Cancer constitutes a heterogenic cellular system with a high level of spatio-temporal complexity.Recent discoveries by systems biologists have provided emerging evidence that cellular responses to anti-cancer modaliti...Cancer constitutes a heterogenic cellular system with a high level of spatio-temporal complexity.Recent discoveries by systems biologists have provided emerging evidence that cellular responses to anti-cancer modalities are stochastic in nature.To uncover the intricacies of cell-to-cell variability and its relevance to cancer therapy,new analytical screening technologies are needed.The last decade has brought forth spectacular innovations in the field of cytometry and single cell cytomics,opening new avenues for systems oncology and high-throughput real-time drug screening routines.The up-and-coming microfluidic Lab-on-a-Chip(LOC)technology and micrototal analysis systems(μTAS)are arguably the most promising platforms to address the inherent complexity of cellular systems with massive experimental parallelization and 4D analysis on a single cell level.The vast miniaturization of LOC systems and multiplexing enables innovative strategies to reduce drug screening expenditures while increasing throughput and content of information from a given sample.Small cell numbers and operational reagent volumes are sufficient for microfluidic analyzers and,as such,they enable next generation high-throughput and high-content screening of anticancer drugs on patient-derived specimens.Herein we highlight the selected advancements in this emerging field of bioengineering,and provide a snapshot of developments with relevance to anti-cancer drug screening routines.展开更多
Cancer stem cells(CSCs)comprise a subpopulation of cancer cells with stem cell properties,which exhibit the characteristics of high tumorigenicity,self-renewal,and tumor initiation and are associated with the occurren...Cancer stem cells(CSCs)comprise a subpopulation of cancer cells with stem cell properties,which exhibit the characteristics of high tumorigenicity,self-renewal,and tumor initiation and are associated with the occurrence,metastasis,therapy resistance,and relapse of cancer.Compared with differentiated cells,CSCs have unique metabolic characteristics,and metabolic reprogramming contributes to the self-renewal and maintenance of stem cells.It has been reported that CSCs are highly dependent on lipid metabolism to maintain stemness and satisfy the requirements of biosynthesis and energy metabolism.In this review,we demonstrate that lipid anabolism alterations promote the survival of CSCs,including de novo lipogenesis,lipid desaturation,and cholesterol synthesis.In addition,we also emphasize the molecular mechanism underlying the relationship between lipid synthesis and stem cell survival,the signal transduction pathways involved,and the application prospect of lipid synthesis reprogramming in CSC therapy.It is demonstrated that the dependence on lipid synthesis makes targeting of lipid synthesis metabolism a promising therapeutic strategy for eliminating CSCs.Targeting key molecules in lipid synthesis will play an important role in anti-CSC therapy.展开更多
In 2002, the Vienna Cancer Stem Cell Club （VCSCC） was inaugurated by a group of scientists at the Medical University of Vienna, with the primary goal to initiate and promote cancer stem cell （CSC） research in Aust...In 2002, the Vienna Cancer Stem Cell Club （VCSCC） was inaugurated by a group of scientists at the Medical University of Vienna, with the primary goal to initiate and promote cancer stem cell （CSC） research in Austria and to exploit knowledge from this new discipline in translational approaches, During the first years following inauguration, the VCSCC-community was small and left without major funding. However, over time the consortium was able to launch several major project-lines, supported in part by the National Science Funds, a Genome Program, and the Ludwig-Boltzmann Society. Today, the VCSCC provides a robust intellectual platform for ongoing research in the field of translational oncology and CSC-research in Austria. In addition, the VCSCC is connected to several major CSC-networks and centers in Europe and in North America, and is a well-recognized group in the field. The VCSCC also organized a series of CSC Meetings and Conferences, and contributed essentially to a recently published classification of CSC. There is also hope that the VCSCC-consortium will further advance the field of CSC research in the future, and will create novel concepts, with the ultimate aim to improve anti-cancer therapy through elimination, suppression, or long-term control of cancer-initiating cells.展开更多
Plant-derived vesicles(PDVs)are membranous structures that originate from plant cells and are responsible for multiple physiological and pathological functions.In the last decade,PDVs have gained much attention for th...Plant-derived vesicles(PDVs)are membranous structures that originate from plant cells and are responsible for multiple physiological and pathological functions.In the last decade,PDVs have gained much attention for their involvement in different biological processes,including intercellular communication and defense response,and recent scientific evidence has opened a new avenue for their applications in cancer treatment.Nevertheless,much remains unknown about these vesicles,and current research remains inconsistent.This review aims to provide a comprehensive introduction to PDVs,from their biological characteristics to purification methods,and to summarize the status of their potential development for cancer therapy.展开更多
Regulated cell death(RCD),including apoptosis,pyroptosis,necroptosis,and ferroptosis,is regulated by a series of evolutionarily conserved pathways,and is required for development and tissue homeostasis.Based on previo...Regulated cell death(RCD),including apoptosis,pyroptosis,necroptosis,and ferroptosis,is regulated by a series of evolutionarily conserved pathways,and is required for development and tissue homeostasis.Based on previous genetic and biochemical explorations of cell death subroutines,the characteristics of each are generally considered distinctive.However,recent in-depth studies noted the presence of crosstalk between the different forms of RCD;hence,the concept of PANoptosis appeared.Cancer,a complex genetic disease,is characterized by stepwise deregulation of cell apoptosis and proliferation,with significant morbidity and mortality globally.At present,studies on the different RCD pathways,as well as the intricate relationships between different cell death subroutines,mainly focus on infectious diseases,and their roles in cancer remain unclear.As cancers are characterized by dysregulated cell death and inflammatory responses,most current treatment strategies aim to selectively induce cell death via different RCD pathways in cancer cells.In this review,we describe five types of RCD pathways in detail with respect to tumorigenesis and cancer progression.The potential value of some of these key effector molecules in tumor diagnosis and therapeutic response has also been raised.We then review and highlight recent progress in cancer treatment based on PANoptosis and ferroptosis induced by small-molecule compounds,immune checkpoint inhibitors,and nanoparticles.Together,these findings may provide meaningful evidence to fill in the gaps between cancer pathogenesis and RCD pathways to develop better cancer therapeutic strategies.展开更多
The H^++CO2 reaction at high energies is relevant in atmospheric chemistry,astrophysics,and proton cancer therapy research.Therefore,we present herein a complete investigation of H^++CO2 at ELab=30 eV with the simples...The H^++CO2 reaction at high energies is relevant in atmospheric chemistry,astrophysics,and proton cancer therapy research.Therefore,we present herein a complete investigation of H^++CO2 at ELab=30 eV with the simplest-level electron nuclear dynamics(SLEND)method.SLEND describes nuclei via classical mechanics and electrons with a singledeterminantal Thouless wavefunction.The 3402 SLEND conducted simulations from 42 independent CO2 target orientations provide a full description of all the reactive processes and their mechanisms in this system:non-charge-transfer scattering(NCTS),charge-transfer scattering(CTS),and single C=O bond dissociation;all this valuable information about reactivity is not accessible experimentally.Numerous details of the projectile scattering patterns are provided,including the appearance and coalescence of primary and secondary rainbow angles as a function of the target orientation.SLEND NCTS and CTS differential cross sections(DCSs)are evaluated in conjunction with advanced semi-classical techniques.SLEND NCTS DCS agrees well with its experimental counterpart at all the measured scattering angles,whereas SLEND CTS DCS agrees well at high scattering angles but less satisfactorily at lower ones.Remarkably,both NCTS and CTS SLEND DCSs predict the primary rainbow angle signatures in agreement with the experiment.展开更多
文摘Cancer constitutes a heterogenic cellular system with a high level of spatio-temporal complexity.Recent discoveries by systems biologists have provided emerging evidence that cellular responses to anti-cancer modalities are stochastic in nature.To uncover the intricacies of cell-to-cell variability and its relevance to cancer therapy,new analytical screening technologies are needed.The last decade has brought forth spectacular innovations in the field of cytometry and single cell cytomics,opening new avenues for systems oncology and high-throughput real-time drug screening routines.The up-and-coming microfluidic Lab-on-a-Chip(LOC)technology and micrototal analysis systems(μTAS)are arguably the most promising platforms to address the inherent complexity of cellular systems with massive experimental parallelization and 4D analysis on a single cell level.The vast miniaturization of LOC systems and multiplexing enables innovative strategies to reduce drug screening expenditures while increasing throughput and content of information from a given sample.Small cell numbers and operational reagent volumes are sufficient for microfluidic analyzers and,as such,they enable next generation high-throughput and high-content screening of anticancer drugs on patient-derived specimens.Herein we highlight the selected advancements in this emerging field of bioengineering,and provide a snapshot of developments with relevance to anti-cancer drug screening routines.
基金Supported by the National Natural Science Foundation of China,No.82001044 and No.81630025the China Postdoctoral Science Foundation,No.2020M673019+1 种基金the Guangdong Basic and Applied Basic Research Foundation,No.2019A1515110071the Natural Science Foundation of Guangdong Province,No.2017A030311033.
文摘Cancer stem cells(CSCs)comprise a subpopulation of cancer cells with stem cell properties,which exhibit the characteristics of high tumorigenicity,self-renewal,and tumor initiation and are associated with the occurrence,metastasis,therapy resistance,and relapse of cancer.Compared with differentiated cells,CSCs have unique metabolic characteristics,and metabolic reprogramming contributes to the self-renewal and maintenance of stem cells.It has been reported that CSCs are highly dependent on lipid metabolism to maintain stemness and satisfy the requirements of biosynthesis and energy metabolism.In this review,we demonstrate that lipid anabolism alterations promote the survival of CSCs,including de novo lipogenesis,lipid desaturation,and cholesterol synthesis.In addition,we also emphasize the molecular mechanism underlying the relationship between lipid synthesis and stem cell survival,the signal transduction pathways involved,and the application prospect of lipid synthesis reprogramming in CSC therapy.It is demonstrated that the dependence on lipid synthesis makes targeting of lipid synthesis metabolism a promising therapeutic strategy for eliminating CSCs.Targeting key molecules in lipid synthesis will play an important role in anti-CSC therapy.
文摘In 2002, the Vienna Cancer Stem Cell Club （VCSCC） was inaugurated by a group of scientists at the Medical University of Vienna, with the primary goal to initiate and promote cancer stem cell （CSC） research in Austria and to exploit knowledge from this new discipline in translational approaches, During the first years following inauguration, the VCSCC-community was small and left without major funding. However, over time the consortium was able to launch several major project-lines, supported in part by the National Science Funds, a Genome Program, and the Ludwig-Boltzmann Society. Today, the VCSCC provides a robust intellectual platform for ongoing research in the field of translational oncology and CSC-research in Austria. In addition, the VCSCC is connected to several major CSC-networks and centers in Europe and in North America, and is a well-recognized group in the field. The VCSCC also organized a series of CSC Meetings and Conferences, and contributed essentially to a recently published classification of CSC. There is also hope that the VCSCC-consortium will further advance the field of CSC research in the future, and will create novel concepts, with the ultimate aim to improve anti-cancer therapy through elimination, suppression, or long-term control of cancer-initiating cells.
基金This research was supported by Korea Institute of Science and Technology(KIST)intramural research grant and the Korean Fund for Regenerative Medicine(21A0503L1)of the Korea government(the Ministry of Science and ICT,the Ministry of Health&Welfare).
文摘Plant-derived vesicles(PDVs)are membranous structures that originate from plant cells and are responsible for multiple physiological and pathological functions.In the last decade,PDVs have gained much attention for their involvement in different biological processes,including intercellular communication and defense response,and recent scientific evidence has opened a new avenue for their applications in cancer treatment.Nevertheless,much remains unknown about these vesicles,and current research remains inconsistent.This review aims to provide a comprehensive introduction to PDVs,from their biological characteristics to purification methods,and to summarize the status of their potential development for cancer therapy.
基金Natural Science Foundation of China(No.82072689)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.2020HXFH010)
文摘Regulated cell death(RCD),including apoptosis,pyroptosis,necroptosis,and ferroptosis,is regulated by a series of evolutionarily conserved pathways,and is required for development and tissue homeostasis.Based on previous genetic and biochemical explorations of cell death subroutines,the characteristics of each are generally considered distinctive.However,recent in-depth studies noted the presence of crosstalk between the different forms of RCD;hence,the concept of PANoptosis appeared.Cancer,a complex genetic disease,is characterized by stepwise deregulation of cell apoptosis and proliferation,with significant morbidity and mortality globally.At present,studies on the different RCD pathways,as well as the intricate relationships between different cell death subroutines,mainly focus on infectious diseases,and their roles in cancer remain unclear.As cancers are characterized by dysregulated cell death and inflammatory responses,most current treatment strategies aim to selectively induce cell death via different RCD pathways in cancer cells.In this review,we describe five types of RCD pathways in detail with respect to tumorigenesis and cancer progression.The potential value of some of these key effector molecules in tumor diagnosis and therapeutic response has also been raised.We then review and highlight recent progress in cancer treatment based on PANoptosis and ferroptosis induced by small-molecule compounds,immune checkpoint inhibitors,and nanoparticles.Together,these findings may provide meaningful evidence to fill in the gaps between cancer pathogenesis and RCD pathways to develop better cancer therapeutic strategies.
基金Present calculations were performed at the Texas Tech University High Performance Computer Center and the Texas Advanced Computing Center at the University of Texas at Austin.Prof.Morales acknowledges financial support from the Cancer Prevention and Research Institute of Texas(CPRIT)grant RP140478.Prof.Yan acknowledges the financial support from the National Natural Science Foundation of China(No.21373064)and the Program for Innovative Research Team of Guizhou Province(No.QKTD[2014]4021).
文摘The H^++CO2 reaction at high energies is relevant in atmospheric chemistry,astrophysics,and proton cancer therapy research.Therefore,we present herein a complete investigation of H^++CO2 at ELab=30 eV with the simplest-level electron nuclear dynamics(SLEND)method.SLEND describes nuclei via classical mechanics and electrons with a singledeterminantal Thouless wavefunction.The 3402 SLEND conducted simulations from 42 independent CO2 target orientations provide a full description of all the reactive processes and their mechanisms in this system:non-charge-transfer scattering(NCTS),charge-transfer scattering(CTS),and single C=O bond dissociation;all this valuable information about reactivity is not accessible experimentally.Numerous details of the projectile scattering patterns are provided,including the appearance and coalescence of primary and secondary rainbow angles as a function of the target orientation.SLEND NCTS and CTS differential cross sections(DCSs)are evaluated in conjunction with advanced semi-classical techniques.SLEND NCTS DCS agrees well with its experimental counterpart at all the measured scattering angles,whereas SLEND CTS DCS agrees well at high scattering angles but less satisfactorily at lower ones.Remarkably,both NCTS and CTS SLEND DCSs predict the primary rainbow angle signatures in agreement with the experiment.
