Aim： To examine the expression of prostate cancer antigen-1 （PCA-1） in prostate cancer （PCa） and to validate it as a potential marker for diagnosis of PCa. Methods： In situ hybridization analysis of PCA-1 mRNA e...Aim： To examine the expression of prostate cancer antigen-1 （PCA-1） in prostate cancer （PCa） and to validate it as a potential marker for diagnosis of PCa. Methods： In situ hybridization analysis of PCA-1 mRNA expression was performed on 40 benign prostate hyperplasia （BPH）, 16 high-grade prostatic intraepithelial neoplasm （HG-PIN）, 74 PCa and 34 other malignant carcinoma specimens. The level of PCA- 1 expression was semiquanfitatively scored by assessing both the percentage and intensity of PCA- 1 positive staining cells in the specimens. We then compared the PCA-1 expression between BPH, HG-PIN and PCa and evaluated the correlation of PCA-1 expression level with clinical parameters of PCa. Results： PCA-1 mRNA was expressed in the majority of both PCa and HG-PIN specimens but not in BPH and other malignant carcinoma. The expression level of PCA-1 increased along with a high Gleason score （P 〈 0.05）, and was unrelated to other clinical parameters of PCa （all P 〉 0.05）. Conclusion： The data suggest that PCA-1 might be a novel diagnostic marker for PCa, and that increased PCA-1 expression might denote more aggressive variants of PCa.展开更多
Objective To investigate the influence of m4-1BBL on anti-tumor effects induced by truncated human prostate specific membrane antigen ( tPSMA ) gene in mice. Methods A eukaryotic expression plasmid encoding tPSMA and ...Objective To investigate the influence of m4-1BBL on anti-tumor effects induced by truncated human prostate specific membrane antigen ( tPSMA ) gene in mice. Methods A eukaryotic expression plasmid encoding tPSMA and m4-1BBL ( pDC316-tPSMA-IRES m4-1BBL) ,pDC316-tPSMA and pDC316 were constructed.展开更多
Breast cancer is the second leading cause of cancerrelated deaths in women worldwide;a prime cancer biomarker to aid in the diagnosis, directed treatment, clinical management, and reoccurrence of this cancer is a MUC1...Breast cancer is the second leading cause of cancerrelated deaths in women worldwide;a prime cancer biomarker to aid in the diagnosis, directed treatment, clinical management, and reoccurrence of this cancer is a MUC1 peptide fragment: cancer antigen 15-3 (CA 15-3). Herein, an immuno-fluorescence assay for CA 15-3 was developed;this ALYGNSA system consists of a protein biolinker (Protein G’) adsorbed onto Poly (methyl methacrylate) (PMMA). The unique interaction of Protein G’ with PMMA, a thermo-plastic polymer has been demonstrated to improve human IgG capture antibody alignment/ orientation and result in greater assay sensitivity. Indeed a previous report (HEALTH 1 325 - 329, 2009) on the shed extracellular domain of HER-2/neu revealed a 10-fold increase in sensitivity of the ALYGSNA assay over a control ELISA assay. Results from this ALYGNSA assay study revealed that a 16-fold increase in detection (≤0.94 U/mL) of CA 15-3 was found in comparison to a commercial control ELISA kit (≤15 U/mL). In conclusion, this enhanced sensitivity of the ALYGNSA assay for CA 15-3, may provide insights into the role/function of this biomarker in normal, as well as, breast cancer and other epithelial cancers.展开更多
Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is a...Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein （IDP） that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun, c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer （PCa）. Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease.展开更多
Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we ident...Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA.miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue,and its expression level correlated inversely with aggressive clinical pathological features.Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation,migration,and invasion,and promoted apoptosis.The miR-3691-3p target genes E2F transcription factor 3(E2F3)and PR domain containing 1,with ZNF domain(PRDM1)were upregulated in miR-3691-3p-overexpressing PCa cells,and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation,migration,and invasion.Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis.Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p,both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue.Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1.These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.展开更多
目的·探讨前列腺癌患者血液中前列腺特异抗原(prostate specific antigen,PSA)、肿瘤异常蛋白(tumor abnormal protein,TAP)及结肠癌转移相关基因1(colon cancer metastasis related gene 1,MACC1)的表达及临床诊断价值。方法·...目的·探讨前列腺癌患者血液中前列腺特异抗原(prostate specific antigen,PSA)、肿瘤异常蛋白(tumor abnormal protein,TAP)及结肠癌转移相关基因1(colon cancer metastasis related gene 1,MACC1)的表达及临床诊断价值。方法·以2019年1月至2020年12月于上海市徐汇区大华医院就诊的107例前列腺癌患者为病例组,另选择同期该院60名健康体检者为对照组。回顾性分析2组患者血液中PSA、TAP及MACC1的水平,及其与Gleason评分、T分期的相关性;采用受试者操作特征(receiver operating characteristic,ROC)曲线评价各项指标诊断前列腺癌的灵敏度和特异度。结果·病例组患者血液PSA、TAP及MACC1水平均显著高于对照组(P<0.05);随着Gleason分级的升高,病例组患者血液PSA、TAP及MACC1水平逐渐升高;随着T分期的进展,病例组患者血液PSA、TAP及MACC1水平逐渐升高;有淋巴结转移的患者血液PSA和MACC1水平高于无淋巴结转移患者,TAP水平低于无淋巴结转移患者,差异均有统计学意义(P<0.05)。血液PSA诊断前列腺癌的ROC曲线下面积(area under the curve,AUC)为0.764,灵敏度为86.12%,特异度为88.63%,截断值为6.01μg/L;血液TAP诊断前列腺癌的AUC为0.796,灵敏度为88.18%,特异度为89.58%,截断值为135.62μm^(2);血液MACC1诊断前列腺癌的AUC为0.873,灵敏度为78.46%,特异度为80.10%,截断值为37.80 pg/mL;3项指标联合检测的AUC为0.941,灵敏度为93.15%,特异度为94.08%,均高于各单项指标(P<0.05)。Spearman相关分析结果显示,血液PSA、TAP及MACC1水平均与Gleason评分呈正相关(r值分别为0.648、0.513和0.501,均P=0.000),与T分期呈正相关(r值分别为0.616、0.537和0.542,均P=0.000)。结论·前列腺癌患者血液PSA、TAP及MACC1水平均与Gleason评分、T分期之间关系密切,对前列腺癌有一定的诊断价值;3项联合检测,诊断价值更高。展开更多
文摘Aim： To examine the expression of prostate cancer antigen-1 （PCA-1） in prostate cancer （PCa） and to validate it as a potential marker for diagnosis of PCa. Methods： In situ hybridization analysis of PCA-1 mRNA expression was performed on 40 benign prostate hyperplasia （BPH）, 16 high-grade prostatic intraepithelial neoplasm （HG-PIN）, 74 PCa and 34 other malignant carcinoma specimens. The level of PCA- 1 expression was semiquanfitatively scored by assessing both the percentage and intensity of PCA- 1 positive staining cells in the specimens. We then compared the PCA-1 expression between BPH, HG-PIN and PCa and evaluated the correlation of PCA-1 expression level with clinical parameters of PCa. Results： PCA-1 mRNA was expressed in the majority of both PCa and HG-PIN specimens but not in BPH and other malignant carcinoma. The expression level of PCA-1 increased along with a high Gleason score （P 〈 0.05）, and was unrelated to other clinical parameters of PCa （all P 〉 0.05）. Conclusion： The data suggest that PCA-1 might be a novel diagnostic marker for PCa, and that increased PCA-1 expression might denote more aggressive variants of PCa.
文摘Objective To investigate the influence of m4-1BBL on anti-tumor effects induced by truncated human prostate specific membrane antigen ( tPSMA ) gene in mice. Methods A eukaryotic expression plasmid encoding tPSMA and m4-1BBL ( pDC316-tPSMA-IRES m4-1BBL) ,pDC316-tPSMA and pDC316 were constructed.
文摘Breast cancer is the second leading cause of cancerrelated deaths in women worldwide;a prime cancer biomarker to aid in the diagnosis, directed treatment, clinical management, and reoccurrence of this cancer is a MUC1 peptide fragment: cancer antigen 15-3 (CA 15-3). Herein, an immuno-fluorescence assay for CA 15-3 was developed;this ALYGNSA system consists of a protein biolinker (Protein G’) adsorbed onto Poly (methyl methacrylate) (PMMA). The unique interaction of Protein G’ with PMMA, a thermo-plastic polymer has been demonstrated to improve human IgG capture antibody alignment/ orientation and result in greater assay sensitivity. Indeed a previous report (HEALTH 1 325 - 329, 2009) on the shed extracellular domain of HER-2/neu revealed a 10-fold increase in sensitivity of the ALYGSNA assay over a control ELISA assay. Results from this ALYGNSA assay study revealed that a 16-fold increase in detection (≤0.94 U/mL) of CA 15-3 was found in comparison to a commercial control ELISA kit (≤15 U/mL). In conclusion, this enhanced sensitivity of the ALYGNSA assay for CA 15-3, may provide insights into the role/function of this biomarker in normal, as well as, breast cancer and other epithelial cancers.
文摘Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein （IDP） that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun, c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer （PCa）. Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease.
基金This study was supported by Shanghai Changning District Committee of Science and Technology(CNKW2016Y01)Shanghai Tongren Hospital Project(TRYJ201501)+3 种基金Suzhou Science and Technology Development Program(SYS201717)the Second Affiliated Hospital of Soochow University Advance Research Program of the Natural Science Foundation of China Grants(SDFEYGJ1705)Open project of Jiangsu State Key Laboratory of Radiation Medicine and Projection(GJS1963)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA.miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue,and its expression level correlated inversely with aggressive clinical pathological features.Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation,migration,and invasion,and promoted apoptosis.The miR-3691-3p target genes E2F transcription factor 3(E2F3)and PR domain containing 1,with ZNF domain(PRDM1)were upregulated in miR-3691-3p-overexpressing PCa cells,and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation,migration,and invasion.Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis.Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p,both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue.Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1.These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.
文摘目的·探讨前列腺癌患者血液中前列腺特异抗原(prostate specific antigen,PSA)、肿瘤异常蛋白(tumor abnormal protein,TAP)及结肠癌转移相关基因1(colon cancer metastasis related gene 1,MACC1)的表达及临床诊断价值。方法·以2019年1月至2020年12月于上海市徐汇区大华医院就诊的107例前列腺癌患者为病例组,另选择同期该院60名健康体检者为对照组。回顾性分析2组患者血液中PSA、TAP及MACC1的水平,及其与Gleason评分、T分期的相关性;采用受试者操作特征(receiver operating characteristic,ROC)曲线评价各项指标诊断前列腺癌的灵敏度和特异度。结果·病例组患者血液PSA、TAP及MACC1水平均显著高于对照组(P<0.05);随着Gleason分级的升高,病例组患者血液PSA、TAP及MACC1水平逐渐升高;随着T分期的进展,病例组患者血液PSA、TAP及MACC1水平逐渐升高;有淋巴结转移的患者血液PSA和MACC1水平高于无淋巴结转移患者,TAP水平低于无淋巴结转移患者,差异均有统计学意义(P<0.05)。血液PSA诊断前列腺癌的ROC曲线下面积(area under the curve,AUC)为0.764,灵敏度为86.12%,特异度为88.63%,截断值为6.01μg/L;血液TAP诊断前列腺癌的AUC为0.796,灵敏度为88.18%,特异度为89.58%,截断值为135.62μm^(2);血液MACC1诊断前列腺癌的AUC为0.873,灵敏度为78.46%,特异度为80.10%,截断值为37.80 pg/mL;3项指标联合检测的AUC为0.941,灵敏度为93.15%,特异度为94.08%,均高于各单项指标(P<0.05)。Spearman相关分析结果显示,血液PSA、TAP及MACC1水平均与Gleason评分呈正相关(r值分别为0.648、0.513和0.501,均P=0.000),与T分期呈正相关(r值分别为0.616、0.537和0.542,均P=0.000)。结论·前列腺癌患者血液PSA、TAP及MACC1水平均与Gleason评分、T分期之间关系密切,对前列腺癌有一定的诊断价值;3项联合检测,诊断价值更高。
