生长因子与感染

生长因子作为一种细胞因子,广泛参与细胞的各种生理病理过程,其中与炎症过程相关的生长因子主要有转化生长因子β(TGF-β),神经生长因子(NGF),胰岛素样生长因子(IGFs),血小板源生长因子(PDGF),成纤维细胞生长因子(FGF),血管内皮生长因子(VEGF)等.以下对上述生长因子作简要评述.     

石棉在恶性间皮瘤发病分子机制中的作用

恶性间皮瘤（malignantmesothelioma,MM）是一种起源于胸膜、腹膜以及心包膜和睾丸鞘膜等部位且预后差的恶性肿瘤,其发病率较低。MM主要见于60岁以上患者,但年龄分布范围很大,偶尔可见于儿童。MM的发病有上升趋势,这个可能与石棉在工、商业中的广泛应用有关。MM的预后很差,国外文献报道的中位生存期为8．9～14．0个月。世界卫生组织将MM分为上皮型、肉瘤型和混合型,但在临床工作中报道的特殊亚型MM包括：印戒细胞样型、小细胞型、黏液样型、肌纤维母细胞型、淋巴组织细胞样型和促纤维增生型等。     

胸膜恶性间皮瘤临床分析

目的对胸膜恶性间皮瘤进行临床分析,探讨其临床表现、影像学及临床确认方法,以期提高诊断治疗水平,减少误诊。方法收集近5年来国内文献报道的资料较为完整的46例患者的临床资料进行综合分析。结果临床症状以刺激性干咳、胸痛、胸闷、气短为主,体征以胸腔积液、消瘦、体表包块为主,临床表现无特征性;影像学以CT或MTI检查常能发现提示性证据;病理上以上皮型多见。结论国内本病多无明确的石棉接触史。如中老年患者出现上述临床表现者应考虑本病的可能。本病确诊主要依赖细胞学、病理学及其免疫组化检查,治疗需根据多种因素综合考虑,多采取综合治疗为宜。     

血管内皮生长因子在恶性骨肿瘤中的表达及其与转移的关系

应用免疫组化方法对21例恶性骨肿瘤进行血管内皮细胞生长因子（VEGF）的免疫检测和血管计数。发现在10例有转移的恶性骨肿瘤中有7例为阳性,且多为强表达;11例无转移的恶性骨肿瘤中有4例为阳性,且多为弱表达（P＜0．05）。在5例强表达者中,有4例发生转移;而在3例弱表达者中只有1例发生转移。肿瘤的血管计数表明：转移组肿瘤微血管数高于无转移组（P＜0．05）。VEGF蛋白阳性组肿瘤血管数高于VEGF蛋白阴性组（P＜0．01）。     

血管内皮生长因子、PTEN与恶性胶质瘤的关系

近年来,胶质瘤的分子生物学研究表明,血管内皮生长因子（vascular endothelial growth factor,VEGF）和人10号染色体上缺失的磷酸酶和张力蛋白类似物（PTEN）基因与胶质瘤尤其恶性胶质瘤（WH02000 Ⅲ—Ⅳ级）的发生和发展关系密切。本文就VEGF、PTEN在结构、功能及其与恶性胶质瘤关系方面作一综述。     

大姚县恶性胸膜间皮瘤20例临床分析

分析大姚县发现的２０例恶性胸膜间皮瘤。全部病例均有直接或间接青石棉接触史。病变在右侧胸膜者１４例，左侧６例，１例合并腹膜间皮瘤。主要临床表现为胸痛、咳嗽、呼吸困难、胸腔积液、发热及远处转移。Ｘ线表现以弥散性胸膜增厚、散在结节状增厚及波浪状增厚，部分呈驼峰样改变为特点。胸水细胞学阳性率３７．５％，针刺胸膜活检阳性率８０％。本病预后差，经随访，２０例均在发病后２年内死亡，自然病程１２．７月。     

恶性腹膜间皮瘤12例诊治分析

<正>恶性腹膜间皮瘤(malignant peritoneal mesothelioma,MPM)是一种极少见的恶性肿瘤,占间皮瘤的17%～32%,起病隐匿,进展迅速,预后极差。目前,对该病仍缺乏规范有效的治疗方法。我院2000年6月至2006年6月共收治恶性间皮瘤23例,其中MPM12例。现将腹膜间皮瘤的诊治情况报告如下。     

腹膜恶性间皮瘤1例伴文献复习

目的探讨腹膜恶性间皮瘤的临床病理特点。方法复习1例腹膜的恶性间皮瘤的临床病理资料并结合文献复习。结果该例患者大网膜、肠系膜、腹膜以及子宫、双侧附件、大小肠管的浆膜面等均见有大小不一的结节,伴大量腹水。该例镜下主要为不规则腺管状结构,少数乳头状,被覆单层立方上皮或扁平上皮,嗜酸性胞质。免疫组化:HBME-1++,EMA+,Calreti-nin+,Vim+。结论腹膜恶性间皮瘤侵袭性强,预后差。     

恶性胸膜间皮瘤概述

恶性间皮瘤是罕见的高度侵袭性肿瘤,起源于胸膜、腹膜和心包腔的被覆间皮细胞。恶性胸膜间皮瘤为最常见类型,约占所有恶性间皮瘤70％。恶性间皮瘤在全世界范围内发病率逐渐升高,因为致病因素石棉仍在广泛应用。这是医学界和公众都在关注的问题。     

14例恶性腹膜间皮瘤的CT表现分析

恶性腹膜间皮瘤较少见,影像学特征常不典型,诊断困难,笔者对１４例恶性腹膜间皮瘤的ＣＴ表现进行了分析。材料与方法本组１４例腹膜间皮瘤均经手术和病理证实。１４例中女１１例,男３例,年龄１９～７０岁,平均４９１４岁。从症状出现到就诊时间９７６个月。临床...     

独一味胶囊对大鼠机械性皮肤损伤的促愈合作用

目的研究独一味胶囊对大鼠机械性皮肤损伤的促愈合作用及其可能机制。方法在SD大鼠背部皮肤造成机械性损伤模型,将损伤模型大鼠分为独一味(生药)4、2、1 g.kg-1组、模型组、阳性对照组,给予大鼠ig独一味胶囊药液或阳性药,连续16 d,观察各创面的愈合情况,计算各创面的愈合率,并于造模后第4、7、10、14、17天分别处死大鼠,取创面标本,分别进行病理组织学检查、毛细血管计数和血管内皮生长因子(VEGF)、表皮生长因子(EGF)的免疫组化测定。结果大鼠灌服独一味胶囊后可明显缩短伤口的愈合时间。造模后第4~14天,生药4.0 g.kg-1组大鼠的创口愈合率、创面组织EGF、VEGF的表达明显高于模型组(P<0.05);造模后第4~7天,生药4.0 g.kg-1组大鼠新生毛细血管计数明显多于模型组(P<0.01)。组织形态学评价结果表明:造模后第4~14天,生药4.0 g.kg-1组大鼠的创口修复情况明显优于模型组,在创口修复早期,能加速成纤维细胞的增生,促进新生毛细血管的生成,减少炎症反应。结论独一味胶囊能促进机械性皮肤损伤的愈合,其作用机制可能与促进新生毛细血管生成,促进组织中内源性EGF、VEGF等相关因子的表达有关。     

IGF作用机理的研究进展及其与生物信息学的联系

类胰岛素生长因子(insulin-like growth factor,IGF)是一类多功能的细胞增殖调控因子,它在肿瘸细胞增殖、肌肉生长、胎儿发育等方面具有重要的调控作用。随着基因组计划的启动,生物信息学作为一门计算机处理生物数据的交叉学科发展起来了。本文介绍了类胰岛素生长因子的研究进展,以及与生物信息学的关系。     

神经生长因子在异丙酚对大鼠海马神经元缺氧/复氧损伤中的作用及机制

目的探讨不同浓度的异丙酚预处理对大鼠海马神经元缺氧/复氧损伤的保护及神经生长因子(Nerve growth factor,NGF)的作用。方法取离体培养的大鼠海马神经元,随机分成7组:对照组(Con组);CoC l2组(CoC l2组):加入300μM CoC l2处理1 h,然后更换正常的培养基培养24 h,之后更换无血清的培养基培养;脂肪乳剂组(Intralipid,Intra组):加入10%脂肪乳剂90μL预处理1 h后加入300μM CoC l2;异丙酚组(prop组)培养孔中加入10、20、50、100μM浓度的异丙酚预处理1 h后,同CoC l2组。MTT法测定细胞增殖,流式细胞技术测定细胞的凋亡。为进一步研究不同浓度的异丙酚对NGF及其受体TrkA表达的影响,本研究将大鼠海马神经元分为6组,分别为对照组,CoC l2组,10、20、50、100μM浓度异丙酚组,用RT-PCR检测NGF mRNA和TrkA mRNA表达。为探讨NGF/TrkA的作用,将细胞随机分为4组:对照组,CoC l2组,50μM异丙酚组,1.0μmol/L K252a组。结果脂肪乳剂组与CoC l2组比较,细胞活性差异无统计学意义(P>0.05),50μM异丙酚预处理可以明显增加大鼠海马神经元的增殖能力,减少凋亡(P<0.01),50μM异丙酚预处理上调NGF mRNA和TrkA mRNA的表达(P<0.05或P<0.01),10、20、100μM异丙酚组与缺氧/复氧组相比差异无统计学意义(P>0.05),异丙酚对海马神经元的保护作用被K252a抑制(P<0.01)。结论 50μM异丙酚预处理对缺氧/复氧后的大鼠海马神经元有保护作用,NGF及其受体TrkA在异丙酚的预处理中起到重要的作用。     

原发性骨质疏松发病机制与胰岛素样生长因子关系的研究进展

在过去的几年时间里,关于胰岛素样生长因子系统在骨骼再建中的作用得到了充分的肯定.在这里我们应用充分的证据说明由骨细胞所产生的IGF-1和IGF-2在调节成骨细胞和破骨细胞中所起的作用,另外,我们也回顾了几个实验室所做的关于胰岛素样生长因子系统的实验结果.有证据表明,其他调节骨代谢的通过IGF系统发挥作用.骨骼局部的IGF-1和IGF-2在骨再建中的作用众所周知,但是关于循环系统中IGF 的作用仍然不是十分明了.有新的研究结果表明血清中的生长因子也起到了一定的作用,最后我们回顾了目前比较公认的重组IGFs对骨再建的作用,然而,关于IGFs对骨值疏松的最终的治疗效果仍有待于进一步研究.     

神经生长因子(NGF)对骨折愈合影响的初步临床观察

目的探讨神经生长因子(NGF)局部注射促进骨折愈合的临床作用。方法对48例四肢新鲜骨折病人进行骨折端经皮局部注射NGF促进骨折愈合的临床治疗观察,其中股骨骨折11例、肱骨骨折7例、胫腓骨骨折16例、尺桡骨骨折14例。据骨折类型、治疗方法相同或相似的原则设立相应的对照组,对骨痂生长情况、骨折临床愈合的时间进行对比研究分析。结果2组病例均获随访,时间为3~9个月,2组骨痂出现的时间、骨痂量的多少2周内无明显不同,3周后骨痂量治疗组多于对照组,治疗组各类型骨折临床愈合时间均较对照组有不同程度的缩短,疗效优于对照组,经统计学处理(P<0.01),2组对比有极显著差异。结论临床应用神经生长因子(NGF)经皮局部注射在骨折中后期有促进骨折愈合修复的作用。     

N-Terminal Site-Specific Mono-PEGylation of Epidermal Growth Factor

Purpose. N-terminal site-specific mono-PEGylation of recombinant human epidermal growth factor (EGF) was accomplished using polyethyleneglycol (PEG) derivatives (Mw = 2000 and 5000) through a reactive terminal aldehyde group. Methods. The site-specific PEG conjugation was conducted at a slightly acidic pH condition (pH 5.5). The mono-PEGylation was targeted to an -amine group at the N-terminal end of EGF to minimize reduction of biologic activity. Tryptic digestion mapping and MALDI-TOF MS techniques were applied to show the occurrence of mono-PEGylation at the N-terminus of EGF. Results. The site-specific mono-PEGylated EGF, when compared with native EGF, fully retained its in vitro biologic activities such as cell proliferation and intracellular signal transduction. This revealed that although a synthetic polymer of a PEG was covalently conjugated to EGF, the internalized complex of PEGylated EGF-receptor within cells did not hamper the intracellular signal transduction events. The PEGylated EGF also exhibited a prolonged circulation in blood stream in vivo and markedly enhanced physical stability when incubated with tissue homogenate. Conclusion. N-terminally mono-PEGylated EGF shows increased physical stability while retaining its biologic activity.     

Cyclosporin A induces apoptosis in rat hepatocytes in culture

Cyclosporin A (CsA) at concentrations up to 1 μM induced apoptosis in a dose-dependent manner in cultured rat hepatocytes for 48 h in the presence of insulin and epidermal growth factor (EGF). The effect of CsA was evidenced by the DNA fragmentation pattern constituted by fragments of multiples of 180–200 base pairs, which is a characteristic of programmed cell death. The metabolic activity did not change significantly in the presence of 0.1 μM CsA and diminished to 49% of control in the presence of 1 μM CsA. Changes in the metabolic activity were correlated with a decrease in both [methyl-³H]thymidine uptake and DNA content, which reflects a decrease in the cell number. The treatment of cells with CsA (1 μM) decreased the metabolic activity/DNA content ratio by 24% with respect to dimethyl sulphoxide (DMSO) control, which also suggests, under these conditions, that the necrosis achieved is at most only 24%. In addition, the changes observed (apoptotic process, arrest of the cell cycle and apparition of a necrotic process) were correlated with an increase in the high-affinity guanosine triphosphatase (GTPase) enzymes. Received: 17 February 1998 / Accepted: 20 April 1998     

The inhibitory effect and mechanism of luteolin 7-glucoside on rat aortic vascular smooth muscle cell proliferation

The abnormal proliferation of aortic vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis and restenosis after angioplasty and possibly also in the development of hypertension. The present study was designed to examine the inhibitory effects and the mechanism of luteolin 7-glucoside (L7G) on the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs. L7G significantly inhibited the PDGF-BB-induced proliferation and the DNA synthesis of the VSMCs in a concentration-dependent manner. Pre-incubation of the VSMCs with L7G significantly inhibited the PDGF-BB-induced extracellular signal-regulated kinase 1/2 (ERK1/2), Akt and the phospholipase C (PLC)-gamma1 activation. However, L7G had almost no affect on the phosphorylation of PDGF-beta receptor tyrosine kinase, which was induced by PDGF-BB. These results suggest that L7G inhibits the PDGF-BB-induced proliferation of VSMCs via the blocking of PLC-gamma1, Akt, and ERK1/2 phosphorylation.     

Epidermal growth factor receptor (EGFR)-targeted therapies in mesothelioma

Introduction: Malignant mesothelioma (MM) is an aggressive malignancy arising from the mesothelial cells lining the pleura and other serosal membranes. It is associated with an extremely poor prognosis and has limited therapeutic options.

Areas covered: Epidermal growth factor receptor (EGFR) is known to be highly overexpressed in mesothelioma with reported EGFR overexpression between 44 to 97%. Given this, several anti-EGFR agents have been trialed in mesothelioma. In this review, we provide an overview of the current available data on anti-EGFR therapies in MM and future directions of investigation with these targeted agents in MM.

Expert opinion: While many anti-EGFR therapies have failed to show significant efficacy in the management of MM, the pathway is biologically active and its abrogation preclinically points toward it being a valid target. Toward targeting the pathway, many novel EGFR-based therapies are still being investigated. Current ongoing research of interest in MM include EGFR-targeted nanotechnology approach for drug delivery, antibodies targeting the extracellular EGFR and potentially anti-EGFR antibody drug conjugates.     

注射用脑蛋白水解物(Ι)对血管性痴呆大鼠的神经保护作用机制

目的 研究注射用脑蛋白水解物（Ι）对血管性痴呆大鼠的神经保护作用机制。方法 采用改良两血管阻断法制备血管性痴呆（VaD）大鼠模型,假手术组仅分离颈总动脉不阻断血管。将大鼠随机分为假手术组、模型组、注射用脑蛋白水解物（Ι）低、中、高剂量（5、10、20 mg/kg）组和脑蛋白水解物注射液（Cerebrolysin,阳性药,10 mg/kg）组。尾iv给药,每天1次,连续给药2周;假手术组和模型组给予等体积生理盐水。给药结束后,腹主动脉采血分离血清,分离大鼠皮层制备匀浆,ELISA法检测VaD大鼠血清中神经生长因子（NGF）和胰岛素样生长因子2（IGF-2）水平、皮层中γ-氨基丁酸（GABA）水平,比色法检测皮层中谷氨酸（Glu）水平。结果 与模型组比较,注射用脑蛋白水解物（Ι）显著升高VaD大鼠血清中NGF、IGF-2水平、皮层中GABA水平,显著降低VaD大鼠皮层中Glu水平;其升高IGF-2和GABA水平的作用优于同剂量Cerebrolysin。结论 注射用脑蛋白水解物（Ι）提高VaD大鼠学习记忆能力的作用机制,可能与升高机体NGF、IGF-2水平,调节兴奋性及抑制性氨基酸类神经递质平衡有关。