Therapeutic Efficacy of Jingangteng Capsules Combined with Guizhi Fuling Capsules in the Treatment of Chronic Pelvic Inflammation and Their Effect on Serum Granulocyte-Macrophage Colony-Stimulating Factor and Matrix Metalloproteinase 2 Levels / 广州中医药大学学报

Objective To investigate the efficacy of Jingangteng Capsules combined with Guizhi Fuling Capsules(GFC)for the treatment of patients with chronic pelvic inflammation of damp-heat and stasis obstruction type and to observe their effects on serum granulocyte-macrophage colony-stimulating factor(GM-CSF)and matrix metalloproteinase 2(MMP-2)levels.Methods Ninety patients with chronic pelvic inflammation of damp-heat and stasis obstruction type were randomly divided into the combined group and the GFC group,with 45 patients in each group.Patients in the GFC group were treated with Guizhi Fuling Capsules,while patients in the combined group were given Jingangteng Capsules together with GFC.The treatment period lasted for 2 weeks and then one-month follow-up was conducted.The changes of traditional Chinese medicine(TCM)scores,serum GM-CSF and MMP-2 levels in the two groups were observed before and after treatment.And the clinical efficacy,time for the relief of symptoms,recurrence of disease and occurrence of adverse reactions in the two groups were compared.Results(1)After 2 weeks of treatment,the total effective rate of the combined group was 93.33%(42/45),and that of the GFC group was 66.67%(30/45).The intergroup comparison showed that the therapeutic effect of the combined group was significantly superior to that of the GFC group when comparing the two groups(P＜0.01).(2)After treatment,the scores of TCM symptoms of lower abdominal pain,lumbosacral pain,leukorrhagia,profuse menstruation,dysmenorrhea,and fatigue in both groups were significantly lower than those before treatment(P＜0.05),and the reduction of TCM syndrome scores in the combined group was significantly superior to that in the GFC group(P＜0.05).(3)The time for leucorrhea recovering normal and the time for the relief of lower abdominal distension and abdominal pain in the combined group were significantly shorter than those in the GFC group after treatment(P＜0.01).(4)After treatment,the serum serological indicators of GM-CSF and MMP-2 levels in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the reduction of serum GM-CSF and MMP-2 levels in the combined group was significantly superior to that in the GFC group(P＜0.05 or P＜0.01).(5)The recurrence rate and the incidence rate of adverse reactions in the combined group were 11.11%(5/45)and 13.33%(6/45),respectively,and were significantly lower than those in the GFC group[all being 35.56%(16/45)],the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Jingangteng Capsules combined with Guizhi Fuling Capsules can significantly enhance the clinical efficacy of the patients with chronic pelvic inflammatory of damp-heat and stasis obstruction type,effectively shorten the time for the relief of symptoms,and decrease the serum GM-CSF and MMP-2 levels.

Application of rhG-CSF in the treatment of chemotherapy-induced oral mucositis in children / 中国现代医生

@#Objective To explore the application effect of recombinant human granulocyte colony stimulating factor(rhG-CSF)in the treatment of chemotherapy-induced oral mucositis in children.Methods Totally 60 children with chemotherapy-induced oral mucositis who underwent chemotherapy in the tumor surgery of our hospital from January 2020 to June 2022 were randomly divided into two groups,30 cases each.The control group was given physiological saline oral care,and the experimental group was given rhG-CSF oral care.Compare the intervention effect,oral mucositis grading,quality of life[short form of health survey(SF-36)]and nursing satisfaction of parents of the two groups.Results The total effective rate of the experimental group was higher than that of the control group(P<0.05).After 5 days of intervention,the score of oral mucositis in the experimental group was better than that in the control group(P<0.05).After 5 days of intervention,the SF-36 score of children in the two groups was higher than that before intervention,and that in the experimental group was higher than that in the control group(P<0.05).The parents'satisfaction in the experimental group was higher than that in the control group(P<0.05).Conclusion rhG-CSF oral care can effectively improve the intervention effect of chemotherapy-induced oral mucositis in children,reduce the grade of oral mucositis,improve the quality of life of children,and improve the nursing satisfaction of parents of children.

Effects of granulocyte macrophage colony-stimulating factor, nerve growth factor and interleukin-17 on autoimmune prostatitis / 现代泌尿外科杂志

【Objective】 To investigate the significance of granulocyte macrophage colony-stimulating factor (GM-CSF), nerve growth factor (NGF) and interleukin-17 (IL-17) in the prostate tissue of rats with experimental autoimmune prostatitis(EAP). 【Methods】 EAP rat models were established and divided into control group, EAP group, anti-GM-CSF group (blocking control group) and anti-GM-CSFEAP group (blocking EAP group). Pain behaviors were tested. The pathological changes were observed with HE staining. The mRNA and protein expressions of GM-CSF, NGF and IL-17 were detected with RT-PCR and Western blot. 【Results】 Pain test showed the anti-GM-CSF group had less chronic pelvic pain than the EAP group. HE staining showed the anti-GM-CSF group had less tissue inflammatory response. The EAP inflammation score was higher in the control group than in the anti-GM-CSF group. Immunohistochemistry showed GM-CSF was positive in the EAP group (mainly in the nucleus). RT-PCR and Western blot results showed the mRNA and protein expressions of IL-17 and NGF significantly decreased 50 days after EAP in the anti-GM-CSF group. 【Conclusion】 Increased expressions of GM-CSF, NGF and IL-17 in prostate tissue of EAP rats may be important inflammatory mediators of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS);decreased expressions of NGF and IL-17 after resistance against GM-CSF indicate that GM-CSF may be a potential therapeutic target for CP/CPPS.

Clinical characteristics of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor autoantibodies / 中华传染病杂志

Objective:To investigate the clinical characteristics and prognosis of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies.Methods:A total of 216 non-acquired immunodeficiency syndrome (AIDS) related cryptococcal meningitis cases with positive cultures of Cryptococcus, hospitalized at Huashan Hospital, Fudan University during January 2014 and December 2021, were retrospectively included. The serum anti-GM-CSF autoantibodies were detected by enzyme linked immunosorbent assay, and the clinical characteristics and prognosis were compared between patients with and without anti-GM-CSF autoantibodies. Statistical comparisons were mainly performed using the chi-square test or Fisher′s exact test. Cox proportional-hazards model was used to analyze the risk factors associated with prognosis. Results:Among 216 enrolled patients, 23 patients were positive of anti-GM-CSF autoantibodies, with a positive rate of 10.6%. Among 23 patients, seven cases were infected with Cryptococcus gattii, and 16 cases were infected with Cryptococcus neoformans. In the group with positive anti-GM-CSF autoantibodies, 30.4%(7/23) of the patients were infected with Cryptococcus gattii, which was higher than that of 1.6%(3/193) in the group with negative anti-GM-CSF autoantibodies, and the difference was statistically significant ( χ2=38.82, P<0.001). In the group with positive anti-GM-CSF autoantibodies, 30.0% (6/20) had mass lesions with a diameter greater than three centimeters in the lungs, and the one-year all-cause mortality rate was 50.0% (10/20), which were both higher than those of 3.4%(5/145) and 16.1% (29/180) in the negative group, respectively. The differences were both statistically significant (both Fisher′s exact test, P<0.01). Age≥60 years (hazard ratio ( HR)=4.146, P=0.002), predisposing factors ( HR=3.160, P=0.021), epilepsy ( HR=6.129, P=0.002), positive anti-GM-CSF autoantibodies ( HR=2.675, P=0.034), white blood cell count of cerebrospinal fluid (CSF)<100 ×10 6/L ( HR=2.736, P=0.039), the titers of cryptococcal capsular polysaccharide antigen of CSF≥1∶1 280 ( HR=4.361, P=0.009) were independent risk factors for one-year all-cause mortality in patients with cryptococcal meningitis. Conclusions:In non-AIDS related cryptococcal meningitis patients, the positive rate of serum anti-GM-CSF autoantibodies is as high as 10.6%. Patients with anti-GM-CSF autoantibodies could be infected with both Cryptococcus neoformans and Cryptococcus gattii, and they have higher proportion of lung mass lesions than patients with negative anti-GM-CSF autoantibodies. The one-year survival rate decreases significantly in patients with anti-GM-CSF autoantibodies, which is an independent risk factor for the prognosis of cryptococcal meningitis.

Relationship between promoting effect of Zuogui Pills on angiogenesis of reproductive organs and mobilization factors GM-CSF, SDF-1, and their receptors of EPCs in early-aging rats / 中国中药杂志

This study aimed to investigate the relationship between the promoting effect of Zuogui Pills on ovarian and vaginal angiogenesis in early-aging rats and mobilization factors granulocyte-macrophage colony-stimulating factor(GM-CSF), stromal cell-derived factor-1(SDF-1), and their receptors of endothelial progenitor cells(EPCs) and explore the mechanism of Zuogui Pills in improving reproductive hypofunction in early-aging rats. Ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) was used to analyze the chemical components of the extract of Zuogui Pills. Forty 14-month-old female early-aging rats with estrous cycle disorder were randomly divided into a blank group, a conjugated estrogen group(conjugated estrogen suspension, 65 μg·kg~(-1)), and low-(11 g·kg~(-1)) and high-dose(33 g·kg~(-1)) Zuogui Pills groups, with 10 rats in each group. In addition, 10 4-month-old female rats were assigned to the youth control group. The rats in the blank group and the youth control group were treated with 20 g·kg~(-1) distilled water by gavage, while those in the groups with drug intervention were treated with corresponding drugs by gavage, once a day for 15 days. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of SDF-1 and GM-CSF in the mobilization of EPCs in serum. Hematoxylin-eosin(HE) staining was used to observe the changes in the number of ovarian follicles at all levels and corpus luteum, the number of vaginal epithelial layers, the number of vaginal folds, and the blood vessels of ovarian and vaginal tissues in the groups with drug intervention. Western blot was used to detect the expression of ER, GM-CSFR, CXCR4, and CXCR7 proteins in ovarian and vaginal tissues. As revealed by the results, the blank group showed decreased number of corpus luteum, gro-wing follicles at all levels, and blood vessels(P<0.05), decreased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal folds, and the number of vessels in the lamina propria(P<0.05), reduced content of SDF-1 and GM-CSF in the peripheral blood(P<0.05), and down-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P<0.05). The groups with drug intervention showed increased number of growing follicles at all levels, corpus luteum, and blood vessels(P<0.05), decreased number of atresia follicles(P<0.05), increased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal mucosal folds, and the number of blood vessels in the lamina propria(P<0.05), increased content of SDF-1 and GM-CSF in the peripheral blood(P<0.05), and up-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P<0.05). This experiment suggests that Zuogui Pills may promote ovarian and vaginal angiogenesis and improve the reproductive function of early-aging rats by up-regulating the levels of mobilization factors SDF-1, GM-CSF, and their receptors of EPCs.

Efficacy analysis of subcutaneous injection of granulocyte-macrophage colony-stimulating factor for prevention of invasive fungal disease in patients with multiple myeloma / 白血病·淋巴瘤

Objective:To explore the efficacy of subcutaneous injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in preventing invasive fungal disease (IFD) in patients with multiple myeloma (MM).Methods:The clinical data of 222 patients who were admitted to the Second Hospital of Harbin Medical University from January 2015 to June 2021 were retrospectively analyzed. The patients was given GM-CSF (3-5 μg·kg -1·d -1, GM-CSF group) or granulocyte colony-stimulating factor (G-CSF, 2-5 μg·kg -1·d -1, G-CSF group) when neutrophils (ANC) ≤1.5×10 9/L after induction chemotherapy. Patients were discontinued when white blood cell count (WBC) ≥10.0×10 9/L. The incidence of IFD (including confirmed, clinical and proposed diagnosis) and breakthrough invasive fungal infections was compared between the two groups. Results:The incidence of IFD was 8.1% (18/222) in all patients. The incidence of IFD was 3.5% (3/85) and 10.9% (15/137) in the GM-CSF and G-CSF groups, respectively, and the difference between the two groups was statistically significant ( χ2 = 3.88, P = 0.049). In 9 patients of GM-CSF group receiving fungal infection prophylaxis and in 15 patients of G-CSF group receiving fungal infection prophylaxis, the incidence of breakthrough invasive fungal infections was 0 and 7 cases, respectively, and the difference between the two groups was statistically significant ( P = 0.022). Conclusions:GM-CSF application in MM patients can reduce the incidence of IFD and breakthrough invasive fungal infections.

Comparison of the Effects of GMCSF-Containing and Traditional Culture Media on Embryo Development and Pregnancy Success Rates

Abstract Objective The use of granulocyte macrophage colony-stimulating factor (GM-CSF)-containing medium, which is a commercial medium that is used for cultivation of embryos in in vitro fertilization (IVF) treatments, has been suggested to increase the efficiency of this procedure in patients with previous multiple unsuccessful attempts. In this retrospective study, we analyzed GM-CSF-containing embryo culture media compared with traditional culture media in terms of development of embryos, pregnancy, and ongoing pregnancy success and live birth rates. Methods This is a prospective case control study conducted in a single center. A total of 131 unexplained infertility patients were included in the study. A cohort of 69 patients whose embryos were cultured in GM-CSF-containing medium and a control group of 62 age-matched patients whose embryos were cultured in conventional Sage One Step medium were included in the study. The major study outcomes were achievement of pregnancy and ongoing pregnancy rate at 12 weeks of gestation. Results The pregnancy and ongoing pregnancy rates of the patients whose embryos were cultured in GM-CSF-containing medium were 39.13% and 36.23%, respectively. These were higher than the rates of the control group, which were 30.65% and 29.03%, respectively, although this difference was not statistically significant. In addition, the 5th-day embryo transfer percentage in the GM-CSF group was higher than in the control group (34.78% versus 27.4%). Conclusion The main findings of our study were that there was no difference between the GM-CSF-enhanced medium and the control group in terms of our major study outcomes. However, blastomere inequality rate and embryo fragmentation rates were lower in the GM-CSF group.

Efficacy and safety of granulocyte and granulocyte-macrophage colony-stimulating factors for the prevention of post-chemotherapy infections in pediatric hematologic neoplasms: a prospective multi-center study / 白血病·淋巴瘤

Objective:To explore the efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and human granulocyte colony-stimulating factor (G-CSF) for the prevention of post-chemotherapy infections in pediatric hematologic neoplasms.Methods:A total of 134 children hospitalized for chemotherapy in 6 tertiary hospitals from July 2016 to June 2018 were collected, including 60 cases in Children's Hospital of Fudan University, 38 cases in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 29 cases in Children's Hospital Affiliated to Soochow University, 4 cases in the Affiliated Hospital of Qingdao University, 2 cases in Northwestern Women and Children's Hospital, and 1 case in Shandong Provincial Qianfoshan Hospital. The children were divided into GM-CSF group (38 cases), G-CSF group (45 cases) and GM-CSF+G-CSF group (51 cases) by using random number table method. The incidence of infections, the recovery time of absolute neutrophil counting (ANC), the decrease of blood platelet count (Plt) and the incidence of adverse reactions were compared among the three groups.Results:In all children, a total of 64 cases (47.8%) had infections during the myelosuppression phase after chemotherapy, of which 18 cases (47.4%) in GM-CSF group, 20 cases (44.4%) in G-CSF group, and 26 cases (51.0%) in GM-CSF+G-CSF group. The incidence of respiratory infection in G-CSF group was higher than that in GM-CSF group and GM-CSF+ G-CSF group [22.2% (10/45) vs. 2.6% (1/38), 4.0% (2/51), χ2 = 12.00, P = 0.002]. The median time to recovery of ANC > 1.5×10 9/L was 10.5 d (8 d, 15 d) in all children, 12 d (10 d, 16 d) in GM-CSF group, 9 d (8 d, 12 d) in G-CSF group, and 10 d (8 d, 16 d) in GM-CSF+G-CSF group. In all children, a total of 101 cases (75.4%) had Plt<50×10 9/L during the myelosuppression phase, and 79 cases (59.0%) had Plt <20×10 9/L. The differences in the incidence of Plt <50×10 9/L and <20×10 9/L among the three groups were not statistically significant (both P > 0.05). In all children, the adverse reactions occurred in 24 cases (17.9%), including 20 cases (14.9%) of fever, 2 cases (1.5%) of sore throat, 1 case (0.7%) of nausea, and 1 case (0.7%) of diarrhea; no adverse reactions of grade 2 or above occurred. The difference in the incidence of adverse reactions among the three groups was not statistically significant ( P>0.05). Conclusions:The efficacy of GM-CSF and G-CSF for the prevention of infections in pediatric hematologic neoplasms during the myelosuppression phase after chemotherapy is roughly equivalent, and combination of both has a good tolerance. The incidence of respiratory infection using GM-CSF alone or GM-CSF+G-CSF is low, which might benefit from the effect of GM-CSF on lung infections.

Progress in mechanism and application of granulocyte-macrophage colony-stimulating factor for prevention and treatment of tumor chemoradiotherapy-induced mucositis / 肿瘤研究与临床

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional hematopoietic growth factor that can promote the recovery of leukopenia caused by tumor chemoradiotherapy, and can also prevent chemoradiotherapy-induced mucositis by promoting a variety of cells such as endothelial cells, epithelial cells, keratinocytes and fibroblasts. This article reviews the domestic and foreign basic and clinical research progress of GM-CSF in recent years, and discusses the mechanism and clinical application of GM-CSF as a mucosal repair agent in the prevention and treatment of tumor chemoradiotherapy-induced mucositis.

Expression and significance of granulocyte colony-stimulating factor and granulocyte- macrophage colony-stimulating factor in patients with acute respiratory distress syndrome / 中国基层医药

Objective:To investigate the expression and significance of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with acute respiratory distress syndrome (ARDS).Methods:The clinical data of 81 patients with ARDS who received treatment between February 2018 and July 2020 in Linhai Second People's Hospital, China (group A) and 69 healthy controls who concurrently received physical examination (group B) were retrospectively analyzed. Serum levels of G-CSF, GM-CSF and oxygenation index (OI) measured before treatment in the group A were compared with the levels measured in the control group. Serum levels of G-CSF and GM-CSF measured before treatment were compared between patients with different disease severities in the group A. The correlation between serum G-CSF and GM-CSF levels and disease condition was analyzed. The significance of serum G-CSF and GM-CSF levels in the diagnosis of ARDS was investigated.Results:Before treatment, serum G-CSF and GM-CSF levels in the group A were (201.89 ± 19.44) ng/L, (48.95 ± 6.03) ng/L, respectively, which were significantly higher than those in the group B [(38.13 ± 5.22) ng/L, (7.71 ± 0.92) ng/L, t = 67.889, 56.228, both P < 0.001]. OI in the group A was significantly lower than that in the group B [(159.09 ± 16.81) mmHg vs. (385.13 ± 20.34) mmHg, t = 74.519, P < 0.001). In group A, serum levels of G-CSF and GM-CSF were (271.99 ± 23.15) ng/L and (65.07 ± 8.38) ng/L respectively in patients with severe acute respiratory distress syndrome ( n = 13), (203.14 ± 18.36) ng/L and (50.91 ± 7.18) ng/L respectively in patients with moderate acute respiratory distress syndrome ( n = 30), and (176.92 ± 15.98) ng/L and (41.89 ± 6.02) ng/L, respectively in patients with mild acute respiratory distress syndrome ( n = 38). There was significant difference among patients with severe, moderate and mild acute respiratory distress syndrome ( F = 133.201, 57.116, both P < 0.05). Serum levels of G-CSF and GM-CSF in group A were negatively correlated with OI ( r = -0.819, -0.824, both P < 0.05). The area under the receiver operating characteristic curve of serum levels of G-CSF and GM-CSF and their combination were 0.780 (95% CI: 0.628-0.933), 0.752 (95% CI: 0.590-0.913) and 0.912 (95% CI: 0.835-0.989), respectively. The Youden index was 0.686, 0.696 and 0.739, respectively. The area under the receiver operating characteristic curve and the Youden index of the combined detection of serum levels of G-CSF and GM-CSF were highest. Conclusion:Serum levels of G-CSF and GM-CSF in patients with ARDS were higher than those in healthy controls. Higher serum levels of G-CSF and GM-CSF led to more severe disease condition. Serum levels of G-CSF and GM-CSF in combination has a higher value in the diagnosis of ARDS than serum levels of G-CSF and GM-CSF alone.

GM-CSF Enhances Mobilization of Bone Marrow Mesenchymal Stem Cells via a CXCR4-Medicated Mechanism

BACKGROUND: This study was conducted to investigate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the mobilization of mesenchymal stem cells (MSCs) from the bone marrow (BM) into the peripheral blood (PB) in rats. METHODS: GM-CSF was administered subcutaneously to rats at 50 µg/kg body weight for 5 consecutive days. The BM and PB of rats were collected at 1, 3, and 5 days during the administration for analysis. RESULTS: Upon GM-CSF administration, the number of mononuclear cells increased rapidly at day 1 both in the BM and PB. This number decreased gradually over time in the BM to below the initial amount by day 5, but was maintained at a high level in the PB until day 5. The colony-forming unit-fibroblasts were increased in the PB by 10.3-fold at day 5 of GM-CSF administration, but decreased in the BM. Compared to GM-CSF, granulocyte-colony stimulating factor (G-CSF) stimulated lower levels of MSC mobilization from the BM to the PB. Immunohistochemical analysis revealed that GM-CSF induced a hypoxic and proteolytic microenvironment and increased C-X-C chemokine receptor type 4 (CXCR4) expression in the BM. GM-CSF added to BM MSCs in vitro dose-dependently increased CXCR4 expression and cell migration. G-CSF and stromal cell derived factor-1 (SDF-1) showed similar results in these in vitro assays. Know-down of CXCR4 expression with siRNA significantly abolished GM-CSF- and G-CSF-induced MSC migration in vitro, indicating the involvement of the SDF-1-CXCR4 interaction in the mechanism. CONCLUSION: These results suggest that GM-CSF is a useful tool for mobilizing BM MSCs into the PB.

Proteinosis alveolar pulmonar / Pulmonary alveolar proteinosis an update

La Proteinosis Alveolar Pulmonar (PAP) es una enfermedad poco frecuente, caracterizada por la acumulación de material lipoproteico derivado del surfactante pulmonar al interior de los alvéolos por una falla de depuración de este material por los macrófagos alveolares, siendo la causa más frecuente de esta disfunción la acción bloqueadora producida por anticuerpos anti factor estimulante de colonias de granulocitos y macrófagos (GM-CSF) lo que lleva a un deterioro del intercambio gaseoso. La evolución es variable abarcando desde la resolución espontánea hasta la insuficiencia respiratoria grave y la muerte. Se describen tres formas de PAP: Genética, secundaria y autoinmune (antes primaria o idiopática) siendo esta última la más frecuente en adultos. Clínicamente, se manifiesta por disnea, tos seca e hipoxemia que pueden ser progresivas. En la radiografía de tórax se encuentran opacidades bilaterales y la tomografía computarizada de tórax de alta resolución (TACAR) muestra vidrio esmerilado con sobre posición de engrosamiento septal intra e interlobulillar, patrón conocido como "crazy paving". El diagnóstico se basa en la clínica y en el lavado broncoalveolar con material PAS positivo. La biopsia quirúrgica es confirmatoria. El tratamiento clásico es el lavado pulmonar total (LPT) para remover el contenido alveolar. Otras alternativas son la administración de GM-CSF subcutáneo o inhalado, plasmaferesis y rituximab, cuyos resultados son variables. Diferentes autores han modificado la forma del LPT y combinado los diferentes métodos de tratamiento con el fin de obtener resultados más rápidos y efectivos.

Pulmonary Alveolar Proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant derived lipoproteinaceous material filling the alveoli, secondary to failure of its clearance by macrophages. Most of the patients are adults that have auto antibodies directed to Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). The evolution is towards disturbed gaseous exchange with a wide spectrum of disease from spontaneous recovery to death. There are three forms of PAP: genetic, secondary and autoimmune. Symptoms are scarce and patients may present with dyspnea, dry cough and hypoxemia. Chest X ray shows bilateral opacities and thorax CT depicts ground glass opacities surrounded by septal widening, the so called "crazy paving" pattern. Diagnosis is made on clinical and radiological grounds and confirmed by PAS positive staining of bronchoalveolar lavage material or surgical lung biopsy. Accepted treatment is whole lung lavage (WLL) with saline. Alternatives are subcutaneous or inhaled GM-CSF, Plasmapheresis or Rituximab, and even modification of the method of WLL and combination of different manner of treatment.

Effectiveness and safeness of granulocyte macrophage colony stimulating factor and whole lung lavage therapy in idiopathic pulmonary alveolar proteinosis / 药学实践杂志

Objective To observe the effectiveness and safeness of granulocyte macrophage colony stimulating factor (GM-CSF)and whole lung lavage therapy for patients with idiopathic pulmonary alveolar proteinosis(IPAP).Methods Two IPAP patients who were hospitalized in Changhai Hospital from August 2015 to March 2017 were enrolled for the study.Both patients were treated with GM-CSF therapy after whole lung lavage.One patient received GM-CSF by subcutaneous injection and the other by inhalation.Results Both patients'conditions were improved after GM-CSF and whole lung lavage therapy. Conclusion Treatment with subcutaneous injection or inhalation of granulocyte macrophage colony stimulating factor and whole lung lavage is safe and effective for IPAP patients.

In vitro anti-tumor effect of mGM-CSF-GnRH3 and mGM-CSF-GRP6 recombinant fusion protein and theirbioinformatics prediction / 中国肿瘤生物治疗杂志

@#Objective: To prepare the fusion protein mGM-CSF-GnRH3 (mGGn) of mouse granulocyte-macrophage colony stimulating factor (mGM-CSF) combining with gonadotropin releasing hormone (GnRH) and the fusion protein mGM-CSF-GRP6 (mG6) of mGM-CSF combining with gastrin-releasing peptide (GRP), and to investigate the inhibitory effect of the above two fusion proteins on B16F10 melanoma in vitro as well as to preliminarily predict their isoelectric point, relative molecular weight, hydrophobicity, stability, subcellular localization, signal peptide, spatial structure and potential epitopes. Methods:After the successful preparation of mGGn and mG6, the effects of different concentrations of fusion proteins on tumor cell morphology, migration, proliferation and cell cycle were detected by microscopic observation, scratch test, CCK-8 method and flow cytometry, respectively. The protein online analysis systems EXPASY, GOR4, SWISS MODEL were used to predict the basic properties and secondary/tertiary structure of recombinant fusion proteins. The B cell epitopes were predicted by IEDB and ABCpred software, the CTL epitopes were comprehensively predicted by SYFPEITHI, BlMAS and NetCTL software, and the Th epitopes were predicted by NetMHCIIpan 3.1 Server and IEDB software. Results:Both mGGn and mG6 inhibited the migration and proliferation of tumor cells. mGGn could block B16F10 cell cycle at G1 phase while mG6 could block B16F10 cell cycle at S phase, all of which prevented cells entering into G2 phase to inhibit tumor cell growth. The mGGn and mG6 fusion proteins got diverse structures and had multiple potential B epitopes, CTL epitopes and Th epitopes. Conclusion: mGGn and mG6 have inhibitory effect on B16F10 melanoma in vitro, and bioinformatics predictions have laid a foundation for further study of the biological functions and immunological activities of these fusion proteins.

Clinical analysis of autologous peripheral blood hematopoietic stem cell mobilization regimen in 56 multiple myeloma patients / 中国肿瘤临床

Objective: To compare the efficacy between chemotherapy plus granulocyte colony-stimulating factor (G-CSF) and chemotherapy plus G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) for the mobilization of peripheral blood stem cells (PBSC) and hematopoietic recovery after transplantation in patients with multiple myeloma (MM). Methods: A retrospective study of autologous PBSC (APBSC) mobilization data of 56 MM patients who were treated with chemotherapy plus G-CSF or chemotherapy plus G-CSF and GM-CSF from May 2008 to July 2016 in Tianjin Medical University Cancer Institute and Hospital was conducted. The mobilization efficacy and hematopoietic recovery were analyzed. Results: In the univariate analysis, the successful collection rate of a single harvest in women and in patients with ISS stage Ⅲ and R-ISS stage Ⅱ/Ⅲ and treated with chemotherapy plus G-CSF was lower (P<0.05). However, age (≤60 years vs.>60 years), subtype, D-S staging (Ⅰ+Ⅱvs.Ⅲ), number of cycles of chemotherapy before mobilization (≤6 cycles vs.>6 cycles), disease phase before mobilization (PR vs. CR), and interval between diagnosis and mobilization (≤18 months vs.>18 months) were not correlated with CD34+ cell collection and successful mobilization rates (P>0.05). In the multivariate model, the successful mobilization rate in patients who received the chemotherapy plus G-CSF and GM-CSF mobilization regimen was higher (OR=12.009, 95% CI=1.961-73.537). The effect of mobilization regimens remained significant (P=0.007). Hematopoietic recovery without transplantation-related mortality occurred successfully in all patients. Conclusions: Chemotherapy plus G-CSF and GM-CSF mobilization regimens can significantly increase the effect of APBSC mobilization and ensure the recovery of hematopoietic function after transplantation. Chemotherapy plus G-CSF and GM-CSF mobilization regimens are safe and effective for mobilizing APBSCs.

Advances of granulocyte-macrophage colony-stimulating factor combinied with radio-therapy / 中国肿瘤临床

The granulocyte-macrophage colony-stimulating factor(GM-CSF)can effectively induce the proliferation of tumor-associat-ed immunocytes as a hematopoietic factor;therefore,the fact that GM-CSF can induce systemic antitumor immune responses has at-tracted much attention.Radiotherapy,as one of the main treatment approaches of cancer,can kill tumor cells directly,and has an ef-fect on anti-tumor immunity.Several clinical studies have shown that radiotherapy combined with the GM-CSF can induce an abscopal effect and confer favorable therapeutic effects for cancer.Herein,we review the research progress on GM-CSF,and radiotherapy com-bined with GM-CSF in tumor treatment.

Secreted CTLA-4 fusion Plasmodium falciparum DNA vaccine combined with GM-CSF enhances immune response of mice / 基础医学与临床

Objective To study effects of secreted cytotoxic T-lymphocyte-associated protein-4(CTLA-4)fusion Plasmodium falciparum DNA vaccine combined with granulocyte-macrophage colony stimulating factor(GM-CSF) on humoral and cellular immune responses in mice.Methods The malaria antigen coding sequence fused with CTLA-4 extracellular region of mouse was constructed as eukaryotic secretory expression vector VR 1012-sES312-CTLA,recombinant protein in culture of transfected HEK 293 cells was detected by Western blot.Balb/c mice were co-administrated with VR1012-sES312-CTLA and GM-CSF expression vector.After immunization specific antibody IgG titers and cytokines IFN-γand IL-4 expression levels were evaluated by ELISA and ELISPOT respectively. Results The introduction of CTLA-4 into malaria DNA vaccine system and application of GM-CSF adjuvant signifi-cantly enhanced the specific immune response to the vaccine.Antibody titers in VR1012-sES312-CTLA and GM-CSF co-immunized mice showed a 190-fold increase compared with the simple designed VR1012-ES312 immunization(P<0.001).Conclusions Humoral and cellular immunity induced by malaria DNA vaccine are significantly en -hanced by both dendritic cell-targeting modification and the introduction of GM-CSF molecular adjuvant into the im-mune system.This result provides a new idea for effectively raising the immune response to malaria DNA vaccine.

Extended Culture of Bone Marrow with Granulocyte Macrophage-Colony Stimulating Factor Generates Immunosuppressive Cells

Bone marrow-derived dendritic cells (BM-DCs) are generated from bone marrow (BM) cells cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) for a week. In this study we investigated the effect of duration on the BM culture with GM-CSF. Within several months, the cells in the BM culture gradually expressed homogeneous levels of CD11c and major histocompatibility complex II on surface, and they became unable to stimulate allogeneic naïve T cells in mixed lymphocyte reaction (MLR). In addition, when the BM culture were sustained for 32 wk or longer, the BM cells acquired ability to suppress the proliferation of allogeneic T cells in MLR as well as the response of ovalbumin-specific OT-I transgenic T cells in antigen-dependent manner. We found that, except for programmed death-ligand 1, most cell surface molecules were expressed lower in the BM cells cultured with GM-CSF for the extended duration. These results indicate that BM cells in the extended culture with GM-CSF undergo 2 distinct steps of functional change; first, they lose the immunostimulatory capacity; and next, they gain the immunosuppressive ability.

The safety and clinical efficacy of recombinant human granulocyte colony stimulating factor injection for colon cancer patients undergoing chemotherapy

Summary Objective: The present study was designed to evaluate safety and efficacy of recombinant human granulocyte colony stimulating factor (G-CSF) injection and whether this regimen could reduce the incidence of adverse events caused by chemotherapy. Method: A total of 100 patients with colon cancer who were treated with chemotherapy in our hospital from January 2011 to December 2014 were randomly divided into two groups, with 50 patients in each group. The patients in the treatment group received G-CSF 24 hours after chemotherapy for consecutive three days; the patients in the control group received the same dose of normal saline. Routine blood tests were performed 7 days and 14 days after chemotherapy. Results: Compared with the control group, the incidences of febrile neutropenia and leukocytopenia in the treatment group were significantly lower (p<0.05). In addition, the incidence of liver dysfunction in the treatment group was lower than that of the control group, without statistical significance. The incidence of myalgia in the treatment was higher than that of the control group without statistical significance. Conclusion: The present study indicated that G-CSF injection after chemotherapy is safe and effective for preventing adverse events in colon cancer patients with chemotherapy.

Evaluation of immunocontraceptive vaccine composed of gonadotropin-releasing hormone conjugated with granulocyte-macrophage colony-stimulating factor in male rats

Surgical castration performed to reduce male-associated problems results in pain and microbial infections in male animals. Therefore, immunocontraception, which is mediated by the animal's own antibodies against reproductive hormones, has been recommended as an alternative to surgical castration when considering the animal's welfare. In this study, a new immunocontraceptive vaccine composed of six tandem copies of gonadotropin-releasing hormone (GnRH) fused to rat granulocyte-macrophage colony-stimulating factor (GM-CSF) was developed, and its efficacy was evaluated in male rats. Three different doses (10, 50, and 100 µg) of recombinant GM-CSF–GnRH protein were injected three times at intervals of two weeks into male rats. The rats vaccinated with three doses of GM-CSF–GnRH produced a significantly higher level of antibodies against GnRH than that in the negative control rats. Severe atrophy of gonads was observed in rats vaccinated with three doses of GM-CSF–GnRH but not in the negative control rats. The results reveal that the new GnRH vaccine conjugated with rat GM-CSF induces efficient immunocontraception in male rats. This formulation of the immunocontraceptive vaccine would be applicable to both domestic and pet male animals.