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 fibrosarcoma 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 TNFR-1 knockout mice. The mechanism relies mainly on the TNFR-1-mediated downregulation 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 remission. However, when FB61-R1 tumors were treated with melphalan, tumor growth was similarly delayed at first and then completely rejected. Our results reveal evidence for TNFR-1 on tumor cells as a prerequisite in chemotherapy for fibrosarcoma, and provide novel insight into the therapeutic approach against some types of tumors using TNFR-1 angonist.
Animals ; Down-Regulation ; drug effects ; Fibrosarcoma ; drug therapy ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Melphalan ; administration & dosage ; Mice ; Molecular Targeted Therapy ; Receptors, Tumor Necrosis Factor, Type I ; genetics ; Signal Transduction ; drug effects ; Vascular Endothelial Growth Factor A ; biosynthesis

Objective To concentrate coagulation Factor Ⅺ(FⅪ)from human plasma.Methods FⅪwas isolated and purified from human plasma via two-step chromatography,including CM-Sepharose fast flow ion exchange and Heparin CL-6B affinity chromatography.Results The recovery rate of FⅪ was(21.02?5.04)%,the specific clotting activity of purified FⅪ was(17.59?1.96) U/mg,and the purification factor was(1162.29?129.64) fold(n=7).Conclusion The two-step chromatography is effective in concentrating FⅨ.

Objective To isolate and purify human coagulation factor Ⅶ from Cohn fraction Ⅲ precipitate.Methods The purification procedure of human factor Ⅶ from Cohn fraction Ⅲ precipitate involves dissolving fraction Ⅲ,absorbing factor Ⅶ onto barium citrate and eluting,ammonium sulfate fractionation and DEAE-Sepharose Fast Flow ion exchange chromatography,and Sephadex G-100 gel filtration chromatography.Results 10.1mg purified FⅦ was obtained from 400g Cohn fraction Ⅲ precipitate.The purified FⅦ has a specific clotting activity of 1775.8U/mg and the overall yield of FⅦ specific clotting activity is 17.6% of the starting material.The purity of FⅦ was judged by SDS-PAGE and there was only one protein band on the gel.Conclusion The procedure of purifying Ⅶ from Cohn fraction Ⅲprecipitate is established with satisfactory purity.

A specific monoclonal antibody(McAb),which could identfy different conformations of protein C(PC) in the presence or absence of Ca24+ .was selected and coupled with Sepharose-4B gel to form an affinity chromatographic column. When fresh plasma passed through this column.its PC would he adsorbed exclusively,and the obtained effuent was PC-deficient plasma (PCDP). The residual PC in the PCDP gained was