190 results on '"Zhu DX"'
Search Results
102. A cationic iridium(III) complex showing aggregation-induced phosphorescent emission (AIPE) in the solid state: synthesis, characterization and properties.
- Author
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Shan GG, Zhang LY, Li HB, Wang S, Zhu DX, Li P, Wang CG, Su ZM, and Liao Y
- Subjects
- Cations, Cell Line, Tumor, Coordination Complexes chemistry, Electrochemistry, Humans, Ligands, Luminescence, Luminescent Measurements, Magnetic Resonance Spectroscopy, Microscopy, Atomic Force, Models, Chemical, Molecular Structure, Oxidation-Reduction, Photochemistry, Quantum Theory, X-Ray Diffraction, Carbazoles chemistry, Coordination Complexes chemical synthesis, Iridium chemistry
- Abstract
We report the synthesis and characterization of two cationic iridium(III) complexes with dendritic carbazole ligands as ancillary ligands, namely, [Ir(ppy)(2)L3]PF(6) (1) and [Ir(ppy)(2)L4]PF(6) (2), where L3 and L4 represent 3,8-bis(3,6-di-tert-butyl-9H-carbazol-9-yl)-1,10-phenanthroline and 3,8-bis(3',6'-di-tert-butyl-6-(3,6-di-tert-butyl-9H-carbazol-9-yl)-3,9'-bi(9H-carbazol)-9-yl)-1,10-phenanthroline, respectively. Their photophysical properties have been investigated and compared. The results have shown that complex 2 is aggregation-induced phosphorescent emission (AIPE) active and exhibits the highest photoluminescent quantum yield (PLQY) of 16.2% in neat film among the reported cationic Ir(III) complexes with AIPE activity. In addition, it also enjoys redox reversibility, good film-forming ability, excellent thermal stability as well as off/on luminescence switching properties, revealing its potential application as a candidate for light-emitting electrochemical cells and organic vapor sensing. To explore applications in biology, 2 was used to image cells.
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- 2012
- Full Text
- View/download PDF
103. [mRNA levels detected by real-time quantitative RT-PCR in chronic lymphocytic leukemia and their clinical significance].
- Author
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Liu L, Fang C, Dong HJ, Wang DM, Zhu DX, Qiao C, Fan L, Miao KR, Liu P, Xu W, and Li JY
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- Adult, Aged, Aged, 80 and over, Cell Cycle Proteins, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Male, Middle Aged, Nuclear Proteins metabolism, Prognosis, Proto-Oncogene Proteins metabolism, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Protein p53 genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Nuclear Proteins genetics, Proto-Oncogene Proteins genetics
- Abstract
This study was aimed to investigate the expression level of murine double minute 4 (MDM4) mRNA in chronic lymphocytic leukemia (CLL) and its prognostic value in CLL. By means of β-actin as internal reference, the real-time quantitative RT-PCR was set up. The expression of MDM4 mRNA in 66 CLL patients was measured by fluorescence dye SYBR Green I. The dispersion of MDM4 expression ratio of groups with different prognostic factors was described by using Mann-Whitney U test. The results showed that the median MDM4 mRNA expression level was 0.037098 (0.088245-0.014875) in CLL patients. The expression level of MDM4 mRNA was significantly higher in patients with P53 gene deletion than that in patients without P53 gene deletion (0.13167 vs 0.030927) (p < 0.001), and also significantly higher in patients with P53 mutation than that in patients without P53 mutation (0.13167 vs 0.03077) (p < 0.001). MDM4 expression was also associated with Binet stages (p = 0.044) and ATM gene deletion (p = 0.046), but was not associated with LDH (p = 0.216), β(2)-MG (p = 0.314), TK1 (p = 0.300), ZAP-70 (p = 0.559), CD38 (p = 0.513) and IgVH mutation status (p = 0.333). It is concluded that the expression level of MDM4 is significantly higher in patients with P53 deletion or mutation. MDM4 expression is significantly associated with Binet stages and ATM gene deletion. MDM4 may be an important prognostic factor in CLL.
- Published
- 2011
104. Prognostic significance of serum immunoglobulin paraprotein in patients with chronic lymphocytic leukemia.
- Author
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Xu W, Wang YH, Fan L, Fang C, Zhu DX, Wang DM, Qiao C, Wu YJ, and Li JY
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- ADP-ribosyl Cyclase 1 blood, Adult, Aged, Aged, 80 and over, Asian People, Chromosome Deletion, Cohort Studies, Cytogenetic Analysis, Female, Follow-Up Studies, Humans, Immunoglobulin Heavy Chains genetics, In Situ Hybridization, Fluorescence, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Male, Middle Aged, Mutation genetics, Paraproteinemias blood, Prognosis, Retrospective Studies, Survival Rate, Thymidine Kinase blood, ZAP-70 Protein-Tyrosine Kinase blood, Immunoglobulin G blood, Leukemia, Lymphocytic, Chronic, B-Cell blood, Paraproteins metabolism
- Abstract
The aim of this study was to explore the clinical and other associated laboratory features of chronic lymphocytic leukemia (CLL) patients with immunoglobulin (Ig) paraproteinemia. Serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) were performed to measure serum Ig paraprotein. The correlations between serum Ig paraprotein and other prognostic factors were analyzed. Univariate and multivariate Cox regression analyses were used to assess associations between survival time and potential risk factors. In 133 Chinese CLL patients, 27 (20.3%) patients occurred Ig paraproteinemia at diagnosis. According to the correlation analysis, advanced Binet stage (r=0.314, P<0.001), direct antiglobulin test (DAT)-positive (r=0.366, P<0.001), high level of serum β2-microglobulin (β2-MG) (r=0.296, P=0.001) and thymidine kinase (TK) 1 (r=0.227, P=0.037), unmutated immunoglobulin heavy chain variable gene (IGHV) status (r=0.284, P=0.002), ZAP-70-positive (r=0.305, P=0.001), CD38-positive (r=0.284, P=0.002), and cytogenetic abnormalities of del(17p13) or del(11q22.3) (r=0.208, P=0.032) emerged as factors significantly related to the occurrence of Ig paraproteinemia. Survival analysis showed that the patients with Ig paraproteinemia had significantly shorter survival times than the patients without serum Ig paraprotein (P=0.013). Binet stage (P=0.028), high levels of lactate dehydrogenase (LDH) (P=0.004), IgG paraproteinemia (P=0.048), IgM paraproteinemia (P=0.001), ZAP-70-positive (P=0.003), DAT-positive (P=0.013), unmutated IGHV status (P=0.009), and del(17p13) (P=0.001) were the adverse factors in determining overall survival (OS). Del(17p13) (P=0.006), ZAP-70 (P=0.030), and IgM paraproteinemia (P=0.040) were the variables strongly associated with OS by multivariate Cox regression analysis. It was showed that serum Ig paraprotein might be applied for the assessment of prognosis in patients with CLL., (Copyright © 2010. Published by Elsevier Ltd.)
- Published
- 2011
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105. The prognostic significance of TP53 mutations in Chinese patients with chronic lymphocytic leukemia is independent of del(17p13).
- Author
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Dong HJ, Zhou LT, Zhu DX, Wang DM, Fang C, Zhu HY, Zhuang Y, Miao KR, Xu W, and Li JY
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell ethnology, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Mutation physiology, Prognosis, Survival Analysis, Asian People genetics, Chromosome Deletion, Chromosomes, Human, Pair 17 genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Tumor Suppressor Protein p53 genetics
- Abstract
The poor prognosis of chronic lymphocytic leukemia (CLL) patients with del(17p13) is well established. Several studies have shown that cases with TP53 mutations and TP53 mutations without del(17p13) may be adverse prognostic factors. We studied 173 well-characterized CLL patients by direct sequencing to detect TP53 mutations (exons 2-11). TP53 mutations were detected in 14.5% (25 of 173) of samples. Most patients with del(17p13) had TP53 mutations (72.2%). Mutations in the absence of del(17p13) were found in 8.3% in our cohort, which were higher than other countries. Compared with cases without TP53 alterations, TP53 mutations and deletions were both associated with advanced stages and unmutated immunoglobulin heavy-chain variable region status. Survival analysis showed that the occurrence of TP53 mutations and del(17p13) were associated with shorter overall survival (OS), treatment-free survival (TFS), and resistance to chemotherapy. TP53 mutations were the variables strongly associated with OS and TFS by multivariate Cox regression analysis. Moreover, we also found that cases with TP53 mutations in the absence of del(17p13) had a similar clinical and biological course and similar poor short OS as cases carrying del(17p13) in Chinese patients with CLL.
- Published
- 2011
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106. [Cytogenetic study of mantle cell lymphoma].
- Author
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Wang DM, Fan L, Fang C, Zhu DX, Dong H, Yang H, Qiu HR, Hong M, Qiao C, Xu W, and Li JY
- Subjects
- Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 14 genetics, Female, Humans, Karyotyping, Lymphoma, Mantle-Cell mortality, Lymphoma, Mantle-Cell pathology, Male, Middle Aged, Neoplasm Staging, Chromosome Aberrations, Lymphoma, Mantle-Cell genetics
- Abstract
Objective: To explore the cytogenetic features of mantle cell lymphoma (MCL)., Methods: Bone marrow cells from 18 MCL patients with bone marrow invasion were cultured for 24 hours, then routine karyotype analysis was performed with R-banding technique. Interphase fluorescence in situ hybridization (FISH) and a panel of 5 probes, including CCND1/IgH, CEP12, D13S319, p53 gene and ATM gene, were used to investigate the cytogenetic features of the samples., Results: Chromosome aberrations were found in 9 (64.3%, 9/14) patients by conventional cytogenetics (CC), 8(57.1%, 8/14) patients had the aberration of t(11; 14), 6(42.9%, 6/14) had complex aberrant karyotypes, of which 2 (14.3%, 2/14) had highly complex aberrant karyotypes. A total of 28 abnormalities were detected, among them 19 (67.9%) were structural abnormalities, the other 9 (32.1%) were numerical aberrations. The aberration of t(11; 14) was found in all 18 (100%) patients with MCL by FISH. Secondary cytogenetic aberrations were detected in 14 patients by FISH. The most common abnormality was del(11q22.3) (57.1%), the rate of aberrations for del(17p13), + 12 and del(13q14) were 42.9%, 35.7% and 21.4%, respectively. Two (14.3%) and 4 (28.6%) patients were detected to have combinations of 2 and 3 aberrations., Conclusion: In addition to t(11; 14), most MCL patients have other chromosome aberrations, especially complex aberrant karyotype.
- Published
- 2011
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107. Aberrant microRNA expression in Chinese patients with chronic lymphocytic leukemia.
- Author
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Zhu DX, Miao KR, Fang C, Fan L, Zhu W, Zhu HY, Zhuang Y, Hong M, Liu P, Xu W, and Li JY
- Subjects
- Adult, Aged, Aged, 80 and over, Asian People genetics, Blotting, Western, China, Female, Humans, Immunoglobulin Heavy Chains genetics, Immunoglobulin Variable Region genetics, In Situ Hybridization, Fluorescence, Leukemia, Lymphocytic, Chronic, B-Cell ethnology, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Male, Middle Aged, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Leukemia, Lymphocytic, Chronic, B-Cell genetics, MicroRNAs genetics
- Abstract
MicroRNAs (miRNAs) are a class of small endogenous RNAs that play important regulatory roles by targeting mRNAs for cleavage or translational repression. Many reports have indicated that miRNAs play a critical role in malignancies, and regulations in the progression of leukemia. However, the miRNAs expression level in Chinese patients with chronic lymphocytic leukemia (CLL), and its prognostic value remain elusive. We identified various degrees of down-regulation of miR-15a, miR-16-1, miR-29b, miR-181a and miR-181b in CLL mononuclear cells. Moreover, we have identified miR-29b and miR-181a/b expression significantly correlated with IGHV mutational status. Transcript levels of predicted target genes BCL-2 and TCL-1 were also determined, and the expression levels were significantly upregulated in CLL patients compared with normal controls (P<0.001). Higher expression of TCL-1 was significantly correlated with aggressive disease features. In addition, an inverse correlation was observed in the CLL samples we examined between miRNAs (miR-16-1, miR-181a, miR-181b) and BCL-2 level; furthermore, an inverse correlation was also observed between miRNAs (miR-16-1, miR-181a, miR-181b) and TCL-1, which suggest that these miRNAs may implicate in negatively regulating target mRNA at transcriptional level. These different miRNAs may play an important role in the pathogenesis of CLL and might be applied for the assessment of prognosis in patients with CLL., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
108. Enhancing the action of rituximab by adding fresh frozen plasma for the treatment of fludarabine refractory chronic lymphocytic leukemia.
- Author
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Xu W, Miao KR, Zhu DX, Fang C, Zhu HY, Dong HJ, Wang DM, Wu YJ, Qiao C, and Li JY
- Subjects
- Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived therapeutic use, Antineoplastic Agents therapeutic use, Disease-Free Survival, Drug Resistance, Neoplasm drug effects, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Rituximab, Salvage Therapy methods, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Antibodies, Monoclonal, Murine-Derived administration & dosage, Antineoplastic Agents administration & dosage, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Plasma
- Abstract
Complement deficiencies have been identified in many chronic lymphocytic leukemia (CLL) patients. Supplying fresh frozen plasma (FFP)-derived complement can enhance complement-dependent cell lysis by the rituximab. The objective of our study was to evaluate the clinical efficacy and safety of the treatment by adding FFP to rituximab in fludarabine refractory CLL patients. Twenty-two patients were treated with two units of FFP followed with rituximab, 375 mg/m(2), as a single agent, repeated every 1-2 weeks. Patients received a median of four courses of the combined FFP and rituximab treatment (range: 2-6). Sixteen patients (72.7%) responded to treatment and seven (31.8%) achieved a complete remission. Three (13.6%) of which had no evidence of minimal residual disease after treatment. Patients with high expression of ZAP-70 or CD38, unmutated immunoglobulin heavy chain variable region, mutated p53, or adverse cytogenetic features, achieved response to treatment at rates that appeared similar to those who did not have such characteristics. With a median follow-up of 12 (4-19) months, the median overall survival and progression free survival have not been achieved. Toxicity was minimal, and the treatment was well tolerated. Our data suggest that the adding FFP to rituximab is an effective nonmyelotoxic regimen for the treatment of fludarabine refractory CLL patients., (Copyright © 2010 UICC.)
- Published
- 2011
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109. Creation of cationic iridium(III) complexes with aggregation-induced phosphorescent emission (AIPE) properties by increasing rotation groups on carbazole peripheries.
- Author
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Shan GG, Zhu DX, Li HB, Li P, Su ZM, and Liao Y
- Abstract
Three cationic iridium complexes containing 4,7-bis(3,6-di-tert-butyl-9H-carbazol-9-yl)-1,10-phenanthroline (L(1)) and 4,7-bis(3',6'-di-tert-butyl-6-(3,6-di-tert-butyl-9H-carbazol-9-yl)-3,9'-bi(9H-carbazol)-9-yl)-1,10-phenanthroline (L(2)) as the ancillary ligands, namely, [Ir(ppy)(2)(L(1))]PF(6) (1), [Ir(ppy)(2)(L(2))]PF(6) (2) and [Ir(oxd)(2)(L(2))]PF(6) (3) (ppy is 2-phenylpyridine, oxd is 2,5-diphenyl-1,3,4-oxadiazole), have been designed and prepared. With more intramolecular rotational units on the ancillary ligand (L(2)), 2 and 3 possess a unique aggregation-induced phosphorescent emission (AIPE) property. This phenomenon was unprecedentedly observed in the cationic iridium(III) complexes. In order to investigate the underlying mechanism of this AIPE behavior, their photophysical, temperature-dependent aggregation properties as well as theoretical calculations, were performed. The results suggest that restricted intramolecular rotation is responsible for the AIPE of cationic complexes. Moreover, photoluminescent quantum yields in the neat film, thermal stabilities and off/on luminescence switching of 2 were investigated, revealing its potential application as a candidate for LECs and organic vapor sensing.
- Published
- 2011
- Full Text
- View/download PDF
110. Intermediate prognosis of 6q deletion in chronic lymphocytic leukemia.
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Wang DM, Miao KR, Fan L, Qiu HR, Fang C, Zhu DX, Qiu HX, Xu W, and Li JY
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- Adult, Aged, Aged, 80 and over, Asian People genetics, Female, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Male, Middle Aged, Prognosis, Survival Rate, Biomarkers, Tumor genetics, Chromosome Deletion, Chromosomes, Human, Pair 6 genetics, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell genetics
- Abstract
Cytogenetic features have an important role in the definition of distinct disease subsets in CLL. The deletion of 6q is known to occur at a relatively low frequency in CLL, and the detailed analysis of hematologic and clinical features of patients with CLL with 6q deletion is limited. To verify the incidence and prognostic significance of 6q deletion in Chinese patients with CLL, fluorescence in situ hybridization (FISH) was used in 240 patients with CLL. del(6q23) was found in 18 patients (7.5%), and only five patients had deletion in 6q23 as the sole abnormality. Strong correlations between del(6q23) and clinical parameters were not found. A difference in terms of survival in patients with del(6q23) as compared with patients without this anomaly was not able to be demonstrated. However, a significant difference was found when comparing the del(6q23) group with the del(17p13) or del(11q22.3) group (p = 0.023), or isolated del(13q14) group (p = 0.019). Our findings place the del(6q23) cytogenetic subset of CLL in an intermediate prognosis position between patients with del(11q22.3) or del(17p13), and patients with isolated del(13q14). FISH probes to detect deletions of 6q might be useful in clinical practice in the work-up of patients with CLL.
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- 2011
- Full Text
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111. [Expression of cyclic nucleotide phosphodiesterase 7B in patients with mantle cell lymphoma and its prognostic significance].
- Author
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Dong HJ, Fan L, Wang DM, Fang C, Zhu DX, Wang YH, Hong M, Zhu Y, Qiao C, Zhuang Y, Xu W, and Li JY
- Subjects
- Adult, Aged, Case-Control Studies, Cyclic Nucleotide Phosphodiesterases, Type 7 genetics, Female, Humans, Lymphoma, Mantle-Cell genetics, Lymphoma, Mantle-Cell pathology, Male, Middle Aged, Polymerase Chain Reaction methods, Prognosis, Cyclic Nucleotide Phosphodiesterases, Type 7 metabolism, Lymphoma, Mantle-Cell metabolism
- Abstract
To investigate the expression level of cyclic nucleotide phosphodiesterase (PDE) 7B mRNA and its prognostic value in mantle cell lymphoma (MCL), the real-time quantitative RT-PCR (QPCR) was used to detect pde7b expression levels of bone marrow mononuclear cells from 20 newly diagnosed MCL patients with bone marrow involvement and peripheral blood mononuclear cells from 20 normal persons, the association of pde7b expression levels with prognostic indexes was analyzed by statistical software. The results showed that the median values of pde7b mRNA expression level in 20 MCL patients and normal controls were 8.7 × 10(-4) (4 × 10(-5) - 6.9 × 10(-3)) and 0.5 × 10(-4)(0.18 × 10(-4) - 1.7 × 10(-4)) respectively (p = 0.001). No association was found between pde7b expression and patients' clinical baseline information (gender and age), as well as certain prognostic factors, leukocyte count, lactate dehydrogenase level, CD38 expression and immunoglobulin heavy-chain variable region mutation status, but pde7b mRNA expression was significantly associated with cytogenetic abnormality, β(2)-microglobulin level and ZAP-70 expression. It is concluded that the pde7b mRNA expression is obviously higher in MCL patients compared with normal controls and significantly correlates with unfavorable cytogenetic characteristics in MCL. The pde7b may be used as a novel prognostic indicator in MCL, and has important clinical significance.
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- 2011
112. [Large granular lymphocytic leukemia].
- Author
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Zhu DX, Xu W, and Li JY
- Subjects
- Humans, Leukemia, Large Granular Lymphocytic
- Published
- 2011
113. [Efficacy of chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab for chronic lymphocytic leukemia].
- Author
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Fang C, Xu W, Xu M, Hong M, Zhu DX, Zhu HY, Wu YJ, Fan L, Qiao C, Zhuang Y, Miao KR, Liu P, and Li JY
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived administration & dosage, Cyclophosphamide administration & dosage, Female, Humans, Male, Middle Aged, Rituximab, Treatment Outcome, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
Objective: To evaluate the efficacy of combination chemoimmunotherapy of fludarabine, cyclophosphamide and rituximab (FCR) in chronic lymphocytic leukemia (CLL)., Methods: Twenty-one patients with CLL were treated with FCR regimen which consisted of fludarabine (25 mg/m(2), days 2 to 4), cyclophosphamide (250 mg/m(2), days 2 to 4) and rituximab (375 mg/m(2), day 1) in a course of 28 days. The minimal residual disease (MRD) was determined by multiparameter flow cytometry. The correlation between the pretreatment characteristics and complete remission (CR) rate was analyzed., Results: Eleven patients (52.4%) achieved CR, 7 (33.3%) achieved partial remission (PR) with a overall response (OR) rate of 85.7%. With a median follow-up time of 19 (7 - 73) months, the overall survival (OS) was 86.0%, and the progression-free survival (PFS) was 72.0%. Pretreatment parameters independently associated with higher CR rates were Binet stage A + B, IgVH mutated and ZAP-70 less than 20%. MRD was less than 1% in 6 patients. The most common toxicities were myelosuppression and gastrointestinal reaction., Conclusion: FCR is an effective regimen for CLL patients.
- Published
- 2011
114. [Clinical and biological features of 8 patients with Richter's syndrome].
- Author
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Zhu HY, Xu W, Miao KR, Hong M, Fang C, Zhu DX, Wu YJ, Qiao C, and Li JY
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- ADP-ribosyl Cyclase 1 metabolism, Aged, Female, Humans, L-Lactate Dehydrogenase blood, Leukemia, Lymphocytic, Chronic, B-Cell blood, Lymphoma, Large B-Cell, Diffuse blood, Male, Middle Aged, Prognosis, Retrospective Studies, Syndrome, ZAP-70 Protein-Tyrosine Kinase metabolism, beta 2-Microglobulin blood, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Lymphoma, Large B-Cell, Diffuse diagnosis
- Abstract
In order to evaluate the clinical, biological features and prognostic factors of Richter's syndrome (RS), 8 RS patients were analyzed retrospectively. The serological test, multiplex parameter flow cytometry, conventional cytogenetic analysis, FISH technique and PCR combined with sequence detection were used to detect the LDH, β(2)-MG, TK1, SF, CA125, ZAP-70, chromosome karyotype, ATM and p53 gene deletion, as well as +12 abnormality and IgVH mutation. The results indicated that 7 out of 8 patients transformed to diffuse large B cell lymphoma (DLBCL) and 1 patient transformed to Hodgkin lymphoma (HL). Among 8 patients, LDH level in 7 patients, β(2)-MG level in 4 patients, SF level in 7 patients, CA-125 level in 4 patients and TK1 level in 1 patient exceeded the normal range. Meanwhile, ZAP-70 and CD38 were expressed positively in 4 and 7 out of 8 patients respectively. Unmutated IgVH was found in 5 patients, and 4 patients had the complex chromosome abnormalities. +12 and p53 deletion was found in 1 patient. 8 patients were divided into two groups (Binet A + B and Binet C), the mean time from diagnosis to progression was 98.5 months in Binet A + B group, compared with 38.3 months in Binet C group, there was significant difference between two groups (p = 0.021). Mean overall survival was 123.8 months and 49.8 months in two groups, respectively (p = 0.049). The mean survival after transformation was 34.5 months in Binet A + B group and 10.3 months in Binet C group. In conclusion, the level of LDH, β(2)-MG and SF are higher in RS patients in Binet C group, and so are the incidence of high expressed ZAP-70 and CD 38, unmutated IgVH. The clinical stage may be the risk and prognostic factors for RS transformation.
- Published
- 2010
115. [Cytogenetics of chronic lymphocytic leukemia stimulated by CpG-oligodeoxynucleotides and IL-2].
- Author
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Wang DM, Xu W, Dong HJ, Fang C, Zhu DX, Cao X, Zhu HY, Zhuang Y, Qiu HR, Yang H, and Li JY
- Subjects
- Adult, Aged, Aged, 80 and over, Cell Line, Tumor drug effects, Chromosome Aberrations, Chromosome Banding, Chromosome Disorders genetics, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Male, Middle Aged, Translocation, Genetic, Cytogenetics, Interleukin-2 pharmacology, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Oligodeoxyribonucleotides pharmacology
- Abstract
This study was to explore the stimulating effect of CpG-oligodeoxynucleotides (CpG-ODN) in combination with interleukin-2 (IL-2) on cytogenetic features of chronic lymphocytic leukemia (CLL) cells. Peripheral blood or bone marrow cells of 115 patients with CLL were cultured for 72 hours with CpG-ODN plus interleukin-2 (IL-2), and routine karyotype analysis was performed with R-banding technique. The metaphase number≥20 was considered as successful stimulation. The results showed that among the 115 CLL patients, successful stimulation rate was 74.8%. The rate of chromosome aberrations was 58.1%. One kind of aberration was detected in 21 cases (24.4%), two kinds of aberration in 6 cases (7.0%), complex aberrant karyotype in 23 cases (26.7%), included highly complex aberrant karyotype in 9 cases (10.5%), respectively. A total of 163 abnormalities of 102 kinds were detected in 86 patients. Number aberrations were 116 (71.2%), and structural abnormalities were 47 (28.8%). The most frequent number aberration was trisomy 12 (14.0%), and structural aberration was 15q+ (5.8%). It is concluded that most of CLL patients have chromosome abnormality, and the number abnormality are more frequent than the structural aberrations. CpG-ODN plus IL-2 can effectively raise the number of cells at metaphase and the detection rate of chromosome aberrations in CLL patients.
- Published
- 2010
116. [Detection of puma mRNA levels by real-time quantitative RT-PCR in chronic lymphocytic leukemia and its clinical significance].
- Author
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Zhu HJ, Xu W, Cao X, Fang C, Zhu DX, Dong HJ, Wang DM, Qiao C, Miao KR, Liu P, and Li JY
- Subjects
- ADP-ribosyl Cyclase 1 metabolism, Aged, Aged, 80 and over, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Male, Middle Aged, Prognosis, Reverse Transcriptase Polymerase Chain Reaction methods, ZAP-70 Protein-Tyrosine Kinase metabolism, Apoptosis Regulatory Proteins genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Proto-Oncogene Proteins genetics, RNA, Messenger genetics
- Abstract
This study was aimed to investigate the expression level of puma (p53 up-regulated modulator of apoptosis) mRNA in chronic lymphocytic leukemia (CLL) and its significance in evaluation of CLL prognosis. The puma mRNA expressions in 100 CLL patients and 11 normal controls were measured by relative quantification RT-PCR with fluorescent dye SYBR Green I, the beta-actin was used as internal reference. The difference of puma expression rate between groups with different prognostic factors was described using the Mann-Whitney U test. The relative quantitative value of puma expression was calculated by means of 2 (-ΔCt). The results indicated that the correlation coefficients of the standard curves in qRT-PCR were ≥ 0.99. The coefficients of variations (CV) within group or between groups were < 5%, and the sensitivity reached 10² copies/microg RNA. The median puma mRNA expression level was 1.038 x 10⁻³ (4.106 x 10⁻⁴ - 2.806 x 10⁻³) in CLL patients, which was 1.220 x 10⁻³ (7.233 x 10⁻⁴ - 1.405 x 10⁻³) in normal controls. There was no difference of puma mRNA expression between CLL patients and normal controls (U = 544.5, p = 0.957). Puma expression was significantly correlated with Binet stages (p < 0.001), expression of CD38 (p = 0.002), ZAP-70 protein (p = 0.012), LDH levels (p = 0.009) and beta₂-MG (p = 0.046). The puma expression level in patients with earlier Binet stage (Binet stage A) was obviously higher than that in patients with later Binet stage (Binet stage B, C). The puma expression levels in patients with positive expression of CD38 and ZAP-70 protein, elevating levels of LDH and beta₂-MG were sharply lower than those in patients without above-mentioned unfavorable factors. The puma expression was also correlated with molecular cytogenetic abnormalities, the puma expression levels in patients with trisomy 12 (p = 0.003) and 14q32 translocation (p = 0.045) detected by FISH were significantly lower than those in patients without above-mentioned molecular cytogenetic abnormalities. It is concluded that the qRT-PCR assay is reliable and sensitive. Puma mRNA expression is significantly correlated with a great deal of prognostic factors, and may be a prognostic marker of CLL.
- Published
- 2010
117. High-dose methylprednisolone can induce remissions in patients with fludarabine-refractory chronic lymphocytic leukaemia.
- Author
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Xu W, Miao KR, Hong M, Zhu DX, Fang C, Dong HJ, Wang DM, Cao X, and Li JY
- Subjects
- Aged, Antineoplastic Agents adverse effects, Disease Progression, Drug Resistance, Neoplasm, Female, Humans, Infusions, Intravenous, Male, Methylprednisolone adverse effects, Middle Aged, Remission Induction methods, Treatment Outcome, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Antineoplastic Agents administration & dosage, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Methylprednisolone administration & dosage
- Abstract
Purpose: To evaluate the clinical efficacy and safety of high-dose methylprednisolone (HDMP) in patients with fludarabine-refractory chronic lymphocytic leukaemia (CLL)., Methods: Twelve patients who were refractory to fludarabine-based treatment were treated with 2-6 cycles of HDMP (1g/m(2) for 5days)., Results: Ten patients (83.3%) responded to treatment and three (25.0%) achieved a complete remission (CR). Two (16.7%) of which had no evidence of minimal residual disease (MRD) after treatment. Patients with leukaemia cells that have high expression of ZAP-70 or CD38, unmutated immunoglobulin heavy chain variable region (IGHV), mutated p53 or adverse cytogenetic features achieved response to treatment at rates that appeared similar to those achieved by patients who did not have such disease characteristics. With a median follow-up of 13 (4-30) months, the median overall survival (OS) and the progression-free survival (PFS) have not been achieved. Treatment with HDMP was well tolerated, notably in the patients having poor myeloid reserve and pretreated cytopaenias., Conclusions: HDMP is an effective non-myelotoxic regimen for the treatment of patients with fludarabine-refractory CLL., (Copyright 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
- Full Text
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118. [Bag3 gene expression in chronic lymphocytic leukemia and its association with patients' prognosis].
- Author
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Chen HY, Liu P, Sun M, Wu LY, Zhu HY, Qiao C, Dong HJ, Zhu DX, Xu W, and Li JY
- Subjects
- ADP-ribosyl Cyclase 1 metabolism, Adaptor Proteins, Signal Transducing metabolism, Adult, Aged, Aged, 80 and over, Apoptosis Regulatory Proteins, Female, Gene Expression, Humans, Male, Middle Aged, Prognosis, ZAP-70 Protein-Tyrosine Kinase metabolism, Adaptor Proteins, Signal Transducing genetics, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell genetics
- Abstract
The aim of this study was to investigate bag3 gene expression in chronic lymphocytic leukemia (CLL)patients and its association with clinical prognosis. A total of 46 blood samples from untreated CLL patients were collected, SYBR Green-based real-time PCR was used to detect the bag3 mRNA expression, and its association with prognostic index was analyzed by statistical software. The results showed that the median values of bag3 level detected by real-time PCR in 46 CLL patients and normal controls were 0.021 (0.0007 - 1.124) and 0.0025 (0.0005 - 0.014) respectively, the former was significantly higher than the latter. The bag3 level in drug-resistant group was obviously higher as compared with the drug-responsive group. No association was found between bag3 expression and patient clinical baseline information (gender and age) as well as established prognostic factors (lymphocyte count, disease stage, IgVH mutation status, cytogenetics analysis and CD38, ZAP 70 expression). It is concluded that the bag3 expression in CLL patients is markedly higher than that in normal controls, while the high bag3 level in CML patients is probably related with drug resistance, but is not related with clinically established prognostic factors.
- Published
- 2010
119. [Detection of miRNA levels in leukemia patients by real-time quantitative PCR].
- Author
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Zhu DX, Miao KR, Zhu YD, Zhu HY, Fan L, Liu P, Xu W, and Li JY
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Humans, Middle Aged, Sensitivity and Specificity, Young Adult, Leukemia genetics, MicroRNAs genetics, Polymerase Chain Reaction methods
- Abstract
This study was purposed to establish a method for detecting miRNA expression by using fluorescent quantitative polymerase chain reaction (RQ-PCR), and to investigate the application value of this method in quantitative detection of miRNA. Total RNA was extracted from the peripheral blood or bone marrow of 82 patients with chronic lymphocytic leukemia (CLL) and 70 patients with acute leukemias (AL). Standard curves of U6 and miRNA were constructed from 10-fold serial dilutions of the cDNA, the quantitative detection was performed by using real-time quantitative PCR with SYBR Green by Roche Light Cycler. U6 RNA was used as the reference, the relative expression levels of miR-15a, miR-16-1, miR-29b, miR-181a and miR-181b in patients with CLL, while miR-128-1, miR-223, let-7b, miR-155 and miR-181a in patients with AL were analyzed by 2((-DeltaDeltaCT)) method. The relative parameters including specificity, linearity range, sensitivity and repeatability were evaluated. The results showed that the RQ-PCR assay could precisely detect the mature miRNA in as few as 10-50 ng of total RNA with the sensitivity of 0.05 ng RNA. Ct values of miRNA and U6 were all within 15 to 30. A good linear relationship (R(2) > 0.980) was obtained from the standard curves, also the efficiency of amplification was above 90%. Only a specific peak was shown on the melting curve diagram. The coefficients of variation (CV) of interrun and intrarun assay was < 4.8% and 6.3% respectively. It is concluded that the RQ-PCR is a sensitive and fast method for the detection of miRNA with its high-flux and low cost, this method will facilitate the research with detection of miRNA.
- Published
- 2010
120. [Prognostic significance of telomere length in patients with chronic lymphocytic leukemia].
- Author
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Hou YQ, Xu W, Miao KR, Qiao C, Zhu HY, Zhu DX, Zhuang Y, Wu YJ, Wang JN, and Li JY
- Subjects
- ADP-ribosyl Cyclase 1 metabolism, Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Male, Middle Aged, Mutation, Prognosis, Telomere chemistry, ZAP-70 Protein-Tyrosine Kinase metabolism, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Telomere genetics, Telomere metabolism
- Abstract
This study was aimed to explore the prognostic significance of telomere length in patients with chronic lymphocytic leukemia (CLL) and to analyze relation of telomere length with Binet stage, IgVH mutation status, CD38, ZAP-70 expression as well as other clinical features. 35 CLL patients who contained 80% or more tumor cells in the peripheral blood or bone marrow samples were selected as objects studied, while 13 healthy donors were served as normal controls. The telomere relative length was detected by using a real-time fluorescent quantitative polymerase chain reaction method (qPCR); the expression of CD38 and ZAP-70 protein were detected by flow cytometry, the IgVH mutation was detected by multiplex PCR. The results showed that the mean telomere relative length in CLL patients and normal controls were 0.384 and 0.443 respectively, but the difference between them was not significant (p > 0.05). The telomere length was significantly correlated with Binet stages and IgVH mutation status. Patients in Binet stage B and C showed significantly shorter telomeres than those in Binet stage A (p = 0.001). Mean telomere relative lengths in patients without IgVH mutation were shorter than those in patients with IgVH mutation (p = 0.015). No relation of telomere length with sex, age, ZAP-70 protein and CD38 were found (p > 0.05). It is concluded that telomere length may have a prognostic significance for CLL patients. Combining telomere length and IgVH mutation status may achieve a better prognostic subclassification for CLL patients.
- Published
- 2010
121. [Correlation of deoxycytidine kinase gene expression with fludarabine resistance in patients with chronic lymphocytic leukemia].
- Author
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Yao L, Xu W, Fan L, Miao KR, Wu YJ, Qiao C, Zhu DX, Zhu HY, Liu P, and Li JY
- Subjects
- Aged, Aged, 80 and over, Case-Control Studies, Female, Gene Expression, Humans, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Male, Middle Aged, Vidarabine pharmacology, Vidarabine therapeutic use, Deoxycytidine Kinase genetics, Drug Resistance, Neoplasm genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Vidarabine analogs & derivatives
- Abstract
The study was purposed to explore the relationship between the expression of deoxycytidine kinase (dCK) gene and fludarabine (Flud) resistance in patients with chronic lymphocytic leukemia (CLL). The real time quantitative polymerase chain reaction (RQ-PCR) technique was used to detect the mRNA expression of dCK gene in the bone marrow or peripheral blood mononuclear cells from 30 CLL patients, the difference of dCK expression levels between CLL patients sensitive to Flud and patients resistant to Flud was analyzed. The results showed that dCK expression level in the Flud-sensitive patients was much higher than that in the Flud-resistant ones (p = 0.001); dCK expression level had no relationship with sex, age, Binet stage, IgVH mutations, CD38, ZAP-70 or p53 gene mutation (p > 0.05). It is concluded that low expression or deficiency of dCK in patients may contribute to resistance against Flud- and the prognostic significance of dCK expression remains to be further studied.
- Published
- 2010
122. [Detection and clinical implication of up-regulated gene 1 mRNA levels with real-time quantitative RT-PCR in chronic lymphocytic leukemia cells.].
- Author
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Gu WJ, Xu W, Miao KR, Zhu DX, Qiao C, and Li JY
- Subjects
- ADP-ribosyl Cyclase 1, Humans, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Leukemia, Lymphocytic, Chronic, B-Cell, ZAP-70 Protein-Tyrosine Kinase
- Abstract
Objectives: To investigate the expression level of chronic lymphocytic leukemia (CLL) up-regulated gene 1 (CLLU1) mRNA in CLL and its prognostic value in CLL., Methods: Real-time quantitative RT-PCR (qRT-PCR) was performed on 41 CLL patients using Taqman probe system. Correlation of CLLU1 expression ratio with other prognostic factors was carried out using Spearman correlation coefficient., Results: The correlation coefficients of the standard curves in qRT-PCR were above 0.99. The coefficients of variation (CV) of interrun assay and intrarun assay were < 5% and the sensitivity reached 10(2) copies/microg RNA. The median CLLU1 mRNA expression level was 0.139 (0 - 5256.912) in 41 CLL patients. CLLU1 expression was significantly associated with Binet stages (P = 0.040) and IgVH mutation status (P = 0.021). CLLU1 expression was also associated with CD(38) expression (P = 0.045)., Conclusion: qRT-PCR assay is reliable and sensitive. CLLU1 mRNA expression significantly correlates with clinical stages, IgVH mutation status and CD(38) expression and might be a prognostic maker of CLL.
- Published
- 2009
123. [Trisomy 8 in chronic lymphocytic leukemia].
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Cao X, Xu W, Liu Q, Zhu DX, Qiao C, Wu YJ, Qiu HX, and Li JY
- Subjects
- Adult, Aged, Aged, 80 and over, Humans, Karyotyping, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Male, Middle Aged, Prognosis, Chromosomes, Human, Pair 8 genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Trisomy
- Abstract
Objective: To investigate the incidence of trisomy 8 in chronic lymphocytic leukemia (CLL) and its significance in prognosis., Methods: A panel of probes and fluorescence in situ hybridization (FISH) were used to detect trisomy 8 in 151 CLL patients combined with chromosome karyotype analysis., Results: There were 2 patients (1.3%) with trisomy 8 in the 151 CLL patients, and the number of trisomy 8 cells was 8% and 10% respectively. The karyotypes were 47,XY,+8[2]/49,XY,+14,+20,+21[2]/ 46,XY[16], and 47,XX,+8[2]/46,XX[18], respectively., Conclusion: Trisomy 8 was rare in CLL, and its significance in prognosis of CLL still remains unknown.
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- 2009
124. Trisomy 8 in two newly diagnosed Chinese patients with chronic lymphocytic leukemia.
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Xu W, Cao X, Liu Q, Fan L, Miao KR, Qiu HR, Zhu DX, Qiu HX, and Li JY
- Subjects
- Adult, Aged, Aged, 80 and over, China, Female, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Asian People genetics, Chromosomes, Human, Pair 8 genetics, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Trisomy diagnosis, Trisomy genetics
- Abstract
Chronic lymphocytic leukemia (CLL) is one of the most common lymphoid malignancies in Western countries, but is infrequent in Asian populations. To verify the incidence of trisomy 8 in Chinese patients with CLL, fluorescence in situ hybridization (FISH) was used in 140 CLL patients after routine chromosome analysis. Only two patients (1.4%) were found with trisomy 8, and the number of trisomy 8 cells was 8 and 10%, respectively. No other aberrations by "panel" probe FISH were found in these two patients. The chromosome karyotypes of two patients were 47,XY,+8[2]/49,XY,+14,+20,+21[2]/46,XY[16] and 47,XX,+8[2]/46,XX[18], respectively. Neither of the patients' present signs of myelodysplastic or myeloproliferative disorder appeared on the bone marrow aspirates and peripheral blood smear. Our study demonstrates that trisomy 8 is rare in CLL, and its role in prognosis of CLL remains unknown.
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- 2009
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125. [Lipoprotein lipase and serum thymidine kinase level in chronic lymphocytic leukemia and their correlations with other prognostic factors].
- Author
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Xu W, Shen QD, Yu H, Qiao C, Wu YJ, Liu Q, Zhu DX, Miao KR, and Li JY
- Subjects
- ADP-ribosyl Cyclase 1 metabolism, Adult, Aged, Aged, 80 and over, Female, Humans, Immunoglobulin Heavy Chains genetics, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Male, Middle Aged, Mutation, ZAP-70 Protein-Tyrosine Kinase metabolism, Leukemia, Lymphocytic, Chronic, B-Cell enzymology, Lipoprotein Lipase blood, Thymidine Kinase blood
- Abstract
Objective: To investigate lipoprotein lipase (LPL) and serum thymidine kinase (TK) levels in chronic lymphocytic leukemia (CLL) and their correlations with other prognostic factors., Methods: LPL expression level in peripheral blood samples of 58 CLL patients was detected by semi-quantitative reverse transcription PCR (RT-PCR). Serum TK1 level in 39 CLL patients was detected by enhanced chemiluminescence (ECL) and TK monoclonal antibody (Anti-TK mAb). IgVH mutation status was detected by multiplex PCR and sequencing of purified PCR products. The expression of ZAP-70 protein and CD38 were determined by flow cytometry . Panel probes and fluorescence in situ hybridization (FISH) were used to detect cytogenetic aberrations., Results: The median LPL expression level in CLL was 0.26 (0 -6.29), while undetectable in normal controls. LPL expression level was significantly correlated with IgVH mutation status, Binet stages, CD38 and cytogenetic aberrations. Patients with unmutated IgVH genes had higher LPL than those with IgVH mutations (P = 0.010). Patients in Binet stage B and C had higher LPL than those in stage A (P = 0.011). LPL level was higher in patients with CD38 > or = 30% (P = 0.001). Higher LPL level was found in patients with unfavorable cytogenetic aberrations (deletion in 17p13 or 11q22) than those with favorable cytogenetics (deletion in 13q as the sole abnormality) (P = 0.002). LPL level was not significantly correlated with sex, age, and ZAP-70 protein (P > 0.05). The level of TK1 was higher in CLL patients than that in normal control (P < 0.05). Patients with higher level of absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), unmutated IgVH genes and ZAP-70 had higher levels of TK1 than those with lower level of ALC, LDH, mutated IgVH genes and ZAP-70 (P = 0.018, P = 0.018, P = 0.030 and P = 0.038, respectively). TK1 level had no correlation with sex, age, Binet stages, CD38, and cytogenetic aberrations (P > 0.05)., Conclusions: LPL expression and serum TK1 levels significantly correlate with other CLL prognostic factors and could be predictive markers for IgVH mutation status. LPL and serum TK1 might be applied to the assessment of prognosis in CLL patients.
- Published
- 2009
126. Bottom-up synthesis of porous coordination frameworks: apical substitution of a pentanuclear tetrahedral precursor.
- Author
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Wang XL, Qin C, Wu SX, Shao KZ, Lan YQ, Wang S, Zhu DX, Su ZM, and Wang EB
- Abstract
Top down goes bottom up: A family of microporous interpenetrating diamond frameworks can be constructed from a pentanuclear tetrahedral complex with nitrate groups at the apical positions as an inorganic precursor. A "bottom-up" methodology was used for substitution of the nitrate groups by linear ditopic carboxylate ligands (see picture). The Langmuir surface area of the resulting frameworks is higher than that of classical zeolites.
- Published
- 2009
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127. [Application of SELDI-TOF-MS in detection of liver metastasis from colorectal cancer].
- Author
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Shi YJ, Zhao Y, Xu JM, Lai YH, Yu XZ, Zhong YS, Wei Y, Ren L, Zhu DX, Liu YK, Niu WX, and Qin XY
- Subjects
- Aged, Biomarkers, Tumor blood, Blood Proteins analysis, Colorectal Neoplasms blood, Female, Humans, Liver Neoplasms blood, Male, Middle Aged, Neoplasm Proteins blood, Peptide Mapping, Sensitivity and Specificity, Colorectal Neoplasms pathology, Liver Neoplasms diagnosis, Liver Neoplasms secondary, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
- Abstract
Objective: To establish a serum protein fingerprint model for prediction of liver metastasis from colorectal cancer by SELDI-TOF-MS analysis, and to determine the differentiatial proteins associated with the metastatic liver cancers., Methods: Data were collected from the Department of General Surgery in Zhongshan Hospital. A group of patients with colorectal cancer (CRC) without liver metastasis (n = 36) and another group with liver metastasis (n = 36) were included in this study. Serum samples were collected from peripheral venous blood before operation. Special serum protein or peptide fingerprint was determined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The obtained data were analyzed by Biomarker Wizard software to screen the serum protein markers discriminating colorectal cancer patients with and without liver metastasis. A serum protein fingerprint model was established. This model was blindly verified in of CRC patients with and 44 cases without liver metastasis., Results: Comparing the characteristic proteins in those two groups of patients, 10 specific protein peaks were identified with statistical significance (P < 0.05). According to m/z growing from small to large, they were: 2398, 2814, 4084, 4289, 4465, 6422, 6619, 11 482, 11 649 and 13 714. The predictive model had a sensitivity of 91.7% and a specificity of 97.2%. The validation showed a sensitivity of 75.0% and a specificity of 81.8%., Conclusion: A predictive model based on differentiatial serum protein fingerprint with high sensitivity and specificity has been successfully established. It should be a very useful tool in detection and diagnosis of liver metastasis in colorectal cancer patients.
- Published
- 2008
128. [Gene atm and chronic lymphocytic leukemia - review].
- Author
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Zhu DX, Xu W, and Li JY
- Subjects
- Ataxia Telangiectasia Mutated Proteins, Gene Deletion, Humans, Mutation, Cell Cycle Proteins genetics, DNA-Binding Proteins genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Protein Serine-Threonine Kinases genetics, Tumor Suppressor Proteins genetics
- Abstract
The ataxia telangiectasia mutated gene (atm) is a tumor-suppressing gene, locates in the human chromosome 11q22-23. This gene mainly participates in recognition and repairment of DNA damage and plays a critical role in signal transduction pathway induced by double strand breaks (DSB). In chronic lymphocytic leukemia (CLL) there is high frequency of loss of heterozygosity (LOH) and mutation of atm gene, which related to pathopoiesis and progression of CLL. This article reviewed the progress of recent studies on the characteristics and mechanism of atm gene, as well as its role in the pathogenesis of CLL.
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- 2008
129. [An experimental study on targeting suicide gene therapy for lung cancer with HSV-TK driven by hTERT promoter].
- Author
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Wang YP, Tang XJ, Zhou QH, Che GW, Chen XH, and Zhu DX
- Subjects
- Adenocarcinoma genetics, Adenocarcinoma pathology, Adenocarcinoma therapy, Animals, Apoptosis genetics, Drug Delivery Systems, Ganciclovir pharmacology, Genetic Therapy, Lung Neoplasms genetics, Lung Neoplasms therapy, Mice, Mice, Nude, Promoter Regions, Genetic genetics, Tumor Cells, Cultured, Genes, Transgenic, Suicide genetics, Herpesvirus 1, Human genetics, Lung Neoplasms pathology, Telomerase genetics, Thymidine Kinase genetics
- Abstract
Objective: To study the approach of targeting expression of suicide gene HSV-TK driven by human telomerase catalytic subunit (hTERT) promoter in lung cancer cells, and to investigate inhibitory effect of HSV-TK/GCV driven by hTERT promoter on proliferation of lung cancer cell line A549 in vitro and in vivo., Methods: (1) Recombinant expression vectors of HSV-TK driven by hTERT promoter and SV40 promoter (pGL3-hTp-TK and pGL3-SV40-TK) were transfected into telomerase-positive human lung adenocarcinoma cell A549 and telomerase-negative human embryonic lung fibroblast cell MRC-5. The mRNA expression of TK gene was detected with RT-PCR method; (2) With the treatment of GCV, the proliferation of above transfected cells was investigated by MTT assay; Influence of GCV on apoptosis and cell cycle of these cells was evaluated with flow cytometry; (3) After the subcutaneously transplantation of A549 cells into nude mice, intra-tumor injection of plasmid-liposome as well as intra-peritoneal injection of GCV were performed to stUdy anti-tumor effects of pGL3-hTp-TK/GCV and pGL3-SV40-TK/GCV in vivo., Results: (1) Enzyme digestion and PCR suggested that recombinant plasmids of pGL3-hTp-TK and pGL3-SV40-TK were successfully constructed; TK mRNA expression was detected in both A549 and MRC-5 cells transfected with pGL3-SV40-TK, also in A549 transfected with pGL3-hTp-TK, but not in MRC-5 transfected with pGL3-hTp-TK; (2) GCV showed significant inhibition effect on proliferation of A549 and MRC-5 transfected with pGL3-SV40-TK in vitro, also on that of A549 transfected with pGL3-hTp-TK, but not of MRC-5 transfected with pGL3-hTp-TK; With the treatment of GCV, apoptosis index (AI) of A549 cells transfected with pGL3-SV40-TK and pGL3-hTp-TK (21.58% and 23.19% respectively) increased significantly, compared with that of A549 transfected with pGL3-hTp and blank control; GCV enhanced the effects on AI in MRC-5 transfected with pGL3-SV40-TK (9.35%), but not with pGL3-hTp-TK (0.88%); (3) Inhibition ratio of pGL3-SV40-TK/GCV and pGL3-hTp-TK/GCV to transplanted tumor of A549 in nude mice (46.7% and 40.5% respectively) were significantly higher than that of negative control groups (9.7%, 14.3%, 7.0% and 8.0% respectively)., Conclusion: TK gene driven by hTERT promoter could express selectively in lung cancer cell. Lung cancer cell could be specifically inhibited by HSV-TK/GCV driven by hTERT promoter in vitro and in vivo.
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- 2008
130. [Establish predictive model of colorectal cancer by using surface enhanced laser desorption/ionization-time of flight-mass spectrometry].
- Author
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Lai YH, Xu JM, Yu XZ, Zhong YS, Wei Y, Ren L, Zhu DX, Liu YK, Niu WX, and Qin XY
- Subjects
- Biomarkers, Tumor blood, Colorectal Neoplasms blood, Female, Humans, Male, Middle Aged, Peptide Mapping, Proteomics methods, Sensitivity and Specificity, Blood Proteins analysis, Colorectal Neoplasms diagnosis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Abstract
Objective: To establish serum proteome fingerprinting predictive models and search for proteins associated with colorectal cancer., Methods: Thirty-six randomly selected colorectal cancer patients and 36 cases with hernia or gall bladder diseases scheduled for elective operation were enrolled as cancer group and control group respectively. Peripheral venous blood samples were collected before the operations. Special serum protein or peptide fingerprint was investigated by using surface enhanced laser desorption/ ionization-time of flight-mass spectrometry (SELDI-TOF-MS) measurement after blood sample had been treated with weak cation exchange protein chip (CM10) for each case. The obtained data were analyzed by Biomarker Wizard software to screen serum proteome tumor markers and set up diagnosis predictive model for colorectal cancer. Blind validation of the model with 44 healthy controls and 88 colorectal cancer patients were carried out by using Biomarker Patterns Software., Results: In comparing colorectal cancer group with control group, 5 specific protein peaks (P < 0.05) were found. The predictive model had a sensitivity of 100% and a specificity of 97.2%. A sensitivity of 71.6% and a specificity of 72.7% was got with the blind validation. The specific protein peaks with a mass-to-charge ratio (m/z) of 8908 and 13,707 showed in all the results and it showed their strong relationship with colorectal cancer., Conclusions: The predictive models built by the differences of serum proteome fingerprint could be a very useful diagnostic tool in colorectal cancer. Proteins with m/z of 8908 and 13,707 would possibly be the tumor markers of colorectal cancer.
- Published
- 2008
131. Involvement of transcription factor activator protein-2alpha in doxazosin-induced HeLa cell apoptosis.
- Author
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Gan L, Zhu DX, Yang LP, Liu RS, Yan F, and Zhang J
- Subjects
- Bisbenzimidazole metabolism, Caspase 3 genetics, Caspase 3 metabolism, Cell Death drug effects, Dose-Response Relationship, Drug, Fluorescent Dyes metabolism, Gene Expression Regulation, Neoplastic, HeLa Cells, Humans, Time Factors, Transcription Factor AP-2 genetics, Adrenergic alpha-Antagonists pharmacology, Apoptosis drug effects, Doxazosin pharmacology, Transcription Factor AP-2 metabolism
- Abstract
Aim: To investigate the pro-apoptotic effects of alpha1-adrenergic inhibitor doxazosin in HeLa cells and the potential involvement of transcription factor activator protein-2alpha (AP-2alpha) in doxazosin-induced apoptosis., Methods: The HeLa cells were exposed to various concentrations of doxazosin for 16 h. Apoptosis was detected using a DNA fragmentation assay, Hoechst 33258 staining, and flow cytometric analysis. The expression of AP-2alpha and caspase-3 was detected by relative quantitative RT-PCR and Western blot assays, respectively. After the respective transfections of the HeLa cells with AP-2alpha overexpressing constructs and an antisense oligonucleotide against AP-2alpha, apoptosis was assessed by flow cytometric analysis, and the expression of AP-2alpha and caspase-3 was detected by relative quantitative RT-PCR and Western blot assays. The colorimetric assay was performed to detect the caspase-3 activity., Results: Treatment with various concentrations of doxazosin for 16 h increased the apoptotic rate and total cell death rate of the HeLa cells in a dose-dependent manner and upregulated the expression of AP-2alpha and caspase-3 in a dose-dependent manner. A dose-dependent increase was observed in the caspase-3 activity. Overexpressing AP-2alpha led to the increased rate of doxazosin-induced apoptosis and the total cell death, whereas doxazosin-induced apoptosis and the total cell death in HeLa cells decreased by antisense AP-2alpha. Furthermore, overexpressing AP-2alpha increased the expression and activity of caspase-3, whereas antisense AP-2alpha in part abolished the increased effects of doxazosin on caspase-3 expression and activity., Conclusion: Doxazosin induces apoptosis in HeLa cells in a dose-dependent manner, and transcription factor AP-2alpha is functionally involved in doxazosin-induced HeLa cell apoptosis.
- Published
- 2008
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132. Derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide as new antibacterial agents: synthesis and bioactivity.
- Author
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Yu WY, Yang LX, Xie JS, Zhou L, Jiang XY, Zhu DX, Muramatsu M, and Wang MW
- Subjects
- Bacteria enzymology, Enzyme Inhibitors pharmacology, Gram-Negative Bacteria drug effects, Gram-Positive Bacteria drug effects, Metalloendopeptidases antagonists & inhibitors, Microbial Sensitivity Tests, Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents pharmacology, Bacteria drug effects, Benzamides chemical synthesis, Benzamides pharmacology, Guanidines chemical synthesis, Guanidines pharmacology
- Abstract
Aim: The aim of the present study was to design, synthesize, and evaluate novel antibacterial agents, derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide., Methods: A total of 44 derivatives of aryl-4-guanidin-omethylbenzoate (series A) and N-aryl-4-guanidinomethylbenzamide (series B) were synthesized and their antibacterial activities were assessed in vitro against a variety of Gram-positive and Gram-negative bacteria by an agar dilution method., Results: Twelve compounds showed potent bactericidal effects against a panel of Gram-positive germs, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), vancomycin-intermediate Staphylococcus aureus (VISA), and methicillin-resistant coagulase-negative staphylococci (MRCNS), with minimum inhibitory concentrations (MIC) ranging between 0.5 and 8 microg/mL, which were comparable to the MIC values of several marketed antibiotics. They exhibited weak or no activity on the Gram-negative bacteria tested. In addition, these compounds displayed high inhibitory activities towards oligopeptidase B of bacterial origin., Conclusion: In comparison with the previously reported MIC values of several known antibiotics, the derivatives of aryl-4-guanidinomethylbenzoate and N-aryl-4-guanidinomethylbenzamide showed comparable in vitro bactericidal activities against VRE and VISA as linezolid. Their growth inhibitory effects on MRSA were similar to vancomycin, but were less potent than linezolid and vancomycin against MRCNS. This class of compounds may have the potential to be developed into narrow spectrum antibacterial agents against certain drug-resistant strains of bacteria.
- Published
- 2008
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133. A novel two-dimensional zinc(II) coordination polymer with 6-mercaptonicotinic acid.
- Author
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Wang Y, Zhu DX, Su ZM, Shao KZ, and Zhao YH
- Abstract
The novel title Zn(II) coordination polymer, poly[bis(mu-6-thioxo-1,6-dihydropyridine-3-carboxylato-kappa(2)S:O)zinc(II)], [Zn(C6H4NO2S)2]n, consists of two crystallographically independent zinc centers and two 6-mercaptonicotinate (Hmna-) ligands. Each Zn(II) atom is four-coordinated and lies at the center of a distorted tetrahedral ZnS2O2 coordination polyhedron, bridged by four Hmna- ligands to form a two-dimensional (4,4)-network. Each Hmna- ion acts as a bridging bidentate ligand, coordinating to two Zn(II) atoms through the S atom and a carboxyl O atom. The metal centers reside on twofold rotation axes. The coordination mode of the S atoms and N-H...O hydrogen-bonding interactions between the protonated N atoms and the uncoordinated carboxyl O atoms give the extended structure a wavelike form.
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- 2008
- Full Text
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134. [Application of the protocol of enhanced recovery after surgery in colorectal surgery].
- Author
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Xu JM, Zhong YS, Zhu DX, Ren L, Wei Y, Xue ZG, Jin L, Niu WX, Qin XY, and Wu ZG
- Subjects
- Adult, Aged, Aged, 80 and over, Clinical Protocols, Colorectal Neoplasms surgery, Combined Modality Therapy, Female, Humans, Male, Middle Aged, Perioperative Care, Young Adult, Colorectal Neoplasms rehabilitation, Colorectal Surgery rehabilitation
- Abstract
Objective: To evaluate enhanced recovery after surgery(ERAS) protocol in colorectal surgery., Methods: From september 2006 to February 2007, 74 patients with colorectal cancer were randomly assigned to ERAS group and control group. The stress index, nutrition and metabolism index, intraoperative index and postoperative index were evaluated., Results: Six patients were excluded, 3 in ERAS group (2 cases received hepatectomy concomitantly and 1 case received partial ileum resection), and 3 in control group (1 case received hepatectomy and 1 case received colorectomy concomitantly, another presented asthma paroxysm). So there were 34 cases in ERAS group and 34 cases in control, with no statistical differences in sex, age, BMI index and operation types. Deviation of HOMA-IR index of ERAS was lower than the control (P>0.05), the same as plasma cortisol at the 1st day after operation (P<0.05), but plasma glucagons in the operation of ERAS group was higher than that of control (P<0.05). Plasma glucose 1st day after operation of ERAS group was lower than control (P<0.05), while plasma triglyceride intraoperation, at 1st day, 2nd day after operation of ERAS was higher than control (P<0.05). Nitrogen negative balance of ERAS group was higher than control at 2nd day after surgery, but is lower intraoperation and at 6th day after operation (P<0.05). The time of exhaust gas and stool, time to eat fluidity and semi-fluidity, out-of-bed time and exercise time per-day, residual time and complication rate in ERAS group were better than those of control (P<0.05). Post-operative expenses of ERAS was lower than that of control (P<0.05)., Conclusion: ERAS can decrease surgical stress, increase functional recovery and reduce complication rate.
- Published
- 2007
135. [Therapeutic effects of hepatic resection in liver metastasis of colorectal cancer].
- Author
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Xu JM, Zhong YS, Fan J, Zhou J, Qin LX, Niu WX, Wei Y, Ren L, Lai YH, Zhu DX, Qin XY, and Wu ZH
- Subjects
- Colorectal Neoplasms pathology, Follow-Up Studies, Humans, Liver Neoplasms secondary, Neoplasm Recurrence, Local, Survival Analysis, Treatment Outcome, Colorectal Neoplasms surgery, Hepatectomy methods, Liver Neoplasms surgery
- Abstract
Objectives: To evaluate therapeutic effects of hepatic resection in liver metastasis of colorectal cancer (LMCC)., Methods: The clinical data of 133 cases of LMCC received hepatic resection from January 1, 2000 to December 31, 2005 in Zhongshan Hospital were analyzed retrospectively. The relationship between hepatic resection and survival rate was also concerned., Results: One hundred and thirty-three cases received curative hepatic resection in all 470 LMCC cases, of which 30 cases from synchronous liver metastasis (SLM) group (totaled 196 cases) and 103 cases from metachronous liver metastasis (MLM) group (totaled 274 cases). Mortality rate during operation was 3.3% in SLM and 1.9% in MLM (P < 0.05). All patients were followed-up till June 31, 2006, the 1, 3, 5 year survival rates and median survival time of SLM were similar to those of MLM, but its recurrence rate was higher (36.7% vs 20.4%, P = 0.030). The 1, 3, 5 year survival rate in the 49 patients who were operable but received non-operation treatment were significantly lower than those in operated patients (P = 0.003). In 30 SLM cases, 22 received I stage resection of their primary and liver metastasis tumor and 8 received liver metastasis resection after the primary surgery (II stage operation), 1, 2, 3 year survival and the median survival time were similar in the two groups. With COX multivariate analysis, incision margin > or = 1 cm (P = 0.036) and reoperation after recurrence (P = 0.041) were protective survival factors, and post-operation recurrence (P = 0.023) was survival risk factor., Conclusions: Curative hepatic resection is the first choice of therapy in liver metastasis of colorectal cancer and it can improve survival.
- Published
- 2007
136. [A study on selective killing effect of Hsv-tk/GCV driven by human telomerase catalytic subunit promoter on human lung cancer cell A549].
- Author
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Tang XJ, Wang YP, Zhou QH, Che GW, Chen XH, and Zhu DX
- Subjects
- Antiviral Agents pharmacology, Apoptosis drug effects, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Flow Cytometry, Gene Expression Regulation, Neoplastic drug effects, Genetic Therapy methods, Humans, Lung Neoplasms genetics, Lung Neoplasms pathology, Lung Neoplasms therapy, Reverse Transcriptase Polymerase Chain Reaction, Simplexvirus enzymology, Simplexvirus genetics, Transfection, Viral Proteins genetics, Ganciclovir pharmacology, Promoter Regions, Genetic genetics, Telomerase genetics, Thymidine Kinase genetics
- Abstract
Objective: To study selective killing effect of herpes simplex virus-thymidine kinase/ganciclovir (Hsv-tk/GCV) driven by human telomerase catalytic subunit (hTERT) promoter on lung cancer cell line A549 in vitro., Methods: (1) Expression plasmids of Hsv-tk gene driven by hTERT promoter and sv40 promoter respectively (pGL3-hTp-tk and pGL3-sv40-tk) were transfected into telomerase-positive human lung adenocarcinoma cell line A549 and telomerase-negative fetal lung fibroblast cell line MRC-5. Reverse transcription-PCR was performed to detect expression of tk gene in above transfected cell lines; (2) Inhibition effect on proliferation of above transfected cell lines treated with GCV was investigated with MTT method; (3) Influence of GCV on apoptosis and cell cycle of above transfected cell lines was investigated with flow cytometry., Results: (1) tk mRNA expression was detected in both A549 and MRC-5 transfected with pGL3-sv40-tk, also in A549 transfected with pGL3-hTp-tk, but not in pGL3-hTp-tk transfected MRC-5; (2) GCV showed significant inhibition effects on proliferation of pGL3-sv40-tk transfected A549 and MRC-5 in vitro, also on that of pGL3-hTp-tk transfected A549, but not on that of pGL3-hTp-tk transfected MRC-5; (3) Treated with GCV, apoptosis index (AI) of pGL3-sv40-tk transfected A549 and MRC-5 as well as pGL3-hTp-tk transfected A549 (21.58%, 9.35% and 23.19% respectively) increased significantly, compared with A549, MRC-5 transfected with pGL3-hTp (0.78% and 0.55% respectively) and A549, MRC-5 without plasmid transfection as blank control (2.17% and 0.60% respectively); GCV had no influence on AI of pGL3-hTp-tk transfected MRC-5 (0.88%)., Conclusion: tk gene driven by hTERT promoter could express selectively in lung cancer cell A549. Hsv-tk/GCV driven by hTERT promoter could selectively inhibit proliferation of lung cancer cell.
- Published
- 2007
137. [Clinical and gene research of X-linked lymphoproliferative disease in a Chinese family].
- Author
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Zhu DX, Du J, Lan HK, Yu L, and Feng ZC
- Subjects
- Antigens, CD analysis, Antigens, Differentiation, Myelomonocytic analysis, Base Sequence, China, DNA Mutational Analysis, Family Health, Female, Genetic Predisposition to Disease, Humans, Immunohistochemistry, Lymphoproliferative Disorders diagnosis, Lymphoproliferative Disorders metabolism, Male, Molecular Sequence Data, Pedigree, Polymerase Chain Reaction, Polymorphism, Single-Stranded Conformational, Retrospective Studies, S100 Proteins analysis, Sequence Homology, Nucleic Acid, Signaling Lymphocytic Activation Molecule Associated Protein, src Homology Domains genetics, Intracellular Signaling Peptides and Proteins genetics, Lymphoproliferative Disorders genetics, Mutation
- Abstract
Objective: To verify the pathogenesis in Chinese and to investigate the genetic rule of X-linked lymphoproliferative disease (XLP) therein., Methods: The case history of a proband of XLP, male, aged 1 year and 5 months, who died 40 days after hospitalization, was reviewed. Fourteen his family members were interviewed for the development history, anamnesis, and underwent physical examination. Single-strand conformation polymorphism (SSCP-PCR) and sequencing were used to detect the SH2D1A mutation among the elder sister, younger brother, and parents of the poband., Results: The proband and his elder brother suffered with virus-associated hemophagocytic syndrome and both died in 40 days after the disease coming on in the last two years in succession. The second exon of SH2D1A of the younger brother of the proband showed a nonsense mutation in SH2D1A gene: the C-T nucleotide substitution at nucleotide position 462 result in a stop codon and pre-mature termination of protein synthesis. The mother was proved as mutation heterozygote of the C and T nucleotide on the same site. The other members of the family were proved normal. The clinical manifestation of the younger brother of the proband was Langerhans cell histiocytosis., Conclusion: Langerhans cell histiocytosis may be a new clinical phenotype of XLP. The gene of SH2D1A is responsible for the disease of XLP in Chinese too. The newly developed method of SH2D1A mutation analysis may be suitable in the diagnosis of XLP in Chinese.
- Published
- 2007
138. [Study on cloning of hTERT promoter and its targeting transcriptional activities in telomerase-positive lung cancer cells].
- Author
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Wang YP, Tang XJ, Chen XH, Che GW, Zhu DX, Sun ZL, and Zhou QH
- Subjects
- Base Sequence, Cloning, Molecular, Humans, Molecular Sequence Data, Promoter Regions, Genetic genetics, RNA, Messenger biosynthesis, RNA, Messenger genetics, Telomerase biosynthesis, Telomerase genetics, Transcription, Genetic, Transcriptional Activation, Lung Neoplasms enzymology, Lung Neoplasms pathology, Telomerase metabolism
- Abstract
Objective: To clone sequence of hTERT promoter and study its transcriptional activity and its relationship with hTERT mRNA expression and telomerase activity in various kinds of human lung cancer cells and normal cells, and to investigate the targeting transcriptional activity of hTERT promoter in tumor cells., Methods: About 1.1 kb promoter of the 5'flanking sequence of the hTERT was amplified from genomic DNA isolated from 293 cells by polymerase chain reaction (PCR). After being confirmed by DNA sequencing, the hTERT promoter was inserted into luciferase reporter vectors (pGL3-basic) to reconstruct a recombinant named pGL3-hTERTp. Then pGL3-hTERTp was transiently transfected into lung cancer cell A549, SPC-A-1, LTEPa-2, NCI-H446, YTMLC-9, GLC-82, 95D, A2, and normal cell of MRC-5. The transcriptional activities of hTERT promoter in various cells were determined by measuring the luciferase activities. hTERT mRNA expression and telomerase activity were determined by RT-PCR and TRAP ELISA., Results: Eelectrophoresis demonstrated that the hTERT promoter amplified by PCR was about 1.1 kb long, and DNA sequencing showed a sequence the same as the hTERT promoter registered in GenBank being 1084 bp in length. The recombinant of plasmid pGL3-hTERTp was confirmed by double digestion and PCR methods with correct results. hTERT mRNA and telomerase activity were expressed in all of eight lung cancer cell lines at varied levels, but not expressed in normal cell. Transient transfection assay and Luciferase assay also revealed that hTERT promoter had different transcriptional activities in various lung cancer cells, but no transcriptional activity was shown in normal cells., Conclusion: 1084 bp hTERT promoter cloned has specific transcriptional activities in various telomerase-positive lung cancer cells, and it may act as control element in tumor-targeting gene therapy.
- Published
- 2006
139. High-level expression and purification of Escherichia coli oligopeptidase B.
- Author
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Yan JB, Wang GQ, Du P, Zhu DX, Wang MW, and Jiang XY
- Subjects
- Cyclohexanecarboxylic Acids chemistry, Escherichia coli chemistry, Escherichia coli Proteins antagonists & inhibitors, Escherichia coli Proteins chemistry, Hot Temperature, Inclusion Bodies enzymology, Recombinant Proteins antagonists & inhibitors, Recombinant Proteins chemistry, Serine Endopeptidases chemistry, Substrate Specificity, Escherichia coli enzymology, Escherichia coli Proteins biosynthesis, Escherichia coli Proteins isolation & purification, Recombinant Proteins biosynthesis, Recombinant Proteins isolation & purification, Serine Endopeptidases biosynthesis, Serine Endopeptidases isolation & purification
- Abstract
Oligopeptidase B (OpdB) of Escherichia coli, previously called protease II, has a trypsin-like specificity, cleaving peptides at lysine and arginine residues and belongs to the prolyl oligopeptidase family of new serine peptidases. In this study, we report the fusion expression of E. coli oligopeptidase B with an N-terminal histidine tag using pET28a as the expression vector. Although most of the recombinant OpdB was produced as inclusion bodies, the solubility of the recombinant protease increased significantly when the expression temperature shifted from 37 to 30 degrees C. Recombinant OpdB (approximately 10 mg) could be purified from the soluble fraction of the crude extract of 1L log-phase E. coli culture containing 1.5 g wet bacterial cells. The purified OpdB has a molecular weight of approximately 80 kDa and a specific activity of 4.8 x 10(4) U/mg. OpdB could also be purified from the inclusion bodies with a lower yield. The recombinant enzyme was very stable under 40 degrees C. By comparison of the substrate specificity of the purified OpdB with that of OpdA, another trypsin-like protease in E. coli, we found that Boc-Glu-Lys-Lys-MCA is a specific substrate for E. coli OpdB. We also found that compared to OpdA, OpdB is much more sensitive to GMCHA-OPh(t)Bu, a synthetic trypsin inhibitor that can retard the growth of E. coli.
- Published
- 2006
- Full Text
- View/download PDF
140. Bactericidal and morphological effects of NE-2001, a novel synthetic agent directed against Helicobacter pylori.
- Author
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Dai G, Cheng N, Dong L, Muramatsu M, Xiao S, Wang MW, and Zhu DX
- Subjects
- Adult, Clarithromycin pharmacology, Drug Resistance, Bacterial, Guanidine pharmacology, Helicobacter Infections drug therapy, Helicobacter Infections microbiology, Helicobacter pylori enzymology, Helicobacter pylori growth & development, Humans, Metronidazole pharmacology, Microbial Sensitivity Tests, Microscopy, Electron, Transmission, Middle Aged, Urease metabolism, Anti-Bacterial Agents pharmacology, Biphenyl Compounds pharmacology, Guanidine analogs & derivatives, Helicobacter pylori drug effects, Helicobacter pylori ultrastructure
- Abstract
The antibacterial activities of NE-2001 were tested against 24 clinical isolates of Helicobacter pylori and compared with those of amoxicillin, clarithromycin, metronidazole, and furazolidone. The MIC(50) and MIC(90) of this synthetic compound on the isolates were 8 and 16 mug/ml, respectively. This action was highly selective against Helicobacter pylori; there was a >4-fold difference between the concentration of NE-2001 required to inhibit the growth of Helicobacter pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of Helicobacter pylori (ATCC43504) to NE-2001 at the MIC (4 mug/ml), or at a greater concentration, resulted in an extensive loss of viability. The phenomenon was also observed at pH levels between 3.0 and 7.0. When two clinical Helicobacter pylori strains were successively cultured at subinhibitory concentrations of NE-2001, no significant changes in the bactericidal effects were found. The morphological alterations of Helicobacter pylori cells (ATCC43504), exposed to NE-2001 at various concentrations for 6 h, were observed using transmission electron microcopy. The bacterium displayed features such as swelling, vacuole-like structures in the cytoplasm, and cell destruction following exposure to NE-2001. The efficacy of NE-2001 was maintained when evaluated in eight clinical isolates resistant to metronidazole and five isolates resistant to both metronidazole and clarithromycin (MIC ranging between 4 and 16 mug/ml). The above-described results suggest that NE-2001 may have the potential to be developed as a candidate agent for the treatment of Helicobacter pylori infection.
- Published
- 2005
- Full Text
- View/download PDF
141. The leucyl aminopeptidase from Helicobacter pylori is an allosteric enzyme.
- Author
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Dong L, Cheng N, Wang MW, Zhang J, Shu C, and Zhu DX
- Subjects
- Allosteric Regulation, Amino Acid Sequence, Anilides metabolism, Cations, Divalent pharmacology, Chelating Agents pharmacology, Cloning, Molecular, Coenzymes, Enzyme Activators pharmacology, Enzyme Inhibitors pharmacology, Enzyme Stability, Helicobacter pylori drug effects, Helicobacter pylori growth & development, Hydrogen-Ion Concentration, Kinetics, Leucine analogs & derivatives, Leucine pharmacology, Leucyl Aminopeptidase antagonists & inhibitors, Leucyl Aminopeptidase genetics, Leucyl Aminopeptidase isolation & purification, Metals pharmacology, Molecular Sequence Data, Molecular Weight, Open Reading Frames, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Temperature, Helicobacter pylori enzymology, Leucyl Aminopeptidase metabolism
- Abstract
This study describes the cloning, genetic analysis and biochemical characterization of a leucyl aminopeptidase (LAP) from Helicobacter pylori. A gene encoding LAP was cloned from H. pylori and the expressed 55 kDa protein displayed homology to aminopeptidases from Gram-negative bacteria, plants and mammals. This LAP demonstrated amidolytic activity against L-leucine-p-nitroanilide. Optimal activity was observed at pH 8.0 and 45 degrees C, with V(max) of 232 mumol min(-1) (mg protein)(-1) and S(0.5) of 0.65 mM. The data suggest that LAP could be allosteric (n(H)=2.27), with regulatory homohexamers, and its activity was inhibited by ion chelators and enhanced by divalent manganese, cobalt and nickel cations. Bestatin inhibited both LAP activity (IC(50)=49.9 nM) and H. pylori growth in vitro. The results point to the potential use of LAP as a drug target to develop novel anti-H. pylori agents.
- Published
- 2005
- Full Text
- View/download PDF
142. A specific anti-Helicobacter pylori agent NE2001: synthesis and its effect on the growth of H. pylori.
- Author
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Cheng N, Xie JS, Zhang MY, Shu C, and Zhu DX
- Subjects
- Anti-Bacterial Agents pharmacology, Biphenyl Compounds pharmacology, Guanidine analogs & derivatives, Helicobacter pylori growth & development, Microbial Sensitivity Tests, Structure-Activity Relationship, Time Factors, Anti-Bacterial Agents chemical synthesis, Biphenyl Compounds chemical synthesis, Guanidine chemical synthesis, Helicobacter pylori drug effects
- Abstract
The synthesis and anti-Helicobacter pylori activity of a novel agent NE2001, 4-(4-methylbenzyl)-4'-[guanidinomethylbenzoyloxy] biphenyl-4-carboxylate hydrochloride, are described. NE2001 had a specific inhibitory effect on the growth of H. pylori preceded by the suppression DNA synthesis in the cell. The effects of NE2001 on RNA and protein syntheses in H. pylori were also examined.
- Published
- 2003
- Full Text
- View/download PDF
143. CDNA Cloning, Heterologous Expression and Characterization of Anti-Neuroexcitation Peptides (ANEPS) of Scorpion Buthus martensii Karsch.
- Author
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Zhang JH, Hua ZC, and Zhu DX
- Published
- 2001
- Full Text
- View/download PDF
144. Expression of anti-neuroexcitation peptide (ANEP) of scorpion Buthus martensii Karsch in Escherichia coli.
- Author
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Zhang JH, Hua ZC, Xu Z, Zheng WJ, and Zhu DX
- Subjects
- Animals, DNA, Complementary metabolism, Male, Mice, Plasmids genetics, Polymerase Chain Reaction, RNA analysis, Recombinant Fusion Proteins isolation & purification, Recombinant Fusion Proteins pharmacology, Scorpion Venoms pharmacology, Scorpions genetics, Seizures chemically induced, Seizures prevention & control, Semicarbazides, Transfection, Escherichia coli genetics, Gene Expression, Scorpion Venoms genetics, Scorpions chemistry
- Abstract
According to the cDNA sequence of anti-neuroexcitation peptide of scorpion Buthus martensii Karsch, the putative mature anti-neuroexcitation peptide (ANEP) encoding DNA fragment was obtained by a PCR method, then was cloned into expression plasmid pET28a, fused with His tag at its 3' end. When expressed in E. coli BL21 (DE3), the expression of recombinant ANEP was 15% of total cellular proteins, while most recombinant ANEP products existed in the form of insoluble inclusion bodies. Coexpression of molecular chaperones or protein disulfide isomerase could not improve its solubility. The recombinant ANEP in the cell lysate was purified to homogeneity by metal chelating affinity chromatography and Superdex 30 chromatography. In bioassay with convulsive mice model induced by thiosemicarbazide, recombinant ANEP could apparently delay the convulsion seizure of model animals by 18% and showed anti-neuroexcitatory activity.
- Published
- 2001
- Full Text
- View/download PDF
145. Effects of rhM-CSF expressed in silkworm on cytokine productions and membrane molecule expressions of human monocytes.
- Author
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Ji XH, Sun LH, Qin JC, Yao K, Ding RN, Li HD, and Zhu DX
- Subjects
- Adult, Animals, Bombyx metabolism, Humans, Interleukin-6 metabolism, Interleukin-8 metabolism, Macrophage Colony-Stimulating Factor biosynthesis, Recombinant Proteins biosynthesis, Recombinant Proteins pharmacology, Leukocytes, Mononuclear metabolism, Macrophage Colony-Stimulating Factor pharmacology, Receptors, IgG biosynthesis, Tumor Necrosis Factor-alpha metabolism
- Abstract
Aim: To study the effects of recombinant human macrophage colony-stimulating factor (rhM-CSF) expressed in silkworm on cytokine productions and membrane molecule expressions of monocytes., Methods: The rhM-CSF was added to the human peripheral blood monocyte cultures and 3 d later, the culture supernatants and cells were collected, respectively. TNF-alpha, IL-6, IL-8, and IFN-alpha levels in the supernatants were detected by biological activity test or ELISA and expressions of CD11b, CD16, HLA I, and HLA II on the cellular surface were examined by the method of alkaline phosphatase anti-alkaline phosphatase complex (APAAP)., Results: The rhM-CSF promoted TNF-alpha, IL-6, and IL-8 inductions of monocytes and increased the percentages of CD11b, CD16, HLA I, and HLA II molecule expression on monocytes., Conclusion: The rhM-CSF plays a role in monocyte function up-regulation and has a certain practical value in immunological therapy.
- Published
- 2000
146. Separation and Characterization of Oligodeoxynucleotides by FPLC.
- Author
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Tang HW, Jin YX, and Zhu DX
- Abstract
The purity of the antisense drugs synthesized by DNA synthesizer should be determined effectively. At pH 12,the oligodeoxynucleotides (ODNs) ranged from 19 bases to 21 bases can be separated successfully on the anion exchange column MONO-Q by elution with a NaCl gradient. The experiments proved that the fast protein liquid chromatography (FPLC) was a useful tool for isolation and identification of the antisense drugs.
- Published
- 1999
147. ATP-sensitive potassium channels regulate in vivo dopamine release in rat striatum.
- Author
-
Zhu DX, Sullivan JP, and Brioni JD
- Subjects
- Animals, Consciousness, Cromakalim pharmacology, Dextroamphetamine pharmacology, Diazoxide pharmacology, Dopamine Uptake Inhibitors pharmacology, Glyburide pharmacology, Hypoglycemic Agents pharmacology, Injections, Subcutaneous, Male, Microdialysis, Movement physiology, Neostriatum drug effects, Potassium Channels drug effects, Rats, Rats, Sprague-Dawley, Vasodilator Agents pharmacology, Adenosine Triphosphate physiology, Dopamine metabolism, Neostriatum metabolism, Potassium Channels physiology
- Abstract
ATP-sensitive K+ channels (K(ATP)) are distributed in a variety of tissues including smooth muscle, cardiac and skeletal muscle, pancreatic beta-cells and neurons. Since K(ATP) channels are present in the nigrostriatal dopamine (DA) pathway, the effect of potassium-channel modulators on the release of DA in the striatum of conscious, freely-moving rats was investigated. The extracellular concentration of DA was significantly decreased by the K(ATP)-channel opener (-)-cromakalim but not by diazoxide. (-)-Cromakalim was effective at 100 and 1000 microM concentrations, and the maximum decrease was 54% below baseline. d-Amphetamine significantly increased extracellular DA levels at the doses of 0.75 and 1.5 mg/kg, s.c. with a 770% maximum increase. (-)-Cromakalim had no effect on d-amphetamine-induced DA release, while glyburide, a K(ATP) blocker, significantly potentiated the effects of a low dose of d-amphetamine. These data indicate that K+ channels present in the nigrostriatal dopaminergic terminals modulate basal release as well as evoked release of DA.
- Published
- 1999
- Full Text
- View/download PDF
148. Drug allergy: identification and characterization of IgE-reactivities to aspirin and related compounds.
- Author
-
Zhu DX, Zhao JL, Mo L, and Li HL
- Subjects
- Adolescent, Adult, Aged, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Anti-Inflammatory Agents, Non-Steroidal immunology, Child, Cross Reactions, Female, Humans, Immunoglobulin E chemistry, Male, Middle Aged, Pyrazoles adverse effects, Pyrazoles immunology, Salicylates adverse effects, Salicylates immunology, Aspirin adverse effects, Aspirin immunology, Drug Hypersensitivity immunology, Immunoglobulin E blood, Pyrazolones
- Abstract
Twenty-seven patients with aspirin (ASA) sensitivity were studied. 14 patients had naso-ocular-bronchial reactions after taking ASA while others had cutaneous and gastrointestinal reactions. The oral challenges with salicylic acid (SA), O-methylsalicylic acid (OMSA), ASA, and the determination of IgE antibodies specific to salicyloyl, O-methylsalicyloyl, acetylsalicyloyl using correspondent disks by RAST, RAST inhibition and RAST crossinhibition assays were performed. The findings suggest that OMSA seems to be the main offender responsible for cutaneous and gastrointestinal reactions, whereas ASA is responsible for naso-ocular-bronchial reactions. The clinical crossreactions between ASA and ASA-like drugs (nonsteroidal anti-inflammatory drugs and pyrazolone drugs) are probably due to "inborn errors of metabolism". The results indicate that genetic factors, mast-cell heterogeneity, and the interindividual variability in drug metabolism, combined with immunological background should be considered as underlying mechanisms.
- Published
- 1997
149. Construction of Urokinase Mutant Glu154-mtcu-PA and Characterization of Its Properties.
- Author
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Peng GH, Ma Z, Xue YM, Chen YH, and Zhu DX
- Abstract
The recombinant single chain urokinase-type plasminogen activator (rscu-PA) and a mutant constructed by in vitro site-specific mutagenesis of Argl54 in rscu-PA to Glul54 (Glul54-mscu-PA) were both expressed in E. coli. The expressed products were both purified to homogeneity by in vitro denaturation and renaturation, followed by Zn(2+) selective precipitation and immuno-affinity chromatography. The plasmin sensitivity assay indicated that the activation of this single chain Glul54-mscu-PA by plasmin was essentially identical to that of rscu-PA. After activation by plasmin, the kinetic constants against synthetic substrate S2444 of the resulted two chain form of Glul54-mscu-PA (Glul54-mtcu-PA) and that of rscu-PA (rtcu-PA) were 87 &mgr;M and 80 &mgr;M, respectively, which indicated that the catalytic active site of the Glul54-mtcu-PA was not changed by the mutation. Whereas, both (125)I-fibrin plasma-clot lysis and fibrinogenolysis in plasma showed that the Glul54-mtcu-PA possessed a better affinity and selectivity for fibrin than rtcu-PA, even better than rscu-PA.
- Published
- 1997
150. Enhancement of in vitro renaturation of recombinant human pro-urokinase by ampicillin.
- Author
-
Hua ZC, Dong C, and Zhu DX
- Subjects
- Arginine, Humans, Lysine, Protein Denaturation drug effects, Recombinant Proteins chemistry, Ampicillin pharmacology, Enzyme Precursors chemistry, Urokinase-Type Plasminogen Activator chemistry
- Abstract
Ampicillin was used in in vitro renaturation process of recombinant human prourokinase and it can obviously improve the yield of the renaturation, although not as well as arginine. When ampicillin was used together with arginine or lysine, it decreased the yield of the renaturation comparing with the yield when arginine or lysine used alone.
- Published
- 1996
- Full Text
- View/download PDF
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