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Clinical application of human urinary colony-stimulating factor.

人尿集落刺激因子的临床应用。

基本信息

批准号：
59870041
负责人：
MOTOYOSHI Kazuo
金额：
$ 3.01万
依托单位：
Jichi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1984
资助国家：
日本
起止时间：
1984 至 1985
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-59870041/
关键词：
Colony-stimulating factor Monocytes Antigranulocytopenic drug Leukemia Granulocyte nadir 末梢血単球

项目摘要

Human urinary colony-stimulating factor(CSF-HU)is one of adherent cell dependent CSFs, which stimulates human peripheral blood monocytes to produce human granulocytic colony-stimulating factor (G-CSF) that stimulates human granulocytic colony-forming cells (G-CFCs) to from granulocytic colonies in a monolayer agar culture. In this research project, we have tried to purify CSF-HU and use it on patients with cancer as an antigranulocytopenic drug. We have extensively purified CSF-HU using the procedure containing DEAE cellulose column, gel filtration, phenyl-Sepharose column, and chromatofocusing and reversed phase HPLC (high performance liquid chromatography) and obtained almost pure CSF-HU of which specific activity was 1.9x10 U/mg protein. We now analyze N-terminal amino acid sequence of this material and establish radioimmunoassay system for CSF-HU using purified CSF-HU and polyclonal antibody against partially purified CSF-HU. CSF-HU did not stimulate cell growth of several human leukemic cell lines and fresh leukemic cells. Preparation I of CSF-HU which we previously used in clinical trials, had partially protected the patients from granulocytopenia after anticancer chemotherapies but it gave several side effects such as fever and chilliness. We have further purified and obtained preparation II of CSF-HU which was 6 fold-higher specific activity and 15 fold-lower endotoxin content. We injected 33 patients with 8x10 U of preparation II for 7 days after the end of chemotherapies. Average granulocyte nadir of 33 patients was 896 871 in preparation II-injected courses and 494 336 in control courses. Duration under 500 granulocytes was 2.9 3.8 days in preparation II-infused courses and 4.7 3.7 days in control courses. These differences were statistically significant. Based on these observations, double blind phase III clinical study will be initiated in near future.

人尿集落刺激因子（human urinary colony-stimulating factor，CSF-HU）是一种粘附细胞依赖性CSF，能刺激人外周血单核细胞产生人粒细胞集落刺激因子（human granulocyte colony-stimulating factor，G-CSF），G-CSF能刺激人粒细胞集落形成细胞（human granulocyte colony-forming cells，G-CFCs）在单层琼脂培养基中形成粒细胞集落。在本研究项目中，我们试图纯化CSF-HU并将其作为抗粒细胞减少症药物用于癌症患者。我们采用DEAE纤维素柱、凝胶过滤、苯基-Sepharose柱、聚焦层析和反相高效液相色谱等方法对CSF-HU进行了广泛的纯化，得到了比活为1.9 × 10 ~ 5 U/mg蛋白的几乎纯的CSF-HU。本研究对该材料的N-末端氨基酸序列进行了分析，并利用纯化的CSF-HU和部分纯化的CSF-HU多克隆抗体建立了CSF-HU的放射免疫分析体系。CSF-HU不刺激几种人白血病细胞系和新鲜白血病细胞的细胞生长。我们以前在临床试验中使用的CSF-HU制剂I部分地保护了患者免受抗癌化疗后的粒细胞减少症，但它产生了一些副作用，如发热和发冷。进一步纯化得到比活提高6倍、内毒素含量降低15倍的CSF-HU制剂II。我们在化疗结束后对33例患者注射8 × 10 U制剂II，持续7天。33例患者的平均粒细胞最低值在制剂II注射过程中为896 871，对照过程中为494 336。在500粒细胞的持续时间为2.9 - 3.8天，在准备II输注的课程和4.7 - 3.7天的控制课程。这些差异具有统计学显著性。基于这些观察结果，将在不久的将来启动双盲III期临床研究。