A serials of novel 5-substituted benzyl-2,4-diamino pyrimidine derivatives have been synthesized and evaluated as inhibitors of c-Fms kinase by the standard MTT method.The results showed that compound 15,5-[3-methoxy...A serials of novel 5-substituted benzyl-2,4-diamino pyrimidine derivatives have been synthesized and evaluated as inhibitors of c-Fms kinase by the standard MTT method.The results showed that compound 15,5-[3-methoxy-4-（pyridine-3-yl）benzyl]-2,4-diamino pyrimidine,had an IC50 of 1.45μmol/L in inhibiting the proliferation of M-CSF-dependent myeloid leukemia cells in mice （NFS-60）,which was similar with GW2580,a selective inhibitor of c-Fms kinase.展开更多
BACKGROUND: Recent research found abnormal expres- sion of the c-fms oncogene, which encodes the macro- phage colony-stimulating factor receptor (CSF-1R), in several human carcinomas including hepatocellular carcino- ...BACKGROUND: Recent research found abnormal expres- sion of the c-fms oncogene, which encodes the macro- phage colony-stimulating factor receptor (CSF-1R), in several human carcinomas including hepatocellular carcino- ma (HCC). But the relationship between the point muta- tion and abnormal expressing of c-fms oncogene in HCC was not clear. This study is to investigate the relationship between point mutation and abnormal expression of c-fms oncogene in hepatocellular carcinoma (HCC) and to clari- fy the mechanism of HCC. METHODS: The expression of c-fms oncogene at different levels of cell, protein and transcription was observed using immune histological ABC, Western blot and Northern blot. PCR-single strand conformation polymorphism and gene sequencing were used to detect the mutation of c-fms in HCC tissues and their surrounding tissues of 30 patients. RESULTS: The expression of c-fms was significantly higher in HCC tissues than in their surrounding tissues (P <0.01). Point mutation of Leu (TTG)—>Ser (TCG) at codon 301 of c-fms amino acids was observed in 21.4% (3/14) HCC tissues. No mutation of c-fms oncogene was detected in the surrounding cancerous tissues. CONCLUSION: Point mutation at codon 301 of c-fms on- cogene is one of the mechanisms of abnormal over-expres- sion in HCC.展开更多
Objective: To study the clinical significance and relationship between c-fms oncogene and hepatocellular carcinogenesis, to further clarify the occurring mechanism of hepatocellular carcinoma (HCC). Methods: PCR-SSCP ...Objective: To study the clinical significance and relationship between c-fms oncogene and hepatocellular carcinogenesis, to further clarify the occurring mechanism of hepatocellular carcinoma (HCC). Methods: PCR-SSCP technique was used to analyse mutation of c-fms oncogene in 30 cases of HCC tissues. Sequencing the PCR products after cloning to prove the mutations, meanwhile the relationship between c-fms mutations and clinical pathology of HCC was investigated. Results: Two abnormal single strands were observed in 10% (3/30) HCC tissues from c-fms DNA corresponding to 301st codon of c-fms amino acids. PCR products of abnormal single strands were sequenced after cloning, it demonstrated that there was transition of T→C at nucleic acid 14855 of c-fms DNA, which corresponded to transition of Leu (TTG)→Ser (TCG) at 301st codon of c-fms amino acids. The mutation was related to malignant degree and type of HCC tissues as well as patient’s age. Conclusion: Mutation of c-fms codon at site 301 implied a molecular mechanism contributing to hepatocellular carcinogenesis.展开更多
基金financially supported by the National High-Tech Research and Development Program of China(863 Program)(No.2006AA10A201)National Natural Science Foundation(No.30472093)
文摘A serials of novel 5-substituted benzyl-2,4-diamino pyrimidine derivatives have been synthesized and evaluated as inhibitors of c-Fms kinase by the standard MTT method.The results showed that compound 15,5-[3-methoxy-4-（pyridine-3-yl）benzyl]-2,4-diamino pyrimidine,had an IC50 of 1.45μmol/L in inhibiting the proliferation of M-CSF-dependent myeloid leukemia cells in mice （NFS-60）,which was similar with GW2580,a selective inhibitor of c-Fms kinase.
基金This study was supported by the National Science Foundation of China( No 30070853 ) and the Science Foundation of Guangdong Province,China (No. 990422)
文摘BACKGROUND: Recent research found abnormal expres- sion of the c-fms oncogene, which encodes the macro- phage colony-stimulating factor receptor (CSF-1R), in several human carcinomas including hepatocellular carcino- ma (HCC). But the relationship between the point muta- tion and abnormal expressing of c-fms oncogene in HCC was not clear. This study is to investigate the relationship between point mutation and abnormal expression of c-fms oncogene in hepatocellular carcinoma (HCC) and to clari- fy the mechanism of HCC. METHODS: The expression of c-fms oncogene at different levels of cell, protein and transcription was observed using immune histological ABC, Western blot and Northern blot. PCR-single strand conformation polymorphism and gene sequencing were used to detect the mutation of c-fms in HCC tissues and their surrounding tissues of 30 patients. RESULTS: The expression of c-fms was significantly higher in HCC tissues than in their surrounding tissues (P <0.01). Point mutation of Leu (TTG)—>Ser (TCG) at codon 301 of c-fms amino acids was observed in 21.4% (3/14) HCC tissues. No mutation of c-fms oncogene was detected in the surrounding cancerous tissues. CONCLUSION: Point mutation at codon 301 of c-fms on- cogene is one of the mechanisms of abnormal over-expres- sion in HCC.
文摘Objective: To study the clinical significance and relationship between c-fms oncogene and hepatocellular carcinogenesis, to further clarify the occurring mechanism of hepatocellular carcinoma (HCC). Methods: PCR-SSCP technique was used to analyse mutation of c-fms oncogene in 30 cases of HCC tissues. Sequencing the PCR products after cloning to prove the mutations, meanwhile the relationship between c-fms mutations and clinical pathology of HCC was investigated. Results: Two abnormal single strands were observed in 10% (3/30) HCC tissues from c-fms DNA corresponding to 301st codon of c-fms amino acids. PCR products of abnormal single strands were sequenced after cloning, it demonstrated that there was transition of T→C at nucleic acid 14855 of c-fms DNA, which corresponded to transition of Leu (TTG)→Ser (TCG) at 301st codon of c-fms amino acids. The mutation was related to malignant degree and type of HCC tissues as well as patient’s age. Conclusion: Mutation of c-fms codon at site 301 implied a molecular mechanism contributing to hepatocellular carcinogenesis.
