HGF及其受体c-Met对毛囊生长的调控作用

肝细胞生长因子（HGF）是由体内多种细胞分泌的一种多功能生长因子，近年来发现它对毛囊和毛发的生长有重要影响，在毛囊和毛发的生长过程中起到重要的调控作用，查阅近年来国外有关资料，综述如下。     

c-Met expression is associated with time to recurrence in patients with glioblastoma multiforme

The aim of this study was to explore the difference in c-Met expression between primary and recurrent glioblastoma multiforme (GBM), and to determine whether the dysregulation of c-Met expression has a role in the malignant progression of GBM. Paired primary and recurrent GBM specimens from the same patient were evaluated using immunohistochemical analysis. The association between c-Met expression and progression-free survival time (PFST) was analyzed. There was a significant difference in c-Met expression between primary and recurrent tumors (p = 0.020), and patients with tumors expressing c-Met at a higher level had a significantly shorter PFST (6.1 months vs. 11.5 months; p = 0.026). Our study indicates that recurrent GBM express c-Met at a higher level and that c-Met overexpression is associated with shorter PFST in patients with GBM. These findings suggest that c-Met potentially has an important role in the treatment of GBM.     

Peritumoral stromal remodeling, pattern of invasion and expression of c-met/HGF in advanced squamous cell carcinoma of the cervix uteri, FIGO stages III and IV

Objective

Different patterns of invasion (PIs) have prognostic impact in several types of cancer and are associated with different grades of peritumoral stromal remodeling, characterized by the desmoplastic stromal response (DSR). One key regulator influencing cellular motility and peritumoral stromal response is c-met/HGF. This study evaluates the association between different PI, peritumoral DSR and its correlation to the expression of c-met/HGF in squamous cell carcinomas of the uterine cervix (CX).

Study design

131 advanced stage CX (FIGO III/IV) were re-evaluated histologically regarding PI, using a two-level scoring system. The tumor grows in solid cords/trabeculae in finger-like PI and in very small groups or single cells in spray-like PI. DSR was categorized as none/weak and moderate/strong. The tumors were stained with antibodies against c-met and HGF. The staining of >30% of tumor cells was defined as overexpression. The PI was correlated to the prognostic outcome, different categories of DSR and expression status of c-met and HGF.

Results

66.4% of the tumors showed a finger-like, and 33.6% a spray-like PI. The spray-like PI showed a reduced two-year overall survival when compared to the finger-like PI (14.0% vs. 29.1%, respectively; p = 0.012), and was associated with moderate/strong DSR. The majority of the tumors showed overexpression of c-met (85.4%) and HGF (74.8%). There was no correlation between the expression status of c-met/HGF and the FIGO stage, peritumoral DSR or the prognostic outcome.

Conclusions

Spray-like PI is of prognostic impact in cervical carcinoma FIGO III/IV and is associated with strong peritumoral stromal remodeling. There is no prognostic impact of the immunohistochemical expression of c-met/HGF in advanced stage cervical carcinomas.     

EGFR和c-Met基因的相对拷贝数在非小细胞肺癌预后中的意义

目的通过研究非小细胞肺癌(NSCLC)病人组织中表皮生长因子受体(EGFR)和c-Met的DNA相对拷贝数的变化,探讨EGFR和c-Met基因在NSCLC发生发展和预测预后过程中的作用。方法采用实时荧光定量PCR方法检测61例NSCLC病人组织中EGFR和c-Met的DNA相对拷贝数,分析它们之间的相关性,以及与各种临床病理特征的关系,并进行生存分析比较。结果 EGFR和c-Met的DNA相对拷贝数的相关系数r=0.352,P=0.005,呈显著性正相关。EGFR和c-Met DNA在吸烟患者中的相对拷贝数分别为0.15和0.13,均高于不吸烟患者;在腺癌中的相对拷贝数分别为0.16和0.14,均高于鳞癌,上述差异经检验有统计学意义(P<0.05)。在鳞癌患者中,EGFR和c-Met DNA相对拷贝数越高则预后越差,经Log-Rank检验,两组病例生存差别有统计学意义(P=0.015,P=0.046)。结论 EGFR和c-Met在NSCLC的发生和发展中可能存在相互或协同作用,能够对鳞癌患者进行预后评估。     

c-Met-targeted RNA interference inhibits growth and metastasis of glioma U251 cells in vitro

This phase II study was designed to determine the objective response rate and 6-month progression free survival of adult patients with recurrent supratentorial anaplastic glioma when treated with the immune modulator, polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC). This was an open-labeled, single arm phase II study. Patients were treated with poly-ICLC alone. Patients may have had treatment for no more than two prior relapses. Treatment with poly-ICLC continued until tumor progression. Fifty five patients were enrolled in the study. Ten were ineligible after central review of pathology. Eleven percent of patients (5 of 45) had a radiographic response. Time to progression was known for 39 patients and 6 remain on treatment. The estimated 6-month progression free survival was 24%. The median survival time was 43 weeks. Poly-ICLC was well tolerated, but there was no improvement in 6-month progression free survival compared to historical database nor was there an encouraging objective radiographic response rate. Based on this study, poly-ICLC does not improve 6moPFS in patients with recurrent anaplastic gliomas but may be worth further study in combination with agents such as temozolomide.     

抗纤抑癌方调控HGF/c-Met mRNA干预肝癌前病变的实验研究

目的：观察抗纤抑癌方对肝癌前病变大鼠HGF/c-Met mRNA的影响,探讨抗纤抑癌方防治肝癌前病变的作用机制。方法：75只SD雄性大鼠随机分为正常组、模型组、抗纤抑癌组、鳖甲软肝组和秋水仙碱组。以二乙基亚硝胺诱发大鼠肝癌前病变模型,用抗纤抑癌方进行干预,并以复方鳖甲软肝片、秋水仙碱片作为对照,采用免疫组化检测肝组织α-SMA的表达情况,实时荧光定量PCR检测各组大鼠肝脏的HGF和c-Met mRNA的表达量。结果：免疫组化显示,与模型组及秋水仙碱组比较,抗纤抑癌组能明显减少α-SMA表达量,差异有统计学意义（P<0.01,P<0.05）。实时荧光定量PCR结果显示,HGF mRNA的相对表达量抗纤抑癌组与模型组比较有统计学意义(P<0.05),与秋水仙碱组比较亦有统计学意义(P<0.05),抗纤抑癌方能显著提高肝癌前病变大鼠HGF mRNA的表达水平。c-Met mRNA在DEN造模的各组中均低表达,各组间差异无统计学意义（P>0.05）。结论：抗纤抑癌方能够提高肝癌前病变大鼠HGF mRNA的表达水平,这可能是其防治肝癌前病变的作用机制之一。     

c-Met-dependent phosphorylation of RhoA plays a key role in gastric cancer tumorigenesis

RhoA has been identified as having a gain-of-function mutation in approximately 20% of diffuse gastric cancer patients. However, the carcinogenic role of RhoA mutations in gastric cancer (GC) is unclear. In the present study, we report that RhoA directly interacts with c-Met and can be phosphorylated by c-Met at Y42 before subsequent K48-linked polyubiquitination and proteasome-mediated protein degradation. Y42C-mutated RhoA exhibits higher protein levels and promotes the proliferation and motility of GC cells. Interestingly, a c-Met inhibitor significantly repressed the growth of GC cells transfected with WT RhoA but not RhoA mutated at Y42 in vivo and in vitro. Analyses of human GC tissues showed that the combined levels of p-c-Met and p-RhoA are a better predictor for prognosis than either factor alone. Taken together, our findings unravel the mechanism by which the RhoA Y42 mutant is linked to poor prognosis in GC. Moreover, this study helps to identify a strategy for patient stratification and optimization of targeted c-Met therapy. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

c-Met蛋白在乳腺癌中的表达及临床病理意义

目的 探讨乳腺癌中c-Met蛋白的表达情况及其临床病理意义.方法 收集我院病理科2011年10月～2012年10月150例乳腺癌石蜡标本,采用免疫组织化学方法对其c-Met蛋白的表达情况进行检测,以统计分析软件SPSS17.0对其与年龄、肿瘤大小、病理分级、淋巴结是否转移、TNM分期之间的关系进行评价.结果 c-Met阳性表达及阴性表达的例数为62（41.33%）、88（58.67%）.c-Met在正常乳腺组织中为阴性表达.淋巴结转移的患者的阳性表达率明显高于无淋巴结转移组;TNM分期中,Ⅲ~Ⅳ组中的阳性表达率明显高于Ⅰ~Ⅱ组,差异有统计学意义（P ＜ 0.05）.多因素分析结果表明,乳腺癌发生发展中c-Met不是其独立的预后因子.结论乳腺癌中的c-Met蛋白的表达差异具有显著性,淋巴结出现转移后及患者具有较高的TNM分期则其表达出现增强,提示c-Met在乳腺癌的发生及侵袭、转移过程中起着非常重要的作用.     

MACC1和c-Met在肾盂癌中的表达及其临床意义

目的:探讨结肠癌转移相关基因1(MACC1)及肝细胞生长因子受体(c-Met)在肾盂癌中的表达及其与肾盂癌发生、发展、浸润转移的关系。方法:采用免疫组织化学染色法检测73例肾盂癌组织及20例癌旁正常组织中MACC1和c-Met的表达情况,并结合临床病理因素进行相关分析。结果:在肾盂癌组织中MACC1和c-Met的高表达率均明显高于正常肾盂黏膜组织(P<0.05)。MACC1和c-Met的高表达与患者性别、年龄、病理分级、吸烟和尿脱落细胞学检查结果无关,而与病理分期相关(P<0.05)。肾盂癌中MACC1的高表达与c-Met的高表达呈正相关(r=0.450,P<0.01)。结论:MACC1和c-Met的异常高表达可能与肾盂癌的发生、发展及浸润转移密切相关,联合检测可作为判断肾盂癌生物学行为的重要指标。