Clinical curative effect of rhGM -CSF joint R -CHOP regimen in the treatment of diffuse large B cell lymphoma / 中国基层医药

Objective To study the clinical curative effect of the recombinant human granulocyte-macro-phage colony-stimulating factor ( rhGM -CSF) joint R-CHOP regimen in the treatment of diffuse large B cell lymphoma (DLBCL).Methods 72 hospitalized patients with DLBCL were chosen from January 2014 to January 2015.The patients were randomly divided into joint CHOP rituxan group ( R-CHOP group,36 cases) and the joint treatment group (36 cases) .The R-CHOP group was treated by R-CHOP regimen,the joint group was given rhGM-CSF on the basis of R-CHOP treatment.Before chemotherapy and 15 days,1 month,3 months after chemotherapy, the peripheral blood was collected,and the monocytes were separated,flow cytometry was used to count HLA-DR, CD197 marked M1 cells and CD68,CDl63 marked M2 cells.4 months after chemotherapy,the curative effect was evaluated.Results 4 months after treatment,the ORR of joint group (91.67%) was significantly higher than that of R-CHOP group (75.00%),and the difference was statistically significant (χ2 =4.372,P<0.05).After treatment, the adverse reactions of joint group,the liver function injuryⅠ-Ⅱlevel 8.33%,Ⅲ-Ⅳlevel 0.00%;White blood cells reduceⅠ-Ⅱlevel 25.00%,Ⅲ-Ⅳ level 5.56%;Thrombocytopenia Ⅰ-Ⅱ level 19.44%,Ⅲ-Ⅳ level;8.33%;Nausea and vomitingⅠ-Ⅱ level 8.33%,Ⅲ-Ⅳ level 0.00%.The adverse reactions after treatment of R-CHOP group,the liver function injury Ⅰ-Ⅱ level 13.89%,grade Ⅲ-Ⅳ2.78%;White blood cells reduceⅠ-Ⅱlevel 36.11%,Ⅲ-Ⅳlevel 11.11%;ThrombocytopeniaⅠ-Ⅱlevel 33.33%,Ⅲ-Ⅳlevel 2.78%;Nau-sea and vomitingⅠ-Ⅱ level 13.89%,Ⅲ-Ⅳ level 0.00%.The increased ratio of TAM quantity in combined treatment group (63.89%) was significantly more than R-CHOP group (38.89%),the difference was statistically significant (χ2 =7.938,P <0.05).In joint group,the positive expression rates of CD68 (46.11%),IL -6 (44.44%),IL-8 (58.33%) were significantly higher than those of R-CHOP group[CD68 (13.89%),IL-6 (19.44%),IL-8 (38.89%)],the differences were statistically significant (χ2 =3.278,3.278,4.489,all P<0.05).Conclusion R-CHOP joint rhGM -CSF has better curative effect than R-CHOP plan and less adverse reaction,and under the induction of rhGM -CSF,mononuclear cells can develop into M1 macrophages,in DLBCL microenvironment,to induce TAM to M1 M2 type in reverse polarization,improve the microenvironment of DLBCL and provide chance for cure of DLBCL.

Recombinant human granulocyte-macrophage colony-stimulating factor: effect of glycosylation on pharmacokinetic parameters

The pharmacokinetic behaviour of the non-glycosylated, bacterially-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and the glycosylated mammalian product was studied after intra and extra vascular administration of a single dose in rodents. Each route of administration gave a different rhGM-CSF concentration-time profile. After extra vascular administration of equivalent doses, a higher peak concentration and faster elimination were observed in the group treated with the E. coli-derived cytokine. The faster elimination resulted in a return to pre-treatment plasma levels after 12 hrs, versus 48 hrs following the administration of glycosylated rhGM-CSF. After intravascular administration, clearance of rhGM-CSF was significantly decreased by the presence of carbohydrates. Non-significant differences in the terminal phase of the biphasic kinetics were found, but the distribution phase was significantly longer for the glycosylated form

Multiplication and differentiation into endothelial cells of bone marrow stromal cells of rats in vitro / 中国康复理论与实践

@#ObjectiveTo explore the feasibility of bone marrow stromal cells (BMSC) of rats differentiating into endothelial cells.MethodsBone marrow cells were obtained by an aseptic technique. Afterwards, the obtained cells were divided into two groups: cells in test group were propagated in 1640 medium with recombinant human GM-CSF (rhGM-CSF) (400ng/ml), and that in control group were propagated in medium with 1640 medium only. The differentiated cells were detected by specific immunology marker by immunocytochemistry and immunofluorescence at day 8.ResultsThe differentiated cells demonstrated the characters of endothelial cells under phase contrast microscopy. Cells of the test groups demonstrated specific characters by immunocytochemistry stain.ConclusionBone marrow stromal cells can multiply vigorously and differentiate into cells with endothelial cells characters in the medium with high concentration rhGM-CSF.

Proliferation and identification of dendritic cells from peripheral blood of patients with bladder cancer in vitro / 中华泌尿外科杂志

Objective To investigate the proliferation and identification of dendritic cells(DC)de- rived from peripheral blood of patients with bladder cancer in vitro.Methods The mononuclear cells were prepared from peripheral blood of patients with bladder cancer by Ficoll-Hypaque centrifugation method,and were induced by the recombinant cytokines hGM-CSF(50 ng/ml),hlL-4(10 ng/ml)and hTNF-?(50 ng/ ml)for 2 weeks.The growth and morphology of DC were observed through the phase contrast or electron mi- croscope,and their pheuotypes were determined by flow cytometry.The capacity of DC to activate T cell-de- pendent anti-tumor immune responses was tested by MTT method.Results The DC cultured in vitro turned into suspensive growth from adhesive situation on the 6th day,then the number of DC increased con- tinuously and the cells showed the irregular morphologic appearance of DC with veiled edges on the 8th day. Flow cytometry showed that the mature DC expressed high levels of specific markers such as CD_(1a),CD_(83), CD_(86)and HLA-DR.T cells activated by DC showed strong cytotoxicity to bladder cancer cell line BIU87 with a killing rate of(48.8?3.7)%,while the killing rate of T cells which were not activated by DC was(25.7?1.5)%;the difference of the rate between them was significant(P＜0.01). Conclusions The DC can be cultured from peripheral blood of patients with bladder cancer by induction of rhGM-CSF,rhIL-4 and hT- NF-?in vitro.This may lay an experimental foundation for further research on DC vaccine.

The Effect of rhG-CSF and rhGM-CSF on Expression of Fc gamma Receptors and beta2 Integrin and Respiratory Burst Function in Human Granulocytes

PURPOSE: Receptors for the Fc of IgG(FcvR) and a beta2 integrin molecule, CD11c/CD18 are important in clearance of microbes by granulocytes. We performed an in vitro study on the effect of recombinant human granulocyte colony-stimulating factor(rhG-CSF), or granulocyte-macrophage colony-stimulating factor(rhGM-CSF) on the expression of Fc R II, Fc R III, CD11c and CD18 and respiratory burst function of granulocytes. METHODS: Peripheral blood was collected from six healthy adults. The isolated granulocytes were stimulated with rhG-CSF, 250mg/mL, rhGM-CSF, 100ng/mL or both of them for 1, 3, 9, 24, and 48 hours. Using flow cytometry, we compared the expression of the Fc R II, Fc R III, CD11c and CD18 of granulocytes before and after stimulation. We also the studied respiratory burst of granulocytes with chemiluminescence assay. RESULTS: Fc R II and CD18 expression were not changed significantly after stimulation. Fc R III expression was decreased significantly after stimulation with rhG-CSF, rhGM-CSF, or both of them. CD11c expression was increased initially but was found to decrease significantly after 9 hours of stimulation. Granulocytes treated with rhG-CSF, rhGM-CSF, or both displayed enhanced respiratory burst. Our results suggest that exposure of granulocyte to growth factor results in granulocyte activation. CONCLUSION: We have shown that rhG-CSF and rhGM-CSF resulted in an activation of peripheral blood granulocytes immunophenotypically and functionally.

Efficacy of Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) and Recombinant Human Granulocyte Macrophage Colony Stimulating Factor (rhGM-CSF) in Neutropenic Children with Malignancies / 대한소아혈액종양학회지

PURPOSE: Current intensive anticancer therapy may cause myelosuppression with an increased risk of severe infections. As a result, the administration of chemotherapy in cancer patients might be delayed often. Hemopoietic growth factors, which are responsible for the differentiation and functional regulation of granulocytes and monocytes, have been cloned and are available as rhG-CSF and rhGM-CSF. The aim of this study was to compare the efficacy and side effects of rhG-CSF and rhGM-CSF in children with cancer who received chemotherapy. METHODS: The study included 55 children ranging in age from 2 to 18 years who received chemotherapy for cancer and had absolute neutrophil count (ANC) under 500/muL. The growth-factors were administered subcutaneously starting in doses of 5~10 mug/ kg/day. The ANC was determined by complete blood counts starting on the first day of administration and every other day thereafter until the ANC rose above 1,000/muL. RESULTS: There was no significant difference in the mean days for increase of the mean ANC value >500/muL (5.0+/-2.9 vs 5.7+/-4.2 days) and >1,000/muL (5.9+/-3.2 vs 6.4+/-4.8 days) after rhG-CSF and rhGM-CSF respectively. Side effects of rhG-CSF and rhGM-CSF were fever, myalgia, bone pain, elevation of ALT and rGT and abdominal pain in order and there was no difference between two growth factors. Also the numbers of transfusion of packed RBCs (0.7+/-0.8 vs 0.7+/-0.8) and platelets (0.8+/-1.0 vs 0.6+/-0.9) were not different after the two growth factors. CONCLUSION: It seems to be that rhG-CSF and rhGM-CSF are comparable in clinical effects and side effects when used for granulocytopenia in children with cancer.

A Clinical Study on the Effect and Toxicity of rhGM-CSF / 대한부인종양콜포스코피학회잡지

Dosage reinforcement of chemotherapeutic agent is thought to be a solution in treating many malignancies, including ovarian cancer and cervical cancer. The remission rate after administration of chemotherapeutic agents has a positive correlation with dosage and in cases where limitations were put on dosage, improved survival rate was achieved with dose-intensive therapy facilitated by autologous bone marrow transplantation(BMT) or the use of cytokines such as G-CSF. Our objectives are to evaluate therapeutic efficacy and toxicity of GM-CSF and to elucidate the effect of premedication which was administered to minimize the toxicity of the GM-CSF. Total number of patients entered into this study was fifty two and they are consisted of thirty seven patients of the uterine cervix, fourteen patients of ovarian cancer and one endometrial cancer patient. The increase in neutrophil count and WBC count was found to be statistically valid, but the changes in the number of platelets, hemoglobin, neutrophil and monocytes were not shown to be meaningful when statistics are brought in. Administration of GM-CSF resulted in mild toxicities such as myalgia, fever, skin reaction and neuropathy. But, one patient had grade 3 myalgia. Premedication brought about meaningful reductions in the toxicities of GM-CSF and can be used safely to reduce the toxicities.

Physical and Chemical Characteristics and Peptide Mapping of Recombinant Human GM-CSF / 中国肿瘤生物治疗杂志

The plysical and chemical characteristics of recombinant human GM - CSF (rhGM - CSF) were studied separatly. rhGM - CSF was treated by GdHCl, reduced by DTT, and the disulfide bond was blocked by idoacetamide. The results showed that the samples aren' t homogeneous in UV absorption spectrum and RP-HPLC analysis after treatment by DTT. There was no remarkable differences in the results of the analysis of SDS-PAGE electrophoresis and western blot between treated and untreated rhGM - CSF samples. The effect of GdHCl on GM-CSF was reversible in all above tests; In peptide mapping analysis, the digestion of the samples with blocked disulfide bond by CNBr and protease is more complete than that without any treatment.