BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,...BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.展开更多
BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and constraints.Current research primarily emphasizes safety in early-phase clinical trials,while systemati...BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and constraints.Current research primarily emphasizes safety in early-phase clinical trials,while systematic reviews prioritize effectiveness,often overlooking safety and translational feasibility.This situation prompts inquiries regarding the readiness for clinical adoption.AIM To offer an up-to-date systematic literature review of clinical trial results concerning stem cell therapy for SCI.METHODS A systematic search was conducted across major medical databases[PubMed,Embase,Reference Citation Analysis(RCA),and Cochrane Library]up to October 14,2023.The search strategy utilized relevant Medical Subject Heading(MeSH)terms and keywords related to"spinal cord","injury","clinical trials","stem cells","functional outcomes",and"adverse events".Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI.RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,496 papers were initially identified,with 237 chosen for full-text analysis.Among them,236 were deemed eligible after excluding 170 for various reasons.These studies encompassed 1086 patients with varying SCI levels,with cervical injuries being the most common(42.2%).Bone marrow stem cells were the predominant stem cell type used(71.1%),with various administration methods.Follow-up durations averaged around 84.4 months.The 32.7%of patients showed functional improvement from American spinal injury association Impairment Scale(AIS)A to B,40.8%from AIS A to C,5.3%from AIS A to D,and 2.1%from AIS B to C.Sensory improvements were observed in 30.9%of patients.A relatively small number of adverse events were recorded,including fever(15.1%),headaches(4.3%),muscle tension(3.1%),and dizziness(2.6%),highlighting the potential for SCI recovery with stem cell therapy.CONCLUSION In the realm of SCI treatment,stem cell-based therapies show promise,but clinical trials reveal potential adverse events and limitations,underscoring the need for meticulous optimization of transplantation conditions and parameters,caution against swift clinical implementation,a deeper understanding of SCI pathophysiology,and addressing ethical,tumorigenicity,immunogenicity,and immunotoxicity concerns before gradual and careful adoption in clinical practice.展开更多
AIMTo describe the development and validation of a novel neuronavigation-based method, which allows the quan-tification of the anatomical features that define anapproach, as well as real-time visualization of the surg...AIMTo describe the development and validation of a novel neuronavigation-based method, which allows the quan-tification of the anatomical features that define anapproach, as well as real-time visualization of the surgicapyramid. METHODSThe method was initially developed with commercially-available hardware for coordinate collection （a digitizerand a frameless navigation system） and software forvolume rendering; dedicated neuronavigation software （ApproachViewer, part of GTx-UHN） was then developed. The accuracy of measurements and the possibility of volumetric rendering of surgical approaches simulated in a phantom were compared among three different methods and commercially-available radiological software. In the anatomy laboratory, ApproachViewer was applied to the comparative quantitative analysis of multiple neurosurgical approaches and was used by many surgeons who were untrained for the research method.RESULTSThe accuracy of ApproachViewer is comparable to com-mercially-available radiological software. In the anatomy laboratory, the method appears versatile. The system can be easily used after brief training. ApproachViewer allows for real-time evaluation and comparison of surgical approaches, as well as post-dissection analyses of collected data. The accuracy of the method depends on the navigation registration： with a 1-2 mm registration error, it is adequate for evaluation and comparison of most neurosurgical approaches.CONCLUSIONThis new research method and software allows semi-automated visualization, quantifcation, and comparison of neurosurgical approaches in the anatomy laboratory.展开更多
文摘BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.
文摘BACKGROUND Previous assessments of stem cell therapy for spinal cord injuries(SCI)have encountered challenges and constraints.Current research primarily emphasizes safety in early-phase clinical trials,while systematic reviews prioritize effectiveness,often overlooking safety and translational feasibility.This situation prompts inquiries regarding the readiness for clinical adoption.AIM To offer an up-to-date systematic literature review of clinical trial results concerning stem cell therapy for SCI.METHODS A systematic search was conducted across major medical databases[PubMed,Embase,Reference Citation Analysis(RCA),and Cochrane Library]up to October 14,2023.The search strategy utilized relevant Medical Subject Heading(MeSH)terms and keywords related to"spinal cord","injury","clinical trials","stem cells","functional outcomes",and"adverse events".Studies included in this review consisted of randomized controlled trials and non-randomized controlled trials reporting on the use of stem cell therapies for the treatment of SCI.RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,496 papers were initially identified,with 237 chosen for full-text analysis.Among them,236 were deemed eligible after excluding 170 for various reasons.These studies encompassed 1086 patients with varying SCI levels,with cervical injuries being the most common(42.2%).Bone marrow stem cells were the predominant stem cell type used(71.1%),with various administration methods.Follow-up durations averaged around 84.4 months.The 32.7%of patients showed functional improvement from American spinal injury association Impairment Scale(AIS)A to B,40.8%from AIS A to C,5.3%from AIS A to D,and 2.1%from AIS B to C.Sensory improvements were observed in 30.9%of patients.A relatively small number of adverse events were recorded,including fever(15.1%),headaches(4.3%),muscle tension(3.1%),and dizziness(2.6%),highlighting the potential for SCI recovery with stem cell therapy.CONCLUSION In the realm of SCI treatment,stem cell-based therapies show promise,but clinical trials reveal potential adverse events and limitations,underscoring the need for meticulous optimization of transplantation conditions and parameters,caution against swift clinical implementation,a deeper understanding of SCI pathophysiology,and addressing ethical,tumorigenicity,immunogenicity,and immunotoxicity concerns before gradual and careful adoption in clinical practice.
基金Supported by Fondazione"Giuseppe Alazio",via Torquato Tasso,22,90144 Palermo,Italy(to Doglietto F)
文摘AIMTo describe the development and validation of a novel neuronavigation-based method, which allows the quan-tification of the anatomical features that define anapproach, as well as real-time visualization of the surgicapyramid. METHODSThe method was initially developed with commercially-available hardware for coordinate collection （a digitizerand a frameless navigation system） and software forvolume rendering; dedicated neuronavigation software （ApproachViewer, part of GTx-UHN） was then developed. The accuracy of measurements and the possibility of volumetric rendering of surgical approaches simulated in a phantom were compared among three different methods and commercially-available radiological software. In the anatomy laboratory, ApproachViewer was applied to the comparative quantitative analysis of multiple neurosurgical approaches and was used by many surgeons who were untrained for the research method.RESULTSThe accuracy of ApproachViewer is comparable to com-mercially-available radiological software. In the anatomy laboratory, the method appears versatile. The system can be easily used after brief training. ApproachViewer allows for real-time evaluation and comparison of surgical approaches, as well as post-dissection analyses of collected data. The accuracy of the method depends on the navigation registration： with a 1-2 mm registration error, it is adequate for evaluation and comparison of most neurosurgical approaches.CONCLUSIONThis new research method and software allows semi-automated visualization, quantifcation, and comparison of neurosurgical approaches in the anatomy laboratory.
