Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reduci...Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reducing the need for extended pelvic lymph node dissection(ePLND).This study aims to evaluate a patient-tailored care pathway in which ePLND is performed only in patients with unfavorable intermediate-or high-risk PC who are deemed at risk for LNI based on PSMA PET/CT findings.Methods:In this interventional cohort study,81 patients were managed according to the new care pathway.ePLND was omitted in cases of negative PSMA PET/CT findings(N0M0),while those with positive PSMA PET/CT findings(N1M0)underwent ePLND.A comparator group of 81 patients was selected from a prospectively generated database for comparison.Results:The intervention group experienced a 75% reduction in the number of ePLNDs performed compared to the comparator group(p<0.001).ePLND-related complications were significantly lower in the intervention group(p=0.008).No significant difference was observed in 3-year biochemical-recurrence free survival(BRFS)between the two groups(p=0.958).Conclusion:Omitting ePLND in patients with negative PSMA PET/CT findings(N0M0)leads to a substantial reduction in the number of ePLNDs performed,resulting in a decrease in morbidity,without compromising early oncological outcomes.展开更多
Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated signi...Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.展开更多
The proteasome,an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles,performs both shared and distinct functions across various tissues and organs.Spermatogenesi...The proteasome,an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles,performs both shared and distinct functions across various tissues and organs.Spermatogenesis,a highly complex developmental process,relies on proteasome activity at multiple stages to regulate protein turnover.In this study,we selected the 20S subunit PSMA1 and 19S regulatory subunit PSMD2 to investigate the potential functions of the proteasome in spermatogenesis.Using Psma1-EGFP and Psmd2-mCherry knock-in mouse models,we confirmed the expression of both subunits in all spermatogenic cell types,with pronounced presence in early germ cell development.To further clarify their functional significance,we specifically knocked out Psma1 and Psmd2 in germ cells.Deletion of either PSMA1 or PSMD2 led to disrupted spermatogenesis,characterized by the complete absence of sperm in the epididymis.Subsequent analysis indicated that loss of these proteasome components impaired meiotic initiation.Psma1 and Psmd2 knockout germ cells showed accumulation of DMRT1,a key regulator of mitosis-to-meiosis transition,leading to a reduction in STRA8 levels and consequent disruption of meiosis initiation.This study sheds light on the molecular mechanisms that govern meiotic initiation and identifies potential genes associated with male infertility.展开更多
Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes...Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes hundreds of thousands of new cases and tens of thousands of male deaths globally each year. The incidence of PCa varies across different regions and populations, generally being higher in developed countries. This disparity may be attributed to lifestyle factors and the widespread availability of screening and diagnostic technologies. Prostate-specific membrane antigen (PSMA) is a membrane-bound enzyme predominantly expressed in prostate tissue and PCa cells, with lower expression in normal tissues. This high expression makes PSMA a critical target for the diagnosis and treatment of PCa, particularly in the field of molecular imaging and radiopharmaceutical therapy. Recently, various studies have emerged on radiopharmaceuticals developed based on PSMA ligands, which can be used to specifically identify and locate PCa cells. Research on the radiomics of these novel drugs has also been updated. This article will discuss the role and limitations of PSMA PET in the diagnosis and management of PCa treatment.展开更多
全球IUU(Illegal,Unreported and Unregulated fishing)严重影响海洋生态,《港口国措施协定》(PSMA)为首个打击IUU捕捞的全球性协定,通过加强港口监管及全链条溯源,重构国际渔业治理。中国于2025年加入PSMA,此举在履行国际义务的同时,...全球IUU(Illegal,Unreported and Unregulated fishing)严重影响海洋生态,《港口国措施协定》(PSMA)为首个打击IUU捕捞的全球性协定,通过加强港口监管及全链条溯源,重构国际渔业治理。中国于2025年加入PSMA,此举在履行国际义务的同时,也对国内渔业治理形成了倒逼改革之势。面临国内制度适配困难:在法律层面,《中华人民共和国渔业法》条款过于笼统,未包含对外国渔船入港审查的具体规则;在监管层面,多个部门各自为政,协作机制缺失;在信息层面,国内信息呈孤岛状态,国际共享渠道受阻;在执法层面,惩罚力度较小,无法抵消违法收益。对此,应从修订《中华人民共和国渔业法》增设涉外港口管理专章、构建跨部门监管协作框架、建立信息共享分层优化机制、加大对违法行为的处罚力度等角度出发,推进中国履行PSMA义务的路径,实现渔业治理现代化。展开更多
Prostate cancer is the second most common cancer in men,accounting for 14.1%of new cancer cases in 2020.The aggressiveness of prostate cancer is highly variable,depending on its grade and stage at the time of diagnosi...Prostate cancer is the second most common cancer in men,accounting for 14.1%of new cancer cases in 2020.The aggressiveness of prostate cancer is highly variable,depending on its grade and stage at the time of diagnosis.Despite recent advances in prostate cancer treatment,some patients still experience recurrence or even progression after undergoing radical treatment.Accurate initial staging and monitoring for recurrence determine patient management,which in turn affect patient prognosis and survival.Classical imaging has limitations in the diagnosis and treatment of prostate cancer,but the use of novel molecular probes has improved the detection rate,specificity,and accuracy of prostate cancer detection.Molecular probe-based imaging modalities allow the visualization and quantitative measurement of biological processes at the molecular and cellular levels in living systems.An increased understanding of tumor biology of prostate cancer and the discovery of new tumor biomarkers have allowed the exploration of additional molecular probe targets.The development of novel ligands and advances in nano-based delivery technologies have accelerated the research and development of molecular probes.Here,we summarize the use of molecular probes in positron emission tomography(PET),single-photon emission computed tomography(SPECT),magnetic resonance imaging(MRI),optical imaging,and ultrasound imaging,and provide a brief overview of important target molecules in prostate cancer.展开更多
前列腺癌(PCa)在全球恶性肿瘤中发病率占第二位,其中它的Gleason分级与生物学行为和预后密切关联,在临床上它作为一个决定治疗方案的重要指标,而影像组学的对于评估具有潜在的、发展性的重要作用。传统的经直肠超声前列腺癌穿刺活检(tra...前列腺癌(PCa)在全球恶性肿瘤中发病率占第二位,其中它的Gleason分级与生物学行为和预后密切关联,在临床上它作为一个决定治疗方案的重要指标,而影像组学的对于评估具有潜在的、发展性的重要作用。传统的经直肠超声前列腺癌穿刺活检(transrectal of ultrasound,TRUS),可能会因病灶的形态、部位和操作者测量方式的不同等方面因素而与术后病理分级存在一定差异,影像组学通过对于图像大量的特征提取,来挖掘出大量的医学信息,从而应用在前列腺癌的诊断、Gleason分级、侵袭性评估、生化复发等方面。本文就影像组学应用于PCa的Gleason分级的研究进展进行综述。展开更多
Objectives:Due to systematic side effects,there is a growing interest in nanoparticle formulation of anticancer drugs.Here,we aimed to synthesize poly(styrene-alt-maleic anhydride)cross-linked by melamine(PSMA/Me)and ...Objectives:Due to systematic side effects,there is a growing interest in nanoparticle formulation of anticancer drugs.Here,we aimed to synthesize poly(styrene-alt-maleic anhydride)cross-linked by melamine(PSMA/Me)and coated with magnetite nanoparticles(MNPs)PSMA/Me/Fe_(3)O_(4).In addition,we aimed to load paclitaxel(PTX)into PSMA/Me/Fe_(3)O_(4)for drug delivery and anticancer investigations.Methods:Novel PSMA/Me was synthesized via free radical copolymerization,coated with Fe_(3)O_(4),and then used as a transporter for PTX delivery.Fabricated copolymer was characterized using SEM,TGA,and XRD techniques.Drug release rate and loading efficiency were investigated.Human ovarian cancer cells(Skov-3)and breast cancer cells(MCF-7 cells)were incubated with the serial concentration of either free PTX or PSMA/Me/Fe_(3)O_(4)/PTX for cell viability and IC_(50)analysis for 24 and 48 h.Results:Characterization methods confirmed PSMA/Me copolymer formation.The results showed a significant encapsulation efficiency of 83%.The drug release analysis exhibited that PSMA/Me/Fe_(3)O_(4)/PTX may be considered pH-sensitive nanocarriers.PSMA/Me/Fe_(3)O_(4)/PTX reduced cell viability both dose and time-dependently(p<0.05).IC50 values of PSMA/Me/Fe_(3)O_(4)/PTX were low when compared to free PTX either 24 or 48 h post-treatment.Conclusions:Our results indicated that PSMA/Me/Fe_(3)O_(4)/PTX was more cytotoxic than PTX in both cancer cells.Findings indicated the potential of PSMA/Me/Fe_(3)O_(4)/PTX as an anticancer nanocarrier system.展开更多
基金supported by a grant from Kom op tegen Kanker(Stand Up to Cancer,Belgium).
文摘Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reducing the need for extended pelvic lymph node dissection(ePLND).This study aims to evaluate a patient-tailored care pathway in which ePLND is performed only in patients with unfavorable intermediate-or high-risk PC who are deemed at risk for LNI based on PSMA PET/CT findings.Methods:In this interventional cohort study,81 patients were managed according to the new care pathway.ePLND was omitted in cases of negative PSMA PET/CT findings(N0M0),while those with positive PSMA PET/CT findings(N1M0)underwent ePLND.A comparator group of 81 patients was selected from a prospectively generated database for comparison.Results:The intervention group experienced a 75% reduction in the number of ePLNDs performed compared to the comparator group(p<0.001).ePLND-related complications were significantly lower in the intervention group(p=0.008).No significant difference was observed in 3-year biochemical-recurrence free survival(BRFS)between the two groups(p=0.958).Conclusion:Omitting ePLND in patients with negative PSMA PET/CT findings(N0M0)leads to a substantial reduction in the number of ePLNDs performed,resulting in a decrease in morbidity,without compromising early oncological outcomes.
文摘Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.
基金supported by the National Science Fund for Distinguished Young Scholars (81925015)Science and Technology Project of Guangzhou (2023A03J0886,2023A03J0871)National Natural Science Foundation of China (82030039,32400709)。
文摘The proteasome,an evolutionarily conserved proteolytic complex comprising the 20S core particle and 19S regulatory particles,performs both shared and distinct functions across various tissues and organs.Spermatogenesis,a highly complex developmental process,relies on proteasome activity at multiple stages to regulate protein turnover.In this study,we selected the 20S subunit PSMA1 and 19S regulatory subunit PSMD2 to investigate the potential functions of the proteasome in spermatogenesis.Using Psma1-EGFP and Psmd2-mCherry knock-in mouse models,we confirmed the expression of both subunits in all spermatogenic cell types,with pronounced presence in early germ cell development.To further clarify their functional significance,we specifically knocked out Psma1 and Psmd2 in germ cells.Deletion of either PSMA1 or PSMD2 led to disrupted spermatogenesis,characterized by the complete absence of sperm in the epididymis.Subsequent analysis indicated that loss of these proteasome components impaired meiotic initiation.Psma1 and Psmd2 knockout germ cells showed accumulation of DMRT1,a key regulator of mitosis-to-meiosis transition,leading to a reduction in STRA8 levels and consequent disruption of meiosis initiation.This study sheds light on the molecular mechanisms that govern meiotic initiation and identifies potential genes associated with male infertility.
文摘Prostate cancer (PCa) is the second most common type of cancer among men worldwide and one of the leading causes of cancer-related deaths. According to data from the World Health Organization (WHO), this cancer causes hundreds of thousands of new cases and tens of thousands of male deaths globally each year. The incidence of PCa varies across different regions and populations, generally being higher in developed countries. This disparity may be attributed to lifestyle factors and the widespread availability of screening and diagnostic technologies. Prostate-specific membrane antigen (PSMA) is a membrane-bound enzyme predominantly expressed in prostate tissue and PCa cells, with lower expression in normal tissues. This high expression makes PSMA a critical target for the diagnosis and treatment of PCa, particularly in the field of molecular imaging and radiopharmaceutical therapy. Recently, various studies have emerged on radiopharmaceuticals developed based on PSMA ligands, which can be used to specifically identify and locate PCa cells. Research on the radiomics of these novel drugs has also been updated. This article will discuss the role and limitations of PSMA PET in the diagnosis and management of PCa treatment.
文摘全球IUU(Illegal,Unreported and Unregulated fishing)严重影响海洋生态,《港口国措施协定》(PSMA)为首个打击IUU捕捞的全球性协定,通过加强港口监管及全链条溯源,重构国际渔业治理。中国于2025年加入PSMA,此举在履行国际义务的同时,也对国内渔业治理形成了倒逼改革之势。面临国内制度适配困难:在法律层面,《中华人民共和国渔业法》条款过于笼统,未包含对外国渔船入港审查的具体规则;在监管层面,多个部门各自为政,协作机制缺失;在信息层面,国内信息呈孤岛状态,国际共享渠道受阻;在执法层面,惩罚力度较小,无法抵消违法收益。对此,应从修订《中华人民共和国渔业法》增设涉外港口管理专章、构建跨部门监管协作框架、建立信息共享分层优化机制、加大对违法行为的处罚力度等角度出发,推进中国履行PSMA义务的路径,实现渔业治理现代化。
基金supported by the Medical Health Science and Technology Project of Zhejiang Provincial Health Com-mission(No.2022RC146)the Zhejiang Provincial Natural Science Foundation of China(No.LQ22H050003).
文摘Prostate cancer is the second most common cancer in men,accounting for 14.1%of new cancer cases in 2020.The aggressiveness of prostate cancer is highly variable,depending on its grade and stage at the time of diagnosis.Despite recent advances in prostate cancer treatment,some patients still experience recurrence or even progression after undergoing radical treatment.Accurate initial staging and monitoring for recurrence determine patient management,which in turn affect patient prognosis and survival.Classical imaging has limitations in the diagnosis and treatment of prostate cancer,but the use of novel molecular probes has improved the detection rate,specificity,and accuracy of prostate cancer detection.Molecular probe-based imaging modalities allow the visualization and quantitative measurement of biological processes at the molecular and cellular levels in living systems.An increased understanding of tumor biology of prostate cancer and the discovery of new tumor biomarkers have allowed the exploration of additional molecular probe targets.The development of novel ligands and advances in nano-based delivery technologies have accelerated the research and development of molecular probes.Here,we summarize the use of molecular probes in positron emission tomography(PET),single-photon emission computed tomography(SPECT),magnetic resonance imaging(MRI),optical imaging,and ultrasound imaging,and provide a brief overview of important target molecules in prostate cancer.
文摘前列腺癌(PCa)在全球恶性肿瘤中发病率占第二位,其中它的Gleason分级与生物学行为和预后密切关联,在临床上它作为一个决定治疗方案的重要指标,而影像组学的对于评估具有潜在的、发展性的重要作用。传统的经直肠超声前列腺癌穿刺活检(transrectal of ultrasound,TRUS),可能会因病灶的形态、部位和操作者测量方式的不同等方面因素而与术后病理分级存在一定差异,影像组学通过对于图像大量的特征提取,来挖掘出大量的医学信息,从而应用在前列腺癌的诊断、Gleason分级、侵袭性评估、生化复发等方面。本文就影像组学应用于PCa的Gleason分级的研究进展进行综述。
文摘Objectives:Due to systematic side effects,there is a growing interest in nanoparticle formulation of anticancer drugs.Here,we aimed to synthesize poly(styrene-alt-maleic anhydride)cross-linked by melamine(PSMA/Me)and coated with magnetite nanoparticles(MNPs)PSMA/Me/Fe_(3)O_(4).In addition,we aimed to load paclitaxel(PTX)into PSMA/Me/Fe_(3)O_(4)for drug delivery and anticancer investigations.Methods:Novel PSMA/Me was synthesized via free radical copolymerization,coated with Fe_(3)O_(4),and then used as a transporter for PTX delivery.Fabricated copolymer was characterized using SEM,TGA,and XRD techniques.Drug release rate and loading efficiency were investigated.Human ovarian cancer cells(Skov-3)and breast cancer cells(MCF-7 cells)were incubated with the serial concentration of either free PTX or PSMA/Me/Fe_(3)O_(4)/PTX for cell viability and IC_(50)analysis for 24 and 48 h.Results:Characterization methods confirmed PSMA/Me copolymer formation.The results showed a significant encapsulation efficiency of 83%.The drug release analysis exhibited that PSMA/Me/Fe_(3)O_(4)/PTX may be considered pH-sensitive nanocarriers.PSMA/Me/Fe_(3)O_(4)/PTX reduced cell viability both dose and time-dependently(p<0.05).IC50 values of PSMA/Me/Fe_(3)O_(4)/PTX were low when compared to free PTX either 24 or 48 h post-treatment.Conclusions:Our results indicated that PSMA/Me/Fe_(3)O_(4)/PTX was more cytotoxic than PTX in both cancer cells.Findings indicated the potential of PSMA/Me/Fe_(3)O_(4)/PTX as an anticancer nanocarrier system.
