Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a com...Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a comprehensive search using online literature databases,including PubMed,Web of Science,and Google Scholar.Study Selection：Literature search was based on the following keywords：Alzheimer＇s disease,tau protein,biomarker,cerebrospinal fluid （CSF）,therapeutics,plasma,imaging,propagation,spreading,seeding,prion,conformational templating,and posttranslational modification.Relevant articles were carefully reviewed,with no exclusions applied to study design and publication type.Results：Amyloid plaques enriched with extracellular amyloid beta （Aβ） and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks ofAD.Although the Aβ hypothesis has dominated AD research for many years,clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset.The research focus in AD has recently shifted to the role oftau in AD.In addition to phosphorylation,tau is acetylated and proteolytically cleaved,which also contribute to its physiological and pathological functions.Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis.Techniques to detect tau at minute levels in CSF and blood have been developed,and improved tracers have facilitated tau imaging in the brain.These advances have potential to accurately determine tau levels at early diagnostic stages in AD.Given that tau is a potential therapeutic target,anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.Conclusion：Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.展开更多
Objective：The optimal management strategy for prostate cancer （PCa） remains controversial.We performed a systemic review of current progress and controversies regarding the diagnosis and treatment of PCa.Data Sour...Objective：The optimal management strategy for prostate cancer （PCa） remains controversial.We performed a systemic review of current progress and controversies regarding the diagnosis and treatment of PCa.Data Sources：We searched PubMed for recently published articles up to July 2017 using the following key words：＂prostate cancer,＂ ＂progress,＂ ＂controversy,＂ ＂immunotherapy,＂ and ＂prevention.＂ Study Selection：Articles were obtained and reviewed to provide a systematic review of the current progress and controversies regarding PCa management.Results：The value of serum prostate-specific antigen （PSA） screening remains controversial,but PSA screening is recommended to facilitate the early diagnosis of PCa in high-risk groups.Prostate biopsy via the transrectal or perineal approach has both advantages and disadvantages.There was a significant correlation between testosterone levels and PCa prognosis.The current research is focused on the mechanisms responsible for PCa.Active surveillance has been proposed as a management strategy for low-risk,localized PCa,but there is an urgent need for further clinical studies to establish the criteria for recommending this approach.The main complications of radical resection for PCa are urinary incontinence and erectile dysfunction,though three-dimensional laparoscopic and robot-assisted laparoscopic techniques have obvious advantages over radical surgery.Radiotherapy is also a therapeutic option for PCa,while immunotherapies may alter the prostate tumor microenvironment.Ongoing studies aim to provide guidance on effective sequential and combination strategies.Prevention remains an important strategy for reducing PCa morbidity and mortality.Conclusions：The diagnosis,treatment,and prevention of PCa are complex issues,worthy of intensive study.Further studies are needed to improve the management of PCa.展开更多
Background：To develop a vaccine-based immunotherapy for sarcoma,we evaluated a mixture of heat shock proteins （mHSPs） as a vaccine for sarcoma treatment in a mouse model.Heat shock protein/peptides （HSP/Ps） are a...Background：To develop a vaccine-based immunotherapy for sarcoma,we evaluated a mixture of heat shock proteins （mHSPs） as a vaccine for sarcoma treatment in a mouse model.Heat shock protein/peptides （HSP/Ps） are autoimmune factors that can induce both adaptive and innate immune responses;HSP/Ps isolated from tumors can induce antitumor immune activity when used as vaccines.Methods：In this study,we evaluated the effects of mHSP/Ps on prophylactic antitumor immunity.We extracted mHSP/Ps,including HSP60,HSP70,GP96,and HSP l 10,from the mouse sarcoma cell lines S 180 and MCA207 using chromatography.The immunity induced by mHSP/Ps was assessed using flow cytometry,ELISPOT,lactate dehydrogenase release,and enzyme-linked immunosorbent assay.Results：Of S180 sarcoma-beating mice immunized with mHSP/Ps isolated from S180 cells,41.2% showed tumor regression and long-term survival,with a tumor growth inhibition rate of 82.3% at 30 days.Of MCA207 sarcoma-bearing mice immunized with mHSP/Ps isolated from MCA207 cells,50% showed tumor regression and long-term survival with a tumor growth inhibition rate of 79.3%.All control mice died within 40 days.The proportions of natural killer cells,CD8＋,and interferon-γ-secreting cells and tumor-specific cytotoxic T-lymphocyte activity were increased in the immunized group.Conclusions：Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors.This mHSP/P vaccine exerted greater antitumor effects than did HSPT0,HSP60,or tumor lysates alone.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81671352, 91232709）, the National Key Project of Research and Development Plan （No. 2016YFC1306404）, the National Institute of Health （No. R21 AG048519, R01 AG021173, R01 AG038710, R01 AG044420, R01 NS046673, RF1 AG056130, and RF1 AG056114）, the Tanz Family Fund as well as scholarship from China Scholarship Council （No. 201608350068）.
文摘Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a comprehensive search using online literature databases,including PubMed,Web of Science,and Google Scholar.Study Selection：Literature search was based on the following keywords：Alzheimer＇s disease,tau protein,biomarker,cerebrospinal fluid （CSF）,therapeutics,plasma,imaging,propagation,spreading,seeding,prion,conformational templating,and posttranslational modification.Relevant articles were carefully reviewed,with no exclusions applied to study design and publication type.Results：Amyloid plaques enriched with extracellular amyloid beta （Aβ） and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks ofAD.Although the Aβ hypothesis has dominated AD research for many years,clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset.The research focus in AD has recently shifted to the role oftau in AD.In addition to phosphorylation,tau is acetylated and proteolytically cleaved,which also contribute to its physiological and pathological functions.Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis.Techniques to detect tau at minute levels in CSF and blood have been developed,and improved tracers have facilitated tau imaging in the brain.These advances have potential to accurately determine tau levels at early diagnostic stages in AD.Given that tau is a potential therapeutic target,anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.Conclusion：Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.
文摘Objective：The optimal management strategy for prostate cancer （PCa） remains controversial.We performed a systemic review of current progress and controversies regarding the diagnosis and treatment of PCa.Data Sources：We searched PubMed for recently published articles up to July 2017 using the following key words：＂prostate cancer,＂ ＂progress,＂ ＂controversy,＂ ＂immunotherapy,＂ and ＂prevention.＂ Study Selection：Articles were obtained and reviewed to provide a systematic review of the current progress and controversies regarding PCa management.Results：The value of serum prostate-specific antigen （PSA） screening remains controversial,but PSA screening is recommended to facilitate the early diagnosis of PCa in high-risk groups.Prostate biopsy via the transrectal or perineal approach has both advantages and disadvantages.There was a significant correlation between testosterone levels and PCa prognosis.The current research is focused on the mechanisms responsible for PCa.Active surveillance has been proposed as a management strategy for low-risk,localized PCa,but there is an urgent need for further clinical studies to establish the criteria for recommending this approach.The main complications of radical resection for PCa are urinary incontinence and erectile dysfunction,though three-dimensional laparoscopic and robot-assisted laparoscopic techniques have obvious advantages over radical surgery.Radiotherapy is also a therapeutic option for PCa,while immunotherapies may alter the prostate tumor microenvironment.Ongoing studies aim to provide guidance on effective sequential and combination strategies.Prevention remains an important strategy for reducing PCa morbidity and mortality.Conclusions：The diagnosis,treatment,and prevention of PCa are complex issues,worthy of intensive study.Further studies are needed to improve the management of PCa.
文摘Background：To develop a vaccine-based immunotherapy for sarcoma,we evaluated a mixture of heat shock proteins （mHSPs） as a vaccine for sarcoma treatment in a mouse model.Heat shock protein/peptides （HSP/Ps） are autoimmune factors that can induce both adaptive and innate immune responses;HSP/Ps isolated from tumors can induce antitumor immune activity when used as vaccines.Methods：In this study,we evaluated the effects of mHSP/Ps on prophylactic antitumor immunity.We extracted mHSP/Ps,including HSP60,HSP70,GP96,and HSP l 10,from the mouse sarcoma cell lines S 180 and MCA207 using chromatography.The immunity induced by mHSP/Ps was assessed using flow cytometry,ELISPOT,lactate dehydrogenase release,and enzyme-linked immunosorbent assay.Results：Of S180 sarcoma-beating mice immunized with mHSP/Ps isolated from S180 cells,41.2% showed tumor regression and long-term survival,with a tumor growth inhibition rate of 82.3% at 30 days.Of MCA207 sarcoma-bearing mice immunized with mHSP/Ps isolated from MCA207 cells,50% showed tumor regression and long-term survival with a tumor growth inhibition rate of 79.3%.All control mice died within 40 days.The proportions of natural killer cells,CD8＋,and interferon-γ-secreting cells and tumor-specific cytotoxic T-lymphocyte activity were increased in the immunized group.Conclusions：Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors.This mHSP/P vaccine exerted greater antitumor effects than did HSPT0,HSP60,or tumor lysates alone.
