Even though liver metastasis accounts for the vast majority of cancer deaths in patients with colorectal cancer (CRC), fundamental questions about the molecular and cellular mechanisms of liver metastasis still remain...Even though liver metastasis accounts for the vast majority of cancer deaths in patients with colorectal cancer (CRC), fundamental questions about the molecular and cellular mechanisms of liver metastasis still remain unanswered. Determination of gene expression profiles by microarray technology has improved our knowledge of CRC molecular pathways. However, defined gene signatures are highly variable among studies. Expression profiles and molecular markers have been specifically linked to liver metastases mechanistic paths in CRC. However, to date, none of the identified signatures or molecular markers has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. To obtain a genetic signature for liver metastasis in CRC, measures to improve reproducibility, to increase consistency, and to validate results need to be implemented. Alternatives to expression profiling with microarray technology are continuing to be used. In the recent past, many genes codifying for proteins that are directly or indirectly involved in adhesion, invasion, angiogenesis, survival and cell growth have been linked to mechanisms of liver metastases in CRC.展开更多
AIM： To investigate dynamic changes and significance of expression of NF-κBp65 in pancreatic tissues of rats with severe acute pancreatitis （SAP）, as well as BN52021 effects. METHODS： Wistar male rats were random...AIM： To investigate dynamic changes and significance of expression of NF-κBp65 in pancreatic tissues of rats with severe acute pancreatitis （SAP）, as well as BN52021 effects. METHODS： Wistar male rats were randomly divided into negative control group （NC group, n = 60）, SAP-model group （SAP group, n = 60）, and BN52021-treated group （BN group, n = 60）, and each of the above groups was respectively divided into 6 subgroups at different time points after operation （1 h, 2 h, 3 h, 6 h, 12 h, and 24 h） （n = 10）. By RT-PCR and Western blot, NF-κBp65 mRNA and its protein expression in pancreatic tissues of rats were detected respectively. RESULTS： The expression of NF-κBp65 mRNA dynamically changed in both SAP groups and BN groups. The mRNA level was higher in SAP groups than NC groups at 2 h, 3 h, 12 h, and 24 h after operation （P 〈 0.05）, higher in BN groups than NC groups at all time points （P 〈 0.05）, and higher in BN groups than SAP group at 1 h （P 〈 0.05）. The NF-κBp65 protein level was higher in SAP groups than NC groups at 1 h, 3 h, and 6 h （P 〈 0.01）, and 2 h, 12 h, and 24 h （P 〈 0.05）, higher in BN groups than NC groups at all time points （P 〈 0.05）, and lower in BN groups than SAP groups at 1 h, 3 h, and 6 h （P 〈 0.05）. CONCLUSION： The expression of NF-κBp65 in pancreatic tissues is dynamically changed and the changes play an important role in pathogenesis of SAR BN52021 exerts therapeutic effects through reducing the expression level of NF-κBp65 protein in the early stage of SAR展开更多
The aim of this study is to discover the molecular mechanism of the 22-week gestated human fetal liver (HFL) which rarely displays both hematopoietic and hepatic functions.Based on large-scale cDNA library sequencing ...The aim of this study is to discover the molecular mechanism of the 22-week gestated human fetal liver (HFL) which rarely displays both hematopoietic and hepatic functions.Based on large-scale cDNA library sequencing and bioinformatic analysis,the largest gene expression profile of human fetal liver in the world was successfully established.A set of gene clusters func- tionally related to the liver development,hepatocarci- nogenesis and hematopoiesis have been identified.This is for the first time that we could panoramically under- stand the molecular mechanism of the dual functions of human fetal liver.Moreover,201 unrecorded human homologous genes and 609 novel genes have been iden- tified and annotated,which accounting for more than 7% of the known human genes in 2001.In the recent human genome annotation map (human genome build 35. 1 ), 45 genes were nominated based on this study. In addition, we have characterized a set of gene fami- lies represented by hepatopoietin (HPO), Semaphorin, LSECtin and ARFGAP.Two distinctive novel pathways, 'extracellular HPO→HPOreceptor→EGF receptor→Raf→MEK→MAPK' for autocrine and 'intracellular HPO→JAB1→c-JUN(AP-1)' for intracrine of HPO, an unusual cytokine functioned in the regeneration of liver, has been reported for the first time, which have shed new lights on the study of the signal transduction of the entire HPO family.We have also demonstrated that HPO could act as a FAD thioloxidase and that only its intracrine pathway is dependent on the enzymatic activi- ty. It is also known for the first time that the enzyme activity is critically important for the cytokine HPO.Re- garding the regulation of the gene expression of HPO,it was demonstrated that HPO promoter includes a nega- tive regulatory element and a core promoter (comprises an initiator and its flanking three tandem IFE elements). Furthermore,two novel members of Semaphorin family, SEMA6C and SEMA6D,were cloned and shown to be able to determine the orientation of the cell growth.We have also discovered and characterized a novel lectin family including LSECtin, CD23,DC-SIGN and DC- SIGNR.The function of LSECtin was also defined to be important in adhesion of the cells.In addition,the first human member of ARFGAP family was cloned and shown to regulate protein secretion.The publications based on this study have been cited for 145 times by SCl journals before 2005.This study has provided im- portant original data for the annotation of human genome and establishment of human transcriptome.It also played an important role in Chinese national achievement of cloning and annotation of the 10% human cDNAs pro- ject and set up the corner-stone for the leading role of China in the international 'Human Liver Proteome Pro- ject'.展开更多
文摘Even though liver metastasis accounts for the vast majority of cancer deaths in patients with colorectal cancer (CRC), fundamental questions about the molecular and cellular mechanisms of liver metastasis still remain unanswered. Determination of gene expression profiles by microarray technology has improved our knowledge of CRC molecular pathways. However, defined gene signatures are highly variable among studies. Expression profiles and molecular markers have been specifically linked to liver metastases mechanistic paths in CRC. However, to date, none of the identified signatures or molecular markers has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. To obtain a genetic signature for liver metastasis in CRC, measures to improve reproducibility, to increase consistency, and to validate results need to be implemented. Alternatives to expression profiling with microarray technology are continuing to be used. In the recent past, many genes codifying for proteins that are directly or indirectly involved in adhesion, invasion, angiogenesis, survival and cell growth have been linked to mechanisms of liver metastases in CRC.
基金the National Natural Science Foundation of China, No. 30300465
文摘AIM： To investigate dynamic changes and significance of expression of NF-κBp65 in pancreatic tissues of rats with severe acute pancreatitis （SAP）, as well as BN52021 effects. METHODS： Wistar male rats were randomly divided into negative control group （NC group, n = 60）, SAP-model group （SAP group, n = 60）, and BN52021-treated group （BN group, n = 60）, and each of the above groups was respectively divided into 6 subgroups at different time points after operation （1 h, 2 h, 3 h, 6 h, 12 h, and 24 h） （n = 10）. By RT-PCR and Western blot, NF-κBp65 mRNA and its protein expression in pancreatic tissues of rats were detected respectively. RESULTS： The expression of NF-κBp65 mRNA dynamically changed in both SAP groups and BN groups. The mRNA level was higher in SAP groups than NC groups at 2 h, 3 h, 12 h, and 24 h after operation （P 〈 0.05）, higher in BN groups than NC groups at all time points （P 〈 0.05）, and higher in BN groups than SAP group at 1 h （P 〈 0.05）. The NF-κBp65 protein level was higher in SAP groups than NC groups at 1 h, 3 h, and 6 h （P 〈 0.01）, and 2 h, 12 h, and 24 h （P 〈 0.05）, higher in BN groups than NC groups at all time points （P 〈 0.05）, and lower in BN groups than SAP groups at 1 h, 3 h, and 6 h （P 〈 0.05）. CONCLUSION： The expression of NF-κBp65 in pancreatic tissues is dynamically changed and the changes play an important role in pathogenesis of SAR BN52021 exerts therapeutic effects through reducing the expression level of NF-κBp65 protein in the early stage of SAR
文摘The aim of this study is to discover the molecular mechanism of the 22-week gestated human fetal liver (HFL) which rarely displays both hematopoietic and hepatic functions.Based on large-scale cDNA library sequencing and bioinformatic analysis,the largest gene expression profile of human fetal liver in the world was successfully established.A set of gene clusters func- tionally related to the liver development,hepatocarci- nogenesis and hematopoiesis have been identified.This is for the first time that we could panoramically under- stand the molecular mechanism of the dual functions of human fetal liver.Moreover,201 unrecorded human homologous genes and 609 novel genes have been iden- tified and annotated,which accounting for more than 7% of the known human genes in 2001.In the recent human genome annotation map (human genome build 35. 1 ), 45 genes were nominated based on this study. In addition, we have characterized a set of gene fami- lies represented by hepatopoietin (HPO), Semaphorin, LSECtin and ARFGAP.Two distinctive novel pathways, 'extracellular HPO→HPOreceptor→EGF receptor→Raf→MEK→MAPK' for autocrine and 'intracellular HPO→JAB1→c-JUN(AP-1)' for intracrine of HPO, an unusual cytokine functioned in the regeneration of liver, has been reported for the first time, which have shed new lights on the study of the signal transduction of the entire HPO family.We have also demonstrated that HPO could act as a FAD thioloxidase and that only its intracrine pathway is dependent on the enzymatic activi- ty. It is also known for the first time that the enzyme activity is critically important for the cytokine HPO.Re- garding the regulation of the gene expression of HPO,it was demonstrated that HPO promoter includes a nega- tive regulatory element and a core promoter (comprises an initiator and its flanking three tandem IFE elements). Furthermore,two novel members of Semaphorin family, SEMA6C and SEMA6D,were cloned and shown to be able to determine the orientation of the cell growth.We have also discovered and characterized a novel lectin family including LSECtin, CD23,DC-SIGN and DC- SIGNR.The function of LSECtin was also defined to be important in adhesion of the cells.In addition,the first human member of ARFGAP family was cloned and shown to regulate protein secretion.The publications based on this study have been cited for 145 times by SCl journals before 2005.This study has provided im- portant original data for the annotation of human genome and establishment of human transcriptome.It also played an important role in Chinese national achievement of cloning and annotation of the 10% human cDNAs pro- ject and set up the corner-stone for the leading role of China in the international 'Human Liver Proteome Pro- ject'.
