BACKGROUND There are few effective tools to predict survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas.AIM To develop comprehensive nomograms to individually estimate the survi...BACKGROUND There are few effective tools to predict survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas.AIM To develop comprehensive nomograms to individually estimate the survival outcome of patients with invasive intraductal papillary mucinous neoplasms of the pancreas.METHODS Data of 1219 patients with invasive intraductal papillary mucinous neoplasms after resection were extracted from the Surveillance,Epidemiology,and End Results database,and randomly divided into the training(n=853)and the validation(n=366)cohorts.Based on the Cox regression model,nomograms were constructed to predict overall survival and cancer-specific survival for an individual patient.The performance of the nomograms was measured according to discrimination,calibration,and clinical utility.Moreover,we compared the predictive accuracy of the nomograms with that of the traditional staging system.RESULTS In the training cohort,age,marital status,histological type,T stage,N stage,M stage,and chemotherapy were selected to construct nomograms.Compared with the American Joint Committee on Cancer 7th staging system,the nomograms were generally more discriminative.The nomograms passed the calibration steps by showing high consistency between actual probability and nomogram prediction.Categorial net classification improvements and integrated discrimination improvements suggested that the predictive accuracy of the nomograms exceeded that of the American Joint Committee on Cancer staging system.With respect to decision curve analyses,the nomograms exhibited more preferable net benefit gains than the staging system across a wide range of threshold probabilities.CONCLUSION The nomograms show improved predictive accuracy,discrimination capability,and clinical utility,which can be used as reliable tools for risk classification and treatment recommendations.展开更多
Thyroid cancer is the most common endocrine system tumor.Ultrasound guided fine needle puncture(FNA)can identify benign and malignant thyroid nodules.However,due to the limitation of cytological detection,some thyroid...Thyroid cancer is the most common endocrine system tumor.Ultrasound guided fine needle puncture(FNA)can identify benign and malignant thyroid nodules.However,due to the limitation of cytological detection,some thyroid nodules are difficult to distinguish benign and malignant.BRAF gene mutation is a common human oncogenic mutation and the highest mutation frequency in papillary thyroid carcinoma.The combination of FNA and BRAF gene detection can significantly improve the diagnostic rate of benign and malignant thyroid nodules and make up for the deficiency of single diagnosis of cytology.Moreover,while the incidence of thyroid cancer is growing rapidly worldwide,its mortality remains stable.The problem of overdiagnosis and overtreatment of thyroid cancer is becoming more and more obvious.However,due to the limitations of current studies on BRAF genes,its prognostic value for papillary thyroid carcinoma remains controversial.Therefore,in order to reduce the adverse effects of overdiagnosis and treatment,the relationship between gene and tumor biological behavior needs further study in the future.展开更多
Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment costs.To date,tumor cells with intrinsic softness have been identified to function as cancer s...Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment costs.To date,tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types.Nonetheless,the existence of soft tumor cells in bladder tumors remains elusive.Thus,our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods:The stiffness of bladder cancer cells was determined by atomic force microscopy(AFM).The modified microfluidic chip was utilized to separate soft cells,and the 3D Matrigel culture system was to maintain the softness of tumor cells.Expression patterns of integrinβ8(ITGB8),protein kinase B(AKT),and mammalian target of rapamycin(mTOR)were determined by Western blotting.Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59(TRIM59).The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.Results:Using our newly designed microfluidic approach,we identified a small fraction of soft tumor cells in bladder cancer cells.More importantly,the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens,in which the number of soft tumor cells was associated with tumor relapse.Furthermore,we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells.Simultaneously,we detected a remarkable up-regulation in ITGB8,TRIM59,and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions:The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness.Meanwhile,the soft tumor cells become more sensitive to chemotherapy after stiffening,that offers new insights for hampering tumor progression and recurrence.展开更多
基金Supported by National Natural Science Foundation of China,No.81702270the Natural Science Foundation of Guangdong,No.2015A030313827The Affiliated Hospital of Guangdong Medical University Clinical Research Program,No.LCYJ2018C012
文摘BACKGROUND There are few effective tools to predict survival in patients with invasive intraductal papillary mucinous neoplasms of the pancreas.AIM To develop comprehensive nomograms to individually estimate the survival outcome of patients with invasive intraductal papillary mucinous neoplasms of the pancreas.METHODS Data of 1219 patients with invasive intraductal papillary mucinous neoplasms after resection were extracted from the Surveillance,Epidemiology,and End Results database,and randomly divided into the training(n=853)and the validation(n=366)cohorts.Based on the Cox regression model,nomograms were constructed to predict overall survival and cancer-specific survival for an individual patient.The performance of the nomograms was measured according to discrimination,calibration,and clinical utility.Moreover,we compared the predictive accuracy of the nomograms with that of the traditional staging system.RESULTS In the training cohort,age,marital status,histological type,T stage,N stage,M stage,and chemotherapy were selected to construct nomograms.Compared with the American Joint Committee on Cancer 7th staging system,the nomograms were generally more discriminative.The nomograms passed the calibration steps by showing high consistency between actual probability and nomogram prediction.Categorial net classification improvements and integrated discrimination improvements suggested that the predictive accuracy of the nomograms exceeded that of the American Joint Committee on Cancer staging system.With respect to decision curve analyses,the nomograms exhibited more preferable net benefit gains than the staging system across a wide range of threshold probabilities.CONCLUSION The nomograms show improved predictive accuracy,discrimination capability,and clinical utility,which can be used as reliable tools for risk classification and treatment recommendations.
基金It was supported by Lanzhou Science and Technology Plan Project(2018-3-58)。
文摘Thyroid cancer is the most common endocrine system tumor.Ultrasound guided fine needle puncture(FNA)can identify benign and malignant thyroid nodules.However,due to the limitation of cytological detection,some thyroid nodules are difficult to distinguish benign and malignant.BRAF gene mutation is a common human oncogenic mutation and the highest mutation frequency in papillary thyroid carcinoma.The combination of FNA and BRAF gene detection can significantly improve the diagnostic rate of benign and malignant thyroid nodules and make up for the deficiency of single diagnosis of cytology.Moreover,while the incidence of thyroid cancer is growing rapidly worldwide,its mortality remains stable.The problem of overdiagnosis and overtreatment of thyroid cancer is becoming more and more obvious.However,due to the limitations of current studies on BRAF genes,its prognostic value for papillary thyroid carcinoma remains controversial.Therefore,in order to reduce the adverse effects of overdiagnosis and treatment,the relationship between gene and tumor biological behavior needs further study in the future.
基金supported by the National Natural Science Foundation of China(Nos.81902578,81974098,8197032158)China Postdoctoral Science Foundation(No.2020M670057ZX)+3 种基金Programs from Science and Technology Department of Sichuan Province(No.2021YJ0462)Post-doctoral Science Research Foundation of Sichuan University(No.2020SCU12041)Post-Doctor Research Project,West China Hospital,Sichuan University(Nos.2018HXBH084,2019HXBH092)the National key research and development program of China(No.2020YFC2008601)
文摘Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment costs.To date,tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types.Nonetheless,the existence of soft tumor cells in bladder tumors remains elusive.Thus,our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods:The stiffness of bladder cancer cells was determined by atomic force microscopy(AFM).The modified microfluidic chip was utilized to separate soft cells,and the 3D Matrigel culture system was to maintain the softness of tumor cells.Expression patterns of integrinβ8(ITGB8),protein kinase B(AKT),and mammalian target of rapamycin(mTOR)were determined by Western blotting.Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59(TRIM59).The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.Results:Using our newly designed microfluidic approach,we identified a small fraction of soft tumor cells in bladder cancer cells.More importantly,the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens,in which the number of soft tumor cells was associated with tumor relapse.Furthermore,we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells.Simultaneously,we detected a remarkable up-regulation in ITGB8,TRIM59,and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions:The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness.Meanwhile,the soft tumor cells become more sensitive to chemotherapy after stiffening,that offers new insights for hampering tumor progression and recurrence.