表皮生长因子受体和转化生长因子-α在宫颈癌中的表达

新疆是子宫颈癌高发区之一 ,特别是维吾尔族妇女宫颈癌患病率高 ,病因较复杂。子宫颈癌的发生可能与某些原癌基因 ,如表皮生长因子受体 (ｅｐｉｄｅｒｍａｌｇｒｏｗｔｈｆａｃｔｏｒｒｅｃｅｐｔｏｒ,ＥＧＦＲ)和转化生长因子 α(ｔｒａｎｓｆｏｒｍｉｎｇｇｒｏｗｔｈｆａｃｔｏｒ α ,ＴＧＦ α)的激活有一定关系。ＥＧＦＲ是一种原癌基因 ,它的作用与Ｖ ｅｒｂ Ｂ癌基因的作用相同〔1〕。ＥＧＦＲ广泛分布于人体组织中 ,常与配位子表皮生长因子 (ＥＧＦ)和ＴＧＦ α结合 ,并在恶性肿瘤组织中有过度表达〔2〕。我们应用免疫组化方法观察…     

人表皮生长因子受体-2在胃癌组织中的表达及意义

目的探讨胃癌组织中人表皮生长因子受体-2(human epidermal growth factor receptor 2,HER-2)的表达及与临床病理特征的关系。方法应用免疫组化Envision二步法检测70例胃癌组织中HER-2的表达情况,并结合其临床病理特点进行分析。结果 HER-2在胃癌组织中的阳性表达率为27.1%(19/70),阳性过表达率为15.7%(11/70)。阳性表达与肿瘤分化程度、侵袭深度、有无淋巴结转移及TNM分期有关(P<0.05),而与患者的性别、年龄、肿瘤部位和大小无关(P>0.05)。结论 HER-2的表达参与胃癌的生长、侵袭和转移过程。检测HER-2有助于筛选对曲妥珠单抗(Herceptin)靶向治疗敏感的胃癌患者,也为胃癌的预后判断提供客观的参考指标。     

smad4基因和转化生长因子β1及其受体在乳腺癌组织中的表达及意义

目的:探讨乳腺癌组织中smad_4 mRNA、转化生长因子β1(TGF-β1)、转化生长因子β1受体(TGF-β1R)的表达及其意义。方法:常规石蜡包埋切片行smad_4 mRNA原位杂交染色及TGF-β1、TGF-β1R免疫组织化学染色。结果:在非浸润性乳腺癌、组织学分级1级和淋巴结无转移组织中smad_4 mRNA、TGF-β1、TGF-β1R的阳性表达率明显高于浸润性乳腺癌、组织学分级2级或3级和淋巴结转移组织,差异均有显著性意义:smad_4 mRNA、TGF-β1和TGF-β1R在乳腺癌中表达密切相关。结论:smad_4 mRNA、TGF-β1和TGF-βR表达可能与乳腺癌发生发展、生物学行为和预后密切相关,可作为重要的生物学标记物     

表皮生长因子受体和转化生长因子受体α对前列腺增生和癌变组织及其预后判断的影响

目的：检测表皮生长因子受体(EGFR)和转化生长因子(TGFα)在前列腺增生(benign prostatic hyperplasia，BPH)和前列腺癌中的表达情况，探讨前列腺增生和前列腺癌的病因和发病机制。方法：实验于2004-08／09在沈阳医学院病理教研室完成。应用免疫组织化学SP法检测40例前列腺增生症及40例前列腺癌中EGFR和TGFα表达情况。结果：正常和增生组织中EGFR和TGFα分别表达在卜皮细胞和基质细胞中。两者在前列腺癌中的共同表达率为65％，二者密切相关(r=0．524)，且与前列腺癌的分期有关（P&;lt;0.01）．此类患者的生存时间也明显小于二者阴性表达行(P&;lt;0.01）。结论：EGFR和TGFα的异常表达在前列腺增生和癌变的发病中起重要的作用。它们可以作为判断前列腺癌临床分床期预后的重要指标。     

人表皮生长因子受体3在乳腺癌组织中的表达及临床意义

目的探讨人表皮生长因子受体(HER)3基因在乳腺癌组织中的表达及其与临床病理学特征和预后的相关性。方法采用免疫组织化学法检测126例乳腺癌组织中HER3的表达,分析其表达与患者年龄、月经情况、TNM分期、肿瘤大小、淋巴结转移、雌激素受体(ER)、孕激素受体(PR)、HER2及预后的关系。结果 (1)乳腺癌组织中HER3的阳性表达率为30.2%。HER3阳性表达在乳腺癌绝经患者中占43.3%,高于未绝经者的18.2%(P0.05);淋巴结转移阳性的乳腺癌患者HER3阳性表达率为40.0%,高于无淋巴结转移患者的21.2%,差异有统计学意义(P0.05);HER2阳性的乳腺癌患者HER3阳性表达率为42.5%,高于HER2阴性者的24.4%,差异有统计学意义(P0.05)。(2)HER3阳性患者的五年无病生存率更低(P0.05)。(3)HER3与HER2均阳性的乳腺癌患者淋巴结转移率较高(P0.05)。结论 HER3的表达可能在乳腺癌的发生和发展过程中起重要作用,并影响其预后,HER3可能成为判断乳腺癌预后的指标及临床治疗的靶点。     

表皮生长因子受体在人输卵管中的表达与变化

目的:探讨表皮生长因子受体(EGFR)在人输卵管上皮组织中的表达和变化规律.方法:收集月经规律、有正常生育史的育龄妇女输卵管组织33例,绝经期妇女输卵管组织15例.育龄妇女输卵管标本取材均包括峡部、壶腹部和伞部,按月经周期分为增生早期组6例,增生中期组5例,增生晚期组5例,分泌早期组7例,分泌中期组5例和分泌晚期组5例.绝经妇女输卵管取壶腹部标本.采用免疫组织化学方法检测榆卵管组织中EGFR的表达,并应用Leica Q550图像分析系统分析阳性细胞表达强弱.结果:育龄妇女输卵管3段上皮和基质中均有EGFR蛋白表达,上皮细胞阳性表达高于基质.壶腹部和伞部上皮细胞EGFR阳性表达高于峡部,且在增生早期较低,增生中晚期和分泌早中期增高,分泌晚期下降.绝经期妇女输卵管上皮EGFR表达最低.结论:人输卵管组织中存在EGFR表达,且具有阶段性和周期性变化,推测EGFR可能参与输卵管多种生理作用.     

生长抑素和表皮生长因子受体在人胃癌组织中的表达及意义

目的探讨生长抑素(SS)在胃癌发生发展中的作用及地位,从而为胃癌的治疗和预后判断提供一个新的途径。方法应用免疫组化SABC(strept avidin biotin complex)法检测78例胃癌组织和20例正常胃黏膜中SS和表皮生长因子受体(EGFR)的表达。结果SS在正常胃黏膜中阳性表达率为85.0%,胃癌组织中阳性表达率为24.3%;高/中分化组和低分化组中的阳性表达率分别为34.2%、13.5%,随分化程度减低而呈下降趋势;浸润黏膜层或黏膜下层和浸润肌层或浆膜层两组的阳性表达率分别为64.3%、15.6%,随浸润程度的加深其阳性表达率呈下降趋势;无淋巴结转移组和有淋巴结转移组的阳性表达率分别为38.7%、14.9%;在TNMⅠ~Ⅱ期和Ⅲ~Ⅳ期此两组中的阳性表达率分别为45.5%、8.9%。以上两组间比较差异均有统计学意义(P<0.05)。SS的阳性表达与EGFR的阳性表达呈负相关系。结论SS的低表达与胃癌的组织学分级、浸润深度、淋巴结转移及TNM分期密切相关。SS可能通过抑制EGFR的表达而抑制胃癌的生长。     

表皮生长因子受体在甲状腺乳头状癌中的表达及其与上皮-间质转化的关系

目的:研究表皮生长因子受体(epidermal growth factor receptor,EGFR)在甲状腺乳头状癌中的表达及其与上皮间质转化的关系.方法:采用免疫组织化学EnVision法检测EGFR、上皮性钙黏附蛋白(E-cadherin)和波形蛋白(vimentin)在44例甲状腺乳头状癌组织、癌旁组织中的表达,并分析其与甲状腺乳头状癌临床病理参数的关系及EGFR与E-cadherin和vimentin的相关性.结果:44例甲状腺乳头状癌中,EGFR、E-cadherin和vimentin阳性表达率分别为68.2％(30/44)、79.5％(35/44)和63.6 ％(28/44),与癌旁组织[6.8 ％(3/44)、4.5 ％(2/44)和9.1％(4/44)]比较,差异有统计学意义(x2 =35.35,P=0.00;x2=50.78,P=0.00;x2=28.59,P=.00).甲状腺乳头状癌组织中EGFR表达与E-cadherin呈负相关(r =-0.306,P=0.043),与vimentin呈正相关(r=0.595,P=0.000).在伴淋巴结转移患者中和不伴淋巴结转移患者中EGFR、E-cadherin和vimentin表达差异均有统计学意义(x2分别为7.79、5.81及4.32,P均＜0.05).结论:甲状腺乳头状癌中EGFR表达升高伴随E-cadherin下调和vimentin上调,它们的变化可能与上皮-间质转化相关,并可能在甲状腺乳头状癌的淋巴结转移中起重要作用.     

表皮生长因子受体和转化生长因子受体α对前列腺增生和癌变组织及其预后判断的影响

目的:检测表皮生长因子受体(EGFR)和转化生长因子(TGFα)在前列腺增生(benignprostatichyperplasia,BPH)和前列腺癌中的表达情况,探讨前列腺增生和前列腺癌的病因和发病机制。方法:实验于2004-08/09在沈阳医学院病理教研室完成。应用免疫组织化学SP法检测40例前列腺增生症及40例前列腺癌中EGFR和TGFα表达情况。结果:正常和增生组织中EGFR和TGFα分别表达在上皮细胞和基质细胞中。两者在前列腺癌中的共同表达率为65%,二者密切相关(r=0.524),且与前列腺癌的分期有关(P<0.01),此类患者的生存时间也明显小于二者阴性表达者(P<0.01)。结论:EGFR和TGFα的异常表达在前列腺增生和癌变的发病中起重要的作用。它们可以作为判断前列腺癌临床分期和预后的重要指标。     

表皮生长因子受体在大肠癌中的表达及其临床意义

对表皮生长因子受体(EGFR)在大肠癌中的表达及其临床意义探讨如下。1对象和方法1.1对象手术切除及结肠镜活检标本且经病理证实的大肠癌患者62例,男24例,女38例,年龄25~73(52.37±14.88)岁。其中大肠癌51例,良性对照11例。术前均未接受过化疗、放疗或其他针对肿瘤的治疗。1.2方法62例组织标本采用SABC法,进行EGFR免疫组化染色。兔抗人EGFR多克隆抗体及SABC试剂盒,均由武汉博士德公司提供。1.3结果判定EGFR阳性[1]染色为位于胞浆及胞膜上、个别位于胞核上的棕黄色颗粒,按染色深度和阳性细胞所占比例分别计分:(1)染色深度:无着色为0;…     

Fibrin stimulates the proliferation of human keratinocytes through the autocrine mechanism of transforming growth factor-alpha and epidermal growth factor receptor

In the field of dermatology and plastic and reconstructive surgery, fibrin gel is regarded as a material that promotes wound healing. To test the hypothesis that fibrin may promote the growth of the epidermis, we examined its effects on the proliferation of cultured keratinocytes. Human keratinocytes were cultivated in fibrin-coated wells, and the cell numbers and transforming growth factor (TGF)-alpha, secreted into the cultured medium, were measured. We also assessed the capacity of epidermal growth factor receptor (EGF-R) that is responsible for all known actions of TGF-alpha and epidermal growth factor. The keratinocytes increased dramatically in their number, and the TGF-alpha secretion and the binding capacity of EGF-R were also increased dramatically in the presence of fibrin. These findings suggest that fibrin supports the proliferation of keratinocytes in an autocrine fashion via EGF-R; namely, fibrin stimulates keratinocytes to secrete TGF-alpha, which in turn increases cell proliferation and EGF-R capacity. We propose that fibrin can support the wound healing process of the epidermis via the TGF-alpha/EGF-R pathway.     

小鼠下颌下腺发育中转化生长因子β受体的表达

背景：小鼠的下颌下腺是研究唾液腺的发育的良好模型,转化生长因子β是器官发育和疾病中重要的生长因子,但是在下颌下腺中转化生长因子β受体的表达以及作用机制至今并不明确。目的：观察胚胎小鼠下颌下腺发育过程中转化生长因子βⅠ型受体和Ⅱ型受体以及p-ERK1／2的表达,揭示转化生长因子β在小鼠涎腺发育中的作用。方法：取C57BL／6J小鼠胚胎期第14.5天的标本,使用转化生长因子βⅠ型受体和Ⅱ型受体以及p-ERK1／2抗体,对小鼠的下颌下腺进行免疫组化染色。取新生小鼠标本,大体观察下颌下腺,并且使用苏木精-伊红染色观察其形态。结果与结论：①小鼠出生时,下颌下腺位于下颌骨下方;苏木精-伊红染色发现小鼠下颌下腺的腺泡、导管和闰管细胞也已经分化完成。②在胚胎期第14．5天,转化生长因子βⅠ型和Ⅱ型受体在腺泡上皮和导管上皮内高表达,而腺体上皮细胞外的间充质没有表达。③p-ERK1／2主要也是表达在下颌下腺的上皮细胞中,与转化生长因子βⅠ型受体和Ⅱ型受体在下颌下腺中的表达基本一致。说明在小鼠下颌下腺的发育过程中,转化生长因子β蛋白可能通过与上皮细胞表面的受体结合,激活ERK信号通路来调节涎腺腺泡和导管的发育。     

Expression of transforming growth factor alpha and epidermal growth factor receptor in human bladder cancer.

We analysed the expression of epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) in human bladder tumours. Tumour biopsies were obtained from 54 patients with primary bladder cancer (18 stage T1 and 36 stage T2-4). The protein and mRNA expression of EGFr and TGF-alpha were quantified by ELISA and competitive RT-PCR, respectively. The EGFr protein level was significantly increased in T2-4 tumours (0.44 x 10(-11); 0.0-27.5 x 10(-11) mol/g) compared with T1 tumours (0.0; 0.0-2.0 x 10(-11) mol/g) (median; range; 2p<0.01). The EGFr protein and mRNA level correlated (Spearman r=0.45, 2p<0.005, n=40). Co-expression of TGF-alpha protein and EGFr protein was significantly associated with muscle invasive tumours (T2-4) (chi-squared=7.9, df=3, p<0.05) and the TGF-alpha protein level correlated significantly with EGFr protein expression (Spearman r=0.56, 2p<0.0001, n=54). While tumour stage correlated with survival, no correlation was observed between survival and the expression of EGFr and/or TGF-alpha. In conclusion, human bladder tumours express both EGFr and TGF-alpha. The expression of EGFr and TGF-alpha are closely correlated, and the expression of EGFr and co-expression of EGFr and TGF-alpha correlate with tumour stage.     

Expression of epidermal growth factor (EGF)/transforming growth factor-alpha by human lung cancer cells determines their response to EGF receptor tyrosine kinase inhibition in the lungs of mice

Epidermal growth factor receptor (EGFR) has been extensively targeted in the treatment of non-small cell lung cancer, producing responses in a small number of patients. To study the role of ligand expression in mediating response to EGFR antagonism, we injected NCI-H441 [EGFR and EGF/transforming growth factor-alpha (TGF-alpha) positive] or PC14-PE6 (EGFR positive and EGF/TGF-alpha negative) human lung adenocarcinoma cells into the lungs of nude mice. We randomized the mice to receive treatment with the EGFR tyrosine kinase inhibitors gefitinib or AEE788 or vehicle. Treatment of mice bearing NCI-H441 but not PC14-PE6 lung tumors resulted in a significant reduction in primary tumor growth, pleural effusion, and lymph node metastasis. Immunohistochemical analyses revealed that NCI-H441 and PC14-PE6 cells expressed EGFR but that the expression of EGF/TGF-alpha was high in NCI-H441 cells and very low in PC14-PE6 cells. Consequently, EGFR was activated in both tumor and tumor-associated endothelial cells in the NCI-H441 tumors but not in the PC14-PE6 tumors. Antagonism of EGFR signaling by treatment of mice with AEE788 decreased proliferation and increased apoptosis of both tumor cells and tumor-associated endothelial cells in NCI-H441 tumors but not in PC14-PE6 tumors. However, after transfection of PC14-PE6 cells with TGF-alpha, lung tumors derived from the transfected cells expressed and activated EGFR in both tumor and tumor-associated endothelial cells and tumors responded to treatment with AEE788. Collectively, these results strongly suggest that the response of human lung cancers growing orthotopically in mice to the inhibition of EGFR signaling is determined by ligand (EGF/TGF-alpha) expression by tumor cells. Our findings provide an additional explanation for the susceptibility of lung cancers to treatment with EGFR tyrosine kinase inhibitors.     

Distinct vascular actions of epidermal growth factor-urogastrone and transforming growth factor-alpha

We compared the effects of epidermal growth factor-urogastrone (EGF-URO) with those of transforming growth factor-alpha (TGF-alpha) on regional blood flow in the anesthetized dog in vivo, and on isolated canine helical coronary artery strips in vitro. Like EGF-URO, TGF-alpha was a potent stimulator of femoral arterial blood flow in vivo; and, when added to the tissue bath in vitro before an agonist, TGF-alpha like EGF-URO was a potent inhibitor of the contractile responses of helical coronary arterial strips to various smooth muscle agonists: norepinephrine (NE), prostaglandin F2 alpha (PGF alpha) and potassium chloride (KCl). Nonetheless, there were marked differences between EGF-URO and TGF-alpha in terms of the two biological responses measured. In terms of blood flow, although the ED50 for the increase in blood flow was similar for EGF-URO and TGF-alpha (ED50 = 0.4 micrograms EGF-URO equivalents per dose), the maximum responsiveness to TGF-alpha (130% increase in flow) was substantially greater than the maximum response to EGF-URO (70% increase in flow). Furthermore, TGF-alpha did not cause tachyphylaxis to subsequent doses of TGF-alpha, whereas a prior dose of either EGF-URO or TGF-alpha desensitized markedly the blood flow preparations to EGF-URO. Different desensitization patterns for the actions of EGF-URO and TGF-alpha also were observed in the arterial strip preparations. The inhibitory action of EGF-URO for agonist (NE, PGF2 alpha or KCl)-mediated contraction was diminished with repeated exposure of the tissue to EGF-URO, whereas the inhibitory action of TGF-alpha persisted with repetitive tissue exposure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recombinant human transforming growth factor-alpha stimulates the formation of osteoclast-like cells in long-term human marrow cultures.

Transforming growth factor-alpha (TGF-alpha) is synthesized by a variety of tumor cell lines and stimulates osteoclastic bone resorption in vitro. The mechanism by which TGF-alpha increases osteoclast activity is unknown. We used a human marrow culture system that forms osteoclast-like multinucleated cells (MNCs) to determine the effects of recombinant human TGF-alpha on MNC formation. Addition of 0.01 ng/ml TGF-alpha for the 1st week followed by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for the subsequent 2 wk significantly increased MNCs. Treatment of these cultures with TGF-alpha without later addition of 1,25(OH)2D3 did not increase MNC formation. Autoradiographic studies revealed that TGF-alpha stimulated proliferation of precursors for MNCs, and 1,25(OH)2D3 increased their rate of fusion into MNCs. Addition of murine epidermal growth factor (EGF) (0.1 ng/ml) followed by 1,25(OH)2D3 also significantly stimulated MNC formation. These data suggest that TGF-alpha and EGF may stimulate bone resorption by increasing the proliferation of osteoclast precursors, which leads to increased numbers of osteoclasts.     

TGF-β2/Smad2在人脑胶质瘤组织中的表达及意义

目的 研究转化生长因子β(TGF-β)信号传导通路中TGF-β2/Smad2在人脑胶质瘤组织中的表达和意义.方法 收集人脑胶质瘤组织样本59例,免疫组织化学法检测TGF-β2、Smad2、磷酸化Smad2(P-Smad2)及Ki-67蛋白在其中表达情况,反转录聚合酶链反应(RT-PCR)检测其中Smad2 mRNA的表达.结果 TGF-β2、Smad2、P-Smad2及Ki67蛋白与人脑胶质瘤病理级别呈正相关(P<0.01),各级别均数比较差异均有统计学意义(P<0.05);TGF-β2、Smad2、P-Smad2蛋白表达之间亦呈正相关(P<0.01);TGF-β2、Smad2及P-Smad2蛋白表达均与增殖指标Ki-67蛋白表达呈正相关(P<0.01).Smad2 mRNA表达与Smad2和P-Smad2蛋白表达呈正相关(P<0.05).结论 TGF-β2/Smad2蛋白表达随肿瘤病理级别增高表达增强,与胶质瘤的恶性进展有关.     

Transforming growth factor-alpha and human cancer

Human transforming growth factor-alpha TGF-alpha, a polypeptide growth factor which causes reversible transformation of normal cells, is composed of 50 amino acid residues, has a 30 to 40% amino acid homology to epidermal growth factor (EGF), and binds the EGF receptor. In human cancers, studies are beginning to show that TGF-alpha could serve as a tumor marker and as a marker for the malignant potential of a tumor. Thus far, the types of carcinomas with which abnormal TGF-alpha expression has been associated include liver, gastrointestinal, breast, skin, lung, brain and ovarian cancers. TGF-alpha may play a role in the processes involved with tumor initiation and tumor growth. In cell lines, TGF-alpha has been found to be associated with autocrine and paracrine types of cellular growth initiation and with increased levels of oncogene expression. In summary, the evidence concerning human TGF-alpha are that TGF-alpha could serve as a marker for human cancers and that an understanding of the basic actions of TGF-alpha could help to explain the self-sustaining nature of tumors.