Objective： To investigate the effect of insulin-like growth factor 1 receptor （IGF1R） small interfering RNA （siRNA） on the growth of human liver cancer SMMC7721 cell xenograft in nude mice. Methods： siRNA target...Objective： To investigate the effect of insulin-like growth factor 1 receptor （IGF1R） small interfering RNA （siRNA） on the growth of human liver cancer SMMC7721 cell xenograft in nude mice. Methods： siRNA targeting IGF1R was designed, and plasmid SMMC7721-1GF1R-siRNA was constructed and transfected into SMMC7721 cells （SMMC7721-1GF1R-siRNA cells）; the cells transfected with SMMC7721-1GF1 R-mutation （SMMC7721-1GF1 R-mutation cells） were used as negative con- trol, and untransfected cells as empty control. Stable cell clones were screened by G418, and transplanted into nude mice to establish cancer xenograft. Tumor growth was monitored. Tumor morphology was observed with HE staining. The expression of IGF1R protein in tumor tissues was detected by Western blot. Microvessel density （MVD） in tumor tissues was detected by SP immunohistochemistry. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） assay. Results： The tumor volume was significantly smaller in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups （P 〈 0.05）. Necrosis and cell apoptosis were found in SMMC7721- IGF1R-siRNA group. The expression of IGF1R protein was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups （P 〈 0.05）. MVD was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups （11.3 ± 4.4 vs. 36.7 ± 7.6 and 28.4 ±6.5, P 〈 0.05）. The apoptosis rate of tumor cells was significantly higher in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups [（50.2 ± 6.4）% vs. （5.4 ± 1.0）% or （6.0 ±2.1）%, P〈0.05]. Conclusion： IGF1R siRNA can inhibit the growth of SMMC7721 cell xenograft in nude mice.展开更多
The distribution of repetitive DNAs along chromosomes is one of the crucial elements for understanding the organization and the evolution of plant genomes.Using a modified genomic in situ hybridization(GISH)procedure,...The distribution of repetitive DNAs along chromosomes is one of the crucial elements for understanding the organization and the evolution of plant genomes.Using a modified genomic in situ hybridization(GISH)procedure,fluorescence in situ hybridization(FISH)with genomic DNA to their own chromosomes(called self-genomic in situ hybridization,self-GISH)was carried out in six selected plant species with different genome size and amount of repetitive DNA.Nonuniform distribution of the fluorescent labeled probe DNA was observed on the chromosomes of all the species that were tested.The signal patterns varied among species and were related to the genome size.The chromosomes of the small Arabidopsis genome were labeled almost only in the pericentromeric regions and the nucleolus organizer regions(NORs).The signals in the relatively small genomes,rice,sorghum,and Brassica oleracea var.capitata L.,were dispersed along the chromosome lengths,with a predominant distribution in the pericentromeric or proximal regions and some heterochromatic arms.All chromosomes of the large genomes,maize and barley,were densely labeled with strongly labeled regions and weakly labeled or unlabeled regions being arranged alternatively throughout the lengths.In addition,enhanced signal bands were shown in all pericentromeres and the NORs in B.oleracea var.capitata,and in all pericentromeric regions and certain intercalary sites in barley.The enhanced signal band pattern in barley was found consistent with the N-banding pattern of this species.The GISH with self-genomic DNA was compared with FISH with Cot-1 DNA in rice,and their signal patterns are found to be basically consistent.Our results showed that the self-GISH signals actually reflected the hybridization of genomic repetitive DNAs to the chromosomes,thus the self-GISH technique would be useful for revealing the distribution of the regions where repetitive DNAs concentrate along chromosomes and some chromatin differentiation associated with repetitive DNAs in plants.展开更多
Even though mutations in LMNA have been reported in patients with typical dilated cardio-myopathy(DCM)and atrioventricular block(AVB)previously,the purpose of this study was to disclose this novel genetic abnormality ...Even though mutations in LMNA have been reported in patients with typical dilated cardio-myopathy(DCM)and atrioventricular block(AVB)previously,the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval.Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2,where the LMNA gene was located.Direct DNA sequence analysis revealed a heterozygous G t...展开更多
Hepatocellular carcinoma is the main type of primary liver cancer,and also one of the most malignant tumors.At present,the pathogenesis mechanisms of liver cancer are not entirely clear.It has been shown that inactiva...Hepatocellular carcinoma is the main type of primary liver cancer,and also one of the most malignant tumors.At present,the pathogenesis mechanisms of liver cancer are not entirely clear.It has been shown that inactivation of tumor suppressor genes and activation of oncogenes play a significant role in carcinogenesis,caused by the genetic and epigenetic aberrance.In the past,people generally thought that genetic mutation is a key event of tumor pathogenesis,and somatic mutation of tumor suppressor genes is in particular closely associated with oncogenesis.With deeper understanding of tumors in recent years,increasing evidence has shown that epigenetic silencing of those genes,as a result of aberrant hypermethylation of CpG islands in promoters and histone modification,is essential to carcinogenesis and metastasis.The term epigenetics refers to heritable changes in gene expression caused by regulation mechanisms,other than changes in the underlying DNA sequence.Specific epigenetic processes include DNA methylation,genome imprinting,chromotin remodeling,histone modification and microRNA regulations.This paper reviews recent epigenetics research progress in the hepatocellular carcinoma study,and tries to depict the relationships between hepatocellular carcinomagenesis and DNA methylation as well as microRNA regulation.展开更多
Using genomic in situ hybridization with genomic DNA, high-order chromatin fibers were successfully exhibited under a light microscope through the cell cycle in barley, rice, maize and field bean. From the interphase ...Using genomic in situ hybridization with genomic DNA, high-order chromatin fibers were successfully exhibited under a light microscope through the cell cycle in barley, rice, maize and field bean. From the interphase to prophase and metaphase of mitosis, the fibers were basically similar. Each was estimated to be around 200 nm in diameter, but the strength of signals was not the same along the fiber length. Through the cell cycle a series of dynamic distribution changes occurred in the fibers. In the interphase, they were unraveled. At the early prophase they were arranged with parallel and mirror symmetry. During late-prophase and metaphase, the fibers were bundled and became different visible chromosomes. The parallel coiling and mirror symmetry structures were visible clearly until the metaphase. In anaphase they disappeared. During telophase, in peripheral regions of congregated chromosome group, borderlines of the chromosomes disappeared and the fibers were unraveled. This demonstrated that mitotic chromosomes are assembled and organized by parallel and adjacent coiling of the fibers and the fibers should be the highest order structure for DNA coiling.展开更多
文摘Objective： To investigate the effect of insulin-like growth factor 1 receptor （IGF1R） small interfering RNA （siRNA） on the growth of human liver cancer SMMC7721 cell xenograft in nude mice. Methods： siRNA targeting IGF1R was designed, and plasmid SMMC7721-1GF1R-siRNA was constructed and transfected into SMMC7721 cells （SMMC7721-1GF1R-siRNA cells）; the cells transfected with SMMC7721-1GF1 R-mutation （SMMC7721-1GF1 R-mutation cells） were used as negative con- trol, and untransfected cells as empty control. Stable cell clones were screened by G418, and transplanted into nude mice to establish cancer xenograft. Tumor growth was monitored. Tumor morphology was observed with HE staining. The expression of IGF1R protein in tumor tissues was detected by Western blot. Microvessel density （MVD） in tumor tissues was detected by SP immunohistochemistry. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL） assay. Results： The tumor volume was significantly smaller in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups （P 〈 0.05）. Necrosis and cell apoptosis were found in SMMC7721- IGF1R-siRNA group. The expression of IGF1R protein was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups （P 〈 0.05）. MVD was significantly lower in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups （11.3 ± 4.4 vs. 36.7 ± 7.6 and 28.4 ±6.5, P 〈 0.05）. The apoptosis rate of tumor cells was significantly higher in SMMC7721-1GF1R-siRNA group than in SMMC7721-1GF1R-mutation and SMMC7721 groups [（50.2 ± 6.4）% vs. （5.4 ± 1.0）% or （6.0 ±2.1）%, P〈0.05]. Conclusion： IGF1R siRNA can inhibit the growth of SMMC7721 cell xenograft in nude mice.
基金This work was supported by the National Natural Sciences Foundation of China(No.39870423).
文摘The distribution of repetitive DNAs along chromosomes is one of the crucial elements for understanding the organization and the evolution of plant genomes.Using a modified genomic in situ hybridization(GISH)procedure,fluorescence in situ hybridization(FISH)with genomic DNA to their own chromosomes(called self-genomic in situ hybridization,self-GISH)was carried out in six selected plant species with different genome size and amount of repetitive DNA.Nonuniform distribution of the fluorescent labeled probe DNA was observed on the chromosomes of all the species that were tested.The signal patterns varied among species and were related to the genome size.The chromosomes of the small Arabidopsis genome were labeled almost only in the pericentromeric regions and the nucleolus organizer regions(NORs).The signals in the relatively small genomes,rice,sorghum,and Brassica oleracea var.capitata L.,were dispersed along the chromosome lengths,with a predominant distribution in the pericentromeric or proximal regions and some heterochromatic arms.All chromosomes of the large genomes,maize and barley,were densely labeled with strongly labeled regions and weakly labeled or unlabeled regions being arranged alternatively throughout the lengths.In addition,enhanced signal bands were shown in all pericentromeres and the NORs in B.oleracea var.capitata,and in all pericentromeric regions and certain intercalary sites in barley.The enhanced signal band pattern in barley was found consistent with the N-banding pattern of this species.The GISH with self-genomic DNA was compared with FISH with Cot-1 DNA in rice,and their signal patterns are found to be basically consistent.Our results showed that the self-GISH signals actually reflected the hybridization of genomic repetitive DNAs to the chromosomes,thus the self-GISH technique would be useful for revealing the distribution of the regions where repetitive DNAs concentrate along chromosomes and some chromatin differentiation associated with repetitive DNAs in plants.
文摘Even though mutations in LMNA have been reported in patients with typical dilated cardio-myopathy(DCM)and atrioventricular block(AVB)previously,the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval.Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2,where the LMNA gene was located.Direct DNA sequence analysis revealed a heterozygous G t...
基金Supported by National Basic Research Program of China(Grant No.2006CD910402)Science and Technology Commission of Shanghai Municipality(Grant No.05DZ22201 and 08JC1416400)
文摘Hepatocellular carcinoma is the main type of primary liver cancer,and also one of the most malignant tumors.At present,the pathogenesis mechanisms of liver cancer are not entirely clear.It has been shown that inactivation of tumor suppressor genes and activation of oncogenes play a significant role in carcinogenesis,caused by the genetic and epigenetic aberrance.In the past,people generally thought that genetic mutation is a key event of tumor pathogenesis,and somatic mutation of tumor suppressor genes is in particular closely associated with oncogenesis.With deeper understanding of tumors in recent years,increasing evidence has shown that epigenetic silencing of those genes,as a result of aberrant hypermethylation of CpG islands in promoters and histone modification,is essential to carcinogenesis and metastasis.The term epigenetics refers to heritable changes in gene expression caused by regulation mechanisms,other than changes in the underlying DNA sequence.Specific epigenetic processes include DNA methylation,genome imprinting,chromotin remodeling,histone modification and microRNA regulations.This paper reviews recent epigenetics research progress in the hepatocellular carcinoma study,and tries to depict the relationships between hepatocellular carcinomagenesis and DNA methylation as well as microRNA regulation.
基金Supported by the National Natural Science Foundation of China(39870423 and 30670736)China Postdoctoral Science Foundation(2003034496).
文摘Using genomic in situ hybridization with genomic DNA, high-order chromatin fibers were successfully exhibited under a light microscope through the cell cycle in barley, rice, maize and field bean. From the interphase to prophase and metaphase of mitosis, the fibers were basically similar. Each was estimated to be around 200 nm in diameter, but the strength of signals was not the same along the fiber length. Through the cell cycle a series of dynamic distribution changes occurred in the fibers. In the interphase, they were unraveled. At the early prophase they were arranged with parallel and mirror symmetry. During late-prophase and metaphase, the fibers were bundled and became different visible chromosomes. The parallel coiling and mirror symmetry structures were visible clearly until the metaphase. In anaphase they disappeared. During telophase, in peripheral regions of congregated chromosome group, borderlines of the chromosomes disappeared and the fibers were unraveled. This demonstrated that mitotic chromosomes are assembled and organized by parallel and adjacent coiling of the fibers and the fibers should be the highest order structure for DNA coiling.
