Research progress on the development of hepatocyte growth factor/c-Met signaling pathway in gastric cancer:A review

Hepatocyte growth factor(HGF)and its receptor,c-Met,play important roles in the occurrence,development,and treatment of gastric cancer(GC).This review explored the function of the HGF/c-Met signaling pathway in GC and its potential targeted therapeutic mechanisms.As one of the most common malignant tumors worldwide,GC has a complex pathogenesis and limited therapeutic options.Therefore,a thorough understanding of the molecular mechanism of GC is very important for the development of new therapeutic methods.The HGF/c-Met signaling pathway plays an important role in the proliferation,migration,and invasion of GC cells and has become a new therapeutic target.This review summarizes the current research progress on the role of HGF/c-Met in GC and discusses targeted therapeutic strategies targeting this signaling pathway,providing new ideas and directions for the treatment of GC.

Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications

Hepatocellular carcinoma(HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor(HGF)/c-mesenchymal-epithelial transition receptor(c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microR NAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials.

Association of hepatocyte-derived growth factor receptor/caudal type homeobox 2 co-expression with mucosal regeneration in active ulcerative colitis

AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected.After preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were performed.Immunostained samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module software.For semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were determined.In case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was determined.Using 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were collected.Gene expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to controls.HGFR/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs scattered) coexpressions were found in blood and lamina propria of UC samples.HGFR/CD133 and CD133/CDX2 coexpressions appeared only in UC lamina propria samples.CDX2,Lgr5 and Musashi-1 expressions in UC blood samples were not accompanied by CK20 mRNA expression.CONCLUSION:In active UC,a portion of circulating HGFR-expressing cells are committed to the epithelial lineage,and may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition.

The involvement of p38 MAPK in transforming growth factor β1-induced apoptosis in murine hepatocytes

We reported in this manuscript that TGF-β1 induces apoptosis in AML12 murine hepatocytes, which is associated with the activation of p38 MAPK signaling pathway. SB202190, a specific inhibitor of p38 MAPK, strongly inhibited the TGF-β1-induced apoptosis and PAI-1 promoter activity. Treatment of cells with TGF-β1 activates p38. Furthermore, over-expression of dominant negative mutant p38 also reduced the TGF-β1-induced apoptosis. The data indicate that the activation of p38 is involved in TGF-β1-mediated gene expression and apoptosis.

Metformin attenuates angiotensin II induced cardiac fibrosis and transforming growth factor-β1 production through the inhibition of hepatocyte nuclear factor4

Aim In diabetic patients, metformin appears to provide cardiovascular protection that cannot be attribu- ted only to its antihyperglycemic effects. Metformin is also known as the AMP-activated protein kinase （AMPK） ac- tivator. Our previous study suggested that metformin inhibits transforming growth factor-β1 （TGF-β1） production in a mouse heart failure model of pressure overload. TGF-β1 is a key factor in cardiac fibrosis and is usually induced by Angiotensin Ⅱ （Ang Ⅱ ） in the pressure overload mouse models. This study investigated the effect of metformin on cardiac fibrosis and TGF-β production induced by AngII and the underlying mechanisms. Methods C57/BL6 wild-type and AMPKα2 knockout mice were used. AngII （3 mg · kg-1 · d-1） was infused subcutaneously into mice for 7 days. Adult mouse cardiac fibroblasts were isolated and treated with AngII （ 1 μmol · L-1） and/or met- formin （1 mmol · L-l）. Results In C57/BL6 mice, metformin inhibits AngII-induced cardiac fibrosis. In cardi-ac fibroblasts, metformin inhibits TGF-β1 expression and production induced by AngII. AMPK inhibitor, com- pound C, reversed the effects of metformin. In vivo, AMPKα2 deficiency further increases AngII-induced TGF-β1 production. In cardiac fibroblasts, metformin inhibited AngII induced hepatocyte nuclear factor4 （HNF4ot protein level increase and HNF4α binding with TGF-β1 promoter using chromatin immunoprecipitation assay. In vivo, AMPKα2 deficiency further increased AngII-induced HNF4α protein level. Using HNF4α adenovirus, overexpress- ing HNF4α led to a 1.5-fold increase in TGF-β1 mRNA expression. HNF4a siRNA blocked AngII induced TGF- β1 production. Luciferase reporter with deleted HNF4a binding sites showed decreased TGFbl transcriptional activ- ity induced by AngII. In AMPK or2-/- heart, the inhibition of metformin on HNF4a protein was attenuated. Con- clusion Metformin inhibits AngII induced cardiac fibrosis and TGF-β1 production through AMPK activation. The underlying mechanism is that AMPK activation inhibits AngII induced HNF4α and then decreases TGF-β1 expres- sion.

Hepatocyte Growth Factor Is a Reliable Marker for Efficient Anti-Bacterial Therapy within the First Day of Treatment

Rapid diagnosis and choice of appropriate antibiotic treatment might be life-saving in serious infectious diseases. Still the available markers that can evaluate and monitor the diagnosis and treatment are few. Hepatocyte growth factor (HGF) has been studied as a potent regenerative factor produced and released during injuries such as infectious diseases. Monitoring of HGF levels might predict therapy results better than C-reactive protein (CRP) within the first day of treatment in pneumonia. For further investigation of previous observations we aimed to study HGF as a first-day marker in over-representing infectious diseases in comparison to procalcitonin (PCT), CRP and body temperature. Fifty-one patients with community acquired infectious diseases were included consequently at admittance and the serum samples were collected before and within 18 - 24 hours of treatment. HGF levels decreased significantly in case of efficient antibiotic therapy and HGF was shown to be better than PCT, CRP and body temperature to evaluate treatment. In patients with pneumonia, monitoring of HGF was most reasonable. HGF might be used as a therapeutic marker within the first day of empiric antibiotic treatment during infection.

Expression of c-erbB-2 oncogene protein, epidermal growth factor receptor, and TGF-β1 in human pancreatic ductal adenocarcinoma

Objective: To detect the relations of c-erbB-2 onco-gene protein, epidermal growth factor receptor (EG-FR) and transforming growth factor-β1 (TGF-β1)to the progression or metastasis of pancreatic carci-noma.Methods: Using streptavidinbiotin complex (SABC)method, c-erbB-2 oncongene protein, we examinedimmunohistochemically EGFR and TGF-β1 expres-sions in wax-tissue sections from 10 individuals withnormal pancreas (NP), 13 patients with chronic pan-creatitis (CP) and 36 patients with pancreatic ductaladenocarcinoma (PC).Results: The positive expression rates of c-cerbB-2oncogene protein, EGFR and TGF-β1 in the NP, CPand PC groups were 0, 0, 10%; 7.7%, 7.7%,7.7%; and 41.7%, 50.0%, 44.4%, respectively.The positive expression rates of the three specific pro-teins increased more significantly in the PC groupthan in the NP and CP groups (P【0.05). The indi-vidual expression of c-erbB-2, EGFR and TGF-β1was not related to the age and sex of the patients aswell as the site, size and histopathological grade oftumors (P】0.05), but to the clinical stage of tumors(P【0.01). The coexpression rate of the three pro-teins was 27.8 % (10/36). This coexpression in thePC group was correlated with the histopathologicalgrades and clinical stages of tumors (P【0.01).Conclusion: Detection of c-erbB-2 oncogene protein,EGFR, and TGF-β1 expressions in pancreatic tissueis helpful to judge the malignancy, progression, andmetastasis of PC.

Expression of vascular endothelial growth fac-tor gene in primary cultured rat hepatocytes

BACKGROUND: It is the key point for vascular endothelialgrowth factor (VEGF121) gene related therapy as to how totransfect and express the gene safely, effectively and repeat-edly. This study was designed to investigate the VEGF121transfection and expression in primary cultured rat hepato-cyte.METHODS: After construction of vector internal ribosomeentry site-enhanced yellow fluorescent protein (pIRES-EY-FP)/VEGF121, the transfection and expression of the exoge-nous VEGF121 gene in primary cultured rat hepatocyteswere observed through RT-PCR, Western blot and fluores-cent microscopy.RESULTS: pIRES-EYFP/VEGF121 plasmid was construct-ed and transfected successfully into primary cultured rathepatocytes, the transfection and expression of gene in pri-mary cultured rat hepatocytes were examined by RT-PCRand Western blot, and yellow-green fluorescence was ob-served through a fluorescent microscope.CONCLUSION: The successful transfection and expressionof plasmid pIRES-EYFP/VEGF121 in primary cultured rathepatocytes provides a foundation for hepatocyte transplan-tation and gene therapy after modification of hepatocytesby the gene.

Epidermal growth factor receptor and K-Ras in non-small cell lung cancer-molecular pathways involved and targeted therapies

Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the intensive research carried out on this field and therapeutic advances,the overall prognosis of these patients remains unsatisfactory,with a 5-year overall survival rate of less than 15%.Nowadays,pharmacogenetics and pharmacogenomics represent the key to successful treatment.Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma:one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor(EGFR).The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR(erlotinib and gefitinib)and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs.This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR,K-Ras and EGFR targeted therapies in NSCLC tumor behavior.

IGFBPrP1 induces liver fibrosis by inducing hepatic stellate cell activation and hepatocyte apoptosis via Smad2/3 signaling

AIM:To investigate the role and mechanism of insulinlike growth factor binding protein-related protein 1(IGFBPrP1)in the development of liver fibrosis.METHODS:An in vitro model using hepatic stellate cell(HSC)-T6 cells and an in vivo model of rat liver overexpressing IGFBPrP1 were established using an IGFBPrP1-expressing recombinant adenovirus.The expression of IGFBPrP1 was examined by immunofluorescence,and the expression of collagen?Ⅰ?and fibronectin was mea-sured by real-time reverse transcription-polymerase chain reaction and Western blot analysis.The expression of Smad2/3 and p-Smad2/3 was examined by Western blot and immunohistochemistry.A shSmad3-expressing recombinant adenovirus(AdshSmad3)was designed and used to knockdown the Smad3 gene in HSC-T6 cells and rat liver fibrosis transfected with IGFBPrP1.The expression of collagen?Ⅰ,fibronectin,andα-smooth muscle actin(α-SMA)was determined by Western blot analysis and immunohistochemistry.Hepatocyte apoptosis was assessed using TUNEL assay.RESULTS:IGFBPrP1 overexpression induced collagen deposition and up-regulated the expression ofα-SMA and p-Smad2/3,and AdshSmad3 inhibited IGFBPrP1-stimulated p-Smad2/3 activation and the expression ofα-SMA,collagen?Ⅰ?and fibronectin in HSC-T6 cells.Similarly,increased hepatocyte apoptosis(38.56%±3.42%vs 0.24%±0.03%,P<0.05),α-SMA positive stained cells(29.84%±1.36%vs 5.83%±1.47%,P<0.05),and increased numbers of Smad3(35.88%±2.15%vs10.24%±1.31%,P<0.05)and p-Smad2/3 positive cells(28.87%±2.73%vs 8.23%±0.98%,P<0.05)were detected in the livers of IGFBPrP1-overexpressing rats compared with the control group.Moreover,AdshSmad3 reduced IGFBPrP1-stimulated Smad3 expression and attenuatedα-SMA expression(29.84%±1.36%vs 8.23%±1.28%,P<0.05),hepatocyte apoptosis(38.56%±3.42%vs 6.75%±0.52%,P<0.05),and both collagen?Ⅰ?and fibronectin deposition in the livers of AdIGFBPrP1-treated rats.CONCLUSION:IGFBPrP1 induces liver fibrosis by mediating the activation of hepatic stellate cells and hepatocyte apoptosis in a Smad3-dependent mechanism.

肝细胞生长因子及受体c-met在乳腺癌中的研究进展

目的 研究肝细胞生长因子及其受体c met在乳腺癌发生、发展中的作用及其与预后的关系。方法 采用文献回顾的方法并结合目前的实验研究 ,对肝细胞生长因子及受体c met在乳腺癌中的研究进展加以综述。结果 肝细胞生长因子对乳腺癌细胞具有促分裂、诱导肿瘤细胞迁移、侵袭以及诱发肿瘤血管生成的作用 ,其与受体c met作用机理的发现 ,进一步揭示了乳腺癌的发生机理。结论 肝细胞生长因子 /c met在乳腺癌发生、发展过程中起重要作用 。

TPO mRNA和HGF/c-Met在甲状腺良恶性结节中的表达及意义

目的探讨甲状腺过氧化物酶(TPO)mRNA和肝细胞生长因子及其受体蛋白(HGF/c-Met)在良恶性甲状腺结节中的表达及意义。方法应用逆转录聚合酶链反应技术检测55例甲状腺结节新鲜标本的TPO mRNA丰度,采用免疫组织化学法检测600例甲状腺结节石蜡标本HGF/c-Met的表达。结果甲状腺癌HGF/c-Met表达率显著高于甲状腺良性结节,乳头状癌高于滤泡型癌(P<0.01)。甲状腺恶性结节TPOmRNA的阳性表达率显著低于甲状腺良性病变。结论HGF/c-Met和TPO的联合检测在良恶性甲状腺病变的鉴别中有一定应用价值。

肝细胞生长因子-C-Met系统与口腔鳞癌相关性研究的进展

肝细胞生长因子(hepatocyte growth factor,HGF)由间质细胞产生的多功能的细胞因子,其受体是由原癌基因C-Met编码产生的跨膜蛋白。人类许多肿瘤的生长,侵袭及转移都与HGF-C-Met系统息息相关。研究HGF-C-Met系统与鳞状细胞癌的生长,侵袭及转移的关系,对临床肿瘤的诊断及预后评估有重要的意义;HGF和C-Met的抑制剂抗肿瘤作用有望成为肿瘤治疗的新方向或靶点。

HGF和其受体c-met在NSCLC组织中的表达及其与VEGF的关系

目的检测肝细胞生长因子(HGF)及其受体(c-met)和血管生长因子(VEGF)在非小细胞肺癌(NSCLC)中的表达,分析其与NSCLC临床病理参数的关系及HGF和VEGF相关关系。方法应用免疫组织化学方法SABC法对68例NSCLC组织中的HGF、c-met和VEGF进行检测。结果68例NSCLC组织中HGF、c-met和VEGF表达率分别为45.6%(31/68)、51.5%(35/68)和41.8%(28/68)。HGF的表达与组织类型、分化程度无关(P>0.05)。c-met的表达与组织类型、分化程度相关(P<0.01,P<0.005)。VEGF的表达与组织类型无关(P>0.05)而与分化程度相关(P<0.05)。HGF的表达与c-met的表达呈明显正相关(P=0.000,γ=0.471),HGF的表达与VEGF的表达亦呈明显正相关(P=0.000,γ=0.662)。结论HGF、c-met及VEGF的增强表达与NSCLC发展演进和肿瘤血管生成有密切关系。

SF/HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma

AIM: To explore the role of SF/HGF-Met autocrine and parscrine in metastasis of hepatocellular carcinoma (HCC).METHODS: SF/HGF and c-met transcription and protein expression in HCC were examined by RT-PCR and Western Blot in 4 HCC cell lines, including HepG2, Hep3B,SMMC7721 and MHCC-1, the last cell line had a higher potential of metastasis. Sf/hgf cDNA was transfected by the method of Lipofectin into SMMC7721. SF/HGF and c-met antibody were used to stimulate and block SF/HGF-c-met signal transduction. Cell morphology, mobility, and proliferation were respectively compared by microscopic observation, wound healing assay and cell growth curve.RESULTS: HCC malignancy appeared to be relative to its met-SF/HGF expression. In MHCC-1, c-met expression was much stronger than that in other cell lines with lower potential of metastasis and only SF/HGF autocrine existed in MHCC-1. After sf/hgf cDNA transfection or conditioned medium of MHCC-1 stimulation, SMMC7721 changed into elongated morphology, and the abilities of proliferation ( P < 0.05) and mobility increased. Such bio-activity could he blocked by c-met antibody ( P< 0.05).CONCLUSION: The system of SF/HGF-c-met autocrine and paracrine played an important role in development and metastasis potential of HCC. Inhibition of SF/HGF-c-met signal transduction system may reduce the growth and metastasis of HCC.

Expression of Ezrin,HGF,C-met in pancreatic cancer and non-cancerous pancreatic tissues of rats

BACKGROUND: Recent studies have confirmed that the expression of Ezrin, hepatocyte growth factor (HGF) and its receptor (C-met) is related to the genesis, progress, invasion and metastasis of some malignant tumors. Researches have also found that the biological function of Ezrin is closely related to HGF/C-met in malignant tumors. However, there is no report on the expression levels of Ezrin, HGF and C-met in rat pancreatic cancer induced by dimethylbenzanthracene (DMBA). This study aimed to detect the expression of Ezrin, HGF and C-met in rat pancreatic cancer and non-cancerous pancreatic tissues, and assess its effect in cancer induction by DMBA. METHODS: Ninety Sprague-Dawley rats were divided into 3 groups randomly: 40 in a pancreatic cancer model group (group A), 40 in a trichostatin A (TSA) intervention group (group B), and 10 in a control group (group C). DMBA was directly implanted into the parenchyma of rat pancreas in group A+group B. The rats of group B were treated with 1 ml of TSA saline solution (1 mu g/ml) via intraperitoneal injection weekly. The carcinogenesis of rats executed within 3-5 months in groups A and B was observed by macrograph and microscopy. Meanwhile, the rats in group C were executed within 5 months. The EnVision (TM) immunohistochemistry for detecting the expression levels of Ezrin, HGF and C-met was used in paraffin-embedded sections of the pancreatic specimens. RESULTS: The incidence of pancreatic cancer in group A was 48.6% and in group B 33.3%. The maximal diameter of tumor mass was significantly larger in group A than that in group B (P<0.05). No pathological changes were observed in the pancreas of group C and other main organs of groups A and B. The positive rates of Ezrin, HGF and C-met were significantly higher in ductal adenocarcinoma than in non-cancerous pancreatic tissues of groups A and B (P<0.01). The positive rates of Ezrin, HGF and C-met were significantly higher in ductal adenocarcinoma of group A than those in non-cancerous pancreatic tissues of group A (P<0.05), but there was no significant difference in group B (P>0.05). The positive rates of Ezrin, HGF and C-met in non-cancerous pancreatic tissues proved mild to severe atypical hyperplasia of the ductal epithelia. The pancreas of group C and 2 cases of fibrosarcoma showed the negative expression of Ezrin, HGF and C-met. There was a trend of consistency in the expression of Ezrin, HGF and C-met in ductal adenocarcinoma (P<0.05 or P<0.01). CONCLUSIONS: DMBA directly implanted into the parenchyma of the pancreas can produce a model of pancreatic cancer with a high incidence in a short time. TSA might inhibit the carcinogenesis and growth of pancreatic cancer, and its effects may be related to the inhibition of the expression of Ezrin, HGF and C-met during the process. Ezrin, HGF and C-met may have positive effects on the carcinogenesis of rat pancreas. (Hepatobiliary Pancreat Dis Int 2010; 9: 639-644)

HGF、c-Met蛋白与左向右分流型肺动脉高压肺血管重构的关系

目的观察肝细胞生长因子(HGF)、c-Met原癌基因编码产物及Caspase-3在左向右分流型大鼠肺动脉高压(PAH)形成过程中肺动脉内的表达,探讨HGF及c-Met在PAH形成中的作用。方法4～5周龄SD大鼠80只,随机均分为分流组与对照组,分流组采用套管法行颈总动脉-颈外静脉分流术以建立左向右分流型肺动脉高压模型,对照组行假手术。两组均在术后第4、8、12、16周行肺血流动力学和病理学检查,采用免疫组织化学法检测HGF、c-Met、Caspase-3在肺动脉壁内的表达。结果分流组术后各时间点肺动脉收缩压(PASP)、肺动脉平均压(mPAP)及肺循环血流量/体循环血流量(Qp/Qs)均明显高于对照组(P<0.01);随时间延长,分流组肺动脉中膜厚度百分比(MT%)及右室肥厚指数(RVHI)明显增高,与对照组比较差异显著(P<0.01);分流组术后8周HGF、c-Met表达明显高于对照组(P<0.01),此后缓慢下降,术后4周Caspase-3表达最高(P<0.01),此后逐渐下降并低于对照组。结论套管法连接颈总动脉与颈外静脉建立左向右分流型肺动脉高压大鼠模型简易可靠。HGF、c-Met在肺循环高灌注大鼠肺血管中的表达与肺动脉压力变化及肺血管重构有关。PAH形成中Caspase-3表达逐渐降低,可能与肺动脉壁平滑肌细胞增殖有关。

C-met蛋白在食管癌组织中的表达及其与临床特征的关系

目的探讨肝细胞生长因子受体(C-met)蛋白在食管癌组织中的表达及其与临床特征的关系。方法选取80例食管癌组织标本及其癌旁组织标本,采用免疫组化染色检测两组标本中的C-met蛋白表达情况,并分析C-met蛋白表达与食管癌临床特征的关系。结果食管癌组织中的C-met蛋白阳性表达率为80.00%,高于癌旁组织的6.25%,差异有统计学意义(P<0.05);TNM分期为Ⅲ+Ⅳ期、浸润深度为T_(3~4)期、发生淋巴结转移的食管癌患者的C-met蛋白阳性表达率高于Ⅰ+Ⅱ期、浸润深度为T_(1~2)期、未发生淋巴结转移的食管癌患者(P<0.05);不同年龄、性别、肿瘤部位、分化程度、病灶直径的食管癌患者C-met蛋白阳性表达率比较,差异均无统计学意义(P>0.05)。结论食管癌组织中的C-met蛋白阳性表达率升高,并且与肿瘤临床分期、浸润深度、淋巴结转移有关。

黄芪建中汤对脾胃虚寒证胃溃疡大鼠胃黏膜保护作用的机制研究

目的基于动物实验研究黄芪建中汤对脾胃虚寒证胃溃疡的治疗作用及抗黏膜损伤机制。方法将大鼠随机分为正常组、模型组、西药组及中药组,每组15只。除正常组外,另3组均应用耗气破气法+饥饱失常法+冰醋酸法复制脾胃虚寒证胃溃疡模型。中药组、西药组各予黄芪建中汤(6.8 g/kg)、奥美拉唑(4.2 mg/kg)灌胃,另两组则灌以等体积蒸馏水。给药20 d后计算胃溃疡指数;HE染色观察胃组织形态;ELISA法检测血清白细胞介素-18(interleukin-18,IL-18)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;RT-PCR检测胃组织肝细胞生长因子(hepatocyte growth factor,HGF)、细胞间质上皮转换因子(cellular-mesenchymal epithelial transition factor,c-Met)、磷脂酰肌醇3-激酶(hosphoinositide 3-kinase,PI3K)、蛋白激酶B(protein kinase B,AKT)、表皮生长因子受体(epidermal growth factor receptor,EGFR)mRNA表达水平;Western blot法检测PI3K、磷酸化AKT(phosphorylated protein kinase B,p-AKT)、EGFR蛋白表达;免疫组织化学检测胃组织HGF、c-Met的表达水平。结果与正常组比较,模型组胃溃疡指数增高(P<0.05),胃组织溃疡损伤明显,血清IL-18、IL-1β、TNF-α水平增高(均P<0.05),胃p-AKT、AKT、EGFR蛋白及mRNA表达下降(均P<0.05);与模型组比较,中药组胃溃疡指数、炎症因子水平(均P<0.05)显著降低,胃黏膜受损程度改善(P<0.05),胃HGF、c-Met、PI3K、p-AKT、EGFR蛋白及mRNA表达水平上调(均P<0.05)。结论黄芪建中汤对胃溃疡有良好的治疗作用,其机制可能与激活HGF/c-Met、PI3K/AKT通路以增强胃黏膜的防御机制和减轻炎症反应有关。

妊娠期糖尿病患者血清NRG4、HGF、SAA与糖脂代谢、不良妊娠结局关系

目的:探讨妊娠期糖尿病(GDM)患者血清神经调节蛋白4(NRG4)、肝细胞生长因子(HGF)、血清淀粉样蛋白A(SAA)表达及与糖脂代谢、不良妊娠结局关系。方法:收集2021年1月-2022年1月本院收治的GDM患者72例为GDM组,产前检查健康孕妇50例为对照组,检测两组血清NRG4、HGF、SAA水平,空腹血糖(FPG)、餐后1h血糖(1hPG)、餐后2h血糖(2hPG)、总胆固醇(TC)、甘油三脂(TG)、载脂蛋白A(apoA)、高密度脂蛋白(HDL)和低密度脂蛋白(LDL)糖脂代谢指标水平,评估两组妊娠结局,根据妊娠结局将GDM组分为妊娠不良组和妊娠良好组,采用Pearson相关性分析。结果:GDM组NRG4、HGF、HDL-C水平均低于对照组,SAA、TG、TC、LDL-C、apoA、FPG、1hPG、2hPG、FINS、HOMA-IR水平均高于对照组;Pearson相关性分析,GDM患者血清NRG4、HGF、SAA与TG、LDL、HDL、apoA、FPG、2hPG、FINS、HOMA-IR均存在相关性(均P<0.05)。不良妊娠结局发生率GDM组(61.1%)高于对照组(8.0%),妊娠良好组血清NRG4、HGF水平均高于妊娠不良组,SAA低于妊娠不良组(均P<0.05);Pearson相关性分析,血清NRG4、HGF、SAA表达与不良妊娠结局均存在相关性(P<0.05)。结论:妊娠中晚期GDM孕妇NRG4、HGF、SAA血清水平发生异常,且表达与糖脂代谢指标和不良妊娠结局均存在相关性。