BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to...BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the prosthesis.Short femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.Currently,the long-term survival and functional outcomes of various short stems are still being investigated in different clinics.AIM To determine the 5-year survival of the Optimys hip stem.METHODS This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands.All patients received the Optimys short stem(Mathys Ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the endpoint.The secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival rate.Log-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery.Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs.RESULTS The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was seen.Baseline questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionnaires and 233 patients(47%)completed the 2-year follow-up.Both outcome measures significantly improved across all domains in the 1st year after the operation(P<0.03 for all domains).In the 2nd year after surgery,no significant changes were observed in any domain in comparison to the 1-year follow-up.CONCLUSION The Optimys stem has a 5-year survival of 98.8%.Patient-reported outcome measures increased significantly in the 1st postoperative year with stabilization at the 2-year follow-up.展开更多
In this study, we aimed to investigate the influencing factors of postoperative 5-year survival rate in non small-cell lung cancer（NSCLC） patients with stage I–III. We enrolled 220 patients who underwent surgical o...In this study, we aimed to investigate the influencing factors of postoperative 5-year survival rate in non small-cell lung cancer（NSCLC） patients with stage I–III. We enrolled 220 patients who underwent surgical operation and survived longer than 3 months, with histologically confirmed adenocarcinoma or squamous cell carcinoma from Jan. 2009 to Dec. 2009. Multiple variables, like age, gender, smoking, alcohol, obesity, family history of cancer, diabetes, hypertension, antidiabetic drugs, tumor staging, pathology, treatments, surgical side as well as lipid levels, were selected. We found that tumor staging was associated with 5-year survival rate of stage I–III NSCLC patients by univariate analysis. Furthermore, diabetes mellitus, hypertension and surgical side were associated with the overall survival of NSCLC patients with stage I, stageⅡand stage III, respectively. In conclusion, the status of chronic disease had potential effect on the postoperative 5-year survival rate of lung cancer patients.展开更多
The prediction of colorectal cancer(CRC) survivability has always been a challenging research issue. Considering the importance of predicting CRC patients’ survival rates, we compared the performance of three data mi...The prediction of colorectal cancer(CRC) survivability has always been a challenging research issue. Considering the importance of predicting CRC patients’ survival rates, we compared the performance of three data mining methods: decision trees(DTs), artificial neural networks(ANNs) and support vector machines(SVMs), for predicting 5-year survival of CRC patients to assist clinicians in making treatment decisions. The CRC dataset used to build the prediction model comes from the surveillance, epidemiology, and end results(SEER) program. The 5-fold cross-validation and random forest algorithm were respectively utilized for measuring the model predictive accuracy and the importance of features. Experimental results show that the predictive accuracy of ANNs(0.73) and SVMs(0.75) were higher than that of DTs, and they also have the best result in the area under the receiver operating characteristic(ROC) curve(area under curve(AUC)=0.82). This result may indicate high predictive power of ANNs and SVMs for predicting 5-year survival of CRC patients.展开更多
BACKGROUND The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil(5-FU) in advanced-stage gastric cancer i...BACKGROUND The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil(5-FU) in advanced-stage gastric cancer is still unelucidated.AIM To explore the long-term survival benefit of using sustained-release 5-FU implants in stage Ⅱ and stage Ⅲ gastric cancer patients.METHODS Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release(SR) chemotherapy with 5-FU was used or not(NSR). The primary end-point was 5-year overall survival. Kaplan–Meier method with logrank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients.RESULTS In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219(70.9%) were men, with an average age of 58.25 years. Furthermore, 56(18.1%) received neoadjuvant chemotherapy, and 191(61.8%) were in TNM stage Ⅲ. In addition, 158 patients received intraoperative sustainedrelease chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate(P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival.CONCLUSION Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer.展开更多
In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to estab...In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfura130 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.展开更多
AIM To investigate the predictive value of PIK3 CA and TP53 mutation status in colorectal cancer(CRC) patients treated with 5-fluorouracil-based chemotherapy.METHODS In this study, a total of 315 patients with histolo...AIM To investigate the predictive value of PIK3 CA and TP53 mutation status in colorectal cancer(CRC) patients treated with 5-fluorouracil-based chemotherapy.METHODS In this study, a total of 315 patients with histologically proven CRC were enrolled from Yangpu Hospital affiliated to Shanghai Tongji University between 2007 and 2011. Of these patients, 241 with stage Ⅱ/Ⅲ CRC received 5-fluorouracil-based adjuvant chemotherapy. Formalin-fixed paraffin-embedded lesion samples of the patients with curatively resected CRC were collected.Next-generation sequencing was performed to identify somatic gene mutations. The correlation of PIK3 CA and TP53 mutation status with overall survival(OS) was analyzed using a Cox proportional hazard model and the Kaplan-Meier method.RESULTS Among the 241 patients with stage Ⅱ/Ⅲ in this cohort, the PIK3 CA and/or TP53 mutation was detected in 177 patients, among which 54 patients had PIK3 CA and TP53 double mutations. The PIK3 CA or TP53 mutation was not significantly correlated with OS in univariate and multivariate analyses. Compared with patients without PIK3 CA and TP53 mutations, those with double PIK3 CA-TP53 mutations showed a significantly worse survival(univariate HR = 2.21; 95%CI: 1.15-4.24; multivariate HR = 2.02; 95%CI: 1.04-3.91). The PIK3 CA mutation located in the kinase domain showed a trend toward a shorter OS compared with wild-type tumors(multivariate HR = 1.56; 95%CI: 1.00-2.44; P = 0.052). The Kaplan-Meier curve showed that patients harboring the PIK3 CA mutation located in the kinase domain had a worse clinical outcome than those with wild-type status(Log-rank P = 0.041)CONCLUSION Double mutation of PIK3 CA and TP53 is correlated with a shorter OS in stage Ⅱ/Ⅲ CRC patients treated with 5-fluorouracil-based therapy.展开更多
目的:探讨Discs大同源物相关蛋白5(Discs large homolog associated protein 5,DLGAP5)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及其临床意义。方法:采用免疫组化法检测144对肝细胞癌组织和对应的癌旁组织样本中DLGAP5蛋白的...目的:探讨Discs大同源物相关蛋白5(Discs large homolog associated protein 5,DLGAP5)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及其临床意义。方法:采用免疫组化法检测144对肝细胞癌组织和对应的癌旁组织样本中DLGAP5蛋白的表达,分析其表达与患者临床病理特征的关系,绘制Kaplan-Meier生存曲线分析DLGAP5表达对患者预后的影响。结果:肝细胞癌组织中DLGAP5表达阳性率77.8%,高于癌旁组织的阳性率38.9%,差异有统计学意义(P<0.01)。DLGAP5表达与肿瘤直径、TNM分级、脉管癌栓及肿瘤包膜完整性有关(均P<0.05),而与患者性别、年龄、乙型肝炎表面抗原、肝硬化及远处转移无关(均P>0.05)。Kaplan-Meier生存曲线分析显示,DLGAP5高表达组患者总生存率显著低于DLGAP5低表达组患者,差异具有统计学意义(P<0.05)。结论:DLGAP5蛋白在肝细胞癌中表达增高,其高表达与患者的预后不良有关。展开更多
Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism betwee...Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.展开更多
Objective: To investigate the factors affecting progno- sis of patients with primary hepatocellular carcinoma (PHC) after resection. Methods: From 1976 to 1992, 213 patients with PHC treated with hepatectomy were foll...Objective: To investigate the factors affecting progno- sis of patients with primary hepatocellular carcinoma (PHC) after resection. Methods: From 1976 to 1992, 213 patients with PHC treated with hepatectomy were followed up for more than 5 years. Thirty-one of the patients who had sur- vived for more than 5 years were compared with 56 patients who had survived for less than 5 years. Results: Early detection of tumor, radical resection, number of tumors, capsule formation, operation safe distance, presence of portal tumor embolus, pre- sence of cirrhosis and tumor size were important fac- tors affecting the prognosis of patients with PHC. The proportion of small liver cancer in the patients who had survived for more than 5 years was greatly larger than that in the control group. Conclusions: Early detection of tumor and radical re- section are of value in raising the 5-year survival rate. Much remains to be investigated about the rela- tionship between safe margin distance and prognosis of patients with PHC.展开更多
Although alpha-synuclein is generally thought to have a pathological role in Parkinson＇s disease, accumulative evidence exists that alpha-synuclein has a neuroprotective effect. The aim of this study was to evaluate ...Although alpha-synuclein is generally thought to have a pathological role in Parkinson＇s disease, accumulative evidence exists that alpha-synuclein has a neuroprotective effect. The aim of this study was to evaluate the effect of extracellular alpha-synuclein on dopaminergic cell survival. We assessed cell viability using the 3-（4,5-dimethyt-thiazol-2-yt）-2,5-diphenyltertazolium bromide （MTT） assay both in undifferentiated SH-SY5Y （SHSY） cells and neuronally-differentiated SH-SY5Y （ndSHSY） cells after 24 hour treatment with monomeric alpha-synuclein at various concentrations （0 [control], 50, 100 nmol/L, 1 IJmol/L）. To determine whether cell viability assessed by MTT assay was affected by cell proliferation, 5-bromo-2＇-deoxyuridine （BrdU） incorporation assay was per- formed. Level of both Akt and phosphorylated Akt was measured using western blot method in ndSHSY cells with or without 24 hour alpha-synuclein treatment. Cell viability was increased in ndSHSY cells at the nanomolar concentration of alpha-synuclein, but not in SHSY cells. Proportion of BrdU-positive ndSHSY cells was decreased in alpha-synuclein-treated group compared with control group. Level of phosphorylated Akt in alpha-synuclein-treated group was higher compared with the control group. Our study shows that extracellular alpha-synuclein at nanomolar concentra- tion benefits dopaminergic cell survival via Akt pathway.展开更多
文摘BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient population.This active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the prosthesis.Short femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population.Currently,the long-term survival and functional outcomes of various short stems are still being investigated in different clinics.AIM To determine the 5-year survival of the Optimys hip stem.METHODS This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands.All patients received the Optimys short stem(Mathys Ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the endpoint.The secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival rate.Log-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery.Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs.RESULTS The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was seen.Baseline questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionnaires and 233 patients(47%)completed the 2-year follow-up.Both outcome measures significantly improved across all domains in the 1st year after the operation(P<0.03 for all domains).In the 2nd year after surgery,no significant changes were observed in any domain in comparison to the 1-year follow-up.CONCLUSION The Optimys stem has a 5-year survival of 98.8%.Patient-reported outcome measures increased significantly in the 1st postoperative year with stabilization at the 2-year follow-up.
基金General Research Program of Medical Health in Zhejiang Province(Grant No.2014KYB039)Zhejiang Provincial Program for the Zhejiang Medical and Health Science and Technology Program(Grant No.2015KYB071)+2 种基金Scientific Research Fund Project of Integrated Chinese and Western Medicine Institute in Zhejiang Province(Grant No.2014LYK021)Science and Technology in Zhejiang Province Chinese Medicine Program(Grant No.2016ZA038)1022 Talent Training Program of Zhejiang Cancer Hospital
文摘In this study, we aimed to investigate the influencing factors of postoperative 5-year survival rate in non small-cell lung cancer（NSCLC） patients with stage I–III. We enrolled 220 patients who underwent surgical operation and survived longer than 3 months, with histologically confirmed adenocarcinoma or squamous cell carcinoma from Jan. 2009 to Dec. 2009. Multiple variables, like age, gender, smoking, alcohol, obesity, family history of cancer, diabetes, hypertension, antidiabetic drugs, tumor staging, pathology, treatments, surgical side as well as lipid levels, were selected. We found that tumor staging was associated with 5-year survival rate of stage I–III NSCLC patients by univariate analysis. Furthermore, diabetes mellitus, hypertension and surgical side were associated with the overall survival of NSCLC patients with stage I, stageⅡand stage III, respectively. In conclusion, the status of chronic disease had potential effect on the postoperative 5-year survival rate of lung cancer patients.
基金supported by the National Key Research and Development Program of China(2017YFC1307705)
文摘The prediction of colorectal cancer(CRC) survivability has always been a challenging research issue. Considering the importance of predicting CRC patients’ survival rates, we compared the performance of three data mining methods: decision trees(DTs), artificial neural networks(ANNs) and support vector machines(SVMs), for predicting 5-year survival of CRC patients to assist clinicians in making treatment decisions. The CRC dataset used to build the prediction model comes from the surveillance, epidemiology, and end results(SEER) program. The 5-fold cross-validation and random forest algorithm were respectively utilized for measuring the model predictive accuracy and the importance of features. Experimental results show that the predictive accuracy of ANNs(0.73) and SVMs(0.75) were higher than that of DTs, and they also have the best result in the area under the receiver operating characteristic(ROC) curve(area under curve(AUC)=0.82). This result may indicate high predictive power of ANNs and SVMs for predicting 5-year survival of CRC patients.
基金the CAMS Initiative for Innovative Medicine,No.2016-I2M-1-007。
文摘BACKGROUND The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil(5-FU) in advanced-stage gastric cancer is still unelucidated.AIM To explore the long-term survival benefit of using sustained-release 5-FU implants in stage Ⅱ and stage Ⅲ gastric cancer patients.METHODS Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release(SR) chemotherapy with 5-FU was used or not(NSR). The primary end-point was 5-year overall survival. Kaplan–Meier method with logrank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients.RESULTS In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219(70.9%) were men, with an average age of 58.25 years. Furthermore, 56(18.1%) received neoadjuvant chemotherapy, and 191(61.8%) were in TNM stage Ⅲ. In addition, 158 patients received intraoperative sustainedrelease chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate(P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival.CONCLUSION Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer.
基金supported by the National Basic Research Program of China (973 Program),No.2003CB517104the National Natural Science Foundation of China,No.30973513+3 种基金Beijing Municipal Science and Technology Program,No.D0206001043191the Natural Science Foundation of Beijing,No.7112061Beijing Key Foundation of Traditional Chinese Medicine,No.KJTS2011-04Beijing Health and Technical Personal of High-Level Plan,No.2009-3-66
文摘In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfura130 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.
基金Supported by the National Natural Science Foundation of China,No.81272480Science and Technology Commi-ssion of Shanghai Municipality,No.15411969900 and No.16DZ2342200
文摘AIM To investigate the predictive value of PIK3 CA and TP53 mutation status in colorectal cancer(CRC) patients treated with 5-fluorouracil-based chemotherapy.METHODS In this study, a total of 315 patients with histologically proven CRC were enrolled from Yangpu Hospital affiliated to Shanghai Tongji University between 2007 and 2011. Of these patients, 241 with stage Ⅱ/Ⅲ CRC received 5-fluorouracil-based adjuvant chemotherapy. Formalin-fixed paraffin-embedded lesion samples of the patients with curatively resected CRC were collected.Next-generation sequencing was performed to identify somatic gene mutations. The correlation of PIK3 CA and TP53 mutation status with overall survival(OS) was analyzed using a Cox proportional hazard model and the Kaplan-Meier method.RESULTS Among the 241 patients with stage Ⅱ/Ⅲ in this cohort, the PIK3 CA and/or TP53 mutation was detected in 177 patients, among which 54 patients had PIK3 CA and TP53 double mutations. The PIK3 CA or TP53 mutation was not significantly correlated with OS in univariate and multivariate analyses. Compared with patients without PIK3 CA and TP53 mutations, those with double PIK3 CA-TP53 mutations showed a significantly worse survival(univariate HR = 2.21; 95%CI: 1.15-4.24; multivariate HR = 2.02; 95%CI: 1.04-3.91). The PIK3 CA mutation located in the kinase domain showed a trend toward a shorter OS compared with wild-type tumors(multivariate HR = 1.56; 95%CI: 1.00-2.44; P = 0.052). The Kaplan-Meier curve showed that patients harboring the PIK3 CA mutation located in the kinase domain had a worse clinical outcome than those with wild-type status(Log-rank P = 0.041)CONCLUSION Double mutation of PIK3 CA and TP53 is correlated with a shorter OS in stage Ⅱ/Ⅲ CRC patients treated with 5-fluorouracil-based therapy.
文摘目的:探讨Discs大同源物相关蛋白5(Discs large homolog associated protein 5,DLGAP5)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及其临床意义。方法:采用免疫组化法检测144对肝细胞癌组织和对应的癌旁组织样本中DLGAP5蛋白的表达,分析其表达与患者临床病理特征的关系,绘制Kaplan-Meier生存曲线分析DLGAP5表达对患者预后的影响。结果:肝细胞癌组织中DLGAP5表达阳性率77.8%,高于癌旁组织的阳性率38.9%,差异有统计学意义(P<0.01)。DLGAP5表达与肿瘤直径、TNM分级、脉管癌栓及肿瘤包膜完整性有关(均P<0.05),而与患者性别、年龄、乙型肝炎表面抗原、肝硬化及远处转移无关(均P>0.05)。Kaplan-Meier生存曲线分析显示,DLGAP5高表达组患者总生存率显著低于DLGAP5低表达组患者,差异具有统计学意义(P<0.05)。结论:DLGAP5蛋白在肝细胞癌中表达增高,其高表达与患者的预后不良有关。
文摘Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.
文摘Objective: To investigate the factors affecting progno- sis of patients with primary hepatocellular carcinoma (PHC) after resection. Methods: From 1976 to 1992, 213 patients with PHC treated with hepatectomy were followed up for more than 5 years. Thirty-one of the patients who had sur- vived for more than 5 years were compared with 56 patients who had survived for less than 5 years. Results: Early detection of tumor, radical resection, number of tumors, capsule formation, operation safe distance, presence of portal tumor embolus, pre- sence of cirrhosis and tumor size were important fac- tors affecting the prognosis of patients with PHC. The proportion of small liver cancer in the patients who had survived for more than 5 years was greatly larger than that in the control group. Conclusions: Early detection of tumor and radical re- section are of value in raising the 5-year survival rate. Much remains to be investigated about the rela- tionship between safe margin distance and prognosis of patients with PHC.
基金supported by the Seoul National University Hospital(SNUH)Research Fund,No.03-2010-0240
文摘Although alpha-synuclein is generally thought to have a pathological role in Parkinson＇s disease, accumulative evidence exists that alpha-synuclein has a neuroprotective effect. The aim of this study was to evaluate the effect of extracellular alpha-synuclein on dopaminergic cell survival. We assessed cell viability using the 3-（4,5-dimethyt-thiazol-2-yt）-2,5-diphenyltertazolium bromide （MTT） assay both in undifferentiated SH-SY5Y （SHSY） cells and neuronally-differentiated SH-SY5Y （ndSHSY） cells after 24 hour treatment with monomeric alpha-synuclein at various concentrations （0 [control], 50, 100 nmol/L, 1 IJmol/L）. To determine whether cell viability assessed by MTT assay was affected by cell proliferation, 5-bromo-2＇-deoxyuridine （BrdU） incorporation assay was per- formed. Level of both Akt and phosphorylated Akt was measured using western blot method in ndSHSY cells with or without 24 hour alpha-synuclein treatment. Cell viability was increased in ndSHSY cells at the nanomolar concentration of alpha-synuclein, but not in SHSY cells. Proportion of BrdU-positive ndSHSY cells was decreased in alpha-synuclein-treated group compared with control group. Level of phosphorylated Akt in alpha-synuclein-treated group was higher compared with the control group. Our study shows that extracellular alpha-synuclein at nanomolar concentra- tion benefits dopaminergic cell survival via Akt pathway.
