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1.
Ang1、Ang2及其受体Tie2在血管瘤组织中的表达及意义   总被引:1,自引:0,他引:1  
目的探讨血管瘤的血管生成与促血管生成素家族(Ang/Tie2)之间的关系。方法通过免疫组化SP法、RT-PCR检测增生期血管瘤17例、消退期血管瘤13例和小儿正常皮肤10例的组织中促血管生成素1(Ang1)、促血管生成素2(Ang2)及其受体Tie2的表达情况。结果增生期血管瘤组织Ang2、Tie2表达高于消退期血管瘤(P〈0.01);Ang2、Tie2在小儿正常皮肤表达较弱或阴性;Ang1在血管瘤和小儿正常皮肤表达均较弱或阴性,二者比较差异无统计学意义(P〉0.05)。结论Ang/Tie2体系在血管瘤的增生和消退过程中可能起重要的作用。  相似文献   

2.
Mesenchymal stem cells (MSCs) are pleiotrophic cells that differentiate to chondrocytes, osteoblasts, or adipocytes, as a result of crosstalk by specific signaling pathways including MAPK pathway. Recently cartilage oligomeric matrix protein angiopoietin1 (COMP‐Ang1), an Ang1 variant which is more potent than native Ang1 in phosphorylating Tie2 receptor was developed. The Ang1/Tie2 signaling system not only plays a pivotal role in vessel growth, remodeling, and maturation, but also protective and recruit effect on MSCs. Thus, the aim of the present study was to investigate the differentiate effect of Ang1/Tie2 signaling on MSCs in the presence of chondrogenic, osteogenic and adipogenic induction medium, and to determine the possible mechanisms. Our results clearly demonstrated that MSCs cultured in each induction medium with COMP‐Ang1 revealed strongly chondrogenic and osteogenic morphological change (3.5‐ and 2‐fold, respectively) as well as up‐regulate each gene, except for adipogenic differentiation. Accordingly, we found that phosphorylation of Tie2 expression lead to phosphorylation of p38 and AKT and then accelerating each differentiation of MSCs to chondrocytes and osteoblasts. Therefore, our findings suggest that COMP‐Ang1 present a portal to promote MSCs differentiation to chondrocytes and osteoblasts through Ang1/Tie2 signaling pathway and provide insights into novel therapies for bone diseases. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1920–1928, 2013  相似文献   

3.
OBJECTIVE: Pigment epithelium-derived factor is known to be an inhibitor of angiogenesis. We hypothesized that in vivo gene transfer of pigment epithelium-derived factor may inhibit tumor angiogenesis and growth in syngeneic models of thoracic malignancies. METHODS: An adenovirus vector encoding the human pigment epithelium-derived factor cDNA (AdPEDF) was used to transduce human lung cancer cells in vitro. Transgene expression was assessed using Western analysis. Three different murine flank tumors (2 lung, 1 colon) were then established in syngeneic mice and treated intratumorally with phosphate-buffered saline, AdPEDF, or an empty vector (AdNull). Endpoints measured included transgene expression, tumor size, and animal survival, as well as microvessel density within the tumor. Additionally, a murine pulmonary metastasis model was established by intravenous injection of a syngeneic colon adenocarcinoma cell line expressing a marker gene (beta-galactosidase). One day later, treatment (phosphate-buffered saline, AdNull, or AdPEDF) was administered intrapleurally. Tumor burden (gross and histologic inspection, lung weight, and beta-galactosidase expression) was then evaluated 13 days after vector dosing, and survival was recorded. RESULTS: AdPEDF-derived expression of pigment epithelium-derived factor was demonstrated in vitro and in vivo. In syngeneic murine lung cancer flank tumors, intratumoral administration of AdPEDF significantly inhibited tumor growth (P <.01), prolonged mouse survival (P <.01), and decreased microvessel density (P <.01) compared with control groups. In the pulmonary metastasis model, AdPEDF-treated mice exhibited significantly reduced lung lesions, lung weight (P <.0005), beta-galactosidase expression (P <.05), and animal survival was prolonged (P <.05). CONCLUSION: Gene transfer of pigment epithelium-derived factor suppresses tumor vascularization and growth, while prolonging survival in syngeneic murine models of thoracic malignancies.  相似文献   

4.
The effect of captopril, angiotensin-converting enzyme inhibitor, on angiogenesis in several reports remained unclear. Its effect on neovascularization in rat abdominal skin flaps was investigated. Flap elevation, based on the right superficial inferior epigastric artery was performed with or without the administration of captopril (10 mg/kg/d), Ang II (100 microg/kg/d), or captopril and Ang II cotreatment. Mean arterial pressure (MAP), microangiography, capillary density measurement, necrosis area determination, laser Doppler flowmetry (LDF), AT1 and vascular endothelial growth factor (VEGF) immunostaining were used to evaluate the effects of captopril and the interaction between captopril and Ang II on the angiogenesis. Ang II and captopril cotreatment improved angiogenesis more than Ang II or captopril alone. The reduction of necrosis, enhancement of vascular network formation, capillary density, VEGF immunostaining, and local blood flow were evident in the cotreated group. We suggest that Ang II and captopril cotreatment improves ischemia-induced angiogenesis and increased viability and vascularity of skin flap in rats.  相似文献   

5.
目的探讨促血管生成素-1(Ang-1)、促血管生成素-2(Ang-2)及其受体Tie2在血管瘤和血管畸形组织中的表达及意义。方法应用免疫组织化学S—P方法,测定血管瘤、血管畸形的血管内皮细胞中Ang-1、Ang-2及Tie2的表达。结果Ang-2、Tie2的表达在增生期血管瘤最强;在退化期血管瘤中的表达次之;而在血管畸形中表达较弱,与小儿正常皮肤表达无显著性差异。而Ang-1的表达,各组差异无统计学意义。结论Ang-1、Ang-2及其受体Tie2在血管瘤的血管生成以及血管瘤的自然消退过程中可能起着重要的作用;Ang-1、Ang-2及其受体Tie2的表达可能与血管畸形的发病无明显关系。  相似文献   

6.
Background: A randomized treating colorectal hepatic metastases demonstrated that hepatic arterial floxuridine (FUdR) with dexamethasone increased tumor response compared with hepatic arterial FUdR alone (Cancer 1992;69:327–34). The mechanism of this improvement is unclear. Methods: We investigated the effect of hepatic arterial dexamethasone with or without FUdR on the growth of colorectal hepatic metastases in an animal model. BD-IX rats were inoculated intrasplenically with 107 K12/TRb colon cancer cells on day 0. On day 14, the hepatic metastases were counted and hepatic arterial catheters placed for chemotherapy. Forty-eight animals were randomized to 4 groups for 14 days of infusion with heparinized saline alone (group A), heparinized saline with dexamethasone 0.03 mg/kg/d (group B), heparinized saline with FUdR 2 mg/kg/d (group C), or heparanized saline with dexamethasone 0.03 mg/kg/d plus FUdR 2 mg/kg/d (group D). The hepatic metastases were recounted by laparotomy on day 28. Response in each rat was expressed in terms of percentage change in number of hepatic nodules between the number of hepatic nodules seen on days 14 and 28. In vitro chemosensitivity of K12/TRb to dexamethasone with or without FUdR was examined using an MTT (3-(4,5-dimethylthiazole-2-yl-2,5-diphenyltetrazolium bromide; Sigma, St. Louis, MO, U.S.A.) assay. The effect of dexamethasone on tumor-induced angiogenesis was tested using an in vivo assay. Results: The mean percentage change in tumor nodules was +129% in group A, +17% in group B, −4% in group C, and −29% in group D (p=0.002 A vs. B, p=0.04 C vs. D). The MTT assay showed that dexamethasone had no direct effect on K12/TRb growth or on tumor FUdR sensitivity. Dexamethasone inhibited K12/TRb-induced angiogenesis in vivo. Conclusions: Hepatic arterial dexamethasone is effective in treating colorectal hepatic metastases and is more effective when combined with hepatic arterial FUdR. The antiangiogenic activity of dexamethasone may partially contribute to its efficacy.  相似文献   

7.
8.
目的 观察生长激素(GH)作用前后胰腺癌细胞中GH-磷酸化Janus激酶2(pJAK2)信号转导通路的特征,探讨GH对胰腺癌细胞作用的分子机制.方法 不同浓度的GH(50、100 μg/L)作用于胰腺癌细胞(SW-1990、Cap-1、ASPC),计数培养24、48、72h后的细胞数;收集SW-1990注射于裸鼠背部皮下,成瘤后随机分为注射GH的实验组(GH组,共21只,每日4 mg/kg共2周,1、2、24 h取材,每组7只)及注入盐水的对照组(NS组,7只),注射期间隔日测量瘤体积.Western blot方法观察GH作用后不同时间(体外,GH 50μg/L:5、10、15、30、45min、1、2 h;体内:1、2、24 h)胰腺癌细胞pJAK2表达变化.结果 GH可刺激SW-1990、Cap-1、ASPC增殖但在体内不促进肿瘤牛长:pJAK2在7株胰腺细胞(SW-1990、Cap-1、Colo、Mia、Aspc、P3、Panc-1)均有不同程度的表达;与细胞毒T淋巴细胞(CTL)比较,GH刺激后pJAK2表达显著增强(5、10、15 min尤为明显),但1、2 h有减弱趋势;GH应用于裸鼠后各时间点(1、2、24 h)pJAK2在移植瘤中的表达差异无统计学意义.结论 GH能促进胰腺癌细胞SW-1990、Cap-1、ASPC增殖,但在体内不刺激肿瘤生长;GH可显著增强pJAK2在SW-1990中的表达,而在体内这种变化不明显.  相似文献   

9.

Objective

Angiopoietin-1 (Ang1) and −2(Ang2) are 2 ligands for the endothelium-specific tyrosine kinase Tie2. Previous studies have shown that reciprocal regulation of Ang1, Ang2, and Tie2 plays an important role in chronic cardiac allograft vasculopathy. This study investigated the expressions of Ang1, Ang2, and Tie2 in rat renal allografts undergoing chronic allograft nephropathy (CAN).

Materials and Methods

Renal transplantations following the procedure of Kamada with our modification were orthotopically performed using Fisher (F344, RT11v1) rats as both donors and recipients in the autograft group. Fisher and Lewis (LEW, RT11) rats were used as donors and recipients in the allograft group, respectively, which was treated with cyclosporine (CsA; 10 mg/kg/d × 10 d). At 4w, 8w, and 12 weeks posttransplantation, serum creatinine (SCr) was measured and pathologic changes assessed according to the Banff 97 criteria. The mRNA (Δct) and protein expressions of Ang1, Ang2, and Tie2 were localized by real-time fluorescence quantitative polymerase chain reaction (PCR) and by immunohistochemistry.

Results

The elevation in SCr and the pathologic changes in CAN were observed in all allografts at 8 and 12 weeks. The expressions of Ang1 and Ang2 were localized to epithelial cells and endothelium of the vascular bundles of the glomeruli; Tie2 was specifically expressed in endothelium of vessels both in auto- and allografts at all time points posttransplantation. At 4 weeks, the differences in mRNA expression of Ang1, Ang2, and Tie2 between the 2 groups were not significant (P > .05). Compared with autografts, the mRNA expression of Ang1 decreased significantly (P = .008 and .003 for 8 and 12 weeks, respectively), and the mRNA expressions of Ang2 and Tie2 significantly increased (P = .001/.006 and .005/.001 for 8 and 12 weeks, respectively). The changes in expression of all 3 genes showed significant correlation with the Banff score in the allografts.

Conclusion

This study suggested that the abnormal expression and reciprocal regulation of Ang1, Ang2, and Tie2 may play important roles in the development of CAN in rat renal allografts.  相似文献   

10.
AIM: The aim of this study was to determine the effect of intravesical EDTA instillation on the development of intravesically implanted tumor cells in normal mice. METHODS: The mouse bladder tumor (MBT-2) model was used in female C3H/eb mice to evaluate the amount of normal urothelial cell shedding, and the degree of tumor growth inhibition following intravesical EDTA instillation in comparison with phosphate-buffered saline (PBS) instillation. RESULTS: At 1 h after instillation, the number of urothelial cells aspirated was 500-1000 per PBS-treated mouse and 10,000-20,000 per EDTA-treated mouse (P < 0.00001). The bladder weight, which reflected the effect of the agent on the tumor, was similar in the untreated and PBS-treated mice (105.46 +/- 46 mg and 106.2 +/- 50 mg, respectively). It was significantly lower in the EDTA-treated mice (80.4 +/- 42 mg) (P = 0.0045). CONCLUSIONS: Intravesical administration of EDTA results in significant normal and neoplastic urothelial cell shedding. Intravesical irrigation with EDTA may prevent adherence of the malignant cells to the bladder wall following tumor resection.  相似文献   

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