目的评估成人胶质母细胞瘤(GBM)脑脊髓神经轴外全身转移的临床及分子病理特征。方法在“PubMed”“Embase”和“Web of Science”数据库中检索截至2023年12月31日报道的发生全身转移的成人GBM病例,收集汇总其临床特征,同时汇总分析报道...目的评估成人胶质母细胞瘤(GBM)脑脊髓神经轴外全身转移的临床及分子病理特征。方法在“PubMed”“Embase”和“Web of Science”数据库中检索截至2023年12月31日报道的发生全身转移的成人GBM病例,收集汇总其临床特征,同时汇总分析报道的分子病理结果以评估转移发生的可能机制。结果通过数据库检索纳入1928年-2023年的113篇文献,共147例全身转移病例。男性多于女性,男女比例为2.3∶1;中位年龄45岁;转移灶几乎可见于全身各个部位,其中常见的转移部位为骨、肺及淋巴结;自GBM初次诊断至转移发生的中位间隔约10个月;自转移发生至患者死亡的中位间隔约4.5个月;中位总体生存约14.8个月。多因素分析显示年龄≤40岁、全切除以及未合并颅内复发与患者生存显著正相关。约39例患者(39/147,26.5%)报道了基因检测的结果。不同的研究所检测的基因项目存在区别,而且不同病例之间检测的基因结果呈现明显异质性。从报道的数量及阳性比例来看,异柠檬酸脱氢酶(IDH)野生型(阳性率27/30)、TERT启动子突变(阳性率11/13)、PTEN突变(阳性率10/11)、TP53突变(阳性率10/13)和RB1突变(阳性率8/9)为相对常见的基因突变。结论成人GBM脑脊髓神经轴外全身转移罕见,年轻患者相对多见,颅内病变的复发或进展仍为决定患者生存的关键因素。转移的发生应为多克隆基因突变进展的结果,其中,促增殖、促侵袭类基因改变例如癌基因或抑癌基因突变以及上皮间质转化类相关基因可能发挥了重要作用。展开更多
Objective To observe the effect of Sunitinib and Baofei Dingchuan Decoction(BDD)on pulmonary vascular remodeling in chronic obstructive pulmonary disease(COPD)complicating diabetes mice model,and to study if its mecha...Objective To observe the effect of Sunitinib and Baofei Dingchuan Decoction(BDD)on pulmonary vascular remodeling in chronic obstructive pulmonary disease(COPD)complicating diabetes mice model,and to study if its mechanism is relevant to the expression of hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial grow factor(VEGF)in lung tissue.Methods Totally 40 ob/ob mice were randomly divided into 4 groups,i.e.,control group,model group,BDD group,and sunitinib group,10 in each group.All the mice except the control group were exposed to cigarette smoke in a homemade box for 14 weeks.On day 1 and 14,lipopolysaccharide(LPS)was dripped into the airway of the mice.After the model was established,mice in the sunitinib group were administered with Sunitinib malate at a dosage of 30 mg/(kg·d)by gastrogavage and mice in the BDD group were administered with BDD at a dosage of 9.3 g/(kg·d)by gastrogavage,for consecutive 2 weeks.The levels of fasting blood glucose(FBG)was measured at week 0,14 and 16.The airway remodeling was observed by HE staining and quantified by total bronchial wall area/basement membrane perimeter(WAt/Pbm),the pulmonary vascular remodeling was quantified by vessel wall thickness/total vascular diameter(WT%)and vessel wall area/total vascular area(WA%).The collagen deposition in peribronchus was observed by Masson staining and quantified by collagen wall area/basement membrane perimeter(WAc/Pbm),the pulmonary vascular smooth muscle layer remodeling was observed by CD31/α-SMA/DAPI immunofluorescence staining.The protein level of HIF-1α and VEGF in lung tissue homogenate were detected by enzyme-linked immunosorbent assay.Relative expressions of HIF-1α and VEGF mRNA in lung tissue were determined by real-time fluorescence quantitative PCR.Results Compared with the control group,the model group showed no significant difference in the level of FBG at week 16(P>0.05),WAt/Pbm,WAc/Pbm,WT% and WA% level increased(P<0.01),thicker pulmonary vascular smooth muscle layer,and increased HIF-1α and VEGF protein level and mRNA level in lung tissue(P<0.01).Compared with the model group,the level of FBG decreased,in the Sunitinib group at week 16(P<0.01)when the BDD group showed no significant difference(P>0.05),both the Sunitinib group and the BDD group showed decreased WAt/Pbm,WAc/Pbm,WT% and WA% level(P<0.01,P<0.05),thinner pulmonary vascular smooth muscle layer,protein and mRNA expressions of HIF-1α and VEGF were decreased in lung tissue(P<0.01,P<0.05).Conclusion Sunitinib and BDD could alleviate the pulmonary vascular remodeling in COPD complicating diabetes mice model by down-regulation of the HIF-1α and VEGF expression in lung tissue.展开更多
文摘目的评估成人胶质母细胞瘤(GBM)脑脊髓神经轴外全身转移的临床及分子病理特征。方法在“PubMed”“Embase”和“Web of Science”数据库中检索截至2023年12月31日报道的发生全身转移的成人GBM病例,收集汇总其临床特征,同时汇总分析报道的分子病理结果以评估转移发生的可能机制。结果通过数据库检索纳入1928年-2023年的113篇文献,共147例全身转移病例。男性多于女性,男女比例为2.3∶1;中位年龄45岁;转移灶几乎可见于全身各个部位,其中常见的转移部位为骨、肺及淋巴结;自GBM初次诊断至转移发生的中位间隔约10个月;自转移发生至患者死亡的中位间隔约4.5个月;中位总体生存约14.8个月。多因素分析显示年龄≤40岁、全切除以及未合并颅内复发与患者生存显著正相关。约39例患者(39/147,26.5%)报道了基因检测的结果。不同的研究所检测的基因项目存在区别,而且不同病例之间检测的基因结果呈现明显异质性。从报道的数量及阳性比例来看,异柠檬酸脱氢酶(IDH)野生型(阳性率27/30)、TERT启动子突变(阳性率11/13)、PTEN突变(阳性率10/11)、TP53突变(阳性率10/13)和RB1突变(阳性率8/9)为相对常见的基因突变。结论成人GBM脑脊髓神经轴外全身转移罕见,年轻患者相对多见,颅内病变的复发或进展仍为决定患者生存的关键因素。转移的发生应为多克隆基因突变进展的结果,其中,促增殖、促侵袭类基因改变例如癌基因或抑癌基因突变以及上皮间质转化类相关基因可能发挥了重要作用。
文摘Objective To observe the effect of Sunitinib and Baofei Dingchuan Decoction(BDD)on pulmonary vascular remodeling in chronic obstructive pulmonary disease(COPD)complicating diabetes mice model,and to study if its mechanism is relevant to the expression of hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial grow factor(VEGF)in lung tissue.Methods Totally 40 ob/ob mice were randomly divided into 4 groups,i.e.,control group,model group,BDD group,and sunitinib group,10 in each group.All the mice except the control group were exposed to cigarette smoke in a homemade box for 14 weeks.On day 1 and 14,lipopolysaccharide(LPS)was dripped into the airway of the mice.After the model was established,mice in the sunitinib group were administered with Sunitinib malate at a dosage of 30 mg/(kg·d)by gastrogavage and mice in the BDD group were administered with BDD at a dosage of 9.3 g/(kg·d)by gastrogavage,for consecutive 2 weeks.The levels of fasting blood glucose(FBG)was measured at week 0,14 and 16.The airway remodeling was observed by HE staining and quantified by total bronchial wall area/basement membrane perimeter(WAt/Pbm),the pulmonary vascular remodeling was quantified by vessel wall thickness/total vascular diameter(WT%)and vessel wall area/total vascular area(WA%).The collagen deposition in peribronchus was observed by Masson staining and quantified by collagen wall area/basement membrane perimeter(WAc/Pbm),the pulmonary vascular smooth muscle layer remodeling was observed by CD31/α-SMA/DAPI immunofluorescence staining.The protein level of HIF-1α and VEGF in lung tissue homogenate were detected by enzyme-linked immunosorbent assay.Relative expressions of HIF-1α and VEGF mRNA in lung tissue were determined by real-time fluorescence quantitative PCR.Results Compared with the control group,the model group showed no significant difference in the level of FBG at week 16(P>0.05),WAt/Pbm,WAc/Pbm,WT% and WA% level increased(P<0.01),thicker pulmonary vascular smooth muscle layer,and increased HIF-1α and VEGF protein level and mRNA level in lung tissue(P<0.01).Compared with the model group,the level of FBG decreased,in the Sunitinib group at week 16(P<0.01)when the BDD group showed no significant difference(P>0.05),both the Sunitinib group and the BDD group showed decreased WAt/Pbm,WAc/Pbm,WT% and WA% level(P<0.01,P<0.05),thinner pulmonary vascular smooth muscle layer,protein and mRNA expressions of HIF-1α and VEGF were decreased in lung tissue(P<0.01,P<0.05).Conclusion Sunitinib and BDD could alleviate the pulmonary vascular remodeling in COPD complicating diabetes mice model by down-regulation of the HIF-1α and VEGF expression in lung tissue.
