Granulocyte colony‐stimulating factor improves neuron survival in experimental spinal cord injury by regulating nucleophosmin‐1 expression

Granulocyte colony‐stimulating factor (G‐CSF) and its related mechanisms were investigated to assess the potential for this factor to exert neuroprotective effects against spinal cord injury in mice. Recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) was injected into mice spinal cord hemisection models. Locomotor activity was assessed by using the Basso‐Bettie‐Bresnahan scale. Neurons isolated from spinal cords were cultured in vitro and used in a neuronal mechanical injury model. Three treatment groups were compared with this model, 1) G‐CSF, 2) G‐CSF + NSC348884 (a nucleophosmin 1‐specific inhibitor), and 3) NSC348884. Immunofluorescence staining and Western blotting were performed to analyze the expression of G‐CSF and nucleophosmin 1 (Npm1). TUNEL staining was performed to analyze apoptosis after G‐CSF treatment. We found that the G‐CSF receptor (G‐CSFR) and Npm1 were expressed in neurons and that Npm1 expression was induced after G‐CSF treatment. G‐CSF inhibited neuronal apoptosis. NSC348884 induced p53‐dependent cell apoptosis and partially blocked the neuroprotective activity of G‐CSF on neurons in vitro. G‐CSF promoted locomotor recovery and demonstrated neuroprotective effects in an acute spinal cord injury model. The mechanism of G‐CSF's neuroprotection may be related in part to attenuating neuronal apoptosis by NPM1. © 2014 Wiley Periodicals, Inc.     

Editorial comment: variables affecting the presence of mesenchymal stromal cells in the peripheral blood and their relationship with apheresis product

Paediatric haematology began to establish itself as a speciality in the UK just over 60 years ago. In that time, clinical trials involving all the specialist centres in the country, and based on scientific advances, have dramatically improved the outlook for children with a range of malignant and non-malignant disorders, but particularly acute leukaemia. As in many specialties, multidisciplinary teams have played a major role in delivering these advances. With these structures in place at a national level, perhaps, of all specialities, paediatric haematology is poised to benefit from the new developments in precision medicine, gene editing and immunotherapy.     

Granulocyte colony-stimulating factor-producing undifferentiated carcinoma of the colon mimicking a pulmonary giant cell carcinoma: a case showing overexpression of CD44 along with highly proliferating nestin-positive tumor vessels

Granulocyte colony-stimulating factor (G-CSF)-producing tumors are known for their aggressive behavior. Only four cases of G-CSF-producing colorectal carcinoma have been previously reported. Herein, we present a case of an undifferentiated carcinoma of the descending colon showing G-CSF production and giant cell carcinoma morphology in a 93-year-old woman. A tumor with a diameter of 80 mm was identified in the descending colon via computed tomography. Descending colectomy was performed involving the abdominal wall where tumor invasion was observed. The white blood cell count, which was elevated before resection, decreased to normal levels after intervention. However, local recurrence at the resected site was detected 39 days after surgery. Upon recurrence, increased white blood cell counts and serum G-CSF were seen. The patient died because of respiratory failure 98 days after colectomy. By using immunohistochemistry, G-CSF expression was detected in tumor cells in the resected specimen, along with overexpression of CD44 and highly proliferating nestin-positive tumor vessels. The poor clinical outcome of this patient is consistent with previous reports that the expression of these three molecules predict poor prognosis. While G-CSF can be a therapeutic target considering its auto/paracrine function to induce tumor growth via the G-CSF receptor, CD44 and nestin may also be possible candidate therapeutic targets. Further studies are required to assess the efficacy of treatments targeting these three molecules.     

沙丁胺醇联合布地奈德雾化吸入对哮喘患儿EOS计数、IgE水平及肺功能的影响

目的探讨沙丁胺醇联合布地奈德雾化吸入对哮喘患儿嗜酸性粒细胞(EOS)计数、免疫球蛋白E(IgE)水平及肺功能的影响。方法选择2017年1月至2018年12月我院收治的哮喘患儿94例,按随机数表法将其分为观察组与对照组,各47例。对照组给予布地奈德雾化吸入,观察组在此基础上给予沙丁胺醇雾化吸入。比较两组治疗前、后EOS计数、IgE水平及肺功能指标。结果治疗后,两组EOS计数、IgE水平均降低,且观察组低于对照组(P<0.05)。治疗后,两组的FEV1、FEV1/FVC、PEF均升高,且观察组高于对照组(P<0.05)。结论沙丁胺醇联合布地奈德雾化吸入治疗小儿哮喘能够显著降低患儿EOS计数、IgE水平,改善肺功能,值得临床推广。     

重组人粒细胞集落刺激因子对肝硬化大鼠外周血干细胞动员的研究

[目的]观察重组人粒细胞集落刺激因子(rhG-CSF)对四氯化碳(CCL4)肝硬化大鼠外周血中CD34+细胞的动员作用,以及对肝硬化大鼠肝脏生化学的影响,寻求一种安全有效、不加重肝损伤的动员CD34+细胞的方法。[方法]50%CCL4橄榄油溶液建立肝硬化大鼠模型,rhG-CSF动员组大鼠皮下注射rhG-CSF10μg.kg-1.d-1,共计5d,对照组给予相同剂量生理盐水。流式细胞仪测定外周血单个核细胞中的CD34+细胞的比例,同时检测ALT、AST、T-BIL和ALB,观察G-CSF对肝硬化大鼠肝脏的影响。[结果]肝硬化大鼠rhG-CSF动员后外周血CD34+细胞占单个核细胞(CD34+/MNC)比例(4.08±1.38)%是生理盐水对照组(0.43±0.21)%的9.5倍;而生化学检测两组没有显著性差异。[结论]G-CSF动员能促进更多的骨髓/造血干细胞源性的肝干细胞在外周血中表达,而且不加重肝硬化大鼠的肝脏损伤。     

rhG-CSF动员的人外周血与骨髓不同比例混合对移植物免疫特性的影响

目的探讨rhG-CSF动员的外周血采集物(G-PB)和骨髓(G-BM)不同比例混合对移植物免疫学特性的影响。方法用流式细胞仪测定G-PB和G-BM中T细胞亚群、树突状细胞(DC)亚群的数量,据有核细胞数将G-PB/G-BM按2∶11、∶11、∶2混合,计算混合移植物的免疫细胞组成;用MTT法和夹心ELISA法测定T细胞增殖能力和IL-4、IFN-γ的分泌。结果3种G-PB/G-BM混合移植物的T细胞增殖能力均低于未动员骨髓(NG-BM)和G-PB(P<0.05)。3种混合移植物与NG-BM、G-BM和G-PB在淋巴细胞、CD3 、CD4 、CD8 T细胞组成上存在差别(P<0.05);3种混合移植物的CD4/CD8比例都高于NG-BM和G-BM(P<0.01),DC1/DC2比值均低于NG-BM(P<0.01),IL-4/IFN-γ的比值均低于G-BM(P<0.05)。在输入相同CD34 细胞以保证植入的前提下,应用3种混合移植物进行移植时输入的Ⅰ型因子及Ⅰ型(Th1/Tc1)和Ⅱ型(Th2/Tc2)T细胞的数量介于NG-BM、G-BM和G-PB之间。结论G-PB/G-BM混合后免疫特性的改变可能在HLA不合移植中发挥作用。     

CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) regimen with granulocyte colony-stimulating factor (G-CSF) for patients with aggressive non-Hodgkin's lymphoma: a pilot study. The Adult Lymphoma Treatment Study Group (ALTSG)

We conducted a multi-institutional collaborative study to examine the usefulness and safety of third-generation chemotherapy CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) combined with granulocyte colony-stimulating factor (G-CSF) in the treatment of aggressive non-Hodgkin's lymphoma (NHL). Subjects included patients with aggressive NHL who were 60 yr of age or younger and had been diagnosed as having a low-intermediate, high-intermediate, or high risk using the International Prognostic Index (IPI). A total of 24 patients were enrolled in the study between May 1997 and March 1998, including 9 low-intermediate-risk cases, 13 high-intermediate-risk cases and 2 high-risk cases. Although all 24 patients were originally enrolled in the study, one adult T-cell leukemia/lymphoma case was subsequently excluded. Thus, in the end, 23 cases were evaluated. Evaluation of the efficacy of therapy revealed complete remission in 20 patients (87%). Of these 20 patients, 8 were low-intermediate-risk cases (89%) and 12 were either high-intermediate- or high-risk cases (86%). Partial remission was achieved in 2 patients (8.7%). The 2-yr survival rate was 91.3%, and the 2-yr disease-free survival rate was 81.8%. Grade 3 or higher adverse reactions were granulocytopenia (87%), thrombocytopenia (17.4%) and liver dysfunction (4.3%). CyclOBEAP therapy has been associated with a high remission rate for aggressive NHL. When combined with G-CSF, a high relative dose intensity was maintained for each drug administered (0.94-0.97). Furthermore, although the observation period was short, both the survival rate and disease-free survival rate were good. Hence, we concluded that there were no problems associated with the procedure in terms of safety.     

丙酸倍氯米松治疗常年性变应性鼻炎的临床研究

目的研究丙酸倍氯米松治疗常年变应性鼻炎的效果,并探讨其临床作用机制。方法对141例常年变应性鼻炎患者,分别用丙酸倍氯米松(丙酸倍氯米松组)和生理盐水喷鼻剂(对照组)进行治疗和疗效对比。结果丙酸倍氯米松组的总有效率为97.45%,对照组为21.38%;丙酸倍氯米松起效时间在45s左右,81%维持时间在3h以上;而生理盐水组起效时间23.15%在6min左右,30.8%维持时间在3h以内。4周后,丙酸倍氯米松组所查鼻分泌物中嗜酸性粒细胞明显减少或消失(P<0.05)。结论丙酸倍氯米松缓解症状迅速,维持时间长,疗效显著,安全性好,对常年变性鼻炎的治疗极为有效。     

Detection and quantification of functionally defined hematopoietic progenitor cells and tissue specific mRNA within the peripheral blood of myeloma patients after administration of granulocyte colony-stimulating factor and erythropoietin

Objective:  Hematopoietic progenitor cells (HPC) as well as tissue committed stem cells expressing mRNA specific to various somatic tissues are thought to be part of the CD34⁺ bone marrow compartment. In this study, we explore and quantify their mobilization in patients with multiple myeloma undergoing chemotherapy upon administration of granulocyte colony-stimulating factor (G-CSF) plus/minus erythropoietin (EPO).
Patients and methods:  HPC were quantified by flow cytometry and functional assays within the blood of healthy donors and myeloma patients before and after chemotherapy followed by G-CSF or G-CSF + EPO given subcutaneously. The mRNA expression was studied by quantitative polymerase chain reaction (PCR). Cytokines and peripheral blood protease levels were measured by an enzyme-linked immunosorbent assay.
Results:  EPO did not significantly alter the number of HPC mobilized by G-CSF alone, and mRNA specific for liver, brain, muscle and kidney was detected in both treatment groups. Quantitative PCR analysis revealed a 2.7-fold increased expression of glial fibrillary acidic protein after G-CSF + EPO administration compared to G-CSF alone ( P  = 0.003). The concentration of G-CSF rose from 62 ± 22 pg/mL and 48 ± 10 pg/mL to 28 ± 9 ng/mL and 85 ± 10 ng/mL after 10 d of treatment with G-CSF and G-CSF + EPO, respectively. The concentration of neutrophil elastase (NE) rose only in the G-CSF group by a factor 1.5.
Conclusion:  The alteration of G-CSF and NE levels as well as the expression of tissue committed RNA after the administration of EPO in addition to G-CSF indicate that different growth factors mobilize different stem cells that might potentially be used for the support of tissue repair in future treatment protocols.