Impaired tumor necrosis factor receptor-1(TNFR-1)signaling has been found in some malignant tumors with poor prognosis.However,the exact role of TNFR-1 signaling in fi brosarcoma remains unclear.Here,we explored the q...Impaired tumor necrosis factor receptor-1(TNFR-1)signaling has been found in some malignant tumors with poor prognosis.However,the exact role of TNFR-1 signaling in fi brosarcoma remains unclear.Here,we explored the question by comparing the growth of TNFR-1 deficient(Tnfr1-)and TNFR-1 competent(Tnfr1+)fibrosarcoma FB61 cells(FB61-m and FB61-R1)in mice.TNFR-1 expression on fibrosarcoma cells delayed their growth in vivo but not in vitro.Moreover,reduced FB61-R1 tumor growth was also obtained in T NFR-1 knockout mice.The mechanism relies mainly on the TNFR-1-mediated down-regulation of vascular endothelial growth factor(VEGF)production by tumor cells.Importantly,treatment of FB61-m tumors with melphalan resulted in a short delay of tumor growth,followed by a quick r emission.However,when FB61-R1 tumors were treated with melphalan,tumor growth was similarly delayed at fi rst and then completely rejected.Our results reveal evidence for TNFR-1 on tumor cells as a prerequisite in chemotherapy for fi brosarcoma,and provide novel insight into the therapeutic approach against some types of tumors using TNFR-1 angonist.展开更多
The expression of silience of death domains (SODD) and its clinical significance and relationship with phospho-NF-κB-p65 proteins in bone marrow cells of childhood acute lymphoblas- tic leukaemia (ALL) were explored,...The expression of silience of death domains (SODD) and its clinical significance and relationship with phospho-NF-κB-p65 proteins in bone marrow cells of childhood acute lymphoblas- tic leukaemia (ALL) were explored, and the expression of SODD and phospho-NF-κB-p65 in Jurkat cells treated with chemotherapeutic drugs was detected in order to find a new chemotherapeutic target. The expression of SODD and phospho-NF-κB-p65 proteins in bone marrow cells was detected by immunohistochemistry in 25 children with ALL. The apoptosis rate was measured by An- nexin-V-Fluorescence/PI double-labeling flow cytometry and the expression of SODD and phos- pho-NF-κB-p65 proteins determined by Western blotting in the Jurkat cells. It was found that the ex- pression of SODD and active P65 in ALL was significantly higher than that in normal control group (P<0.05). The expression of the SODD and phospho-NF-κB-p65 proteins in the high-risk (HR) group was significantly higher than that in the standard-risk (SR) group (P<0.05). The Pearson rank correla- tion analysis revealed that there was a positive correlation between SODD and phospho-NF-κB-p65 expression (P<0.01, r=0.69). VCR could effectively induce the apoptosis of Jurkat cells, and down-regulate the expression of SODD and phospho-NF-κB-p65 proteins in a time-dependent man- ner, but DNR could not down-regulate the expression of SODD effectively. It was concluded that SODD may be closely related to the clinical classification and prognosis of ALL in children. The ex- pression of SODD and phospho-NF-κB-p65 had a definite synergistic relationship with the onset and development of ALL. VCR could down-regulate the expression of SODD and inhibit the NF-κB ac- tivation, which could recover the sensibility of apoptosis in leukemic cells.展开更多
基金supported by the Ministry of Science and Technology of China(Grant No.2012CB917103)National Natural Science Foundation of China(Grant Nos.81030049 and 91229203).
文摘Impaired tumor necrosis factor receptor-1(TNFR-1)signaling has been found in some malignant tumors with poor prognosis.However,the exact role of TNFR-1 signaling in fi brosarcoma remains unclear.Here,we explored the question by comparing the growth of TNFR-1 deficient(Tnfr1-)and TNFR-1 competent(Tnfr1+)fibrosarcoma FB61 cells(FB61-m and FB61-R1)in mice.TNFR-1 expression on fibrosarcoma cells delayed their growth in vivo but not in vitro.Moreover,reduced FB61-R1 tumor growth was also obtained in T NFR-1 knockout mice.The mechanism relies mainly on the TNFR-1-mediated down-regulation of vascular endothelial growth factor(VEGF)production by tumor cells.Importantly,treatment of FB61-m tumors with melphalan resulted in a short delay of tumor growth,followed by a quick r emission.However,when FB61-R1 tumors were treated with melphalan,tumor growth was similarly delayed at fi rst and then completely rejected.Our results reveal evidence for TNFR-1 on tumor cells as a prerequisite in chemotherapy for fi brosarcoma,and provide novel insight into the therapeutic approach against some types of tumors using TNFR-1 angonist.
基金a grant from National Natu-ral Sciences Foundation of China (No. 39970778)
文摘The expression of silience of death domains (SODD) and its clinical significance and relationship with phospho-NF-κB-p65 proteins in bone marrow cells of childhood acute lymphoblas- tic leukaemia (ALL) were explored, and the expression of SODD and phospho-NF-κB-p65 in Jurkat cells treated with chemotherapeutic drugs was detected in order to find a new chemotherapeutic target. The expression of SODD and phospho-NF-κB-p65 proteins in bone marrow cells was detected by immunohistochemistry in 25 children with ALL. The apoptosis rate was measured by An- nexin-V-Fluorescence/PI double-labeling flow cytometry and the expression of SODD and phos- pho-NF-κB-p65 proteins determined by Western blotting in the Jurkat cells. It was found that the ex- pression of SODD and active P65 in ALL was significantly higher than that in normal control group (P<0.05). The expression of the SODD and phospho-NF-κB-p65 proteins in the high-risk (HR) group was significantly higher than that in the standard-risk (SR) group (P<0.05). The Pearson rank correla- tion analysis revealed that there was a positive correlation between SODD and phospho-NF-κB-p65 expression (P<0.01, r=0.69). VCR could effectively induce the apoptosis of Jurkat cells, and down-regulate the expression of SODD and phospho-NF-κB-p65 proteins in a time-dependent man- ner, but DNR could not down-regulate the expression of SODD effectively. It was concluded that SODD may be closely related to the clinical classification and prognosis of ALL in children. The ex- pression of SODD and phospho-NF-κB-p65 had a definite synergistic relationship with the onset and development of ALL. VCR could down-regulate the expression of SODD and inhibit the NF-κB ac- tivation, which could recover the sensibility of apoptosis in leukemic cells.
