萎缩性胃炎患者幽门螺杆菌根除后表皮生长因子及其受体的变化

目的　研究幽门螺杆菌 (Helicobacterpylori,H .pylori)感染对胃黏膜表皮生长因子受体 (epidermalgrowthfactorreceptor ,EGFR)、血清表皮生长因子 (epidermalgrowthfactor,EGF)水平的影响。方法　对 60例H pylori检测阳性的慢性萎缩性胃炎患者进行根除治疗 ,在治疗前及疗程结束 3个月后分别进行胃镜检查 ,并采用免疫组化及放射免疫法测定H pylori根除前后胃黏膜EGFR和血清EGF含量。 3 0例H pylori检测阴性且胃镜检查无明显异常者作为正常对照组。结果　 60例H pylori检测阳性的CAG患者的胃黏膜EGFR阳性率及血清EGF水平均高于正常对照 ,其差异有显著性 (P <0 0 5 ,P <0 0 1)。有 3 1例在根除治疗 3个月后进行了复查 ,其中 2 4例H pylori得到成功根除。 2 4例H pylori得到根除的CAG患者 ,根除后血清EGF水平明显下降 (P <0 0 1) ,而EGFR阳性率无改变 (P >0 0 5 )。结论　H pylori感染引起胃黏膜EGFR阳性率及血清EGF水平增加 ,根除H pylori后血清EGF可恢复至正常水平 ,而胃黏膜EGFR阳性率在短期内没有明显改变     

蒲元和胃胶囊治疗慢性胃炎伴胃窦糜烂前后EGF、MVD的表达

目的:观察蒲元和胃胶囊治疗幽门螺杆菌(Helicobacter pylori,H.pylori)阴性慢性胃炎伴胃窦糜烂患者前后胃黏膜表皮生长因子(epidermal growth factor,EGF)及微血管密度(microvessel density,MVD)表达水平的变化.方法:采用随机对照方法,将H.pylori阴性糜烂性胃窦炎患者60例随机分为治疗组和对照组,其中治疗组30例患者给予蒲元和胃胶囊及与替普瑞酮相同的安慰剂治疗,对照组30例患者给予蒲元和胃胶囊和替普瑞酮;疗程为4 wk,治疗前后两组患者均以免疫组织化学进行胃黏膜EGF及MVD表达水平比较.结果:治疗组及对照组中糜烂处胃黏膜EGF阳性表达率治疗前(20.0%vs 16.7%)、治疗后(56.7%vs 46.7%)比较,差异有统计学意义(P0.05),糜烂旁处治疗前(10.0%vs13.3%)、治疗后(26.7%v s 16.7%)两组比较,差异有统计学意义(P0.05).治疗组、对照组中糜烂处胃黏膜MVD表达水平治疗前(36.83个/HP±9.36个/HP vs 39.90个/HP±9.03个/HP)及治疗后(50.07个/HP±18.35个/HPvs 48.93个/HP±14.59个/HP)比较,差异有统计学意义(P0.05),治疗组、对照组中糜烂旁处胃黏膜MVD表达水平治疗前(25.37个/HP±6.11个/HP vs 25.87个/HP±6.12个/HP)及治疗后(28.30个/HP±6.23个/HP vs 28.77个/HP±5.70个/HP)比较,差异无统计学意义(P0.05)治疗组和对照组治疗前后在EGF、MVD表达水平方面无统计学意义.结论:蒲元和胃胶囊能够上调糜烂性胃窦炎MVD及EGF的表达水平,这可能是其发挥治疗作用的机制之一.     

萎缩性胃炎表皮生长因子及其受体表达的临床意义探讨

目的通过对萎缩性胃炎表皮生长因子（EGF）和表皮生长因子受体（EGFR测定，探讨EGFR对萎缩性胃炎转归影响作用。方法应用EGFR单抗免疫组化ABC技术和放射免疫法对50例萎缩性胃炎和25例胃癌及19例“正常”胃粘膜组织EGFR和血清EGF水平进行检测。结果萎缩性胃炎EGFR表达的阳性率为60％，血清EGF水平平均3．54土1．47ug／L，较“正常”组（11％和1．77土0．60μg／L）明显增高，与胃癌（73％，3．72士1．84μg／L）十分接近。伴有Ⅱb型肠化者EGF水平更高。并发现EGF的高水平与EGFR高表达具有一致性。结论萎缩性胃炎体内有高水平EGF和EGFR表达。对目前使用促EGF药物治疗萎缩性胃炎提出质疑。     

胃黏膜癌变过程中表皮生长因子受体、环氧合酶-2和三叶因子1的表达及其意义

胃黏膜癌变过程中存在癌基因激活和抑癌基因失活所致的细胞无限增殖和凋亡抑制，因此联合检测细胞增殖和凋亡相关因子对揭示胃黏膜的变化规律具有重要意义。目的：探讨表皮生长因子受体（EGFR）、环氧合酶（COX）．2和三叶因子（TFF）1在胃黏膜癌变过程中的变化规律及其意义。方法：经病理检查确诊的19例慢性非萎缩性胃炎、19例慢性萎缩性胃炎、18例慢性萎缩性胃炎伴肠化生、16例异型增生和16例胃腺癌纳入研究。以免疫组化方法检测各病变组织中EGFR、COX-2和TFF1的表达，并分析其间的相关性。结果：EGFR在非萎缩性胃炎组织中的表达显著低于其他胃黏膜病变组织（P〈0．01）；从非萎缩性胃炎→萎缩性胃炎→肠化生→异型增生→胃癌，COX-2的表达逐渐增高，而TFF1的表达逐渐减低。EGFR与COX-2的表达呈正相关（P〈0．01），与TFF1的表达呈负相关（P〈0．01）：COX-2与TFF1的表达呈负相关（P〈0．01）。结论：细胞增殖和凋亡相关因子EGFR、COX-2和TFF1表达异常在胃黏膜癌变过程中发挥重要作用。     

复方中药安胃汤提高大鼠胃溃疡愈合质量的机制

目的:通过实验性乙酸大鼠胃溃疡模型,研究复方中药安胃汤提高慢性胃溃疡愈合质量机制．方法:40只Wistar大鼠随机平均分为正常对照组、模型组、安胃汤组和雷尼替丁．采用乙酸浸渍法建立胃溃疡模型,造模3 d后前两组分别用生理盐水灌胃,后两组分别用安胃汤和雷尼替丁灌胃．采用放射免疫方法和免疫组织化学方法观察复方中药安胃汤对大鼠胃溃疡模型愈合时血清表皮生长因子(EGF)和胃黏膜 EGF,表皮生长因子受体(EGFR)及转化生长因子-β1(TGF-β1)表达的影响．结果:模型组相比,安胃汤组和雷尼替丁组可提高血清EGF(1．12±0．24,0．99±0．15μg／L vs0．52±0．13μg／L,P<0．01),安胃汤组与雷尼替丁组相比差异也有显著意义(P<0．05)．与模型组相比,安胃汤组和雷尼替丁组可显著增强胃黏膜EGF、EGFR及TGF-β1表达(EGF: 29．7％±1．9％,26．5％±1．6％vs18．4％±2．0％, P<0．01:EGFR:29．6％±2．6％,25．9％±1．0％vs 20．4％±1．8％,P<0．01;TGF-β1:67．0％±2．0％, 49．5％±1．1％vs27．3％±1．0％,P<0．01),安胃汤组强于雷尼替丁组(均P<0．01)．结论:安胃汤可能通过提高血清EGF和增强胃黏膜EGF,EGFR及TGF-β1表达,增强胃黏膜保护作用而提高溃疡愈合质量．     

幽门螺杆菌相关性胃炎活动性与TNF-α,EGF的相关性

目的:研究肿瘤坏死因子(tumor necrosisfactor-α,TNF-α)和表皮生长因子(epidermal growth factor,EGF)水平与幽门螺杆菌(Helicobacterpylori,Hpylori)相关性胃炎炎症活动性的关系.方法:通过快速尿素酶试验和血清HpIgG抗体水平判断H pylori感染;组织学方法评定胃窦炎症活动性;放射免疫法测定胃窦黏膜中TNF-α,EGF的含量.结果:Hpylori阳性的慢性胃炎组胃窦黏膜炎性活动性显著重于Hpylori阴性组;胃窦黏膜中TNF-α水平在H pylori阳性组显著高于H pylori阴性组(0.103±0.034vs 0.062±0.022;P＜0.05),且随黏膜炎症活动加剧而增高;胃窦黏膜中EGF水平在Hpylori阳性组显著低于Hpylori阴性组(0.215±0.102 vs 0.319±0.187;P＜0.05),与黏膜炎症活动性无明显相关性.结论:TNF-α在Hpylori致炎过程中起重要作用,且与炎症活动性成正相关;EGF水平在Hpylori感染中下降,可能减弱了对组织细胞损伤的保护作用,与炎症活动性无关.     

表皮生长因子受体与胰腺癌的关系及以其为靶向治疗的研究进展

表皮生长因子受体（epidermal growth factor receptor，EGFR）是一种糖蛋白．具有酪氨酸蛋白激酶的活性，对表皮生长因子（epidermal growth factor，EGF）或转化生长因子（TGF）-α具有高度的亲和性．两者特异性结合后能激活一系列与细胞生长、增殖、转化有关的生化过程，并可参与肿瘤的发生和生长。而EGFR在胰腺癌中的表达明显高于正常胰腺组织，并且可能与胰腺癌的增殖、侵袭关系密切。近年来针对EGFR的信号转导系统．设计和合成特异性的EGFR抑制物，可望对胰腺癌的防治开辟新的途径。本文就EGFR与胰腺癌的关系以及以EGFR为靶向治疗胰腺癌方面的新进展作一综述。     

胃癌患者检测表皮生长因子及受体的意义

目的:探讨表皮生长因子(EGF)及其受体(EGFR)的表达与胃癌发生及胃癌生物学行为的关系。方法:采用免疫组化S-P法对50例胃癌进行研究。结果:EGF和EGFR在早期胃癌中的阳性率均为20％(2/10),在进展期胃癌的阳性率分别为62.5％(25/40)和60％(24/40),进展期胃癌EGF和EGFR的阳性率均显著高于早期胃癌(P<0.05)。有转移组的EGF及EGFR阳性率高于无转移组(P<0.05)。EGF及EGFR的表达与胃癌的组织学类型有关。结论:EGF及EGFR阳性的肿瘤可能具有更强的浸润与转移能力,检测EGF和EGFR有助于判断胃癌预后。     

瘦素和TGF-α在幽门螺杆菌感染慢性胃炎和胃溃疡患者胃黏膜内的表达及意义

目的:探讨瘦素和转化生长因子-α(TGF-α)在幽门螺杆菌(Hpylori)感染的胃黏膜表达之间的关系.方法:用免疫组织化学法检测Hpylori阳性(Hpylori+)和阴性(Hpylori)慢性胃炎和胃溃疡患者胃体和胃窦部活检标本.结果:瘦素在正常人的胃体黏膜内有弱阳性表达.瘦素和TGF-α在Hpylori+胃炎和胃溃疡患者胃体黏膜内的过表达率较Hpylori者明显增强(瘦素:73.33%vs 23.08%,P＜0.05;70.59% vs 25.00%,P＜0.05;TGF-α:73.33% vs 15.38%,P＜0.05;76.47% vs 25.00%,P＜0.05).瘦素在四组患者的胃窦部表达无差别(P＞0.05).TGF-α在Hpylori+胃炎患者胃窦部的表达较Hpylori-胃炎患者显著增强(53.33% vs 7.69%,P＜0.05).胃体部瘦素与TGF-α的表达呈显著正相关(r=0.80,P＜0.01),胃窦部二者无相关关系.结论:胃体部瘦素与TGF-α在幽门螺杆菌感染慢性胃炎和胃溃疡患者的表达呈显著正相关,胃窦部二者无相关关系.     

紧密连接蛋白Occludin及ZO-1在根除幽门螺杆菌慢性胃炎组织中的表达

目的观察闭锁蛋白(Occludin)及闭锁小带蛋白(zonula occludens-1,ZO-1)在根除幽门螺杆菌(Helicobacter pylori,H.pylori)慢性胃炎组织中的表达变化,探讨其与患者临床病理及预后的关系。方法采用免疫组织化学法检测H.pylori阴性正常人(25例)、根除H.pylori前后慢性浅表性胃炎(30例)及慢性萎缩性胃炎(30例)患者胃窦黏膜标本中Occludin、ZO-1的蛋白表达。结果 H.pylori阴性的正常人胃黏膜Occludin、ZO-1蛋白表达较H.pylori阳性慢性胃炎患者高,差异有统计学意义(P0.05),H.pylori阳性的慢性浅表性胃炎组织Occludin及ZO-1蛋白表达较慢性萎缩性胃炎增强,差异有统计学意义(P0.05);H.pylori根除治疗后,慢性浅表性胃炎组织中Occludin及ZO-1表达量较治疗前增强(P0.05),慢性萎缩性胃炎组织Occludin、ZO-1表达无明显变化(P0.05);H.pylori未根除患者,Occludin及ZO-1蛋白变化差异无显著性(P0.05)。结论 H.pylori阳性的慢性胃炎患者胃黏膜屏障受损,萎缩发生前根除H.pylori治疗可提高Occludin及ZO-1蛋白表达,进而修复H.pylori引起的胃黏膜损伤。     

Human epidermal growth factor receptor residue covalently cross-linked to epidermal growth factor.

An epidermal growth factor (EGF) receptor monoclonal antibody (mAb), mAb LA22, was used to analyze the covalent coupling of human EGF receptors to mouse EGF by the amine-reactive cross-linking agent disuccinimidyl suberate. A soluble Mr 105,000 truncated form of the receptor secreted by A-431 epidermoid carcinoma cells and consisting of the ligand-binding extracellular domain was cross-linked to 125I-labeled EGF. Digestion of this complex with an endoproteinase that specifically cleaves at the COOH side of glutamyl residue released a single radiolabeled glycosylated fragment of Mr 18,000 that reacted with mAb LA22. As the epitope for mAb LA22 resided between Ala-351 and Asp-364 of the mature receptor, this result localized the cross-linked receptor residue(s) to the 47-amino acid interval from Phe-321 to Glu-367. The receptor residue(s) involved in the covalent coupling of rat 125I-labeled transforming growth factor alpha was similarly localized to this region of the receptor. This receptor interval, which included two glycosylated asparaginyl residues at positions 328 and 337, contained but three amino acid residues that were potentially reactive with disuccinimidyl suberate: Lys-332, Lys-333, and Lys-336. Characterization of mAb LA22-reactive 125I-EGF-labeled receptor fragments generated by an endoproteinase specific for the COOH side of lysyl residue placed the NH2 termini of the two smallest fragments between the glycosylated residues Asn-328 and Asn-337. These results indicated that disuccinimidyl suberate cross-linked the NH2 group of EGF residue Asn-1 to the human EGF receptor residue Lys-336. Our results further suggest that EGF and transforming growth factor alpha, two members of the EGF family of peptide growth factors, interact with closely apposed or identical features of the receptor.     

Mammalian epidermal growth factor promotes plant growth

Application of mouse submaxillary gland epidermal growth factor to young sorghum seedlings at low concentrations (≈0.4-4 μM) increased shoot growth significantly over 3- and 6-day periods. The effects were dose dependent.     

Nuclear localization of epidermal growth factor and epidermal growth factor receptors in human thyroid tissues.

Epidermal growth factor (EGF) has widespread growth effects, and in some tissues proliferation is associated with the nuclear localization of EGF and epidermal growth factor receptor (EGFR). In the thyroid, EGF promotes growth but differs from thyrotropin (TSH) in inhibiting rather than stimulating functional parameters. We have therefore studied the occurrence and cellular distribution of EGF and EGFR in normal thyroid, in Graves' disease, where growth is mediated through the thyrotropin receptor (TSHR), and in a variety of human thyroid tumors. In the normal gland the staining was variable, but largely cytoplasmic, for both EGF and EGFR. In Graves' disease there was strong cytoplasmic staining for both EGF and EGFR, with frequent positive nuclei. Nuclear positivity for EGF and particularly for EGFR was also a feature of both follicular adenomas and follicular carcinomas. Interestingly, nuclear staining was almost absent in papillary carcinomas. These findings document for the first time the presence of nuclear EGF and EGFR in thyroid. Their predominant occurrence in tissues with increased growth (Graves' disease, follicular adenoma, and carcinoma) may indicate that nuclear EGF and EGFR play a role in growth regulation in these conditions. The absence of nuclear EGF and EGFR in papillary carcinomas would suggest that the role played by EGF in growth control differs between papillary carcinoma and follicular adenomas/carcinomas of the thyroid.     

The epidermal growth factor receptor family

The epidermal growth factor receptor family consists of four receptor genes and at least 11 ligands, several of which are produced in different protein forms. They create an interacting system that has the ability to receive and process information that results in multiple outputs. The family has an important role in directing and coordinating many normal processes, including growth and development, normal tissue turnover and wound healing. Its members are also aberrantly activated by overexpression or mutation in many common human tumour types and as such have been the target for anticancer drug development.     

Comparative effects of epidermal growth factor, an insulin-glucagon combination, and a hepatocyte growth factor preparation on epidermal growth factor receptors.

We investigated the changes in cell surface epidermal growth factor (EGF) receptors in the liver after partial hepatectomy, and in primary adult rat hepatocyte cultures following stimulation with either EGF, or a preparation of hepatocyte growth factor, or an insulin-glucagon combination. We confirmed a reduction in EGF receptors on hepatocytes after partial hepatectomy and a rapid down-regulation of EGF receptors on normal hepatocytes in vitro following exposure to EGF. Insulin and glucagon and hepatocyte growth factor, whilst initiating hepatocyte DNA synthesis, had only slight effects on their EGF binding capacity and EGF-receptor affinity. These results indicate that changes in cell membranes early in proliferation have only non-specific effects on EGF receptors, and, therefore, support the role of ligand binding to the EGF receptor as an important component of hepatocyte proliferation in vivo.     

Monoclonal antibodies against receptor for epidermal growth factor induce early and delayed effects of epidermal growth factor.

Mice were immunized with human epidermoid carcinoma cells (A-431 cell line) that possess an unusually high number of membrane receptors for epidermal growth factor (EGF). Spleen cells from these mice were fused with NSI cells, a nonsecreting murine myeloma. The immunoglobulins secreted by the obtained hybridomas were screened for specific binding to A-431 cells and selected according to their ability to inhibit the binding of radiolabeled EGF to the membrane of A-431 cells. Several antibodies secreted by cloned hybrid lines were found to inhibit the binding of radiolabeled EGF to membrane receptors of living A-431 cells, human foreskin fibroblasts, and mouse 3T3 fibroblasts and also to membrane preparations from A-431 cells. These monoclonal antibodies induced the early and delayed biological effects mediated by EGF. Like EGF, the antibodies induced morphological changes in A-431 cells and enhanced the phosphorylation of endogenous membrane proteins in membranes from these cells. They also stimulated DNA synthesis in human foreskin fibroblasts. These observations support the notion that the biological information of the EGF-receptor complex resides in the membrane receptor. Furthermore, the antibodies offer a powerful tool to study the structure, processing, and mode of action of EGF receptors.     

Overexpression of epidermal growth factor and epidermal growth factor-receptor mRNAs in dyshormonogenetic goiters.

Thyroid malignancy has been induced by long-term endogenous thyrotropin (TSH) stimulation in experimental animals, leading to local and distant metastasis. It has been postulated that constant and prolonged endogenous TSH stimulation in dyshormonogenetic thyroid tissues could result in thyroid neoplasia. The possible role of growth factors and oncogenes in goitrogenesis and favoring neoplasia has also been mentioned. Overexpression of certain growth factors and/or their receptors, and of oncogenes implicated in growth promotion may play a significant role in the relatively frequent finding of thyroid malignancy in congenital goiters. In this study the expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGF-R), transforming growth factor-beta (TGF-beta), c-myc, and p53 mRNAs was determined in 14 thyroid tissue samples: 6 from patients with thyroid peroxidase (TPO) gene mutations, 4 with thyroglobulin (Tg) gene defects and 4 normal thyroid tissues. EGF mRNA overexpression was seen in 7 of 10 dyshormonogenetic tissues (3.5 to 12.0 arbitrary optical densitometry units [AODU]) and considered significantly higher (p < 0.01) when compared to normal thyroid tissues (0.25 to 0.32 AODU). Moreover, overexpression of EGF-R mRNA was present in 6 of 10 dyshormonogenetic tissues (2.23 to 13.03 AODU) and considered significantly higher (p < 0.01) when compared to normal thyroid tissues (0.42 to 0.65 AODU). There was no difference in c-myc, p53, and TGF-beta mRNAs expression between dyshormonogenetic and normal tissues. The overexpression of EGF and EGF-R mRNAs found in dyshormonogenetic tissues may suggest that this growth factor may play a role in cellular proliferation and contribute to goiter formation.