Effects of G-CSF Gene Therapy bn the Number and Functions of Peripheral Neutrophils of Colon Adenocarcinoma-Bearing Mice Receiving High-Dose Chemotherapy / 中国肿瘤生物治疗杂志

Neutrophils play important role in anti - tumor response of tumor-bearing host as a kind of important effector cells. In order to identify the anti-tumor mechanisms of G-CSF gene therapy, we investigated the number and functions of the peripheral neutrophils in the C-26 colon adenocarcinoma-bearing mice receiving G - CSF gene therapy and high - dose chemotherapy. After G - CSF gene therapy, the number of neutrophils in peripheral blood was increased markedly in C-26 mice receiving high - dose 5 - Fu as compared with control groups including in vivo administration of rhG - CSF. The more potent cytotoxicity to C - 26 cells could be detected. The phagocytic activity, the secretion of IL-1, TNF, NO of the neutrophils were significantly enhanced. These data showed that G - CSF gene therapy can increase the number of neutrophils, activate the functions more effectively than in vivo administration of rhG - CSF.

Antitumor Effects of G-CSF Gene Therapy on Colon Adenocarcinoma-Bearing Mice Receiving High-Dose Chemotherapy / 中国肿瘤生物治疗杂志

Granulocyte colony - stimulating factor (G - CSF) is a hematopoietic growth factor that is responsible for the differentiation and proliferation of hematopoietic progenitor cells to mature granulocyte, and can increase the number of peripheral neutrophils. It has been demonstrated that it could inhibit the metastasis of the murine tumors in spontaneous and experimental metastasis models by in vivo administration of recombinant human G - CSF. In order to examine the antitumor effect of G - CSF gene therapy on mice receiving high - dose chemotherapy, C - 26 colon adenocarcinoma - bearing mice which were prepared by S. c. injection of 1?105C-26 cells were i. p. injected with rhG-CSF (2?g/day?14day) or implanted with 1?107 collagen encapsulated NIH3T3-G-CSF cells which secrete high level of G - CSF after gene transfection. In our experiment, rhG-CSF could inhibit the tumor growth and extend the survival time of early stage C-26 bearing mice. However, G - CSF gene therapy could inhibit the tumor growth and prolong the survival both in early or middle stage C-26 mice. The results showed that both rhG - CSF and G - CSF gene therapy have exact antitumor effect and G - CSF gene therapy show more effective than rhG - CSF in vivo. Then we investigated the therapeutic effects of G - CSF gene therapy on C-26-bearing mice receiving high - dose chemotherapy (5-Fu 150mg/mice i. p.) . More effective results could be observed in C-26 - bearing mice receiving high dose chemotherapy after G - CSF gene therapy. The results also suggested that G-CSF gene therapy can inhibit the tumor growth more effectively both in C-26-bearing mice or C-26-bearing mice receiving high - dose chemotherapy.

The Enhancing Effects of Fibroblast-Mediated G-CSF Gene Therapy on the Recovery of Hematopoiesis / 中国肿瘤生物治疗杂志

In the present study, the effects of G-CSF gene therapy was investigated on the recovery of murine hematopoietic suppression induced by high dose of cyclophosphomide (Cy) . The results showed that G-CSF gene therapy could slow down the Cy-induced decreasing of peripheral WBCs and platelets, and accerelate their recovery.It also could increase the CFU-GM, CFU - MK, CFU-S derived from the splenocyte and bone marrow cells in the chemotherapy-treated mice. The data demonstrated that fibroblast-mediated G-CSF gene therapy could significantlyreduce the hematopoietic damage to less extent, and accerelate hematopoietic recovery after chemotherapy.