tailieunhanh - Báo cáo y học: "Effect of a structurally modified human granulocyte colony stimulating factor, G-CSFa, on leukopenia in mice and monkeys"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Effect of a structurally modified human granulocyte colony stimulating factor, G-CSFa, on leukopenia in mice and monkeys. | Jiang et al. Journal of Hematology Oncology 2011 4 28 http content 4 1 28 JOURNAL OF HEMATOLOGY ONCOLOGY RESEARCH Open Access Effect of a structurally modified human granulocyte colony stimulating factor G-CSFa on leukopenia in mice and monkeys Yongping Jiang1 Wenhong Jiang1 Yuchang Qiu1 and Wei Dai2 Abstract Background Granulocyte colony stimulating factor G-CSF regulates survival proliferation and differentiation of neutrophilic granulocyte precursors Recombinant G-CSF has been used for the treatment of congenital and therapy-induced neutropenia and stem cell mobilization. Due to its intrinsic instability recombinant G-CSF needs to be excessively and or frequently administered to patients in order to maintain a plasma concentration high enough to achieve therapeutic effects. Therefore there is a need for the development of G-CSF derivatives that are more stable and active in vivo. Methods Using site-direct mutagenesis and recombinant DNA technology a structurally modified derivative of human G-CSF termed G-CSFa was obtained. G-CSFa contains alanine 17 instead of cysteine 17 as in wild-type G-CSF as well as four additional amino acids including methionine arginine glycine and serine at the aminoterminus. Purified recombinant G-CSFa was tested for its in vitro activity using cell-based assays and in vivo activity using both murine and primate animal models. Results In vitro studies demonstrated that G-CSFa expressed in and purified from E. coli induced a much higher proliferation rate than that of wild-type G-CSF at the same concentrations. In vivo studies showed that G-CSFa significantly increased the number of peripheral blood leukocytes in cesium-137 irradiated mice or monkeys with neutropenia after administration of clyclophosphamide. In addition G-CSFa increased neutrophil counts to a higher level in monkeys with a concomitant slower declining rate than that of G-CSF indicating a longer half-life of G-CSFa. Bone marrow smear analysis also .