In the current settings of osteosarcoma research and drug screening,in vitro three-dimensional(3D)models,which overcome the limitations of traditional models,are favored.In in vitro 3D models,tumor microenvironment si...In the current settings of osteosarcoma research and drug screening,in vitro three-dimensional(3D)models,which overcome the limitations of traditional models,are favored.In in vitro 3D models,tumor microenvironment simulation,particularly of the mechanical microenvironment,is crucial for estimating the biological effects of a tumor.However,current in vitro osteosarcoma model construction is often limited to a single mechanical signal,which fails to simulate the diversity of osteosarcoma mechanical stimuli.In this study,we utilized embedded bioprinting technology and the multiple response properties of calcium ions in soft and hard stiffness systems with osteosarcoma cell biological functions to construct an integrated gradient biomechanical signal-tailored osteosarcoma model(IGBSTOM).We achieved this by printing a fibrinogen bioink containing calcium ions and osteosarcoma tumor spheroids within an extracellular matrix composed of methacryloylated alginate,methacryloylated gelatin,thrombin,and transglutaminase,which is rich in polysaccharides and proteins and exhibits self-healing properties.Our in vitro and in vivo studies showed that the IGBSTOM enhanced tumor stemness,proliferation,and migration,and successfully reproduced the nest-like structure of tumors,providing an in vitro research platform that is more similar to the natural tumor than the existing models.This study proposes a novel IGBSTOM construction and provides a new strategy for the clinical understanding of tumor development,drug screening,and exploration of drug resistance and metastasis mechanisms.展开更多
Transforming growth factor-β(TGF-β) signaling regulates cell proliferation, differentiation, migration and death, and plays a critical role in embryogenesis and tissue homeostasis. Its deregulation results in variou...Transforming growth factor-β(TGF-β) signaling regulates cell proliferation, differentiation, migration and death, and plays a critical role in embryogenesis and tissue homeostasis. Its deregulation results in various diseases including tumor formation.Receptor tyrosine kinases(RTKs), such as epidermal growth factor receptor(EGFR), fibroblast growth factor receptor(FGFR),vascular endothelial growth factor receptor(VEGFR) and platelet-derived growth factor receptor(PDGFR), also play key roles in the development and progression of many types of tumors. It has been realized that TGF-β signaling and RTK pathways interact with each other and their interplay is important for cancer development. They are mutually regulated and cooperatively modulate cell survival and migration, epithelial-mesenchymal transition, and tumor microenvironment to accelerate tumorigenesis and tumor metastasis. RTKs can modulate Smad-dependent transcription or cooperate with TGF-β to potentiate its oncogenic activity,while TGF-β signaling can in turn control RTK signaling by regulating their activities or expression. This review summarizes current understandings of the interplay between TGF-β signaling and RTKs and its influence on tumor development.展开更多
This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of v...This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of various developmental toxicants. The results showed that 2 of 3 developmental toxicants under consideration, sodium pentobarbital and ethanol, significantly inhibited S180cells attachment to Concanavalin A-coaed surfaces. Inhibition was dependent on concentration, and the IC50 (the concentration tha reduced attachment by 50% ), of these 2 chemicals was 1.2×10-3mol/L and 1 .0 mol/L, respectively. Anoher developmental toxiant, hydmiortisone, did not show inhibitory activity. Two non-developmental toxicants, sodium chloride and glycine were also tested and these did not decrease attachment rates. The main results reported here were generally sindlar to those obtained with ascitic mouse ovdrian tumor cells as a model. Therefore, this study added further evidence to the conclusion that cell specificity does not lindt attachment inhibition to Con A-coated surfaces, so S180 cell may serve as an altemative cell model, especially when other cell lines are unavailable. Furthermore, after optimal validation, it can be suggested that an S180 cell attachment assay may be a candidate for a series of assays to detect developmental toxicants.展开更多
Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify onco...Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto展开更多
BACKGROUND To observe the endoscopic and pathological characteristics of laterally spreading tumors(LSTs)and explore the risk factors for carcinogenesis and submucosal infiltration.AIM To analyze the clinicopathologic...BACKGROUND To observe the endoscopic and pathological characteristics of laterally spreading tumors(LSTs)and explore the risk factors for carcinogenesis and submucosal infiltration.AIM To analyze the clinicopathological features of colorectal LSTs treated endoscopically and determine risk factors associated with carcinogenesis and submucosal invasion,providing evidence-based guidance for optimal treatment strategy selection.METHODS This study retrospectively analyzed the sex,age,and endoscopic and pathological features of patients who underwent endoscopic treatment for colorectal LSTs in our hospital from January 2021 to July 2024.Single-factor analysis was used to identify the risk factors for cancer and submucosal infiltration,and the factors with statistical significance were included in multivariate logistic regression analysis.RESULTS A total of 422 patients,including 224 males and 198 females,aged 63.45±9.23 years,were included.There were 456 LST lesions in total.The length of the endoscopically resected specimens was 3.01±0.48 cm,and the length of the lesions was 2.37±1.59 cm.It was located in 115 rectums(25.2%),40 sigmoid colon(8.8%),26 descending colon(5.7%),109 transverse colon(23.9%),112 ascending colon(24.6%),and 54 ileocecal regions(11.8%).Endoscopic submucosal dissection(ESD)was performed in 237 patients(52.0%),and endoscopic mucosal resection(EMR)was performed in 95 patients(20.8%).There were 113 EMR with precutting cases(24.8%),11 ESD with snare cases(2.4%),4 delayed bleeding cases and 5 intraoperative perforations.The pathological results revealed 119 cases of low-grade intraepithelial neoplasia(26.1%),221 cases of high-grade intraepithelial neoplasia(48.5%),82 cases of intramucosal carcinoma(18.0%),and 34 cases of submucous invasive carcinoma(7.5%).Multiple logistic regression analyses revealed that lesion size(>2 cm),lesion location(rectal)and endoscopic classification[false depressed tubulovillous adenoma(LST-NG pseudodepressed type,LST-NG-PD),type 1 particles(LST-G homogenous type),and LST-G nodular mixed type],accompanied by large nodules(with)were independent risk factors for carcinogenesis;endoscopic classification(LST-NG-PD)and the presence of large nodules were independent risk factors for submucosal infiltration.CONCLUSION These risk factors provide practical guidance for treatment selection:LST-NG-PD with large nodules should prioritize ESD,while high-risk rectal lesions>2 cm may require additional imaging evaluation before endoscopic resection.展开更多
Many digestive system malignant tumors are characterized by high incidence and mortality rate.Increasing evidence has revealed that the tumor microenvironment(TME)is involved in cancer initiation and tumor progression...Many digestive system malignant tumors are characterized by high incidence and mortality rate.Increasing evidence has revealed that the tumor microenvironment(TME)is involved in cancer initiation and tumor progression.Tumor-associated macrophages(TAMs)are a predominant constituent of the TME,and participate in the regulation of various biological behaviors and influence the prognosis of digestive system cancer.TAMs can be mainly classified into the antitumor M1 phenotype and protumor M2 phenotype.The latter especially are crucial drivers of tumor invasion,growth,angiogenesis,metastasis,immunosuppression,and resistance to therapy.TAMs are of importance in the occurrence,development,diagnosis,prognosis,and treatment of common digestive system malignant tumors.In this review,we summarize the role of TAMs in common digestive system malignant tumors,including esophageal,gastric,colorectal,pancreatic and liver cancers.How TAMs promote the development of tumors,and how they act as potential therapeutic targets and their clinical applications are also described.展开更多
Multiplex Ligation-Dependent Probe Amplification (MLPA) was used to study the integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiatio...Multiplex Ligation-Dependent Probe Amplification (MLPA) was used to study the integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation. WTK1 cells contain a p53 mutation, whereas the TK6 cell line has the native p53 tumor-suppressor gene. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. Using probes that target specific regions on chromosomes associated with a distinct subset of microdeletions and microduplications either established or thought to be responsible for intellectual disability or developmental delay, we have demonstrated that WTK1 and TK6 are not impacted in the same way by irradiation. Instead, each cell line presents its own unique MLPA profile. The most notable differences are the appearance of nine unique probe signals only seen in WTK1 cells. These results are important in the study of how different cell lines can be affected in significantly different ways depending on the presence or absence of wild type p53.展开更多
Malignant tumor has become a major threat affecting human health,and is one of the main causes of human death.Recent studies have shown that many traditional Chinese medicines(TCM)have good anti-tumor activity,which m...Malignant tumor has become a major threat affecting human health,and is one of the main causes of human death.Recent studies have shown that many traditional Chinese medicines(TCM)have good anti-tumor activity,which may improve the therapeutic effect of routine treatment and quality of life with lower toxicity.However,the efficacy of TCM alone for the treatment of tumors is limited.Metal ions are essential substances for maintaining normal physiological activities.This article summarized the multiple mechanisms in which metal ions are involved in the prevention and treatment of tumors in TCM.展开更多
使用TALEN技术制作p53基因敲除大鼠模型,建立种群并分析大鼠表型。设计特异性识别p53基因外显子2的TALEN蛋白并构建相应载体,将体外转录的TALEN m RNA注射SD大鼠受精卵,出生后从仔鼠中通过测序筛选靶位点正确剪切的阳性小鼠。结果显示,...使用TALEN技术制作p53基因敲除大鼠模型,建立种群并分析大鼠表型。设计特异性识别p53基因外显子2的TALEN蛋白并构建相应载体,将体外转录的TALEN m RNA注射SD大鼠受精卵,出生后从仔鼠中通过测序筛选靶位点正确剪切的阳性小鼠。结果显示,注射得到11只新生仔鼠,通过测序发现其中有10只靶位点发生剪切。选取其中4只作为首建鼠进行繁殖。p53基因敲除纯合子表现出肿瘤易发性,主要自发性肿瘤类型为恶性纤维组织肉瘤。此外,p53基因敲除纯合子大鼠表现出眼睛发育异常,视网膜变性及晶状体纤维排列紊乱。通过TALEN技术高效地获得了p53基因敲除大鼠模型,纯合子敲除大鼠除了易发肿瘤并伴有眼发育异常,因而该敲除大鼠模型除了可用于研究肿瘤发生机制外,也可用于研究p53基因在眼发育过程中的功能。展开更多
辅助性T细胞的新亚群Th17,主要分泌IL-17A、IL-17F、IL-21和IL-22等细胞因子,并特异性表达转录因子ROR-γt,能够在IL-6/IL-21与TGF-β(小鼠)或IL-6/IL-23与IL-1β(人)的作用下由初始CD4+T细胞分化而来。Th17细胞在宿主防御微生物感染、...辅助性T细胞的新亚群Th17,主要分泌IL-17A、IL-17F、IL-21和IL-22等细胞因子,并特异性表达转录因子ROR-γt,能够在IL-6/IL-21与TGF-β(小鼠)或IL-6/IL-23与IL-1β(人)的作用下由初始CD4+T细胞分化而来。Th17细胞在宿主防御微生物感染、介导炎症反应以及自身免疫病方面具有重要作用。调节性T细胞(Regulatory T cell,Treg)又被称为抑制性T细胞,在TGF-β的作用下由初始T细胞分化而来,主要分泌TGF-β、IL-10等细胞因子,并特异性表达转录因子Foxp3。Treg能够通过抑制效应T细胞活性介导免疫耐受,阻止组织损伤。Th17与Treg细胞在肿瘤发展进程中具有重要作用,并且在肿瘤免疫中的作用都具有双重性。同时,肿瘤微环境中两者具有发育可塑性,能够在肿瘤微环境中处于动态平衡。因此,深入而全面的研究Th17和Treg细胞变得尤为重要。文章综述了Th17以及Treg细胞的特性以及在调控肿瘤免疫中的作用,以便更加全面的了解和掌握它们,为科学研究提供理论基础。展开更多
基金appreciate financial support from the National Key R&D Program of China(No.2022YFA1104600)2022 Lingang Laboratory“Seeking Outstanding Youth Program”Open Project(No.LGQS-202206-04)+3 种基金Shanghai Ninth People’s Hospital–Shanghai Jiao Tong University School of Medicine–Shanghai University of Science and Technology Cross-funded Collaborative Program(No.JYJC202233)the National Natural Science Foundation of China(No.82372377)Biomaterials and Regenerative Medicine Institute Cooperative Research Project by Shanghai Jiao Tong University School of Medicine(No.2022LHBO8),Shanghai Key Laboratory of Orthopaedic Implants,Department of Orthopaedics by Shanghai Ninth People’s Hospital–Shanghai Jiao Tong University School of Medicine(No.KFKT202206),the Key R&D Program of Jiangsu Province Social Development Project(No.BE2022708)the Project of Shanghai Science and Technology Commission(No.22015820100).
文摘In the current settings of osteosarcoma research and drug screening,in vitro three-dimensional(3D)models,which overcome the limitations of traditional models,are favored.In in vitro 3D models,tumor microenvironment simulation,particularly of the mechanical microenvironment,is crucial for estimating the biological effects of a tumor.However,current in vitro osteosarcoma model construction is often limited to a single mechanical signal,which fails to simulate the diversity of osteosarcoma mechanical stimuli.In this study,we utilized embedded bioprinting technology and the multiple response properties of calcium ions in soft and hard stiffness systems with osteosarcoma cell biological functions to construct an integrated gradient biomechanical signal-tailored osteosarcoma model(IGBSTOM).We achieved this by printing a fibrinogen bioink containing calcium ions and osteosarcoma tumor spheroids within an extracellular matrix composed of methacryloylated alginate,methacryloylated gelatin,thrombin,and transglutaminase,which is rich in polysaccharides and proteins and exhibits self-healing properties.Our in vitro and in vivo studies showed that the IGBSTOM enhanced tumor stemness,proliferation,and migration,and successfully reproduced the nest-like structure of tumors,providing an in vitro research platform that is more similar to the natural tumor than the existing models.This study proposes a novel IGBSTOM construction and provides a new strategy for the clinical understanding of tumor development,drug screening,and exploration of drug resistance and metastasis mechanisms.
文摘Transforming growth factor-β(TGF-β) signaling regulates cell proliferation, differentiation, migration and death, and plays a critical role in embryogenesis and tissue homeostasis. Its deregulation results in various diseases including tumor formation.Receptor tyrosine kinases(RTKs), such as epidermal growth factor receptor(EGFR), fibroblast growth factor receptor(FGFR),vascular endothelial growth factor receptor(VEGFR) and platelet-derived growth factor receptor(PDGFR), also play key roles in the development and progression of many types of tumors. It has been realized that TGF-β signaling and RTK pathways interact with each other and their interplay is important for cancer development. They are mutually regulated and cooperatively modulate cell survival and migration, epithelial-mesenchymal transition, and tumor microenvironment to accelerate tumorigenesis and tumor metastasis. RTKs can modulate Smad-dependent transcription or cooperate with TGF-β to potentiate its oncogenic activity,while TGF-β signaling can in turn control RTK signaling by regulating their activities or expression. This review summarizes current understandings of the interplay between TGF-β signaling and RTKs and its influence on tumor development.
文摘This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of various developmental toxicants. The results showed that 2 of 3 developmental toxicants under consideration, sodium pentobarbital and ethanol, significantly inhibited S180cells attachment to Concanavalin A-coaed surfaces. Inhibition was dependent on concentration, and the IC50 (the concentration tha reduced attachment by 50% ), of these 2 chemicals was 1.2×10-3mol/L and 1 .0 mol/L, respectively. Anoher developmental toxiant, hydmiortisone, did not show inhibitory activity. Two non-developmental toxicants, sodium chloride and glycine were also tested and these did not decrease attachment rates. The main results reported here were generally sindlar to those obtained with ascitic mouse ovdrian tumor cells as a model. Therefore, this study added further evidence to the conclusion that cell specificity does not lindt attachment inhibition to Con A-coated surfaces, so S180 cell may serve as an altemative cell model, especially when other cell lines are unavailable. Furthermore, after optimal validation, it can be suggested that an S180 cell attachment assay may be a candidate for a series of assays to detect developmental toxicants.
文摘Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto
文摘BACKGROUND To observe the endoscopic and pathological characteristics of laterally spreading tumors(LSTs)and explore the risk factors for carcinogenesis and submucosal infiltration.AIM To analyze the clinicopathological features of colorectal LSTs treated endoscopically and determine risk factors associated with carcinogenesis and submucosal invasion,providing evidence-based guidance for optimal treatment strategy selection.METHODS This study retrospectively analyzed the sex,age,and endoscopic and pathological features of patients who underwent endoscopic treatment for colorectal LSTs in our hospital from January 2021 to July 2024.Single-factor analysis was used to identify the risk factors for cancer and submucosal infiltration,and the factors with statistical significance were included in multivariate logistic regression analysis.RESULTS A total of 422 patients,including 224 males and 198 females,aged 63.45±9.23 years,were included.There were 456 LST lesions in total.The length of the endoscopically resected specimens was 3.01±0.48 cm,and the length of the lesions was 2.37±1.59 cm.It was located in 115 rectums(25.2%),40 sigmoid colon(8.8%),26 descending colon(5.7%),109 transverse colon(23.9%),112 ascending colon(24.6%),and 54 ileocecal regions(11.8%).Endoscopic submucosal dissection(ESD)was performed in 237 patients(52.0%),and endoscopic mucosal resection(EMR)was performed in 95 patients(20.8%).There were 113 EMR with precutting cases(24.8%),11 ESD with snare cases(2.4%),4 delayed bleeding cases and 5 intraoperative perforations.The pathological results revealed 119 cases of low-grade intraepithelial neoplasia(26.1%),221 cases of high-grade intraepithelial neoplasia(48.5%),82 cases of intramucosal carcinoma(18.0%),and 34 cases of submucous invasive carcinoma(7.5%).Multiple logistic regression analyses revealed that lesion size(>2 cm),lesion location(rectal)and endoscopic classification[false depressed tubulovillous adenoma(LST-NG pseudodepressed type,LST-NG-PD),type 1 particles(LST-G homogenous type),and LST-G nodular mixed type],accompanied by large nodules(with)were independent risk factors for carcinogenesis;endoscopic classification(LST-NG-PD)and the presence of large nodules were independent risk factors for submucosal infiltration.CONCLUSION These risk factors provide practical guidance for treatment selection:LST-NG-PD with large nodules should prioritize ESD,while high-risk rectal lesions>2 cm may require additional imaging evaluation before endoscopic resection.
基金Supported by National Natural Science Foundation of China,No.82272396Suzhou Medical and Health Science and Technology Innovation Project,No.SKY2022057The Youth Medical Talent of Jiangsu Province,No.QNRC2016475.
文摘Many digestive system malignant tumors are characterized by high incidence and mortality rate.Increasing evidence has revealed that the tumor microenvironment(TME)is involved in cancer initiation and tumor progression.Tumor-associated macrophages(TAMs)are a predominant constituent of the TME,and participate in the regulation of various biological behaviors and influence the prognosis of digestive system cancer.TAMs can be mainly classified into the antitumor M1 phenotype and protumor M2 phenotype.The latter especially are crucial drivers of tumor invasion,growth,angiogenesis,metastasis,immunosuppression,and resistance to therapy.TAMs are of importance in the occurrence,development,diagnosis,prognosis,and treatment of common digestive system malignant tumors.In this review,we summarize the role of TAMs in common digestive system malignant tumors,including esophageal,gastric,colorectal,pancreatic and liver cancers.How TAMs promote the development of tumors,and how they act as potential therapeutic targets and their clinical applications are also described.
文摘Multiplex Ligation-Dependent Probe Amplification (MLPA) was used to study the integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation. WTK1 cells contain a p53 mutation, whereas the TK6 cell line has the native p53 tumor-suppressor gene. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. Using probes that target specific regions on chromosomes associated with a distinct subset of microdeletions and microduplications either established or thought to be responsible for intellectual disability or developmental delay, we have demonstrated that WTK1 and TK6 are not impacted in the same way by irradiation. Instead, each cell line presents its own unique MLPA profile. The most notable differences are the appearance of nine unique probe signals only seen in WTK1 cells. These results are important in the study of how different cell lines can be affected in significantly different ways depending on the presence or absence of wild type p53.
文摘Malignant tumor has become a major threat affecting human health,and is one of the main causes of human death.Recent studies have shown that many traditional Chinese medicines(TCM)have good anti-tumor activity,which may improve the therapeutic effect of routine treatment and quality of life with lower toxicity.However,the efficacy of TCM alone for the treatment of tumors is limited.Metal ions are essential substances for maintaining normal physiological activities.This article summarized the multiple mechanisms in which metal ions are involved in the prevention and treatment of tumors in TCM.
文摘使用TALEN技术制作p53基因敲除大鼠模型,建立种群并分析大鼠表型。设计特异性识别p53基因外显子2的TALEN蛋白并构建相应载体,将体外转录的TALEN m RNA注射SD大鼠受精卵,出生后从仔鼠中通过测序筛选靶位点正确剪切的阳性小鼠。结果显示,注射得到11只新生仔鼠,通过测序发现其中有10只靶位点发生剪切。选取其中4只作为首建鼠进行繁殖。p53基因敲除纯合子表现出肿瘤易发性,主要自发性肿瘤类型为恶性纤维组织肉瘤。此外,p53基因敲除纯合子大鼠表现出眼睛发育异常,视网膜变性及晶状体纤维排列紊乱。通过TALEN技术高效地获得了p53基因敲除大鼠模型,纯合子敲除大鼠除了易发肿瘤并伴有眼发育异常,因而该敲除大鼠模型除了可用于研究肿瘤发生机制外,也可用于研究p53基因在眼发育过程中的功能。
文摘辅助性T细胞的新亚群Th17,主要分泌IL-17A、IL-17F、IL-21和IL-22等细胞因子,并特异性表达转录因子ROR-γt,能够在IL-6/IL-21与TGF-β(小鼠)或IL-6/IL-23与IL-1β(人)的作用下由初始CD4+T细胞分化而来。Th17细胞在宿主防御微生物感染、介导炎症反应以及自身免疫病方面具有重要作用。调节性T细胞(Regulatory T cell,Treg)又被称为抑制性T细胞,在TGF-β的作用下由初始T细胞分化而来,主要分泌TGF-β、IL-10等细胞因子,并特异性表达转录因子Foxp3。Treg能够通过抑制效应T细胞活性介导免疫耐受,阻止组织损伤。Th17与Treg细胞在肿瘤发展进程中具有重要作用,并且在肿瘤免疫中的作用都具有双重性。同时,肿瘤微环境中两者具有发育可塑性,能够在肿瘤微环境中处于动态平衡。因此,深入而全面的研究Th17和Treg细胞变得尤为重要。文章综述了Th17以及Treg细胞的特性以及在调控肿瘤免疫中的作用,以便更加全面的了解和掌握它们,为科学研究提供理论基础。
