AIM: To investigate the effects of antisense human telomerase RNA (hTR)on the biologic behavior of human gastric cancer cell line: MKN-45 by gene transfection and its potential role in the gene therapy of gastric canc...AIM: To investigate the effects of antisense human telomerase RNA (hTR)on the biologic behavior of human gastric cancer cell line: MKN-45 by gene transfection and its potential role in the gene therapy of gastric cancer. METHODS: The hTR cDNA fragment was cloned from MKN-45 through RT-PCR and subcloned into eukaryotic expression vector (pEF6/V5-His-TOPO) in cis-direction or trans-direction by DNA recombinant methods. The constructed sense, antisense and empty vectors were transfected into MKN-45 cell lines separately by lipofectin-mediated DNA transfection technology. After drug selection, the expression of antisense hTR gene in stable transfectants and normal MKN-45 cells was detected by RT-PCR, the telomerase activity by TRAP, the apoptotic features by PI and Hoechst 33258 staining, the cell cycle distribution by flow cytometry and the population doubling time by cell counting. Comparison among the stable transfectants and normal MKN-45 cells was made. RESULTS: The sense, antisense hTR eukaryotic expression vectors and empty vector were successfully constructed and proved to be the same as original design by restriction endonuclease analysis and sequencing. Then, they were successfully transfected into MKN-45 cell lines separately with lipofectin. The expression of antisense hTR gene was only detected in MKN-45 cells stably transfected with antisense hTR vector (named as MKN-45-ahTR) but not in the control cells. In MKN-45-ahTR, the telomerase activity was inhibited by 75%, the apoptotic rate was increased to 25.3%, the percentage of cells in the G0/G1 phase was increased to 65%, the proliferation index was decreased to 35% and the population doubling time was prolonged to 35.3 hours. However, the telomerase activity, the apoptotic rate, the distribution of cell cycle, the proliferation index and the population doubling time were not different among the control cells. CONCLUSION: Antisense hTR can significantly inhibit telomerase activity and proliferation of MKN-45 cells and induce cell apoptosis. Antisense gene therapy based on telomerase inhibition can be a potential therapeutic approach to the treatment of gastric cancer.展开更多
AIM： To clarify alterations of Dickkopfs （Dkks） and Kremen2 （Krm2） in gastrointestinal cancer. METHODS： We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestin...AIM： To clarify alterations of Dickkopfs （Dkks） and Kremen2 （Krm2） in gastrointestinal cancer. METHODS： We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR, tissue microarray analysis, and methylation specific PCR （MSP）. Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor. WST-8 assays and/n y/tro invasion assays after treatment with specific siRNA for those genes were performed. RESULTS： Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues. This was correlated with promoter hypermethylation. There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer. In colorectal cancers with beta-catenin over-expression, Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without. Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro.CONCLUSION： Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis.展开更多
AIM: To detect the expression of DPC4 in malignant and non-malignant specimens of human pancreas,and observe the inhibition of retroviral pLXSN containing DPC4 on pancreatic carcinoma cells in vitro.METHODS: The expre...AIM: To detect the expression of DPC4 in malignant and non-malignant specimens of human pancreas,and observe the inhibition of retroviral pLXSN containing DPC4 on pancreatic carcinoma cells in vitro.METHODS: The expression of DPC4 was determined in 40 pancreatic adenocarcinoma and 36 non-malignant pancreatic specimens by reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohisto-chemistry.Furthermore,we constructed retroviral vectors containing DPC4,which then infected the pancreatic carcinoma cell line BxPC-3.Cell growth in vitro after being infected was observed,and the vascular endothelial growth factor (VEGF) mRNA level in the daughter cells was determined by semi-quantitative PCR assay.RESULTS: The RT-PCR assay showed a positive rate of DPC4 mRNA in 100% (36/36) of normal specimens,compared to 40% (16/40) in adenocarcinoma specimens.The regional and intense positive cases of DPC4 expression in adenocarcinoma detected by immunohistochemistry were 10 and four,whereas it was all positive expression in normal tissues.There was a significant difference of DPC4 expression between them.The stable expression of DPC4 in the pancreatic carcinoma cells BxPC-3 could be resumed by retroviral vector pLXSN transfection,and could inhibit cell growth in vitro.Rather,DPC4 could decrease VEGF mRNA transcription levels.CONCLUSION: The deletion of DPC4 expression in pancreatic carcinoma suggests that loss of DPC4 may be involved in the development of pancreatic carcinoma.The retroviral vector pLXSN containing DPC4 can inhibit the proliferation of pancreatic carcinoma cells,and down-regulate the level of VEGF.展开更多
AIM: To study the inhibitory effect of baculovirus- mediated normal epithelial cell specific-1 (NES1) gene therapy on gastric cancer (GC) in vitro and in vivo. METHODS: We first constructed recombinant baculovirus vec...AIM: To study the inhibitory effect of baculovirus- mediated normal epithelial cell specific-1 (NES1) gene therapy on gastric cancer (GC) in vitro and in vivo. METHODS: We first constructed recombinant baculovirus vectors and then transfected them into gastric cancer cells (SGC-7901). Efficiency of the baculovirus for gene transfer into SGC-7901 cells and cell growth curves were detected by fluorescence microscopy, Western blot and 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro, respectively. The therapeutic effect of this gene therapy on GC was confirmed in xenografted nude mice. Tumor growth was determined by tumor volume, and expression of NES1 in tumor was analyzed by immunohistochemistry. RESULTS: Baculovirus vectors were successfully transfected into SGC-7901 cells. SGC-7901 cells transfected with the NES1 gene inhibited cell growth. In the Bac-NES1 treated group, tumor growth was significantly reduced with a high level of NES1 expression CONCLUSION: Baculovirus-mediated NES1 gene can be used in gene therapy for GC.展开更多
AIM:To investigate the utility of Beclin-1 and LC3,two autophagy-related proteins,in predicting the cetuximab efficacy in advanced colorectal cancer(ACRC) . METHODS:The data of 85 patients with ACRC treated at the Sun...AIM:To investigate the utility of Beclin-1 and LC3,two autophagy-related proteins,in predicting the cetuximab efficacy in advanced colorectal cancer(ACRC) . METHODS:The data of 85 patients with ACRC treated at the Sun Yat-sen University Cancer Center from March 1,2005 to December 31,2008 were studied,including 45 cases treated with cetuximab-containing chemotherapy and 40 cases treated with non-cetuximab-containing chemotherapy.Beclin-1 and LC3 expression was evaluated by immunohistochemistry,and KRAS status was evaluated by polymerase chain reaction. RESULTS:Beclin-1 and LC3 expression in ACRC wassignificantly correlated(r=0.44,P<0.01);however,LC3 was more highly expressed in cancerous tissues than in normal tissues(Z=-2.63,P<0.01) .In the cetuximab-containing chemotherapy group,patients with low LC3 expression had higher objective response rates(ORRs) than those with high LC3 expression(52.9%vs 17.9%,P=0.01) ,and patients with low Beclin-1 expression had a longer median progressionfree survival(PFS) than their counterparts with higher Beclin-1 expression(9.0 mo vs 3.0 mo,P=0.01) . However,neither of these predictive relationships was detected in the group treated with non-cetuximabcontaining chemotherapy.Patients with wild-type KRAS had higher ORRs(42.3%vs 9.1%,P=0.049) and disease control rates(DCRs)(73.1%vs 36.4%,P= 0.035) ,and longer median PFS(5.5 mo vs 2.5 mo,P= 0.02) than those with mutant KRAS in the cetuximabcontaining chemotherapy group.Neither Beclin-1(P= 0.52) nor LC3(P=0.32) expression was significantly correlated with KRAS status. CONCLUSION:Patients with low Beclin-1 expression had a longer PFS than those with high Beclin-1 expression,and patients with low LC3 expression had a higher ORR in ACRC patients treated with cetuximab-containing chemotherapy.展开更多
Accumulation of mutations and alterations in the expression of various genes result in carcinogenesis,and the development of microarray technology has enabled us to identify the comprehensive gene expression alteratio...Accumulation of mutations and alterations in the expression of various genes result in carcinogenesis,and the development of microarray technology has enabled us to identify the comprehensive gene expression alterations in oncogenesis.Many studies have applied this technology for hepatocellular carcinoma(HCC),and identified a number of candidate genes useful as biomarkers in cancer staging,prediction of recurrence and prognosis,and treatment selection.Some of these target molecules have been used to develop new serum diagnostic markers and therapeutic targets against HCC to benefit patients.Previously,we compared gene expression profiling data with classification based on clinicopathological features,such as hepatitis viral infection or liver cancer progression.The next era of gene expression analysis will require systematic integration of expression profiles with other types of biological information,such as genomic locus,gene function,and sequence information.We have reported integration between expression profiles and locus information,which is effective in detecting structural genomic abnormalities,such as chromosomal gains and losses,in which we showed that gene expression profiles are subject to chromosomal bias.Furthermore,array-based comparative genomic hybridization analysis and allelic dosage analysis using genotyping arrays for HCC were also reviewed,with comparison of conventional methods.展开更多
OBJECTIVE To observe anti-tumor effects of PVAX-PSMA gene vaccine. METHODS The PSMA gene was inserted into a mammalian expression vector, PVAX-1, to construct the DNA vaccine candidate, and was then used to vaccinate ...OBJECTIVE To observe anti-tumor effects of PVAX-PSMA gene vaccine. METHODS The PSMA gene was inserted into a mammalian expression vector, PVAX-1, to construct the DNA vaccine candidate, and was then used to vaccinate C57BL/6 mice. Animals vaccinated with PVAX-1 and NaC1 were used as controls. Anti-PSMA antibody was detected in sera of the animals. The proliferation and cytotoxicity of the spleen cells were observed. The immunized mice were inoculated with RM-1 cells. The mice were inoculated with RM-1 cells, and then the mice were immunized. The anti-tumor efficacy of the gene vaccine was evaluated by the ratio of tumor formation, tumor volume, tumor mass before and after gene vaccination and evaluated by survival rate of the immunized mice. RESULTS High level of anti-PSMA antibody was induced in the PVAX-PSMA group. The splenocytes from PVAX-PSMA group were stimulated to produce strong proliferation responses and significant cytotoxic T-cells （CTL） activity. After the mice were immunized with PVAX-PSMA gene, tumor occurrence was decreased, and the growth velocity of tumor was markedly reduced, resulting in prolonged tumor-free time （P 〈 0.05）. CONCLUSION PVAX-PSMA gene vaccine has significant anti- tumor effects and provides an experimental basis for primary prevention and immunotherapy of prostate cancer.展开更多
The absence of effective therapies for castration-resistant prostate cancer(CRPC) establishes the need to develop novel therapeutic modality, such as targeted gene therapy, which is ideal for the treatment of CRPC. Bu...The absence of effective therapies for castration-resistant prostate cancer(CRPC) establishes the need to develop novel therapeutic modality, such as targeted gene therapy, which is ideal for the treatment of CRPC. But its application has been limited due to lack of favorable gene vector and the reduction of "bystander effect". Consequently, scientists all over the world focus their main experimental research on the following four aspects: targeted gene, vector, transfer means and comprehensive therapy. In this paper, we reviewed the latest advances of experimental research on targeted gene therapy for prostate cancer.展开更多
Objective： The aim of this study was to explore the relationship between p53 gene and triple-negative breast cancer （TNBC）, and determine that whether p53 gene could be a new effective therapeutic target. Methods：...Objective： The aim of this study was to explore the relationship between p53 gene and triple-negative breast cancer （TNBC）, and determine that whether p53 gene could be a new effective therapeutic target. Methods： We identified studies with quantitative data on the relation of p53 gene and TNBC through searching 12 databases online （Oct. 1999-Oct. 2012） and reviewing the references, which were written in English or Chinese. Summary estimates of odds ratio （OR） was calculated using the fixed-effects model or the random-effects model as appropriate. Results： We identified 12 eligible stud- ies with 1532 cases of TNBC patients and 6329 controls of non-TNBC patients. The test for homogeneity resulted in X^2 = 200.16 （P 〈 0.05）, it showed significant heterogeneity so that a random effect model was applied. Our results showed that the expression of p53 gene could be much stronger in TNBC group than that in non-TNBC group [OR = 2.10, 95% confidence interval （CI） = 1.21-3.65]. In ethnicity-subgroup analysis, we found that in Caucasian group, the expression of p53 gene were stronger in TNBC group （OR = 2.60, 95% CI = 1.21-5.57）, but there was no statistical significance in Asian group （OR = 1.69, 95% CI = 0.83-3.45）. Conclusion： P53 gene could be an effective predictor and a good therapeutic target for TNBC patients in the future, especially in Caucasian. Further researches focusing on p53 gene would gain a breakthrough in the treatment of TNBC.展开更多
AIM： To investigate the effects of mutations in domain Ⅲ of the hepatitis C virus （HCV） internal ribosome entry sequences （IRES） on the response of chronic HCV genotype 4a patients to interferon therapy.METHODS...AIM： To investigate the effects of mutations in domain Ⅲ of the hepatitis C virus （HCV） internal ribosome entry sequences （IRES） on the response of chronic HCV genotype 4a patients to interferon therapy.METHODS： HCV RNA was extracted from 19 chronic HCV 4a patients receiving interferon/ribavirin therapy who showed dramatic differences in their response to combination therapy after initial viral clearance. IRES domain Ⅲ was cloned and 15 clones for each patient were sequenced. The obtained sequences were aligned with genotype 4a prototype using the ClustaIW program and mutations scored. Prediction of stem-loop secondary structure and thermodynamic stability of the major quasispecies in each patient was performed using the MFOLD 3.2 program with Turner energies and selected constraints on base pairing.RESULTS： Analysis of RNA secondary structure revealed that insertions in domain Ⅲ altered WatsonCrick base pairing of stems and reduced molecular stability of RNA, which may ultimately reduce binding affinity to ribosomal proteins. Insertion mutations in domain - were statistically more prevalent in sustained viral response patients （SVR, n = 14） as compared to breakthrough （BT, n = 5） patients.CONCLUSION： The influence of mutations within domain Ⅲ on the response of HCV patients to combination therapy depends primarily on the position, but not the frequency, of these mutations within IRES domain Ⅲ.展开更多
基金the National Natural Science Foundation of China,No.39770725
文摘AIM: To investigate the effects of antisense human telomerase RNA (hTR)on the biologic behavior of human gastric cancer cell line: MKN-45 by gene transfection and its potential role in the gene therapy of gastric cancer. METHODS: The hTR cDNA fragment was cloned from MKN-45 through RT-PCR and subcloned into eukaryotic expression vector (pEF6/V5-His-TOPO) in cis-direction or trans-direction by DNA recombinant methods. The constructed sense, antisense and empty vectors were transfected into MKN-45 cell lines separately by lipofectin-mediated DNA transfection technology. After drug selection, the expression of antisense hTR gene in stable transfectants and normal MKN-45 cells was detected by RT-PCR, the telomerase activity by TRAP, the apoptotic features by PI and Hoechst 33258 staining, the cell cycle distribution by flow cytometry and the population doubling time by cell counting. Comparison among the stable transfectants and normal MKN-45 cells was made. RESULTS: The sense, antisense hTR eukaryotic expression vectors and empty vector were successfully constructed and proved to be the same as original design by restriction endonuclease analysis and sequencing. Then, they were successfully transfected into MKN-45 cell lines separately with lipofectin. The expression of antisense hTR gene was only detected in MKN-45 cells stably transfected with antisense hTR vector (named as MKN-45-ahTR) but not in the control cells. In MKN-45-ahTR, the telomerase activity was inhibited by 75%, the apoptotic rate was increased to 25.3%, the percentage of cells in the G0/G1 phase was increased to 65%, the proliferation index was decreased to 35% and the population doubling time was prolonged to 35.3 hours. However, the telomerase activity, the apoptotic rate, the distribution of cell cycle, the proliferation index and the population doubling time were not different among the control cells. CONCLUSION: Antisense hTR can significantly inhibit telomerase activity and proliferation of MKN-45 cells and induce cell apoptosis. Antisense gene therapy based on telomerase inhibition can be a potential therapeutic approach to the treatment of gastric cancer.
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (H.Y. and F.I.)Grants-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan (H.Y. and F.I.)
文摘AIM： To clarify alterations of Dickkopfs （Dkks） and Kremen2 （Krm2） in gastrointestinal cancer. METHODS： We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR, tissue microarray analysis, and methylation specific PCR （MSP）. Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor. WST-8 assays and/n y/tro invasion assays after treatment with specific siRNA for those genes were performed. RESULTS： Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues. This was correlated with promoter hypermethylation. There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer. In colorectal cancers with beta-catenin over-expression, Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without. Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro.CONCLUSION： Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis.
文摘AIM: To detect the expression of DPC4 in malignant and non-malignant specimens of human pancreas,and observe the inhibition of retroviral pLXSN containing DPC4 on pancreatic carcinoma cells in vitro.METHODS: The expression of DPC4 was determined in 40 pancreatic adenocarcinoma and 36 non-malignant pancreatic specimens by reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohisto-chemistry.Furthermore,we constructed retroviral vectors containing DPC4,which then infected the pancreatic carcinoma cell line BxPC-3.Cell growth in vitro after being infected was observed,and the vascular endothelial growth factor (VEGF) mRNA level in the daughter cells was determined by semi-quantitative PCR assay.RESULTS: The RT-PCR assay showed a positive rate of DPC4 mRNA in 100% (36/36) of normal specimens,compared to 40% (16/40) in adenocarcinoma specimens.The regional and intense positive cases of DPC4 expression in adenocarcinoma detected by immunohistochemistry were 10 and four,whereas it was all positive expression in normal tissues.There was a significant difference of DPC4 expression between them.The stable expression of DPC4 in the pancreatic carcinoma cells BxPC-3 could be resumed by retroviral vector pLXSN transfection,and could inhibit cell growth in vitro.Rather,DPC4 could decrease VEGF mRNA transcription levels.CONCLUSION: The deletion of DPC4 expression in pancreatic carcinoma suggests that loss of DPC4 may be involved in the development of pancreatic carcinoma.The retroviral vector pLXSN containing DPC4 can inhibit the proliferation of pancreatic carcinoma cells,and down-regulate the level of VEGF.
基金The Doctoral Fund from the Ministry of Education of China, No. BXJ0710
文摘AIM: To study the inhibitory effect of baculovirus- mediated normal epithelial cell specific-1 (NES1) gene therapy on gastric cancer (GC) in vitro and in vivo. METHODS: We first constructed recombinant baculovirus vectors and then transfected them into gastric cancer cells (SGC-7901). Efficiency of the baculovirus for gene transfer into SGC-7901 cells and cell growth curves were detected by fluorescence microscopy, Western blot and 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro, respectively. The therapeutic effect of this gene therapy on GC was confirmed in xenografted nude mice. Tumor growth was determined by tumor volume, and expression of NES1 in tumor was analyzed by immunohistochemistry. RESULTS: Baculovirus vectors were successfully transfected into SGC-7901 cells. SGC-7901 cells transfected with the NES1 gene inhibited cell growth. In the Bac-NES1 treated group, tumor growth was significantly reduced with a high level of NES1 expression CONCLUSION: Baculovirus-mediated NES1 gene can be used in gene therapy for GC.
基金Supported by Grants from Science and Technology Planning Project of Guangdong Province,China,No.2010B031600317Administration of Traditional Chinese Medicine of Guangdong Province,China,No.20111169National Natural Science Foun-dation of China,No.81071872
文摘AIM:To investigate the utility of Beclin-1 and LC3,two autophagy-related proteins,in predicting the cetuximab efficacy in advanced colorectal cancer(ACRC) . METHODS:The data of 85 patients with ACRC treated at the Sun Yat-sen University Cancer Center from March 1,2005 to December 31,2008 were studied,including 45 cases treated with cetuximab-containing chemotherapy and 40 cases treated with non-cetuximab-containing chemotherapy.Beclin-1 and LC3 expression was evaluated by immunohistochemistry,and KRAS status was evaluated by polymerase chain reaction. RESULTS:Beclin-1 and LC3 expression in ACRC wassignificantly correlated(r=0.44,P<0.01);however,LC3 was more highly expressed in cancerous tissues than in normal tissues(Z=-2.63,P<0.01) .In the cetuximab-containing chemotherapy group,patients with low LC3 expression had higher objective response rates(ORRs) than those with high LC3 expression(52.9%vs 17.9%,P=0.01) ,and patients with low Beclin-1 expression had a longer median progressionfree survival(PFS) than their counterparts with higher Beclin-1 expression(9.0 mo vs 3.0 mo,P=0.01) . However,neither of these predictive relationships was detected in the group treated with non-cetuximabcontaining chemotherapy.Patients with wild-type KRAS had higher ORRs(42.3%vs 9.1%,P=0.049) and disease control rates(DCRs)(73.1%vs 36.4%,P= 0.035) ,and longer median PFS(5.5 mo vs 2.5 mo,P= 0.02) than those with mutant KRAS in the cetuximabcontaining chemotherapy group.Neither Beclin-1(P= 0.52) nor LC3(P=0.32) expression was significantly correlated with KRAS status. CONCLUSION:Patients with low Beclin-1 expression had a longer PFS than those with high Beclin-1 expression,and patients with low LC3 expression had a higher ORR in ACRC patients treated with cetuximab-containing chemotherapy.
文摘Accumulation of mutations and alterations in the expression of various genes result in carcinogenesis,and the development of microarray technology has enabled us to identify the comprehensive gene expression alterations in oncogenesis.Many studies have applied this technology for hepatocellular carcinoma(HCC),and identified a number of candidate genes useful as biomarkers in cancer staging,prediction of recurrence and prognosis,and treatment selection.Some of these target molecules have been used to develop new serum diagnostic markers and therapeutic targets against HCC to benefit patients.Previously,we compared gene expression profiling data with classification based on clinicopathological features,such as hepatitis viral infection or liver cancer progression.The next era of gene expression analysis will require systematic integration of expression profiles with other types of biological information,such as genomic locus,gene function,and sequence information.We have reported integration between expression profiles and locus information,which is effective in detecting structural genomic abnormalities,such as chromosomal gains and losses,in which we showed that gene expression profiles are subject to chromosomal bias.Furthermore,array-based comparative genomic hybridization analysis and allelic dosage analysis using genotyping arrays for HCC were also reviewed,with comparison of conventional methods.
文摘OBJECTIVE To observe anti-tumor effects of PVAX-PSMA gene vaccine. METHODS The PSMA gene was inserted into a mammalian expression vector, PVAX-1, to construct the DNA vaccine candidate, and was then used to vaccinate C57BL/6 mice. Animals vaccinated with PVAX-1 and NaC1 were used as controls. Anti-PSMA antibody was detected in sera of the animals. The proliferation and cytotoxicity of the spleen cells were observed. The immunized mice were inoculated with RM-1 cells. The mice were inoculated with RM-1 cells, and then the mice were immunized. The anti-tumor efficacy of the gene vaccine was evaluated by the ratio of tumor formation, tumor volume, tumor mass before and after gene vaccination and evaluated by survival rate of the immunized mice. RESULTS High level of anti-PSMA antibody was induced in the PVAX-PSMA group. The splenocytes from PVAX-PSMA group were stimulated to produce strong proliferation responses and significant cytotoxic T-cells （CTL） activity. After the mice were immunized with PVAX-PSMA gene, tumor occurrence was decreased, and the growth velocity of tumor was markedly reduced, resulting in prolonged tumor-free time （P 〈 0.05）. CONCLUSION PVAX-PSMA gene vaccine has significant anti- tumor effects and provides an experimental basis for primary prevention and immunotherapy of prostate cancer.
文摘The absence of effective therapies for castration-resistant prostate cancer(CRPC) establishes the need to develop novel therapeutic modality, such as targeted gene therapy, which is ideal for the treatment of CRPC. But its application has been limited due to lack of favorable gene vector and the reduction of "bystander effect". Consequently, scientists all over the world focus their main experimental research on the following four aspects: targeted gene, vector, transfer means and comprehensive therapy. In this paper, we reviewed the latest advances of experimental research on targeted gene therapy for prostate cancer.
基金supported by a grant from the Key Project of National 12th Five-Years Research Program of China (No. 2012ZX-09303016-002)
文摘Objective： The aim of this study was to explore the relationship between p53 gene and triple-negative breast cancer （TNBC）, and determine that whether p53 gene could be a new effective therapeutic target. Methods： We identified studies with quantitative data on the relation of p53 gene and TNBC through searching 12 databases online （Oct. 1999-Oct. 2012） and reviewing the references, which were written in English or Chinese. Summary estimates of odds ratio （OR） was calculated using the fixed-effects model or the random-effects model as appropriate. Results： We identified 12 eligible stud- ies with 1532 cases of TNBC patients and 6329 controls of non-TNBC patients. The test for homogeneity resulted in X^2 = 200.16 （P 〈 0.05）, it showed significant heterogeneity so that a random effect model was applied. Our results showed that the expression of p53 gene could be much stronger in TNBC group than that in non-TNBC group [OR = 2.10, 95% confidence interval （CI） = 1.21-3.65]. In ethnicity-subgroup analysis, we found that in Caucasian group, the expression of p53 gene were stronger in TNBC group （OR = 2.60, 95% CI = 1.21-5.57）, but there was no statistical significance in Asian group （OR = 1.69, 95% CI = 0.83-3.45）. Conclusion： P53 gene could be an effective predictor and a good therapeutic target for TNBC patients in the future, especially in Caucasian. Further researches focusing on p53 gene would gain a breakthrough in the treatment of TNBC.
基金Supported by A grant from National Research Center to M.Awady and grant from Yousef Jameel Science&Technology Research Center(YJ-STRC)at the American University in Cairo to H.Azzazy
文摘AIM： To investigate the effects of mutations in domain Ⅲ of the hepatitis C virus （HCV） internal ribosome entry sequences （IRES） on the response of chronic HCV genotype 4a patients to interferon therapy.METHODS： HCV RNA was extracted from 19 chronic HCV 4a patients receiving interferon/ribavirin therapy who showed dramatic differences in their response to combination therapy after initial viral clearance. IRES domain Ⅲ was cloned and 15 clones for each patient were sequenced. The obtained sequences were aligned with genotype 4a prototype using the ClustaIW program and mutations scored. Prediction of stem-loop secondary structure and thermodynamic stability of the major quasispecies in each patient was performed using the MFOLD 3.2 program with Turner energies and selected constraints on base pairing.RESULTS： Analysis of RNA secondary structure revealed that insertions in domain Ⅲ altered WatsonCrick base pairing of stems and reduced molecular stability of RNA, which may ultimately reduce binding affinity to ribosomal proteins. Insertion mutations in domain - were statistically more prevalent in sustained viral response patients （SVR, n = 14） as compared to breakthrough （BT, n = 5） patients.CONCLUSION： The influence of mutations within domain Ⅲ on the response of HCV patients to combination therapy depends primarily on the position, but not the frequency, of these mutations within IRES domain Ⅲ.
