Backgroud and Objective Lung cancer has become the most frenquent malignant tumor in the world which its mortality and morbidity is increasing fastest among all the cancers。
Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the main cause of failure to cure and lose their life of the
Background and objective Invasion and metastasis is not only the malignant phenotypes of lung cancer but also the main cause of death. Elucidating the molecular mechanism of
Background and Objective Lung cancer, which threatens human’s health and life, is the malignant tumor with the most rapid increase of morbidity. Although recent years the basic
Background and Objective Cancer metastasis is not only the malignant characteristics of lung cancer, but also the key cause of failure to cure and high mortality. It has been proved
Background and objective Lung Cancer is one of the most malignant cancers threatening people’s health and life and one of the most rapid increasing cancers both in morbidity
Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the key cause of failure to cure and lose their life of the patients
Background:Elucidation of the post-transcriptional modification has led to novel strategies to treat intractable tumors,especially glioblastoma(GBM).The ubiquitin-proteasome system(UPS)mediates a reversible,stringent ...Background:Elucidation of the post-transcriptional modification has led to novel strategies to treat intractable tumors,especially glioblastoma(GBM).The ubiquitin-proteasome system(UPS)mediates a reversible,stringent and stepwise post-translational modification which is closely associated with malignant processes of GBM.To this end,developing novel therapeutic approaches to target the UPS may contribute to the treatment of this disease.This study aimed to screen the vital and aberrantly regulated component of the UPS in GBM.Based on the molecular identification,functional characterization,and mechanism investigation,we sought to elaborate a novel therapeutic strategy to target this vital factor to combat GBM.Methods:We combined glioma datasets and human patient samples to screen and identify aberrantly regulated E3 ubiquitin ligase.Multidimensional database analysis and molecular and functional experiments in vivo and in vitro were used to evaluate the roles of HECT,UBA and WWE domain-containing E3 ubiquitin ligase 1(HUWE1)in GBM.dCas9 synergistic activation mediator system and recombinant adeno-associated virus(rAAV)were used to endogenously overexpress full-length HUWE1 in vitro and in glioma orthotopic xenografts.Results:Low expression of HUWE1 was closely associated with worse prognosis of GBM patients.The ubiquitination and subsequent degradation of N-Myc mediated by HUWE1,leading to the inactivation of downstream Delta-like 1(DLL1)-NOTCH1 signaling pathways,inhibited the proliferation,invasion,and migration of GBM cells in vitro and in vivo.A rAAV dual-vector system for packaging and delivery of dCas9-VP64 was used to augment endogenous HUWE1 expression in vivo and showed an antitumor activity in glioma orthotopic xenografts.Conclusions:The E3 ubiquitin ligase HUWE1 acts through the N-Myc-DLL1-NOTCH1 signaling axis to suppress GBM progression.Antitumor activity of rAAV dual-vector delivering dCas9-HUWE1 system uncovers a promising therapeutic strategy for GBM.展开更多
Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the presen...Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the present study assessed the morphology of small subcortical infarcts in the basal ganglia in a Chinese cohort.Methods:Patients who had experienced a recent,single,small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging(MRI)scan were retrospectively identified from January 2014 to June 2018.Time to followup imaging,baseline infarct size,vascular risk factors,and other clinical data,as well as the morphologic changes of the index infarct and surrounding white matter were recorded.Demographic,clinical and MRI characteristics were respectively compared among three groups(white matter hyper-intensitie[WMH]vs.cavitation vs.absent)and between with and without new WMH formation groups.In addition,logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation.Results:Seventy-eight subjects were included with a median follow-up time of 304 days(range:124–552 days).We found a significant reduction in infarct size at follow-up:46 of 78(59.0%)infarctions showed some degree of cavitation,19 of 78(24.4%)index lesions resembled non-cavitated WMH,and 13 of 78(16.7%)infarcts had disappeared at follow-up MRI.No factors were found to be associated with differential outcomes of the infarcts.In addition,8 of 78(10.3%)patients demonstrated new WMH formation surrounding the index infarct;white matter progression(odds ratio=15.95,95%confidence interval=1.65–153.99;P=0.017)was an independent risk factor of new WMH formation.Conclusions:More than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities,demonstrating that these infarcts can be reduced and go undetected.The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases.Additionally,white matter progression is an independent risk factor,which may be a potential therapeutic target.展开更多
基金supported by the grant from the Key Project of National Natural Science Foundation of China (to Qinghua ZHOU)(No.30430300)grants from the National Natural Science Foundation of China.(to Qinghua ZHOU and Lunxu LIU )(No.30070333 and No 30100075)
文摘Backgroud and Objective Lung cancer has become the most frenquent malignant tumor in the world which its mortality and morbidity is increasing fastest among all the cancers。
基金supported by grants from National Natural Sciences Foundation of China (to Qinghua ZHOU, No.3007033 )
文摘Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the main cause of failure to cure and lose their life of the
基金supported by grants from the Key Project of National Natural Science Foundation of China (to Qinghua ZHOU) (No.30430300)National Natural Science Foundation of China (to Qinghua ZHOU) (No.30070333)
文摘Background and objective Invasion and metastasis is not only the malignant phenotypes of lung cancer but also the main cause of death. Elucidating the molecular mechanism of
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU) (No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU) (No. 30670922)
文摘Background and Objective Lung cancer, which threatens human’s health and life, is the malignant tumor with the most rapid increase of morbidity. Although recent years the basic
基金supported by the grants from the National Natural Science Foundation of ChinaScience Foundation of Sichuan University (No. 30070333 and No.200349)
文摘Background and Objective Cancer metastasis is not only the malignant characteristics of lung cancer, but also the key cause of failure to cure and high mortality. It has been proved
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU) (No. 30430300)
文摘Background and objective Lung Cancer is one of the most malignant cancers threatening people’s health and life and one of the most rapid increasing cancers both in morbidity
基金supported by grants from the Key Project of National Natural Science Foundation of China (to Qinghua ZHOU) (No.30430300)National Natural Science Foundation of China (to Qinghua ZHOU) (No.30070333)
文摘Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the key cause of failure to cure and lose their life of the patients
基金from National Key R&D Program of China(2016YFA0101200 to XWB)the National Natural Science Foundation of China(81602196 to TL)+1 种基金the Special Grant for Chongqing Postdoctoral Researcher Research Project(xmT2017001 to TL)the Postdoctoral Support Program for Innovative Talent(BX201600022 to TL)'Open Project of Key Laboratory of Tumor Immunopathology of Ministry of Education(2020jsz603 to YY).
文摘Background:Elucidation of the post-transcriptional modification has led to novel strategies to treat intractable tumors,especially glioblastoma(GBM).The ubiquitin-proteasome system(UPS)mediates a reversible,stringent and stepwise post-translational modification which is closely associated with malignant processes of GBM.To this end,developing novel therapeutic approaches to target the UPS may contribute to the treatment of this disease.This study aimed to screen the vital and aberrantly regulated component of the UPS in GBM.Based on the molecular identification,functional characterization,and mechanism investigation,we sought to elaborate a novel therapeutic strategy to target this vital factor to combat GBM.Methods:We combined glioma datasets and human patient samples to screen and identify aberrantly regulated E3 ubiquitin ligase.Multidimensional database analysis and molecular and functional experiments in vivo and in vitro were used to evaluate the roles of HECT,UBA and WWE domain-containing E3 ubiquitin ligase 1(HUWE1)in GBM.dCas9 synergistic activation mediator system and recombinant adeno-associated virus(rAAV)were used to endogenously overexpress full-length HUWE1 in vitro and in glioma orthotopic xenografts.Results:Low expression of HUWE1 was closely associated with worse prognosis of GBM patients.The ubiquitination and subsequent degradation of N-Myc mediated by HUWE1,leading to the inactivation of downstream Delta-like 1(DLL1)-NOTCH1 signaling pathways,inhibited the proliferation,invasion,and migration of GBM cells in vitro and in vivo.A rAAV dual-vector system for packaging and delivery of dCas9-VP64 was used to augment endogenous HUWE1 expression in vivo and showed an antitumor activity in glioma orthotopic xenografts.Conclusions:The E3 ubiquitin ligase HUWE1 acts through the N-Myc-DLL1-NOTCH1 signaling axis to suppress GBM progression.Antitumor activity of rAAV dual-vector delivering dCas9-HUWE1 system uncovers a promising therapeutic strategy for GBM.
文摘Background:Data on the evolution of recent small sub-cortical infarcts are limited,especially in the Chinese.Previous studies have reported a large heterogeneity in cavitation and infarct location;therefore,the present study assessed the morphology of small subcortical infarcts in the basal ganglia in a Chinese cohort.Methods:Patients who had experienced a recent,single,small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging(MRI)scan were retrospectively identified from January 2014 to June 2018.Time to followup imaging,baseline infarct size,vascular risk factors,and other clinical data,as well as the morphologic changes of the index infarct and surrounding white matter were recorded.Demographic,clinical and MRI characteristics were respectively compared among three groups(white matter hyper-intensitie[WMH]vs.cavitation vs.absent)and between with and without new WMH formation groups.In addition,logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation.Results:Seventy-eight subjects were included with a median follow-up time of 304 days(range:124–552 days).We found a significant reduction in infarct size at follow-up:46 of 78(59.0%)infarctions showed some degree of cavitation,19 of 78(24.4%)index lesions resembled non-cavitated WMH,and 13 of 78(16.7%)infarcts had disappeared at follow-up MRI.No factors were found to be associated with differential outcomes of the infarcts.In addition,8 of 78(10.3%)patients demonstrated new WMH formation surrounding the index infarct;white matter progression(odds ratio=15.95,95%confidence interval=1.65–153.99;P=0.017)was an independent risk factor of new WMH formation.Conclusions:More than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities,demonstrating that these infarcts can be reduced and go undetected.The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases.Additionally,white matter progression is an independent risk factor,which may be a potential therapeutic target.
