Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; Humans ; Recombinant Fusion Proteins ; therapeutic use

The precise mechanism whereby granulocytes proliferate when haematopoietic colony stimulating factors (CSFs) are used in neutropenic cancer patients is poorly understood. The purpose of this study was to investigate whether these cytokines bring about leucocyte proliferation by increasing the levels of multiple forms of dihydrofolate reductase (DHFR). Blood samples were collected from 36 cancer patients (25 males and 11 females) with chemotherapy-induced neutropenia. One sample of blood from each patient was obtained before therapy either with CSF, such as granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) or with placebo, and another one at the time of resolution of neutropenia. Peripheral blood leucocytes in these blood samples were counted, separated and lysed. From lysates, cytoplasmic samples were prepared and analyzed for active DHFR by a methotrexate-binding assay and for total immunoreactive DHFR by an enzyme linked immunosorbent assay. The increase in total leucocyte count (TLC) was most prominent (P < 0.005) in the CSF group and less so (P < 0.05) in the placebo group. The mean +/- SD concentration values of active DHFR before and after stimulation with GM-CSF found were to be 0.34 +/- 0.4 ng/mg protein and 0.99 +/- 0.82 ng/mg protein, respectively, and in the group treated with G-CSF, 0.24 +/- 0.32 ng/mg protein and 1.18 +/- 2.4 ng/mg protein, respectively. This increase in active DHFR after stimulation with CSF was statistically significant (P <0.05). Similarly, concentration values of immunoreactive but nonfunctional form of DHFR (IRE) were 110 +/- 97 ng/mg protein and 605 +/- 475 ng/mg protein before and after stimulation with GM-CSF, and 115 +/- 165 ng/mg protein and 1,054 +/- 1,095 ng/ mg protein before and after stimulation with G-CSF. This increase in concentration of IRE after stimulation with GM-CSF or G-CSF was statistically significant (P < 0.005). In the control group, there was an increase in the concentration of both active DHFR and IRE after treatment with placebo. However, this was not statistically significant. Resolution of neutropenia was quicker in the groups treated with CSF compared to the control group. Results of this study indicate that colony stimulating factors (G-CSF and GM-CSF) induce white cell proliferation by increasing the levels of multiple forms of DHFR.
Adolescence ; Adult ; Cell Division/drug effects ; Child ; Female ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Granulocyte Colony-Stimulating Factor/pharmacology* ; Granulocyte Colony-Stimulating Factor/adverse effects ; Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology* ; Granulocyte-Macrophage Colony-Stimulating Factor/adverse effects ; Human ; Isoenzymes/metabolism ; Isoenzymes/biosynthesis ; Leukocyte Count ; Leukocytes/pathology ; Leukocytes/enzymology ; Leukocytes/drug effects ; Male ; Middle Age ; Neoplasms/enzymology ; Neoplasms/drug therapy ; Neoplasms/blood* ; Neutropenia/metabolism* ; Neutropenia/chemically induce ; Neutropenia/blood ; Tetrahydrofolate Dehydrogenase/metabolism* ; Tetrahydrofolate Dehydrogenase/biosynthesis

OBJECTIVETo evaluate the efficacy and safety of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) hydrogel in wound healing in patients with deep partial thickness burn.

METHODSThe study was a multicenter, randomized, double-blind, placebo-controlled parallel clinical trial. Three hundred and twenty-one patients (302 cases finally fulfilled the protocol) with deep partial thickness burn were divided into A group (n = 200, with treatment of rhGM-CSF hydrogel, 100 microg/10 g/100 cm2/d), C group (n = 102,with treatment of placebo). Side-effect, systemic condition, wound healing time, wound healing rate, and total effective rate at different time points were observed.

RESULTSThere were no obvious differences in vital signs, wound secretion, wound edge reaction, blood and urine routine, liver and kidney function between two groups (P > 0.05). No side-effect was observed. The median wound healing time was 17 days in A group, which was obviously shorter than that in C group (20 days, P < 0.01). The mean wound healing rate in A group was 24.5%, 70.5%, 95.3%, 99.6% respectively on 8th, 14th, 20th, 28th day after treatment, which were obviously higher than that in C group (15.1%, 51.4%, 84.6%, 97.1%, respectively, P < 0.01). The total effective rates in A group on 8th, 14th, 20th day after treatment were also higher than that in C group (P < 0.01).

CONCLUSIONrhGM-CSF hydrogel can significantly accelerate wound healing in patients with deep partial thickness burn with certain safety.

Burns ; drug therapy ; Double-Blind Method ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; adverse effects ; therapeutic use ; Humans ; Hydrogels ; therapeutic use ; Male ; Placebos ; Recombinant Proteins ; Wound Healing

Immunosuppressive therapy (IST) is essential to treat aplastic anemia. The pharmacological mechanism, therapeutic effect of main drugs and their application method, reasonable dosage, synergistic action are briefly reviewed in this article. These reviewed drugs include ATG/ALG, CsA, ALG/ATG + CsA, IIST (ALG + CsA) + HGFs, McAb-T, HD-MP and HD-IVIG. The purpose of this review was to direct to clinical therapy for patients with aplastic anemia.
Anemia, Aplastic ; drug therapy ; Antilymphocyte Serum ; therapeutic use ; Cyclosporine ; therapeutic use ; Drug Therapy, Combination ; Erythropoietin ; therapeutic use ; Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; Humans ; Immunosuppressive Agents ; therapeutic use ; Recombinant Proteins

Anti-Bacterial Agents ; therapeutic use ; Bacterial Infections ; diagnosis ; therapy ; China ; Communicable Diseases ; diagnosis ; therapy ; Cross Infection ; prevention & control ; therapy ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; Humans ; Immunoglobulins, Intravenous ; therapeutic use ; Infant, Newborn ; Sepsis ; diagnosis ; therapy

OBJECTIVETo evaluate the effects of autologous tumor vaccines in preventing recurrences of hepatocellular carcinoma (HCC).

METHODSFrom March 1999 to June 2003, 80 patients with HCC undergoing resections were randomly assigned into a tumor vaccine group (n=40) and a control group (n=40). Tumor vaccines, consisting of formalin-fixed HCC tissue fragments, biodegradable sustained-releasers of granulocyte-macrophage-colony stimulating factor, interleukin-2, and an adjuvant, were developed. Every vaccine group patient received 3 vaccinations at a 2-week interval and the control group just received the adjuvant. Delayed-type-hypersensitivity (DTH) test and recurrent rates were analyzed.

RESULTSEight patients of the vaccine group and five patients of the control group were lost in the follow-up. Thirty-two patients completed the tumor vaccine procedure and no essential adverse effects occurred. 23/32 patients developed DTH responses against the fragments of HCC. The follow-up averaged 34.3 months (from 15 to 55 months). 1-, 2-, 3-year recurrence rates of the vaccine group were 12.6%, 35.9% and 54.0%, respectively; 1-, 2-, 3-year recurrence rates of the control group were 31.6%, 61.3% and 72.1%, respectively. The recurrent rate was significantly better in the tumor vaccine group than in the control group (P = 0.037).

CONCLUSIONSAutologous tumor vaccine is a promising adjunctive modality to prevent recurrence of human HCC.

Adult ; Aged ; Cancer Vaccines ; therapeutic use ; Carcinoma, Hepatocellular ; surgery ; therapy ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; Humans ; Interleukin-2 ; therapeutic use ; Liver Neoplasms ; surgery ; therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Postoperative Period ; Vaccination

OBJECTIVETo observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) or hepatitis B immunoglobulin (HBIG) plus recombinant hepatitis B vaccine (rHBvac).

METHODSA total of 27 chronic HBV infected children, who were born to HBV carrier mothers and received hepatitis B immunoprophylaxis at birth, were randomized into 2 groups: one receiving a combined therapy of 50 micro g of GM-CSF plus 10 micro g of rHBvac injected intramuscularly at the same location (GM-CSF group, 14 children) or 200 IU HBIG and 10 micro g rHBvac in different muscles (HBIG group, 13 children) on a monthly four-dose schedule. HBV-DNA quantification and other HBV serological markers were tested before and after the four-dose therapy.

RESULTSTwelve children in each group completed the study. Of them, 3 children in the GM-CSF group and 4 in the HBIG group had elevated serum alanine transaminase (ALT) before the trial, and then 2 in each group became ALT normal after the treatment. Before the therapy, hepatitis B e antigen (HBeAg) positivity was found in nine children in the GM-CSF group and 10 in the HBIG group. One from each group had an HBeAg/anti-HBe seroconversion after the treatment. The quantity of HBV-DNA was significantly lower after the treatment (P = 0.023) in GM-CSF group, but was not significantly reduced in HBIG group. No subjects were found to be negative for hepatitis B surface antigen (HBsAg) after the treatment, and no serious adverse events occurred in either group.

CONCLUSIONCombined GM-CSF and rHBvac therapy inhibit HBV replication in carrier children who were not protected after treatment with immunoprophylaxis.

Carrier State ; therapy ; Child ; Child, Preschool ; Combined Modality Therapy ; DNA, Viral ; blood ; Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; Hepatitis B Vaccines ; immunology ; Hepatitis B, Chronic ; therapy ; Humans ; Immunoglobulins ; therapeutic use ; Pilot Projects ; Vaccines, Synthetic ; immunology

OBJECTIVETo observe the therapeutic efficacy of 131I-labeled granulocyte macrophage colony-stimulating factor (GM-SCF) in SCID mouse-acute myeloid leukemia model, and the relationship between dose and effect.

METHODSSCID-mouse acute myeloid leukemia model was established by injecting HL-60 cells through tail vein. GM-CSF was labeled with 131I by the chloramines-T method. SCID mice were randomly divided into 6 groups. Groups I, II and III treatment groups were given 9.25 x 10(5), 22.20 x 10(5) and 37.00 x 10(5) Bq of 131I-GM-CSF, respectively. Group IV was given 131I. Group V was given blending of 131I and GM-CSF. Group VI was control. Changes of HL-60 cells in blood and marrow, as well as white blood cells, red blood cells and platelets in blood were detected. Survival time of the SCID mice was calculated.

RESULTIt was observed that WBC, HL-60 cells in blood and marrow were less in treatment groups than that in control groups, especially in groups II, III. After 2 weeks of treatment, BPC of II, III groups increased remarkably (P < 0.01). Survival time of the SCID mice was prolonged in treatment groups (P < 0.01), especially in group III, the longest survival time of 60 days.

CONCLUSION131I-GM-CSF could increase leukemic SCID mice survival rate. The therapeutic efficacy of low dose and mediate dose of 131I-GM-CSF is dose-dependent. 131I-GM-CSF is an effective radiation immunity therapy for leukemic mice.

Animals ; Antineoplastic Agents ; therapeutic use ; Dose-Response Relationship, Drug ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Mice ; Mice, SCID ; Xenograft Model Antitumor Assays

This study was purposed to evaluate the long-term outcome and the safety of autologous peripheral blood mononuclear cells (PBMNC) treated by interleukin 2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF) in the therapy of patients with aplastic anemia (AA). The therapy of 49 patients admitted BG in hospital from April 2001 to December 2007 were analyzed retrospectively. PBMNC were isolated and cultured for 48 hours in presence of IL-2 and GM-CSF. Cells were collected, and 6 × 10(6) - 1 × 10(8) PBMNC were intravenously injected weekly for 4 - 22 months. Hematopoietic recovery was evaluated by examinations of peripheral blood, bone marrow aspirates and bone marrow biopsy. Flow cytometry was used to assess the peripheral T cell subsets before and after treatment. Polymerase chain reaction was performed to observe the clonal diversity of T cell receptor variable β-chain (TCR-Vβ) recombination. The results showed that 37 cases were cured and none of them relapsed during the follow-up, 5 cases were in partial remission, 3 cases got improvement, and 4 cases showed no response. The total efficiency reached up to 91.8%. The ratios of CD4(+)/CD8(+) subsets were abnormal in 39 patients prior to the treatment, and 31 cases restored to the normal range after cell transfusions. Analysis on the clonal diversity of TCR-Vβ recombination in 11 patients showed the transition from monoclonal or biclonal spectratype to polyclonal one. No long-term side effects were documented. It is concluded that the treatment with PBMNC treated by IL-2 and GM-CSF is generally safe and effective. The underlying mechanisms may be in relation to the restoration of cell immunity.
Adolescent ; Adult ; Anemia, Aplastic ; therapy ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; Humans ; Interleukin-2 ; therapeutic use ; Male ; Middle Aged ; Monocytes ; transplantation ; Peripheral Blood Stem Cell Transplantation ; methods ; Transplantation, Autologous ; Young Adult

We describe a case with acute myelogenous leukemia (AML; M2) who developed prolonged marrow hypoplasia with residual leukemic blasts and recurrent infections after induction chemotherapy. He was treated successfully with a sequential treatment of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and low-dose cytosine arabinoside (LD AraC). To the best of our knowledge this is the first reported case of a successful treatment of a patient with AML, who showed prolonged markedly hypocellular bone marrow with significant residual leukemic cells after induction chemotherapy, with a sequential treatment of GM-CSF and LD AraC.
Bone Marrow Diseases/chemically induced/*drug therapy ; Case Report ; Cytarabine/*administration & dosage ; Granulocyte-Macrophage Colony-Stimulating Factor/*therapeutic use ; Human ; Leukemia, Myelocytic, Acute/*drug therapy/pathology ; Male ; Middle Age