Legumain在人眼眶横纹肌肉瘤中的表达及其与肿瘤侵袭性的关系
发布时间:2018-01-24 22:20
本文关键词: 眼眶 横纹肌肉瘤 legumain α-SMA TGF-β RD 出处:《天津医科大学》2010年博士论文 论文类型:学位论文
【摘要】: 目的 1检测人眼眶横纹肌肉瘤(rhabdomyosarcoma,RMS)组织中legumain的表达,观察legumain的表达与RMS生物学行为之间的关系。并对横纹肌肉瘤患者的多个临床指标与患者预后进行多因素分析,对影响生存率的独立因素进行分析讨论。 2检测经不同浓度的转化生长因子β(transforming growth factorβ,TGF-β)刺激之后人胚胎型RMS细胞系RD细胞中legumain及α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)表达的变化,探讨legumain在RD细胞中的作用,为肿瘤的治疗提供新的思路和策略。 方法 1应用免疫组化SP法检测56例人眼眶RMS患者手术标本中legumain的表达,并引入年龄、性别、组织学类型、肿瘤大小、是否累及眼睑等因素进行统计学分析,观察各因素与患者预后的关系。 2首先利用细胞免疫荧光法检测1egumain在RD细胞中的表达情况,并使用不同浓度的TGF-β对RD细胞进行刺激,通过RT-PCR以及Western-blot技术检测刺激前后legumain及α-SMA在RD细胞中表达的变化。 结果 1 legumain在56例RMS组织中有25例高表达,并且其表达高低、肿瘤大小、组织学类型、是否累及眼睑等因素是影响横纹肌肉瘤患者生存率的独立临床因素。 2通过细胞免疫荧光法检测到RD细胞中存在legumain的表达,并且legumain及α-SMA的表达在2.5ng/ml的TGF-β刺激后较正常对照组明显升高,而5ng/ml刺激后RD细胞中legumain及α-SMA的表达较正常对照组明显降低。 结论 1 legumain在RMS组织中具有较高的表达,检测人眼眶RMS组织中legumain的表达有望成为判断肿瘤恶性程度以及患者预后的生物学指标,并为以后临床治疗眼眶RMS提供实验基础。 2 Legumian低表达、肿瘤"f5cm、胚胎型RMS、肿瘤未累及眼睑的病人均具有较高生存率。而患者的年龄、性别因素与患者的预后无关。 3低浓度的TGF-p刺激提高了RD细胞中legumain及α-SMA的表达,而高浓度的TGF-β刺激降低了RD细胞中legumain及α-SMA的表达,由于低浓度的TGF-β可以促进RD细胞的生长,而高浓度的TGF-β可以通过某种途径抑制RD细胞的生长,因此,legumain可能通过某种途径参与了TGF-β调控RD细胞生长的环节,从而增加了肿瘤细胞的侵袭性。
[Abstract]:Purpose 1the expression of legumain in human orbital rhabdomyosarcoma sarcoma (RMS) was detected. To observe the relationship between the expression of legumain and the biological behavior of RMS, and to analyze the multiple clinical indexes and prognosis of patients with rhabdomyosarcoma. The independent factors affecting survival rate were analyzed and discussed. 2TGF- 尾 -transforming growth factor 尾 was detected at different concentrations. TGF- 尾 stimulated legumain and 伪 -smooth muscle actin in human embryonic RMS cell line Rd. To explore the role of legumain in Rd cells and to provide new ideas and strategies for the treatment of tumors. Method 1 Immunohistochemical SP method was used to detect the expression of legumain in 56 patients with orbital RMS. Age, sex, histological type and tumor size were introduced. Whether the eyelid was involved or not was analyzed statistically to observe the relationship between the factors and the prognosis of the patients. 2Firstly, the expression of 1egumain in Rd cells was detected by cell immunofluorescence assay, and different concentrations of TGF- 尾 were used to stimulate Rd cells. The expression of legumain and 伪 -SMA in Rd cells was detected by RT-PCR and Western-blot techniques before and after stimulation. Results 1 there were 25 cases of high expression of legumain in 56 cases of RMS, and its expression level, tumor size, histological type. Whether the eyelid is involved or not is an independent clinical factor affecting the survival rate of patients with rhabdomyosarcoma. 2the expression of legumain in Rd cells was detected by immunofluorescence assay. The expression of legumain and 伪 -SMA was significantly higher than that of the control group after stimulation with 2.5 ng / ml TGF- 尾. The expression of legumain and 伪 -SMA in Rd cells after 5 ng / ml stimulation was significantly lower than that in normal control group. Conclusion 1 legumain was highly expressed in RMS. Detection of the expression of legumain in human orbital RMS is expected to be a biological index to judge the malignancy and prognosis of the tumor and to provide experimental basis for clinical treatment of orbital RMS. 2 low expression of Legumian, tumor. The survival rate was higher in patients with F5 cm, embryonic RMS, tumor without eyelid involvement, but age and sex factors were not associated with prognosis. (3) low concentration of TGF-p increased the expression of legumain and 伪 -SMA in Rd cells. The high concentration of TGF- 尾 decreased the expression of legumain and 伪 -SMA in Rd cells, and the low concentration of TGF- 尾 could promote the growth of Rd cells. However, high concentration of TGF- 尾 can inhibit the growth of Rd cells through some way, so legumain may participate in the regulation of the growth of Rd cells through some way. This increases the invasiveness of tumor cells.
【学位授予单位】:天津医科大学
【学位级别】:博士
【学位授予年份】:2010
【分类号】:R739.7
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