刺猬蛋白在宫颈癌组织中的表达及其临床意义

目的检测刺猬蛋白(Sonic Hedgehog,SHH)在正常宫颈、宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及宫颈癌组织中的表达情况,探讨其与宫颈癌发生发展的关系。方法采用免疫组化SP法,检测正常宫颈组织、CIN及宫颈癌组织中SHH的表达。结果 SHH在宫颈癌组织中高表达。结论 SHH在宫颈癌中的异常表达表明Hedgehog(Hh)信号传导通路可能参与宫颈癌的发生过程。     

Tetramethylpyrazine inhibits the proliferation,invasiveness and migration of cervical cancer C33A cells by retarding the Hedgehog signaling pathway

Cervical carcinoma (CC) ranks among the top four most common cancers in women worldwide. Over the last 10 years, several studies have confirmed the inhibitory effects of tetramethylpyrazine (TMP) on numerous types of cancer. To investigate the inhibitory effect of TMP on the CC C33A cell line, MTT and colony formation assays were performed to determine how TMP affects C33A cell survival and proliferation. Proliferation-, migration- and hedgehog (Hh) signaling pathway-related protein expression levels were analyzed via western blotting. Wound-healing and Transwell assays were used to detect the migration and invasion abilities of C33A cells, respectively. The results indicated that TMP markedly reduced the C33A cell survival rate compared with the cervical epithelial Ect1 cell line, which was unaffected by TMP treatment. C33A cell proliferation was downregulated by TMP treatment in a dose-dependent manner. TMP treatment also significantly inhibited C33A cell migration and invasiveness in a dose-dependent manner. Furthermore, TMP inhibited the Hh signaling pathway, as demonstrated by a dose-dependent reduction in Hh-related protein expression levels following TMP treatment. Subsequently, treatment with smoothened agonist increased the proliferation, invasiveness and migration abilities of TMP-treated C33A cells. In conclusion, TMP inhibited the proliferation, migration and invasiveness of CC cells via inhibition of the Hh signaling pathway.     

Oncogenic properties and signaling basis of the PAX8-GLIS3 fusion gene

Hyalinizing trabecular tumors of the thyroid are rare and mostly benign epithelial neoplasms of follicular cell origin, which have recently been shown to be underpinned by the PAX8-GLIS3 fusion gene. In our study, we sought to investigate the potential oncogenic mechanisms of the PAX8-GLIS3 fusion gene. Forced expression of PAX8-GLIS3 was found to increase proliferation, clonogenic potential and migration of human nonmalignant thyroid (Nthy-ori 3-1) and embryonic kidney (HEK-293) cells. Moreover, in xenografts, Nthy-ori 3-1 PAX8-GLIS3 expressing cells generated significantly larger and more proliferative tumors compared to controls. These oncogenic effects were found to be mediated through activation of the Sonic Hedgehog (SHH) pathway. Targeting of smoothened (SMO), a key protein in the SHH pathway, using the small molecule inhibitor Cyclopamine partially reversed the increased proliferation, colony formation and migration in PAX8-GLIS3 expressing cells. Our data demonstrate that the oncogenic effects of the PAX8-GLIS3 fusion gene are, at least in part, due to an increased activation of the SHH pathway.     

大鼠失舌神经对舌味蕾Shh表达的影响

目的：探讨SD大鼠失舌神经对舌味蕾Shh表达的影响。方法：216只SD大鼠随机分为3组即正常组、单侧失神经组和双侧失神经组,每组各72只。腹腔注射麻醉后,正常组于下颌磨牙舌侧切开显露舌神经后直接缝合口底黏膜,单侧失神经组暴露并剪除右侧舌神经约0.5cm,双侧失神经组暴露并剪除双侧舌神经各0.5cm。分别于术后6h、12h、1d、2d、3d、5d、10d、15d、20d、1个月、2个月、3个月时处死动物,切取舌前2/3组织,以免疫组织化学法及原位杂交法检测味蕾Shh（sonic hedgehog）基因及蛋白的表达。结果：大鼠失舌神经支配后,舌味蕾Shh的表达逐渐降低,一侧失神经不影响健侧Shh的表达;在一定时间内,单侧失神经组可观察到术侧舌味蕾Shh表达的恢复,而双侧失神经组未见恢复。结论：SD大鼠失舌神经后,舌味蕾Shh表达明显减弱。     

胚胎发育信号通路Sonic hedgehog在胰腺癌组织中的表达及意义

目的 研究胚胎发育信号通路Sonic hedgehog(SHH)在胰腺癌组织中的表达及其临床意义.方法 逆转录聚合酶链反应(RT-PCR)技术和免疫组化方法检测胰腺癌组织及癌旁组织中SHH mRNA和蛋白的表达情况.结果 78.9%(30/38)胰腺癌组织中检测到SHH mRNA)18.4%(7/38)癌旁正常组织SHH mRNA阳性.免疫组化结果显示:84.2%(32/38)胰腺癌组织SHH蛋白呈阳性表达;癌旁胰腺组织SHH阳性率为21.1%(8/38).两组差异有显著意义(P<0.01).SHH蛋白表达与年龄、肿瘤大小、TNM分期、淋巴结转移状况、组织学类型和肿瘤部位均无关(P>0.05).结论 SHH信号分子在胰腺癌组织中表达增高,SHH信号途径可能在胰腺癌发生发展过程中起重要作用.