EGF、TGF-α及其受体在垂体瘤中的表达

垂体瘤的形成受多步骤多信号途径调节.由于许多生长因子参与细胞的生长分化及功能调节[1],所以生长因子及其受体的异常可能有助于垂体瘤的发展.本研究旨在证明垂体瘤中有表皮生长因子受体(epidermolgrowthfactorreceptor,EGFR)及其配体EGF、TGF α的表达和它们的自分泌/旁分泌刺激机制可能对垂体瘤的发生、发展的作用.     

垂体瘤中EGF、TGF-α及其受体的表达

目的：揭示垂体瘤中生长因子的生长刺激机制,为其受体拮抗剂的治疗应用提供实验依据。方法：用免疫组织化学方法研究了３０例垂体瘤中ＥＧＦＲ及其配体ＥＧＦ、ＴＧＦ－α的表达。结果：大部分功能性腺瘤及所有非功能性腺瘤均有ＥＧＦＲ的表达,大部分腺瘤中有ＥＧＦ、ＴＧＦ－α表达,但它们的表达呈多相性,即免疫阳性细胞的分布疏密不一、细胞免疫染色浓淡不一、ＥＧＦＲ及其配体在不同瘤中的表达方式不一;免疫组化结果与肿瘤的     

表皮生长因子受体家族与肿瘤关系的研究进展

细胞膜上具有酪氨酸激酶活性(ｔｙｒｏｓｉｎｅｋｉｎａｓｅａｃｔｉｖｉｔｙ)的跨膜蛋白受体在细胞内信号转导中起着较为重要的作用。该激酶活性启动了一系列导致细胞增殖和分化的信号级联(ｓｉｇｎａｌｃａｓｃａｄｅ)反应的发生,而表皮生长因子(ＥＧＦ)受体家族是涉及?..     

胃癌上皮生长因子及其受体与雌激素受体的表达及相互关系

用免疫组化ＡＢＣ方法，检测胃癌和正常胃粘膜中上皮生长因子（ＥＧＦ）及其受体（ＥＧＦＲ）、雌激素受体（ＥＲ）的表达。结果：６４例胃癌中，ＥＧＦ阳性３９例（６０．９％），ＥＧＦＲ阳性３３例（５１．６％），ＥＲ阳性１２例（１８．８％）；５８例正常胃组织中，ＥＧＦ、ＥＧＦＲ阳性各３例，ＥＲ阴性。癌与正常对照组间差异有显著性（Ｐ＜０．０５）。提示，ＥＧＦ、ＥＧＦＲ、ＥＲ与胃癌有关。胃癌ＥＧＦ、ＥＧＦＲ的阳性率又非常显著高于ＥＲ（Ｐ＜０．００５），说明ＥＧＦ、ＥＧＦＲ在胃癌发展中的调节作用远较雌激素重要。结果还提示，ＥＧＦ、ＥＧＦＲ、ＥＲ的相互关系影响胃癌细胞的发生、种植和转移。     

原发性肝癌表皮生长因子受体和雄激素受体的表达及其关系

原发性肝癌表皮生长因子受体和雄激素受体的表达及其关系程计林１＊刘宝玲２牛正先１黄孝立１杜晓光表皮生长因子（ＥＧＦ），通过与其受体—表皮生长因子受体（ＥＧＦＲ），特异性结合而发挥调节多种细胞增殖、分化的功能。ＥＧＦＲ的组织学分布较广泛，近发现某些肿瘤细...     

易瑞沙在24例化疗后进展的晚期非小细胞肺癌中的作用

背景与目的 易瑞沙（Iressa）是小分子表皮生长因子受体酪氨酸激酶抑制剂，主要用于治疗晚期非小细胞肺癌（NSCLC）。本研究探讨易瑞沙单药治疗化疗后进展的晚期非小细胞肺癌的疗效与不良反应。方法 24例化疗后进展的晚期NSCLC患者接受治疗，其中二线以上治疗后进展者占62．5％。易瑞沙250mg口服，每日1次，服用至疾病进展或出现不可耐受的不良反应。治疗后每4周复查一次，16周后每8周复查一次。结果本组24例患者均可评价疗效。其中完全缓解1例，部分缓解8例，无变化3例，进展12例。有效率为37．5％，稳定率为12．5％，临床获益率为50．0％，中位肿瘤进展时间为87天。随访2年，1和2年生存率分别为33．3％和12．5％。常见不良反应为Ⅰ、Ⅱ度皮肤改变和腹泻，未发生Ⅲ度以上不良反应。有2例患者因怀疑发生肺部间质性改变而结束治疗。结论 易瑞沙治疗化疗后进展的晚期NSCLC的疗效显著，不良反应轻，是晚期NSCLC患者二、三线用药的最佳选择之一。     

表皮生长因子受体抑制剂在大肠癌治疗中的应用

结直肠癌的发病率和死亡率均较高各种生长因子、生长因子抑制剂、生长因子受体在结直肠癌细胞的增殖、发展中起着重要的作用.65%～70%的结直肠癌中存在表皮生长因子受体邋(EGFR)的表达.多个研究显示,EGFR在细胞内信号传导过程中具有重要作用,EGFR的表达与结直肠癌的病情进展、预后密切相关,针对EGFR信号传导通路的治疗药物可抑制细胞的增殖,这些药物包括抗EGFR单克隆抗体、酪氨酸激酶抑制剂等,本文综述了这些表皮生长因子受体抑制剂在大肠癌治疗中的应用.     

表皮生长因子受体表达与乳腺癌激素受体水平和预后的关系

应用免疫组化ＡＢＣ方法研究７５例乳腺癌冰冻组织表皮生长因子受体（ＥＧＦＲ）的表达，结合临床资料和ＥＲ、ＰＲ测定结果进行分析，探讨ＥＧＦＲ表达与乳腺癌预后的关系。结果表明，ＥＧＦＲ阳性３０例（４０％），ＥＧＦＲ表达与肿瘤大小、腋淋巴结状况，临床分期和年龄无关，与ＥＲ、ＰＲ存在着显著的负相关（Ｐ＜０．００５）。全组中位随诊时间为６０个月，ＥＧＦＲ阳性组术后总生存率明显低于阴性组（Ｐ＜０．００１）。在无腋淋巴结转移的病例中，ＥＧＦＲ阳性组和阴性组术后生存情况也有显著差异（Ｐ＜０．０１），提示ＥＧＦＲ表达与乳腺癌不良的预后有关。调整分析乳腺癌有关的预后因素，各组病例中均以ＥＧＦＲ表达阳性组的预后为差，说明ＥＧＦＲ对乳腺癌预后具有独立的作用，不受其他因素的影响。经Ｃｏｘ模型多因素分析显示，ＥＧＦＲ和腋淋巴结受累与否是对乳腺癌术后生存情况有显著性影响的两个因素。     

表皮生长因子受体的表达与喉癌预后关系的初步研究

采用免疫组化ＬＳＡＢ法，用抗ＥＧＦ－Ｒ单克隆抗体对３８例喉鳞状细胞癌进行标记，用图像分析技术对染色结果定量分析， 阳性单位ＰＵ值代替染色级别。结果显示：喉鳞状细胞癌Ⅲ极的ＰＵ值明显高于Ⅰ－Ⅱ级的ＰＵ值，淋巴结转移组的ＰＵ值高于无淋巴结转移组的ＰＵ值，取得完整随访资料３４例，绘ａｐｌａｎ－Ｍｅｉｅｒ生存曲线，经Ｌｏｇｒａｎｋ检验，ｘ＾２＝８．６２，Ｐ〈０．０５。     

癌变和增生前列腺组织中雄激素与EGFR之间的相关关系

为探讨雄激素与ＥＧＦＲ在前列腺增生及癌变过程中相互关系，应用免疫组化方法检测ＥＧＦＲ和ＡＢＳ（雄激素结合位点）在前列腺组织中表达。结果显示：ＥＧＦＲ和ＡＢＳ在前列腺增生和癌变组织中表达均显著高于正常前列腺组织；而且ＥＧＦＲ表达与肿瘤病理分级正相关。ＥＧＦＲ与ＡＢＳ表达之间在正常组织中呈负相关、增生组织中无相关而癌变组织中呈正相关。研究表明：ＥＧＦＲ和ＡＢＳ异常表达及两者之间调控关系紊乱可能是前列腺增生和癌变的发生发展重要原因之一。     

Study of the Correlation of EGFR and K-RAS Gene Mutations with Its Protein Expression in Non-small Cell Lung Cancer

OBJECTIVE To investigate gene mutations of epidermal growth factor receptor (EGFR) and K-RAS (Kirsten rat sarcoma viral oncogene) in Chinese patients with non-small cell lung cancer (NSCLC), and study the correlation with its protein expression and its clinical significance on gefitinib. METHODS Detect the EGFR and K-RAS gene mutations status by gene sequencing and use the method of Immunohistochemistry to detect EGFR and K-RAS protein expression. RESULTS The frequency of EGFR mutations was 33%, mainly located in exon 19 and exon 21. The frequency of K-RAS mutations was 5.5%, mainly located in codon 12. There was no case which both had EGFR and K-RAS mutations, suggesting a mutually exclusive relationship between the two. EGFR mutations are more common in adenocarcinomas (particularly those with bronchioloalveolar features), nonsmokers and females. 16% were detected EGFR positive expression and had no correlation with EGFR mutation (P > 0.05), but had significant correlation with mutation in exon 19 (P < 0.05). The frequency of K-RAS positive expression was 52.5% and had no correlation with K-RAS mutation (P > 0.05). Twelve (8 cases were protein-negative) out of 15 gefitinib-treated NSCLC patients with disease control carry EGFR mutations. CONCLUSION EGFR protein expression has some correlation with exon 19 mutations. Combined detection of EGFR and K-RAS gene mutations can help clinicians to choose patients who may benefit from EGFR tyrosine kinase inhibitor (EGFR-TKI) and to predict the response and prognosis of gefitinib.     

EGFR and EGFRvIII Expression in Primary Breast Cancer and Cell Lines

EGFRvIII is a constitutively activated truncated variant of the epidermal growth factor receptor (EGFR) which has been shown to increase tumorgenicity. There are conflicting reports on the extent of EGFRvIII expression in tissues which may in part stem from the use of different assay methodologies. We investigated the expression of both EGFRvIII and wild-type EGFR (EGFRwt) in cell lines and primary breast cancers. First, we used a RT-PCR assay that can simultaneously measure EGFRwt and EGFRvIII mRNA to screen 55 tumor cell lines. We show that except for EGFRvIII transfected cells, only EGFRwt was detected. We then validated a real-time PCR assay and used this to screen 170 formalin fixed paraffin-embedded primary breast cancers for evidence of EGFRwt and EGFRvIII expression. No samples were positive for EGFRvIII expression except for control transfectants and glioblastomas. In contrast, EGFRwt was expressed at varying levels in the majority of samples tested. We conclude that the expression of EGFRvIII is extremely rare in breast cancer and therefore it does not contribute to the malignant phenotype.     

埃克替尼对表皮生长因子受体突变型晚期非小细胞肺癌的临床疗效观察

目的 探讨埃克替尼对化疗后表皮生长因子受体(EGFR)突变型晚期非小细胞肺癌的临床疗效.方法 选取60例EGFR突变型晚期非小细胞肺癌患者,随机分为对照组和试验组,对照组采用常规化疗干预,试验组在一线化疗基础上口服盐酸埃克替尼片,125 mg,3次/d,观察比较临床总有效率、生存质量评分及不良反应差异,观察血浆血管内皮生长因子(VEGF)、细胞间黏附分子-1(ICAM-1)及肿瘤标志物[鳞状细胞癌相关抗原(SCC-Ag)、癌胚抗原(CEA)、癌抗原125(CA125)]含量差异.结果试验组总有效率(60.00%)及总控制率(86.67%)显著高于对照组(P<0.01);生存质量评分(123.84±32.63)明显低于对照组(P<0.05);VEGF水平(21.27±1.76)及ICAM-1水平(328.23±28.81)明显低于对照组(P<0.05);肿瘤标志物SCC-Ag(2.56±0.32)、CEA(5.49±1.55)、CA125(21.37±1.87)明显低于对照组(P<0.05);不良反应皮疹(16.67%)、骨髓抑制(3.33%)、腹泻(16.28%)、口腔溃疡(13.33%)发生率明显低于对照组(P<0.01).结论埃克替尼能有效治疗EGFR突变型晚期非小细胞肺癌,降低不良反应,提高患者的生存质量,值得临床推广.     

The Effects of HER2 Alterations in EGFR Mutant Non-small Cell Lung Cancer

BackgroundHER2 alteration (mutation and/or amplification) is associated with poor survival in NSCLC and can mediate resistance to EGFR tyrosine kinase inhibitors.MethodsWe retrospectively analyzed de-identified molecular information from 12,946 NSCLC samples that underwent next-generation sequencing (NGS) with Caris Life Sciences. The objectives were to determine the prevalence and type of HER2 alterations with and without EGFR as a co-mutation. Insurance claims were utilized to obtain outcomes data.ResultsThree hundred and twenty-one patients (2.5%) had HER2 alteration: mutation in 197 patients and amplification in 134. Median age was 65 years and 62% were female. A total of 84% were adenocarcinoma. HER2 exon 20 insertion was most common (69%). A total of 1551 (12%) patients had EGFR mutations. Among samples with EGFR mutations, 24 (1.5%) had concurrent HER2 alteration (8 with HER2 mutation and 16 with amplification). Among 8 patients who had both EGFR and HER2 mutations, 3 had EGFR exon 19 deletions and exon 8 HER2 mutation (S310F). One-third of the patients (7/21) with HER2 extracellular domain (ECD) mutation had co-occurring EGFR mutations. All 7 were S310. Patients with concurrent EGFR mutation and HER2 amplification had longer median time on treatment with EGFR TKI(s) than those with EGFR mutation without HER2 amplification (HR 2.284, P =.004).ConclusionA minority of NSCLC samples with EGFR mutations had HER2 alterations. In patients with both mutations, exon 21 mutations for EGFR and exon 8 mutations for HER2 were common. It will be critical to continue to accumulate valuable clinical data for further real-world outcomes analysis.     

EGFR Inhibitor Enhances Cisplatin Sensitivity of Oral Squamous Cell Carcinoma Cell Lines

Epidermal growth factor receptor (EGFR) is involved in multiple aspects of cancer cell biology. EGFR has already been identified as an important target for cancer therapy, with various kinds of EGFR inhibitors currently used in treatment of several human cancers. Recently, EGFR and its downstream signaling pathways were identified as being associated with cisplatin sensitivity. In addition, EGFR inhibitors have shown significant promise for patients who failed cisplatin-based therapy. In this study, we investigated whether treatment with an EGFR inhibitor improves cisplatin sensitivity in oral squamous cell carcinoma (OSCC) cell lines. The effects of a combination of AG1478, a specific EGFR tyrosine kinase inhibitor, with cisplatin were evaluated in cultured OSCC cell lines and cisplatin-resistant sublines. Higher expression of EGFR and p-EGFR was found in the two cisplatin-resistant cell lines compared with the corresponding parental cell lines. In addition, augmented inhibition of OSCC cell growth by the combination of AG1478 with cisplatin was found in both cell lines. These results suggest that the combination of an EGFR inhibitor and cisplatin may be useful as a rational strategy for the treatment of patients with oral cancer with acquired cisplatin resistance.     

表皮生长因子及其受体在胃癌患者中的表达

采用放射免疫法测定２６例胃癌病人血清、尿液ＥＧＦ水平，同时采用免疫组化ＳＡＢＣ法检测胃粘膜组织切片中ＥＧＦＲ染色的阳性率，并与正常对照进行比较分析。结果表明：胃癌患者血清和尿ＥＧＦ水平均显著高于正常对照（３．７２±１．８３μｇ／Ｌ与１．７７±０．６０μｇ／Ｌ，Ｐ＜０．０１；１８．４４±１７．８８ｎｇ／ｍｇ与５．１９±６．３７ｎｇ／ｍｇ，Ｐ＜０．０１），胃粘膜组织切片ＥＧＦＲ染色阳性率也明显高于正常对照（７３％与１１％，Ｐ＜０．０１）。胃癌病人中，ＥＧＦＲ染色阳性者血清ＥＧＦ水平显著高于ＥＧＦＲ阴性者（Ｐ＜０．０５），但两者尿ＥＧＦ水平无显著性差异。胃癌患者血清、尿ＥＧＦ水平与胃癌大小、分化程度及淋巴结转移无显著性相关。     

鼻腔鼻窦鳞状细胞癌组织中PCNA和EGFR的表达

目的　探讨增殖细胞核抗原 (PCNA )和表皮生长因子受体 (EGFR )在鼻腔鼻窦鳞状细胞癌组织中的表达 ,并分析其与临床病理特征的关系。方法　采用免疫组化方法 ,对 45例鼻腔鼻窦鳞癌组织进行PCNA和EGFR检测 ,并用 15例正常鼻黏膜作对照。结果　PCNA和EGFR在各级鼻腔鼻窦鳞癌组织中均有表达 ,与正常鼻黏膜比较有显著性差异 ,均有随鳞癌分级的升高而表达增强的趋势。PCNA、EGFR在鼻腔鼻窦鳞癌中的表达有显著的相关性。结论　PCNA和EGFR的表达均能反映鼻腔鼻窦鳞癌的增殖活性 ,表达强度可反映鳞癌细胞增殖活性的高低