Effect of recombinant human granulocyte colony stimulating factor (lenograstim) on chemotherapy induced neutropenia in patients with urothelial cancer

BACKGROUND: A multicenter cooperative study to evaluate clinical usefulness of recombinant human granulocyte colony stimulating factor (rG-CSF; lenograstim) in the treatment of neutropenia associated with cancer chemotherapy was conducted in patients with urothelial cancer. METHODS: Therapeutic responses were compared within each patient between the observation and study treatment phases. RESULTS: Treatment with rG-CSF raised the nadir of the neutrophil count (343 to 3015/mm3), reduced the duration of neutropenia (6.2 to 0.4 days) and hastened recovery from the neutropenic state (23.5 to 5.5 days). Febrile neutropenia was encountered in 12 patients during the observation phase alone and in only one patient during the study treatment phase alone. The mean duration of febrile neutropenia was also shortened (0.39 to 0.12 days). In addition, the duration of antibiotic therapy was significantly reduced during treatment. The percentage of patients completing the chemotherapeutic regimens of combination M-VAC therapy was markedly increased to 81.0% as a result of rG-CSF therapy compared with 44.8% in the observation phase. Adverse reactions were observed in four patients and abnormal laboratory values were found in nine patients. None of these adverse events was of a serious nature. CONCLUSIONS: These results indicate that rG-CSF is a useful drug for the treatment of neutropenia associated with chemotherapy in urothelial cancer.     

Incidence of acute cellular rejection following granulocyte colony‐stimulating factor administration in lung transplantation: A retrospective case‐cohort analysis

Granulocyte colony‐stimulating factor (GCSF) is an option to treat leukopenia in lung transplant recipients. Conflicting evidence exists regarding its effects on acute cellular rejection (ACR). A retrospective, case‐cohort study was conducted to assess whether the use of GCSF in lung transplant recipients is associated with an increased incidence of ACR. Patients had to have received at least one dose of GCSF but were excluded if they received GCSF within 30 days prior to transplant or received a lymphocyte‐depleting agent within 14 days of GCSF administration. Thirty‐five patients who received GCSF within 3 months of transplant met inclusion criteria and 105 patients were identified as controls based on a 1:3 allocation scheme. Incidence of ACR was 57.1% in the GCSF group versus 50.5% in the control group (relative risk (RR)=1.13; 95% CI, 0.80 to 1.59; P=.48). At 3 months post‐transplant, 74.3% of the GCSF group had a dose reduction or discontinuation of their antiproliferative agent versus 17.1% of the control group (RR=4.33; 95% CI, 2.73 to 6.89; P<.0001). Rejection severity and incidence of infections was similar among groups. These findings show that GCSF administration within 3 months following lung transplantation was not associated with a higher incidence or severity of ACR.     

Tumor-related immunity in prostate cancer patients treated with human recombinant granulocyte monocyte-colony stimulating factor (GM-CSF)

BACKGROUND: Granulocyte monocyte-colony stimulating factor (GM-CSF) supports the survival, expansion, and differentiation of lymphoid and myeloid derived dendritic cells (DCs). We hypothesized that systemic therapy with GM-CSF in prostate cancer patients could augment prostate cancer-related immunity and induce clinical response. METHODS: Eligible patients were randomly assigned to receive either 125 or 250 microg/m(2) GM-CSF subcutaneously three times a week until clinical progression. Prostate-specific antigen (PSA) T cell precursor frequencies were determined by a flow cytometric method. RESULTS: We were able to show, for the first time, a statistically significant correlation between pre-treatment PSA level and PSA-specific CD4(+) T cell precursors and a trend between pre-treatment PSA level and PSA-specific CD8(+) T cell precursors (P<0.0001 and P=0.059, respectively). CONCLUSIONS: These results suggest that existent immunity to PSA in prostate cancer patients may be a promising target for future immunotherapeutic approaches to prostate cancer.     

Protection of spermatogenesis in mice against gamma ray induced damage by Hippophae rhamnoides

The radioprotective action of a preparation from Hippophae rhamnoides berries RH-3, already reported to render >80% survival against whole body 10 Gy gamma irradiation, was further investigated with respect to the testicular system. RH-3 was administered to mice 30 min before gamma irradiation (5 and 10 Gy) and histological parameters such as testis weight, sperm count, frequency of abnormal sperm, repopulation index, stem cell survival index and seminiferous tubular diameter were assessed on the 35th day. RH-3 administration partially countered radiation induced reduction in testis weight, sperm count, repopulation index and stem cell survival index (p < 0.01). The increase in the frequency of abnormal sperm (15.17 +/- 1.046%) caused by irradiation (5 Gy) was counteracted by pre-irradiation treatment with RH-3, which significantly decreased the level of abnormal spermatozoa to 7.99 +/- 0.918% (p < 0.001), i.e. 52% abnormalities in comparison with 5 Gy irradiated group. RH-3 treatment alone did not elicit any toxic or adverse effect on the process of spermatogenesis. The present study suggests that RH-3 treatment protected spermatogenesis by enhancing the spermatogonial proliferation, enhancing the stem cell survival and reducing sperm abnormalities. The presence of polyphenolic flavonoids and tannins in the extract and the radical scavenging activity might be responsible for the radioprotective action of RH-3.     

重组人粒细胞集落刺激因子促进骨髓间充质干细胞增殖

目的探讨重组人粒细胞集落刺激因子(rhG-CSF)对小鼠骨髓间充质干细胞(MSCs)增殖的影响。方法将昆明小鼠随机分为2组(n=15),G-CSF组采髓前皮下注射重组人粒细胞集落刺激因子(rhG-CSF)80μg·kg-1·d-1,连用5d,对照组皮下注射等量生理盐水。每组分别于最后一次注射后6h、12h及7d(168h)取小鼠骨髓,分离、培养MSCs,计数成纤维样细胞集落形成单位(CFU-F)的个数;应用流式细胞仪检测单个核细胞(MNCs)细胞周期及CFU-F细胞表面抗原特征。结果应用rhG-CSF后,培养MNCs所获得的CFU-F数目增加(P<0.01),CFU-F数与取材时间(6h、12h、7d)呈负相关(P<0.05),但12h取材者与7d取材者比较,CFU-F数目的差异无统计学意义(P>0.05)。MNCs培养形成的CFU-F,其细胞表面抗原呈CD34-、CD133-、CD90+、CD105+,分别占2.5%、3.1%、67.0%和78.0%。G-CSF组各时间点获得的MNCs,其G0/G1期细胞百分率较对照组低(P<0.05),而S+G2/M期增高(P<0.05),且6h取材者S+G2/M期细胞百分率明显高于12h和7d取材者(P<0.05)。结论rhG-CSF可促进骨髓MNCs进入细胞增殖周期,增殖的高峰在应用G-CSF后6h左右。     

粒细胞-单核巨噬细胞集落刺激因子对人皮肤成纤维细胞血管内皮细胞生长因子表达的影响

目的探讨粒细胞-单核巨噬细胞集落刺激因子（granulocyte-macrophage colony stimulating factor,GM—CSF）对人皮肤成纤维细胞血管内皮细胞生长因子（vascular endothelial cell growth factor,VEGF）表达的影响。方法分别用含GM—CSF（GM—CSF组）和不含GM—CSF（对照组）培养液,孵育离体培养的人皮肤成纤维细胞,作用不同时间后,采用逆转录-聚合酶链反应（RTPCR）、蛋白质印迹法（Western印迹法）、酶联免疫吸附试验（EI,1SA）分别检测人皮肤成纤维细胞VEGF mRNA表达和蛋白表达。结果GM—CSF作用1、3、6、12h后,人皮肤成纤维细胞VEGF mRNA表达均较对照组显著增强（P〈0．05）,其中GM—CSF作用6h后VEGFmRNA表达最强;与对照组比较,GM—CSF作用12、24、48h后。成纤维细胞内VEGF蛋白表达旺著增强,其中24h表达最强;细胞培养上清液中VEGF蛋白分泌堪随时间延长逐渐增加,各时相点GM-CSF组VEGF蛋白分泌量高于对照组（P〈0．01）。结论GM—CSF可促进人皮肤成纤维细胞VEGF的表达,这可能是GM-CSF加速创面血管新生化的机制之一。     

Simultaneous production of granulocyte colony-stimulating factor and parathyroid hormone-related protein in bladder cancer

A case of bladder cancer with simultaneous production of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) is reported. An 81-year-old male patient was admitted to the Saitama Medical School for treatment of gross hematuria, leukocytosis and hypercalcemia and diagnosed as having advanced bladder cancer. Immediately after a cystectomy was carried out, his white cell count and serum calcium levels returned to normal. However, the tumors recurred locally and the recurrence was accompanied by an increase in the serum G-CSF and PTHrP levels with a recurrent elevation of white cell count and the serum calcium level. The production of G-CSF and PTHrP in the tumor cells was confirmed by immunohistochemistry.     

Effect of granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced oral mucositis

In this study, the ability of granulocyte colony-stimulating factor (G-CSF) to treat or prevent chemotherapy-induced oral mucositis in patients with advanced breast cancer was evaluated. A total of 14 patients who received intra-arterial (i.a.) adriamycin (ADM) preoperatively were divided into two groups according to whether or not G-CSF was given. Thus, group A (n=7) was given G-CSF and group B (n=7) was not. G-CSF therapy reduced both the incidence and duration of ADM-induced oral mucositis, and a positive correlation was also seen between the incidence of mucositis and ADM-induced leukopenia (<2,000/mm³). Group A was further divided into two subgroups according to whether G-CSF was given after or before the leukopenia had dropped below 2,000/mm³: group A-1 (n=3) and group A-2 (n=4), respectively. ADM-induced mucositis was observed in two of the three patients in group A-1, but in none of the four patients in group A-2. These results strongly support the idea that G-CSF can effectively treat and prevent ADM-induced oral mucositis.     

尾静脉注射质粒巨噬细胞-粒细胞集落刺激因子诱导扩增小鼠肝脏CD11c+树突状细胞

目的 探讨载粒巨噬细胞-粒细胞集落刺激因子(GM-CSF)基因质粒在小鼠体内扩增肝脏CD11c+树突状细胞(DC)的方法.方法 采用快速尾静脉椎注法将含20 μg GM-CSF基因质粒的生理盐水2.0 ml导入小鼠肝脏内,对照组注射增强型绿色荧光蛋白(EGFP)基因.第7天取肝,胶原酶消化、密度梯度离心、磁珠标记等分选出DC.Giemsa染色作形态学观测,采用流式细胞术分析其免疫表型.结果 实验组小鼠肝脏非实质细胞(NPC)大量增殖,主要分布于门静脉及其周围区域,质粒处理组中CD11c+DC比例较对照组显著增多(29.31％比6.77％,P＜0.05).Giemsa染色显示两组DC细胞核形状不规则,胞质无颗粒,然而实验组DC较对照组有明显凸起.流式细胞仪检测结果显示实验组DC较对照组明显成熟,CD40、CD80、CD86表达显著增高(P＜0.05).结论 经快速尾静脉推注质粒GM-CSF的方法可显著可靠地扩增肝脏CD11c+DC的数量.     

粒细胞集落刺激因子对大剂量盐酸戊乙奎醚所致大鼠认知功能障碍的影响

目的观察粒细胞集落刺激因子(G-CSF)对大剂量盐酸戊乙奎醚所致大鼠认知功能障碍的影响。方法 24只14个月龄Wistar成年雄性大鼠随机分为三组:空白组(N组)、盐酸戊乙奎醚组(P组)和G-CSF治疗组(G组),每组8只。N组腹腔注射生理盐水1ml,P组腹腔注射盐酸戊乙奎醚2.56mg/kg,G组腹腔注射盐酸戊乙奎醚2.56mg/kg后皮下注射G-CSF 50μg/kg,连续5d。第1、3、5天给药后用Morris水迷宫测试其空间学习记忆能力的改变,末次水迷宫实验后用免疫组化法观察海马胆碱乙酰转移酶(ChAT)阳性细胞表达个数。结果与第1天比较,第3天和第5天三组潜伏期和游泳距离均明显缩短(P<0.05),且第5天N组和G组明显短于P组(P<0.05)。与P组比较,N组和G组海马区ChAT阳性细胞个数均明显增多(P<0.05)。结论 G-CSF可以改善大剂量盐酸戊乙奎醚引起的大鼠认知功能障碍。     

Paraneoplastic neurological and hematological syndromes associated with prostate cancer

Paraneoplastic neurological syndromes are defined as the remote effects of cancer on the nervous system. Here we report a 68-year-old man who initially presented with worsening paresthesia in the lower extremities. Although the culprit lesion remained to be identified, he coincidentally had diagnosis of prostate cancer by an annual prostate-specific antigen examination. Leukocytosis and elevated granulocyte colony-stimulating factor in serum were also detected. Neurological symptoms and leukocytosis improved after initiation of androgen-deprivation therapy followed by external beam radiotherapy. A total of 9 months after treatment, the patient showed no evidence of cancer recurrence or neurological signs. Paraneoplastic neurological syndromes are rare in prostate cancer and therefore have received little attention. We should be aware that when paraneoplastic neurological syndromes occur, they usually occur as the first sign of or during progression of prostate cancer. Furthermore, we should take into account the existence of malignancy when the cause of neurological symptoms cannot be specified.     

Association between elevated plasma granulocyte colony-stimulating factor and the degree of surgical stress in patients undergoing gastrointestinal surgery

To characterize the changes in perioperative plasma granulocyte colony-stimulating factor (G-CSF) and analyze the effect of surgical stress on its kinetics, 41 patients undergoing gastrointestinal surgery with varying degrees of surgical stress were examined. The plasma levels of G-CSF significantly increased immediately after the operation, probably in response to surgical injury. This elevation was much higher in the 15 esophagectomy patients, at 883±300 pg/ml on postoperative day (POD) O, than in the 14 gastrectomy patients, with a value of 233±151 on POD O, (P<0.01) or in the 12 cholecystectomy patients, with a value of 64±41 on POD 1 (P<0.01). These findings led us to conclude that G-CSF levels increase significantly in the immediate postoperative period and are most likely associated with the degree of surgical stress. In addition, we studied the priming effect of G-CSF on polymorphonuclear leukocytes (PMNs). G-CSF enhanced PMN superoxide anion (O^– ₂) production and luminol-dependent chemiluminescence (CL) induced by opsonized zymosan in a dose-dependent manner. A significant enhancement was seen in the G-CSF level (1 ng/ml) which was almost the same as the maximum G-CSF level in the esophagectomy patients. Furthermore, postoperative PMN activation occurred after the elevation of plasma G-CSF. Thus, we propose that elevated G-CSF may act as one of the mediators which activate PMN function postoperatively.     

The role of cyclophosphamide and granulocyte colony-stimulation factor in achieving high-level chimerism in allotransplanted limbs.

The establishment of a high-level of chimerism may be the most stable strategy for donor-specific tolerance. The purpose of this study was to evaluate the efficacy of a new protocol using cyclophosphamide (CYP) and granulocyte colony-stimulation factor (G-CSF) to induce high-level chimerism following rat whole-limb allotransplantation. Seventy-three whole-limb allotransplants from LacZ transgenic rats to LEW rats were performed. CYP was injected at day 2, and G-CSF was given from day 0 to 3. Nontreated limb allografts were rejected after 4.2 days. In FK506-treated group for 28 days, the survival time was prolonged to 64 days. In the group treated with CYP/G-CSF, limb allografts were rejected after 5.4 days and 5 of 15 recipients showed acute lethal graft-versus-host disease (GVHD). Polymerase chain reaction (PCR) study showed a high level of chimerism even within 1 week after transplantation. Fourteen of 30 recipients given CYP/G-CSF/FK506 died within 2 weeks. The limb survival was significantly prolonged, however, with three grafts surviving more than 300 days. Seven recipients (24%) showed chronic GVHD. A high-level of chimerism was maintained when limb allografts were not rejected by recipients. Limb allografting could function as a vascularized carrier for bone marrow transplantation, provide a continuous source of donor cells and contribute to a high level of chimerism in the recipient. Pretransplant CYP followed by G-CSF and FK506 treatment significantly prolonged the survival of limb allografts but frequently caused chronic GVHD in the recipients.     

Use of G‐CSF‐stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review

Chang Y‐J, Huang X‐J. Use of G‐CSF‐stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review.
Clin Transplant 2011: 25: 13–23. © 2010 John Wiley & Sons A/S. Abstract: In recent years, several researchers have unraveled the previously unrecognized effects of granulocyte colony‐stimulating factor (G‐CSF) on hematopoiesis and the immune cell functions of bone marrow in healthy donors. In human leukocyte antigen‐matched or haploidentical transplant settings, available data have established the safety of using G‐CSF‐stimulated bone marrow grafts, as well as the ability of this source to produce rapid and sustained engraftment. Interestingly, G‐CSF‐primed bone marrow transplants could capture the advantages of blood stem cell transplants, without the increased risk of chronic graft‐versus‐host disease that is associated with blood stem cell transplants. This review summarizes the growing body of evidence that supports the use of G‐CSF‐stimulated bone marrow grafts as an alternative stem cell source in allogeneic hematopoietic stem cell transplantation.     

宫腔灌注粒细胞集落刺激因子在不明原因反复种植失败患者中的应用评价

目的 研究宫腔灌注粒细胞集落刺激因子(G-CSF)对不明原因反复种植失败(URIF)患者的子宫内膜容受性及妊娠结局的影响.方法 采用前瞻性随机对照的研究方法,选择2019年1月至2020年9月期间于大连市妇女儿童医疗中心就诊的,拟行人工周期-冻融胚胎移植的U RIF患者120例,将患者随机分为试验组和对照组(每组各60...     

重组人粒细胞巨噬细胞集落刺激因子在压疮护理中的应用

目的:探讨重组人粒细胞巨噬细胞集落刺激因子凝胶在Ⅱ~Ⅲ期压疮治疗护理中的临床效果。方法:选取2011年2月~2013年2月Ⅱ~Ⅲ期带压疮入院患者85例(98处),试验组应用重组人粒细胞巨噬细胞集落刺激因子凝胶治疗,对照组创面应用SD-Ag霜。分别对两组疗效、细菌存在情况及PUSH评分进行观察。结果:试验组平均愈合时间为(16.75±1.22)天,有效率96.49%,对照组平均愈合时间为(21.73±4.55)天,有效率78.05%。换药14天后,试验组的PUSH评分为(5.76±2.59)分,对照组为(8.59±3.23)分,各项指标对比均具有显著性差异(P0.01)。结论:重组人粒细胞巨噬细胞集落刺激因子凝胶能减少Ⅱ~Ⅲ期压疮创面细菌繁殖,促进肉芽组织生成,显著缩短愈合时间。     

重组人粒细胞/巨噬细胞集落刺激因子联合水凝胶敷料治疗深Ⅱ度烧伤创面临床观察

目的:观察外用重组人粒细胞/巨噬细胞集落刺激因子(rhGM-CSF)联合水凝胶敷料治疗深Ⅱ度烧伤创面的临床效果.方法:选择四肢部位有深Ⅱ度烧伤创面的住院患者24例,48处研究创面,每例患者2个创面,分别位于不同肢体.研究分为4组.随机选取12例患者,每例患者随机选取一个创面作为rhGM-CSF联合外用水凝胶敷料治疗组(联合治疗组,创面清创后外涂外用重组人粒细胞巨噬细胞刺激因子凝胶,覆盖医用水凝胶敷料),另一个创面作为rhGM-CSF联合外用凡士林油纱治疗组(rhGM-CSF对照组,创面清创后外涂外用重组人粒细胞巨噬细胞刺激因子凝胶,覆盖凡士林油纱);余12例患者每例随机选择一处创面作为水凝胶敷料治疗组(水凝胶对照组,创面直接覆盖医用水凝胶敷料);另一处创面作为凡士林油纱对照组(凡上林对照组,创面直接覆盖凡士林油纱).每组12处创面.观察各组创面愈合时间及创面感染情况,创面分泌物行细菌培养,比较创面细菌感染阳性率.结果:联合治疗组创面愈合时间较其他3组明显缩短(P＜0.05);rhGM-CSF对照组和水凝胶对照组创面愈合时间较凡士林对照组缩短(P＜0.05).rhGM-CSF联合外用水凝胶敷料治疗组创面洁净,细菌检出率低(16.7％):rhGM-CSF治疗组感染状况也较轻,细菌检出率较低(25.0％),凡士林对照组感染状况重,细菌检出率最高(83.3％,P＜0.01).结论:深Ⅱ度烧伤创面外用rhGM-CSF联合水凝胶敷料治疗,可以明显减少创面细菌感染概率,缩短创面愈合时间.     

The granulocyte colony-stimulating factor produced in the human lung and its effect on liquid movement in the rabbit lung

Levels of the granulocyte colony-stimulating factor (G-CSF) were determined in the plasma and resected lung tissue from patients who underwent pulmonary resection. Moreover, the effect of recombinant human (rh) G-CSF on the permeability of pulmonary endothelium and on liquid clearance from the alveolar spaces was investigated in rabbits. The plasma levels of G-CSF increased from 30 pg/ml preoperatively to 409 ± 236 pg/ml 3 h postoperatively (P < 0.05), while the levels of G-CSF in the resected lung tissue were increased in the alveolar fluid, to 1,834 ± 1,054 pg/ml, and in the pulmonary blood, to 5,466 ± 2,019 pg/ml. It was found that rh G-CSF 25 g administered into the subcutaneous tissue of rabbits increased extravascular lung water to 3.45 ± 0.26 vs 2.98 ± 0.20 in control experiments (P < 0.05); however, rhG-CSF 0.75 pg/kg administered into the alveloar spaces did not affect liquid clearance from the alveolar spaces. The findings of this study led us to conclude that G-CSF is synthesized in the human lung and increases the permeability of pulmonary endothelium, but not liquid clearance across the alveolar epithelium.