Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties.It also exhibits significant anti-tumor activity,suppressing tumor growth in vitro and in vivo.The curre...Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties.It also exhibits significant anti-tumor activity,suppressing tumor growth in vitro and in vivo.The current body of research on Britanin includes thirty papers predominantly related to neoplasms,the majority of which are gastrointestinal tumors that have not been summarized before.To drive academic debate,the present paper reviews the available research on Britanin in gastrointestinal tumors.It also outlines novel research directions using data not directly concerned with the digestive system,but which could be adopted in future gastrointestinal research.Britanin was found to counteract liver,colorectal,pancreatic,and gastric tumors,by regulating proliferation,apoptosis,autophagy,immune response,migration,and angiogenesis.As confirmed in pancreatic,gastric,and liver cancer,its most commonly noted molecular effects include nuclear factor kappa B and B-cell lymphoma 2 downregulation,as well as Bcl-2-associated X protein upregulation.Moreover,it has been found to induce the Akt kinase and Forkhead box O1 axis,activate the AMP-activated protein kinase pathway,elevate interleukin-2 and peroxisome proliferator-activated receptor-γlevels,reduce interleukin-10,as well as downregulate matrix metalloproteinase-9,Twist family bHLH transcription factor 1,and cyclooxygenase-2.It also inhibits Myc–HIF1αinteraction and programmed death ligand 1 transcription by interrupting the Ras/RAF/MEK/ERK pathway and mTOR/P70S6K/4EBP1 signaling.Future research should aim to unravel the link between Britanin and acetylcholinesterase,mast cells,osteolysis,and ischemia,as compelling data have been provided by studies outside the gastrointestinal context.Since the cytotoxicity of Britanin on noncancerous cells is significantly lower than that on tumor cells,while still being effective against the latter,further in-depth studies with the use of animal models are merited.The compound exhibits pleiotropic biological activity and offers considerable promise as an anti-cancer agent,which may address the current paucity of treatment options and high mortality rate among patients with gastrointestinal tumors.展开更多
AIM: To clarify the biological role of stem cell factor (SCF)-mediated wild-type KIT receptor activation in gastrointestinal stromal tumor (GIST) growth. METHODS: The co-expression of wild-type KIT receptor and SCF wa...AIM: To clarify the biological role of stem cell factor (SCF)-mediated wild-type KIT receptor activation in gastrointestinal stromal tumor (GIST) growth. METHODS: The co-expression of wild-type KIT receptor and SCF was evaluated in 51 GIST samples using mutation analysis and immunohistochemistry, and the results were correlated with clinicopathological param- eters, including the mitotic count, proliferative index (Ki-67 immunohistochemical staining), mitotic index (phospho-histone H3 immunohistochemical staining) and apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Using primary cultured GIST cells, the effect of SCF-mediated wild-type KIT receptor activation was determined by western blotting, methyl thiazolyl tetrazolium (MTT), and apoptosis assays. RESULTS: We found that wild-type KIT receptor and SCF protein were expressed in 100% and 76.5% of the 51 GIST samples, respectively, and the co-expression of wild-type KIT receptor and SCF was associated with known indicators of poor prognosis, including larger tumor size (P = 0.0118), higher mitotic count (P = 0.0058), higher proliferative index (P = 0.0012), higher mitotic index (P = 0.0282), lower apoptosis index (P = 0.0484), and increased National Institutes of Health risk level (P = 0.0012). We also found that the introduction of exogenous SCF potently increased KIT kinase activity, stimulated cell proliferation (P < 0.01) and inhibited apoptosis (P < 0.01) induced by serum starvation, while a KIT immunoblocking antibody suppressed proliferation (P = 0.01) and promoted apoptosis (P < 0.01) in cultured GIST cells. CONCLUSION: SCF-mediated wild-type KIT receptor activation plays an important role in GIST cell growth. The inhibition of SCF-mediated wild-type KIT receptor activation may prove to be particularly important for GIST therapy.展开更多
OBJECTIVE： To explore the anticancer mechanism of aqueous extract of Taxus Chinensis （Pilger） Rehd （AETC）. METHODS： The serum pharmacological method was used to avoid interference from administration of the crud...OBJECTIVE： To explore the anticancer mechanism of aqueous extract of Taxus Chinensis （Pilger） Rehd （AETC）. METHODS： The serum pharmacological method was used to avoid interference from administration of the crude medicinal herbs. Eight purebred NewZealand rabbits were used for preparation of serum containing various concentrations of AETC. For- ty-eight Balb/c-nu mice were used for in vivo experi- ments. The effects of serum containing AETC on the proliferation of A549 cells and expression levels of the epidermal growth factor receptor/mito- gen-activated protein kinase （EGFR/MAPK） path- way-related proteins in vitro were investigated. Ad- ditionally, the effects on the growth of A549 xeno- grafts in nude mice, and expression levels of the EG- FR/MAPK pathway-related proteins in the xeno- grafts, were investigated. RESULTS： 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl- tetrazolium bromide （MTT） assay revealed that the serum containing AETC significantly decreased the viability of A549 cells in a dose-dependent manner. Western blot showed that the serum containing various concentrations of AETC strongly reduced the levels of phospho-Jun N-terminal kinase （p-JNK） and phospho-extracellular signal-regulated kinasel/2 （ERK1/2） while it increased the level of p-p38. However, no significant effects on the ex- pression levels of JNK, ERK1/2, and p38 MAPK were found. In addition, an anticancer effect from AETC was observed in vivo in the Balb/c-nu mice bearing A549 xenografts.CONCLUSION： AETC has significant effects on the growth of A549 xenografts and on the activity of the EGFR/MAPK pathway. Therefore, AETC may be beneficial in lung carcinoma treatment.展开更多
Objective To investigate the effects of insulin-like growth factor binding protein 7(IGFBP7)on the proliferation,cell cycle of gastric cancer cell and the expression of cynlin D1,cyclin-dependent kinase(CDK)4,and to o...Objective To investigate the effects of insulin-like growth factor binding protein 7(IGFBP7)on the proliferation,cell cycle of gastric cancer cell and the expression of cynlin D1,cyclin-dependent kinase(CDK)4,and to observe the effects of IGFBP7 on the growth of gastric tumor xenografts in nude mice.Methods The MKN-28cell line was interfered by small interfere ribonucleic acid(siRNA)(interfered group),and blank control group,展开更多
目的生长动态的监测是肿瘤学重要的研究内容之一,现有的各种生长动态的监测方法存在诸多缺陷。文中研究活体成像技术(in vivo imaging technique,IVIT)在肿瘤生长动态监测中的应用。方法在18只Babl/C小鼠背部皮下注射1×106/mL B16-...目的生长动态的监测是肿瘤学重要的研究内容之一,现有的各种生长动态的监测方法存在诸多缺陷。文中研究活体成像技术(in vivo imaging technique,IVIT)在肿瘤生长动态监测中的应用。方法在18只Babl/C小鼠背部皮下注射1×106/mL B16-F10-luc-G5细胞100μL,建立种植瘤模型。肿块出现后每天测量肿瘤并计算肿瘤体积,并于第0、3、5、7、9、14天每次取3只小鼠以活体成像系统(in vivo imaging system,IVIS)检测肿瘤生物发光,检测后处死取肿瘤组织制成石蜡切片行病理学检查。结果所有小鼠接种成功肿瘤,第5天肿瘤可见。第5、7、9、14天肿瘤大小分别为[(2.86E+00)±1.21]、[(4.87E+00)±1.66]、[(9.27E+01)±6.31]、[(2.60E+02)±7.88]mm3;所有移植瘤生物发光均被IVIS检测到,第0、3、5、7、9、14天肿瘤平均实测光子数为[(6.35E+05)±7655]、[(1.12E+05)±1820]、[(1.62E+05)±2090]、[(2.40E+05)±3515]、[(1.18E+06)±11530]、[(2.23E+06)±17934]photon/(cm2·ser·s);移植瘤平均实测光子数与体积之间存在线性回归关系(R2=0.97);以IVIS监测结果绘制的肿瘤生长曲线,揭示了B16F10移植瘤生长动态特点。结论 IVIT可连续监测标记肿瘤的生长动态,准确灵敏、具有一定实用价值。展开更多
文摘Britanin is a bioactive sesquiterpene lactone known for its potent anti-inflammatory and anti-oxidant properties.It also exhibits significant anti-tumor activity,suppressing tumor growth in vitro and in vivo.The current body of research on Britanin includes thirty papers predominantly related to neoplasms,the majority of which are gastrointestinal tumors that have not been summarized before.To drive academic debate,the present paper reviews the available research on Britanin in gastrointestinal tumors.It also outlines novel research directions using data not directly concerned with the digestive system,but which could be adopted in future gastrointestinal research.Britanin was found to counteract liver,colorectal,pancreatic,and gastric tumors,by regulating proliferation,apoptosis,autophagy,immune response,migration,and angiogenesis.As confirmed in pancreatic,gastric,and liver cancer,its most commonly noted molecular effects include nuclear factor kappa B and B-cell lymphoma 2 downregulation,as well as Bcl-2-associated X protein upregulation.Moreover,it has been found to induce the Akt kinase and Forkhead box O1 axis,activate the AMP-activated protein kinase pathway,elevate interleukin-2 and peroxisome proliferator-activated receptor-γlevels,reduce interleukin-10,as well as downregulate matrix metalloproteinase-9,Twist family bHLH transcription factor 1,and cyclooxygenase-2.It also inhibits Myc–HIF1αinteraction and programmed death ligand 1 transcription by interrupting the Ras/RAF/MEK/ERK pathway and mTOR/P70S6K/4EBP1 signaling.Future research should aim to unravel the link between Britanin and acetylcholinesterase,mast cells,osteolysis,and ischemia,as compelling data have been provided by studies outside the gastrointestinal context.Since the cytotoxicity of Britanin on noncancerous cells is significantly lower than that on tumor cells,while still being effective against the latter,further in-depth studies with the use of animal models are merited.The compound exhibits pleiotropic biological activity and offers considerable promise as an anti-cancer agent,which may address the current paucity of treatment options and high mortality rate among patients with gastrointestinal tumors.
基金Supported by The National Natural Science Foundation of China, No.30700809 and No.30972876
文摘AIM: To clarify the biological role of stem cell factor (SCF)-mediated wild-type KIT receptor activation in gastrointestinal stromal tumor (GIST) growth. METHODS: The co-expression of wild-type KIT receptor and SCF was evaluated in 51 GIST samples using mutation analysis and immunohistochemistry, and the results were correlated with clinicopathological param- eters, including the mitotic count, proliferative index (Ki-67 immunohistochemical staining), mitotic index (phospho-histone H3 immunohistochemical staining) and apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Using primary cultured GIST cells, the effect of SCF-mediated wild-type KIT receptor activation was determined by western blotting, methyl thiazolyl tetrazolium (MTT), and apoptosis assays. RESULTS: We found that wild-type KIT receptor and SCF protein were expressed in 100% and 76.5% of the 51 GIST samples, respectively, and the co-expression of wild-type KIT receptor and SCF was associated with known indicators of poor prognosis, including larger tumor size (P = 0.0118), higher mitotic count (P = 0.0058), higher proliferative index (P = 0.0012), higher mitotic index (P = 0.0282), lower apoptosis index (P = 0.0484), and increased National Institutes of Health risk level (P = 0.0012). We also found that the introduction of exogenous SCF potently increased KIT kinase activity, stimulated cell proliferation (P < 0.01) and inhibited apoptosis (P < 0.01) induced by serum starvation, while a KIT immunoblocking antibody suppressed proliferation (P = 0.01) and promoted apoptosis (P < 0.01) in cultured GIST cells. CONCLUSION: SCF-mediated wild-type KIT receptor activation plays an important role in GIST cell growth. The inhibition of SCF-mediated wild-type KIT receptor activation may prove to be particularly important for GIST therapy.
基金Supported by Natural Science Foundation of Zhejiang Province(No.Y2081051)Science and Technology Planning Key Project of Zhejiang Province(No.2009ZA003)
文摘OBJECTIVE： To explore the anticancer mechanism of aqueous extract of Taxus Chinensis （Pilger） Rehd （AETC）. METHODS： The serum pharmacological method was used to avoid interference from administration of the crude medicinal herbs. Eight purebred NewZealand rabbits were used for preparation of serum containing various concentrations of AETC. For- ty-eight Balb/c-nu mice were used for in vivo experi- ments. The effects of serum containing AETC on the proliferation of A549 cells and expression levels of the epidermal growth factor receptor/mito- gen-activated protein kinase （EGFR/MAPK） path- way-related proteins in vitro were investigated. Ad- ditionally, the effects on the growth of A549 xeno- grafts in nude mice, and expression levels of the EG- FR/MAPK pathway-related proteins in the xeno- grafts, were investigated. RESULTS： 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl- tetrazolium bromide （MTT） assay revealed that the serum containing AETC significantly decreased the viability of A549 cells in a dose-dependent manner. Western blot showed that the serum containing various concentrations of AETC strongly reduced the levels of phospho-Jun N-terminal kinase （p-JNK） and phospho-extracellular signal-regulated kinasel/2 （ERK1/2） while it increased the level of p-p38. However, no significant effects on the ex- pression levels of JNK, ERK1/2, and p38 MAPK were found. In addition, an anticancer effect from AETC was observed in vivo in the Balb/c-nu mice bearing A549 xenografts.CONCLUSION： AETC has significant effects on the growth of A549 xenografts and on the activity of the EGFR/MAPK pathway. Therefore, AETC may be beneficial in lung carcinoma treatment.
文摘Objective To investigate the effects of insulin-like growth factor binding protein 7(IGFBP7)on the proliferation,cell cycle of gastric cancer cell and the expression of cynlin D1,cyclin-dependent kinase(CDK)4,and to observe the effects of IGFBP7 on the growth of gastric tumor xenografts in nude mice.Methods The MKN-28cell line was interfered by small interfere ribonucleic acid(siRNA)(interfered group),and blank control group,
文摘目的生长动态的监测是肿瘤学重要的研究内容之一,现有的各种生长动态的监测方法存在诸多缺陷。文中研究活体成像技术(in vivo imaging technique,IVIT)在肿瘤生长动态监测中的应用。方法在18只Babl/C小鼠背部皮下注射1×106/mL B16-F10-luc-G5细胞100μL,建立种植瘤模型。肿块出现后每天测量肿瘤并计算肿瘤体积,并于第0、3、5、7、9、14天每次取3只小鼠以活体成像系统(in vivo imaging system,IVIS)检测肿瘤生物发光,检测后处死取肿瘤组织制成石蜡切片行病理学检查。结果所有小鼠接种成功肿瘤,第5天肿瘤可见。第5、7、9、14天肿瘤大小分别为[(2.86E+00)±1.21]、[(4.87E+00)±1.66]、[(9.27E+01)±6.31]、[(2.60E+02)±7.88]mm3;所有移植瘤生物发光均被IVIS检测到,第0、3、5、7、9、14天肿瘤平均实测光子数为[(6.35E+05)±7655]、[(1.12E+05)±1820]、[(1.62E+05)±2090]、[(2.40E+05)±3515]、[(1.18E+06)±11530]、[(2.23E+06)±17934]photon/(cm2·ser·s);移植瘤平均实测光子数与体积之间存在线性回归关系(R2=0.97);以IVIS监测结果绘制的肿瘤生长曲线,揭示了B16F10移植瘤生长动态特点。结论 IVIT可连续监测标记肿瘤的生长动态,准确灵敏、具有一定实用价值。
