BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expres...BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.展开更多
AIM: To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue, affects the growth of gastric cancer cells and its mechanisms. METHODS: A series of genist...AIM: To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue, affects the growth of gastric cancer cells and its mechanisms. METHODS: A series of genistein analogues were prepared by difluoromethylation and alkylation, and human gastric cancer cell lines AGS and SGC-7901 cultured in vitro were treated with various concentrations of genistein and genistein analogues. The cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were incubated by DFOG at different concentrations. The growth inhibitory effects were evaluated using MTT and clonogenic assay. The distribution of the phase in cell cycle was analyzed using flow cytometric analysis with propidium iodide staining. The expression of the transcription factor forkhead box M1 (FOXM1) was analyzed by reverse transcription-polymerase chain reaction and Western blotting. The expression levelsof CDK1, Cdc25B, cyclin B and p27KIP1 protein were detected using Western blotting. RESULTS: Nine of the genistein analogues had more effective antitumor activity than genistein. Among the tested analogues, DFOG possessed the strongest activity against AGS and SGC-7901 cells in vitro. DFOG significantly inhibited the cell viability and colony formation of AGS and SGC-7901 cells. Moreover, DFOG efficaciously arrested the cell cycle in G2/M phase. DFOG decreased the expression of FOXM1 and its downstream genes, such as CDK1, Cdc25B, cyclin B, and increased p27KIP1 at protein levels. Knockdown of FOXM1 by small interfering RNA before DFOG treatment resulted in enhanced cell growth inhibition in AGS cells. Up-regulation of FOXM1 by cDNA transfection attenuated DFOG-induced cell growth inhibition in AGS cells. CONCLUSION: DFOG inhibits the growth of human gastric cancer cells by down-regulating the FOXM1 expression.展开更多
Forkhead box protein P1（FOXP1）is a transcription factor belonging to the forkhead box（FOX）proteins,a family of transcriptional regulators sharing a highly conserved forkhead DNA-binding domain（Bacon and Rappold,2...Forkhead box protein P1（FOXP1）is a transcription factor belonging to the forkhead box（FOX）proteins,a family of transcriptional regulators sharing a highly conserved forkhead DNA-binding domain（Bacon and Rappold,2012）.Previous reports have proposed a role for FOXP1 in functionally regulating the central nervous system（CNS）,while mutations in FOXP1 have been implicated in cognitive abnormalities（Bacon and Rappold, 2012）.展开更多
FOXM1(Forkhead box protein M1)是调控细胞增殖的重要转录因子,近年来研究表明与肿瘤发生密切相关,但与卵巢癌的关系尚不明确.通过检测68例卵巢癌标本、21例卵巢良性肿瘤标本、24例正常卵巢标本以及3株卵巢癌细胞系(A2780细胞、OVCAR3...FOXM1(Forkhead box protein M1)是调控细胞增殖的重要转录因子,近年来研究表明与肿瘤发生密切相关,但与卵巢癌的关系尚不明确.通过检测68例卵巢癌标本、21例卵巢良性肿瘤标本、24例正常卵巢标本以及3株卵巢癌细胞系(A2780细胞、OVCAR3细胞、SKOV3细胞)中FOXM1的表达情况,分析其与临床参数之间的相关性及临床意义.结果显示卵巢癌中FOXM1表达明显高于卵巢良性肿瘤及正常卵巢组织,差异极为显著,其中低分化细胞中表达强于中高分化细胞(P=0.013),Ⅲ～Ⅳ期表达强于Ⅰ～Ⅱ期(P=0.011),但与病理类型无关;FOXM1在3株卵巢癌细胞系中均有较强表达.FOXM1在卵巢癌组织及3种卵巢癌细胞系中存在高表达,且与卵巢癌分化程度及临床分期有关.展开更多
AIM: To investigate the expression of forkhead box protein M1(Fox M1) in the process of epithelial mesenchymal transition in hepatocellular carcinoma(HCC) and its role in metastasis.METHODS: Fox M1 and E-cadherin expr...AIM: To investigate the expression of forkhead box protein M1(Fox M1) in the process of epithelial mesenchymal transition in hepatocellular carcinoma(HCC) and its role in metastasis.METHODS: Fox M1 and E-cadherin expression in HCC tissue microarray specimens was evaluated by immunohistochemical staining,and statistical methods were applied to analyze the correlation between FoxM 1 and epithelial-mesenchymal transition(EMT).KaplanMeier analysis of the correlation between the Fox M1 expression level and recurrence or overall survival of HCC patients was performed.The expression of FoxM 1,E-cadherin and snail homologue 1(SNAI1) in HCC cell lines was evaluated by real-time reverse transcriptionpolymerase chain reaction and Western blot.Hepatocyte growth factor(HGF) was used to induce EMT and stimulate cell migration in HCC cells.The expression of Fox M1 and SNAI1 was regulated by transfection with plasmids pc DNA3.1 and si RNAs in vitro.The occurrence of EMT was evaluated by Transwell assay,morphologic analysis and detection of the expression of EMT markers(E-cadherin and vimentin).Luciferase and chromatin immunoprecipitation assays were used to evaluate whether SNAI1 is a direct transcriptional target of FoxM 1.RESULTS: FoxM 1 expression was increased significantly in HCC compared with para-carcinoma(10.7 ± 0.9 vs 8.2 ± 0.7,P < 0.05) and normal hepatic(10.7 ± 0.9 vs 2.7 ± 0.4,P < 0.05) tissues.Overexpression of Fox M1 was correlated with HCC tumor size,tumor number,macrovascular invasion and higher TNM stage,but was negatively correlated with E-cadherin expression in microarray specimens and in cell lines.Fox M1 overexpression was correlated significantly with HCC metastasis and EMT.In vitro,we found that FoxM 1 plays a key role in HGF-induced EMT,and overexpression of Fox M1 could suppress E-cadherin expression and induce EMT changes,which were associated with increased HCC cell invasiveness.Next,we confirmed that FOXM1 directly binds to and activates the SNAI1 promoter,and we identified SNAI1 as a direct transcriptional target of FOXM1.Moreover,inhibiting the expression of SNAI1 significantly inhibited FoxM 1-mediated EMT.CONCLUSION: Fox M1 overexpression promotes EMT and metastasis of HCC,and SNAI1 plays a critical role in FoxM 1-mediated EMT.展开更多
AIM: To investigate the effect of knockdown of Forkhead box M1 (FoxM1) on the proliferation and invasion capacities of human gallbladder carcinoma (GBC)-SD cells.
文摘BACKGROUND Breast infiltrating ductal carcinoma(BIDC)represents the largest heterotypic tumor group,and an in-depth understanding of the pathogenesis of BIDC is key to improving its prognosis.AIM To analyze the expression profiles and clinical implications of forkhead box M1(FOXM1),cyclooxygenase-2(COX-2),and glucose-regulated protein 78(GRP78)in BIDC.METHODS A total of 65 BIDC patients and 70 healthy controls who presented to our hospital between August 2019 and May 2021 were selected for analysis.The peripheral blood FOXM1,COX-2,and GRP78 levels in both groups were measured and the association between their expression profiles in BIDC was examined.Additionally,we investigated the diagnostic value of FOXM1,COX-2,and GRP78 in patients with BIDC and their correlations with clinicopathological features.Furthermore,BIDC patients were followed for 1 year to identify factors influencing patient prognosis.RESULTS The levels of FOXM1,COX-2,and GRP78 were significantly higher in BIDC patients compared to healthy controls(P<0.05),and a positive correlation was observed among them(P<0.05).Receiver operating characteristic analysis demonstrated that FOXM1,COX-2,and GRP78 had excellent diagnostic value in predicting the occurrence of BIDC(P<0.05).Subsequently,we found significant differences in FOXM1,COX-2,and GRP78 levels among patients with different histological grades and metastasis statuses(with vs without)(P<0.05).Cox analysis revealed that FOXM1,COX-2,GRP78,increased histological grade,and the presence of tumor metastasis were independent risk factors for prognostic death in BIDC(P<0.001).CONCLUSION FOXM1,COX-2,and GRP78 exhibit abnormally high expression in BIDC,promoting malignant tumor development and closely correlating with prognosis.These findings hold significant research implications for the future diagnosis and treatment of BIDC.
基金National Natural Science Foundation of China, No. 81172375Hunan Provincial Natural Science Foundation, No. 03JJY5009
文摘AIM: To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue, affects the growth of gastric cancer cells and its mechanisms. METHODS: A series of genistein analogues were prepared by difluoromethylation and alkylation, and human gastric cancer cell lines AGS and SGC-7901 cultured in vitro were treated with various concentrations of genistein and genistein analogues. The cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were incubated by DFOG at different concentrations. The growth inhibitory effects were evaluated using MTT and clonogenic assay. The distribution of the phase in cell cycle was analyzed using flow cytometric analysis with propidium iodide staining. The expression of the transcription factor forkhead box M1 (FOXM1) was analyzed by reverse transcription-polymerase chain reaction and Western blotting. The expression levelsof CDK1, Cdc25B, cyclin B and p27KIP1 protein were detected using Western blotting. RESULTS: Nine of the genistein analogues had more effective antitumor activity than genistein. Among the tested analogues, DFOG possessed the strongest activity against AGS and SGC-7901 cells in vitro. DFOG significantly inhibited the cell viability and colony formation of AGS and SGC-7901 cells. Moreover, DFOG efficaciously arrested the cell cycle in G2/M phase. DFOG decreased the expression of FOXM1 and its downstream genes, such as CDK1, Cdc25B, cyclin B, and increased p27KIP1 at protein levels. Knockdown of FOXM1 by small interfering RNA before DFOG treatment resulted in enhanced cell growth inhibition in AGS cells. Up-regulation of FOXM1 by cDNA transfection attenuated DFOG-induced cell growth inhibition in AGS cells. CONCLUSION: DFOG inhibits the growth of human gastric cancer cells by down-regulating the FOXM1 expression.
文摘Forkhead box protein P1（FOXP1）is a transcription factor belonging to the forkhead box（FOX）proteins,a family of transcriptional regulators sharing a highly conserved forkhead DNA-binding domain（Bacon and Rappold,2012）.Previous reports have proposed a role for FOXP1 in functionally regulating the central nervous system（CNS）,while mutations in FOXP1 have been implicated in cognitive abnormalities（Bacon and Rappold, 2012）.
文摘FOXM1(Forkhead box protein M1)是调控细胞增殖的重要转录因子,近年来研究表明与肿瘤发生密切相关,但与卵巢癌的关系尚不明确.通过检测68例卵巢癌标本、21例卵巢良性肿瘤标本、24例正常卵巢标本以及3株卵巢癌细胞系(A2780细胞、OVCAR3细胞、SKOV3细胞)中FOXM1的表达情况,分析其与临床参数之间的相关性及临床意义.结果显示卵巢癌中FOXM1表达明显高于卵巢良性肿瘤及正常卵巢组织,差异极为显著,其中低分化细胞中表达强于中高分化细胞(P=0.013),Ⅲ～Ⅳ期表达强于Ⅰ～Ⅱ期(P=0.011),但与病理类型无关;FOXM1在3株卵巢癌细胞系中均有较强表达.FOXM1在卵巢癌组织及3种卵巢癌细胞系中存在高表达,且与卵巢癌分化程度及临床分期有关.
基金Supported by The National Natural Science Foundation of China,No.30872482 and No.81072051
文摘AIM: To investigate the expression of forkhead box protein M1(Fox M1) in the process of epithelial mesenchymal transition in hepatocellular carcinoma(HCC) and its role in metastasis.METHODS: Fox M1 and E-cadherin expression in HCC tissue microarray specimens was evaluated by immunohistochemical staining,and statistical methods were applied to analyze the correlation between FoxM 1 and epithelial-mesenchymal transition(EMT).KaplanMeier analysis of the correlation between the Fox M1 expression level and recurrence or overall survival of HCC patients was performed.The expression of FoxM 1,E-cadherin and snail homologue 1(SNAI1) in HCC cell lines was evaluated by real-time reverse transcriptionpolymerase chain reaction and Western blot.Hepatocyte growth factor(HGF) was used to induce EMT and stimulate cell migration in HCC cells.The expression of Fox M1 and SNAI1 was regulated by transfection with plasmids pc DNA3.1 and si RNAs in vitro.The occurrence of EMT was evaluated by Transwell assay,morphologic analysis and detection of the expression of EMT markers(E-cadherin and vimentin).Luciferase and chromatin immunoprecipitation assays were used to evaluate whether SNAI1 is a direct transcriptional target of FoxM 1.RESULTS: FoxM 1 expression was increased significantly in HCC compared with para-carcinoma(10.7 ± 0.9 vs 8.2 ± 0.7,P < 0.05) and normal hepatic(10.7 ± 0.9 vs 2.7 ± 0.4,P < 0.05) tissues.Overexpression of Fox M1 was correlated with HCC tumor size,tumor number,macrovascular invasion and higher TNM stage,but was negatively correlated with E-cadherin expression in microarray specimens and in cell lines.Fox M1 overexpression was correlated significantly with HCC metastasis and EMT.In vitro,we found that FoxM 1 plays a key role in HGF-induced EMT,and overexpression of Fox M1 could suppress E-cadherin expression and induce EMT changes,which were associated with increased HCC cell invasiveness.Next,we confirmed that FOXM1 directly binds to and activates the SNAI1 promoter,and we identified SNAI1 as a direct transcriptional target of FOXM1.Moreover,inhibiting the expression of SNAI1 significantly inhibited FoxM 1-mediated EMT.CONCLUSION: Fox M1 overexpression promotes EMT and metastasis of HCC,and SNAI1 plays a critical role in FoxM 1-mediated EMT.
基金supported by Science Foundation of the First Affiliated Hospital of Medical College,Xi’an Jiaotong University,No.2010YK1
文摘AIM: To investigate the effect of knockdown of Forkhead box M1 (FoxM1) on the proliferation and invasion capacities of human gallbladder carcinoma (GBC)-SD cells.
