Etoposide is widely used for cancer chemotherapy in the clinic.However,long-term etoposide treatment can lead to adverse effects or drug resistance.To improve the situation,we evaluated the therapeutic efficiency of e...Etoposide is widely used for cancer chemotherapy in the clinic.However,long-term etoposide treatment can lead to adverse effects or drug resistance.To improve the situation,we evaluated the therapeutic efficiency of etoposide combined with inhibitors of bromodomain and extraterminal(BET)family proteins,which have recently emerged as novel anti-cancer targets due to their critical roles in cancer development.Firstly,we showed BRD4,one of the main targets of BET inhibitors,was involved in DNA damage response(DDR)via the homologous recombination(HR)repair pathway.展开更多
Photothermal therapy(PTT)induces thermoresistance through cellular heat shock response,which impairs the therapeutic efficacy of the PTT.To resolve this problem,we developed a photothermal theranostics(denoted as PMH)...Photothermal therapy(PTT)induces thermoresistance through cellular heat shock response,which impairs the therapeutic efficacy of the PTT.To resolve this problem,we developed a photothermal theranostics(denoted as PMH),which integrated the photothermal conversion agent of PdMo bimetallene with histone deacetylase 6(HDAC6)selected inhibitor(ACY-1215),showing the synergistic antitumor effect both in vitro and in vivo.Mechanistically,under the photoacoustic imaging(PA)navigation,the released ACY-1215 triggered by NIR laser irradiation decrease the heat shock proteins(HSPs)expression and weaken the HDAC6-regulated HSP90 deacetylation,thus hindering the degradation of PTT-induced misfolded or unfold proteins through proteasome dependent pathway.Moreover,mild photothermal therapy(mPTT)treatment compromised the autophagy,which induced by HDAC6 inhibition,leading to mPTTinduced misfolded or unfold proteins further accumulation.Given that inhibition of HDAC6 plus m PTT contribute to tumor eradication.This study develops a promising combination strategy based on m PTT for future cancer treatment.展开更多
The innate immune system plays a crucial role in the host defense against viral and microbial infection.Exosomes constitute a subset of extracellular vesicles(EVs)that can be released by almost all cell types.Owing to...The innate immune system plays a crucial role in the host defense against viral and microbial infection.Exosomes constitute a subset of extracellular vesicles(EVs)that can be released by almost all cell types.Owing to their capacity to shield the payload from degradation and to evade recognition and subsequent removal by the immune system,exosomes efficiently transport functional components to recipient cells.Accumulating evidence has recently shown that exosomes derived from tumor cells,host cells and even bacteria and parasites mediate the communication between the invader and innate immune cells and thus play an irreplaceable function in the dissemination of pathogens and donor cell-derived molecules,modulating the innate immune responses of the host.In this review,we describe the current understanding of EVs(mainly focusing on exosomes)and summarize and discuss their crucial roles in determining innate immune responses.Additionally,we discuss the potential of using exosomes as biomarkers and cancer vaccines in diagnostic and therapeutic applications.展开更多
基金supported by the National Key R&D Program of China(No.2017YFA0503900)the National Natural Science Foundation of China(No.32090033,81720108027,81530074,82103275,82002986)+3 种基金the Science and Technology Program of Guangdong Province in China(No.2017B030301016)China Postdoctoral Science Foundation(No.2019M663092)Basic and Applied Basic Research Foundation of Guangdong Province(No.2019A1515110039,2019A1515110041,2021A1515011126)Shenzhen Municipal Commission of Science and Technology Innovation(China)(No.JCYJ20170818092450901,JCYJ20200109114214463).
文摘Etoposide is widely used for cancer chemotherapy in the clinic.However,long-term etoposide treatment can lead to adverse effects or drug resistance.To improve the situation,we evaluated the therapeutic efficiency of etoposide combined with inhibitors of bromodomain and extraterminal(BET)family proteins,which have recently emerged as novel anti-cancer targets due to their critical roles in cancer development.Firstly,we showed BRD4,one of the main targets of BET inhibitors,was involved in DNA damage response(DDR)via the homologous recombination(HR)repair pathway.
基金financially supported by National Key R&D Program of China(Nos.2020YFA0908800,2018YFA0704000)Basic Research Program of Shenzhen(Nos.JCYJ20200109105620482,JCYJ20180507182413022)Shenzhen Science and Technology Program(No.KQTD20190929172538530)。
文摘Photothermal therapy(PTT)induces thermoresistance through cellular heat shock response,which impairs the therapeutic efficacy of the PTT.To resolve this problem,we developed a photothermal theranostics(denoted as PMH),which integrated the photothermal conversion agent of PdMo bimetallene with histone deacetylase 6(HDAC6)selected inhibitor(ACY-1215),showing the synergistic antitumor effect both in vitro and in vivo.Mechanistically,under the photoacoustic imaging(PA)navigation,the released ACY-1215 triggered by NIR laser irradiation decrease the heat shock proteins(HSPs)expression and weaken the HDAC6-regulated HSP90 deacetylation,thus hindering the degradation of PTT-induced misfolded or unfold proteins through proteasome dependent pathway.Moreover,mild photothermal therapy(mPTT)treatment compromised the autophagy,which induced by HDAC6 inhibition,leading to mPTTinduced misfolded or unfold proteins further accumulation.Given that inhibition of HDAC6 plus m PTT contribute to tumor eradication.This study develops a promising combination strategy based on m PTT for future cancer treatment.
基金supported by a special program from the Chinese National Natural Science Funds(31701232 to F.X.,31671457 and 91753139 to L.Z.,and 31871405 and 31571460 to F.Z.)the National Postdoctoral Program for Innovative Talents(BX201700165 to F.X.)+4 种基金the National Science Foundation for Postdoctoral Scientists of China(BX201700165 to F.X.)Distinguished Young Scholars of Jiangsu Province(BK20180043 to F.Z.)the Key Project of University Natural Science Foundation of Jiangsu Province(19KJA550003 to F.Z.)the Shenzhen Basic Research Program(JCYJ20180507182203049 to S.Z.)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘The innate immune system plays a crucial role in the host defense against viral and microbial infection.Exosomes constitute a subset of extracellular vesicles(EVs)that can be released by almost all cell types.Owing to their capacity to shield the payload from degradation and to evade recognition and subsequent removal by the immune system,exosomes efficiently transport functional components to recipient cells.Accumulating evidence has recently shown that exosomes derived from tumor cells,host cells and even bacteria and parasites mediate the communication between the invader and innate immune cells and thus play an irreplaceable function in the dissemination of pathogens and donor cell-derived molecules,modulating the innate immune responses of the host.In this review,we describe the current understanding of EVs(mainly focusing on exosomes)and summarize and discuss their crucial roles in determining innate immune responses.Additionally,we discuss the potential of using exosomes as biomarkers and cancer vaccines in diagnostic and therapeutic applications.