Studies on rodents and humans demonstrate an inherited predisposition to hepatocellular carcinoma （HCC）. Analysis of the molecular alterations involved in the acquisition of a phenotype resistant or susceptible to h...Studies on rodents and humans demonstrate an inherited predisposition to hepatocellular carcinoma （HCC）. Analysis of the molecular alterations involved in the acquisition of a phenotype resistant or susceptible to hepatocarcinogenesis showed a deregulation of G1 and S phases in HCC of genetically susceptible F344 rats and a G1-S block in lesions of resistant Brown norway （BN） rats. Unrestrained extracellular signal-regulated kinase （ERK） activity linked to proteasomal degradation of dual-specificity phosphatase 1 （DUSP1）, a specific ERK inhibitor, by the CKS1-SKP2 ubiquitin ligase complex occurs in more aggressive HCC of F344 rats and humans. This mechanism is less active in HCC of BN rats and human HCC with better prognosis. Upregulation of iNos cross-talk with IKK/NF-KB and RAS/ERK pathways occurs in rodent liver lesions at higher levels in the most aggressive models represented by HCC of F344 rats and c-Myc-TGF-α transgenic mice. iNOS, IKK/NF-κB, and RAS/ERK upregulation is highest in human HCC with a poorer prognosis and positively correlates with tumor proliferation, genomic instability and microvascularization, and negatively with apoptosis. Thus, cell cycle regulation and the activity of signal transduction pathways seem to be modulated by HCC modifier genes, and differences in their efficiency influence the susceptibility to hepatocarcinogenesis and probably the prognosis of human HCC.展开更多
The purpose of this investigation was to study the therapeutic effect of Lamivudine on HBVDNA in peripheral blood mononudear cells （PBMC） and serum, and the level of cytokines in serum of the patients with chronic h...The purpose of this investigation was to study the therapeutic effect of Lamivudine on HBVDNA in peripheral blood mononudear cells （PBMC） and serum, and the level of cytokines in serum of the patients with chronic hepatitis B. The patients were divided into two groups （A = 47, B = 34）, and treated by Lamivudine, routine medicine, respectively. The levels of HBV-DNA in PBMC and serum and eytokines were all detected before and after treatment. After the treatment of Lamivndine for 36 weeks, the total conversion negative rates of HBV-DNA in PBMC and serum of the patients treated with Lamivudine were 55.32% （26/47） and 61.70% （29/47）, respectively. The total negative conversion rates of HBV-DNA in PBMC and serum of the patients treated by routine medicine were 26.47 % （9/34） and 32.35% （11/34）, respectively. There was significant difference between Lamivudine group and routine medicine group （ P 〈 0.01 ）. The negative conversion rates of HBeAg in serum of the patients were 46.81% （22/47） and 68.09% （32/47） at the end of 24 weeks and 36 weeks, and were higher than those of routine medicine group （ P 〈 0.05 and P 〈 0.01 ）. The levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, ALT/AST in serum of the patients after being treated by Lamivudine, routine medicine were down-regulated to （30.1 ± 9.6） U/ml, （32.3 ±10.7） U/ml, 0.9 ±0.1 and （48.4±10.7） U/ml, （44.7 ±11.0） U/ml, 1.1 ±0.2. After the analysis of variance, the high significant difference was obvious between the two groups （ P 〈 0.01）. It was due to the high levels of IL-6, IL-8 and TNF-α in chronic hepatitis B which could be down-regulated to （250.5 ±33.3） pg/ml, （153.4 ±22.2） pg/ml, （232.6 ±21.2） pg/ml by Lamivudine, which was more obvious than that of routine medicine （ P 〈 0.01）. Lamivudine has high therapeutic effect on the treatment of HBVDNA in PBMC and serum and has better therapeutic effect than that of routine therapy. Lamivudine may also have higher down-regtdated inflananatory infdtration and secretion in local site caused by chemotactic cytokines and produce promotional effect on the recovery of liver function.展开更多
Virus-induced gene silencing is regarded as a powerful and efficient tool for the analysis of gene function in plants because it is simple, rapid and transformation-free. It has been used to perform both forward and r...Virus-induced gene silencing is regarded as a powerful and efficient tool for the analysis of gene function in plants because it is simple, rapid and transformation-free. It has been used to perform both forward and reverse genetics to identify plant functional genes. Many viruses have been developed into virus-induced gene silencing vectors and gene functions involved in development, biotic and abiotic stresses, metabolism, and cellular signaling have been reported. In this review, we discuss the development and application of virus-induced gene silencing in plant functional genomics.展开更多
基金Supported by Grants from the"Associazione Italiana Ricerche sul Cancro"
文摘Studies on rodents and humans demonstrate an inherited predisposition to hepatocellular carcinoma （HCC）. Analysis of the molecular alterations involved in the acquisition of a phenotype resistant or susceptible to hepatocarcinogenesis showed a deregulation of G1 and S phases in HCC of genetically susceptible F344 rats and a G1-S block in lesions of resistant Brown norway （BN） rats. Unrestrained extracellular signal-regulated kinase （ERK） activity linked to proteasomal degradation of dual-specificity phosphatase 1 （DUSP1）, a specific ERK inhibitor, by the CKS1-SKP2 ubiquitin ligase complex occurs in more aggressive HCC of F344 rats and humans. This mechanism is less active in HCC of BN rats and human HCC with better prognosis. Upregulation of iNos cross-talk with IKK/NF-KB and RAS/ERK pathways occurs in rodent liver lesions at higher levels in the most aggressive models represented by HCC of F344 rats and c-Myc-TGF-α transgenic mice. iNOS, IKK/NF-κB, and RAS/ERK upregulation is highest in human HCC with a poorer prognosis and positively correlates with tumor proliferation, genomic instability and microvascularization, and negatively with apoptosis. Thus, cell cycle regulation and the activity of signal transduction pathways seem to be modulated by HCC modifier genes, and differences in their efficiency influence the susceptibility to hepatocarcinogenesis and probably the prognosis of human HCC.
文摘The purpose of this investigation was to study the therapeutic effect of Lamivudine on HBVDNA in peripheral blood mononudear cells （PBMC） and serum, and the level of cytokines in serum of the patients with chronic hepatitis B. The patients were divided into two groups （A = 47, B = 34）, and treated by Lamivudine, routine medicine, respectively. The levels of HBV-DNA in PBMC and serum and eytokines were all detected before and after treatment. After the treatment of Lamivndine for 36 weeks, the total conversion negative rates of HBV-DNA in PBMC and serum of the patients treated with Lamivudine were 55.32% （26/47） and 61.70% （29/47）, respectively. The total negative conversion rates of HBV-DNA in PBMC and serum of the patients treated by routine medicine were 26.47 % （9/34） and 32.35% （11/34）, respectively. There was significant difference between Lamivudine group and routine medicine group （ P 〈 0.01 ）. The negative conversion rates of HBeAg in serum of the patients were 46.81% （22/47） and 68.09% （32/47） at the end of 24 weeks and 36 weeks, and were higher than those of routine medicine group （ P 〈 0.05 and P 〈 0.01 ）. The levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, ALT/AST in serum of the patients after being treated by Lamivudine, routine medicine were down-regulated to （30.1 ± 9.6） U/ml, （32.3 ±10.7） U/ml, 0.9 ±0.1 and （48.4±10.7） U/ml, （44.7 ±11.0） U/ml, 1.1 ±0.2. After the analysis of variance, the high significant difference was obvious between the two groups （ P 〈 0.01）. It was due to the high levels of IL-6, IL-8 and TNF-α in chronic hepatitis B which could be down-regulated to （250.5 ±33.3） pg/ml, （153.4 ±22.2） pg/ml, （232.6 ±21.2） pg/ml by Lamivudine, which was more obvious than that of routine medicine （ P 〈 0.01）. Lamivudine has high therapeutic effect on the treatment of HBVDNA in PBMC and serum and has better therapeutic effect than that of routine therapy. Lamivudine may also have higher down-regtdated inflananatory infdtration and secretion in local site caused by chemotactic cytokines and produce promotional effect on the recovery of liver function.
基金supported by the National Transgenic Research Projects of China (Grant No. 2009ZX08009-026B)
文摘Virus-induced gene silencing is regarded as a powerful and efficient tool for the analysis of gene function in plants because it is simple, rapid and transformation-free. It has been used to perform both forward and reverse genetics to identify plant functional genes. Many viruses have been developed into virus-induced gene silencing vectors and gene functions involved in development, biotic and abiotic stresses, metabolism, and cellular signaling have been reported. In this review, we discuss the development and application of virus-induced gene silencing in plant functional genomics.
