Objective:There is currently no consensus on whether extra-gastrointestinal stromal tumors(EGISTs)and gastrointestinal stromal tumors(GISTs)are the same type of tumor,and whether the diagnosis and treatment of EGISTs ...Objective:There is currently no consensus on whether extra-gastrointestinal stromal tumors(EGISTs)and gastrointestinal stromal tumors(GISTs)are the same type of tumor,and whether the diagnosis and treatment of EGISTs can directly replicate the current diagnostic and treatment standards for GISTs.This study aims to further elucidate the clinical and pathological characteristics,diagnosis,treatment,and prognosis of EGISTs by analyzing the research results of domestic scholars in the field of EGISTs in the past decade.Methods:A review was conducted on original Chinese and English research articles published from 2013 to 2022 focusing on EGISTs.A descriptive approach was used to extract key information from the literature,including patient demographics,tumor location,tumor diameter,mitotic figures,risk stratification,immunohistochemical markers,cell type,and prognostic factors.The data were subjected to statistical analysis.Results:A total of 12 articles containing 780 EGIST patients were included.The male-to female incidence of EGISTs was 0.92꞉1.The most common sites of EGISTs were mesentery(30.96%),peritoneum or retroperitoneum(28.53%),omentum(20.32%),and pelvic cavity(12.52%).52.77%of EGISTs had tumor diameters greater than 10 cm,and the proportions of EGISTs with nuclear fission patterns greater than 5/50 high power field(HPF)and greater than 10/50 HPF were 51.24%and 26.11%,respectively.The proportion of high-risk EGISTs was 79.05%.The positive rates of immune markers CD117,CD34,and DOG-1 in EGISTs were 82.3%,69.0%,and 79.5%,respectively.The proportion of Ki-67>5%was 49.2%,and the proportion of Ki-67>10%was 24.8%.The proportions of EGISTs in spindle cells,epithelial cells,and mixed cells were 74.4%,14.8%,and 13.1%,respectively.The diameter of the tumor,resection method,risk level,Ki-67 index,mitotic counts,presence of rupture/bleeding/necrosis/peripheral tissue invasion/recurrence and metastasis,as well as the use of imatinib treatment after surgery were important factors affecting the prognosis of EGISTs.Conclusion:Current medical research is relatively well cognizant of GISTs with primary sites in the gastrointestinal tract.Compared with GISTs,EGISTs have large tumor diameters,high mitotic counts,a high percentage of high-risk grades,relatively unique molecular expression,and high aggressiveness.EGISTs differ from GISTs in clinicopathological characteristics.Whether EGISTs and GISTs share a common origin remains unclear.If they are distinct tumor entities,separate diagnostic and treatment guidelines for EGISTs should be established.If EGISTs are ultimately confirmed to be a special subtype of GISTs,then directly applying existing GIST-based standards to EGISTs may be inappropriate.A more scientific approach would involve subclassifying EGISTs based on anatomical location and then tailoring treatment strategies accordingly with reference to GIST guidelines.展开更多
In this work,iron-doped carbon dots(Fe-CDs)with strong peroxidase-mimicking activity were synthesized for tumor-specific therapy.Their intrinsic red fluorescence enabled high-contrast cellular imaging,revealing prefer...In this work,iron-doped carbon dots(Fe-CDs)with strong peroxidase-mimicking activity were synthesized for tumor-specific therapy.Their intrinsic red fluorescence enabled high-contrast cellular imaging,revealing preferen⁃tial mitochondrial accumulation.In the acidic and hydrogen peroxide(H_(2)O_(2))-rich tumor microenvironment,Fe-CDs catalyzed hydroxyl radical(·OH)generation,inducing oxidative stress and lipid peroxidation,ultimately triggering ferroptosis.In vitro and in vivo studies demonstrated potent tumor inhibition.Furthermore,Fe-CDs exhibited excel⁃lent biocompatibility with no significant systemic toxicity.By integrating fluorescence imaging and catalytic therapy,this study presents a promising nanoplatform for tumor treatment and ferroptosis research.展开更多
Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is asso...Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatically reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC 50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of human STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Furthermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regulating the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a potential inhibitory factor affecting the occurrence and progression of STAD.展开更多
Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in ...Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma.Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment.Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway.Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.展开更多
基金supported by the National Natural Science Foundation(81960508)。
文摘Objective:There is currently no consensus on whether extra-gastrointestinal stromal tumors(EGISTs)and gastrointestinal stromal tumors(GISTs)are the same type of tumor,and whether the diagnosis and treatment of EGISTs can directly replicate the current diagnostic and treatment standards for GISTs.This study aims to further elucidate the clinical and pathological characteristics,diagnosis,treatment,and prognosis of EGISTs by analyzing the research results of domestic scholars in the field of EGISTs in the past decade.Methods:A review was conducted on original Chinese and English research articles published from 2013 to 2022 focusing on EGISTs.A descriptive approach was used to extract key information from the literature,including patient demographics,tumor location,tumor diameter,mitotic figures,risk stratification,immunohistochemical markers,cell type,and prognostic factors.The data were subjected to statistical analysis.Results:A total of 12 articles containing 780 EGIST patients were included.The male-to female incidence of EGISTs was 0.92꞉1.The most common sites of EGISTs were mesentery(30.96%),peritoneum or retroperitoneum(28.53%),omentum(20.32%),and pelvic cavity(12.52%).52.77%of EGISTs had tumor diameters greater than 10 cm,and the proportions of EGISTs with nuclear fission patterns greater than 5/50 high power field(HPF)and greater than 10/50 HPF were 51.24%and 26.11%,respectively.The proportion of high-risk EGISTs was 79.05%.The positive rates of immune markers CD117,CD34,and DOG-1 in EGISTs were 82.3%,69.0%,and 79.5%,respectively.The proportion of Ki-67>5%was 49.2%,and the proportion of Ki-67>10%was 24.8%.The proportions of EGISTs in spindle cells,epithelial cells,and mixed cells were 74.4%,14.8%,and 13.1%,respectively.The diameter of the tumor,resection method,risk level,Ki-67 index,mitotic counts,presence of rupture/bleeding/necrosis/peripheral tissue invasion/recurrence and metastasis,as well as the use of imatinib treatment after surgery were important factors affecting the prognosis of EGISTs.Conclusion:Current medical research is relatively well cognizant of GISTs with primary sites in the gastrointestinal tract.Compared with GISTs,EGISTs have large tumor diameters,high mitotic counts,a high percentage of high-risk grades,relatively unique molecular expression,and high aggressiveness.EGISTs differ from GISTs in clinicopathological characteristics.Whether EGISTs and GISTs share a common origin remains unclear.If they are distinct tumor entities,separate diagnostic and treatment guidelines for EGISTs should be established.If EGISTs are ultimately confirmed to be a special subtype of GISTs,then directly applying existing GIST-based standards to EGISTs may be inappropriate.A more scientific approach would involve subclassifying EGISTs based on anatomical location and then tailoring treatment strategies accordingly with reference to GIST guidelines.
文摘In this work,iron-doped carbon dots(Fe-CDs)with strong peroxidase-mimicking activity were synthesized for tumor-specific therapy.Their intrinsic red fluorescence enabled high-contrast cellular imaging,revealing preferen⁃tial mitochondrial accumulation.In the acidic and hydrogen peroxide(H_(2)O_(2))-rich tumor microenvironment,Fe-CDs catalyzed hydroxyl radical(·OH)generation,inducing oxidative stress and lipid peroxidation,ultimately triggering ferroptosis.In vitro and in vivo studies demonstrated potent tumor inhibition.Furthermore,Fe-CDs exhibited excel⁃lent biocompatibility with no significant systemic toxicity.By integrating fluorescence imaging and catalytic therapy,this study presents a promising nanoplatform for tumor treatment and ferroptosis research.
文摘Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatically reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC 50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of human STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Furthermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regulating the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a potential inhibitory factor affecting the occurrence and progression of STAD.
基金This work was supported by the National Natural Science Foundation(82172594 and 82373046)the Hunan Graduate Research Innovation Project(CX20230318),China.
文摘Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma.Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment.Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway.Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.
