ABSTRACT
Objective: To investigate the pharmacokinetics, tissue distribution and excretion characteristics of Fc- G- CSF (the fusion protein of Fc and granulocyte colony stimulating factor)in rats. Methods: Fc-G-CSF was labeled with 125I by the chloramine T method, and the content of 125I-Fc-G-CSF in each biological sample was determined by the trichloroacetic acid(TCA)precipitation method. Results: After a single subcutaneous injection of 125I-Fc-G-CSF 30 μg/kg, the AUC was(362.1±48.1)μg•h/L and the Cmax was(27.0±3.0)μg/L. Up to 36 hours of the drug administration, the drug exposure was highest in serum but lowest in brain. Up to 96 hours of the drug administration, the cumulative excretion rate through urine was about 57.5%, and the cumulative excretion rate through feces was about 23.5%. Conclusion: The blood concentration of 125I-Fc-G-CSF reached a peak after 12 h of the subcutaneous injection in rats, and the serum concentration was continuously higher than the concentrations in other tissues. The 125I-Fc-G-CSF excretion mainly adopted the urinary excretion.
ABSTRACT
BACKGROUND: This study was performed to assess serial cytokine changes and their clinical impact in children with cerebral palsy (CP) who received granulocyte-colony stimulating factor (G-CSF) followed by infusion of autologous mobilized peripheral blood mononuclear cells (mPBMCs). METHODS: Peripheral blood (PB) samples were collected from 16 CP children at enrollment, and 1 month and 7 months after G-CSF infusion as well as at the end of the study. Cytokine levels were measured by enzyme-linked immunosorbent assays with plasma samples. RESULTS: There were no significant differences in cytokine levels between the mPBMC and placebo groups over 6 months. However, when clinical responders and non-responders were compared, interleukin (IL)-6 (P = 0.050) as well as G-CSF (P = 0.010) were higher in the responders than the non-responders at 1 month, while brain-derived neurotrophic factor (BDNF) (P = 0.030) and insulin-like growth factor (IGF)-1 (P = 0.001) were lower. In addition, BDNF was higher at baseline in the responders than the non-responders (P = 0.030). CONCLUSION: The changes of G-CSF itself, as well as G-CSF-induced cytokines such as IL-6, may be associated with the clinical improvement of neurologic functions. The G-CSF-induced changes of IL-6, BDNF and IGF-1, and BDNF levels before treatment, could be used as prognostic factors in G-CSF trials in CP children.
Subject(s)
Child , Humans , Brain-Derived Neurotrophic Factor , Cerebral Palsy , Cytokines , Enzyme-Linked Immunosorbent Assay , Granulocyte Colony-Stimulating Factor , Insulin-Like Growth Factor I , Interleukin-6 , Interleukins , PlasmaABSTRACT
Objective To investigate the protective effects and mechanisms of granulocyte-colony-stimulating factor (G-CSF)on a rabbit model of chronic myocardial ischemia.Methods Myocardial ischemia models were created by partial ligation of the left anterior descending coronary artery in Japanese white male rabbits.Rabbits were subcutaneously injected with G-CSF (G-CSF group)or saline (control group)for 6 days after myocardial ischemia.The percentage of CD34-positive cells in the peripheral blood was evaluated by flow cytometry,and CD34-positive cells homing and vWF expression in the ischemic myocardium were determined by immunohistochemistry.Results Rabbits in G-CSF group had a higher survival rate than those in control group (P <0.05).Immunohistochemistry of the ischemic myocardium showed that compared with control group,G-CSF group had increased homing of CD34-positive cells on day 7 post-surgery,and more vessels on day 28 post-surgery by anti-von Willebrand factor staining.In addition,we observed an increase in the percentage of CD34-positive cells in the peripheral blood in G-CSF group.Conclusion G-CSF produces an obvious protective effect against chronic myocardial ischemia in rabbits by increasing stem cell mobilization,homing to ischemic myocardium and accelerating neovascularization.
ABSTRACT
<b>Objective:</b> The aim of the present study was to investigate the differences between therapeutic granulocyte-colony stimulating factor (G-CSF) cycles and prophylactic G-CSF cycles in patients receiving paclitaxel and carboplatin combination chemotherapy for ovarian cancer.<br><b>Material and Method:</b> Medical records of 15 women who received paclitaxel and carboplatin combination chemotherapy for ovarian cancer between January 2003 and December 2012 were analyzed retrospectively. All 15 patients completed 6 cycles of paclitaxel and carboplatin as the first-line chemotherapy. The complications were compared between therapeutic G-CSF cycles and prophylactic G-CSF cycles.<br><b>Results:</b> The number of chemotherapy cycles correlated with the ratio of prophylactic G-CSF cycles. It was considered that earlier prophylactic G-CSF injections were chosen due to a gradual decrease in WBC and neutrophil counts. The WBC and neutrophil counts were significantly higher in prophylactic G-CSF cycles than in therapeutic G-CSF cycles. However, there were no significant differences in the intervals of chemotherapy, delay of chemotherapy, and incidence of febrile neutropenia between the therapeutic G-CSF and prophylactic G-CSF cycles.<br><b>Conclusion:</b> Prophylactic G-CSF injections were not effective in preventing the incidence of febrile neutropenia in patients receiving paclitaxel and carboplatin combination chemotherapy for ovarian cancer.
ABSTRACT
<b>Objective:</b> The aim of the present study was to investigate the differencesbetween therapeutic granulocyte-colony stimulating factor (G-CSF) cycles and prophylacticG-CSF cycles in patients receiving paclitaxel and carboplatin combination chemotherapy forovarian cancer.<br><b>Material and Method:</b> Medical records of 15 women who received paclitaxel andcarboplatin combination chemotherapy for ovarian cancer between January 2003 and December2012 were analyzed retrospectively. All 15 patients completed 6 cycles of paclitaxel andcarboplatin as the first-line chemotherapy. The complications were compared betweentherapeutic G-CSF cycles and prophylactic G-CSF cycles.<br><b>Results:</b> The number of chemotherapy cycles correlated with the ratio ofprophylactic G-CSF cycles. It was considered that earlier prophylactic G-CSF injectionswere chosen due to a gradual decrease in WBC and neutrophil counts. The WBC and neutrophilcounts were significantly higher in prophylactic G-CSF cycles than in therapeutic G-CSFcycles. However, there were no significant differences in the intervals of chemotherapy,delay of chemotherapy, and incidence of febrile neutropenia between the therapeutic G-CSFand prophylactic G-CSF cycles.<br><b>Conclusion:</b> Prophylactic G-CSF injections were not effective in preventingthe incidence of febrile neutropenia in patients receiving paclitaxel and carboplatincombination chemotherapy for ovarian cancer.
ABSTRACT
Objective: To determine the survival of children ≤18y, treated with immunosuppresive therapy (IST) using equine antithymocyte globulin (e-ATG) and cyclosporine (CsA). Design: Prospective data entry as per a specified format. Setting: Tertiary care hospital. Patients: From January 1998 to December 2009, 40 children were diagnosed with acquired aplastic anemia; 33 patients, who received IST, were analyzed. 31 children (94%) received one course of e-ATG and CsA. 2 patients (6%) received two courses of ATG. Intervention: Immunosuppressive therapy using equine ATG and cyclosporine. Main Outcome Measures: Overall response and overall survival. Results: The overall response (complete response + partial response) to IST at 6 months was 87.9%. 8 (24.2%) patients achieved CR, 21 (63.6%) patients had PR and 4 (12.1%) patients did not respond to IST. Median follow-up was 24 (6-102) months. Overall survival at 24 months was 90%, with an acturial survival of 85.4% at 5 years. Seventeen patients (51.5%) received G-CSF for a median duration of 32 (23-64) days. The patients who received G-CSF had fewer infectious complications (P=0.002), but G-CSF administration did not influence survival/ outcome. No patient developed myelodysplastic syndrome or acute leukemia. Conclusions: The survival of patients who respond to IST is excellent. Also, G-CSF reduces the infectious complications without conferring any survival advantage.
ABSTRACT
BACKGROUND: It is a well known fact that granulocyte colony-stimulating factor (G-CSF) can reduce the severity and duration of neutropenia after chemotherapy. The aim of this study was to evaluate the efficacy and safety of newly developed G-CSF, Leukoup(R) by comparing with those of already approved G-CSF, Grasin(R). METHODS: This study was designed as a randomized, multicenter, open label, phase III trial. Both G-CSFs were subcutaneously injected at the dose of 50 g/m2 daily from 24 hours after the end of chemotherapy and continued for 10 days. The primary end point was the time for neutrophil recovery to 2,000/mm3. RESULTS: A total of 222 patients were enrolled in this study (110 for Leukoup(R) arm, 112 for Grasin(R) arm), and 184 completed the study. The mean of the days for neutrophil recovery in Leukoup(R) arm was 16.5 days, and that of Grasin was 15.9 days; the difference between two groups was 0.67 days, and 95% confidence interval was 1.51~2.86 days. Although the difference in neutrophil recovery between the two groups is not significantly different and still within the usual non-inferiority margin (50% of difference between G-CSF group and no treatment group: 3.15 days), this study couldn't demonstrate the non-inferiority of Leukoup(R) to Grasin(R) by pre-defined noninferiority margin (30% of difference between G-CSF group and no treatment group: 1.89 days). The results of other assessment points, the incidence and severity of adverse events showed no difference between the two groups. CONCLUSION: The present study showed that Leukoup(R) was effective and safe as good as Grasin(R) for the prevention of chemotherapy-induced neutropenia, although the noninferiority of Leukoup(R) to Grasin(R) could not be demonstrated by the predefined non-inferiority margin.
Subject(s)
Humans , Arm , Drug Therapy , Granulocyte Colony-Stimulating Factor , Incidence , Neutropenia , NeutrophilsABSTRACT
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is commonly used to reduce leukopenic period during treatment of malignancy including acute leukemia. Leukemic blasts expressing granulocyte colony-stimulating factor receptor (G-CSFR) were reported and also may proliferate in response to therapeutic administration of G-CSF. However, it is not clear whether G-CSFR expression on leukemic blasts is related to clinical outcome such as leukocyte recovery or leukemia relapse. Current study evaluated expression of G-CSFR in acute leukemia and correlated with hematologic and clinical parameters. METHODS: Peripheral blood or bone marrow aspirate was evaluated from 20 patients with acute myelogenous leukemia (AML) and 10 with acute lymphoblastic leukemia (ALL), 2 with acute undifferentiated leukemia (AUL), 1 with acute biphenotypic leukemia (ABL), 1 with acute mixed-lineage leukemia (AMLL). G-CSFR expression was analyzed using flow cytometry and was correlated with immunophenotype and response for chemotherapy. RESULTS: More than 20% of blasts were positive for G-CSFR in 65% (13/20) of AML, 40% (4/10) of ALL, and all negative in ABL, AMLL, and AUL. Except that all 6 monocytic lineage leukemias (M4, M5) and all three cases of ALL with CD33 expression were positive, no consistent correlation was observed among G-CSFR expression pattern, type of acute leukemia, response to induction therapy and relapse (P>0.05). CONCLUSION: Current study revealed G-CSFR was expressed on not only myelogenous leukemic cells but also lymphoid ones. Although our data suggest G-CSFR expression does not affect therapeutic outcome, it remains to be determined whether G-CSF therapy is safe in G-CSFR-positive acute leukemia.
Subject(s)
Humans , Bone Marrow , Drug Therapy , Flow Cytometry , Granulocyte Colony-Stimulating Factor , Granulocytes , Leukemia , Leukemia, Biphenotypic, Acute , Leukemia, Myeloid, Acute , Leukocytes , Precursor Cell Lymphoblastic Leukemia-Lymphoma , RecurrenceABSTRACT
BACKGROUND: Recently, the use of peripheral blood stem cell (PBSC) instead of bone marrow stem cells is associated with faster engraftment and reduced transplantation related complications. Several studies revealed that intermediate dose of Granulocyte-Colony Stimulating Factor (G-CSF) (less than 5ng/kg) is enough to be effective in the mobilization of stem cells for autologous transplantation. Also, to simplify mobilization procedure and reduce the cost for mobilization, a fixed dose of G- CSF (250 ng/patient/day) needs to be tested for its clinical feasibility. METHODS: Patients with various malignant diseases were referred to the Ajou University Hospital (N=106) for PBSC transplantation with high dose chemotherapy. All patients were given fixed dose of G-CSF (250 ng/patient/ day) for mobilization and engraftment. RESULTS: Except for a few complaints of mild bone pain, all of the patients tolerated the treatment well during the mobilization. Early engraftment and yield of mobilization were related to the accumulated cycle of prior chemotherapy and prior radiotherapy. CONCLUSION: Fixed dose of G-CSF without accordance to the body weight of the patient showed no significant difference compared to the current reports on the mobilization of stem cells and engraftment after transplantation. The total number of chemotherapy cycles exposed before transplantation and the prior radiation therapy history were certainly the most important influencing factor in stem cell transplantation and mobilization.
Subject(s)
Humans , Autografts , Body Weight , Bone Marrow , Drug Therapy , Granulocyte Colony-Stimulating Factor , Radiotherapy , Stem Cell Transplantation , Stem Cells , Transplantation, AutologousABSTRACT
OBJECTIVE: To investigate the influence of granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) on preimplantation development and implantation in mouse embryos. MATERIAL AND METHODS: Eight-cell stage mouse embryos were cultured for 96 hours with G-CSF or GM-CSF at concentrations of 10 pg/ml, 100 pg/ml, 1 ng/ml and 10 ng/ml. Embryos not treated with G-CSF or GM-CSF were served as control. The percentages of embryos which developed to expanded, hatched blastocyst stage and in vitro implantation at 96 hours were determined. Results were analyzed with Kolmogorov-Smirnov test and analysis of variance (ANOVA). The statistical significance was defined as p<0.05. RESULTS: The percentages of fully expanded blastocysts in all G-CSF and GM-CSF treatment groups were not significantly different from the control. The percentages of hatched blastocysts were significantly higher in 100 pg/ml and 10 ng/ml of G-CSF treatment group compared to the control (p<0.05, p<0.05, respectively). The percentages of hatched blastocysts were significantly lower in 1 ng/ml of GM-CSF treatment group compared to the control, 10 pg/ml, and 100 pg/ml of GM-CSF treatment group (p<0.05, p<0.05, p<0.05, respectively), and the percentages of hatched blastocysts were also significantly lower in 10 ng/ml of GM-CSF treatment group compared to the control and 100 pg/ml of GM-CSF treatment group (p<0.05, p<0.05, respectively). The percentages of implanted blastocysts in vitro were significantly higher following incubation with all concentrations of G-CSF compared to the control and, especially in 100 pg/ml and 10 ng/ml of G-CSF treatment groups compared to the control and other treatment groups. The percentages of implanted blastocysts in vitro were significantly higher in 10 pg/ml of GM-CSF treatment group than the control and 100 pg/ml of GM-CSF treatment groups (p<0.05, p<0.05, respectively). CONCLUSION: G-CSF and GM-CSF might influence on embryonic development and implantation in mouse embryos.
Subject(s)
Animals , Female , Mice , Pregnancy , Blastocyst , Colony-Stimulating Factors , Embryonic Development , Embryonic Structures , Granulocyte Colony-Stimulating Factor , Granulocyte-Macrophage Colony-Stimulating Factor , GranulocytesABSTRACT
Objective To observe the safety and feasibility of autologous peripheral blood stem cell (PBSC) transplantation by intracoronory infusion in patients with acute myocardial infarction (AMI).Methods Totally 27 patients with AMI were randomly allocated to receive either inclusive type granulocyte colony-stimulating factor (G-CSF),or excretory type G-CSF to mobilize the stem cells.They received the dose of G-CSF 300-600?g/d by hypodermic injection for 5 days.On the sixth day,PBSCs were separated by Baxter CS 3000 blood cell separator into 50ml suspending liquid.The suspending liquid without treatment was infused into the infarct-related artery (IRA)by occluding the over-the-wire balloon and infusing artery through balloon center lumen.During PBSC mobilization,the following side-effects should be paid attention to,such as bone pain,lethargy,tetter,fever,gastrointestinal effects (nausea,vomiting,constipation),angina or deteriorated heart failure,as well as some rare complications (spontaneous spleen rupture,severe purulent infection, hypercoagulable state,and autoimmune diseases).When the PBSCs were being separated and collected,some complications were observed,for example,low calcium effects (mouth numbness and spasm),pale and dizziness due to vagus reflect,pale and dizziness owing to low blood volume,deterioration of angina or heart failure.The complications should also be observed during the PBSC transplantation by intracoronary infusion:arrhythmia including bradycardia (because of balloon occlusion),sinus arrest or the third degree of atrial ventricular block (because of coronary spasm due to balloon stimulating stent), ventricular fibrillation or hypotension,etc.Results There were 22 cases with complications during the mobilization,separation,collection, and infusion of PBSCs.The incidence of complications during mobilization was 44.4%(12/27),during separation and collection is 25.9%(7/27),and during PBSC transplantation by intracoronary infusion 11.1%(3/27).Conclusion In patients with AMI,Intracoronary infusion of PBSC is feasible and safe.
ABSTRACT
BACKGROUND: G-CSF or GM-CSF was frequently used in treatment of acute myeloid leukemia patients. But it has been argued whether this increases the apoptosis of tumor cells in synergy with chemotherapeutic agent, or decreases apoptosis of leukemic cells. We attempted to determine the effect of granulocyte colony-stimulating factor (G-CSF) on leukemic cell line after cytosine arabinoside (Ara-C) treatment. METHODS: KG-1 and HL60 cell lines were incubated with Ara-C for 48 hours, and then washed with media, divided into two groups, one being with the addition of G-CSF and the other being without G-CSF and incubated for another 48 hours. The controls were the same cell lines incubated without Ara-C. The absolute cell counts and apoptotic percentage measured by flowcytometry after stained with 7-aminoactinomycin D (7-AAD) were compared among three groups at 0, 48, and 96 hours. RESULTS: KG-1 cell line showed decreased cell count and increased apoptotic percent in Ara-C/G-CSF and Ara-C group compared with the control group at 48 and 96 hours, and did not showed significant difference between G-CSF group and nonG-CSF group. In HL60, control group showed higher cell count at 48 hours, and G-CSF/Ara-C group showed lower cell count and higher apoptosis than Ara-C group in all trials. CONCLUSIONS: The treatment of G-CSF after Ara-C did not protect apoptosis nor increase the tumor cells in KG-1 and HL60 cell lines. We concluded it would be safe to use G-CSF after administration of chemotherapeutic drug.