Uterine cervical cancer is the second most common gynecological malignancy. It is estimated that over 35% of tumors are diagnosed at locally advanced disease, stage ⅠB2-ⅡB with an estimated 5-year overall survival o...Uterine cervical cancer is the second most common gynecological malignancy. It is estimated that over 35% of tumors are diagnosed at locally advanced disease, stage ⅠB2-ⅡB with an estimated 5-year overall survival of 60%. During the last decades, the initial treatment for these women has been debated and largely varies through different countries. Thus, radical concurrent chemoradiation is the standard of care in United Sated and Canada, and neoadjuvant chemotherapy followed by radical surgery is the first line of treatment in some institutions of Europe, Asia and Latin America. Until today, there is no evidence of which strategy is better over the other. This article describe the evidence as well as the advantages and disadvantages of the main strategies of treatment for women affected by uterine cervical cancer stage ⅠB2-ⅡB.展开更多
Background Histone deacetylase （HDAC） inhibitors are a group of small chemical molecules that inhibit histone deacetylase. At cell level, HDAC inhibitors have multiple biological effects such as cell cycle arrest, a...Background Histone deacetylase （HDAC） inhibitors are a group of small chemical molecules that inhibit histone deacetylase. At cell level, HDAC inhibitors have multiple biological effects such as cell cycle arrest, apoptosis, cell differentiation and auotophagy. At molecular level, HDAC inhibitors cause histone and nonhistone acetylation and induce gene expression. HDAC inhibitors are widely used in cancer therapy because of its function of inducing apoptosis. However, the mechanisms of apoptosis effect are not fully understood. TSA is a classical HDAC inhibitor and widely used in epigenetic and anti-cancer research. In this study, we selected Trichostatin A （TSA） to investigate the mechanisms of HDAC inhibitors apoptotic effect on cancer cells. Methods Cervical cancer cell lines such as Hela, Caski and normal human keratinocyte line HaCaT were treated with various concentrations of TSA. Crystal violent assay and 3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay were performed to determine cell number. PARP cleavage and FITC-AnexinV were performed to determine apoptosis. DNA-methyltransferase （DNMT）I, DNMT3A and DNMT3B were determined by regular PCR, qPCR and Western Blotting. Small interfering RNA （SiRNAi） was used to knock down DNMT3B. Results HDAC inhibitors only induce cervical cancer cell apoptosis. At 1 Iumol/L of TSA, 86% of Hela cell and 76% of Caski went apoptosis. For normal cells, HDAC inhibitors have no cytotoxic effect at therapeutic dosage, （90.0＋8.4）% of normal cell survive after treated with 1 IJmol/L of TSA. We compared 1 pmol/L group with untreated control with t-test. There was no significance between 1 pmol/L group and untreated control for normal cell （P 〉0.05）. HDAC inhibitors decreased DNMT3B in cancer cell but not in normal cell. Manually knock-down of DNMT3B induced Hela and Caski cell apoptosis. More than 99% of Hela and Caski cell went apoptosis after deprived of DNMT3B. Conclusions DNMT3B was essential to cervical cancer cell survival. Down-regulated DNMT3B by HDAC inhibitors may play an important role in the toxicity of HDAC inhibitors on cervical cancer cells.展开更多
目的探讨p63、TLR3和Leptin在宫颈癌中的表达及其临床意义。方法纳入118例妇科手术标本作为研究对象,其中宫颈癌标本75例,正常宫颈组织标本43例。采用免疫组化法检测各标本中p63、TLR3和Leptin表达水平。结果与正常宫颈组织相比,宫颈癌...目的探讨p63、TLR3和Leptin在宫颈癌中的表达及其临床意义。方法纳入118例妇科手术标本作为研究对象,其中宫颈癌标本75例,正常宫颈组织标本43例。采用免疫组化法检测各标本中p63、TLR3和Leptin表达水平。结果与正常宫颈组织相比,宫颈癌组织中p63、Leptin表达阳性率较高,TLR3表达的阳性率较低,差异均具有统计学意义(P<0.05)。p63的表达与宫颈癌FIGO临床分期、分化程度相关(P<0.05),与年龄无关(P>0.05)。TLR3的表达与宫颈癌分化程度相关(P<0.05),与临床分期、年龄无关(P>0.05)。Leptin的表达与临床分期、分化程度相关(P<0.05),与年龄无关(P>0.05)。TLR3与Leptin和p63的表达均呈显著负相关(γ_(TLR3 vs Leptin)=-0.549,P _(TLR3 vs Leptin)=0.000;γ_(TLR3 vs p63)=-0.645,P _(TLR3 vs p63)=0.000),Leptin与p63呈显著正相关关系(γ=0.677,P=0.000)。结论p63、TLR3、Leptin均在宫颈癌组织中异常表达,与病理分期、分化程度存在相关性,且三者之间存在一定的关联。p63、TLR3、Leptin可作为宫颈癌的可靠标志物,用以评估患者病情和预后。展开更多
文摘Uterine cervical cancer is the second most common gynecological malignancy. It is estimated that over 35% of tumors are diagnosed at locally advanced disease, stage ⅠB2-ⅡB with an estimated 5-year overall survival of 60%. During the last decades, the initial treatment for these women has been debated and largely varies through different countries. Thus, radical concurrent chemoradiation is the standard of care in United Sated and Canada, and neoadjuvant chemotherapy followed by radical surgery is the first line of treatment in some institutions of Europe, Asia and Latin America. Until today, there is no evidence of which strategy is better over the other. This article describe the evidence as well as the advantages and disadvantages of the main strategies of treatment for women affected by uterine cervical cancer stage ⅠB2-ⅡB.
基金This article was supported by the grants from the National Natural Science Foundation of China，the “985” Project of the Peking University Health Science Center and the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry
文摘Background Histone deacetylase （HDAC） inhibitors are a group of small chemical molecules that inhibit histone deacetylase. At cell level, HDAC inhibitors have multiple biological effects such as cell cycle arrest, apoptosis, cell differentiation and auotophagy. At molecular level, HDAC inhibitors cause histone and nonhistone acetylation and induce gene expression. HDAC inhibitors are widely used in cancer therapy because of its function of inducing apoptosis. However, the mechanisms of apoptosis effect are not fully understood. TSA is a classical HDAC inhibitor and widely used in epigenetic and anti-cancer research. In this study, we selected Trichostatin A （TSA） to investigate the mechanisms of HDAC inhibitors apoptotic effect on cancer cells. Methods Cervical cancer cell lines such as Hela, Caski and normal human keratinocyte line HaCaT were treated with various concentrations of TSA. Crystal violent assay and 3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay were performed to determine cell number. PARP cleavage and FITC-AnexinV were performed to determine apoptosis. DNA-methyltransferase （DNMT）I, DNMT3A and DNMT3B were determined by regular PCR, qPCR and Western Blotting. Small interfering RNA （SiRNAi） was used to knock down DNMT3B. Results HDAC inhibitors only induce cervical cancer cell apoptosis. At 1 Iumol/L of TSA, 86% of Hela cell and 76% of Caski went apoptosis. For normal cells, HDAC inhibitors have no cytotoxic effect at therapeutic dosage, （90.0＋8.4）% of normal cell survive after treated with 1 IJmol/L of TSA. We compared 1 pmol/L group with untreated control with t-test. There was no significance between 1 pmol/L group and untreated control for normal cell （P 〉0.05）. HDAC inhibitors decreased DNMT3B in cancer cell but not in normal cell. Manually knock-down of DNMT3B induced Hela and Caski cell apoptosis. More than 99% of Hela and Caski cell went apoptosis after deprived of DNMT3B. Conclusions DNMT3B was essential to cervical cancer cell survival. Down-regulated DNMT3B by HDAC inhibitors may play an important role in the toxicity of HDAC inhibitors on cervical cancer cells.
文摘目的探讨p63、TLR3和Leptin在宫颈癌中的表达及其临床意义。方法纳入118例妇科手术标本作为研究对象,其中宫颈癌标本75例,正常宫颈组织标本43例。采用免疫组化法检测各标本中p63、TLR3和Leptin表达水平。结果与正常宫颈组织相比,宫颈癌组织中p63、Leptin表达阳性率较高,TLR3表达的阳性率较低,差异均具有统计学意义(P<0.05)。p63的表达与宫颈癌FIGO临床分期、分化程度相关(P<0.05),与年龄无关(P>0.05)。TLR3的表达与宫颈癌分化程度相关(P<0.05),与临床分期、年龄无关(P>0.05)。Leptin的表达与临床分期、分化程度相关(P<0.05),与年龄无关(P>0.05)。TLR3与Leptin和p63的表达均呈显著负相关(γ_(TLR3 vs Leptin)=-0.549,P _(TLR3 vs Leptin)=0.000;γ_(TLR3 vs p63)=-0.645,P _(TLR3 vs p63)=0.000),Leptin与p63呈显著正相关关系(γ=0.677,P=0.000)。结论p63、TLR3、Leptin均在宫颈癌组织中异常表达,与病理分期、分化程度存在相关性,且三者之间存在一定的关联。p63、TLR3、Leptin可作为宫颈癌的可靠标志物,用以评估患者病情和预后。
