Basic fibroblast growth factor and epidermal growth factor reverse impaired ulcer healing of the rabbit oral mucosa

BACKGROUND: The therapies for refractory ulcers on the oral mucosa are symptomatic and very unsatisfactory. We hypothesized that application of growth factors might be able to achieve successful remission of the lesion. We evaluated the effects of systemic administration and topical application of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on impaired wound healing of ulcers in the rabbit gingiva. METHODS: Almost uniform round ulcers could be created on the gingiva of the rabbits by chemical injury with acetic acid. When the submandibular glands were removed or i.v. injection of cisplatin (CDDP) and peplomycin sulfate was performed before ulcer formation, healing of the ulcers took longer than in untreated rabbits. To ascertain whether or not human EGF and bFGF affect rabbit cells, we first examined the effects of EGF and bFGF on the proliferation of the cells derived from rabbit gingiva. We then applied EGF or bFGF in these impaired healing models. RESULTS: EGF and bFGF promoted proliferation of the fibroblasts, and EGF also promoted proliferation of the keratinocytes isolated from gingival tissue of rabbits in vitro. Systemic injections of EGF and bFGF in rabbits, which had their submandibular glands removed, and topical application of bFGF accelerated healing of ulcers created in rabbits injected with CDDP and peplomycin sulfate. The ability of bFGF to promote the healing of ulcers was much greater than that of EGF. CONCLUSION: Basic FGF may be effective for refractory oral mucosal lesions.     

无血清培养人肝癌细胞增生率的变化和bFGF在细胞中的表达

采用无血清培养体系 ,研究肿瘤细胞自分泌调控机制。将人肝癌细胞培养在无血清无外源分裂因子培养基中 ,采用细胞原位计数法和免疫组织化学染色法 ,观察不同时相人肝癌细胞增生率的变化以及碱性成纤维细胞生长因子 (bFGF)的表达情况。结果 :人肝癌细胞生长良好 ,其增生速度与其分泌的bFGF量成正比。提示 :肝癌细胞在无外源生长因子的条件下通过分泌bFGF ,以自分泌和旁分泌的方式作用于自身和相邻细胞 ,促进细胞生长和增生。     

Sex cord-stromal tumors of the ovary

The developmental relationship between granulosa and stromal cells in the fetal ovary was reviewed. The proliferation and expression of basic fibroblast growth factor (bFGF) and luteinizing hormone receptor (LHR) of both the granulosa and theca cells was examined in the adult ovary. Ovarian granulosa cell tumors were then studied under light and electron microscopy and for immunohistochemical expression of bFGF and LHR. In the follicular development of the adult ovary, bFGF expression in the granulosa cells was correlated with theca cell proliferation. In ovarian granulosa cell tumors, estrogen-producing tumors showed a stratified or microfollicular pattern being accompanied by theca cells which had ultrastructural features of steroid-production, and these tumor cells exhibited immunoreactivity for bFGF. In contrast, tumors with no apparent hormone-production showed a solid or gyriform pattern without admixture of theca cells, and were negative for bFGF. LHR was expressed in both types of tumor. Accordingly, bFGF may play an important role in association with the theca cell component in granulosa cell tumors.     

Ad-METH1对培养的内皮细胞分泌活性的影响

目的：研究基因重组血管抑制剂Ad-METH1（metalloprotease and thrombospondin1）对培养的内皮细胞分泌活性的影响,探讨血管生成抑制防治增生性瘢痕的可能机制。方法：制备重组血管抑制剂Ad-METH1,转染培养的人脐静脉内皮细胞,通过放射免疫分析法及酶联免疫分析法研究Ad-METH1对内皮细胞分泌内皮素-1（endothelin-1,ET-1）及碱性成纤维细胞生长因子（basic fibroblast growth factor,bFGF）的影响。结果：基因转染后24h内皮细胞ET-1、bFGF分泌受到明显抑制。结论：Ad-METH1对内皮细胞ET-1、bFGF分泌活性有影响,此是其早期参与抑制增生性瘢痕形成的可能机制之一。     

Time-dependent changes in distribution of basic fibroblast growth factor immunoreactive cells in hippocampus after kainic acid injection in rat pups

Five-day-old Wistar albino rats were injected with kainic acid (KA) or saline i.p. to investigate time-dependent alterations in morphology and number of basic fibroblast growth factor (bFGF) immunoreactive (-ir) astrocytes and neurons in hippocampus at 15, 30, and 90 days after the injections. Sections were stained with cresyl violet for morphological evaluation and bFGF immunohistochemistry was used for quantitative evaluation of bFGF-ir cell density. Fifteen days after KA injection, there was gliosis but no neuronal loss although disorganization in CA1, CA3, CA4 pyramidal layers and neuronal loss were evident 30 and 90 days after the injection. KA injected rats demonstrated significantly increased number of bFGF-ir astrocytes throughout the hippocampus and pyramidal neurons in CA2 after 15 days and decreased number of bFGF-ir cells after 30 and 90 days. The decrease in the number of bFGF-ir astroglia and neurons in long term after KA injection may indicate a decrease in the production of bFGF and/or number of bFGF-ir cells suggesting that protective effects of bFGF may be altered during epileptogenesis in hippocampus.     

慢性低氧性肺动脉高压大鼠血清碱性成纤维细胞生长因子含量的变化

为探讨碱性成纤维细胞生长因子（ｂＦＧＦ）在慢性低氧性肺动脉高压肺血管重建中的作用及机理，采用慢性低氧性肺动脉高压大鼠模型，用酶联免疫吸附法测定其血清ｂＦＧＦ含量，并用原位杂交法观察肺、心、脑、肾等器官ｂＦＧＦｍＲＮＡ表达的变化。结果显示：低氧组血清ｂＦＧＦ含量（３５．９±２３．５ｐｇ．ｍｌ－１）明显高于对照组（６．３０±０．９７ｐｇ．ｍｌ－１，Ｐ＜０．００５）；低氧组肺小动脉ｂＦＧＦｍＲＮＡ表达明显增强，而心、脑、肾ｂＦＧＦｍＲＮＡ表达无变化。提示ｂＦＧＦ参与了慢性低氧性肺动脉高压肺小动脉重建的调控。     

人表皮生长因子与碱性成纤维细胞生长因子纳米缓释剂对成纤维细胞的影响

目的:制备碱性成纤维细胞生长因子(bFGF)、人表皮生长因子(EGF)可降解缓释微球,考察其生物活性的保存情况,以及它们对成纤维细胞的作用。方法:采用改良的乳化冷凝法交联制备复合bFGF、EGF的明胶缓释微球,将它们加入成纤维细胞的培养液中,用细胞计数法、四甲基偶氮唑盐微量反应比色法(MTT法)测定细胞增殖情况。结果:复合bFGF、EGF的缓释微球平均粒径(11.32±3.64)μm;培养1天后各组细胞计数、吸光度(A)值差异均无显著性;5天后,两种生长因子缓释微球组细胞计数、吸光度(A)值明显高于对照组;7天后,两种生长因子缓释微球组值仍高于其它组,但差异无显著性。结论:复合bFGF、EGF的缓释微球制备工艺简便,成球性好;能较长时间地持续释放活性bFGF、EGF,可促进成纤维细胞的增殖。     

Vascular endothelial growth factor overproduced by tumour cells acts predominantly as a potent angiogenic factor contributing to malignant progression

To elucidate the role of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, in tumour angiogenesis and malignant progression, an expression vector harboring human VEGF cDNA was stably transfected into three human cancer cell lines with poor VEGF productivity. Though their in vitro growth rate and intrinsic productivity of another angiogenic factor, basic fibroblast growth factor (bFGF), were not changed by transfection, those clones with higher VEGF production were endowed with tumorigenic and angiogenic potentials as follows: firstly, nontumorigenic, lung carcinoma QG90 cells having lower bFGF productivity acquired tumorigenicity as well as significant in vivo angiogenesis-inducing ability, secondly, tumorigenic colorectal carcinoma RPMI4788 cells having higher potency for bFGF production could form more vascularized solid tumour with faster growth rate and thirdly, oestrogen-dependent breast carcinoma MCF-7 cells, which did not produce detectable bFGF, acquired tumorigenicity even in the absence of oestrogen and the solid tumour growth rate was remarkably enhanced, accompanied with increased vascularization, in the presence of oestrogen. These results suggest that tumour progression closely depends on angiogenesis, and VEGF significantly contributes to malignant progression of a variety of tumour cells through its potent angiogenic activity, independent on the bFGF productivity of tumour cells.     

bFGF对胚胎神经干细胞分化为神经元及神经胶质细胞的影响

本研究观察了碱性成纤维生长因子对胚胎神经干细胞生长和分化的影响。从孕 12 d大鼠胚胎神经管分离神经干细胞 ,进行体外培养 ,分为碱性成纤维生长因子组及对照组。培养过程中观察神经干细胞的生长 ,于培养第 3、5、10 d用免疫组化方法检测培养细胞神经元特异烯醇化酶和胶质纤维酸性蛋白的表达 ,以观察神经干细胞分化为神经元及神经胶质细胞的状况。碱性成纤维生长因子可明显地促进培养细胞的生长和分化。免疫组化细胞计数显示 ,培养第 3 d,特异烯醇化酶、胶质纤维酸性蛋白阳性细胞数均明显增加 ;培养第 5 d,特异烯醇化酶阳性细胞数是对照组的 1.9倍 ,胶质纤维酸性蛋白阳性细胞数为对照组的 1.6倍 ,前者表达增加明显 ;培养第 10 d,两者的阳性细胞数仍高于对照组 ,但增加不明显。不同培养时间的胞体最长突起长度也均高于对照组 ;胞体直径及表面积随培养时间延长而增大。说明 ,碱性成纤维生长因子既能促进胚胎神经干细胞的生长 ,也可促使其分化为神经元及神经胶质细胞 ,尤以神经元为明显     

Effects of EGF and bFGF on Irradiated Parotid Glands

Radiotherapy is common treatment for head-and-neck cancer, during which the salivary glands are often included within the radiation field. The most common side effect of this treatment is the development of oral dryness (xerostomia). This study considers the administration of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF or FGF2) at physiological concentrations before and after irradiation in order to repair radiation-induced damage in salivary gland cells. As a preliminary examination of the efficacy of this approach we have characterized the effects of EGF and bFGF on the apoptotic response of 15-Gy irradiated rat salivary glands in vitro. Also, we have developed a controlled-release delivery system to effectively administer the growth factor to the gland since local delivery is essential to avoid unwanted protection of cancer cells. In vitro administration of bFGF prior to and immediately after irradiation partially protected (44%) the rat parotid gland. EGF did not show any significant radioprotective effect on parotid glands after a single 15-Gy irradiation dose. Encapsulation, storage and release of bFGF from biodegradable 50/50 PLGA microspheres did not affect the functionality of the growth factor in vitro.