Growth factor regulation of integrin-mediated cell motility

Summary Cell motility, a primary component of tumor cell invasion, is a continuum of sequential events in which the cell extends pseudopodia, forms nascent attachments, assembles and contracts the cytoskeleton, and finally, as it translocates forward, disengages distal adhesions. What triggers cells to move? Substratum contact mediated by integrin adhesion receptors is important, but other signals such as chemokinetic factors appear to be required for continued crawling. It is now apparent that integrins do not simply bind cells to matrix in a Velcrolike fashion, but also are potent signaling molecules. Initial engagement of integrins induces their condensation into focal contacts, forming anchors to the extracellular matrix and discrete signal-transducing complexes on the cytoplasmic surface. A number of growth factors, through either autocrine or paracrine pathways, can activate the cellular machinery that mobilizes the cell. Thus, these two classes of receptors - the integrin receptors that bind specific extracellular adhesion molecules, and growth factor receptors that bind their respective ligands - can regulate cell locomotion. Not surprisingly, there is cross-talk between integrin and growth factor receptors that occurs through their common intracellular signaling pathways. In this way, each receptor type can either amplify or attenuate the other's signal and downstream response. An example of growth factor-induced motility is the epithelial-mesenchymal transition induced by hepatocyte growth factor/scatter factor (HGF/SF). When bound to its receptor, the c-met proto-oncogene product, HGF/SF induces a phenotypic conversion that appears to be an important aspect of tumor progression in malignant carcinomas. The motogenic response produced by HGF/SF in carcinoma cells occurs in discrete steps in which integrins and focal adhesion kinase (p125^FAK) are first recruited to focal contacts. This is rapidly followed by cell spreading, disruption of focal adhesions and cell-cell contacts, and, finally, cell crawling. The precise mechanism by which growth factors such as HGF/SF and its receptor induce this motogenic response and modulate integrin function has not been clearly defined but appears to involve several signaling pathways. Understanding the process by which growth factor and integrin receptors interact and regulate motility may suggest novel targets for therapeutic intervention.     

Recombinant human growth hormone in infants and young children with chronic renal insufficiency

Children with chronic renal insufficiency (CRI) secondary to congenital structural abnormalities frequently have significant growth retardation by 2 years of age. In a multicenter placebo-controlled study of the use of recombinant human growth hormone (rhGH), 30 of 125 (24%) participants were<2.5 years of age at enrollment. Since the treatment arms of the study were balanced for age at randomization, data for these patients were examined for efficacy and safety. During the first 2 years of the study, approximately two-thirds of the patients (n=19) received rhGH 0.05 mg/kg per day subcutaneously and one-third (n=11) received placebo injections. At entry into the study, the mean (± SD) calculated creatinine clearance was 29.2±14.3 (range 12.0–63.7) ml/min per 1.73 m² in the rhGH-treated group and 23.3±15.1 (range 8.0–59.4) ml/min per 1.73 m² in the placebo-treated group. The 1st year growth rate was 14.1±2.6 cm/year for the rhGH-treated group and 9.3±1.5 cm/year in the placebo-treated group (P<0.00005). During the 2nd year of the study, the growth rate was 8.6±1.2 cm/year in the rhGH-treated group compared with 6.9±1.0 in the placebo groupP=0.025). The height standard deviation score was +2.0±0.7 for the rhGH-treated group compared with –0.2±1.1 in the placebo-treated group (P<0.00005) during the 2 years of the study. Minor adverse events occurred with similar frequency in both groups. These data suggest that rhGH is efficacious and safe in children with CRI under age 2.5 years. rhGH therapy may correct significant loss of growth at this age when used in conjunction with optimal medical management.     

Interleukin-1Β, interleukin-6, and growth hormone levels in human follicular fluid

Purpose To investigate possible relationships of interleukin-1 (IL-1, interleukin-6 (IL-6), and growth hormone (GH) with biochemical variables in human follicular fluid (FF) and selected in vitro fertilization (IVF) parameters.Methods A total of 67 FF samples (n=67 patients undergoing oocyte retrieval for IVF) was evaluated. IL-1, IL-6, GH, hLH, FSH, PRL, hCG, testosterone, total protein, fibrinogen, sialic acid, ₁-antitrypsin, plasminogen levels, and spectrophotometric absorbance at 458 nm were analyzed for selected FF. IL-6 and GH levels of serum and FF samples were also compared (n=23).Results Immunoreactive levels of IL-1, IL-6, and GH were detected in all FF samples. A positive correlation existed for IL-6 (r=0.5069, P=0.0161 when serum-to-FF levels were compared (concentration ratio, 11.857). Smaller-volume follicles (<4 ml) were associated with high IL-1 levels (P=0.0229, and an additional tendency of IL-1 to decrease with increasing embryo cleavage and scoring was observed. With the exception of a weak positive correlation between follicular IL-1 and testosterone levels (r=0.3128, P=0.025, no other relationship with biochemical variables or IVF parameters (etiology, e.g., endometriosis) could be implicated.Conclusions Substantially higher IL-6 levels occurred in FF compared to serum, thus supporting intrafollicular production. Interleukin- 1,IL-6, and GH levels in FF are, however, unsuitable markers for in vitro fertilization outcome.     

基于神经营养因子探讨经颅直流电刺激对缺血性脑卒中患者的影响

目的 探讨经颅直流电刺激（tDCS）对缺血性脑卒中患者的影响,以及与外周血神经营养因子的相关性。 方法 将40例缺血性脑卒中患者按随机数字表法分为对照组与治疗组,每组20例。2组患者均给予常规药物治疗及康复训练,治疗组在此基础上增加tDCS,强度2.0 mA,每次20 min,每日1次,共14次,对照组给予伪刺激。治疗前及治疗2周后（治疗后）,采用改良Barthel指数（MBI）、简易精神状态量表(MMSE) 、汉密尔顿抑郁量表（HAMD）、抑郁自评量表(SDS)对2组患者进行评估,用ELISA法测定外周血脑源性神经营养因子(BDNF）、神经生长因子(NGF）水平。 结果 治疗前,2组患者MBI、MMSE、HAMD、SDS评分及外周血BDNF、NGF水平比较,差异均无统计学意义（P>0.05）。与组内治疗前比较,2组患者治疗后上述指标均改善（P<0.05）。与对照组比较,治疗组治疗后MBI评分［（68.00±14.81）分］、MMSE评分［（24.85±3.12）分］较高（P<0.05）,HAMD评分［（19.70±2.11）分］较低（P<0.05）,外周血BDNF水平［（108.20±36.96）pg/ml］、NGF水平［（2.90±1.03）pg/ml］较高（P<0.05）。 结论 tDCS可以有效改善缺血性脑卒中患者的认知功能,减轻抑郁症状,提高生活自理能力,其作用机制可能与神经营养因子水平升高有关。     

含重组人碱性成纤维细胞生长因子和重组人骨形态发生蛋白-2骨水泥在骨质疏松性腰椎压缩性骨折治疗的应用价值

目的:探讨含重组人碱性成纤维细胞生长因子(recombinant human basic fibroblast growth factor,rhbFGF)和重组人骨形态发生蛋白-2(recombinant human bone morphogenetic protein-2,rhBMP-2)骨水泥在骨质疏松性腰椎压缩性骨折(osteoporotic vertebral compression fracture,OVCF)患者经皮椎体后凸成形术(percutaneous kyphoplasty,PKP)治疗的应用价值。方法:回顾性分析2018年1月至2021年1月收治的103例行PKP手术治疗的OVCF患者,男40例,女63例;年龄61~78(65.72±3.29)岁。受伤原因:滑倒33例,跌倒42例,提重物受伤28例。根据填充骨水泥不同分为3组:磷酸钙组34例,男14例,女20例,年龄(65.1±3.3)岁,填充磷酸钙骨水泥;rhBMP-2组34例,男12例,女22例,年龄(64.8±3.2)岁,填充含rhBMP-2的骨水泥;rhbFGF+rhBMP-2组35例,男14例,女21例,年龄(65.1±3.6)岁,填充含rhbFGF和rhBMP-2的骨水泥。比较3组Oswestry 功能障碍指数(Oswestry dysfunction index,ODI)、骨密度、椎体前缘丢失高度、伤椎前缘压缩率、疼痛视觉模拟评分(visual simulation score,VAS)及再骨折发生率。结果:所有患者获得12个月随访。3组术后ODI、VAS呈下降(P<0.001),骨密度增高(P<0.001),椎体前缘丢失高度、伤椎前缘压缩率呈先下降后缓慢上升趋势(P<0.001),rhbFGF+rhBMP-2组术后第1、6、12个月ODI、VAS均低于rhBMP-2组和磷酸钙组(P<0.05),术后第6、12个月骨密度大于rhBMP-2组和磷酸钙组(P<0.05)。rhbFGF+rhBMP-2组术后第6、12个月椎体前缘丢失高度、伤椎前缘压缩率均低于rhBMP-2组和磷酸钙组(P<0.05)。3组再骨折发生率比较差异无统计学意义(P>0.05)。结论:含rhbFGF和rhBMP-2骨水泥可更有效地增加OVCF患者骨密度,获得术后满意的临床和放射学效果,显著改善临床症状。     

神经生长因子对老年退变性膝骨关节炎疼痛模型的影响

目的:探讨体外模型评价神经生长因子(nerve growth factor,NGF)抗体在膝骨关节炎(knee osteoarthritis,KOA)疼痛模型中的作用。方法:选取30只8周龄雄性SPF大鼠,分为空白组10只;其余20只行右膝关节单碘乙酸 (monoiodoacetate,MIA) 注射,制备骨性关节炎疼痛模型。造模成功后,再根据干预方法不同分为对照组(生理盐水腹腔注射)、治疗组(抗NGF 腹腔注射),每组10只。所有动物右膝关节进行荧光金 (fluorogold,FG) 逆行神经示踪剂注射。分别在治疗前,治疗后1、2周使用猫道步态分析系统评估步态。治疗后3周,从L₃-L₅水平切除右背根神经节(dorsal root ganglia,DRG),进行降钙素基因相关肽 (calcitonin gene-related peptide,CGRP) 免疫染色,并计算DRG数量。结果:在使用猫道系统的步态分析中,与空白组相比,对照组、治疗组占空比、摆动速度和触地面积比率明显降低(P<0.05);与对照组相比,治疗组占空比、摆动速度明显改善(P<0.05),触地面积比率与空白组比较,差异无统计学意义(P>0.05)。对照组中FG标记的DRG神经元数量高于治疗组和空白组(P<0.05);对照组CGRP表达上调,与治疗组比较,差异有统计学意义(P<0.05)。结论:腹腔注射抗 NGF抗体抑制了步态损伤和 DRG 神经元中CGRP 的上调。这些发现提示抗神经生长因子治疗可能对治疗膝关节疼痛有价值。NGF可能是治疗KOA疼痛的重要靶点。     

矽肺相关蛋白的纯化,鉴定及其促成纤维细胞增殖作用

目的分离、鉴定与矽肺发生、发展过程相关的几种蛋白质,并测定其促成纤维细胞增殖的活性。方法采用高压液相色谱技术包括凝胶过滤柱层析、离子交换柱层析、反相Ｃ４高压液相色谱柱层析,分别对矽肺大鼠肺泡灌洗液（ＢＡＬＦ）、肺泡巨噬细胞冻融物（ＡＭＥ）及其条件培养液（ＡＭＣＭ）进行分离纯化,并通过Ｎ末端氨基酸序列的测定来鉴定这些蛋白质。结果（１）染尘２１天后,矽肺大鼠ＢＡＬＦ中白蛋白含量明显升高;（２）从ＢＡＬＦ、ＡＭＥ和ＡＭＣＭ中除纯化到相对分子质量为１５４００的溶菌酶外（其刺激成纤维细胞增殖的活性为１４０％）,还纯化到一种新的具有明显促成纤维细胞增殖的细胞因子（Ｆｉｂｒｏｂｌａｓｔｇｒｏｗｔｈｐｒｏｍｏｔｉｎｇｆａｃｔｏｒ,ＦＧＰＦ）,其最适作用浓度为２．０～６．０μｇ／ｍｌ。结论巨噬细胞分泌的ＦＧＰＦ和溶菌酶在矽肺纤维化过程中可能有重要作用。     

IGF-1与矽肺纤维化的关系

目的了解胰岛素样生长因子１（ＩＧＦ１）与矽肺纤维化的关系。方法用免疫组化（ＳＡＢＣ法）技术对大白兔染石英尘后９０天、１８０天兔肺组织ＩＧＦ１表达及矽结节数目进行研究。结果染尘后９０天、１８０天兔肺组织ＩＧＦ１阳性表达率分别为７０％和１００％（Ｐ＜００１）,染尘后９０天、１８０天兔肺组织矽结节平均数分别为１９８±２０和３０３±１１（Ｐ＜０００５）,肺组织ＩＧＦ１阳性表达强度与肺纤维化程度存在明显相关（ｒ＝０６８５７）。结论ＩＧＦ１可能在矽肺纤维化形成过程中发挥重要作用。     

江湾地区婴儿体格发育分析

目的了解和掌握江湾地区婴儿体格发育状况。方法对江湾地区１９９６年１月～１９９７年９月出生的２１７名婴儿（男１１４名,女１０３名）体重、身长进行系统监测至１２个月,其实际测量均值与ＷＨＯ国际参照值作比较。结果江湾地区婴儿（无论男女）体重、身长在各年龄组均达到或高于ＷＨＯ国际参照值。结论江湾地区婴儿体格发育状况良好。     

安徽省7—18岁学生体质状况分析

本文对安徽省７—１８岁城乡学生１９９５年与１９８５年体质状况资料比较分析,显示本省学生生长发育过程符合生长发育的一般规律,形态发育水平明显提高;发育速度处于长期趋势快速增长阶段;发育高峰年龄有提前趋势;发育匀称度以细长型为主;呼吸机能的肺活量明显下降;身体素质发育有不同程度下降;本省学生体质状况处于全国平均水平以下。