β-catenin在乳腺发育及乳腺癌中的研究进展

β-catenin是存在于细胞膜表面和细胞质的一种多功能蛋白.在乳腺发育和肿瘤发生过程中,β-catenin通过细胞粘附、信号转导和对细胞内特定基因的表达调控来发挥重要作用.近年来研究表明,β-catenin在乳腺发育的多个阶段对干细胞的生物学特性起关键调控作用;而β-catenin信号的异常活化、聚集,将导致细胞生长、分化、代谢及生物学行为异常,诱导肿瘤发生.本文就β-catenin的相关信号通路及其在乳腺发育和乳腺癌发生发展中的作用作一综述.     

大肠癌中Gli1和β-catenin的表达及其相关性研究

 目的　探讨Hedgehog信号通路、Wnt信号通路关键组成成员Gli1和β-catenin在大肠癌组织及肠癌细胞系中的表达协同情况,以及两种蛋白之间的相互作用关系。方法　采用荧光定量反转录聚合酶链反应（RT-PCR）结合Western blot方法检测Gli1、β-catenin在4例大肠癌组织及肠癌HCT116、HT-29、DLD1、SW620细胞系中表达情况,应用免疫共沉淀技术检测二者之间是否存在相互作用。结果　与癌旁正常组织相比,Gli1和β-catenin在大肠癌组织中均高表达[平均增长倍数分别为42.69和72.11（P＜0.05）]。与HCT116相比,Gli1与β-catenin在HT-29、DLD1及SW620 3株大肠癌病变程度高的细胞中表达均升高[增长倍数分别为52.54、17.23、5.54及5.30、6.34、2.78（均P＜0.05）],二者的表达具有协同性。免疫共沉淀结果显示Gli1与β-catenin两蛋白之间存在相互作用。结论　Gli1和β-catenin在大肠癌中协同表达,蛋白之间存在相互作用,提示Gli1、β-catenin共同参与肠癌发生、发展调控,可能是Hedgehog、Wnt信号通路交互作用的一条途径,对大肠癌的预防治疗可能有提示作用。     

Loss of beta-catenin expression associated with disease progression in malignant melanoma

BACKGROUND: beta-catenin plays a crucial role in the function of cell adhesion molecules and also participates in growth regulatory signalling pathways that may be involved in malignant transformation. OBJECTIVES: To examine beta-catenin expression in lesions of melanocytic origin for associations with clinicopathological markers of disease progression and for its significance as a predictor of disease recurrence and prognosis. METHODS: beta-catenin expression was examined by immunoperoxidase staining in 50 melanocytic naevi and 91 primary and 50 metastatic melanomas. RESULTS: beta-catenin was expressed in 96% of melanocytic naevi, in 94% and 65%, respectively, of radial and vertical growth phase primary melanomas, and in 38% of metastatic melanomas. Benign and malignant melanocytic lesions had distinct patterns of beta-catenin localization. Most lesions expressing beta-catenin exhibited cytoplasmic staining; however, over 40% of benign lesions also displayed nuclear staining, which was present only in 10% of primary and 15% of metastatic melanomas. Absent or weak expression of beta-catenin in primary melanomas was associated with several markers of disease progression, including tumour thickness and presence of lymph node metastases. A similar but not statistically significant trend was observed for the association of beta-catenin expression with disease recurrence and prognosis. CONCLUSIONS: These results suggest that loss or downregulation of beta-catenin expression in melanoma cells plays a significant role in progression of the disease.     

The potential role of abnormal E-cadherin and α-, β- and γ-catenin immunoreactivity in the determination of the biological behaviour of keratoacanthoma

BACKGROUND: Failure of E-cadherin and its associated proteins alpha-, beta- and gamma-catenin is believed to lead to disruption of cell-cell adhesion and to contribute to neoplasia. OBJECTIVES: To determine the pattern of E-cadherin and alpha-, beta- and gamma-catenin immunostaining in keratoacanthoma (KA) and to evaluate its potential value in routine histopathology in differentiating KA with benign from that with malignant biological behaviour. METHODS: We examined the expression of E-cadherin and alpha-, beta- and gamma-catenin in KA and correlated the histopathological features with the immunohistochemical findings. Next, we compared the immunohistochemical findings of KA with those found in malignant (squamous cell carcinoma, SCC) and benign (warts) lesions. In addition to the established histopathological criteria we used the Ki-67 index, a well-known marker of cell proliferation. Immunoperoxidase staining of E-cadherin and alpha-, beta- and gamma-catenin, and Ki-67 determination, were performed in paraffin-embedded sections of 12 KAs taken from archival material. On reviewing the histology, seven of the 12 KAs were characterized as 'classical' KA, and the rest as 'borderline' KA or KA resembling SCC. Additionally, 28 well, nine moderately and five poorly differentiated SCCs and 20 warts were examined. RESULTS: Most 'classical' KAs (79-86%) showed normal membranous immunostaining and a low Ki-67 index. The remaining 'classical' KAs showed abnormal expression, in a staining pattern resembling that of well-differentiated SCC. All 'borderline' KAs showed a high Ki-67 index (> 40%) and abnormal expression of the adhesion molecules studied, identical to that of poorly differentiated SCC. Expression of E-cadherin and alpha-, beta- and gamma-catenin was found to be more frequently abnormal in 'borderline' KA compared with that in 'classical' KA (P < 0.05). Among E-cadherin and alpha-, beta- and gamma-catenin expression and Ki-67 index, only the expression of beta-catenin was more frequently found to be abnormal in total SCC than in total KA (P < 0.05). Expression of E-cadherin and alpha-, beta- and gamma-catenin was more frequently found to be abnormal in well-differentiated SCC than in 'classical' KA (P < 0.05). In total, as well as in 'classical' or 'borderline' KA, an agreement between expression of E-cadherin and of catenins was seen. CONCLUSIONS: These findings suggest that E-cadherin and catenins may be very helpful in distinguishing between 'classical' and 'borderline' KA, as the expression of these adhesion molecules in 'classical' KA is identical to that found in normal epidermis, overlapping with well-differentiated SCC in some cases. In 'borderline' KA, expression of adhesion molecules is identical to that in poorly differentiated SCC.     

通脉平胶囊中挥发油提取工艺及其β-CD包合工艺的研究

目的:探讨通脉平胶囊中挥发油的提取工艺及β-CD包合工艺。方法:以采用单因素试验,用正交试验法对挥发油的提取工艺进行优选,以挥发油体积为指标,以浸泡时间(A)、提取时间(B)、加水量(C)为因素进行正交试验。采用正交试验法,以包合物得率和包合率为评价指标进行包合工艺的研究。采用研磨法制备肉桂挥发油的β-环糊精(β-CD)包合物,为寻求最佳的包合工艺,选择挥发油与β-CD的投料比、搅拌时间、包合温度3个因素,采用正交试验方法进行试验。结果:挥发油的最佳提取工艺是将药材加8倍量水浸泡1h,水蒸气蒸馏6h。最佳包合工艺为挥发油与β-CD投料比1:8,搅拌时间1个小时,包合温度为60℃。并采用紫外分析法对包合物进行验证。结论:挥发油提取工艺及其β-CD包合工艺合理可行。     

紫英颗粒对过敏性紫癜患者尿β2微球蛋白和尿微量白蛋白的影响

目的 观察紫英颗粒对过敏性紫癜(热毒血瘀证)患者尿β2微球蛋白和微量白蛋白的影响.方法 将患者随机分为两组,治疗组口服紫英颗粒,对照组口服强的松;4周为1疗程.结果 两组患者尿β2微球蛋白和尿微量白蛋白治疗后均明显下降,治疗组优于对照组.结论 紫英颗粒能明显降低过敏性紫癜患者尿β2微球蛋白和尿微量白蛋白的表达水平.     

糖尿病大鼠血、尿TGF-β1的相关性及糖肾安对其表达的影响

目的:观察糖尿病大鼠血、尿TGF-β1的变化,探讨其相关性以及糖肾安煎剂对血、尿TGF-β1表达的影响。方法:STZ诱导的糖尿病大鼠给予糖肾安治疗8周后,检测大鼠血、尿TGF-β1、尿mALB水平,HE、PAS染色观察肾组织的病理学改变。结果:模型组大鼠血、尿TGF-β1、尿mALB明显高于空白对照组(P0.01),中药组、西药组明显低于模型组(P0.01),与空白对照组比较无统计学差异(P0.05)。各组大鼠血、尿TGF-β1均呈显著正相关。HE染色中药组、西药组肾小球毛细血管壁狭窄甚至闭塞较模型组减轻。PAS染色模型组肾小球基底膜成分明显增加,而中药组、西药组的基底膜成分较模型组明显降低。结论:糖肾安煎剂能降低尿mALB水平,减轻肾脏组织病理学改变,其肾脏保护作用可能与调节TGF-β1水平有关。     

过敏性紫癜肾脏损伤相关因素分析

目的探讨过敏性紫癜肾脏损伤的相关因素。方法回顾性分析过敏性紫癜248例患者的临床及实验室资料,进行统计学分析,建立回归方程。结果腹痛、上呼吸道感染、潜血、补体C3、性别、类风湿因子、血小板计数对患者尿白蛋白有影响。腹痛、尿潜血、年龄、类风湿因子、血小板计数、皮疹持续时间对患者尿球蛋白有影响。关节痛、肾区叩击痛、腹痛对患者尿微蛋白有影响。结论腹痛是肾脏损伤的重要相关因素,尿潜血则是肾脏发生较为严重损伤的实验室指标,性别、血小板计数、感染因素、皮疹持续时间、年龄、关节痛、肾区叩击痛与肾脏损伤的发生存在一定相关性。