Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms ...Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms of overall survival(OS),progression-free survival(PFS),and rates of discontinuation and adverse effects during the treatment period.Methods:This is a retrospective,nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017.We focused on patients at either“favorable”or“intermediate”risk according to the International mRCC Database Consortium criteria,and they were followed up(median 335 days).Finally,a total of 1409 patients were selected as the study population.We generated a Cox proportional hazard model adjusted for covariates,and the different therapy schemes were statistically tested in terms of OS as well as PFS.In addition,frequencies of discontinuation and adverse events were compared among the therapy schemes.Results:Of the primary patterns of treatment sequences(24 sequences),“sunitinib epazopanib”and“sunitinibeeverolimuseimmunotherapy”showed the most beneficial results in both OS and PFS with significantly lower hazards than“sunitinib”,which is the most commonly treated agent in Korea.Considering that the“TKIeTKI”structure showed relatively higher discontinuation rates with higher adverse effects,the overall beneficial sequence would be“sunitinibeeverolimuseimmunotherapy”.Conclusion:Among several sequential therapy starting with TKIs,“sunitinibeeverolimuse immunotherapy”was found to be the best scheme for mRCC patients with“favorable”or“intermediate”risks.展开更多
Pancreatic cancer is the fourth most common cause of cancer deaths worldwide. Although recent therapeutic developments for patients with pancreatic cancer have provided survival benefits, the outcomes for patients wit...Pancreatic cancer is the fourth most common cause of cancer deaths worldwide. Although recent therapeutic developments for patients with pancreatic cancer have provided survival benefits, the outcomes for patients with pancreatic cancer remain unsatisfactory. Molecularly targeted cancer therapy has advanced in the past decade with the use of a number of pathways as candidates of therapeutic targets. This review summarizes the molecular features of this refractory disease while focusing on the recent clinical and experimental findings on pancreatic cancer. It also discusses the data supporting current standard clinical outcomes, and offers conclusions that may improve the management of pancreatic cancer in the future.展开更多
目的探讨β-羟基丁酸(β-hydroxybutyrate,BHB)对β样淀粉肽(β-amyloidpeptide,Aβ)处理的神经细胞保护作用及其可能的机制,为防治阿尔茨海默病(Alzheimer’s disease,AD)提供依据。方法将体外培养的SH-SY5Y细胞进行分组,单纯BHB组、BH...目的探讨β-羟基丁酸(β-hydroxybutyrate,BHB)对β样淀粉肽(β-amyloidpeptide,Aβ)处理的神经细胞保护作用及其可能的机制,为防治阿尔茨海默病(Alzheimer’s disease,AD)提供依据。方法将体外培养的SH-SY5Y细胞进行分组,单纯BHB组、BHB干预组细胞以终浓度为5 m M BHB预处理3 h,再向Aβ处理组、BHB干预组细胞加入终浓度为20μM的Aβ,同时设立对照组,24 h后收集细胞;采用qRT-PCR、Western Blot法检测各组细胞Trk A、HDAC1和HDAC3mRNA及其蛋白相对表达水平。以siRNA沉默HDAC1/3,分析细胞Trk A mRNA及其蛋白相对表达水平。结果与对照组相比,单纯BHB组细胞的Trk A mRNA及其蛋白相对表达水平明显升高(P<0.05)、HDAC1和HDAC3 mRNA及其蛋白相对表达水平显著降低(P<0.05),Aβ组细胞Trk A mRNA及其蛋白相对表达水平显著降低(P<0.01)、HDAC1和HDAC3 mRNA及其蛋白相对表达水平显著升高(P<0.01);与Aβ组相比,BHB干预组Trk A mRNA及其蛋白相对表达水平显著升高(P<0.01)、HDAC1和HDAC3 mRNA及其蛋白相对表达水平显著降低(P<0.01)。沉默HDAC1/3后细胞Trk A mRNA及其蛋白相对表达水平显著升高(P<0.05)。结论 BHB可通过抑制HDAC1/3,上调Aβ处理的SH-SY5Y细胞Trk A的表达。展开更多
Brain metastases are significant causes of morbidity or mortality for patients with metastatic cancer.With the application of novel systematic therapy and improvement of overall survival,the prevalence of brain metast...Brain metastases are significant causes of morbidity or mortality for patients with metastatic cancer.With the application of novel systematic therapy and improvement of overall survival,the prevalence of brain metastases is increasing.The paradigm of treatment for brain metastases evolved rapidly during the last 30 years due to the development of technology and emergence of novel therapy.Brain metastases used to be regarded as the terminal stage of cancer and left life expectancy to only 1 month.The application of whole brain radiotherapy for patients with brain metastases increased the life expectancy to 4–6 months in the 1980s.Following studies established surgical resection followed by the application of whole brain radiotherapy the standard treatment for patients with single metastasis and good systematic performance.With the development of stereotactic radiosurgery,stereotactic radiosurgery plus whole brain radiotherapy provides an alternative modality with superior neurocognitive protection at the cost of overall survival.In addition,stereotactic radiosurgery combined with whole brain radiotherapy may offer a promising modality for patients with numerous multiple brain metastases who are not eligible for surgical resection.With the advancing understanding of molecular pathway and biological behavior of oncogenesis and tumor metastasis,novel targeted therapy including tyrosine-kinase inhibitors and immunotherapy are applied to brain metastases.Clinical trials had revealed the efficacy of targeted therapy.Furthermore,the combination of targeted therapy and radiotherapy or chemotherapy is the highlight of current investigation.Advancement in this area may further change the treatment paradigm and offer better modality for patients who are not suitable for surgical resection or radiosurgery.展开更多
文摘Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms of overall survival(OS),progression-free survival(PFS),and rates of discontinuation and adverse effects during the treatment period.Methods:This is a retrospective,nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017.We focused on patients at either“favorable”or“intermediate”risk according to the International mRCC Database Consortium criteria,and they were followed up(median 335 days).Finally,a total of 1409 patients were selected as the study population.We generated a Cox proportional hazard model adjusted for covariates,and the different therapy schemes were statistically tested in terms of OS as well as PFS.In addition,frequencies of discontinuation and adverse events were compared among the therapy schemes.Results:Of the primary patterns of treatment sequences(24 sequences),“sunitinib epazopanib”and“sunitinibeeverolimuseimmunotherapy”showed the most beneficial results in both OS and PFS with significantly lower hazards than“sunitinib”,which is the most commonly treated agent in Korea.Considering that the“TKIeTKI”structure showed relatively higher discontinuation rates with higher adverse effects,the overall beneficial sequence would be“sunitinibeeverolimuseimmunotherapy”.Conclusion:Among several sequential therapy starting with TKIs,“sunitinibeeverolimuse immunotherapy”was found to be the best scheme for mRCC patients with“favorable”or“intermediate”risks.
基金Supported by(in part)Grant-in-Aid for Scientific ResearchNo.23390329
文摘Pancreatic cancer is the fourth most common cause of cancer deaths worldwide. Although recent therapeutic developments for patients with pancreatic cancer have provided survival benefits, the outcomes for patients with pancreatic cancer remain unsatisfactory. Molecularly targeted cancer therapy has advanced in the past decade with the use of a number of pathways as candidates of therapeutic targets. This review summarizes the molecular features of this refractory disease while focusing on the recent clinical and experimental findings on pancreatic cancer. It also discusses the data supporting current standard clinical outcomes, and offers conclusions that may improve the management of pancreatic cancer in the future.
文摘目的探讨β-羟基丁酸(β-hydroxybutyrate,BHB)对β样淀粉肽(β-amyloidpeptide,Aβ)处理的神经细胞保护作用及其可能的机制,为防治阿尔茨海默病(Alzheimer’s disease,AD)提供依据。方法将体外培养的SH-SY5Y细胞进行分组,单纯BHB组、BHB干预组细胞以终浓度为5 m M BHB预处理3 h,再向Aβ处理组、BHB干预组细胞加入终浓度为20μM的Aβ,同时设立对照组,24 h后收集细胞;采用qRT-PCR、Western Blot法检测各组细胞Trk A、HDAC1和HDAC3mRNA及其蛋白相对表达水平。以siRNA沉默HDAC1/3,分析细胞Trk A mRNA及其蛋白相对表达水平。结果与对照组相比,单纯BHB组细胞的Trk A mRNA及其蛋白相对表达水平明显升高(P<0.05)、HDAC1和HDAC3 mRNA及其蛋白相对表达水平显著降低(P<0.05),Aβ组细胞Trk A mRNA及其蛋白相对表达水平显著降低(P<0.01)、HDAC1和HDAC3 mRNA及其蛋白相对表达水平显著升高(P<0.01);与Aβ组相比,BHB干预组Trk A mRNA及其蛋白相对表达水平显著升高(P<0.01)、HDAC1和HDAC3 mRNA及其蛋白相对表达水平显著降低(P<0.01)。沉默HDAC1/3后细胞Trk A mRNA及其蛋白相对表达水平显著升高(P<0.05)。结论 BHB可通过抑制HDAC1/3,上调Aβ处理的SH-SY5Y细胞Trk A的表达。
文摘Brain metastases are significant causes of morbidity or mortality for patients with metastatic cancer.With the application of novel systematic therapy and improvement of overall survival,the prevalence of brain metastases is increasing.The paradigm of treatment for brain metastases evolved rapidly during the last 30 years due to the development of technology and emergence of novel therapy.Brain metastases used to be regarded as the terminal stage of cancer and left life expectancy to only 1 month.The application of whole brain radiotherapy for patients with brain metastases increased the life expectancy to 4–6 months in the 1980s.Following studies established surgical resection followed by the application of whole brain radiotherapy the standard treatment for patients with single metastasis and good systematic performance.With the development of stereotactic radiosurgery,stereotactic radiosurgery plus whole brain radiotherapy provides an alternative modality with superior neurocognitive protection at the cost of overall survival.In addition,stereotactic radiosurgery combined with whole brain radiotherapy may offer a promising modality for patients with numerous multiple brain metastases who are not eligible for surgical resection.With the advancing understanding of molecular pathway and biological behavior of oncogenesis and tumor metastasis,novel targeted therapy including tyrosine-kinase inhibitors and immunotherapy are applied to brain metastases.Clinical trials had revealed the efficacy of targeted therapy.Furthermore,the combination of targeted therapy and radiotherapy or chemotherapy is the highlight of current investigation.Advancement in this area may further change the treatment paradigm and offer better modality for patients who are not suitable for surgical resection or radiosurgery.
