Immunoreactive low-molecular-weight epidermal growth factor in urine of patients with renal cell carcinoma

Summary A specific heterogeneous enzyme-linked immunosorbent assay (ELISA) has been established in order to determine levels of low-molecular-weight epidermal growth factor (EGF) in the urine of patients with renal cell carcinoma who had undergone unilateral radical nephrectomy. Urine specimens, i.e., 20 pre- and postsurgical specimens from a group of patients and 22 from a control group, were assaved after the urine had been freed from high-molecular-weight proteins (>30kDa) and salts. EGF levels were expressed as urinary EGF/creatinine ratios, and a highly significant decrease (=0.0005 by Student's t-test) of urinary EGF was found in the patient group prior to surgery. The cancer patients also showed an additional loss of urinary EGF after unilateral nephrectomy (=0.0005 by Student's t-test). These data correlate with our previous findings that pro-EGF gene expression is decreased in human renal carcinoma and support the concept that low-molecular-weight urinary EGF is derived from high-molecular-weight kidney pro-EGF.Supported by a grant from Deutsche Krebshife, Bonn, FRG (W70/87 Pe-2).     

胆管癌表皮生长因子受体,增殖细胞核抗原的表达

为研究胆管癌组织中表皮生长因子受体（ＥＧＦＲ）、增殖细胞核抗原（ＰＣＮＡ）的表达及其生物学意义，并探讨ＥＧＦＲ表达与血型Ａ抗原的关系，通过应用免疫组织化学方法（ＡＢＣ法）检测３０例肝外胆管癌。结果发现１５例（５０％）为ＥＧＦＲ阳性，ＰＣＮＡ阳性７例（２３．３３％），对照组５例为非肿瘤胆总管，ＥＧＦＲ、ＰＣＮＡ均为阴性。胆管癌与非肿瘤胆总管组ＥＧＦＲ及ＰＣＮＡ表达率有显著差异，细胞分化差、有胆管外转移的胆管癌ＥＧＦＲ的表达率高于细胞分化好、无胆管外转移病例。胆管癌各组间ＰＣＮＡ表达率均无显著性差异。ＥＧＦＲ表达与血型Ａ抗原无关。结果提示：检测ＥＧＦＲ表达是判断胆管癌增生活性的有效手段，而ＰＣＮＡ尚需进一步研究。     

转化因子-α及表皮生长因子受体在胃肠道间质瘤中的表达

目的　研究表皮生长因子受体 (EGFR)及转化因子 (TGF α)与胃肠道间质瘤 (GIST)的发生发展关系。方法　采用免疫组织化学方法观察 3 1例GIST(其中 9例恶性间质瘤 ,8例良性间质瘤 ,14例潜在恶性间质瘤 )的EGFR、TGF α的表达情况。结果　EGFR在恶性间质瘤、潜在恶性间质瘤、良性间质瘤 3组中的免疫组织化学方法检出率分别为 88.89%、64 .2 8%、3 7.5 0 % ,后两组与恶性间质瘤组相比差异有显著性 (P <0 .0 5 )。 80 .65 %胃肠道间质瘤表达TGF α ,良性、潜在恶性、恶性的TGF α表达差异无显著性 (P >0 .0 5 )。所有EGFR阳性的GIST均TGF α表达阳性。结论　EGFR在恶性间质瘤中有较高水平的表达 ,在潜在恶性间质瘤中亦呈较高表达 ,表明EGFR在恶性GIST的发生发展中起着重要的作用。GIST存在生长因子自泌循环 ,可能是癌细胞失控生长的主要原因之一     

表皮生长因子受体Ⅲ型突变体在原发性胆囊癌中的表达及其意义

目的 检测表皮生长因子受体Ⅲ型突变体(EGFRvⅢ)在原发性胆囊癌中的表达,探讨其与胆囊癌发生的关系.方法 采用免疫组化SABC法检测68例原发性胆囊癌病人中EGFRvⅢ的表达水平,并运用免疫组化图像分析法进行半定量.结果 原发胆囊癌组织EGFRvⅢ表达的总阳性率为53%,其中腺癌的阳性率为51%.依据病理分级.EGFRvⅢ表达水平由高到低分别为Ⅲ级>Ⅱ级>Ⅰ级,其差异具有统计学意义(q=2.49,P=0.02,q=3.63,P<0.01,q=5.69,P<0.01).不同性别者EGFRvⅢ表达水平无显著差异(t=1.29,P=0.20);EGFRvⅢ表达与年龄无显著相关性(r=0.03,P=0.88).结论 EGFRvⅢ在原发性胆囊癌组织存在高表达.对胆囊癌的发生、发展起一定作用.     

Defining the role of the epidermal growth factor receptor in pancreatic cancer grown in vitro

BACKGROUND: The purpose of this study was to determine the effect of a novel epidermal growth factor (EGF) receptor tyrosine kinase inhibitor, Erlotinib, on pancreatic cancer cell lines of varying differentiation in vitro. METHODS: Six pancreatic cancer cell lines (AsPc-1, CAPAN-1, HPAC, HPAF-II, Mia PaCa-2, PANC-1) were grown in the presence of 50 microM or 100 microM of Erlotinib or recombinant EGF. Cell proliferation was determined using the MTT assay over 72 hours. The EGF receptor gene and protein expression were determined by polymerase chain reaction and immunohistochemistry respectively. RESULTS: All cell lines demonstrated the presence of the EGF receptor gene and its gene product. Five of six cell lines showed significant growth inhibition at 72 hours compared with controls (P <0.05). The EGF augmentation increased proliferation of each cell line but this increase was only significant in AsPc-1. CONCLUSIONS: Inhibition of EGF receptor is a valid therapeutic strategy in pancreatic cancer.     

表皮生长因子及其受体分布在青、老年大鼠肾切除术后留存肾代偿早期的改变

目的 观察表皮生长因子（EGF）蛋白及其受体（EGFR）表达的改变,比较青、老年大鼠留存肾代偿过程的差异。方法 雄性Wistar大鼠青年组60只,老年组32只。行左肾切除术;并分别于术后1、3、7、14d随机处死青年组各12只,老年组各8只。取右肾为代偿肾。EGF及EGFR免疫组织化学染色采用链菌素亲生物素蛋白－过氧化酶连接法。用IBSA－2000图像处理系统对EGFR含量进行半定量分析。结果 术后14d青、老年组留存肾增重分别为54．5％和14．2％。肾代偿时EGF由原局限性发布变为弥漫性分布,其表达增加程度以青年组为明显;EGFR蛋白分布量在布皮质均有增加,老年组增加较青年组迟缓。结论 EGF及EGFR在留存肾代偿早期起重要作用,肾代偿时,肾内EGF通过自分泌和旁分泌而发生作用。     

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。     

Epidermal growth factor receptor in adenocarcinoma of the kidney

Summary Epidermal growth factor receptor (EGF-R) was estimated in Hypernephroma by saturation analysis using 125-I EGF as ligand. Tissue levels of this oncogene related protein were increased five-fold (24 to 99 fmol/mg protein) in comparison with the surrounding tumor free tissue (3 to 18 fmoles/mg protein). There was no apparent correlation to the stage of tumor growth or tumor differentiation and there was no correlation of EGF serum levels with tumor growth. EGF serum levels in the tumor patients did not exceed levels in control patients.     

表皮生长因子受体相关蛋白在胃癌组织中的表达及临床意义

目的 观察表皮生长因子受体相关蛋白(ERRP)的表达以及细胞增殖在胃癌分化和发展中的作用.方法 观察47例患者胃癌的手术标本中ERRP的表达和定位,并将其与良性胃黏膜比较,确定他们与细胞增殖和分化的关系.检测3种不同的胃癌细胞株中ERRP的表达,并用表皮生长因子(EGF)诱导EGFR磷酸化激活MKN-28胃癌细胞,检测ERRP对此效应的作用.结果 与良性胃黏膜(66％标本阳性)比较,胃癌(33％标本阳性)中ERRP的表达显著降低.正常胃黏膜的ERRP染色评分是2.9(0.3),高分化、中度分化和低分化癌的评分分别是2.6(0.6)、0.9(0.6)和1.0(0.5),ERRP表达的降低与恶性程度的组织学分级呈负相关(P＜0.05).ERRP阴性癌细胞[35.3(1.1)％;P＜0.01]中增殖程度是ERRP附性癌细胞[9.4(0.6)％]的3.5倍,ERRP在癌细胞中的表达与细胞增殖也呈负相关.与源于非转移性癌的细胞AGC比较,源于转移性胃癌细胞MKN-28和NCI-N87中ERRP的表达量分别是其的1.7倍和2倍.外源性的ERRP蛋白明显抑制了EGF诱导的胃癌细胞MKN-28中EGFR的磷酸化,抑制程度为45倍.结论 ERRP的下调可能在胃癌分化和发展中起重要的作用.ERRP对肿瘤细胞增殖具有负调控作用,其抑制作用可能部分是通过减弱EGFR的活化来实现的.     

Epidermal growth factor in urine from patients with bladder cancer

Epidermal growth factor (EGF), a mitogenic polypeptide with a molecular weight of 6000, is excreted in human urine in nanomolar quantities. Recently, some reports showed that urothelial neoplasm was related to the concentration of EGF in urine. In this study, EGF concentration in urine was measured by enzyme-linked immunosorbent assay (ELISA) in 207 samples from 112 male patients (30–90 years old, median 66.2) who had previously been treated for bladder cancer. Then, we tried to clarify the significance of urinary EGF as a marker for recurrence of bladder cancer in comparison with urine cytology. The samples were collected on occasional follow up cystoscopy. Urine from nine age-adjusted males without urological disease was also measured to obtain normal control values. In 123 samples from patients without tumors, EGF concentrations in urine decreased with age. In 84 samples obtained from patients with recurrent tumor, EGF concentrations were significantly lower than those in 123 samples from patients without tumors (P < 0.001) Furthermore, EGF concentrations in longitudinal samples collected the same patients during tumor recurrence and at the times when no tumor was detected were measured in 56 patients. EGF concentrations in the samples collected during tumor recurrence was significantly lower than that in specimens collected when there was no tumor (P < 0.01). There were no significant differences between the same samples collected during tumor recurrence with regard to tumor grade, stage shape and number of tumors. However, EGF concentration in urine from patients with carcinoma in situ (CIS) was lower than that in specimens from patients without CIS. These results indicate the usefulness of determining the EGF concentration as a marker for detecting bladder cancer recurrence. Urine cytology was also examined in the same series and findings were compared with those of urinary EGF. On cytology, class IV and V were considered positive, and on urinary EGF, less than l0 ng/mgCr were considered positive. Sensitivity was 25% for cytology and 57% for urinary EGF, while specificity was 98% and 66%, respectively. The predictive positive value was 0.88 and 0.53, respectively. With the combined use of urinary EGF and cytology, the sensitivity, specificity and predictive positive value were 68%, 64% and 0.92, respectively. In conclusion, urinary EGF seems to be a useful marker for detecting bladder cancer recurrence if performed in addition to cytology. Received: 8 April 1999 / Accepted: 3 January 2000     

Expression of the epidermal growth factor receptor in fetal kidney

Formation of the human kidney begins at the 6th week of fetal life when the first generations of nephrons are generated from foci of metanephric mesenchyme through contact with the branches of the ureteric bud. This process requires a proliferative burst which must be tightly regulated by local signals. In this report, we review the evidence that the epidermal growth factor receptor molecule is an important arbiter of these events.     

肺癌中表皮生长因子受体过表达与女性、非吸烟、腺癌和基因突变的关系

目的探讨女性和非吸烟的肺腺癌标本中表皮生长因子受体（EGFR）过表达与EGFR基因突变的关系。方法应用组织微阵列和免疫组织化学方法检测137例国人非小细胞肺癌标本（鳞癌71例、腺癌66例）中EGFR的表达，采用测序的方法检测EGFR基因突变。结果EGFR过表达率在肺鳞癌中为63．4％显著高于腺癌的43．9％（P〈0．05），其与性别、吸烟情况无关，也与基因突变无关。结论EGFR的过表达率在女性、非吸烟、腺癌及存在EGFR突变的标本中未见升高，提示这些人群中EGFR抑制剂效果较好的原因与蛋白过表达无关。     

大蒜素对幽门螺杆菌阴性的慢性萎缩性胃炎患者血清表皮生长因子和胃黏膜病理、表皮生长因子受体的影响

目的观察大蒜素对幽门螺杆菌（Hp）阴性慢性萎缩性胃炎（CAG）患者血清表皮生长因子（EGF）及胃黏膜病理、表皮生长因子受体（EGFR）表达水平的影响。方法采用随机对照方法,将Hp阴性慢性萎缩性胃炎患者120例随机分为治疗组和空白对照组,其中治疗组60例患者给予大蒜素治疗,对照组60例患者给予与大蒜素剂型相同的安慰剂;疗程为24周,治疗前后两组患者均进行血清EGF、胃黏膜EGFR表达以及病理积分比较。结果治疗组患者大蒜素治疗后EGF、EGFR表达水平以及病理积分较治疗前降低,差异有统计学意义（P均〈0.05）;对照组患者治疗前后EGF、EGFR表达水平以及病理积分差异无统计学意义（P均〉0.05）。结论大蒜素对慢性萎缩性胃炎的病理积分有改善作用,且能够降低萎缩性胃炎EGF及EGFR的表达水平,这可能是其发挥作用的机制之一。     

非小细胞肺癌中表皮生长因子受体基因拷贝的检测及其临床意义

目的 检测国人非小细胞肺癌标本中表皮生长因子受体(EGFR)基因高拷贝的发生率及与临床特征的关系.方法 236例非小细胞肺癌标本制作成组织微阵列,使用Vysis公司的荧光原位杂交探针检测EGFR基因拷贝数.结果 193例标本得到结果 ,检测到EGFR基因高拷贝81例(占42.0%),其中42例(21.8%)为高多倍体,39例(20.2%)为基因扩增.其发生与病理、分期、性别、吸烟等临床特征无明显相关,与患者的1-3年生存率无明显相关.结论 国人肺癌中EGFR基因拷贝数的分布情况与西方人类似,与临床特征及预后无明显相关.     

GnRHR与EGFR在原发性肝癌组织中表达及意义

目的研究促性激素释放激素受体（GnRHR）和表皮生长因子受体（EGFR）在原发性肝癌组织中的表达及临床意义。方法应用免疫组织化SP及原位定量法,对30例原发性肝癌组织中GnRHR、EGFR的表达进行检测及半定量分析。结果在原发性肝癌各种不同分化的癌组织均显示不同程度的GnRHR和EGFR阳性免疫反应,原位定量显示GnRHR表达阳性27例（90.00%）,EGFR表达阳性15例（50.00%）,原位定量显示GnRHR的表达高分化13例、中分化9例、低分化5例,随着组织分化程度增高而增高,EGFR的表达高分化3例、中分化5例、低分化7例,随着组织分化程度增高而降低（P〈0.05）,并且GnRHR较EGFR阳性免疫反应强。结论 GnRHR与EGFR的表达量可能与原发性肝癌的发生及发展有关。     

Targeting epidermal growth factor receptor in head and neck cancer

It is well known that growth factors play an important role in normal cell proliferation by means of stimulation of growth factor receptors located on the surface of cells. Tumor cells express high levels of growth factor receptors that can theoretically serve as therapeutic targets in cancer treatment. Tyrosine kinase (type 1) growth factor receptors include the family of erbB receptors. The most extensively studied receptor in the erbB family is the human epidermal growth factor receptor (EGFR), also known as erbB1. Studies have shown that overexpression of EGFR is involved in the development and progression of head and neck squamous cell carcinoma (HNSCC). Blocking this receptor in HNSCC cell lines and animal models inhibits tumor growth. Strategies have been developed to target EGFR, including monoclonal antibodies, tyrosine kinase-specific inhibitors, ligand-linked immunotoxins, and antisense approaches. Laboratory studies and clinical trials are under way to explore the safety and efficacy of these various approaches in a variety of cancers, including HNSCC. Preliminary results from early phase clinical trials are encouraging and may lead to the incorporation of these EGFR targeting strategies into the management of HNSCC.     

RNA干扰靶向抑制表皮生长因子受体表达对大肠癌细胞增殖的影响

目的观察RNA干扰（RN加）技术能否有效抑制大肠癌LoVo细胞株表皮生长因子受体（EGFR）的表达以及对细胞增殖的影响。方法构建质粒表达载体pU6-EGFR-shRNA-1和pU6-EGFR-shRNA-2；脂质体瞬时转染后24、48、72、96、144h实时荧光定量PCR（Real Time PCR）和Western blot检测EGFR表达，流式细胞仪检测细胞周期和凋亡，并绘制细胞生长曲线；分5组：A组：Lov0细胞组；B组：Lipofectamine2000组；C组：对照载体HK组；D组：pU6-EGFR-shRNA-1组；E组：pU6-EGFR-shRNA-2组。结果D组E组细胞转染shRNA后mRNA和蛋白表达降低，G0～G1期细胞增加，S期细胞减少，细胞凋亡率增加，对数生长期延迟，以48h效果最显著，和A组B组C组比较差异有统计学意义（P〈0．05）；但随着时间的推移其干扰作用降低。结论两条EGFR-shRNA均可有效抑制大肠癌LoVo细胞EGFR表达，阻滞更多的细胞位于Go～G1期，促进细胞凋亡而抑制细胞增殖。     

支气管内超声引导纵隔淋巴结穿刺活检术检测非小细胞肺癌表皮生长因子突变

目的 探讨经气管超声引导内镜穿刺(EBUS-TBNA)纵膈淋巴结穿刺标本中表皮生长因子受体(EGFR)突变检测的可行性.方法 收集2010年2月至2010年7月全部26例经EBUS-TBNA纵膈淋巴结穿刺诊断为肺腺癌的标本.穿刺针为EBUS标准22G针,待涂片快速细胞学病理诊断腺癌后,在同一部位穿刺,将穿刺标本推入生理盐水中.经离心后首先提取组织DNA,采用胸外科优化的突变体富集法检测外显子19及21的突变.首先经过特异性消化野生型EGFR基因的限制性内切酶切割,再进行聚合酶链反应(PCR)扩增.因绝大部分野生型基因已断裂,无法作为PCR反应模板,使得扩增产物中突变型基因的比例大大增加.结果 全部26例患者均成功提取DNA,男16例,女10例,平均年龄62.1岁(34～ 79岁).经EBUS穿刺2组、4组、7组或10组淋巴结,诊断为肺腺癌,涂片标本均显示淋巴细胞背景中可见多量腺癌细胞.经改良突变体富集法检测示其中12例存在EGFR突变,突变率达到46.2％,7例为外显子19突变,5例为外显子21突变,余14例阴性全部标本均进行测序验证,14例阴性者测序也为阴性,12例突变者测序仅7例为阳性,余5例测序为阴性.全部12例EGFR突变患者中4例患者通过新辅助化疗后进行了根治性手术,术后对肿瘤标本再次检测EGFR基因突变,检测结果与术前相同.结论 采用EBUS-TBNA穿刺纵膈淋巴结组织标本来检测EGFR突变是可行的,通过高灵敏度的检测方法可获得更高的检出率.     

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。