Chronic,unresolved inflammation correlates with persistent hepatic injury and fibrosis,ultimately progressing to hepatocellular carcinoma(HCC).Bisdemethoxycurcumin(BDMC)demonstrates therapeutic potential against HCC,y...Chronic,unresolved inflammation correlates with persistent hepatic injury and fibrosis,ultimately progressing to hepatocellular carcinoma(HCC).Bisdemethoxycurcumin(BDMC)demonstrates therapeutic potential against HCC,yet its mechanism in preventing hepatic"inflammation-carcinoma transformation"remains incompletely understood.In the current research,clinical HCC specimens underwent analysis using hematoxylin-eosin(H&E)staining and immunohistochemistry(IHC)to evaluate the expression of fibrosis markers,M2 macrophage markers,and CXCL12.In vitro,transforming growth factor-β1(TGF-β1)-induced LX-2 cells and a co-culture system of LX-2,THP-1,and HCC cells were established.Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT),flow cytometry,and Transwell assays.Reverse transcription-quantitative polymerase chain reaction(RT-qPCR),Western blotting and immunofluorescence evaluated the differential expression of molecules.The interaction betweenβ-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation(Co-IP),dual luciferase,and chromatin immunoprecipitation(ChIP)assays.A DEN-induced rat model was developed to investigate BDMC’s role in liver fibrosis-associated HCC(LFAHCC)development in vivo.Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages.BDMC delayed liver fibrosis progression to HCC in vivo.BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells(HSCs).Furthermore,BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis.Mechanistically,BDMC repressed TCF4/β-catenin complex formation,thereby reducing CXCL12 transcription in LX-2 cells.Moreover,CXCL12 overexpression reversed BDMC’s inhibitory effect on macrophage M2 polarization and its mediation of fibrosis,as well as HCC proliferation and metastasis.BDMC significantly suppressed LFAHCC development through CXCL12 in rats.In conclusion,BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressingβ-catenin/TCF4-mediated CXCL12 transcription.展开更多
The contribution of angiogenesis inhibitor TNP- 4 70 to the growth and m etastasis of ACHN renal cell carcinom a (RCC) was studied. TNP- 4 70 (40 m g/ kg,every two days) was ad- ministrated to BABL / c nude m ice be...The contribution of angiogenesis inhibitor TNP- 4 70 to the growth and m etastasis of ACHN renal cell carcinom a (RCC) was studied. TNP- 4 70 (40 m g/ kg,every two days) was ad- ministrated to BABL / c nude m ice bearing ACHN RCC. The mice were sacrificed after a treatment duration of 31days and the weight and volum e of subcutaneous tum ors as well as foci of lung m etastasis were m easured.The microvascular density(MVD) of the tumor as well as the PCNA index and apoptotic index of the tum or cells were evaluated imm unohistochem ically. Result showed that the growth of ACHN RCC was suppressed significantly and none metastasis was ob- served in TNP- 4 70 - treated m ice. Compared with the control group,the MVD was decreased m arkedly (P<0 .0 1) and the apoptotic index was increased significantly (P<0 .0 1) in the treated group. The tumor volume was positively correlated to the MVD (r=0 .714 4 ,P<0 .0 1) and in- versely correlated to the apoptotic index(r=- 0 .86 0 7,P<0 .0 1) ,and MVD was conversely cor- related to the apoptotic index.It was determ ined that TNP- 4 70 could effectively inhibit angiogene- sis of ACHN RCC,which resulting in ischemia and hypoxia,leading to increased apoptosis,thus obviously suppressing the growth and metastasis of ACHN RCC in nude m ice.展开更多
目的:从中国卫生体系角度出发,评估纳武利尤单抗联合吉西他滨、顺铂化疗对比单纯吉西他滨、顺铂化疗在晚期尿路上皮癌治疗方面的经济性。方法:基于CheckMate-901临床试验数据构建三状态Markov模型,应用成本-效用分析进行经济性评价,并...目的:从中国卫生体系角度出发,评估纳武利尤单抗联合吉西他滨、顺铂化疗对比单纯吉西他滨、顺铂化疗在晚期尿路上皮癌治疗方面的经济性。方法:基于CheckMate-901临床试验数据构建三状态Markov模型,应用成本-效用分析进行经济性评价,并对模型涉及相关参数进行单因素敏感性分析和概率敏感性分析以检验结果的稳健性。结果:研究结果显示,相比对照组,试验组每多获得一个质量调整生命年(quality-adjusted life year,QALY),纳武利尤单抗联合吉西他滨、顺铂化疗方案需额外花费1612021.74元。结论:纳武利尤单抗与吉西他滨、顺铂化疗联合治疗相比单独化疗,在晚期尿路上皮癌的治疗上并不具备经济性优势。展开更多
基金supported by the National Natural Science Foundation of China(No.81904182)the Training Program for Excellent Young Innovators of Changsha(No.kq2209020)+1 种基金the Excellent Youth Project of Hunan University of Chinese Medicine(No.2022XJB006)the Excellent Youth Project of Natural Science Foundation of Heilongjiang Province(No.YQ2022H015).
文摘Chronic,unresolved inflammation correlates with persistent hepatic injury and fibrosis,ultimately progressing to hepatocellular carcinoma(HCC).Bisdemethoxycurcumin(BDMC)demonstrates therapeutic potential against HCC,yet its mechanism in preventing hepatic"inflammation-carcinoma transformation"remains incompletely understood.In the current research,clinical HCC specimens underwent analysis using hematoxylin-eosin(H&E)staining and immunohistochemistry(IHC)to evaluate the expression of fibrosis markers,M2 macrophage markers,and CXCL12.In vitro,transforming growth factor-β1(TGF-β1)-induced LX-2 cells and a co-culture system of LX-2,THP-1,and HCC cells were established.Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT),flow cytometry,and Transwell assays.Reverse transcription-quantitative polymerase chain reaction(RT-qPCR),Western blotting and immunofluorescence evaluated the differential expression of molecules.The interaction betweenβ-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation(Co-IP),dual luciferase,and chromatin immunoprecipitation(ChIP)assays.A DEN-induced rat model was developed to investigate BDMC’s role in liver fibrosis-associated HCC(LFAHCC)development in vivo.Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages.BDMC delayed liver fibrosis progression to HCC in vivo.BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells(HSCs).Furthermore,BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis.Mechanistically,BDMC repressed TCF4/β-catenin complex formation,thereby reducing CXCL12 transcription in LX-2 cells.Moreover,CXCL12 overexpression reversed BDMC’s inhibitory effect on macrophage M2 polarization and its mediation of fibrosis,as well as HCC proliferation and metastasis.BDMC significantly suppressed LFAHCC development through CXCL12 in rats.In conclusion,BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressingβ-catenin/TCF4-mediated CXCL12 transcription.
文摘The contribution of angiogenesis inhibitor TNP- 4 70 to the growth and m etastasis of ACHN renal cell carcinom a (RCC) was studied. TNP- 4 70 (40 m g/ kg,every two days) was ad- ministrated to BABL / c nude m ice bearing ACHN RCC. The mice were sacrificed after a treatment duration of 31days and the weight and volum e of subcutaneous tum ors as well as foci of lung m etastasis were m easured.The microvascular density(MVD) of the tumor as well as the PCNA index and apoptotic index of the tum or cells were evaluated imm unohistochem ically. Result showed that the growth of ACHN RCC was suppressed significantly and none metastasis was ob- served in TNP- 4 70 - treated m ice. Compared with the control group,the MVD was decreased m arkedly (P<0 .0 1) and the apoptotic index was increased significantly (P<0 .0 1) in the treated group. The tumor volume was positively correlated to the MVD (r=0 .714 4 ,P<0 .0 1) and in- versely correlated to the apoptotic index(r=- 0 .86 0 7,P<0 .0 1) ,and MVD was conversely cor- related to the apoptotic index.It was determ ined that TNP- 4 70 could effectively inhibit angiogene- sis of ACHN RCC,which resulting in ischemia and hypoxia,leading to increased apoptosis,thus obviously suppressing the growth and metastasis of ACHN RCC in nude m ice.
文摘目的:从中国卫生体系角度出发,评估纳武利尤单抗联合吉西他滨、顺铂化疗对比单纯吉西他滨、顺铂化疗在晚期尿路上皮癌治疗方面的经济性。方法:基于CheckMate-901临床试验数据构建三状态Markov模型,应用成本-效用分析进行经济性评价,并对模型涉及相关参数进行单因素敏感性分析和概率敏感性分析以检验结果的稳健性。结果:研究结果显示,相比对照组,试验组每多获得一个质量调整生命年(quality-adjusted life year,QALY),纳武利尤单抗联合吉西他滨、顺铂化疗方案需额外花费1612021.74元。结论:纳武利尤单抗与吉西他滨、顺铂化疗联合治疗相比单独化疗,在晚期尿路上皮癌的治疗上并不具备经济性优势。
