AIM: To examine the correlation of phosphatidylinositol 3-kinase (PIK3) CB expression with preoperative radiotherapy response in patients with stage II/III rectal adenocarcinoma.
BACKGROUND Mesenchymal stem cells(MSCs)are a type of stem cells that possess relevant regenerative abilities and can be used to treat many chronic diseases.Diabetes mellitus(DM)is a frequently diagnosed chronic diseas...BACKGROUND Mesenchymal stem cells(MSCs)are a type of stem cells that possess relevant regenerative abilities and can be used to treat many chronic diseases.Diabetes mellitus(DM)is a frequently diagnosed chronic disease characterized by hyperglycemia which initiates many multisystem complications in the long-run.DM patients can benefit from MSCs transplantation to curb down the pathological consequences associated with hyperglycemia persistence and restore the function of damaged tissues.MSCs therapeutic outcomes are found to last for short period of time and ultimately these regenerative cells are eradicated and died in DM disease model.AIM To investigate the impact of high glucose or hyperglycemia on the cellular and molecular characteristics of MSCs.METHODS Human adipose tissue-derived MSCs(hAD-MSCs)were seeded in low(5.6 mmol/L of glucose)and high glucose(25 mmol/L of glucose)for 7 d.Cytotoxicity,viability,mitochondrial dynamics,and apoptosis were deplored using specific kits.Western blotting was performed to measure the protein expression of phosphatidylinositol 3-kinase(PI3K),TSC1,and mammalian target of rapamycin(mTOR)in these cells.RESULTS hAD-MSCs cultured in high glucose for 7 d demonstrated marked decrease in their viability,as shown by a significant increase in lactate dehydrogenase(P<0.01)and a significant decrease in Trypan blue(P<0.05)in these cells compared to low glucose control.Mitochondrial membrane potential,indicated by tetramethylrhodamine ethyl ester(TMRE)fluorescence intensity,and nicotinamide adenine dinucleotide(NAD+)/NADH ratio were significantly dropped(P<0.05 for TMRE and P<0.01 for NAD+/NADH)in high glucose exposed hAD-MSCs,indicating disturbed mitochondrial function.PI3K protein expression significantly decreased in high glucose culture MSCs(P<0.05 compared to low glucose)and it was coupled with significant upregulation in TSC1(P<0.05)and downregulation in mTOR protein expression(P<0.05).Mitochondrial complexes I,IV,and V were downregulated profoundly in high glucose(P<0.05 compared 展开更多
目的·分析线粒体核糖体蛋白L12(mitochondrial ribosomal protein L12,MRPL12)在肺腺癌(lung adenocarcinoma,LUAD)和正常组织中的表达差异和对患者预后的影响,以及预测其生物学功能。方法·利用肿瘤浸润性免疫细胞分析数据库T...目的·分析线粒体核糖体蛋白L12(mitochondrial ribosomal protein L12,MRPL12)在肺腺癌(lung adenocarcinoma,LUAD)和正常组织中的表达差异和对患者预后的影响,以及预测其生物学功能。方法·利用肿瘤浸润性免疫细胞分析数据库TIMER和GEPIA(gene expression profiling and interactive analyses)交互式网站服务器分析癌症基因组图谱(The Cancer Genome Atlas,TCGA)中MRPL12在不同癌组织中的表达情况的影响。利用Sangerbox生物信息分析平台对MRPL12差异表达的癌症类型进行Cox回归和Kaplan-Meier生存分析,评估风险比(hazard ratio,HR)、95%置信区间(confidence interval,CI)和Log-rank P值。采用UALCAN数据分析平台评估MRPL12蛋白表达与临床病理参数的关系。使用LinkedOmics数据库筛选与MRPL12表达相关的基因。采用DAVID数据库进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。定量聚合酶链反应验证MRPL12在细胞中的转录水平。结果·MRPL12在多种癌组织中显著高表达,但只有在LUAD中MRPL12的高表达与患者较差的总体生存期(overall suivival,OS)和疾病特异性生存期(disease-specific survival,DSS)相关;肿瘤分级程度越高的LUAD患者MRPL12蛋白表达水平越高;在LUAD基因表达数据集中与MRPL12负相关的基因富集到癌症通路(P=0.000)、癌症蛋白聚糖(P=0.000)、非小细胞肺癌(P=0.000)等癌症相关的通路。MRPL12在LUAD细胞(H1395、H1975和HCC827)中的mRNA表达水平高于正常细胞(Beas-2B),差异有统计学意义(P<0.05)。结论·MRPL12高表达的LUAD患者可能预后较差;MRPL12可以作为LUAD预后不良的潜在生物标志物和潜在的治疗新靶点。展开更多
肝癌是临床上具有高致死率的常见恶性肿瘤之一,发现新靶点、开发新药对于疾病的治疗至关重要。本文从生物功能和网络的角度分析了与肝癌发生、发展相关的差异表达基因,旨在筛选出肝癌早期诊断的分子标志物和免疫治疗靶点。首先对两组肝...肝癌是临床上具有高致死率的常见恶性肿瘤之一,发现新靶点、开发新药对于疾病的治疗至关重要。本文从生物功能和网络的角度分析了与肝癌发生、发展相关的差异表达基因,旨在筛选出肝癌早期诊断的分子标志物和免疫治疗靶点。首先对两组肝癌相关基因表达数据进行差异表达筛选;然后通过GO(Gene ontology)功能和KEGG(The kyoto encyclopedia of genes and genomes)通路分析,得到同时在主要功能和信号通路上显著富集的128个目标基因;最后通过基因调控网络探讨目标基因的相互作用规律,找出10个关键基因并进行生存分析验证。结果表明,得到的CYP3A4、CYP3A5、CYP2C9和CYP2C8这4个基因适合作为肝癌标志物或靶向治疗靶点。本文为肝癌发生、发展的机制研究,肿瘤标志物的筛选及药物靶点选择提供了参考,为进一步开展相关的功能研究提供了基础。展开更多
Objective:The aim of our study was to comprehensively access current status of radiotherapy physicians' opinions in post-mastectomy radiotherapy(PMRT) for breast cancer in Guangdong province.Methods:From June 2007...Objective:The aim of our study was to comprehensively access current status of radiotherapy physicians' opinions in post-mastectomy radiotherapy(PMRT) for breast cancer in Guangdong province.Methods:From June 2007 to June 2008,questionnaires on the clinical value,sequencing with chemotherapy and endocrine therapy,indications and irradiated targets for PMRT were sent to physicians of all radiotherapy departments registering at Radiotherapy Professional Committee of Guangdong Anti-cancer Association.Results:There were 126 physicians joining this investigation.Proportions of physicians who accepted the views that PMRT could merely improve local control or can improve both local control and overall survival were 100% and 25.2%.The most common sequences of PMRT and chemotherapy or endocrine therapy were "sandwich" and sequential modes,performed 46.9% and 59.5% respectively.The median interval of surgery and PMRT was 8 weeks.Proportions of physicians who accepted T3-4 diseases,or four or more axillary lymph nodes metastasis,or T1-2 with 1-3 positive lymph nodes,or T1-2N0 with primary tumor located in the center or inner quadrant as the indications of PMRT were 97.6%,100%,46.8%,13.5%,respectively.Proportions of physicians who accepted chest wall,supraclavicular region,internal mammary chain or axilla as irradiated targets were 86.5%,100%,49.2% and 38.9% respectively.Conclusion:For Radiotherapy physicians of Guangdong Province,there is still lacking of consensus in the opinions of whether PMRT can improve survival,and optimal sequencing with chemotherapy or endocrine therapy,and how to make decision for patients with T1-2 with 1-3 positive lymph nodes,and rational irradiated targets,which requires advanced professional training for physicians and further prospective clinical trial evidences to guide clinical practice.展开更多
基金Supported by Grants from the National Natural Science Foundation of China No.30872923the Peking University People’s Hospital Research and Development Fund No.RDB2007-47,No.RDK2008-01 and No.RDB2011-25
文摘AIM: To examine the correlation of phosphatidylinositol 3-kinase (PIK3) CB expression with preoperative radiotherapy response in patients with stage II/III rectal adenocarcinoma.
文摘BACKGROUND Mesenchymal stem cells(MSCs)are a type of stem cells that possess relevant regenerative abilities and can be used to treat many chronic diseases.Diabetes mellitus(DM)is a frequently diagnosed chronic disease characterized by hyperglycemia which initiates many multisystem complications in the long-run.DM patients can benefit from MSCs transplantation to curb down the pathological consequences associated with hyperglycemia persistence and restore the function of damaged tissues.MSCs therapeutic outcomes are found to last for short period of time and ultimately these regenerative cells are eradicated and died in DM disease model.AIM To investigate the impact of high glucose or hyperglycemia on the cellular and molecular characteristics of MSCs.METHODS Human adipose tissue-derived MSCs(hAD-MSCs)were seeded in low(5.6 mmol/L of glucose)and high glucose(25 mmol/L of glucose)for 7 d.Cytotoxicity,viability,mitochondrial dynamics,and apoptosis were deplored using specific kits.Western blotting was performed to measure the protein expression of phosphatidylinositol 3-kinase(PI3K),TSC1,and mammalian target of rapamycin(mTOR)in these cells.RESULTS hAD-MSCs cultured in high glucose for 7 d demonstrated marked decrease in their viability,as shown by a significant increase in lactate dehydrogenase(P<0.01)and a significant decrease in Trypan blue(P<0.05)in these cells compared to low glucose control.Mitochondrial membrane potential,indicated by tetramethylrhodamine ethyl ester(TMRE)fluorescence intensity,and nicotinamide adenine dinucleotide(NAD+)/NADH ratio were significantly dropped(P<0.05 for TMRE and P<0.01 for NAD+/NADH)in high glucose exposed hAD-MSCs,indicating disturbed mitochondrial function.PI3K protein expression significantly decreased in high glucose culture MSCs(P<0.05 compared to low glucose)and it was coupled with significant upregulation in TSC1(P<0.05)and downregulation in mTOR protein expression(P<0.05).Mitochondrial complexes I,IV,and V were downregulated profoundly in high glucose(P<0.05 compared
文摘目的·分析线粒体核糖体蛋白L12(mitochondrial ribosomal protein L12,MRPL12)在肺腺癌(lung adenocarcinoma,LUAD)和正常组织中的表达差异和对患者预后的影响,以及预测其生物学功能。方法·利用肿瘤浸润性免疫细胞分析数据库TIMER和GEPIA(gene expression profiling and interactive analyses)交互式网站服务器分析癌症基因组图谱(The Cancer Genome Atlas,TCGA)中MRPL12在不同癌组织中的表达情况的影响。利用Sangerbox生物信息分析平台对MRPL12差异表达的癌症类型进行Cox回归和Kaplan-Meier生存分析,评估风险比(hazard ratio,HR)、95%置信区间(confidence interval,CI)和Log-rank P值。采用UALCAN数据分析平台评估MRPL12蛋白表达与临床病理参数的关系。使用LinkedOmics数据库筛选与MRPL12表达相关的基因。采用DAVID数据库进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。定量聚合酶链反应验证MRPL12在细胞中的转录水平。结果·MRPL12在多种癌组织中显著高表达,但只有在LUAD中MRPL12的高表达与患者较差的总体生存期(overall suivival,OS)和疾病特异性生存期(disease-specific survival,DSS)相关;肿瘤分级程度越高的LUAD患者MRPL12蛋白表达水平越高;在LUAD基因表达数据集中与MRPL12负相关的基因富集到癌症通路(P=0.000)、癌症蛋白聚糖(P=0.000)、非小细胞肺癌(P=0.000)等癌症相关的通路。MRPL12在LUAD细胞(H1395、H1975和HCC827)中的mRNA表达水平高于正常细胞(Beas-2B),差异有统计学意义(P<0.05)。结论·MRPL12高表达的LUAD患者可能预后较差;MRPL12可以作为LUAD预后不良的潜在生物标志物和潜在的治疗新靶点。
文摘肝癌是临床上具有高致死率的常见恶性肿瘤之一,发现新靶点、开发新药对于疾病的治疗至关重要。本文从生物功能和网络的角度分析了与肝癌发生、发展相关的差异表达基因,旨在筛选出肝癌早期诊断的分子标志物和免疫治疗靶点。首先对两组肝癌相关基因表达数据进行差异表达筛选;然后通过GO(Gene ontology)功能和KEGG(The kyoto encyclopedia of genes and genomes)通路分析,得到同时在主要功能和信号通路上显著富集的128个目标基因;最后通过基因调控网络探讨目标基因的相互作用规律,找出10个关键基因并进行生存分析验证。结果表明,得到的CYP3A4、CYP3A5、CYP2C9和CYP2C8这4个基因适合作为肝癌标志物或靶向治疗靶点。本文为肝癌发生、发展的机制研究,肿瘤标志物的筛选及药物靶点选择提供了参考,为进一步开展相关的功能研究提供了基础。
文摘Objective:The aim of our study was to comprehensively access current status of radiotherapy physicians' opinions in post-mastectomy radiotherapy(PMRT) for breast cancer in Guangdong province.Methods:From June 2007 to June 2008,questionnaires on the clinical value,sequencing with chemotherapy and endocrine therapy,indications and irradiated targets for PMRT were sent to physicians of all radiotherapy departments registering at Radiotherapy Professional Committee of Guangdong Anti-cancer Association.Results:There were 126 physicians joining this investigation.Proportions of physicians who accepted the views that PMRT could merely improve local control or can improve both local control and overall survival were 100% and 25.2%.The most common sequences of PMRT and chemotherapy or endocrine therapy were "sandwich" and sequential modes,performed 46.9% and 59.5% respectively.The median interval of surgery and PMRT was 8 weeks.Proportions of physicians who accepted T3-4 diseases,or four or more axillary lymph nodes metastasis,or T1-2 with 1-3 positive lymph nodes,or T1-2N0 with primary tumor located in the center or inner quadrant as the indications of PMRT were 97.6%,100%,46.8%,13.5%,respectively.Proportions of physicians who accepted chest wall,supraclavicular region,internal mammary chain or axilla as irradiated targets were 86.5%,100%,49.2% and 38.9% respectively.Conclusion:For Radiotherapy physicians of Guangdong Province,there is still lacking of consensus in the opinions of whether PMRT can improve survival,and optimal sequencing with chemotherapy or endocrine therapy,and how to make decision for patients with T1-2 with 1-3 positive lymph nodes,and rational irradiated targets,which requires advanced professional training for physicians and further prospective clinical trial evidences to guide clinical practice.