BACKGROUND Accurate assessment of the prognosis after colorectal cancer surgery is of great significance in patients with colorectal cancer.However,there is no systematic analysis of factors affecting the prognosis of...BACKGROUND Accurate assessment of the prognosis after colorectal cancer surgery is of great significance in patients with colorectal cancer.However,there is no systematic analysis of factors affecting the prognosis of colorectal cancer currently.AIM To systematically analyze the influence of clinical data and serological and histological indicators on the prognosis of patients with colorectal cancer,and to explore the indicators that can accurately assess the prognosis of patients with colorectal cancer.METHODS A total of 374 patients with colorectal cancer were enrolled.The clinical data,tumor-node-metastasis(TNM)stage,and Dukes stage were recorded.All patients received examinations including carcinoembryonic antigen(CEA),carbohydrate antigen 199,C-reactive protein,albumin,D-dimer,and fibrinogen as well as routine blood tests one week before surgery.The tumor location,size,depth of invasion,lymph node metastasis,and distant metastasis were recorded during surgery.The pathological tissue typing and expression of proliferating cell nuclear antigen(PCNA)and p53 were observed.All patients were followed for 3 years,and patients with endpoint events were defined as a poor prognosis group,and the remaining patients were defined as a good prognosis group.The differences in clinical data,serology,and histology were analyzed between the two groups.Multivariate COX regression was used to analyze the independent influencing factors for the prognosis of colorectal cancer.The receiver operating characteristic curve was used to evaluate the predictive value of each of the independent influencing factors and their combination for the prognosis of colorectal cancer.RESULTS The follow-up outcomes showed that 81 patients were in the good prognosis group and 274 patients in the poor prognosis group.The TNM stage,PCNA,Glasgow prognostic score(GPS),neutrophil-lymphocyte ratio(NLR),C-reactive protein/albumin ratio(CAR),D-dimer,and CEA were independent influencing factors for the prognosis of colorectal cancer(P=0.000).NLR had the highest predictive power for colorectal cancer prognosis[area under the receiver operating characteristic curve(AUC)=0.925],followed by D-dimer(AUC=0.879)and GPS(AUC=0.872).The accuracy of the combination of all indicators in predicting the prognosis of colorectal cancer was the highest(AUC=0.973),which was significantly higher than that of any of the indicators alone(P<0.05).The sensitivity and specificity of the combination were 92.59%and 90.51%,respectively.CONCLUSION The independent influence factors for the prognosis of colorectal cancer include TNM stage,PCNA,GPS,NLR,CAR,D-dimer,and CEA.The combined assessment of the independent factors is the most accurate predictor of the prognosis after colorectal cancer surgery.展开更多
BACKGROUND Breast cancer is a common malignant tumor that seriously threatens women’s health.Breast cancer stem cell(CSC)-like cell population may be the main factor for breast cancer metastasis.Therefore,targeted th...BACKGROUND Breast cancer is a common malignant tumor that seriously threatens women’s health.Breast cancer stem cell(CSC)-like cell population may be the main factor for breast cancer metastasis.Therefore,targeted therapy for CSCs has great potential significance.Hypoxia-inducible factor is a transcription factor widely expressed in tumors.Studies have shown that down-regulation of the hypoxia signaling pathway inhibits tumor stem cell self-renewal and increases the sensitivity of stem cells to radiotherapy and chemotherapy mediated by hypoxiainducible factor-2α(HIF-2α).However,the specific mechanism remains unclear and further research is necessary.AIM To investigate the effect of HIF-2αdown-regulation on stem cell markers,microsphere formation,and apoptosis in breast cancer cell line MDA-MB-231 under hypoxia and its possible mechanism.METHODS Immunohistochemistry was used to detect the expression of HIF-2αand CD44 in triple-negative breast cancer(TNBC)and non-TNBC tissues.Double-labeling immunofluorescence was applied to detect the co-expression of HIF-2αand CD44 in MDA-MB-231 cells and MCF-7 cells.HIF-2αwas silenced by RNA interference,and the expression of CD44 and transfection efficiency were detected by real-time fluorescent quantitative PCR.Further,flow cytometry,TdT-mediated X-dUTP nick end labeling,and mammosphere formation assays were used to evaluate the effect of HIF-2αon CSCs and apoptosis.The possible mechanisms were analyzed by Western blot.RESULTS The results of immunohistochemistry showed that HIF-2αwas highly expressed in both TNBC and non-TNBC,while the expression of CD44 in different molecular types of breast cancer cells was different.In in vitro experiments,it was found that HIF-2αand CD44 were expressed almost in the same cell.Compared with hypoxia+negative-sequence control,HIF-2αsmall interfering ribonucleic acid transfection can lower the expression of HIF-2αand CD44 mRNA(P<0.05),increase the percentage of apoptotic cells(P<0.05),and resulted in a reduction of CD44+/CD24−population(P<0.05)and mammosphere formation(P<0.05)in hypoxic MDA-MB-231 cells.Western blot analysis revealed that phosphorylated protein-serine-threonine kinase(p-AKT)and phosphorylated mammalian target of rapamycin(p-mTOR)levels in MDA-MB-231 decreased significantly after HIF-2αsilencing(P<0.05).CONCLUSION Down-regulation of HIF-2αexpression can inhibit the stemness of human breast cancer MDA-MB-231 cells and promote apoptosis,and its mechanism may be related to the CD44/phosphoinosmde-3-kinase/AKT/mTOR signaling pathway.展开更多
Background:Traditional Chinese medicine(TCM)syndrome,also named syndrome,are comprehensive and integral analyses of clinical information which helps to guide different individualized treatment prescriptions.Methods:Th...Background:Traditional Chinese medicine(TCM)syndrome,also named syndrome,are comprehensive and integral analyses of clinical information which helps to guide different individualized treatment prescriptions.Methods:Thirty healthy controls and 80 colorectal cancer(CRC)patients(including 33 Spleen Qi Deficiency syndrome,23 Dampness Heat syndrome,17 Blood Stasis syndrome and 7 other syndrome)were enrolled into this study.Human mRNAs were extracted from peripheral blood mononuclear cells.The gene expression for CRC patients with different TCM syndrome was determined by microarray and qRT-PCR.Results:Spleen Qi Deficiency,Dampness Heat and Blood Stasis were the most common syndromes in CRC patients.There is a significant difference was found in mRNA expression levels(especially for PIK3CA,STAT3,SOX9 and KDM5C)among Spleen Qi Deficiency,Dampness Heat and Blood Stasis syndrome groups.The higher mRNA levels of JNK1,TP53,MLH1,MSH6,PMS2,SOCS3,TCF7L2,FAM123B,PSAP,FBXW7,SALL4 and the lower expression of inflammatory cytokine IL-6 were found in Spleen Qi Deficiency group but not other syndrome types.The higher mRNA levels of KRAS,MUC16,EGFR,GRASP65,PIK3CA,MAPK7,CD24,STAT3,SLC11A1,Bcl-2,TXNDC17 and some inflammatory cytokines(IL-6,IL-23,TNF-a,CXCR4)were found in Dampness Heat group but not other syndrome types.Blood Stasis syndrome showed higher expression of SOX9,MLH1,MSH6,KDM5C,PCDH11X,PSAP and SALL4,and lower mRNA levels of PIK3CA,CD24,STAT3,CXCR4,TXNDC17 and TP53.The CRC patients with Dampness Heat syndrome might have a poor prognosis than other syndrome types.Conclusion:The identification of syndrome conditions had different impacts on CRC prognosis,and which might be related with different mRNA expression levels.Some oncogenes and pro-inflammatory cytokines were highly expressed in Dampness Heat group but not other syndrome types,suggesting that the CRC patients with Dampness Heat syndrome might have a poor prognosis.Our results prelimitarily uncovered the molecular basis of syndrome differences in CRC prognosis,a better understanding for TCM treatment of CRC.展开更多
文摘BACKGROUND Accurate assessment of the prognosis after colorectal cancer surgery is of great significance in patients with colorectal cancer.However,there is no systematic analysis of factors affecting the prognosis of colorectal cancer currently.AIM To systematically analyze the influence of clinical data and serological and histological indicators on the prognosis of patients with colorectal cancer,and to explore the indicators that can accurately assess the prognosis of patients with colorectal cancer.METHODS A total of 374 patients with colorectal cancer were enrolled.The clinical data,tumor-node-metastasis(TNM)stage,and Dukes stage were recorded.All patients received examinations including carcinoembryonic antigen(CEA),carbohydrate antigen 199,C-reactive protein,albumin,D-dimer,and fibrinogen as well as routine blood tests one week before surgery.The tumor location,size,depth of invasion,lymph node metastasis,and distant metastasis were recorded during surgery.The pathological tissue typing and expression of proliferating cell nuclear antigen(PCNA)and p53 were observed.All patients were followed for 3 years,and patients with endpoint events were defined as a poor prognosis group,and the remaining patients were defined as a good prognosis group.The differences in clinical data,serology,and histology were analyzed between the two groups.Multivariate COX regression was used to analyze the independent influencing factors for the prognosis of colorectal cancer.The receiver operating characteristic curve was used to evaluate the predictive value of each of the independent influencing factors and their combination for the prognosis of colorectal cancer.RESULTS The follow-up outcomes showed that 81 patients were in the good prognosis group and 274 patients in the poor prognosis group.The TNM stage,PCNA,Glasgow prognostic score(GPS),neutrophil-lymphocyte ratio(NLR),C-reactive protein/albumin ratio(CAR),D-dimer,and CEA were independent influencing factors for the prognosis of colorectal cancer(P=0.000).NLR had the highest predictive power for colorectal cancer prognosis[area under the receiver operating characteristic curve(AUC)=0.925],followed by D-dimer(AUC=0.879)and GPS(AUC=0.872).The accuracy of the combination of all indicators in predicting the prognosis of colorectal cancer was the highest(AUC=0.973),which was significantly higher than that of any of the indicators alone(P<0.05).The sensitivity and specificity of the combination were 92.59%and 90.51%,respectively.CONCLUSION The independent influence factors for the prognosis of colorectal cancer include TNM stage,PCNA,GPS,NLR,CAR,D-dimer,and CEA.The combined assessment of the independent factors is the most accurate predictor of the prognosis after colorectal cancer surgery.
文摘BACKGROUND Breast cancer is a common malignant tumor that seriously threatens women’s health.Breast cancer stem cell(CSC)-like cell population may be the main factor for breast cancer metastasis.Therefore,targeted therapy for CSCs has great potential significance.Hypoxia-inducible factor is a transcription factor widely expressed in tumors.Studies have shown that down-regulation of the hypoxia signaling pathway inhibits tumor stem cell self-renewal and increases the sensitivity of stem cells to radiotherapy and chemotherapy mediated by hypoxiainducible factor-2α(HIF-2α).However,the specific mechanism remains unclear and further research is necessary.AIM To investigate the effect of HIF-2αdown-regulation on stem cell markers,microsphere formation,and apoptosis in breast cancer cell line MDA-MB-231 under hypoxia and its possible mechanism.METHODS Immunohistochemistry was used to detect the expression of HIF-2αand CD44 in triple-negative breast cancer(TNBC)and non-TNBC tissues.Double-labeling immunofluorescence was applied to detect the co-expression of HIF-2αand CD44 in MDA-MB-231 cells and MCF-7 cells.HIF-2αwas silenced by RNA interference,and the expression of CD44 and transfection efficiency were detected by real-time fluorescent quantitative PCR.Further,flow cytometry,TdT-mediated X-dUTP nick end labeling,and mammosphere formation assays were used to evaluate the effect of HIF-2αon CSCs and apoptosis.The possible mechanisms were analyzed by Western blot.RESULTS The results of immunohistochemistry showed that HIF-2αwas highly expressed in both TNBC and non-TNBC,while the expression of CD44 in different molecular types of breast cancer cells was different.In in vitro experiments,it was found that HIF-2αand CD44 were expressed almost in the same cell.Compared with hypoxia+negative-sequence control,HIF-2αsmall interfering ribonucleic acid transfection can lower the expression of HIF-2αand CD44 mRNA(P<0.05),increase the percentage of apoptotic cells(P<0.05),and resulted in a reduction of CD44+/CD24−population(P<0.05)and mammosphere formation(P<0.05)in hypoxic MDA-MB-231 cells.Western blot analysis revealed that phosphorylated protein-serine-threonine kinase(p-AKT)and phosphorylated mammalian target of rapamycin(p-mTOR)levels in MDA-MB-231 decreased significantly after HIF-2αsilencing(P<0.05).CONCLUSION Down-regulation of HIF-2αexpression can inhibit the stemness of human breast cancer MDA-MB-231 cells and promote apoptosis,and its mechanism may be related to the CD44/phosphoinosmde-3-kinase/AKT/mTOR signaling pathway.
基金This research was supported by grants from National Natural Science Foundation of China(grant No.81874380,81672932,81730108 and 81973635)Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars(grant No.LR18H160001)+6 种基金Zhejiang Province Science and Technology Project of TCM(grant No.2019ZZ016)Zhejiang Province Medical Science and Technology Project(grant No.2017RC007)Talent Project of Zhejiang Association for Science and Technology(grant No.2017YCGC002)Key Project of Hangzhou Ministry of Science and Technology(grant No.20162013A07)Zhejiang Provincial Project for the Key Discipline of Traditional Chinese Medicine(grant No.2017-XK-A09)the Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica(No.JKLPSE201807)the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Background:Traditional Chinese medicine(TCM)syndrome,also named syndrome,are comprehensive and integral analyses of clinical information which helps to guide different individualized treatment prescriptions.Methods:Thirty healthy controls and 80 colorectal cancer(CRC)patients(including 33 Spleen Qi Deficiency syndrome,23 Dampness Heat syndrome,17 Blood Stasis syndrome and 7 other syndrome)were enrolled into this study.Human mRNAs were extracted from peripheral blood mononuclear cells.The gene expression for CRC patients with different TCM syndrome was determined by microarray and qRT-PCR.Results:Spleen Qi Deficiency,Dampness Heat and Blood Stasis were the most common syndromes in CRC patients.There is a significant difference was found in mRNA expression levels(especially for PIK3CA,STAT3,SOX9 and KDM5C)among Spleen Qi Deficiency,Dampness Heat and Blood Stasis syndrome groups.The higher mRNA levels of JNK1,TP53,MLH1,MSH6,PMS2,SOCS3,TCF7L2,FAM123B,PSAP,FBXW7,SALL4 and the lower expression of inflammatory cytokine IL-6 were found in Spleen Qi Deficiency group but not other syndrome types.The higher mRNA levels of KRAS,MUC16,EGFR,GRASP65,PIK3CA,MAPK7,CD24,STAT3,SLC11A1,Bcl-2,TXNDC17 and some inflammatory cytokines(IL-6,IL-23,TNF-a,CXCR4)were found in Dampness Heat group but not other syndrome types.Blood Stasis syndrome showed higher expression of SOX9,MLH1,MSH6,KDM5C,PCDH11X,PSAP and SALL4,and lower mRNA levels of PIK3CA,CD24,STAT3,CXCR4,TXNDC17 and TP53.The CRC patients with Dampness Heat syndrome might have a poor prognosis than other syndrome types.Conclusion:The identification of syndrome conditions had different impacts on CRC prognosis,and which might be related with different mRNA expression levels.Some oncogenes and pro-inflammatory cytokines were highly expressed in Dampness Heat group but not other syndrome types,suggesting that the CRC patients with Dampness Heat syndrome might have a poor prognosis.Our results prelimitarily uncovered the molecular basis of syndrome differences in CRC prognosis,a better understanding for TCM treatment of CRC.
