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。     

表皮生长因子受体靶向治疗结直肠癌的临床进展

当今,靶向治疗成为肿瘤治疗模式里越来越重要的因子,而靶向治疗中研究最多的是关于表皮生长因子受体(epidermal growth factor receptor,EGFR)靶向治疗药物.随着临床的深入研究,EGFR分子靶向药物的临床应用利弊也成为关注的焦点.此文就EGFR在结直肠癌靶向治疗中的研究进展作一综述.     

人胃癌细胞膜表皮生长因子受体的表达

用~(125)Ⅰ标记的人类表皮生长因子(~(125)Ⅰ-EGF)与分离制备的胃癌和癌旁组织细胞膜进行放射配体结合试验。胃癌细胞膜~(125)Ⅰ-EGF结合量为13.5±3.84fmol/mg膜蛋白,癌旁组织为6.15±1.65fmol/mg膜蛋白,两者差异显著(22例,t=8.25,P<0.01)。高分化组胃癌~(125)Ⅰ-EGF结合量显著低于低分化组胃癌(P<0.05)。Scatchard分析表明,胃组织细胞膜EGF受体是一种单一亲和力的受体。胃癌~(125)Ⅰ-EGF最大结合力(B_(max)=26.15±2.17fmol/mg膜蛋白)高于癌旁正常组织(B_(max)=19.87±2.81 fmol/mg膜蛋白),两者差异显著(t=2.95,P<0.05)。胃癌EGF受体的亲和力(K_D=11.13±0.22nM)大于癌旁正常组织(K_D=1.79±0.23nM),两者差异显著(t=3.59,P<0.05)。本研究表明,胃癌细胞膜表面EGF受体在数量和亲和力两方面都有显著改变,提示在胃癌的发生发展过程中,EGF受体与其配体所形成的自/旁分泌增殖环可能起着重要的生长调节作用     

表皮生长因子及其受体与胃癌关系研究进展

表皮生长因子（epidermagrowthfactor，EGF）及其受体（epldermalgrowthfactorreceptor，EGpo是细胞信号传导系统的一部分，EGF通过与细胞膜上EGFR特异性结合，引起靶细胞内一系列生物效应，控制着细胞的代谢、生长、分化和癌变．近年来，一些研究表明某些胃癌细胞中有EGF及其受体过度表达，对胃癌的发生和发展具有一定作用，故EGF及其受体及胃癌关系的研究，日益受到人们的关注和重视，本文就将这方面研究的进展综述如下．一、EGF＆其受体的生物学特性EGF是一个由53个氨基酸组成的多肽类激素，含有3个二硫键，分子量为6023，主要…     

表皮生长因子受体及其与胃癌的关系研究

胃癌是人类常见的恶性肿瘤之一,占我国恶性肿瘤的第一或第二位,占癌症死亡原因第二位,严重危害人类的生命健康.目前胃癌的治疗以手术为主,结合术前或术后的辅助治疗.早期胃癌术后生存率达85%～90%以上,但进展期胃癌总体预后较差,5年生存率＜10%,中位生存期仅6～9个月.目前胃癌发现时多处于进展期,因此胃癌的治疗棘手,依然是世界关注的焦点.表皮生长因子受体(EGFR)分布广泛,主要位于哺乳动物多种细胞表面,EGFR的高表达不仅有促进肿瘤细胞的增殖、肿瘤内及周围血管生成、肿瘤细胞黏附、侵袭和转移作用,还具有抑制肿瘤细胞凋亡的作用,有多篇文献报道EGFR在正常胃黏膜中表达阴性或低表达,而在胃癌组织中高表达,EGFR与胃癌的发生发展密切相关.EGFR作为肿瘤治疗靶点的前景已被普遍看好,对其研究也较为成熟,许多药物如吉非替尼、埃罗替尼等已用于临床,在胃癌治疗方面取得了一些进展.     

非小细胞肺癌表皮生长因子受体突变的检测与分子靶向治疗

目的探讨非小细胞肺癌患者表皮生长因子受体(EGFR)基因突变率和突变类型,分析其临床特征,并观察EGFR突变与表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗疗效的相关性。方法收集203例非小细胞肺癌患者外科手术、淋巴结活检、经皮肺穿刺活检、气管镜活检和胸腔积液沉渣石蜡标本,应用ADx-ARMS法进行EGFR基因突变检测,分析基因的突变率及其与临床特征的关系;观察非小细胞肺癌(NSCLC)接受EGFR-TKIs治疗的非小细胞肺癌患者的疗效。应用SPSS23.0软件进行统计学分析,计数资料比较采用χ2检验,采用Kaplan-Meier法计算患者的PFS,采用Log-Rank检验分析各种因素对生存期的影响。结果 203例NSCLC患者,男性116例,女性87例,年龄为25~82岁。吸烟指数≥400支/者61例,小于400支/年和不吸烟者142例,腺癌152例,鳞癌21例,腺鳞癌14例,其他NSCLC16例。203例NSCLC患者EGFR总突变率为51.2%(104/203),包括19外显子缺失突变51例(49.0%),21外显子L858R突变44例(42.3%),19del及L858R总突变率占所有突变的96.1%,18外显子G719X点突变3例(2.9%),19del+L858R双突变3例(2.9%),1例20ins,2例T790M突变分别为1例19del+T790M和1例L858R+T790M。EGFR基因阳性突变率女性组高于男性组(66.7%vs.36.2%);非吸烟组高于吸烟组(63.4%vs.16.4%);腺癌组高于鳞癌组(53.3%vs.33.3%),P0.05。而EGFR基因突变状况与标本类型如手术、淋巴结活检、肺穿刺活检、气管镜活检和胸腔积液沉渣标本间无统计学差异,P=0.418。101例接受TKI治疗的NSCLC患者客观缓解率(ORR)为61.4%,疾病控制率(DCR)为71.3%,中位疾病无进展生存期(PFS)为10个月。其中EGFR突变阳性患者接受EGFR-TKIs治疗的ORR及DCR均要显著高于EGFR突变阴性及EGFR突变状态未明确人群(88.6%vs.16.7%vs.43.1%,P=0.000;95.5%vs.16.7%vs.56.9%,P=0.000)。EGFR突变阳性患者接受EGFR-TKIs治疗的中位PFS较EGFR突变阴性及EGFR突变状态未明确患者延长,有统计学差异(P=0.001)。进一步分析EGFR突变阳性19del组NSCLC患者ORR、DCR均高于L858R组(91.2%vs.85%,P=0.646;100%vs.90%,P=0.201);19del组NSCLC患者TKI治疗后中位PFS 14.5个月较L858R组10个月长,有统计学差异(P=0.010)。结论非小细胞肺癌患者EGFR突变高,以女性、不吸烟、腺癌为优势人群,EGFR敏感突变阳性者对EGFR-TKI疗效好,EGFR突变中19del者较L858R疗效更佳,基因检测结果可以较好地预测分子靶向药物的疗效,降低肿瘤进展的风险。     

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。     

表皮生长因子受体通路阻断在胰腺癌治疗中的进展

胰腺癌在全球肿瘤发病率中位居第13位,死亡率居第8位[1]。2011年我国新确诊胰腺癌80 344例,在我国肿瘤发病率中位居第10位,死亡72 723例,位居肿瘤所致死亡原因的第6位[2]。手术切除是治愈胰腺癌的唯一有效手段。然而,由于胰腺癌在发病早期缺乏特异性症状,多数患者确诊时已是局部进展期或发生远处转移而无法手术,能接受手术治疗者仅占15%~20%[3]。化学治疗(化疗)可改善晚期胰腺     

非小细胞肺癌表皮生长因子受体基因突变与分子靶向治疗

肺癌分子靶向治疗近年来取得较大进展.特别是针对表皮生长因子受体(EGFR)分子靶向药物表现出确定的临床效果.临床应用表明,EGFR基因酪氨酸激酶域体细胞突变与非小细胞肺癌患者对酪氨酸激酶抑制剂吉非替尼的敏感性相关.本文就EGFR生物学特点、EGFR在肺癌中的表达、EGFR基因突变率、EGFR基因突变与EGFR酪氨酸激酶抑制剂疗效的关系作一综述.     

EGFR靶向治疗在结直肠癌中的研究进展

表皮生长因子受体酪氨酸激酶(EGFR)家族的异常表达和活化,与肿瘤的发生和进展、肿瘤转移关系密切,抑制受体活性可以有效的抑制肿瘤.EGFR信号在结直肠癌形成中具有重要的作用, 随着对肿瘤分子生物学的深入研究,针对EGFR的分子靶向药物已进入结直肠癌治疗的临床研究阶段,此文就EGFR在结直肠癌靶向治疗中的研究进展作一综述.     

Increased epidermal growth factor receptors in gastric carcinomas

The epidermal growth factor and the homologous alpha-tumor growth factor are mitogenic polypeptides that act by binding to the epidermal growth factor receptor. The present study investigated whether increased production of epidermal growth factor/alpha-tumor growth factor or increased density of epidermal growth factor receptors may occur in gastric carcinomas as compared with normal mucosa from the same individuals. Epidermal growth factor receptors were measurable by (125I)EGF-binding assays in 13 of 15 normal mucosas and in 15 of 15 carcinomas. The epidermal growth factor-binding capacity was significantly higher in carcinomas than in mucosa. A comparison of pairs of mucosa and carcinomas showed an increase of epidermal growth factor receptors in 9 of 15 carcinomas, no change in 3, and a decrease in 2 carcinomas. One mucinous adenocarcinoma contained extreme numbers of epidermal growth factor receptors (2445 fmol/mg protein) corresponding to a 320-fold increase over normal mucosa. Epidermal growth factor-like activity was increased in 2 of 22 carcinomas compared with mucosa. We conclude that relative overexpression of epidermal growth factor receptors occurs in a fraction of gastric carcinomas. Whether increased expression of epidermal growth factor receptors is associated with particular patterns of tumor progression needs to be investigated.     

Clinical significance of epidermal growth factor (EGF) expression in gastric cancer

BACKGROUND/AIMS: Epidermal growth factor (EGF) is involved in cancer development and proliferation. We measured preoperative serum EGF, and serologically investigated the clinical significance of EGF expression in gastric cancer. We also performed immunohistological staining at the same time, and investigated its relationship with serum EGF. METHODOLOGY: There were 79 patients who underwent surgery for gastric cancer. For the measurement, one-step sandwich EIA was performed. Of 79 cases of gastric cancer in which the serum EGF level was measured, EGF immunostaining was performed in 50 cases. RESULTS: In Serology, the EGF level was 345.6 +/- 260.6 pg/mL in m-sm cases, and 212.2 +/- 170.4 pg/mL in mp-si cases (p < 0.05). The EGF level was 294.4 +/- 236.0 pg/mL in ly0 cases, and 194.2 +/- 142.5 pg/mL in ly1-3 cases (p < 0.05). The EGF level was 323.5 +/- 233.4 pg/mL in cases staged IA-IB, and 202.8 +/- 176.8 pg/mL in cases staged II-IV (p < 0.05). In immunohistology the EGF positivity rate was 36.4% in the differentiated types, and 67.9% in the poorly differentiated types (p < 0.05). The EGF positivity rate was 25.0% in m-sm cases, and 63.1% in mp-si cases (p < 0.05). CONCLUSIONS: The above findings suggest that EGF uptake by cancer cells increases when cancer cells are poorly differentiated, and that invasion in the surrounding tissue is severe.     

Presence of epidermal growth factor receptors on human thyroid membranes

The nature of epidermal growth factor (EGF) receptors in normal and pathological thyroid membranes was studied on a crude membrane fraction (10,000 X g pellet) of tissue homogenate. Optimal binding of 125I-EGF to human thyroid membranes was obtained at 25 degrees C with 1-h incubation at pH 7.4. The study revealed the presence of both high and low affinity receptors in normal and pathological thyroid membranes. The association constants of high affinity receptor (3.2 X 10(-9) mol/l) and of low affinity receptor (1.8 X 10(-8) mol/l) observed in normal thyroid membranes were similar to those of thyroid membranes from neoplastic as well as thyrotoxic thyroid tissues. [3H]thymidine incorporation into DNA of cultured human thyroid cells was stimulated by EGF in a dose-dependent manner. A half-maximal stimulation was found around 1 X 10(-10) mol/l. These results suggest that EGF may have a possible role in the regulation of thyroid growth and function in physiological and pathological situations.     

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.     

Up-regulation and co-expression of fibroblast growth factor receptors in human gastric cancer

Fibroblast growth factor (FGF), a key regulatory factor of cell growth and differentiation, is involved in embryonic development, angiogenesis, and tumorigenesis. To date, four different FGF receptors (FGFRs) have been cloned and characterized. We examined the expression of four FGFRs in human gastric cancer tissues and cell lines using Northern analysis, ribonuclease protection assay, and immunohistochemistry. The mRNAs of FGFR-1 (10/14), FGFR-2 (9/14), and FGFR-4 (9/14) were up-regulated in cancer compared with normal tissues. FGFR-3 mRNAs were barely detectable in both normal and cancer tissues. These FGFR mRNAs were co-expressed in various combinations of two or three in the same tissue. Immunohistochemistry confirmed specific staining of multiple FGFRs, except FGFR-3, in the cancer specimens. To investigate the functional significance of FGFR co-expression we examined the invasive property of SNU-16 cells, which exhibited gene amplification of FGFR-2, -3, and -4 as well as over-expression of keratinocyte growth factor receptor (KGFR), a splice variant of FGFR-2, and FGFR-4 mRNA. KGF plus acidic FGF (aFGF), KGF, and aFGF treatment enhanced the invasive potential of SNU-16 cells over the control by 100%, 107%, and 47%, respectively, indicating that neither additive nor synergistic effect was induced by stimulation with aFGF plus KGF. These results suggest that co-expression of FGFRs in various combinations may cause subtle changes in the progression of gastric cancer. Received: 16 February 1999 / Accepted: 6 March 2000     

胃癌患者血清表皮生长因子的变化

目的探讨人血清表皮生长因子（ｈＥＧＦ）水平与胃癌的关系．方法胃癌患者３３例，男３０例，女３例，年龄３５岁～８１岁，平均６４９岁；慢性胃炎患者３８例，男２５例，女１３例，年龄１８岁～７５岁，平均４３２岁；正常人２０例，男１０例，女１０例．应用ＲＩＡ法检测血清中的ｈＥＧＦ．结果胃癌组血清ｈＥＧＦ（μｇ／Ｌ）为１３５±０６７，正常对照组为０９０±０３３，统计学差异非常显著（ｔ＝２８２５，Ｐ＜００１），慢性胃炎组血清ｈＥＧＦ为０８６±０３３，与正常对照组比较差异无显著性（ｔ＝０４１，Ｐ＞００５）．结论胃癌患者血清ｈＥＧＦ水平升高可能与胃癌发生密切相关．     

The epidermal growth factor receptor as a target for cancer therapy

Epidermal growth factor (EGF) receptors are expressed at high levels in about one third of epithelial cancers, and autocrine activation of EGF receptors appears to be critical for the growth of many tumors. We hypothesized that blockade of the binding sites for EGF and transforming growth factor-alpha on EGF receptors with an antireceptor monoclonal antibody (mAb) might be an effective anti-cancer therapy. We produced murine mAb 225 against EGF receptors and demonstrated blockade of receptor function, as well as inhibition of cell growth in cultures and in nude mouse xenografts. mAb C225 is the human:murine chimeric version of mAb 225. Cell cycle inhibition occurred in G(1) phase, and was due to upregulation of p27(Kip1), resulting in inhibition of cyclin E/cyclin dependent kinase-2 activity and hypophosphorylation of Rb. In addition, the amount and/or activities of a number of proapoptotic molecules were enhanced. The antitumor activity in vivo against xenografts was at least partly attributable to reduced vascularization, resulting from decreased vascular endothelial growth factor and basic fibroblast growth factor production by the tumor cells. Metastasis of xenografts was curtailed with mAB C225 treatment, accompanied by a decrease in tumor production of MMP-9. Further studies showed that mAbs 225 and C225 enhanced the cytotoxicity of chemotherapy against xenografts of a variety of human cancer cell lines. Well established xenografts resistant to either mAb or drug treatment alone were eradicated by the combination therapy. Drugs for which this has been demonstrated include doxorubicin, paclitaxel, cisplatin, and topotecan. Antibody treatment also potentiated the responsiveness of human tumor xenografts to radiation therapy. These findings led to clinical trials of human:murine chimeric mAb C225 in combination with chemotherapy or radiotherapy. Results from phase I and II trials involving more than 500 patients are quite promising, in particular in advanced head and neck cancer treated with C225 plus cisplatin or radiation, in advanced colon cancer treated with C225 plus CPT-11, and in advanced pancreatic cancer treated with C225 plus gemcitabine. Phase III trials are now underway.     

表皮生长因子受体及增殖细胞核抗原在胃癌中的表达及意义

为探讨表皮生长因子受体 ( EGFR)及增殖细胞核抗原 ( PCNA)在胃癌中的表达 ,应用免疫组织化学技术 ,对胃癌和胃良性肿瘤组织中 EGFR和 PCNA分别进行定性和半定量检测 ,分析其与临床病理参数的关系。结果显示 1在胃良性肿瘤组织中 EGFR的表达率为 2 3 .0 8% ,PCNA L I为 2 7.80± 12 .2 0 ,明显低于胃癌组织中的表达率 ( 49.0 9% ,PCNA L I5 2 .73± 12 .2 5 ,P<0 .0 1)。2胃癌组织中 EGFR和 PCNA的表达与患者性别、年龄、病变部位、分型、组织学类型及分化程度无关 ( P均 >0 .0 5 ) ,而与临床分期、浸润深度及淋巴结转移情况相关 ( P <0 .0 5 ) ,表明联合检测 EGFR和 PCNA可作为判断胃癌恶性程度、预测淋巴结转移、制定合理治疗方案及评估预后的重要指标