AIM: To study the effect of IGF-1/IGF-1R and gastrin/CCK-BR on carcinogenesis and development of human gastric carcinoma and to explore its mechanism and provide a credible theoretical foundation for early diagnosis a...AIM: To study the effect of IGF-1/IGF-1R and gastrin/CCK-BR on carcinogenesis and development of human gastric carcinoma and to explore its mechanism and provide a credible theoretical foundation for early diagnosis and molecular therapy of gastric carcinoma.METHODS: mRNA expression levels of IGF-1/IGF-1R and gastrin/CCK-BR were assessed by RT-PCR method in gastric cancer tissues, adjacent mucosa, and tumor-free tissues from 56 patients with gastric carcinoma and normal gastric mucosae from 56 healthy controls. Tissue specimens were obtained by biopsy and confirmed by histological evaluation.RESULTS: The mRNA levels of IGF-1/IGF-1R were increased in gastric cancer tissues compared with normal tissues from healthy controls and successively increased in tumor-free tissues, adjacent mucosa, and gastric cancer tissues. The mRNA levels of gastrin/CCK-BR were increased in gastric cancer tissues compared with normal tissues from healthy controls. There was a significant difference between gastric cancer tissues and adjacent mucosa and tumor-free tissues, but the mRNA levels of gastrin were not significantly increased in adjacent mucosa and gastric cancer tissues compared with tumorfree tissues. The mRNA levels of CCK-BR were increased in gastric cancer tissues and adjacent mucosa compared with tumor-free tissues, but not significantly increased in adjacent mucosa and gastric cancer tissues compared with gastric cancer tissues.CONCLUSION: Overexpression of IGF-1/IGF-1R and gastrin/CCK-BR promotes the disorderly proliferation of gastric mucosa epithelia and it is of great significance in the carcinogenesis and development of gastric carcinoma.展开更多
Bacteriorhodopsin(BR)exhibits,as a membrane protein in Halobacterium salinarum,unique photoresponsive behaviors,and shows promise as a functional information material.A new mutant of BR with the 96th aspartic acid rep...Bacteriorhodopsin(BR)exhibits,as a membrane protein in Halobacterium salinarum,unique photoresponsive behaviors,and shows promise as a functional information material.A new mutant of BR with the 96th aspartic acid replaced by valine(BR-D96V)was obtained and then a composite film of BR-D96V in a synthetic polymer matrix was prepared in this research.The mutant BR-D96V was expressed in a bacterio-opsin deficient halobacterial strain(L33)by gene engineering.Although valine is very hydrophobic,this point mutant keeps the basic biological activities,namely,photoelectric and photochromic responses.Nevertheless,the lifetime of M intermediate in the BR mutant is nearly two orders of magnitude longer than that of wild-type BR in neutral aqueous solution,which benefits its potential application as an information material.The M lifetime is further significantly prolonged after embedding BR-D96V into poly(vinyl alcohol)(PVA).It was also found that BR-D96V is very sensitive to water content in comparison with wild-type BR and another BR mutant.展开更多
Proteolysis targeting chimeras（PROTACs） are bispecific molecules containing a target protein binder and a ubiquitin ligase binder connected by a linker. Recently, some heterobifunctional small molecule bromodomain-c...Proteolysis targeting chimeras（PROTACs） are bispecific molecules containing a target protein binder and a ubiquitin ligase binder connected by a linker. Recently, some heterobifunctional small molecule bromodomain-containing protein 4（BRD4） degraders based on the concept of PROTACs were designed to induce the degradation of BRD4 protein. Herein, we synthesized a new class of PROTAC BRD4 degraders. One of the most promising compound 22f exhibited robust potency of BRD4 inhibition with IC50 value of （9.4±0.6） nmol/L. Furthermore, com- pound 22f potently inhibited cell proliferation in BRD4-sensitive cell lines RS4;11 with IC50 value of （27.6±1.6） nmol/L and capable of inducing degradation of BRD4 protein at 0.5-1.0 μmol/L in the RS4;11 cells. These data establish that compound 22f is a potent and efficacious BRD4 degrader.展开更多
基金Supported by the Natural Science Foundation of Shandong Province, No. Y2001C15
文摘AIM: To study the effect of IGF-1/IGF-1R and gastrin/CCK-BR on carcinogenesis and development of human gastric carcinoma and to explore its mechanism and provide a credible theoretical foundation for early diagnosis and molecular therapy of gastric carcinoma.METHODS: mRNA expression levels of IGF-1/IGF-1R and gastrin/CCK-BR were assessed by RT-PCR method in gastric cancer tissues, adjacent mucosa, and tumor-free tissues from 56 patients with gastric carcinoma and normal gastric mucosae from 56 healthy controls. Tissue specimens were obtained by biopsy and confirmed by histological evaluation.RESULTS: The mRNA levels of IGF-1/IGF-1R were increased in gastric cancer tissues compared with normal tissues from healthy controls and successively increased in tumor-free tissues, adjacent mucosa, and gastric cancer tissues. The mRNA levels of gastrin/CCK-BR were increased in gastric cancer tissues compared with normal tissues from healthy controls. There was a significant difference between gastric cancer tissues and adjacent mucosa and tumor-free tissues, but the mRNA levels of gastrin were not significantly increased in adjacent mucosa and gastric cancer tissues compared with tumorfree tissues. The mRNA levels of CCK-BR were increased in gastric cancer tissues and adjacent mucosa compared with tumor-free tissues, but not significantly increased in adjacent mucosa and gastric cancer tissues compared with gastric cancer tissues.CONCLUSION: Overexpression of IGF-1/IGF-1R and gastrin/CCK-BR promotes the disorderly proliferation of gastric mucosa epithelia and it is of great significance in the carcinogenesis and development of gastric carcinoma.
基金supported by the National Basic Research Program of China(2009CB930000)National Natural Science Foundation of China(50533010)
文摘Bacteriorhodopsin(BR)exhibits,as a membrane protein in Halobacterium salinarum,unique photoresponsive behaviors,and shows promise as a functional information material.A new mutant of BR with the 96th aspartic acid replaced by valine(BR-D96V)was obtained and then a composite film of BR-D96V in a synthetic polymer matrix was prepared in this research.The mutant BR-D96V was expressed in a bacterio-opsin deficient halobacterial strain(L33)by gene engineering.Although valine is very hydrophobic,this point mutant keeps the basic biological activities,namely,photoelectric and photochromic responses.Nevertheless,the lifetime of M intermediate in the BR mutant is nearly two orders of magnitude longer than that of wild-type BR in neutral aqueous solution,which benefits its potential application as an information material.The M lifetime is further significantly prolonged after embedding BR-D96V into poly(vinyl alcohol)(PVA).It was also found that BR-D96V is very sensitive to water content in comparison with wild-type BR and another BR mutant.
文摘Proteolysis targeting chimeras（PROTACs） are bispecific molecules containing a target protein binder and a ubiquitin ligase binder connected by a linker. Recently, some heterobifunctional small molecule bromodomain-containing protein 4（BRD4） degraders based on the concept of PROTACs were designed to induce the degradation of BRD4 protein. Herein, we synthesized a new class of PROTAC BRD4 degraders. One of the most promising compound 22f exhibited robust potency of BRD4 inhibition with IC50 value of （9.4±0.6） nmol/L. Furthermore, com- pound 22f potently inhibited cell proliferation in BRD4-sensitive cell lines RS4;11 with IC50 value of （27.6±1.6） nmol/L and capable of inducing degradation of BRD4 protein at 0.5-1.0 μmol/L in the RS4;11 cells. These data establish that compound 22f is a potent and efficacious BRD4 degrader.
