表皮生长因子受体在梗阻性黄疸肝内胆管上皮细胞的表达及意义

目的:观察表皮生长因子受体在梗阻性黄疸肝内胆管上皮细胞的表达.方法:通过大白鼠胆总管结扎模型,观察胆道梗阻时肝内胆管增生在肝纤维化中的作用;表皮生长因子(EGF)与肝内胆管增生的关系.结果:胆总管结扎2周后肝小叶汇管区有明显的胆管增生和肝纤维化,胆总管结扎4周导致肝硬变形成;透射电镜显示胆总管结扎2周时胆管上皮细胞基底侧可见大量的胶原纤维和增厚的基底膜物质.胶原纤维与胆管上皮细胞紧贴:肝脏EGF受体免疫组化染色显示胆总管结扎2周时肝内胆管上皮细胞胞浆、胞膜及胞核出现阳性染色反应.结论:胆道梗阻时增生的胆管通过破坏肝小叶结构和产生胶原纤维及基底膜物质,参与肝纤维化过程;EGF在胆道梗阻肝内胆管增生过程中起重要作用     

表皮生长因子受体拮抗剂对慢性增生性胆管炎的实验疗效探讨

目的探讨表皮生长因子受体(EGFR)拮抗剂能否抑制慢性增生性胆管炎(CPC)的过度增殖行为和成石潜力,以期为肝内胆管结石的防治探索新的治疗途径。方法将46只健康SD大鼠随机分为5组:CPC模型组(10只),仅行造模处理;3种剂量EGFR拮抗剂AG-1478治疗组(分为3mg/kg、6mg/kg和12mg/kg组,各10只),在行造模术的同时经胆总管内注入相应剂量的AG-1478,术后7d内腹腔内注射AG-1478 1.5mg/(kg.d);假手术组(SO组,6只),仅行开腹术后即关腹。于术后7d剖腹取胆管标本组织分别行病理组织学观察、免疫组化染色、RT-PCR和Western blot检测,比较各组EGFR、5-溴脱氧尿核苷(BrdU)、Ki-67、黏蛋白5AC和Ⅰ型胶原蛋白的mRNA或蛋白表达情况,以评估AG-1478对病变胆管黏膜过度增殖行为(EGFR、Ki-67、BrdU、Ⅰ型胶原蛋白)和成石潜力(黏蛋白5AC)的影响。结果 与CPC模型组比较,治疗组的EGFR、Ki-67及BrdU表达明显降低,组织学观察所见的胆管黏膜上皮和胶原纤维的过度增殖行为也得到了有效的抑制;此外,治疗组的黏蛋白5AC mRNA和Ⅰ型胶原蛋白表达水平也较CPC模型组明显降低(P<0.05)。结论 EGFR拮抗剂可有效抑制CPC病变胆管黏膜的过度增殖和成石潜力,有望成为CPC新的治疗手段。     

吉非替尼对小鼠睾丸癌I-10细胞生长抑制及诱导凋亡作用

目的:观察吉非替尼对体外培养的小鼠睾丸癌细胞(I-10)生长抑制及诱导凋亡作用。方法:将不同浓度(0、1.25、2.5、5、10、20、40μmol/L)吉非替尼作用于对数生长期的睾丸癌I-10细胞。MTT法检测吉非替尼对I-10细胞生长的抑制作用;Annexin V/PI双染法观察吉非替尼作用后I-10细胞的早期凋亡;Hoechst 33258荧光染色法观察吉非替尼作用后I-10细胞晚期凋亡;Western印迹法检测吉非替尼作用后凋亡相关蛋白Bcl-2、Bax、caspase 3/9的变化。结果:10、20μmol/L的吉非替尼对I-10细胞增殖有明显抑制作用,与对照组相比差异有显著性(P0.05),40μmol/L的吉非替尼作用下,I-10细胞的生存率为(32.4±2.8)%,与对照组相比差异显著(P0.01);40μmol/L吉非替尼组I-10细胞的早期和晚期凋亡率分别为(26.7±4.2)%和(59.33±10.2)%,与对照组相比差异显著(P0.05、P0.01);吉非替尼(10、20、40μmol/L)作用后,与对照组相比,促凋亡蛋白Bax表达分别增加了(41.9±7.1)%、(60.1±9.8)%、(69.0±11.3)%(P均0.05)而抑凋亡蛋白Bcl-2表达分别减少了(50.3±8.9)%、(63.9±6.9)%、(88.7±13.9)%(P0.05);剪切的caspase3表达分别增加(69.0±6.9)%、(71.5±8.1)%、(110.9±14.2)%(P0.05);剪切的caspase9表达分别增加了(51.8±4.9)%、(54.7±6.7)%、(43.8±11.8)%(P均0.05)。结论:吉非替尼可以增加I-10细胞的细胞毒性并诱导细胞凋亡,其机制与线粒体凋亡信号通路有关。     

生长抑素与表皮生长因子受体在胃癌中表达的相关性及意义

观察胃癌组织中生长抑素（ＳＳ）表达与表皮生长因子受体（ＥＧＦＲ）表达的相互关系,探讨其抑癌的可能机制。方法应用免疫组化ＬＳＡＢ法及即用型ＳＰ法,对１４７例各组织学类型胃癌中ＳＳ及ＥＧＦＲ的表达进行观察比较,并对其中１２７例患者进行预后随访。结果胃癌中ＳＳ阳性表达率为２５．７％。ＳＳ阳性及ＳＳ阴性两组胃癌ＥＧＦＲ的表达差异有显著意义（Ｐ＜０．０１）。ＳＳ阳性胃癌组ＥＧＦＲ的表达明显减少。伴有ＳＳ阴性表达的ＥＧＦＲ阳性胃癌预后尤其差。结论ＳＳ及ＥＧＦＲ在人体胃癌组织中的表达有一定拮抗性。ＳＳ阴性的ＥＧＦＲ阳性胃癌预后更差。ＳＳ的抑癌机制之一可能是干扰了生长因子的合成。     

应用c-myc shRNA治疗慢性增生性胆管炎在肝内胆管结石治疗中的价值

目的探讨能否通过局部应用c-myc shRNA抑制慢性增生性胆管炎(CPC)增殖相关基因的表达而抑制CPC的过度增殖行为和成石潜力。方法经十二指肠乳头向胆总管逆行插入5-0尼龙缝合线建立CPC动物模型(CPC组)。c-myc shRNA治疗组在CPC组基础上向胆总管内分别注入3种c-myc shRNA即分别为c-myc shRNA-1、c-myc shRNA-2及c-myc shRNA-3,另设阴性对照组和假手术组。应用HE、Massion和PAS/AB染色观察胆管组织病理学变化,免疫组化法检测c-myc蛋白表达,免疫荧光法检测5-溴脱氧尿核苷(BrdU)蛋白表达,实时(RT)-PCR检测c-myc、Mucin 3和ProcollagenⅠmRNA的表达,Western blot法检测Ki-67蛋白的表达,改良Fisherman法检测β-葡萄糖醛酸酶(β-G)的活性。结果①与CPC组及阴性对照组比较,c-myc shRNA治疗组的胆管黏膜上皮(HE染色)、黏膜下酸性黏液腺体(PAS/AB染色中蓝色)和胆管壁胶原纤维(Massion染色蓝染)的过度增生程度明显减弱,BrdU蛋白表达也明显减弱。②c-myc、Mucin 3和ProcollagenⅠmRNA,c-myc蛋白,Ki-67蛋白,以及β-G活性在c-myc shRNA治疗组均明显低于CPC组及阴性对照组(P0.05),但均高于假手术组(P0.05)。结论 c-myc shRNA治疗能够有效地抑制CPC的过度增殖行为和成石潜力,可能会有助于预防胆管再狭窄和肝内胆管结石的术后复发。     

乳腺癌细胞中表皮生长因子对雌激素受体表达的影响及机制

目的研究表皮生长因子（EGF）在雌激素受体（ER）阳性及阴性乳腺癌细胞株中对ER表达的影响及其可能的机制。方法以逆转录-聚合酶链反应（RT—PCR）技术分别研究EGF途径以及抑制该途径的信号传导后，对乳腺癌细胞株中ERcxmRNA的影响。结果在ER阳性乳腺癌细胞株中，EGF能显著抑制ERα mRNA的表达（P〈0．05），而通过抑制表皮生长因子受体（EG-FR）、磷脂酰肌醇3激酶（P13K）阻断EGF信号传导可减弱上述抑制作用（P〈0．05）；在ER阴性乳腺癌细胞株中，ERα mRNA无显著变化。结论EGF能够明显抑制ER阳性乳腺癌细胞株中ER的表达，这种抑制作用可能通过EGFR、蛋白激酶B（PKB，又称AKt）信号传导途径完成；这种作用在ER阴性乳腺癌细胞株中并不明显。     

雄,雌激素对睾丸表皮生长因子及受体表达的影响

运用＾１２５Ｉ－ＥＧＦ放射受体法，探讨对不同周龄Ｗｉｓｔａｒ鼠使用雄、雄激素过程中及停药后睾丸表皮生长因子与ＥＧＦ受体结合情况，结果表明：ＥＧＦ与睾丸细胞膜在２７℃孵育７０分钟结合最大，年龄增长与睾丸重量呈正比，与ＥＧＦ呈反比；雄激素治疗中，睾丸重量、ＥＧＦ均上升，且大于正常（Ｐ＜０．０１），ＲＴ骤各；停药时，ＥＧＦ降至正常；雌激素治疗时，ＥＧＦ亦高于正常（Ｐ＜０．０１），ＫＤ微上升，停药时，ＥＧ     

免疫组化结合图像分析研究膀胱癌中表皮生长因子受体的分布及意义

应用免疫组化方法结合图像分析研究58例膀胱肿瘤表皮生长因子受体（EGFR）与膀胱肿瘤之间的关系。结果显示EGFR阳性率为34.5％,其阳性显色分别定位于细胞膜（占55％）和胞浆内（占 45％）。其阳性率在肿瘤的病理分级、临床分期及预后等方面差异显著（P<0.05）。提示EGFR的异常表达可作为判定膀胱肿瘤恶性程度及预后的一项重要指标。     

乳腺癌组织中表皮生长因子受体4的表达及其临床病理意义

目的探讨人表皮生长因子受体4（HER-4）在人类表皮生长因子受体2（HER-2）强阳性与阴性乳腺癌组织中的表达差异,分析其与雌激素受体α（ERα）、孕激素受体（PR）表达情况及其TNM分期和腋窝淋巴结状况的关系。方法随机选择中山大学附属第一医院在2004年12月至2007年12月收治的HER-2高表达（＋＋＋）51例与无表达（-）49例乳腺浸润性导管癌病例,分别检测乳腺癌组织的HER-4、HER-2、ERα、ERβ、ER131、ER13CX、PR的表达水平,分析HER-4与以上各指标以及与肿瘤TNM分期、腋窝淋巴结转移等临床指标的相关性。结果HER-4、ERd、ERβ、ERβ1、ERβcx、PR在HER-2（＋＋＋）组的阳性表达率分别为43．13％、33．33％、45．10％、47．06％、78．43％、64．71％,在HER-2（-）组中的阳性表达率分别为69．38％、71．42％、81．63％、87．75％、87．75％、79．59％;两组中上述指标的表达差异均有统计学意义（P〈0．05或P〈0．01）。两组的HER-4表达与ERα、ERβ、PR、ERβ1、ERβcx呈正相关（P〈0．05或P〈0．01）。细胞膜、细胞质及细胞核表达率在HER-2（＋＋＋）组中分别为41．17％、37．25％、3．90％;在HER-2（-）组中分别为69．38％、48．97％、2．05％。两组中HER-4的细胞膜表达率差异有统计学意义（P〈0．01）,但在细胞质及细胞核的表达率未显示出明显差异。结论HER-4可作为乳腺癌预后良好的指标,在乳腺病理诊断中增加UHER-4的检测对治疗和判断预后有一定的指导作用。HER-4在亚细胞中的不同定位值得进一步研究。     

转化生长因子调控表皮生长因子受体在雄激素非依赖型前列腺癌细胞中表达的意义

目的 :探讨转化生长因子 (TGF)α对前列腺癌雄激素非依赖型细胞系中表皮生长因子受体 (EGFR)表达的调控。　方法 :采用逆转录 多聚酶链式反应和Western印迹法对TGFα刺激前列腺癌雄激素非依赖型细胞系PC3、ARCaP后EGFRmRNA表达及其蛋白水平进行定量分析。　结果 :TGFα引起PC3、ARCaP的EGFRmRNA表达升高 ,分别为 5 .0 1± 0 .4 5和 9.0 5± 0 .6 3,明显高于对照组 (P <0 .0 5 )。PC3细胞系TGFα治疗后EGFR蛋白水平为 2 .2 8±0 .5 3,明显高于对照组 (P <0 .0 5 ) ;而ARCaP细胞系TGFα治疗后EGFR仅为 1 .2 4± 0 .2 2 ,和对照组比较无差别 (P >0 .0 5 )。　结论 :TGFα可以明显提高前列腺癌细胞的EGFR表达量 ;TGFα EGFR自分泌环参与雄激素非依赖型前列腺癌的形成     

Epidermal Growth Factor Receptor Expression in Spindle Cell Carcinomas of the Head and Neck

Spindle cell carcinoma (SpCC) is an uncommon head and neck squamous cell carcinoma (SCC) variant consisting of spindled and/or pleomorphic cells with epithelial differentiation. Epidermal growth factor receptor (EGFR) is expressed by >90 % of conventional SCC, and high level expression is associated with a poorer prognosis. Anti-EGFR therapies are commonly used to treat head and neck SCC. However, no studies have evaluated EGFR expression in SpCC. Cases of SpCC were retrieved from department files. The diagnosis required either a biphasic lesion with a squamous neoplastic component, or a purely spindle cell or pleomorphic tumor with immunohistochemical positivity for epithelial markers. EGFR immunohistochemistry was performed and was quantified in quartiles. Medical records were reviewed for clinical follow up information. EGFR was expressed in 21/30 (70 %) cases, including in the squamous component in 18/19 (95 %) and the spindle cell component in only 12/30 (40 %). Where the spindle cell component was positive, the intensity and distribution were lower than for the squamous component. Recurrent tumors were predominantly (80–90 %) of the spindle cell component, and had low (or absent) EGFR expression. Kaplan–Meier survival analysis showed no statistically significant differences in overall or disease free survival between the EGFR expressing and non-expressing groups (p = 0.414 and 0.19, respectively). SpCCs of the head and neck have a poor prognosis, and markedly reduced EGFR expression. EGFR-specific therapies may not be ideal for SpCC patients, which may lack EGFR expression, but further studies are needed.

Electronic supplementary material

The online version of this article (doi:10.1007/s12105-014-0604-y) contains supplementary material, which is available to authorized users.     

Clinical Significance of the Epidermal Growth Factor Receptor and HER2 Receptor in Resectable Gastric Cancer

Background: Epidermal growth factor receptor (EGFR or HER1) and its homolog c-erbB-2 (HER2) are membrane receptors. Both EGFR and HER2 genes are overexpressed in a variety of solid human cancers and are related to poor prognosis of the patients. The objective of this work was to evaluate the EGFR and HER2 contents in resectable gastric cancer, their possible relationship with clinicopathologic parameters of tumors, and their prognostic significance.Methods: This was a prospective analysis of 63 patients with resectable gastric carcinomas, with a mean follow-up period of 40.7 months. Membranous EGFR levels were examined by radioligand binding assays, and cytosolic HER2 levels were examined by means of an immunoenzymatic assay.Results: There was a wide variability of EGFR (1–1,239 fmol/mg of protein) and HER2 (7–20,863 NHU/mg of protein) levels in tumors. There was no significant correlation between these levels and patient or tumor characteristics. However, high levels of EGFR and HER2 were significantly associated with a shorter overall survival period (P = .03 and P = .02, respectively).Conclusions: There is a wide variability in membranous EGFR levels and in cytosolic HER2 levels in gastric cancer, which seems to be related to the biological heterogeneity of these tumors. In addition, high tumor EGFR and HER2 levels were associated with an unfavorable outcome in patients with resectable gastric cancer.     

表皮生长因子受体,多胺与肺癌的关系

探讨表皮生长因子受体（ＥＧＦＲ）和多胺（ＰＡ）对人肺癌及正常肺组织生长、分化的影响。方法放射性配体结合法检测ＥＧＦＲ含量；高效液相色谱分析法测ＰＡ含量。结果肺癌组织中ＥＧＦＲ的含量（５．６２±４．２６ｆｍｏｌ／ｍｇ膜蛋白）高于非癌肺组织（３．９０５±２．２７９ｆｍｏｌ／ｍｇ膜蛋白），有显著性差异（Ｐ＜０．０１）；肺癌组织ＰＡ的含量亦高于正常肺组织（Ｐ＜０．０１）。结论ＥＧＦＲ和ＰＡ可促使肺癌发展，可作为肺癌的肿瘤标记物     

Prognostic Significance of Epidermal Growth Factor Receptor Expression in Colon Cancer Patients Undergoing Curative Surgery

Background To investigate the role of epidermal growth factor receptor (EGFR) expression as a prognostic marker for prediction of cancer behavior and clinical outcomes in colon cancer patients undergoing potentially curative surgery. Methods EGFR determination using a commercially available immunohistochemistry kit was performed in tissues from 149 colon cancer patients receiving primary surgical treatment and in 25 normal colon mucosa specimens from noncancer patients. EGFR positivity was correlated in univariate and multivariate analyses with disease recurrence and survival. In addition, p27, p53, and vascular endothelial growth factor expression were assessed by immunohistochemistry in 104 patients and correlated with EGFR tumor expression and clinical outcome. Results EGFR expression was detected in approximately one third of colon cancer patients (53 of 149; 35.6%). In 126 curatively treated patients, EGFR expression was correlated with disease recurrence and worse survival in both univariate and multivariate analyses. In a multivariate model for predicting recurrence and survival, Dukes’ staging, p27, and EGFR expression were the only independent covariates. In particular, in Dukes’ A and B patients the 5-year survival probability was 96% for EGFR-negative and high p27 expression cases and was 30.7% for EGFR-positive and low p27 expression cases. Conclusions EGFR expression was an independent prognostic indicator of disease recurrence and poor survival in colon cancer patients undergoing curative surgery. In the context of novel therapeutic options such as molecularly targeted therapies, these findings suggest that anti-EGFR drugs could be evaluated in the adjuvant treatment of EGFR-positive colon cancer patients.     

Elevated Serum Epidermal Growth Factor Receptor Level in Stage IV Thymoma

Using the enzyme immunoassay for epidermal growth factor receptor (EGFR), we investigated whether serum EGFR levels could be used as a predictor of the development and extension of thymoma. Serum samples were collected from 31 patients with thymoma and 16 patients with nonmalignant thoracic disease before clinical treatment. There was no difference between the serum EGFR levels of the patients with thymoma and the nonmalignant controls, being 49.1 ± 136.3 and 22.6 ± 7.3fm/ml, respectively (P = 0.11). However, patients with stage IV thymoma had significantly higher EGFR levels than those with stage I or stage II thymoma, the respective values being 127.8 ± 243.9, 10.9 ± 9.2 (P = 0.02), and 19.7 ± 10.6 (P = 0.0433) fm/ml. The serum EGFR levels were similar in the pathological subtypes. These findings suggest that serum EGFR levels may serve as a marker that could be used as a diagnostic indicator of the invasion of thymoma.     

胸腺瘤表皮生长因子受体、增殖细胞核抗原、Bcl-2和Bax表达及临床意义

目的　探讨胸腺瘤表皮生长因子受体 ( EGFR)、增殖细胞核抗原 ( PCNA)、Bcl- 2和 Bax的表达与胸腺瘤临床病理特征的关系及临床意义。　方法　应用免疫组织化学链霉素亲生物蛋白 -过氧化酶 ( S- P)法检测 4 6例胸腺瘤患者EGFR、PCNA、Bcl- 2和 Bax的表达。　结果　胸腺瘤 EGFR阳性表达率为 71.7% ,PCNA标记指数为 4 .0 0 %± 1.87% ,Bcl- 2、Bax阳性率分别为 4 1.3 %、15 .2 %。EGFR表达与胸腺瘤 Masaoka分期、肿瘤性质有明显关系 ,EGFR阴性者术后生存率显著高于阳性者 ( P=0 .0 0 5 )。 PCNA标记指数和 Bcl- 2与胸腺瘤肿瘤性质有明显关系 ,Bcl- 2阴性者术后生存率显著高于阳性者 ( P=0 .0 0 2 )。EGFR、PCNA、Bcl- 2和 Bax表达均与胸腺瘤组织学类型、是否合并重症肌无力无明显关系。　结论　EGFR与胸腺瘤的发生、发展有关 ,可作为 Masaoka分期的补充推测预后。Bcl- 2与胸腺癌发生有关 ,可作为胸腺癌的标记物用于鉴别诊断。     

表皮生长因子及其受体在睾丸中的分布与功能

睾丸Sertoli细胞和早期生精细胞不仅存在表皮生长因子 (EGF)而且存在EGF受体 (EGFR) ,睾丸Leydig细胞也含有EGFR。EGF通过和EGFR结合 ,发挥特定的生物学效应 ,能刺激睾丸雄激素的合成和生精细胞的成熟。但是高浓度的EGF反而会抑制生精细胞的成熟。     

表皮生长因子及其受体对雄性生殖系统的影响

表皮生长因子 (EGF)是首先从小鼠颌下腺分离出来的含 5 3个氨基酸残基的单链多肽 ,通过与其受体(EGFR)相结合发挥多种生物学效应。近年来发现 ,在人类和其他动物的雄性生殖系统有EGF与EGFR表达 ,对雄性生殖器官的发育、维持及变异起着重要的作用 ,同时 ,对雄性激素的分泌和精子发生也有很大的影响。EGFR在睾丸的支持细胞和间质细胞上均有表达 ,可影响睾酮的分泌 ;能维持正常前列腺组织的生长发育 ,刺激前列腺增生组织和前列腺癌组织的生长和分化 ;EGF参与精子发生 ,其作用点主要在减数分裂过程 ;可影响性分化 ,在雄激素诱导下使胚胎向雄性方向发育。     

膜表面核仁素参与表皮生长因子受体信号启动的研究

目的探讨膜表面核仁素（nucleiolin,NCL）在表皮生长因子受体（epidermal growth factor receptor,EGFR）信号启动中的作用。方法采用免疫组化法检测NCL及EGFR在甲状腺乳头状癌组织中的表达;Western blot法检测甲状腺乳头状癌细胞TPC-1中磷酸化EGFR（phosphorylation EGFR,p-EGFR）的表达水平;Transwell小室试验检测TPC-1细胞的迁移能力。结果免疫组化染色结果显示,甲状腺乳头状癌组织中NCL及EGFR的表达阳性率分别为100％（56／56）和80.4％（45／56）;NCL及EGFR的表达与淋巴结转移有关（P〈0.05）,且NCL的表达与EGFR的表达呈正相关关系（r=0.635,P〈0.01）。Western blot法检测结果显示,拮抗甲状腺乳头状癌TPC-1细胞的NCL或EGFR后,其p-EGFR表达水平均明显下调（P〈0.01）。Transwell小室试验发现,拮抗NCL和EGFR后,可明显减少TPC-1细胞的穿膜细胞数（P〈0.01）。结论膜表面NCL可能是EGFR受体信号启动的必要成分,可能通过EGFR参与肿瘤的生长与转移。以NCL为靶点将开拓肿瘤新的治疗领域。