Epidermal growth factor receptor levels increase but epidermal growth factor receptor ligand levels decrease in mouse mammary tumors during progression from hormone dependence to hormone independence

Summary Twenty-six serially transplanted Grunder (GR) strain mouse mammary tumors were analyzed for epidermal growth factor receptor (EGFR) and EGFR-ligand levels, in addition to steroid hormone receptors (estrogen receptor, ER, progesterone receptor, PgR). In concordance with earlier studies, hormone dependent (HD) and hormone responsive (HR) tumors were found to be positive for both ER and PgR, whereas hormone independent (HI) tumors contained only 30% of the ER concentration that was found in the HD tumors. PgR was undetectable in HI tumors. HI tumors contained 2.5 to 3-fold higher EGFR levels than HD/HR tumors, an observation which shows remarkable concordance with studies on EGFR in human breast cancer. On the other hand, the level of EGFR-ligand(s) was positively associated with ER levels and was three-fold higher in HD/HR tumors than in HI tumors. The low EGFR in HD/HR tumors relative to HI tumors may be the result of downregulation by EGFR ligands produced under ER control. During progression to hormone independence this downregulation of EGFR is then abolished in absence of ER. The increase in EGFR may therefore be a secondary effect rather than a key event in the progression to hormone independence in this mouse mammary tumor model.Abbreviations EGF Epidermal Growth Factor - EGFR Epidermal Growth Factor Receptor - ER Estrogen Receptor - PgR Progesterone Receptor - HD Hormone Dependent - HR Hormone Responsive - HI Hormone Independent - HAP Hydroxylapatite - DCC Dextran Coated Charcoal - GR Grunder - TGF- Transforming Growth Factor-     

贲门部浸润性癌预后的探讨

探讨贲门部浸润性癌的预后;与幽门部浸润性癌进行对比分析。方法贲门部癌５０例,对照组幽门部部５０例,采用临床病理学资料和免疫组织化学方法进行对比分析。结果①临床病理学,Ｃ．Ｃａｓ和Ｐ．Ｃａｓ之间除淋巴结转移（Ｐ〈０．０５）有显著差异外,其它无显著性差异。②生存曲线分析,Ｃ．Ｃａｓ和Ｐ．Ｃａｓ之间,在淋巴结转移（Ｐ〈０．０１）和淋巴管侵入（Ｐ〈０．０５）方面有显著差异;在１００例进行性胃癌当中癌的浸润     

Molecular targeting for epidermal growth factor receptor expressed on breast cancer cells by human fusion protein

Recombinant human ribonuclease 1 (RNasel) was chemically linked to recombinant human epidermal growth factor (EGF). The cytotoxicity of this conjugate was assayed using MTT assay. The EGF-RNase conjugate showed dose-dependent cytotoxicity against breast and squamous cell carcinomas overexpressing the EGF receptor (EGFR). The cytotoxicity of the conjugate correlated positively with the level of EGFR expression by each cell line. These results suggest that the EGF-RNase conjugate is a more effective anticancer agent with less immunogenicity and toxicity than conventional chimeric breast cancer toxins.     

Epidermal Growth Factor Receptor Inhibition in Cancer Therapy: Biology, Rationale and Preliminary Clinical Results

The epidermal growth factor receptor (EGFR), a growth factor receptor involved in the regulation of cellular differentiation and proliferation, is highly expressed by many tumor cells. In light of a relationship between overexpression of EGFR and clinically aggressive malignant disease, EGFR has emerged as a promising target for cancer therapy. In recent years, several molecular strategies have been explored to modulate either the EGFR itself, or the downstream signal beyond the cell surface receptor. One of the most promising current strategies involves the use of anti-EGFR monoclonal antibodies (mAbs), either alone or in combination with conventional cytotoxic modalities such as chemotherapy or radiotherapy. This review focuses primarily on recent progress in the development of anti-EGFR mAbs, and examines their potential in the treatment of cancer.     

表皮生长因子在膀胱癌中的表达及意义

目的探讨膀胱癌中表皮生长因子(EGFR)的表达与生物学行为的关系。方法应用免疫组织化学ABC法对74份膀胱癌标本进行研究。结果正常膀胱粘膜EGFR均为阴性;EGFR在浸润性膀胱癌中表达的阳性率高于浅表性膀胱癌(P<0.05);EGFR随着膀胱癌病理分级的增高阳性率逐渐增加(P<0.05)。ECFR阳性病例1、3、5年的生存率低于EGFR阴性者(P<0.01)。结论EGFR与膀胱癌的临床分期、病理分级有关,可作为估计病人预后的参考指标之一。     

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     

表皮生长因子受体和细胞外信号调节激酶的表达与舌鳞状细胞癌转移关系的观察

目的　了解表皮生长因子受体 (EGFR )和细胞外信号调节激酶 (ERK )在舌鳞状细胞癌中的表达 ,探讨EGFR和ERK与肿瘤增殖、转移的关系。方法　应用免疫组织化学SABC方法 ,分别对 90例舌鳞状细胞癌术后组织标本的EGFR、活化ERK 1/2和Ki 67进行检测 ,并对各因子间的表达关系进行统计分析。结果　在 90例舌鳞状细胞癌组织中 ,2 6例证实有颈部淋巴结转移 ,EGFR、活化ERK 1/2及Ki 67的阳性表达率分别为 93 .3 3 % ( 84/90 )、10 0 .0 0 % ( 90 /90 )和 10 0 .0 0 % ( 90 /90 ) ,阳性细胞分布和反应强度均以肿瘤深部边界区域最为明显 ,统计分析显示EGFR、活化ERK 1/2与肿瘤细胞增殖和肿瘤转移之间呈明显的正相关 (P <0 .0 1)。结论　EGFR、活化ERK 1/2在舌鳞状细胞癌细胞中多呈现过度表达与肿瘤的增殖、转移密切相关     

ZD1839（Iressa）在晚期非小细胞肺癌治疗中的应用

目的　探讨表皮生长因子受体酪氨酸激酶抑制剂———ZD183 9(Iressa)治疗晚期非小细胞肺癌的疗效和毒副反应。方法　分析 2 0 0 2年 12月至 2 0 0 3年 8月期间我院 3 9例晚期非小细胞肺癌患者经ZD183 92 5 0mg/d口服治疗的情况。应用 χ2 检验、t检验、Kaplan Meier进行统计分析。并采用欧洲癌症研究和治疗组织 (EuropeanOrganizationforResearchandTreatmentofCancer ,EORTC)简体中文版的生活质量调查核心问卷QLQ C3 0和肺癌专用问卷QLQ LC13对患者的生活质量进行评价。结果　全组患者有效率 (完全缓解 +部分缓解 )为 2 8.2 %,疾病控制率 (有效 +稳定 )为 5 9.0 %。疗效与患者性别和病理类型有密切关系。综合生活质量改善率为 3 4.8%,功能状态改善率为 65 .2 %,临床症状缓解率为 73 .9%。全组无疾病进展时间为 6.6月± 1.6月 ( 95 %CI为 3 .4～ 9.7) ,到截尾时间 5 6.4%( 2 2 /3 9)的患者仍存活 ,1年生存率为 5 4.3 %( 19/3 5 )。毒副反应主要为Ⅰ、Ⅱ度皮疹和腹泻 ,经对症处理可缓解。结论　ZD183 9治疗晚期非小细胞肺癌疗效确切 ,同时可改善生活质量     

Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid malignant tumors.

BACKGROUND: This phase I dose-escalating study investigated the tolerability and toxicity of the selective epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Japanese patients with solid tumors. Thirty-one patients were included. PATIENTS AND METHODS: Patients initially received a single oral dose of gefitinib followed by 10-14 days of observation. Oral gefitinib was subsequently administered on 14 consecutive days, every 28 days. Dose escalation was from 50 mg/day to a maximum of 925 mg/day or dose-limiting toxicity (DLT). RESULTS: Most adverse events were mild (grade 1/2); the most frequent were an acne-like rash and gastrointestinal effects. Two of six patients at 700 mg/day had DLT; no further dose escalation occurred. C(max) was reached within 3-7 h and exposure to gefitinib increased with dose. Mean terminal half-life following multiple dosing was 50.1 h (range 27.8-79.7 h). A partial response (duration 35-361 days) was observed in five of the 23 patients with non-small-cell lung cancer over a range of doses (225-700 mg/day), and seven patients with a range of tumors had disease stabilization (duration 40-127 days). CONCLUSIONS: In conclusion, gefitinib showed a favorable tolerability profile in Japanese patients. The safety profile, pharmacokinetic parameters and antitumor activity observed in our study are comparable to those observed in patients from the USA and Europe.     

CD44v6、EGFR及nm23-H1基因蛋白在食管鳞癌组织中的表达及意义

 目的　探讨食管鳞癌中CD4 4v6、EGFR及nm2 3 H1蛋白表达的意义。方法　应用免疫组化S P法检测 5 0例食管鳞癌中CD4 4v6、EGFR及nm2 3 H1蛋白表达。结果　CD4 4v6、EGFR、nm2 3 H1蛋白表达总阳性率分别 6 4 %、70 %、5 0 % ;显示CD4 4v6及EGFR阳性表达率与食管鳞癌分化程度、浸润深度及淋巴结转移率呈正相关 (P <0 .0 5及P <0 .0 1) ,与患者预后呈负相关 (P <0 .0 0 5 ) ;而nm2 3 H1蛋白表达则与以上两者表达状况相反。结论　同时检测食管鳞癌中CD4 4v6、EGFR及nm2 3 H1基因蛋白表达水平 ,对判断食管鳞癌恶性程度、浸润转移潜能及评估患者预后有一定参考价值。