OBJECTIVE To investigate the role of connexin proteins(Cx),which form gap junctions(GJ),in progression and chemotherapeutic sensitivity of cervical cancer(CaC x).METHODS We analyze the expression of Cx26,Cx30,Cx32 and...OBJECTIVE To investigate the role of connexin proteins(Cx),which form gap junctions(GJ),in progression and chemotherapeutic sensitivity of cervical cancer(CaC x).METHODS We analyze the expression of Cx26,Cx30,Cx32 and Cx43 in human specimens consisting of:Normal cervix(n=78),CaCx FIGO stageⅠ(n=148),CaCx FIGO stageⅡ(n=165).In CaCx cell lines,Hela-Cx32(induced expression by doxycycline),C-33A(endogenously express Cx32)and si Ha(transiently transfected plasmid with Cx32),we detected the role of Cx32 against tostreptonigrin/cisplatin-induced apopotosisin presence or absence of functional GJ through using GJ inhibitors or low density cultural.Furtherly,we observed the relativity of Cx32 and EGFR expression in human specimens.Also,we detected the role of EGFR signaling pathway in the process of Cx32 anti-apoptosis through suppressed EGFR expression by inhibitors or si RNA sequences in cell lines.RESULTS We firstly demonstrated the expression of Cx32 was highly upregulated and accumulated in cytoplasm in the CaCx specimens,and the degree of upregulation correlated with advanced FIGO stages.Thus,in three human cervical cell lines,Cx32 was shown to suppress apoptosis when GJ formation is inhibited.No matter in cases of CaCx or cell lines,Cx32 expression was highly correlated with expression of EGFR and the EGFR pathway is an essential component of the Cx32-induced anti-apoptotic effect.CONCLUSION Cx32,traditionally tumor suppressive protein,was shown to be tumor protective against chemotherapy through EGFR pathway in a GJ-independent way.展开更多
OBJECTIVE Cervical cancer is the third most malignant tumor in the world.Farnesoid X receptor(FXR) is a member of nuclear receptor superfamily.It is highly expressed in liver,kidney and small intestine,while it showed...OBJECTIVE Cervical cancer is the third most malignant tumor in the world.Farnesoid X receptor(FXR) is a member of nuclear receptor superfamily.It is highly expressed in liver,kidney and small intestine,while it showed low expression level in other tissues.It not only plays an important role in the metabolism of bile acids and sugars,but also in the production of chronic inflammation in the early stage of cancer,the proliferation and migration of tumor.Compared with the normal tissue,the expression of FXR in most tumor tissues decreased.But there is no correlation between cervical cancer and FXR.So we aimed to find out the relationship between FXR and cervical cancer.METHODS A clinical study using q PCR,western blot and immunohistochemistry detected the expression of FXR in tumor tissues and normal tissues of clinical patients.FXR was activated by agonists or over-expressed by lentivirus.MTT,clone formation and flow cytometry were used to detect the relationship between FXR and proliferation of cervical cell lines.Tumor growth ability of FXR was detected by nude mice tumorigenicity.The interaction between FXR and CDKN2A-p14^(ARF)-MDM2-p53 pathway was detected by q PCR,Western blot and immunohistochemistry.RESULTS FXR was decreased in cancer tissues compared to normal control.Activation of FXR by agonist or constitutively-over-expression of FXR inhibited cervical cell proliferation.Over-expressed FXR attenuated Caski,Hela and Siha xenograft tumor growth in nude mice compared with control.Over-expression of FXR caused G1 cell-cycle arresting and up-regulated CDKN2A-p14^(ARF)-MDM2-p53 pathway.CONCLUSION FXR inhibits cervical cancer cell proliferation and cervical tumorigenicity which is related to CDKN2A-p14^(ARF)-MDM2-p53 pathway.Activation or overexpression of FXR may be a potential target for the treatment of cervical cancer.展开更多
目的采用两种不同的人工智能(artificial intelligence,AI)算法技术构建两种不同的宫颈液基薄层细胞涂片(liquid-based cytology,LBC)质控模型,通过混合AI辅助,对比两种算法模型对宫颈LBC的质量控制水平的提高总用。方法使用了105例宫颈...目的采用两种不同的人工智能(artificial intelligence,AI)算法技术构建两种不同的宫颈液基薄层细胞涂片(liquid-based cytology,LBC)质控模型,通过混合AI辅助,对比两种算法模型对宫颈LBC的质量控制水平的提高总用。方法使用了105例宫颈LBC样本,分别采用卷积神经网络(convolutional neural network,CNN)算法和Transformer网络算法作为具体的AI算法。标记的特征包括片内细胞量、红细胞过多、炎细胞过多、气泡,涂片样本经过涂片预处理和数字化,然后进行图像分割和特征提取。利用标记的特征数据,进行机器学习模型的训练和优化。统计两种AI模型与医师的质控结果,计算KAPPA指数、灵敏度、特异度、曲线下面积(area under the curve,AUC)等指标对AI质控结果进行分析。结果CNN算法在正常涂片、炎性背景和血性背景方面的质控结果与专家复核质控结果具有统计学差异(P<0.001);Transformer算法质控结果与专家复核结果相似,差异不具有统计学意义(P>0.05);普通医师质控结果与专家复核质控结果在正常涂片检出率和血性背景方面具有统计学差异(P<0.001)。CNN算法Kappa值=0.567,与专家复核结果一致性中等;Transformer算法Kappa值=0.890,与专家复核结果一致性最好;普通医师Kappa值=0.675,与专家复核结果一致性较好。以专家复核结果作为参考标准,对Transformer算法与普通医师的质控结果预测效能进行评价,在检出血性背景与正常涂片方面,Transformer算法的预测效能(炎性背景:AUC=1.000;正常涂片:AUC=0.768)高于普通医师(血性背景:AUC=0.849;正常涂片:AUC=0.500)。结论Transformer算法能够有效辅助医师进行宫颈LBC质控评分,提高涂片样本质量控制的效率和准确性,为宫颈癌细胞学筛查提供了一种新的质量控制方法,具有潜在的临床应用前景。展开更多
基金supported by National Nature Science Foundation of China(U1303221)National Natural Science Foundation of China(81373439,81473234)Construction of Technique Plate for Evaluation of the Pharmacodynamics of New Drugs in Xinjiang from the Department of Science and Technology of Xinjiang Province(201233150)
文摘OBJECTIVE To investigate the role of connexin proteins(Cx),which form gap junctions(GJ),in progression and chemotherapeutic sensitivity of cervical cancer(CaC x).METHODS We analyze the expression of Cx26,Cx30,Cx32 and Cx43 in human specimens consisting of:Normal cervix(n=78),CaCx FIGO stageⅠ(n=148),CaCx FIGO stageⅡ(n=165).In CaCx cell lines,Hela-Cx32(induced expression by doxycycline),C-33A(endogenously express Cx32)and si Ha(transiently transfected plasmid with Cx32),we detected the role of Cx32 against tostreptonigrin/cisplatin-induced apopotosisin presence or absence of functional GJ through using GJ inhibitors or low density cultural.Furtherly,we observed the relativity of Cx32 and EGFR expression in human specimens.Also,we detected the role of EGFR signaling pathway in the process of Cx32 anti-apoptosis through suppressed EGFR expression by inhibitors or si RNA sequences in cell lines.RESULTS We firstly demonstrated the expression of Cx32 was highly upregulated and accumulated in cytoplasm in the CaCx specimens,and the degree of upregulation correlated with advanced FIGO stages.Thus,in three human cervical cell lines,Cx32 was shown to suppress apoptosis when GJ formation is inhibited.No matter in cases of CaCx or cell lines,Cx32 expression was highly correlated with expression of EGFR and the EGFR pathway is an essential component of the Cx32-induced anti-apoptotic effect.CONCLUSION Cx32,traditionally tumor suppressive protein,was shown to be tumor protective against chemotherapy through EGFR pathway in a GJ-independent way.
基金supported by Medical Science and Technology Research Foundation of Guangdong Province(2015120104622949)
文摘OBJECTIVE Cervical cancer is the third most malignant tumor in the world.Farnesoid X receptor(FXR) is a member of nuclear receptor superfamily.It is highly expressed in liver,kidney and small intestine,while it showed low expression level in other tissues.It not only plays an important role in the metabolism of bile acids and sugars,but also in the production of chronic inflammation in the early stage of cancer,the proliferation and migration of tumor.Compared with the normal tissue,the expression of FXR in most tumor tissues decreased.But there is no correlation between cervical cancer and FXR.So we aimed to find out the relationship between FXR and cervical cancer.METHODS A clinical study using q PCR,western blot and immunohistochemistry detected the expression of FXR in tumor tissues and normal tissues of clinical patients.FXR was activated by agonists or over-expressed by lentivirus.MTT,clone formation and flow cytometry were used to detect the relationship between FXR and proliferation of cervical cell lines.Tumor growth ability of FXR was detected by nude mice tumorigenicity.The interaction between FXR and CDKN2A-p14^(ARF)-MDM2-p53 pathway was detected by q PCR,Western blot and immunohistochemistry.RESULTS FXR was decreased in cancer tissues compared to normal control.Activation of FXR by agonist or constitutively-over-expression of FXR inhibited cervical cell proliferation.Over-expressed FXR attenuated Caski,Hela and Siha xenograft tumor growth in nude mice compared with control.Over-expression of FXR caused G1 cell-cycle arresting and up-regulated CDKN2A-p14^(ARF)-MDM2-p53 pathway.CONCLUSION FXR inhibits cervical cancer cell proliferation and cervical tumorigenicity which is related to CDKN2A-p14^(ARF)-MDM2-p53 pathway.Activation or overexpression of FXR may be a potential target for the treatment of cervical cancer.
文摘目的采用两种不同的人工智能(artificial intelligence,AI)算法技术构建两种不同的宫颈液基薄层细胞涂片(liquid-based cytology,LBC)质控模型,通过混合AI辅助,对比两种算法模型对宫颈LBC的质量控制水平的提高总用。方法使用了105例宫颈LBC样本,分别采用卷积神经网络(convolutional neural network,CNN)算法和Transformer网络算法作为具体的AI算法。标记的特征包括片内细胞量、红细胞过多、炎细胞过多、气泡,涂片样本经过涂片预处理和数字化,然后进行图像分割和特征提取。利用标记的特征数据,进行机器学习模型的训练和优化。统计两种AI模型与医师的质控结果,计算KAPPA指数、灵敏度、特异度、曲线下面积(area under the curve,AUC)等指标对AI质控结果进行分析。结果CNN算法在正常涂片、炎性背景和血性背景方面的质控结果与专家复核质控结果具有统计学差异(P<0.001);Transformer算法质控结果与专家复核结果相似,差异不具有统计学意义(P>0.05);普通医师质控结果与专家复核质控结果在正常涂片检出率和血性背景方面具有统计学差异(P<0.001)。CNN算法Kappa值=0.567,与专家复核结果一致性中等;Transformer算法Kappa值=0.890,与专家复核结果一致性最好;普通医师Kappa值=0.675,与专家复核结果一致性较好。以专家复核结果作为参考标准,对Transformer算法与普通医师的质控结果预测效能进行评价,在检出血性背景与正常涂片方面,Transformer算法的预测效能(炎性背景:AUC=1.000;正常涂片:AUC=0.768)高于普通医师(血性背景:AUC=0.849;正常涂片:AUC=0.500)。结论Transformer算法能够有效辅助医师进行宫颈LBC质控评分,提高涂片样本质量控制的效率和准确性,为宫颈癌细胞学筛查提供了一种新的质量控制方法,具有潜在的临床应用前景。
