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Sheng-Qi Wang

Publications and source records attributed to Sheng-Qi Wang.

At least 37 records · Page 2Linked to original sources
PubMed2005

HBVPathDB: a database of HBV infection-related molecular interaction network.

AIM: To describe molecules or genes interaction between hepatitis B viruses (HBV) and host, for understanding how virus' and host's genes and molecules are networked to form a biological system and for perceiving mechanism of HBV infection. METHODS: The knowledge of HBV infection-related reactions was organized into various kinds of pathways with carefully drawn graphs in HBVPathDB. Pathway information is stored with relational database management system (DBMS), which is currently the most efficient way to manage large amounts of data and query is implemented with powerful Structured Query Language (SQL). The search engine is written using Personal Home Page (PHP) with SQL embedded and web retrieval interface is developed for searching with Hypertext Markup Language (HTML). RESULTS: We present the first version of HBVPathDB, which is a HBV infection-related molecular interaction network database composed of 306 pathways with 1 050 molecules involved. With carefully drawn graphs, pathway information stored in HBVPathDB can be browsed in an intuitive way. We develop an easy-to-use interface for flexible accesses to the details of database. Convenient software is implemented to query and browse the pathway information of HBVPathDB. Four search page layout options-category search, gene search, description search, unitized search-are supported by the search engine of the database. The database is freely available at http://www.bio-inf.net/HBVPathDB/HBV/. CONCLUSION: The conventional perspective HBVPathDB have already contained a considerable amount of pathway information with HBV infection related, which is suitable for in-depth analysis of molecular interaction network of virus and host. HBVPathDB integrates pathway data-sets with convenient software for query, browsing, visualization, that provides users more opportunity to identify regulatory key molecules as potential drug targets and to explore the possible mechanism of HBV infection based on gene expression datasets.

Databases, Genetic↗
PubMed2005

Screening of specific antigens for SARS clinical diagnosis using a protein microarray.

In this study several SARS-CoV structural proteins and fragments were expressed in E. coli as GST or TRX fusion proteins. They were fabricated on a microarray and tested with sera from SARS patients. Antigenic screening indicated that recombinant GST-N2 fusion protein, the carboxy-terminus 213aa-423aa of N protein, was strongest positive and weakest non-specific compared with others. An indirect antibody ELISA method was developed and clinical positive and negative sera for their antibodies against GST-N2 fusion protein were assayed. 311 out of the 442 sera from clinical SARS inpatients, as well as 229 out of 302 sera from convalescent patients gave positive reactivities; positive rates were 70.4% and 75.8% respectively. Sera from a total of 2726 non-SARS patients and healthy individuals were tested and the false positive rate was only 0.07%. When the sensitivity control sample was diluted 1 : 64, it yielded OD values above the cutoff value. Reported data showed that this was a relatively high degree of sensitivity and specificity for SARS-CoV antibody testing. The data indicate that GST-N2 fusion protein, which was screened by protein microarray, may be a valuable diagnostic antigen for the development of serological assays for SARS. In addition, protein microarray assay presents a higher positive rate and sensitivity (86.1% and 1 : 200) compared with the traditional ELISA screening method, and could provide a rapid, parallel and high-throughput antigen screening platform.

Antibodies, Viral↗
PubMed2005

Protein chip for detection of different HCV antibodies: preparation, quality control, and clinical evaluation.

INTRODUCTION: As a contagious disease caused by hepatitis C virus (HCV) hepatitis C is a serious threat to human health. Therefore, the detection and verification of HCV infection is very important in the treatment of hepatitis C. This study investigated the preparation, quality control, and clinical evaluation of a protein chip capable of simultaneously detecting different HCV antibodies. The aim was to establish a convenient method for the detection of HCV. METHOD: To prepare the protein chip, six antigens including five recombinant HCV antigens (chimeric, core, NS3, NS4, and NS5) and interleukin (IL)-1 were arrayed onto aldehyde-coated slides and blocked using 10% calf serum in phosphate buffered saline. After dilution with sample solution, the serum sample was added to a reaction well on the protein chip. After incubation for 30 minutes at 37 degrees C, fluorescence Cy3-labeled rabbit antihuman IgG was added and incubated again for 30 minutes at 37 degrees C, and then scanned. Positive or negative controls were established from serum samples with or without HCV infection. Clinical evaluation was done by detecting 490 serum samples using the protein chips and ELISA reagents, with 150 of the 490 serum samples confirmed by recombinant immunoblot assay (RIBA). RESULTS: The protein chip for detection of five HCV antibodies was successfully prepared. Fifteen positive controls and 15 negative controls were established as standard samples for quality control. The quality control-passed protein chip was tested again using the standard of the National Institute for the Control of Pharmaceutical and Biological Products (NICPBP), and met the quality control criteria prescribed by the NICPBP. In the clinical evaluation with 490 samples, the coincidence rates between the protein-chip assay and ELISA were 97.4% for positive and 100% for negative results. Five inconsistent samples that were positive in ELISA, but non-positive (four samples) or negative (one) in the protein-chip assay, were confirmed by RIBA (gold standard) to be four non-positive and one negative. The results of 150 samples showed the coincidence rates between protein chip and RIBA were 98.15% for positive and 96.88% for single-segment positive. CONCLUSION: The protein-chip assay has higher sensitivity and specificity than ELISA and has a high coincidence rate with RIBA. The protein chip, characterized by its easy operation and low economic cost, will be very useful for in vitro detection of HCV antibodies.

Hepacivirus↗
PubMed2005

Fabrication and optimization of the multiplex PCR-based oligonucleotide microarray for detection of Neisseria gonorrhoeae, Chlamydia trachomatis and Ureaplasma urealyticum.

To detect and identify the pathogens responsible for sexually transmitted diseases (STDs) at the early stage of infection and with a high throughput, a new microarray with a bifunctional probe modification was prepared using Neisseria gonorrhoeae, Chlamydia trachomatis and Ureaplasma urealyticum as a model system. During the fabrication of the microarray, an asymmetric fluorescently labeled multiplex PCR was introduced. The fabrication optimization proved that the best hybridization results would be obtained by spotting N. gonorrhoeae probe at a position near the side of the fluorescently labeled reverse primer within its target gene and spotting each probe at a concentration of 50 microM onto the aldehyde-derived glass slides using spotting solution S1 and using hybridization solution H2 for hybridization. The probes designed by our laboratory could specifically discriminate the pathogens of N. gonorrhoeae, C. trachomatis and U. urealyticum in the presence of the internal control on the microarray simultaneously and separately. By incorporating the key features of DNA microarray with those of multiplex PCR, the microarray provides a fast high throughput platform for multiple infections and multiple samples to be detected and identified simultaneously for STD clinics. It also provides a new platform for other diseases and gene mutations to be detected and identified at a high throughput.

Chlamydia trachomatis↗
PubMed2005

Identification of differentially expressed genes contributing to radioresistance in lung cancer cells using microarray analysis.

Radiotherapy has played a key role in the control of tumor growth in many cancer patients. It is usually difficult to determine what fraction of the tumor cell population is radioresistant after a course of radiotherapy. The response of tumor cells to radiation is believed to be accompanied by complex changes in the gene expression pattern. It may be possible to use these to sensitize radioresistant tumor cells and improve radiocurability. Based on the biological effects of ionizing radiation, in the present study, we developed one oligonucleotide microarray to analyze the expression of 143 genes in cells of two lung cancer cell lines with different radiosensitivities. Compared to NCI-H446 cells, expression of 18 genes significantly increased the basal levels in the radioresistant A549 cells, in which eight genes were up-regulated and 10 genes were down-regulated. In A549 cells irradiated with 5 Gy, 22 (19 up-regulated and three down-regulated) and 26 (eight up-regulated and 18 down-regulated) differentially expressed genes were found 6 and 24 h after irradiation, respectively. In NCI-H446 cells, the expression of 17 (nine up-regulated and eight down-regulated) and 18 (six up-regulated and 12 down-regulated) genes was altered 6 and 24 h after irradiation, respectively. RT-PCR was performed, and we found that MDM2, BCL2, PKCZ and PIM2 expression levels were increased in A549 cells and decreased in NCI-H446 cells after irradiation. Genes involved in DNA repair, such as XRCC5, ERCC5, ERCC1, RAD9A, ERCC4 and the gene encoding DNA-PK, were found to be increased to a higher level in A549 cells than in NCI-H446 cells. Antisense suppression of MDM2 resulted in increased radiosensitivity of A549 cells. Taken together, these results demonstrate the possibility that a group of genes involved in DNA repair, regulation of the cell cycle, cell proliferation and apoptosis is responsible for the different radioresistance of these two lung cancer cells. This list of genes may be useful in attempts to sensitize the radioresistant lung cancer cells.

Cell Line, Tumor↗
PubMed2005

Clinical evaluation of oligonucleotide microarrays for the detection of HBV mutants associated with lamivudine resistance.

OBJECTIVES: Long-term lamivudine administration in hepatitis B virus (HBV)-infected patients induces the emergence of HBV mutants with lamivudine resistance. The aim of the present study was to evaluate the clinical application of an oligonucleotide microarray in detecting HBV mutants associated with lamivudine resistance. METHODS: 947 HBV DNA-positive sera from: 388 patients receiving lamivudine treatment, 559 chronic hepatitis B patients not receiving lamivudine treatment, and 359 from HBV DNA-negative controls, were assayed for HBV mutations using the oligonucleotide microarray. Furthermore, follow-up studies were performed using 255 clinical samples from 51 patients treated with lamivudine at various periods. The results were compared with sequencing and real-time polymerase chain reaction (PCR). RESULTS: The HBV DNA polymerase Tyr-Met-Asp-Asp motif (YMDD) mutation was detected in all 388 samples containing lamivudine-resistant mutations identified by microarray. For the codons rt180, rt204 and rt207, the agreements between the microarray and sequencing data are 96.6, 98.5 and 100%, respectively. Two previously unreported mutants were also found in those samples. In the 947 samples collected from different patients, which were detected positive for HBV DNA by quantitative PCR, all but three weak-positive samples were positive by the microarray, demonstrating an agreement of 99.7%. In all the positive samples, mutations could be detected in the relevant loci of HBV DNA polymerase with lamivudine resistance. All of the 359 HBsAg-negative samples were shown to be negative for HBV DNA using the microarray method. Follow-up detection of the clinical samples from 51 patients treated with lamivudine demonstrated that the microarray method was able to detect mutations in mixed viruses that were infecting prior to sequencing. CONCLUSION: The oligonucleotide microarray can be conveniently utilized to detect mutant HBV in clinical serum samples.

Antiviral Agents↗
PubMed2005

[The effect of Siwu Tang on EPO and G-CSF gene expression in bone marrow of irradiated blood deficiency mice].

OBJECTIVE: To observe the blood enriching function of Siwu Tang and its effect on Epo and G-CSF gene expressions in bone marrow of blood deficiency mice, and thus provide the basis for understanding the molecular mechanism of blood enriching function of Siwu Tang. METHOD: The animal model of blood deficiency were established in the mice by using 3.5 Gy60Co gamma-ray. Peripheral blood cells were analyzed and CFU-GM, BFU-E, CFU-E and CFU-mix were counted in bone marrow colony cultured. Both Epo and G-CSF gene expressions in bone marrow were measured with RT-PCR. RESULT: Siwu Tang significantly increased the number of peripheral blood cells and the amount of CFU-GM, BFU-E, CFU-E and CFU-mix in bone marrow and enhanced Epo and G-CSF gene expression in bone marrow in the mice with blood deficiency. CONCLUSION: The promotion of Epo and G-CSF gene expressions in bone marrow may be one of the mechanisms underlying the blood enriching function of Siwu Tang decoction.

Animals↗
PubMed2005

[Study on PBPs genes of penicillin-resistant Streptococcus pneumonia in Zhejiang province].

To elucidate alternations in gene/amino acid sequence of penicillin-binding proteins (PBPs) 1A, 2B, 2X from clinical isolates of penicillin-resistant Streptococcus pneumonia (PRSP) in Zhejiang Province, 26 strains of Streptococcus pneumonia were collected from November 2001 to January 2004. The antibiotics susceptibility of these strains was detected. PCR amplification and direct sequencing of PBP1A, 2B, 2X genes were performed. The sequence variations of PBP genes of the PRSPs in this region were studied by sequence BLAST analysis. It was shown that the main alternations of PBP1A were the four consecutive amino acid substitutions (Thr574Ala, Ser575Thr, Gln576Gly, Phe577Tyr) following the conservative motif KTG and the amino acid substitution Thr371Ser in the conservative motif STMK. The main alternation of PBP2B was Thr451Ala following the conservative motif SSN, and the main alternation of PBP2X was Thr338Ala in conservative motif STMK. The above mutation sites and drug resistant level were consistent to the data reported previously. Neither new gene mutation specific to these strains nor certain amino acid substitutions related to penicillin resistance reported was identified in the genes.

Amino Acid Sequence↗
PubMed2004

[Telomerase antisense inhibition and chemotherapeutic combination treatments for the proliferation of endometrial cancer in vitro and in vivo].

OBJECTIVE: To investigate the antitumor effects of telomerase antisense oligodeoxynucleotide (AODN). METHODS: Human endometrial cancer cells of HEC-1A line were cultured at the concentrations of 0.8 and 1.6 micromol/L respectively and transfected with human telomerase AODN, as telomerase inhibitors, twice. 24, 48, 72, 96, and 128 hours after the first transfection MTT method was used to detect the absorbance at the wave length of 490 nm so as to determine the cell survival rate. HEC-1A cells were collected after transfection of 0.05, 0.1, 0.2, 0.4, and 0.8 micromol/L of AODN and the total DNA was extracted. Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of hTERT mRNA. Telomeric repeat amplification protocol (TRAP)-ELISA was used to detect the activity of telomerase. HEC-1A cells were injected subcutaneously into the axillary fossae of Balb/c nude mice, Four days after when tumors were touchable the nude mice were divided into 5 groups to undergo intratumoral injection of high-dosage ADON (25 mg/kg, 1/d), low-dosage ADON (12.5 mg/kg, 1/d), cis-dichlorodiamine plastinum (DDP, cisplatin, 12.5 mg/kg, 1/d), AODN + DDP (AODN 12.5 mg/kg and DDP 5 microg/kg, 1/d alternatively), and normal saline respectively. The tumor size, tumor weight, and tumor relative volume were measured and calculated. Twenty-one days after the mice were killed and their organs were examined. RESULTS: AODN effectively and dose-dependently inhibited the growth of HEC-1A cells. There was a plateau of inhibition. The inhibition rate rose further 4 days after transfection. Five days after transfection the proliferation inhibition rate of AODN of the concentrations of 0.4, 0.8, and 1.6 microm were 46.35%, 65.22%, and 79.45% respectively. The relative inhibition rate of hTERT mRNA expression increased dose-independently along with the increase of concentration of transfected AODN. The tumor inhibition rate of nude mice were 34.20%, 89.21%, 79.82%, and 72.41% in the low-dosage AODN group, high-dosage AODN group, DDP group, and AODN + DDP group respectively. However, AODN began to show significant inhibitory effect 8 days after administration. The tumor inhibition rate of the AODN+DDP group was 72.4%, similar to those of the high dosage AODN and DDP groups (both P < 0.05). The telomerase activity in tumor of the AODN (25 mg/kg) group was 509 +/- 377, decreased by 87.23% in comparison with that of the control group (64 +/- 23, P < 0.05). CONCLUSION: Antisesne oligonucleotide of hTERT effectively inhibits the abnormal activation of telomerase, thus the growth of endometrial cancer cells. Telomerase inhibitor may be a new strategy for chemotherapy or chemoprevention in endometrial cancer.

Animals↗
PubMed2004

Polymerase synthesis and potential interference of a small-interfering RNA targeting hPim-2.

AIM: To synthesize three small-interference RNAs (siRNAs) by T7 RNA polymerase-catalyzed reaction, and to investigate their efficacy on modulating the expression of serine/threonine kinase Pim-2 in human colon cancer cell line. METHODS: siRNA I, II and III were synthesized by T7 RNA polymerase-directed in vitro transcription, then transfected into human colon cancer cells SW-480. After incubation for 6 h at 37 degrees, 100 mL/L FBS in RPMI 1640 was substituted in each well. After the transfection was repeated twice to three times in each kind of siRNA, hPim-2 mRNA and protein expression were measured by RT-PCR and Western blotting, respectively. RESULTS: Compared to the control group, after transfected for 48 h with hPim-2 siRNA I, II and III, the relative inhibition rates of hPim-2 mRNA expression in colon cancer cells were 65.4% (P<0.05), 46.2% (P<0.05) and 56.1% (P<0.05), respectively. The protein level of hPim-2 was decreased at 72 h compared to the untransfected cells. The relative inhibition percentages of hPim-2 protein by siRNA I, II, III were 61.6% (P<0.05), 45.8% (P<0.05) and 55.6% (P<0.05), respectively. CONCLUSION: The in vitro transcribed siRNAs can be useful for silencing oncogene hPim-2 expression specifically and efficiently. This may open a new path toward the use of siRNAs as a gene-specific therapeutic tool.

Cell Line, Tumor↗
PubMed2004

Preparation and property analysis of a hepatocyte targeting pH-sensitive liposome.

AIM: To develop a hepatocyte targeting pH-sensitive liposome for drug delivery based on active targeting technology mediated by asialoglycoprotein receptors. METHODS: Four types of targeting molecules with galactose residue were synthesized and mixed with pH-sensitive lipids DC-chol/DOPE to prepare liposome with integrated property of hepatocyte specificity and pH sensitivity. Liposome 18-gal was selected with the best transfection activity through cellular uptake experiment. Property analysis was made through experiments of competitive inhibition of receptors, red blood cell hemolysis, in vitro cytotoxicity test by MTS assay and mediation of inhibitory effects of antisense phosphorothioate ODN on gene expression, etc. RESULTS: Liposome 18-gal had the desired properties of hepatocyte specificity, pH sensitivity, low cytotoxicity, and high transfection efficiency. CONCLUSION: Liposome 18-gal can be further developed as a potential hepatocyte- targeting delivery system.

Cell Line, Tumor↗
PubMed2004

[Identification of acute leukemia-specific genes from leukemia recipient/sibling donor pairs by distinguishing study with oligonucleotide microarrays].

To explore differentially expressed genes in leukemia gene expression profile and identify main related genes in acute leukemia, gene expression profiles were analyzed in bone marrow/leucopheresis peripheral blood stem cells samples from 9 acute leukemia patients and their sibling donors with the use of oligonucleotide microarrays. 163 reported leukemia-related genes were involved in the study. The oligonucleotide primers were designed, synthesized and spotted on the chemical-material-coated-glass plates in array. The total RNAs were isolated from nine patients' bone marrow or leucopheresis peripheral blood cells and from nine their sibling donors peripheral blood stem cells treated by G-CSF, then collected by CS-3000 cell selection machine, and were reversely transcribed to cDNAs with the incorporations of fluorescent dUTP. The mixed probes were then hybridized to the oligonucleotide microarray. The results showed that in four patient/donor pairs with B-ALL, 5 up-regulated (RIZ, STK-1, T-cell leukemia/lymphoma 1A, Cbp/p300, Op18) and 1 down-regulated genes (hematopoietic proteoglycan core protein) were identified; In five patient/donor pairs with AML-M(4) and AML-M(5), 6 up-regulated (STAT5B, ligand p62 for the Lck SH2, CST3, LTC4S, myeloid leukemia factor 2 and epb72) and 1 down-regulated genes (CCR5) were identified. In conclusion, on the basis of distinguishing study of specific genetic related recipient/sibling donor pairs, screening leukemia-related genes with oligonucleotide microarrays, a set of 13 up-regulated or down-regulated genes among 163 leukemia-related genes has been identified. The result has further confirmed that above genes play critical role in the molecular mechanism of acute leukemia.

Blood Donors↗
PubMed2004

[The anti-cancer effect of siRNA targeting human telomerase reverse transcriptase in SMMC-7721 cells].

OBJECTIVE: To explore the anti-cancer effects of siRNAs targeting hTERT in SMMC-7721 cells. METHODS: Two siRNAs targeting hTERT mRNA were designed and synthesized by T7 transcription system in vitro. MMT, RT-PCR and Western blot were applied to evaluate effects on inhibiting cell growth, hTERT mRNA and protein expression in SMMC-7721 cells. RESULTS: siRNAs decreased cell proliferation in a dose-dependent manner. At a concentration of 100 nmol/L, siRNAs exhibited obvious effects on inhibiting hTERT mRNA and protein expression in SMMC-7721 cells. CONCLUSION: siRNAs targeting hTERT have significant inhibitory effects on hTERT gene expression in SMMC-7721 cells. siRNA has the possibility to become a new anti-cancer agent

DNA-Binding Proteins↗
PubMed2004

[Identification bcr-abl fusion gene in leukemia cells with oligonucleotide microarray].

To explore the application value of bcr-abl fusion gene deterction microarray in diagnosis, typing, choosing of treatment variant and prognosis judgment, probe for fusion gene detection was designed, oligonucleotide microarray was prepared; total RNA was extracted, reverse-transcripted and labeled by fluorescence, then cDNA was hybridized with microarray in order to detect bcr-abl fusion gene in leukemia cells. The results showed that better reaction conditions were gained by exploration of hybridizotion temperature and elution conditions, bcr-abl fusion gene in leukemia cells was detected by prepared miccroarray. In conclusion, oligonucleotide microarray is effective in detecting the fusion gene and has some unique advantages and certain clinical application value, but has some deficiency too. If microarray can be improved further, it could be used widely in the field of hematology.

Fusion Proteins, bcr-abl↗
PubMed2003

[Identification of differentially expressed genes of acute hypoxia-treated HepG2 cells and hypoxia-acclimatized HepG2 cells].

To provide necessary information for further understanding of molecular mechanism of hypoxia acclimatization, the differentially expressed genes of HepG2 cells exposed to normoxia, acute hypoxia-treated cells which were exposed to 1% oxygen for 48 h, and hypoxia-acclimatized HepG2 cells which were cultured for 6 circles of alternate low oxygen (1% oxygen for 24 h) and normal oxygen (21% oxygen for 24 h), were identified respectively by combining the suppression subtractive hybridization (SSH) and cDNA microarray. Thirty-seven genes were expressed differentially in cells exposed to 1% oxygen for 48 h compared with those in cells exposed to normoxia. The expression of all these 37 genes was down-regulated, including the genes participating in cell cycle, cell response to stimulus, and cell signal transduction, and cell cytoskeleton formation, the genes associated with transcription and cell metabolism, 4 expressed sequence tags (ESTs), and 12 genes of which the functions are not known. There is a novel gene sequence, which has not been found in existing databases. There were only 6 genes differentially expressed in the hypoxia-acclimatized cells compared with cells exposed to normoxia, including two mitochondrion genes, metalloprotease-1 gene, ferritin gene, thymosin beta-4 and TPT1 genes. The expressions of mitochondrion ND4, ferritin, thymosin beta-4 and TPT1 were up-regulated, while the expressions of mitochondrion ND1 gene and metalloproease-1 gene were down-regulated. Cell tolerance to hypoxia increased after the cells were hypoxia-acclimatized. The different gene expression patterns of the acute hypoxia-treated cells and the hypoxia-acclimatized cells may be related to the increased tolerance of the cells to hypoxia.

Adaptation, Physiological↗
PubMed2003

Rapid detection of the known SNPs of CYP2C9 using oligonucleotide microarray.

AIM: Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of a large number of clinically important drugs. Individuals with mutant enzymes may risk serious side effects under routine therapy with certain drugs metabolized by CYP2C9. In order to facilitate the detection of the known SNPs of CYP2C9, an allele-specific oligonucleotide (ASO) based microarray was made. METHODS: An oligonucleotide microarray was made to facilitate the SNP (single nucleotide polymorphism) screening and was applied for the detection of CYP2C9 polymorphism in 62 high blood pressure (HBP) patients who received Irbesartan for treatment. Part of the genotyping results was confirmed by direct sequencing. And the relation between CYP2C9 polymorphism and therapeutic outcome of Irbesartan was statistically analyzed. RESULTS: Heterozygous alleles of CYP2C9*1/*3 were found in 7 out of 62 subjects. No mutant alleles of CYP2C9*2, *4 and *5 and no homozygous mutant alleles were detected. The 7 heterozygous CYP2C9*1/*3 and 13 random wild type DNA samples were subjected to direct sequencing with purified PCR products and same genotyping results were obtained with the 20 DNA samples. There was no significant difference in the odds of effectiveness of Irbesartan between the wild type (normal) group and CYP2C9*1/*3 (mutant) group (P>0.05). CONCLUSION: The oligonucleotide microarray made in this study is a reliable assay for detecting the CYP2C9 known alleles and the heterozygous CYP2C9*1/*3 has no significant effects on the therapeutic outcome of Irbesartan.

Alleles↗
PubMed2003

Antitumor mechanism of antisense cantide targeting human telomerase reverse transcriptase.

AIM: To investigate the anti-tumor mechanism of antisense oligodeoxynucleotide cantide against hTERT. METHODS: Tumor cells were cultured overnight and grown to 50-60 % confluence. HepG2 and SMMC-7721 were treated with cantide mixed with lipofectin, or lipofectin alone. After inducted for 6 h at 37 degrees, 10 % FCS in DMEM was replaced in each well. After the treatment repeated twice to three times in each concentration of cantide, hTERT mRNA and protein expression were measured by RT-PCR and Western blot analysis, respectively. Telomerase activity was determined by TRAP-ELISA assay. CPP32- and ICE-like activity was also investigated using CasPACE assay system at 48 h after cantide treatment, and apoptosis was evaluated using the DeadEnd assay at 24, 48 and 72 h after cantide treatment. RESULTS: Compared to the control cells, the cells treated with cantide showed a dose-dependent decrease in hTERT mRNA levels at 24 h and in protein levels at 48 h respectively. The telomerase activity was decreased as the concentration of cantide increased at 48 h. At the concentration of 800 nM, the telomerase activity in the treated HepG2 and SMMC-7721 cells was only 17.1 % (P<0.01) and 20.3 % (P<0.01) of that in untreated cells. The levels of CPP32-like protease activity in HepG2 and SMMC-7721 increased by 2.8- and 3.0-fold (P<0.05) at 48 h, and the levels of ICE-like protease activity also increased by 2.6- and 3.2-fold (P<0.05) respectively. The percentage of apoptosis in HepG2 and SMMC-7721 cells treated with 800 nM cantide at 72 h was 63 % and 52 % (P<0.01), respectively. By contrast, 8 % and 9 % of the cells were apoptosis after 72 h treatment with lipofectin alone. CONCLUSION: Cantide can decrease telomerase activity by inhibiting the expression of hTERT gene and has a rapid anti-tumor effect through inducing the Caspase-dependent apoptosis. The rapid inhibitory effect of cantide on tumor growth demonstrates its feasibility in cancer treatment.

Antineoplastic Agents↗