>CONCLUSIONS</b>There are divergences of P genes and amino acids within and between HBV genotypes, which should be considered when amino acid changes are analyzed whether they are proposed to be drug-resistance mutations or the results from quasispecies-selected. Moreover, these divergences may affect the antiviral effect of nucleoside analogues on HBV with different genotypes.</p>
Subject(s)
Humans , Amino Acid Sequence , DNA, Viral , Genetics , DNA-Directed DNA Polymerase , Genetics , Gene Products, pol , Genetics , Genetic Heterogeneity , Genotype , Hepatitis B virus , Genetics , Physiology , Molecular Sequence Data , Mutation , PhylogenyABSTRACT
Overexpression of procollagen gene can cause the extraordinary increase of collagen's synthesis and therefore lead to the keloid and hypertrophic scar. To utilize ribozyme to suppress the expression of procollagen genes, a eukaryotic expression recombinant plasmid containing a dual-ribozyme gene against alpha 1 (I) and alpha 1 (III) procollagen genes was constructed. The ribozyme from in vitro transcription was incubated with target transcripts from recombinant plasmids which separately contained the fragments of the second exons of pro alpha 1 (I) and pro alpha 1 (III) collagen genes under various experimental conditions. The results showed that the dual-ribozyme could efficiently catalyze the specific cleavage of the target RNAs at 37 degrees C, 42 degrees C, 50 degrees C and Mg2+ concentration from 10 mmol/L to 20 mmol/L. This work provided a basis for further study on the ribozyme to suppress the expression of procollagen genes and control the cicatrization.