参附注射液对单侧输尿管梗阻大鼠肾脏肝细胞生长因子表达的影响

目的：探讨单侧输尿管梗阻后大鼠肾间质纤维化发生过程中肝细胞生长因子（HGF）的表达及中药参附注射液对其的影响。方法：采用单侧输尿管结扎（UUO）制造梗阻性肾病模型，将56只大鼠随机分为对照组（假手术组）、手术组（UUO组）和治疗组（UUO＋参附），术后7d、14d观察肾组织病理改变，应用免疫组织化学方法检测肾组织中HGF的表达。结果：与对照组相比，手术组肾间质出现了明显的纤维化，HGF的表达在术后第7天明显增加，第14天较第7天减弱，与手术组相比，治疗组肾间质纤维化明显减轻，而且HGF的表达在术后第7天明显上调，第14天较第7天上调更明显，有统计学差异（P〈0．05）。结论：参附注射液可以上调肾组织HGF的表达，减轻肾小管一间质纤维化，发挥肾保护作用。     

c-Met及HGF在胃癌及其肝转移灶中的表达

目的:探讨胃癌肝细胞生长因子受体(c-Met)及肝细胞生长因子(HGF)表达与胃癌肝转移间的相关性。方法:晚期胃癌标本59例,其中11例同时有取自左肝外叶的肝转移标本,应用免疫组化方法对上述组织石蜡标本进行检测。结果:59例胃癌中,c-Met阳性率55.8%(33/59),HGF阳性率28.8%(17/59);在29例发生了同时或异时性肝转移的胃癌标本中,c-Met表达率为75.9%(22/29),HGF阳性率为37.9%(11/29),其中c-Met表达率在有和无肝转移组间有显著差异(P<0.05);在11例胃癌肝转移灶中,9例c-Met阳性表达率为81.8%,3例HGF阳性表达率为27.3%。结论:胃癌组织c-Met表达可能与胃癌肝转移行为相关。     

Growth factor-dependent activation of the MAPK pathway in human pancreatic cancer: MEK/ERK and p38 MAP kinase interaction in uPA synthesis

Increased expression of the hepatocyte growth factor (HGF) receptor (c-met) and urokinase type plasminogen (uPA) correlated with the development and metastasis of cancers. To investigate the role of HGF/c-met signaling on metastasis in cancer cells stimulated with HGF, we examined the effects of a specific MEK1 inhibitor (PD98059) and a p38 MAP kinase inhibitor (SB203580) on HGF-induced uPA expression in pancreatic cancer cell lines, L3.6PL and IMIM-PC2. Pretreatment of PD98059 decreased HGF-mediated phosphorylation of extracellular receptor kinase (ERK), uPA secretion and expression of matrix metalloproteinases (MMP-2 and MMP-9) in a dose-dependent manner. In contrast, SB203580 pretreatment increased HGF-stimulated ERK phosphorylation, uPA secretion and expression of MMPs. SB203580 also reversed the inhibition of HGF-mediated ERK activation and uPA secretion in the PD98059-pretreated cells. These results suggest that ERK activation by HGF might play important roles in the metastasis of pancreatic cancer and the p38 MAPK pathway also involved in the HGF-mediated uPA secretion and metastasis by regulation of ERK pathway. This revised version was published online in July 2006 with corrections to the Cover Date.     

Social isolation stress augments angiogenesis induced by colon 26-L5 carcinoma cells in mice

We have previously shown that tumor necrosis factor-α (TNF-α), which is an important angiogenesis-related factor, was over-secreted in male BALB/c mice under social isolation stress as compared with the control, and closely associated with a remarkable elevation of tumor invasion and metastasis of colon 26-L5 carcinoma cells. In the present study, we explored the effect of isolation stress on the angiogenesis caused by colon 26-L5 carcinoma cells in vivo and in vitro. Social isolation lead to the enhancement of tumor growth after intrahepatic implantation with a fragment of colon 26-L5 tumor. Angiogenic response (number of vessels oriented towards tumor mass) and tumor growth (size) were significantly increased in the socially isolated mouse relative to that in the group-housed mice. Furthermore, higher protein level of hepatic TNF-α was found in the stressed mice than that in the control. Expression of mRNA for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also elevated in the tumor regions and liver tissues of the stressed mice in comparison with that in group-housed mice. On the other hand, hepatic sinusoidal endothelial (HSE) cells treated with TNF-α exhibited a marked promotion of the migration, invasion, expression of mRNA for matrix metalloproteinase (MMP)-9, and tube-like formation, but no cytotoxicity against the cells in vitro. The above data suggest that the social isolation stress augmented the tumor-induced angiogenesis probably by up-regulating the angiogenesis-related factors, including TNF-α, VEGF and HGF, and consequently mediating the functions of endothelial cells such as migration, invasion, and tube-like formation.     

Adhesion dependent release of hepatocyte growth factor and interleukin-1 receptor antagonist from human blood granulocytes and monocytes: Evidence for the involvement of plasma IgG,complement C3 and β2 integrin

Objective:Evolving evidence of anti-inflammatory effects is observed in patients with rheumatoid arthritis or ulcerative colitis following periodic adsorptive granulocyte and monocyte (GM) apheresis with a column containing cellulose acetate (CA) beads as apheresis carriers. This study was undertaken to obtain insights into mechanisms of anti-inflammatory actions of adsorptive GM apheresis with CA beads. Methods:In a series of in-vitro experiments, we investigated the effects of plasma proteins and the leucocytes 2 integrin (CD18) on granulocyte adsorption to CA beads. Results:Granulocyte adsorption to CA beads required plasma IgG, the complement C3 and was inhibited by an antibody to leucocytes CD18. Further, hepatocyte growth factor (HGF) and interleukin-1 receptor antagonist (IL-1ra) which have strong anti-inflammatory actions were released by granulocytes that adhered to CA beads. Conclusions:Plasma IgG, C3 derived complement activation fragments and leucocytes CD18 are involved in granulocyte adhesion to CA beads and hence the release of HGF and IL-1ra.Received 27 October 2003; returned for revision 16 December 2003; accepted by M. J. Parnham 8 January 2004     

肝细胞生长因子及其受体在肿瘤中的研究进展

肝细胞生长因子是一种多肽生长因子,与其受体结合后,具有强促分裂、组织成形、诱导肿瘤细胞迁移、侵袭以及诱导血管生成等作用。肝细胞生长因子受体c-Met广泛存在于多种正常组织细胞和体内外恶性肿瘤细胞内,肝细胞生长因子与其受体和肿瘤的发生、发展以及肿瘤新生血管形成有密切关系。     

HGF介导DXR诱导肝癌细胞的凋亡作用

 为了解肝细胞生长因子(HGF)对DXR诱导凋亡效用.方法:肝癌细胞处理分为单用组:DXR、ActinD和HGF.联合组DXR(0.0lug/ml)＋HGF(l0,20,30ng/ml)、DXR＋ActinD＋HGF;生理盐水及牛血清白蛋白对照组.测定MTT值,H-E染色及Hoe-chest33258荧光染色观察细胞形态.结果:24h大剂量DXR引起10%癌细胞凋亡、54%细胞死亡,小剂量者无明显诱导凋亡作用;大剂量ActinD凋亡细胞<30%.HGF10-50ng/ml无明显诱导凋亡效用.DXR(0.0lug/ml)＋HGF(10,20,30ng/ml)组48h后随HGF剂量加大细胞凋亡数亦增加.依次加入DXR、放线菌素D后对HGF介导的效用有抑制性.结论:合用DXR和HGF能够诱导肝癌细胞凋亡,可能与HGF介导的信号传导有关.     

细胞因子HGF体外增强骨肉瘤细胞株的增殖和黏附性

【目的】研究肝细胞生长因子，离散因子（HGF／SF）及其受体蛋白c-Met在骨肉瘤细胞株MG-63和HOS中的表达及对瘤细胞生物学行为的影响，探讨HGF／c-Met系统在骨肉瘤细胞生长侵袭过程中的作用。【方法】用流式细胞术检测HGF-α、HGF-β、c-Met在2株骨肉瘤细胞株中的表达；外源性HGF刺激此2株细胞株后，用MTT法、黏附性检测方法研究细胞增殖速率和黏附性的变化。【结果】HGF-α、HGF-β、c-Met在2株骨肉瘤细胞株中的阳性表达率均低于3％。HGF浓度达50ng／mL以上时．MG-63和HOS的增殖速率显著增高，P〈0．01。当外源性HGF的浓度分别达5ng／mL和10ng／mL时，MG-63和HOS的黏附性指标即显著升高，P〈0．01。外源性HGF刺激后HGF-α、HGF-β、c-Met在2株骨肉瘤细胞株中的表达略有变化，但差异无统计学意义，P〉0．05。【结论】HGF可以促进骨肉瘤细胞株MG-63和HOS的体外增殖和黏附能力。     

肝细胞生长因子研究进展

肝细胞生长因子是一个多效应生长因子，参与机体多种器官组织细胞的生长、再生和重塑等过程。本文综述近年来肝细胞生长因子在生物学方面的研究，包括HGF／c-met受体的结构、信号转导和生物学功能等方面。