声波与手用器械联合预备后牙感染根管的临床观察

目的评价声波和手用器械联合预备感染的后牙根管的临床效果。方法对129例慢性根尖周炎的155颗后牙,随机分为实验组：76颗,163个根管,用MM1500声波手机及其配套的Rispisonic锉针,结合手用不锈钢K型锉预备根管;对照组：79颗,168个根管,单纯手用不锈钢K型锉预备。两组均用甘油一氢氧化钙糊剂根管内封药消毒,符合根充条件即行根管充填。对两组的疗程次数,根管治疗期间急症发生率,根管充填质量进行比较。结果实验组的疗程次数少于对照组（P〈0．05）;两组的急症发生率、根管充填质量无统计学意义（P〉0．05）。结论用声波器械结合手用器械预备感染的后牙根管,其虽不能提高根管充填质量和减少EIE的发生,但能减少治疗感染根管的疗程次数,具有临床应用的可行性。     

Hedgehog信号转导途径对乳腺癌MDA-MB-231细胞增殖与凋亡以及对CycinD1表达的影响

目的:本实验通过Hedgehog(HH)信号转导途径的抑制剂cyclopamine作用于人乳腺癌MDA-MB-231细胞,研究Hedgehog信号转导途径对乳腺癌MDA-MB-231细胞增殖与凋亡以及对CycinD1表达的影响.方法:以MDA-MB-231细胞为研究对象,应用Cyclopamine处理后,用MTT方法检测细胞增殖活性的改变;用流式细胞术检测细胞周期与凋亡的情况;RT-PCR检测GLI1、CyclinD1的mRNA的变化;用免疫细胞化学术检测细胞中的CyclinD1蛋白表达的变化.结果:与对照组相比,Cyclopamine可显著抑制MDA-MB-231细胞的生长并呈时效-量效关系;流式细胞术检测MDA-MB-231细胞,发现Cyclopamine能提高细胞周期G0/G1期的比例,48 h后出现明显的"亚G1"峰;GLI1,CyclinD1的mRNA以及CyclinD1蛋白的表达降低.结论:乳腺癌MDA-MB-231细胞有Hedgehog信号转导途径的激活;Hedgehog信号转导途径的抑制剂Cyclopamine能明显抑制MDA-MB-231细胞生长并能诱导其凋亡,减少CyclinD1的表达.     

雌激素受体α在乳腺癌细胞中对Gli1转录活性和表达的影响

目的:在先前研究发现Hedgehog信号通路的下游转录因子Gli1能够抑制乳腺癌细胞中的雌激素信号通路活性的基础上,观察雌激素受体ERα在乳腺癌细胞MCF-7中对转录因子Gli1的转录活性和表达的影响,以探讨两条信号通路之间是否存在着交互作用。方法:应用荧光素酶报告基因转录活性分析的方法,将Gli1的表达质粒和Gli的报告基因质粒pGli-BS-luc以及ERα的表达质粒或者空载体共同瞬时转染到乳腺癌细胞MCF-7中,观察Gli1转录活性的变化。然后分别用实时定量PCR和蛋白质印迹的方法检测乳腺癌细胞中ERα的过表达对Gli1 mRNA和蛋白表达的影响。结果:荧光素酶的活性随着ERα过表达剂量的增加而增加,ERα的质粒量在500 ng/孔时可将荧光素酶的活性升高到对照细胞的3.5倍(P<0.001)。雌激素处理后,荧光素酶的活性无显著变化。过表达ERα后可将Gli1 mRNA的表达水平提高为原来的2倍(P<0.01),也可明显增加Gli1蛋白的表达水平。结论:ERα在MCF-7细胞中的过表达能够明显增强Gli1的转录活性,增加Gli1的表达。这表明乳腺癌细胞中,转录因子ERα和Gli1之间存在着交互作用。     

Hedgehog信号通路及其抑制物在抗肿瘤治疗中的研究进展

目的:Hedgehog信号通路不仅与胚胎的发育、组织的形成、成人组织再生及修复相关,同时已被证实与多种肿瘤细胞的形成、生长和转移具有相关性。当该信号通路异常激活时,会引起肿瘤的发生和发展。因此,对多种肿瘤中Hedgehog信号通路的了解,将有助于针对其特异性治疗药物的研发和应用。目前,第一个针对Hedgehog信号通路的小分子抑制剂GDC-0449已进入临床试验阶段,并显示了良好的临床疗效。本文就此途径与肿瘤的关系及在肿瘤治疗中的应用进行综述。     

卵巢和卵巢肿瘤中Hedgehog 信号通路的表达

目的探讨正常卵巢和卵巢肿瘤中Hedgehog信号通路的表达。方法采用RT—PCR和免疫组织、细胞化学染色检测26例卵巢肿瘤组织、3例卵巢癌细胞株（SKOV3、A2780和COC1）和7例正常卵巢组织中Hedgehog信号通路的信号分子SHH、IHH、PTCH、SMO和GLI1的mRNA和蛋白表达情况;通过实时定量RT—PCR对随机抽取的11例卵巢肿瘤组织和5例正常卵巢组织进行PTCH和GLI1 mRNA水平的比较。结果SHH、IHH、PTCH、SMO和GLI1的mRNA在卵巢肿瘤组织中均有表达;SHH mRNA在正常卵巢组织中不表达,而IHH、PTCH、SMO和GLI1的mRNA在正常卵巢组织中有表达;在卵巢肿瘤组织中,PTCH和GLI1的mRNA表达水平高于正常组织（P〈0．05）。SHH、IHH、PTCH、SMO和GLI1蛋白在卵巢肿瘤组织中均呈阳性表达,在正常卵巢组织中不表达。卵巢癌细胞株SKOV3、A2780和COC1均有IHH、PTCH、SMO和GLI1的mRNA和蛋白的表达;SHH仅在SKOV3和A2780中表达。结论卵巢肿瘤中存在Hedgehog信号通路,在部分卵巢肿瘤中有Hedgehog信号通路过度激活的现象。     

Hedgehog signalling in androgen independent prostate cancer

Objectives

Androgen-deprivation therapy effectively shrinks hormone-naïve prostate cancer, both in the prostate and at sites of distant metastasis. However prolonged androgen deprivation generally results in relapse and androgen-independent tumour growth, which is inevitably fatal. The molecular events that enable prostate cancer cells to proliferate in reduced androgen conditions are poorly understood. Here we investigate the role of Hedgehog signalling in androgen-independent prostate cancer (AIPC).

Methods

Activity of the Hedgehog signalling pathway was analysed in cultured prostate cancer cells, and circulating prostate tumour cells were isolated from blood samples of patients with AIPC.

Results

AIPC cells were derived through prolonged culture in reduced androgen conditions, modelling hormone therapy in patients, and expressed increased levels of Hedgehog signalling proteins. Exposure of cultured AIPC cells to cyclopamine, which inhibits Hedgehog signalling, resulted in inhibition of cancer cell growth. The expression of the Hedgehog receptor PTCH and the highly prostate cancer–specific gene DD3^PCA3 was significantly higher in circulating prostate cancer cells isolated from patients with AIPC compared with samples prepared from normal individuals. There was an association between PTCH and DD3^PCA3 expression and the length of androgen-ablation therapy.

Conclusions

Our data are consistent with reports implicating overactivity of Hedgehog signalling in prostate cancer and suggest that Hedgehog signalling contributes to the androgen-independent growth of prostate cancer cells. As systemic anti-Hedgehog medicines are developed, the Hedgehog pathway will become a potential new therapeutic target in advanced prostate cancer.