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ABSTRACT: To study the relationship between glutathione S-transferase genes GSTT1 and GSTM1 polymorphisms and the susceptibility to infectious mononucleosis (IM) and acute lymphocytic leukemia (ALL) in children.
The case-control study involved 106 children with IM, 41 children with ALL and a control group of 100 children with non-hematologic and nontumorous diseases. The genetic polymorphisms of GSTT1 and GSTM1 were detected with multiplex polymerase chain reaction (PCR). Distribution of the genotypes in the children was analyzed.
The frequency of GSTT1 null genotype in children with IM was significantly higher than in the control group (P<0.05). The risk of IM in children carrying GSTT1 null genotype was 2.186 times higher than in those carrying GSTT1 non-null genotype. The children carrying both GSTT1 and GSTM1 null genotype had a higher risk of suffering from IM compared to those carrying only one of the null genotypes (OR=4.937). The frequency of GSTM1 null genotype in children with ALL was significantly higher than in the control group (P<0.05). The risk of ALL in children carrying GSTM1 null genotype was 2.242 times higher than in those in carrying GSTT1 non-null genotype. Children carrying both GSTT1 and GSTM1 null genotype had a higher risk of suffering from ALL compared with those carrying only one of the null genotypes (OR=8.552).
Children carrying GSTT1 or GSTM1 null genotype have a high risk of suffering from IM or ALL. Still more increased susceptibility to IM or ALL may occur in children who carry both GSTT1 and GSTM1 null genotype. GSTT1 and GSTM1 might play a potential role in the pathogenesis of both IM and ALL.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 04/2012; 14(4):260-3.
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ABSTRACT: To study the regulation of methylation inhibitor 5-aza-2'-deoxycytidine on transcription of EphB4 gene and effects on the proliferation and apoptosis of human acute lymphocyte leukemia cell line CEM.
Bisulfite sequencing PCR was used to detect CpG island methylation density in EphB4 promoter. The expression of EphB4 mRNA and protein was determined by Q-PCR and Western blot. MTS assay and flow cytometry were used to detect the apoptosis of CEM cells after treatment with different concentrations of 5-aza-2'-deoxycytidine (1.0, 2.5 and 5 μmol/L).
Methylation of EphB4 gene promoter was detected in CEM cells (31.4%). The methylation level of EphB4 gene was down-regulated after treatment with various concentrations of 5-aza-2'-deoxycytidine. The EphB4 mRNA and protein expression in CEM cells increased after 5-aza-2'-deoxycytidine treatment. 5-Aza-2'-deoxycytidine significantly inhibited the cell growth in dose and time dependent manners. Early apoptosis rates of CEM cells increased from 4.1% to 24.8% 96 hrs after 5-aza-2'-deoxycytidine treatment. CEM cells in G1 phase decreased from 62.4% to 46.8%, cells in G2 phase increased from 2.1% to 16.2%, and CEM cells were arrested in G2 phase after treatment with 5 μmol/L 5-aza-2'-deoxycytidine for 96 hrs.
5-Aza-2'-deoxycytidine, an inhibitor of specific methylation transferase, can induce expression of the silent EphB4 gene in CEM cells, inhibit the proliferation of leukemia cells and induce cell apoptosis.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 03/2012; 14(3):205-9.
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ABSTRACT: Abnormal miRNA expression is associated with prostate cancer progression. However, the relationship between miRNA and biochemical recurrence after radical prostatectomy is not well established. Thus, we evaluated the miRNA miR-21 as a biomarker to predict the risk of biochemical failure, and as a potential drug target for prostate cancer therapy.
miR-21 levels were assayed using locked nucleic acid in situ hybridization coupled with tissue microarray techniques in 169 radical prostatectomy tissue samples. The Cox proportional hazard model was used to analyze miR-21 expression as an independent predictor of biochemical recurrence. The association of miR-21 with recurrence was estimated using the Kaplan-Meier method. miR-21 was also evaluated as a potential drug target for prostate cancer therapy.
miR-21 expression in prostate cancer tissue samples was significantly associated with pathological stage, lymph node metastasis, capsular invasion, organ confined disease, Gleason score, biochemical recurrence and patient followup. Multivariate analysis also indicated that miR-21 expression could be an independent predictor of biochemical recurrence. The 5-year recurrence-free probability for patients positive vs negative for miR-21 expression was 33.9% vs 44.5%. In vivo treatment with antagomir-21 also repressed the tumor growth of DU145 cells in nude mice.
Positive miR-21 expression was associated with poor biochemical recurrence-free survival and predicted the risk of biochemical recurrence in patients with prostate cancer after radical prostatectomy. Accordingly gene therapy using miR-21 inhibition strategies may prove useful for prostate cancer therapy.
The Journal of urology 02/2012; 187(4):1466-72. · 4.02 Impact Factor
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ABSTRACT: We have previously found that connective tissue growth factor (CTGF) is highly expressed in a rat model of liver cancer. Here, we examined expression of CTGF in human hepatocellular carcinoma (HCC) cells and its effect on cell growth.
Real-time PCR was used to observe expression of CTGF in human HCC cell lines HepG2, SMMC-7721, MHCC-97H and LO2. siRNA for the CTGF gene was designed, synthesized and cloned into a Plk0.1-GFP-SP6 vector to construct a lentivirus-mediated shRNA/CTGF. CTGF mRNA and protein expression in HepG2 cells treated by CTGF-specific shRNA was evaluated by real-time PCR and Western blotting. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to evaluate the growth effect, and a colony formation assay was used for observing clonogenic growth. In vivo, tumor cell proliferation was evaluated in a nude mouse model of xenotransplantation. Statistical significance was determined by t test for comparison between two groups, or analysis of variance (ANOVA) for multiple groups.
Immunohistochemical staining of CTGF was seen in 35 of 40 HCC samples (87.5%). CTGF was overexpressed 5-fold in 20 HCC tissues, compared with surrounding non-tumor liver tissue. CTGF mRNA level was 5 - 8-fold higher in HepG2, SMMC-7721 and MHCC-97H than in LO2 cells. This indicated that the inhibition rate of cell growth was 43% after knockdown of CTGF expression (P < 0.05). Soft agar colony formation assay showed that siRNA mediated knockdown of CTGF inhibited colony formation in soft agar of HepG2 cells (P < 0.05). The volume of tumors from CTGF-shRNA-expressing cells only accounted for 35% of the tumors from the scrambled control-infected HepG2 cells (P < 0.05).
CTGF was overexpressed in human HCC cells and downregulation of CTGF inhibited HCC growth in vitro and in vivo. Knockdown of CTGF may be a potential therapeutic strategy for treatment of HCC.
Chinese medical journal 11/2011; 124(22):3794-9. · 0.86 Impact Factor
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Lian Wang,
Bin Yao,
Qiu Li,
Kai Mei,
Jian-Rong Xu,
Hong-Xia Li,
Yong-Sheng Wang,
Yan-Jun Wen,
Xiao-Dong Wang,
Han-Shuo Yang, Yu-Hua Li,
Feng Luo,
Yang Wu,
Yan-You Liu,
Li Yang
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ABSTRACT: Adenovirus (Ad)-based antiangiogenesis gene therapy is a promising approach for cancer treatment. Downregulation or loss of coxsackievirus and adenovirus receptor (CAR) is often detected in various human cancers, which hampers adenoviral gene therapy approaches. Cationic liposome-complexed adenoviral vectors have been proven useful in CAR-deficient cells to enhance therapeutic gene transfer in vivo. Here, we investigated the antitumor effects of recombinant adenovirus encoding endostatin (Ad-hE) encapsulated in cationic liposome (Ad-hE/Lipo) on CAR-deficient CT26 colon carcinoma murine models. In vitro, Ad-hE/Lipo enhanced adenovirus transfection in CAR-deficient cells (CT26), and endostatin gene expression was measured by both qualitative and quantitative detection. In addition, an antibody neutralizing assay indicated that neutralizing serum inhibited naked adenovirus 5 (Ad5) at rather higher dilution than the complexes of Ad5 and cationic liposomes (Ad5-CL), which demonstrated that Ad5-CL was more capable of protecting Ad5 from neutralization. In vivo, Ad-hE/Lipo treatment in the murine CT26 tumor model by intratumoral injection resulted in marked suppression of tumor growth and prolonged survival time, which was associated with a decreased number of microvessels and increased apoptosis of tumor cells. In conclusion, recombinant endostatin adenovirus encapsulated with cationic liposome effectively inhibited CAR-deficient tumor growth through an antiangiogenic mechanism in murine models without marked toxicity, thus showing a feasible strategy for clinical applications.
Human gene therapy 05/2011; 22(9):1061-9. · 4.20 Impact Factor
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ABSTRACT: There are currently few published studies that compare hippocampal volume (HCV) in children with temporal lobe epilepsy (TLE). Aims : T0 o compare HCVs in children with TLE and in relation to normal controls (NC), and to analyze HCV change in the acute phase in pediatric subjects using magnetic resonance imaging (MRI). Setting and Design : T0 he case group (n=24) was matched in gender and age range with NC subjects (n=24). Subjects were divided into three groups according to age: 2-5.9 years, 6-8.9 years and 9-13 years.
M0 anual measurements were used to obtain HCVs on oblique coronary MRI images obtained by three-dimensional magnetization-prepared rapid gradient-echo (3D-MPRAGE) sequence. Statistical Analyses : T0 he HCV was calculated and normalized. Paired t-tests were used to compare the right and left HCVs within each study group. Analysis of covariance (ANCOVA) was used to consider the impact of age and gender on HCVs.
T0 wenty-two patients were diagnosed with definite/probable TLE, and two were non-syndromic focal epilepsy which was distributed in the 2-5.9 years group. The range of left to right mean HCVs of the case and NC group aged 2-13 years was 2014.14 ± 54.32 mm 3 to 2165.31 ± 80.99 mm 3 and 2015.46 ± 26.97 mm 3 to 2100.93 ± 57.33 mm 3 respectively. There were age-related differences in left and right HCV, but no effect of gender. Relative to NC subjects, cases group aged 2-5.9 years had significantly different HCVs, while no significant difference was found in the other two groups. There was significant difference in the right to left HCVs in the case subjects aged 2-5.9 years, but not in the other age groups.
T0 he heterogeneity in the 2-5.9 years age cohort may relate to the increased HCVs. The HCV data from NC subjects may be used as a reference to assess hippocampal abnormalities in clinical practice.
Neurology India 60(1):29-35. · 0.96 Impact Factor
