We compared the predictive ability of the 2014 and 2005 Gleason grading systems in 568 patients initially diagnosed with metastatic prostate cancer （PCa）. Outcomes included the duration of castration-resistant prost...We compared the predictive ability of the 2014 and 2005 Gleason grading systems in 568 patients initially diagnosed with metastatic prostate cancer （PCa）. Outcomes included the duration of castration-resistant prostate cancer-free survival （CFS） and overall survival （OS）. Univariate analyses and log-rank tests were used to identify prognosis indicators and assess univariable differences in CFS and OS in Gleason score （GS） groups. Cox proportional hazards and area under the curves of receiver operator characteristics methods were used to evaluate the predictive efficacy of the 2005 and 2014 ISUP grading systems. Univariate analyses showed that the 2005 and 2014 grading systems were prognosticators for CFS and OS; both systems could distinguish the clinical outcome of patients with GS 6, GS 7, and GS 8-10. Using the 2014 criteria, no statistical differences in patient survival were observed between GS 3 ＋ 4 and GS 4 ＋ 3 or GS 8 and GS 9-10. The predictive ability of the 2014 and 2005 grading systems was comparable for CFS and OS （P = 0.321）. However, the 2014 grading system did not exhibit superior predictive efficacy in patients initially diagnosed with PCa and bone metastasis; trials using larger cohorts are required to confirm its predictive value. To the best of our knowledge, ours is the first study to compare the 2005 and 2014 grading systems in initially diagnosed PCa with bone metastasis. At present, we recommend that both systems should be used to predict the prognosis of patients with metastatic PCa.展开更多
Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in ca...Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in cancer(6.6%in pan-cancer).Currently,the clinical significance of KMT2C mutations in prostate cancer is understudied.Methods:We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study.We investigated the association between KMT2C mutations,other mutations,and pathways.Furthermore,we evaluated the prognostic value of KMT2C mutations,measured by overall survival(OS)and castration resistance-free survival(CRFS).Also,we explored the prognostic value of KMT2C mutations in different patient subgroups.Lastly,we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade(CAB)and abiraterone(ABI)as measured by PSA progression-free survival(PSA-PFS).Results:The KMT2C mutation rate in this cohort is 7.24%(16/221).KMT2C-mutated patients showed worse survival than KMT2C-wild type(WT)patients regarding both CRFS and OS(CRFS:mutated:9.9 vs.WT:22.0 months,p=0.015;OS:mutated:71.9 vs.WT 137.4 months,p=0.012).KMT2C mutations were also an independent risk factor in OS[hazard ratio:3.815(1.461,9.96),p=0.006]in multivariate analyses.Additionally,we explored the association of KMT2C mutations with other genes.This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11(STK11,p=0.004)and Catenin Beta 1(CTNNB1,p=0.008)mutations.In the CAB treatment,KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients.(PSA-PFS:mutated:9.9 vs.WT:17.6 months,p=0.014).Moreover,KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups.Conclusions:KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS,and KMT2C mutations were associated with STK11 and CTNNB1 mutations.Furthermore,KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.展开更多
Prostate cancer is a leading cause of cancer-related death in men worldwide.Luteinizing hormone-releasing hormone receptor(LHRH-R)agonists and antagonists are known to achieve castration-level testosterone suppression...Prostate cancer is a leading cause of cancer-related death in men worldwide.Luteinizing hormone-releasing hormone receptor(LHRH-R)agonists and antagonists are known to achieve castration-level testosterone suppression;however,long-term data comparing the survival benefits of these therapies are insufficient to inform treatment decisions.Furthermore,the advent of nextgeneration hormonal agents(NHAs),such as abiraterone and enzalutamide,have shifted the paradigm of managing prostate cancer.Although LHRH-R agonists and antagonists remain the cornerstone treatment across various stages of prostate cancer,they are increasingly administered with NHAs,because the combination treatment confers a survival advantage.Nevertheless,the differences in efficacy and safety profiles among various combinations of LHRH-R agonists and antagonists and NHAs remain unclear.Hence,this narrative review is aimed at providing a comprehensive overview of the long-term outcomes of various LHRH-R agonists and antagonists.Key data from major clinical studies are summarized,categorized by disease stage.LHRH-R agonists and antagonists,particularly goserelin,have demonstrated long-term survival benefits in patients with localized and locally advanced prostate cancer.The clinical outcomes of different LHRH-R agonists and antagonists in combination with NHAs have also been evaluated.Among the various combinations,goserelin plus abiraterone appears to have a manageable safety profile with relatively low rates of hot flushes and fatigue.Overall,long-term survival data and safety profiles should be considered in selecting optimal combination therapies for prostate cancer treatment.展开更多
Antibody drugs,such as monoclonal antibodies and antibody-drug conjugates,have shown significant potential in treating diseases due to their high specificity and affinity.In vivo analysis of antibody drugs with non-in...Antibody drugs,such as monoclonal antibodies and antibody-drug conjugates,have shown significant potential in treating diseases due to their high specificity and affinity.In vivo analysis of antibody drugs with non-invasive and real-time techniques is of importance to understand dynamic behavior of drugs within living organisms,and help evaluate their pharmacokinetics and efficacies.This review summarizes the advances and in vivo analysis methods of antibody drugs,including the techniques of radiolabeled imaging,near-infrared fluorescence imaging and surface-enhanced Raman spectroscopy.The principles,applications,and challenges of each technique are discussed,which provides insights for the development of antibody drugs and in vivo analytical methods.展开更多
Molecular imaging was developed from basic molecular recognition.It can visualize not only the expression levels of specific molecules in a living system but also specific biological processes,thus providing guidance ...Molecular imaging was developed from basic molecular recognition.It can visualize not only the expression levels of specific molecules in a living system but also specific biological processes,thus providing guidance for early detection and treatment of diseases.As a noninvasive method,imaging agents are one of the foundations of high spatial resolution imaging,and their sensitivity and specificity can be improved by coupling targeting ligands to imaging probes.Among the various targeting ligands(antibodies,aptamers,etc.),targeting peptides are widely used in various modalities of molecular imaging due to their high affinities toward the molecular target and their excellent physicochemical properties.In this review,we summarize the design concepts and methods of targeting peptides in molecular imaging,introduce the combination of targeting peptides and imaging probes in different imaging modalities(e.g.,fluorescence imaging,radionuclide imaging),and provide examples of their applications in bioimaging.Finally,the challenges and strategies for clinical translation and practical application of targeting peptide-based imaging reagents are briefly discussed.展开更多
基金This work was supported by the Natural Science Foundation of China （NSFC 81172439, 81272820, and 81402110）.
文摘We compared the predictive ability of the 2014 and 2005 Gleason grading systems in 568 patients initially diagnosed with metastatic prostate cancer （PCa）. Outcomes included the duration of castration-resistant prostate cancer-free survival （CFS） and overall survival （OS）. Univariate analyses and log-rank tests were used to identify prognosis indicators and assess univariable differences in CFS and OS in Gleason score （GS） groups. Cox proportional hazards and area under the curves of receiver operator characteristics methods were used to evaluate the predictive efficacy of the 2005 and 2014 ISUP grading systems. Univariate analyses showed that the 2005 and 2014 grading systems were prognosticators for CFS and OS; both systems could distinguish the clinical outcome of patients with GS 6, GS 7, and GS 8-10. Using the 2014 criteria, no statistical differences in patient survival were observed between GS 3 ＋ 4 and GS 4 ＋ 3 or GS 8 and GS 9-10. The predictive ability of the 2014 and 2005 grading systems was comparable for CFS and OS （P = 0.321）. However, the 2014 grading system did not exhibit superior predictive efficacy in patients initially diagnosed with PCa and bone metastasis; trials using larger cohorts are required to confirm its predictive value. To the best of our knowledge, ours is the first study to compare the 2005 and 2014 grading systems in initially diagnosed PCa with bone metastasis. At present, we recommend that both systems should be used to predict the prognosis of patients with metastatic PCa.
基金This work was supported by the Natural Science Foundation of China(NSFC 81902577)the Research Foundation for the Postdoctoral Program of Sichuan University(2021SCU12014).
文摘Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in cancer(6.6%in pan-cancer).Currently,the clinical significance of KMT2C mutations in prostate cancer is understudied.Methods:We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study.We investigated the association between KMT2C mutations,other mutations,and pathways.Furthermore,we evaluated the prognostic value of KMT2C mutations,measured by overall survival(OS)and castration resistance-free survival(CRFS).Also,we explored the prognostic value of KMT2C mutations in different patient subgroups.Lastly,we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade(CAB)and abiraterone(ABI)as measured by PSA progression-free survival(PSA-PFS).Results:The KMT2C mutation rate in this cohort is 7.24%(16/221).KMT2C-mutated patients showed worse survival than KMT2C-wild type(WT)patients regarding both CRFS and OS(CRFS:mutated:9.9 vs.WT:22.0 months,p=0.015;OS:mutated:71.9 vs.WT 137.4 months,p=0.012).KMT2C mutations were also an independent risk factor in OS[hazard ratio:3.815(1.461,9.96),p=0.006]in multivariate analyses.Additionally,we explored the association of KMT2C mutations with other genes.This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11(STK11,p=0.004)and Catenin Beta 1(CTNNB1,p=0.008)mutations.In the CAB treatment,KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients.(PSA-PFS:mutated:9.9 vs.WT:17.6 months,p=0.014).Moreover,KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups.Conclusions:KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS,and KMT2C mutations were associated with STK11 and CTNNB1 mutations.Furthermore,KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.
文摘Prostate cancer is a leading cause of cancer-related death in men worldwide.Luteinizing hormone-releasing hormone receptor(LHRH-R)agonists and antagonists are known to achieve castration-level testosterone suppression;however,long-term data comparing the survival benefits of these therapies are insufficient to inform treatment decisions.Furthermore,the advent of nextgeneration hormonal agents(NHAs),such as abiraterone and enzalutamide,have shifted the paradigm of managing prostate cancer.Although LHRH-R agonists and antagonists remain the cornerstone treatment across various stages of prostate cancer,they are increasingly administered with NHAs,because the combination treatment confers a survival advantage.Nevertheless,the differences in efficacy and safety profiles among various combinations of LHRH-R agonists and antagonists and NHAs remain unclear.Hence,this narrative review is aimed at providing a comprehensive overview of the long-term outcomes of various LHRH-R agonists and antagonists.Key data from major clinical studies are summarized,categorized by disease stage.LHRH-R agonists and antagonists,particularly goserelin,have demonstrated long-term survival benefits in patients with localized and locally advanced prostate cancer.The clinical outcomes of different LHRH-R agonists and antagonists in combination with NHAs have also been evaluated.Among the various combinations,goserelin plus abiraterone appears to have a manageable safety profile with relatively low rates of hot flushes and fatigue.Overall,long-term survival data and safety profiles should be considered in selecting optimal combination therapies for prostate cancer treatment.
基金support from the National Natural Science Foundation of China(Grant Nos.:22322403 and 22074006)the Beijing Natural Science Foundation(Grant No.:2222029)the Beijing Institute of Technology Research Fund Program for Young Scholars.
文摘Antibody drugs,such as monoclonal antibodies and antibody-drug conjugates,have shown significant potential in treating diseases due to their high specificity and affinity.In vivo analysis of antibody drugs with non-invasive and real-time techniques is of importance to understand dynamic behavior of drugs within living organisms,and help evaluate their pharmacokinetics and efficacies.This review summarizes the advances and in vivo analysis methods of antibody drugs,including the techniques of radiolabeled imaging,near-infrared fluorescence imaging and surface-enhanced Raman spectroscopy.The principles,applications,and challenges of each technique are discussed,which provides insights for the development of antibody drugs and in vivo analytical methods.
基金support from Beijing Natural Science Foundation(No.2222029)National Natural Science Foundation of China(Nos.22322403 and 22074006)Beijing Institute of Technology Research Fund Program for Young Scholars.
文摘Molecular imaging was developed from basic molecular recognition.It can visualize not only the expression levels of specific molecules in a living system but also specific biological processes,thus providing guidance for early detection and treatment of diseases.As a noninvasive method,imaging agents are one of the foundations of high spatial resolution imaging,and their sensitivity and specificity can be improved by coupling targeting ligands to imaging probes.Among the various targeting ligands(antibodies,aptamers,etc.),targeting peptides are widely used in various modalities of molecular imaging due to their high affinities toward the molecular target and their excellent physicochemical properties.In this review,we summarize the design concepts and methods of targeting peptides in molecular imaging,introduce the combination of targeting peptides and imaging probes in different imaging modalities(e.g.,fluorescence imaging,radionuclide imaging),and provide examples of their applications in bioimaging.Finally,the challenges and strategies for clinical translation and practical application of targeting peptide-based imaging reagents are briefly discussed.
