Expression of c-Met receptor and hepatocyte growth factor/scatter factor in synovial sarcoma and epithelioid sarcoma

 Overexpression of c-Met receptor/hepatocyte growth factor (scatter factor) system (c-Met/HGF/SF) as a physiologically paracrine cellular signaling system is thought to be involved in the progression of malignant tumours. In 26 synovial sarcomas and epithelioid sarcomas, c-Met and HGF/SF expression was analysed immunohistochemically. There were 10 biphasic synovial sarcomas, 7 of which showed moderate to strong c-Met expression in epithelial areas compared with the fibrous component, with corresponding expression of HGF/SF. Six of 9 monophasic fibrous synovial sarcomas showed only very faint c-Met and corresponding HGF/SF expression. In 7 epithelioid sarcomas strong expression of c-Met and HGF/SF was observed within epithelioid tumour cells. Non-radioactive in situ hybridization demonstrated the synthesis of c-Met receptor in tumor cells by detecting c-met-mRNA. This analysis shows that in synovial sarcomas and epithelioid sarcomas, tumour entities with epithelial and mesenchymal structures, c-Met and HGF/SF overexpression can be detected, indicating a role of this signaling system in these subtypes of sarcoma, and especially in the more epithelioid tumour phenotype. An autocrine interaction between overexpressed c-Met receptor and HGF/SF may be hypothesized. Received: 21 July 1997 / Accepted: 19 November 1997     

溃疡性结肠炎结肠黏膜修复中HGF,c-Met,EGFR的作用

目的:观察并分析肝细胞生长因子(HGF)及其受体c-Met与表皮生长因子受体(EGFR)在溃疡性结肠炎(UC)活动和非活动阶段患者结肠黏膜的表达情况,探讨其表达的临床意义．方法:根据改良Williams疾病活动指数(DAI) 将42例UC患者分为活动期(n=25)和非活动期(n=17)2组,对照组(n=20)为门诊健康体检者或肠易激综合征患者．结肠镜下活检各组患者结肠黏膜组织,采用免疫组化SABC法检测各组患者结肠黏膜HGF及c-Met表达;SP法检测EGFR及增殖细胞核抗原(PCNA)表达．结果:对照组、活动期UC患者、非活动期 UC患者HGF阳性表达率分别为22％,88％, 100％(X2=62．84,P<0．01);c-Met阳性表达率分别为25％,92％,100％(X2=62．34,P<0．01); EGFR阳性表达率分别为25％,92％,1 00％(X2 =54．34,P<0．01);PCNA过表达率分别为0, 36％,100％(X2=67．50,P<0．01),组间比较差异显著．HGF,c-Met和EGFR在UC患者结肠黏膜表达与PCNA过表达正相关(r=0．648,0．645, 0．565,P<0．01)．结论:HGF,c-Met,EGFR及PCNA在非活动期UC患者结肠黏膜中的表达较活动期UC患者和对照组明显增加．HGF及其受体c-Met与 EGFR在UC患者结肠炎症黏膜修复过程中可能起一定作用．     

浸润性乳腺癌中Hepsin和c-Met的表达及临床病理意义

目的 探讨浸润性乳腺癌组织中Hepsin和c-Met的表达及临床病理意义.方法 采用免疫组化PV-6000方法检测106例浸润性乳腺癌中Hepsin和c-Met的表达.结果 106例浸润性乳腺癌组织中,Hepsin的阳性表达率为66.0%,c-Met的阳性表达率为58.5%,Hepsin与c-Met的表达呈正相关(rs=0.192,P<0.05);Hepsin和c-Met的表达与浸润性乳腺癌的病理分级呈正相关(rs=0.31,P<0.01;rs=0.245,P<0.01),与淋巴结转移亦呈正相关(rs=0.29,P<0.01;rs=0.26,P<0.01).结论 Hepsin和c-Met与提示浸润性乳腺癌的不良预后因素有关,可作为预测浸润性乳腺癌预后的参考指标之一.     

c-Met、MMP-2、MMP-9在肝细胞癌中的表达及临床意义

目的 研究c-Met、基质金属蛋白酶-2(matrix metalloproteinase-2, MMP-2)、基质金属蛋白酶-9(matrix metalloproteinase-9, MMP-9)在肝细胞癌(hepatocellular carcinoma, HCC)中的表达,探讨三者的表达与肝癌侵袭转移间的关系,并初步明确在肝细胞癌预后判断中的作用.方法 采用免疫组化对47例肝细胞癌手术切除标本中c-Met、MMP-2、MMP-9的表达进行检测,评估c-Met的表达与HCC临床病理因素的关系及与MMP-2、MMP-9表达的关系.结果 c-Met、MMP-2、MMP-9在肝细胞癌组织中的阳性表达率分别为38.3%、72.3%、89.4%,与正常肝组织比较差异有统计学意义(分别为12%、16%、12%,P<0 05);c-Met阳性表达率与肝细胞癌的转移、淋巴浸润、包膜形成以及肿瘤分化有关(P<0 05),而与性别、年龄、肿瘤的大小、分期无关;MMP-2的阳性表达率仅与肝细胞癌的包膜形成有关(P=0 028);MMP-9的阳性表达率与HCC的各项临床病理因素无关; c-Met阳性表达与MMP-2的异常表达有关(P<0 001).结论 在HCC的转移中, HGF/c-Met与HCC的转移有关,并且与MMP系统之间存在联系,可能影响MMP-2、MMP-9的表达,对于HCC的转移防治及预后具有一定的临床意义.     

宫颈癌中肝细胞生长因子受体蛋白表达及其与血管生成的关系

目的:研究肝细胞生长因子受体(c-Met)在宫颈癌浸润转移中的作用,探讨其与血管形成的关系。方法:运用免疫组织化学SP法对14例慢性宫颈炎和50例宫颈癌组织中的c-Met进行检测。用CD34单克隆抗体检测微血管密度(MVD)。结果:慢性宫颈炎c-Met表达率为14.3%(2/14),而在宫颈癌中表达率为62.0%(31/50),二者比较差异有显著性(P<0.05)。c-Met的表达与分化程度和淋巴结转移有关(P<0.05),与临床分期和组织学类型无关(P>0.05)。c-Met阳性表达组的MVD明显高于c-Met表达阴性组(P<0.01),c-Met的表达与MVD密切关联。结论:c-Met的表达与宫颈癌血管形成密切关联,可作为宫颈癌诊断和判断预后的一个指标。     

基于c—Met信号通路的抗癌药物研究进展

c-Met的持续激活将破坏肿瘤细胞间的粘附、促进细胞运动及肿瘤新生血管的生成,使肿瘤细胞易于进入血液循环并获得侵袭转移的能力。因而,c-Met已成为抗癌药物研究的一个极有希望的新靶点。本文简要阐述了近年来基于c-Met信号通路的抗癌药物研究进展,重点综述了其中的ATP竞争性酪氨酸激酶小分子抑制剂。     

Biological Significance and the Related Molecular Mechanism of Etsl mRNA Expression in Lung Cancer by Tissue Microarray （TMA）

Objective： To investigate the expressions and proteins in the pathogenesis, progression of lung molecular mechanism of Ets-1 mRNA, and TGFβ1 and c-Met cancer by tissue microarray （TMA） method. Methods： The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were detected in 89 primary lung cancers, 12 lung cancer with lymph-node metastasis and 12 precancerous lesions by FISH（fluorescence in situ hybridization） and immunohistochemical method, and 10 normal lung tissues were used as controls. Results： The expressions of Ets-1 rnRNA, and TGFβ1 and c-Met proteins were significantly higher in 89 primary lung cancer than in the control group （P〈0.05）. The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were related to lymph node metastasis and clinical stages. There was a positive correlation between the Ets-1 mRNA expression and TGFβ1 and c-Met proteins （P〈0.05）. Conclusion： Ets-1 mRNA, TGFβ1 and c-Met proteins may be related to the pathogenesis, progression and malignant behavior of lung cancer. They may play an important role in prognosis assessment of lung cancer.     

肝细胞生长因子与急性肾衰竭

肝细胞生长因子（HGF）是一种问充质来源的一种多效性因子，对多种器官的多种细胞具有促有丝分裂，细胞移动及形态发生等多种生物学作用。在急性肾衰竭（ARF）中可减轻小管损伤，并加速肾小管细胞的功能恢复，促进肾小管生成，有较强的细胞保护和营养作用。     

c-Met kinase inhibitors: an update patent review (2014-2017)

Introduction: The receptor tyrosine kinase c-Met is involved in the formation, metastasis and invasion of various malignant tumors thus it has been an attractive target for anti-tumor drug designing. Many compositions targeting c-Met have been developed in pharmaceutical industry for cancer therapy and some of them are in clinical study now. Among them, Crizotinib was the first small molecular inhibitor approved by FDA in 2011.

Areas covered: This review briefly summarizes the signal transduction pathway about c-Met, its role in oncogenesis, most recent patents of small-molecule inhibitors and antibodies of c-Met from 2014 to 2017.

Expert opinion: To date, some c-Met inhibitors have been launched in the market. In addition, their clinical performances have shown encouraging value in cancer therapy. Many potential agents are still in preclinical or clinical study now and achieve some promising progressions. Some patients have developed resistance to c-Met inhibitors which results in the need to develop inhibitors with novel structures. Development of several potent drugs also tends to be pharmacodynamically active against multiple targets.