Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherap...Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.展开更多
The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)satellite is a small magnetosphere–ionosphere link explorer developed cooperatively between China and Europe.It pioneers the use of X-ray imaging technology...The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)satellite is a small magnetosphere–ionosphere link explorer developed cooperatively between China and Europe.It pioneers the use of X-ray imaging technology to perform large-scale imaging of the Earth’s magnetosheath and polar cusp regions.It uses a high-precision ultraviolet imager to image the overall configuration of the aurora and monitor changes in the source of solar wind in real time,using in situ detection instruments to improve human understanding of the relationship between solar activity and changes in the Earth’s magnetic field.The SMILE satellite is scheduled to launch in 2025.The European Incoherent Scatter Sciences Association(EISCAT)-3D radar is a new generation of European incoherent scatter radar constructed by EISCAT and is the most advanced ground-based ionospheric experimental device in the high-latitude polar region.It has multibeam and multidirectional quasi-real-time three-dimensional(3D)imaging capabilities,continuous monitoring and operation capabilities,and multiple-baseline interferometry capabilities.Joint detection by the SMILE satellite and the EISCAT-3D radar is of great significance for revealing the coupling process of the solar wind–magnetosphere–ionosphere.Therefore,we performed an analysis of the joint detection capability of the SMILE satellite and EISCAT-3D,analyzed the period during which the two can perform joint detection,and defined the key scientific problems that can be solved by joint detection.In addition,we developed Web-based software to search for and visualize the joint detection period of the SMILE satellite and EISCAT-3D radar,which lays the foundation for subsequent joint detection experiments and scientific research.展开更多
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Ministry of Science and ICT(MSIT)(No.2021R1A2C2012808)Technology Innovation Program(Alchemist Project)(No.20012378)funded by the Ministry of Trade,Industry&Energy(MOTIE),South Korea.
文摘Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.
基金supported by the Stable-Support Scientific Project of the China Research Institute of Radio-wave Propagation(Grant No.A13XXXXWXX)the National Natural Science Foundation of China(Grant Nos.42174210,4207202,and 42188101)the Strategic Pioneer Program on Space Science,Chinese Academy of Sciences(Grant No.XDA15014800)。
文摘The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)satellite is a small magnetosphere–ionosphere link explorer developed cooperatively between China and Europe.It pioneers the use of X-ray imaging technology to perform large-scale imaging of the Earth’s magnetosheath and polar cusp regions.It uses a high-precision ultraviolet imager to image the overall configuration of the aurora and monitor changes in the source of solar wind in real time,using in situ detection instruments to improve human understanding of the relationship between solar activity and changes in the Earth’s magnetic field.The SMILE satellite is scheduled to launch in 2025.The European Incoherent Scatter Sciences Association(EISCAT)-3D radar is a new generation of European incoherent scatter radar constructed by EISCAT and is the most advanced ground-based ionospheric experimental device in the high-latitude polar region.It has multibeam and multidirectional quasi-real-time three-dimensional(3D)imaging capabilities,continuous monitoring and operation capabilities,and multiple-baseline interferometry capabilities.Joint detection by the SMILE satellite and the EISCAT-3D radar is of great significance for revealing the coupling process of the solar wind–magnetosphere–ionosphere.Therefore,we performed an analysis of the joint detection capability of the SMILE satellite and EISCAT-3D,analyzed the period during which the two can perform joint detection,and defined the key scientific problems that can be solved by joint detection.In addition,we developed Web-based software to search for and visualize the joint detection period of the SMILE satellite and EISCAT-3D radar,which lays the foundation for subsequent joint detection experiments and scientific research.
