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1.
Urinary immunoreactive epidermal growth factor (EGF) levels decrease, and renal immunoreactive EGF levels increase in rats with ischaemic acute renal failure (ARF). We investigated the immunohistochemical localization of EGF and EGF receptor in rabbits with ischaemic ARF to clarify the significance of renal EGF. Male New Zealand White rabbits underwent right nephrectomy prior to a 60 min renal artery clamp. At 3, 6, 24, 48, 72 and 96 h after ischaemia, serum urea nitrogen and serum creatinine were determined. Guinea pig anti-rabbit EGF antibody and monoclonal anti-EGF receptor antibody were used for the primary incubation. EGF was immunolocalized to the ascending limb of Henle and the distal convoluted tubule in the normal right kidneys. However, in the post ischaemic left kidneys at 6, 24, 48 and 72 h, immunoreactivity of EGF was associated with proximal tubules. In the normal kidneys, antibody to EGF receptor reacted with distal tubules and collecting ducts. In the ischaemic kidneys, EGF receptor was localized in the basolateral membrane in the proximal tubules. The expression of EGF and EGF receptor in renal tubules may play an important role in repair following ischaemic renal damage.  相似文献   

2.
Cbl proteins play important roles in downregulation of growth factor receptors by acting as ubiquitin ligases and multi-adapter proteins. Ligand-induced desensitization of the epidermal growth factor receptor (EGFR) has been shown to be controlled by Cbl. In the present study, we examined the expression of Cbl in gastric carcinomas and studied the correlation of Cbl expression with clinicopathological characteristics as well as EGFR expression. Cbl protein was expressed in 67% (82/122) of gastric carcinomas, and diffuse expression of Cbl was detected in 29% (35/122) of the cases. The incidence of cases with diffuse expression of Cbl was significantly higher in advanced cases (28/70, 40%) than in early cases (7/52, 14%) (P=0.0010). Diffuse expression of Cbl was significantly associated with metastasis of tumor cells in lymph nodes (P=0.0318). Diffuse expression of EGFR was significantly associated with depth of invasion (P=0.0057), lymph-node metastasis (P=0.0371) and tumor stages (P=0.0278). As the grades of Cbl expression became stronger, the cases with diffuse EGFR expression increased, the positive correlation being significant (P=0.049). All the cases with diffuse expression of Cbl and EGFR were found to show nodal metastasis and to be at an advanced stage. Moreover, the prognosis of the patients with synchronous diffuse expression of Cbl and EGFR was significantly poorer than that of the patients negative for Cbl and focal or negative for EGFR (P=0.0086). The expression of Cbl protein was clearly induced in gastric carcinoma cell lines by transforming growth factor- treatment. These results suggest that Cbl in connection with the EGFR system may be associated with stomach carcinogenesis, invasion and metastasis. Cbl may serve as a novel molecular marker for aggressive gastric carcinoma.  相似文献   

3.
Summary To determine the role of epidermal growth factor (EGF) receptors in thyroid tumorigenesis, EGF binding was compared in membranes from malignant and from benign thyroid tumors. Surgical specimens were obtained from 28 patients with thyroid carcinomas (3 papillary, 13 follicular, 6 undifferentiated, and 6 medullary carcinomas) and from 30 patients with benign thyroid tumors (15 scintigraphically functional and 15 nonfunctional nodules). In 30 cases normal tissue adjacent to the tumor was also obtained. EGF binding was seen to be increased not only in thyroid carcinomas but also in benign thyroid tumors, particularly in functional thyroid adenomas. The highest EGF binding was found in undifferentiated carcinomas. A direct comparison of the EGF binding characteristics in tumor and adjacent normal thyroid tissue revealed that the increased binding of EGF is due mainly to an increase in the number of binding sites rather than an alteration in receptor affinities. EGF binding capacities were 18.4±16.7 fmol/mg protein in thyroid carcinomas and 10.5±5.2 fmol/mg in the corresponding normal tissue (P<0.05, K d 0.84±0.26 nM, n=11). In autonomously functioning thyroid adenomas binding capacities were 14.2±8.2 fmol/mg in the nodules and 8.9±4.8 fmol/mg in normal tissue (P < 0.01, K d 0.73±0.62 nM, n = 15). In conclusion, EGF receptor levels are increased not only in malignant thyroid tumors but also in well-differentiated benign thyroid nodules. The data indicate that an increased expression of EGF receptors, although likely to be important in the regulation of thyroid growth in vivo, is not by itself associated with malignant cell transformation and loss of differentiated function.Abbreviations EGF epidermal growth factor - EGFr epidermal growth factor receptor - TGF- transforming growth factor- Dedicated to Prof. Dr. G. Paumgartner on the occasion of his 60th birthday  相似文献   

4.
The epidermal growth factor receptor in human pancreatic cancer.   总被引:9,自引:0,他引:9  
The epidermal growth factor receptor (EGFR) and its ligands are thought to be important in the control of proliferation of many epithelial systems, including the exocrine pancreas. Abnormalities in expression of two of the known ligands of the EGFR, transforming growth factor alpha and epidermal growth factor, occur frequently in ductal adenocarcinoma of the human pancreas. We have examined an archival series of cases of pancreatic pathology for expression of the EGFR using the anti-EGFR antiserum 12E and found that there is almost ubiquitous overexpression of EGFR in pancreatic cancer and in chronic pancreatitis. Southern blot analysis showed no evidence of amplification or rearrangement of the EGFR gene. We conclude that an autocrine loop involving the EGFR system may be involved in the genesis of both neoplasia and reactive hyperplasia of pancreatic ductal epithelium.  相似文献   

5.
We examined the immunofluorescence labelling epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR), as well as differential interference contrast (DIC) images, during the morphogenesis of filiform papillae and the keratinization of the lingual epithelium of rats on semi-ultrathin sections of epoxy resin-embedded samples using laser-scanning microscopy. We also examined semi-ultrathin sections of epoxy resin-embedded, toluidine blue-stained samples by light microscopy to obtain details of cell histology and morphology. No immunoreactivity specific for EGF and EGFR was detected on the lingual epithelium of fetuses on days 12 and 16 after conception (E12 and E16), during which time the number of layers of cuboidal cells in the lingual epithelium increased from one to several. Immunoreactivity specific for EGF and EGFR was first detected on the lingual epithelium of fetuses at birth or on postnatal day 0 (P0). Immunoreactivity specific both for EGF and EGFR appeared in the connective tissue and the basal cells of the papillary and interpapillary cell columns. The lingual epithelium was composed of stratified squamous cells. The rudiments of filiform papillae were compactly arranged and interpapillary cell columns were very narrow. Immunoreactivity specific for EGF and EGFR was distinct on the cell membrane of basal cells of the papillary cell column and weakly positive on the cell membrane of basal cells of the interpapillary cell column on postnatal day 21 (P21). Thus, the patterns of immunoreactivity of EGF and EGFR differed as the filiform papillae developed. Filiform papillae developed gradually from P0 to P21. The width of interpapillary spaces also increased during this period. These observations indicate a possibility that EGF might affect the expression of keratins in the lingual epithelium via epithelium-mesenchymal interactions.  相似文献   

6.
Expression of epidermal growth factor receptors by odontogenic jaw cysts   总被引:5,自引:0,他引:5  
The expression of epidermal growth factor receptor (EGFr) by odontogenic epithelium was studied in odontogenic cysts (n=35), ameloblastoma (n=6), and periapical granulomas containing proliferating epithelial rests of Malassez (n=7) using a panel of monoclonal antibodies to EGFr (clone E30, F4 and C11) known to react with formalin-fixed, paraffin-embedded sections. Odontogenic epithelium in all specimens demonstrated immunoreactivity with all three antibodies. Clone E30 consistently gave the most intense, membrane located staining pattern of the three antibodies tested. Generally, staining of epithelial cells progressively diminished with movement away from the basal cell layers toward the most superficial layers of cystic lining or centre of epithelial rests and tumour islands. Developmental odontogenic cysts (odontogenic keratocysts,n= 13; dentigerous cysts,n=11) and ameloblastoma (follicular type,n=5; unicystic type,n=1) expressed a higher level of EGFr staining than inflammatory cysts (radicular cysts,n=11) and the proliferating epithelial rests in periapical granulomas. However, foci of weak EGFr staining of odontogenic keratocyst lining, similar to that seen in radicular cysts, were found in areas associated with inflammation. In addition, epithelial rests not associated with inflammatory cell infiltrates exhibited stronger reactivity for EGFr than proliferating rests within periapical granulomas. These results indicate that the level of EGFr expression by odontogenic cysts and rests is related to the presence of inflammation within adjacent connective tissue and that there is no detectable difference in receptor expression between developmental cysts and ameloblastoma.  相似文献   

7.
Summary Using the monoclonal antibody EGFR1, normal mammary gland and a series of 213 unselected primary breast tumours were investigated immunohistochemically for expression of epidermal growth factor receptor (EGFR). In normal breast EGFR was expressed in variable patterns in lobular, ductal, and myoepithelial cells. In fibroadenoma, EGFR was detectable in variable numbers of ductal and myoepithelial cells and in stromal fibroblasts. The myoepithelial compartment of 2 cystosarcomas phyllodes also expressed EGFR. Among the 197 carcinomas tested only 20.3% contained EGFR expressing tumour cells which represented a minority in 12.2%, the majority in 2.1%, and the entire neoplastic population in 6.1% of the cases. Again, non-neoplastic ductal remnants often contained EGFR positive myoepithelial and ductal cells whereas stromal fibro-blasts expressed EGFR only occasionally. We conclude that in contrast to the normal state, EGFR-expression is a rather rare phenomenon in breast carcinoma cells, positively correlated with a declining grade of differentiation (p<0.025) and at least occasionally associated with squamous metaplasia within the tumour, that EGFR expression is not exclusively restricted to cells of the epithelial lineage, and that EGFR may have other functions not related to proliferation, since it is commonly detectable in myoepithelial cells.  相似文献   

8.
表皮生长因子受体在肝细胞癌及胆管细胞癌中的表达   总被引:2,自引:0,他引:2  
目的:比较表皮生长因子受体(EGFR) 在肝细胞癌及胆管细胞癌中表达的差异。方法:采用免疫组化及原位杂交方法检测92 例肝细胞癌及50 例胆管细胞癌组织中EGFR蛋白及m RNA的表达。结果:92 例肝细胞癌标本中,42 例EGFR 蛋白或mRNA阳性,占45-7% 。50 例胆管细胞癌中,36 例EGFR蛋白或mRNA 阳性,占72-0 % 。结论:与肝细胞癌相比,胆管细胞癌的发生、发展与EGFR 表达增高的关系更加密切。  相似文献   

9.
Summary Epidermal growth factor and its receptor (EGFR) constitute an important and well-characterized mitogenic system in various ectodermal tissues including glial cells. Over-expression of the EGFR due to gene amplification has been reported in primary brain tumours of glial origin. Using a monoclonal antibody to the EGFR and immunohistochemical analysis, we examined the expression and distribution of EGFR in 103 astrocytic tumours. In addition, selected tumours were studied by Western blotting using a polyclonal antibody to EGFR and by Southern blot analysis. Glioblastomas (WHO grade IV) showed EGFR expression in 37% of cases, whereas pilocytic (WHO grade I), low-grade (WHO grade II) or anaplastic astrocytoma (WHO grade III) were invariably EGFR negative. Generally, there was a close correlation between the presence of EGFR gene amplification and over-expression of receptor protein. Different patterns of immunoreactive cells and significant intratumour heterogeneity of EGFR expression were observed in glioblastomas. The specific association of EGFR over-expression with glioblastoma may provide a useful diagnostic tool for distinguishing anaplastic astrocytoma (WHO grade III) and glioblastoma multiforme (WHO grade IV).  相似文献   

10.
The coexistence of gastrointestinal stromal tumors (GISTs) and pregnancy is very rare. We are the first to add to the literature a case report of GIST occurring during pregnancy with immunohistochemical staining for epidermal growth factor receptor (EGFR) and progesterone receptor (PgR). A role of PgR and EGFR in tumor growth should not be excluded, and these findings indicate that the expression of these receptors could provide pertinent biological information required to determine adequate therapeutic regimens. In conclusion, considering that GIST occurring during pregnancy is a rare event, with frequent delay in diagnosis, it is important to consider this diagnosis for early recognition, correct diagnosis, and a better outcome.  相似文献   

11.
Male breast carcinomas are probably hormone-dependent, but receptor studies are few because this is a relatively rare tumour. We have studied 21 cases of male breast carcinoma immunohistochemically for oestrogen receptor (ER) and epidermal growth factor receptor (EGFR) expression employing the antibodies ER-ICA and 12E on formalin-fixed, paraffin-embedded material. In our series, 86 per cent of male breast cancers were ER-positive and 76 per cent were EGFR-positive. Male breast carcinomas do not exhibit the inverse correlation between ER and EGFR expression that characterizes female breast carcinomas. Owing to the limitations of a small series, we were unable to comment on the relationship between ER and EGFR expression and patient survival. However, the relatively high incidence of ER expression may provide a growth advantage for this tumour in a male environment characterized by low levels of oestrogen. In addition, high EGFR expression may also contribute to a poor prognosis independent of ER status.  相似文献   

12.
There is currently no prognostic tool that reliably predicts the risk of metastasis in cutaneous squamous cell carcinoma, most of which occur in the head and neck region. Epidermal growth factor receptor has received much interest in recent years with the advent of epidermal growth factor receptor-targeted molecular therapy in clinical oncology. We investigate the role of epidermal growth factor receptor as a biomarker for head and neck cutaneous squamous cell carcinoma. Using immunohistochemistry and fluorescence in situ hybridization, we assessed the epidermal growth factor receptor protein expression and gene copy in 3 groups of head and neck cutaneous squamous cell carcinoma: primary lesions not associated with metastasis (P), primary lesions associated with subsequent metastasis (PM), and metastatic nodal disease (M). Epidermal growth factor receptor overexpression was detected in 36% and 79% of P and PM cases, respectively. Epidermal growth factor receptor overexpression was significantly associated with PM (P = .03) and was found to be an independent prognostic factor for metastasis on multivariate analysis (P = .05). However, epidermal growth factor receptor overexpression was only maintained in 47% of cases in the M group. None of the 27 cases that overexpressed the epidermal growth factor receptor protein showed gene amplification: the results were uninterpretable in 2, and polysomy and balanced disomy were detected in 5 and 20 cases, respectively. These observations may have important prognostic and therapeutic implications for head and neck cutaneous squamous cell carcinoma.  相似文献   

13.
Summary An immunohistochemical study of the epidermal growth factor (EGF) receptor in non-neoplastic pleural mesothelium (35 cases) and in human malignant mesothelioma (36 cases) was made, using a murine monoclonal antibody OM-11-951. All malignant mesotheliomas and non-neoplastic pleural biopsies exhibited a strong cytoplasmic immunoreactivity in mesothelial cells. Nuclear immunoreactivity was detected in mesothelial cells of all specimens of both malignant and non-neoplastic pleura. No statistically significant differences were found between malignant mesothelioma and non-neoplastic pleural mesothelium. There were differences, between the three subtypes of mesothelioma, in the number of cells that exhibited nuclear staining. Statistically significant differences were noted between the epithelial subtype and the mesenchymal subtype (P< 0.005), epithelial subtype versus the mixed cell type (P< 0.005) and between the mesenchymal component of the mixed cell type and the mesenchymal type (P<0.0005). We conclude that there is strong expression of EGF receptor in both malignant mesothelioma and in non-neoplastic pleural mesothelium. Different staining patterns are seen when comparing the different subtypes of mesotheliomas with each other. EGF receptor expression cannot be used to distinguish between malignant and benign mesothelium.  相似文献   

14.
目的 探讨宫颈癌组织中表皮生长因子受体(epidermal growth factor receptor,EGFR)和环氧合酶2(cyclooxygenase,COX-2)蛋白的表达及其与临床病理特征的关系.方法 采用免疫组化的方法分别检测正常宫颈、宫颈癌中EGFR和COX-2蛋白的表达.结果 EGFR和COX-2蛋白的在宫颈癌组织中的阳性表达率,均显著高于正常宫颈组织.EGFR和COX-2的阳性表达均与患者的年龄及肿瘤大小无关(P>0.05).多元生存分析显示,EGFR和COX-2是独立的预后因子,相对危险度分别为2.52(P=0.004)和1.88(P=0.039).结论 EGFR和COX-2在宫颈组织中的表达水平可能与肿瘤的发生、发展、浸润和转移密切相关,可作为宫颈癌恶性程度判断和预后的重要指标.  相似文献   

15.
Summary The expression of epidermal growth factor (EGF) was examined on various human tissues by radioimmunoassay, immunohistochemistry and Northern blot analysis. Immunoreactive EGF was found in most of the human tissues by radioimmunoassay at various levels. Large quantities of EGF were detected in the kidney and thyroid gland. Immunohistochemically, EGF immunoreactivity was detected mainly in the epithelial cells of the lung, stomach, duodenum, pancreas, kidney, pituitary gland, thyroid gland, mammary gland, ovary, uterus and placenta. Weakly EGF-positive cells were also found in the adrenal gland. The results of EGF-immunostaining were not always consistent with the data from radioimmunoassay. We consider that the amount of EGF measured by radioimmunoassay reflects the density of EGF-positive cells in the tissues and the concentration of EGF in individual EGF-positive cells. Furthermore, EGF mRNA was expressed in the salivary gland, thyroid gland, mammary gland and kidney. It is thus evident that EGF is produced by a variety of human tissues. The kidney expressed exceptionally high levels of EGF mRNA which was about one-tenth of the expression in mouse submandibular gland, suggesting that most of EGF in the urine is produced and secreted by the epithelial cells of renal tubules.  相似文献   

16.
It has been well established that tumor-associated macrophages (TAMs) play a tumor-promoting role in endometrial endometrioid adenocarcinoma (EEC). However, the association with TAMs and the triple-negative phenotype (TNP) in EEC has not yet been reported. We used immunohistochemistry to examine the expression of CD68, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) in 186 cases of EEC. Fluorescent in situ hybridization (FISH) was also used for HER2 amplification, and the association with TAMs count, EGFR expression, and triple-negative phenotype was analyzed. Twenty-eight of 186 patients (15.05%) had the TNP. It was associated with advanced stage disease (P < 0.0001), high grade disease (P < 0.0001), depth of myometrial invasion (P = 0.003), pelvic lymph node metastasis (P < 0.001), lymphovascular space invasion (P = 0.001), and EGFR expression (P = 0.032). Margin TAMs count was also significantly increased in the TNP-positive group, the EGFR-positive group, and the PR-negative group (P < 0.001, respectively). The TNP was associated with a significantly worse overall survival (OS) (log rank test, P = 0.018). The estimated 5-year OS of patients with TNP was 59.1%, while that without TNP was 78.5%. Multivariate analysis showed high margin TAMs, and the histopathological grades were significantly associated with OS. The TNP in EEC is associated with poor prognostic surgical–pathological factors, worse prognosis, as well as with high margin TAMs and overexpression of EGFR, which may serve as potential targeted therapies for the special phenotype in EEC.  相似文献   

17.
目的 探讨干扰表皮生长因子受体(EGFR)的磷酸化过程对裸鼠乳腺癌移植瘤生长的影响及其作用机制.方法 建立裸鼠乳腺癌移植瘤模型,成型后随机分为Ad5-hSulf1组、Ad5-EGFP组和对照组,干预治疗后,测量计算移植瘤生长率,采用免疫组化法检测各组裸鼠移植瘤hSulf-1、EGFR和p-EGFR阳性表达,采用Western blot法检测各组裸鼠移植瘤hSulf-1、EGFR和p-EGFR蛋白表达.结果 Ad5-hSulf1组裸鼠注射治疗后第14天、21天和28天的肿瘤生长率[(165.9±23.8)%,(172.6±25.9)%,(377.3±30.5)%]明显小于同期的对照组,差异均具有统计学意义(t=12.153,21.247,14.587;P =0.000).Ad5-hSulf1组裸鼠移植瘤p-EGFR阳性表达率(46.7%)和蛋白表达[(52.7±7.4)%]明显低于Ad5-EGFR组和对照组,差异均有统计学意义(x2=8.146,t=7.384,7.587;P =0.004、0.000、0.000).结论 使用hSulf1基因抑制乳腺癌细胞的EGFR磷酸化过程,可产生明显的肿瘤抑制效应,对寻求肿瘤基因治疗的一个很有潜力的靶点具有很好的借鉴参考意义.  相似文献   

18.
To evaluate the clinical significance of the expression of epidermal growth factor receptor (EGFr) in oral squamous cell carcinoma (SCC), 100 formalin-fixed, paraffin-embedded cases of this tumour and ten samples of normal oral mucosa were immunostained with a monoclonal anti-EGFr antibody using an immunoalkaline phosphatase (APAAP) technique. EGFr immunoreactivity was detected in 36 of 100 tumours and in all samples of normal mucosa. Tumour cells demonstrated distinct membrane staining in 14 cases and predominantly cytoplasmic staining in 22 additional cases. EGFr was exclusively localized on the cell membrane of normal epithelial cells. Kaplan–Meyer survival curves and Cox proportional hazard regression models were used to assess overall survival and disease-free survival. A significant positive correlation was shown between EGFr membranous immunoreactivity and prolonged survival, in both univariate and multivariate analyses. Accordingly, patients with oral SCC showing down-regulated expression of membranous EGFr, who are more likely to suffer recurrence and death, should be strictly followed up and possibly treated with more aggressive therapeutic regimens. © 1998 John Wiley & Sons, Ltd.  相似文献   

19.
目的 探讨肺腺癌CT征象对表皮生长因子受体(EGFR)基因突变的预测价值.方法 回顾性分析200例经手术切除的肺腺癌患者的CT资料,统计其术后病理标本的EGFR基因检测结果,分析两者之间的相关性.结果 单因素分析显示非吸烟、女性患者、CT征象中的含气支气管征及较小肿瘤直径与肺腺癌EGFR基因突变存在明显相关性,突变组与野生组的差异均有统计学意义(P<0.05),EGFR基因突变组肺腺癌磨玻璃密度(GGO)发生率高于野生组,但差异无统计学意义(P>0.05),其他临床及CT征象如年龄、分叶征、毛刺征、钙化、空洞、胸膜凹陷征均与EGFR基因突变无关,突变组与野生组的差异均无统计学意义(P>0.05).Logistics回归分析显示非吸烟及含气支气管征与EGFR基因突变明显相关,突变组与野生组的差异均有统计学意义(P<0.05),而性别及肿物大小与EGFR基因突变与否无明显相关性,突变组与野生组的差异均无统计学意义(P>0.05).结论 非吸烟、含气支气管征可作为肺腺癌EGFR基因突变的预测因素.  相似文献   

20.
目的:构建异种EGFR蛋白疫苗并研究其抗肿瘤效果.方法:用PCR方法获得鸡EGFR胞外片段, 与pGEX- 4T-2载体连接, 并在E.coli BL21(DE3)中表达鸡的EGFR胞外片段与GST的融合蛋白, 融合蛋白经Ni2 亲和层析柱纯化、复性后, 免疫小鼠, 免疫3次后, 接种小鼠Lewis细胞, 观测肿瘤生长情况, ELISA检测小鼠血清中抗EGFR蛋白的抗体效价.结果:成功构建了EGFR胞外段基因的原核表达载体; SDS-PAGE显示成功表达了目的融合蛋白; 融合蛋白免疫小鼠后, ELISA法检测到特异性抗EGFR抗体; 实验组与对照组肿瘤体积的比较结果显示, 融合蛋白疫苗能够在一定程度上抑制肿瘤的生长.结论:异种EGFR蛋白能够克服免疫耐受问题, 诱导机体产生抗体, 有一定的抗肿瘤效果, 为后续的肿瘤疫苗研究打下了基础.  相似文献   

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