AIM:To evaluate the antitumoral effect of combined inhibitors of angiogenesis and histone deacetylases in an experimental rat hepatoma model.METHODS:MH7777A hepatoma cells were injected into the liver of male Buffalo ...AIM:To evaluate the antitumoral effect of combined inhibitors of angiogenesis and histone deacetylases in an experimental rat hepatoma model.METHODS:MH7777A hepatoma cells were injected into the liver of male Buffalo rats.After 7 d treatment with the vascular endothelial growth factor receptor antagonist PTK787/ZK222584(PTK/ZK),the histone deacetylase inhibitor MS-275,tamoxifen(TAM) and/or retinoic acid was initiated(n ≥ 8 animals/group).Natural tumor development was shown in untreated control groups(control 1 with n = 12,control 2 with n = 8).The control groups were initiated at different time points to demonstrate the stability of the hepatoma model.For documentation of possible side effects,we documented any change in body weight,loss of fur and diarrhea.After 21 d treatment,the rats were euthanized.Main target parameters were tumor size and metastasis rate.Additionally,immunohistochemistry for the proliferating cell nuclear antigen(PCNA) and TdT-mediated dUTP-biotin nick end labeling(TUNEL) assay were performed.RESULTS:The control groups developed large tumor nodules with extrahepatic tumor burden in the lung and abdominal organs(control 1:6.18 cm3 ± 4.14 cm3 and control 2:8.0 cm3 ± 4.44 cm3 28 d after tumor cell injection).The tumor volume did not differ significantly in the control groups(P = 0.13).As single agents MS-275 and PTK/ZK reduced tumor volume by 58.6% ± 2.6% and 48.7% ± 3.2% vs control group 1,which was significant only for MS-275(P = 0.025).The combination of MS-275 and PTK/ZK induced a nearly complete and highly significant tumor shrinkage by 90.3% ± 1%(P = 0.005).Addition of TAM showed no further efficacy,while quadruple therapy with retinoic acid increased antitumoral efficacy(tumor reduction by 93 ± 1%) and side effects.PCNA positive cells were not significantly reduced by the single agents,while dual therapy(MS-275 and PTK/ZK) and quadruple therapy reduced the PCNA-positive cell fraction significantly by 9.1 and 20.6% vs control 1(P < 0.05).The number of TUNEL-positive cells,markers for ongoing apoptosis,was increased significantly by the single agents(control 1:6.9%,PTK/ZK:11.4%,MS-275:12.2% with P < 0.05 vs control 1).The fraction of TUNEL-positive cells was upregulated highly significantly by dual therapy(18.4%) and quadruple therapy(24.8%,P < 0.01 vs control 1).For the proliferating(PCNA positive) and apoptotic cell fraction,quadruple therapy was significantly superior to dual therapy(P = 0.01).CONCLUSION:Combined PTK/ZK and MS-275 were highly effective in this hepatoma model.Quadruple therapy enhanced the effects microscopically,but not macroscopically.These results should be investigated further.展开更多
The absence of effective therapies for castration-resistant prostate cancer(CRPC) establishes the need to develop novel therapeutic modality, such as targeted gene therapy, which is ideal for the treatment of CRPC. Bu...The absence of effective therapies for castration-resistant prostate cancer(CRPC) establishes the need to develop novel therapeutic modality, such as targeted gene therapy, which is ideal for the treatment of CRPC. But its application has been limited due to lack of favorable gene vector and the reduction of "bystander effect". Consequently, scientists all over the world focus their main experimental research on the following four aspects: targeted gene, vector, transfer means and comprehensive therapy. In this paper, we reviewed the latest advances of experimental research on targeted gene therapy for prostate cancer.展开更多
We argue that the topological charge density wave phase in the quasi-2D Kagome superconductor AV3Sb5 is a chiral flux phase.Considering the symmetry of the Kagome lattice,we show that the chiral flux phase has the low...We argue that the topological charge density wave phase in the quasi-2D Kagome superconductor AV3Sb5 is a chiral flux phase.Considering the symmetry of the Kagome lattice,we show that the chiral flux phase has the lowest energy among those states which exhibit 2×2 charge orders observed experimentally.This state breaks the time-reversal symmetry and displays anomalous Hall effect.The explicit pattern of the density of state in real space is calculated.These results are supported by recent experiments and suggest that these materials are new platforms to investigate the interplay between topology,superconductivity and electron–electron correlations.展开更多
基金Supported by The Schering AG,Berlin (Germany) which friendly provided PTK787/ZK222584 and MS-275
文摘AIM:To evaluate the antitumoral effect of combined inhibitors of angiogenesis and histone deacetylases in an experimental rat hepatoma model.METHODS:MH7777A hepatoma cells were injected into the liver of male Buffalo rats.After 7 d treatment with the vascular endothelial growth factor receptor antagonist PTK787/ZK222584(PTK/ZK),the histone deacetylase inhibitor MS-275,tamoxifen(TAM) and/or retinoic acid was initiated(n ≥ 8 animals/group).Natural tumor development was shown in untreated control groups(control 1 with n = 12,control 2 with n = 8).The control groups were initiated at different time points to demonstrate the stability of the hepatoma model.For documentation of possible side effects,we documented any change in body weight,loss of fur and diarrhea.After 21 d treatment,the rats were euthanized.Main target parameters were tumor size and metastasis rate.Additionally,immunohistochemistry for the proliferating cell nuclear antigen(PCNA) and TdT-mediated dUTP-biotin nick end labeling(TUNEL) assay were performed.RESULTS:The control groups developed large tumor nodules with extrahepatic tumor burden in the lung and abdominal organs(control 1:6.18 cm3 ± 4.14 cm3 and control 2:8.0 cm3 ± 4.44 cm3 28 d after tumor cell injection).The tumor volume did not differ significantly in the control groups(P = 0.13).As single agents MS-275 and PTK/ZK reduced tumor volume by 58.6% ± 2.6% and 48.7% ± 3.2% vs control group 1,which was significant only for MS-275(P = 0.025).The combination of MS-275 and PTK/ZK induced a nearly complete and highly significant tumor shrinkage by 90.3% ± 1%(P = 0.005).Addition of TAM showed no further efficacy,while quadruple therapy with retinoic acid increased antitumoral efficacy(tumor reduction by 93 ± 1%) and side effects.PCNA positive cells were not significantly reduced by the single agents,while dual therapy(MS-275 and PTK/ZK) and quadruple therapy reduced the PCNA-positive cell fraction significantly by 9.1 and 20.6% vs control 1(P < 0.05).The number of TUNEL-positive cells,markers for ongoing apoptosis,was increased significantly by the single agents(control 1:6.9%,PTK/ZK:11.4%,MS-275:12.2% with P < 0.05 vs control 1).The fraction of TUNEL-positive cells was upregulated highly significantly by dual therapy(18.4%) and quadruple therapy(24.8%,P < 0.01 vs control 1).For the proliferating(PCNA positive) and apoptotic cell fraction,quadruple therapy was significantly superior to dual therapy(P = 0.01).CONCLUSION:Combined PTK/ZK and MS-275 were highly effective in this hepatoma model.Quadruple therapy enhanced the effects microscopically,but not macroscopically.These results should be investigated further.
文摘The absence of effective therapies for castration-resistant prostate cancer(CRPC) establishes the need to develop novel therapeutic modality, such as targeted gene therapy, which is ideal for the treatment of CRPC. But its application has been limited due to lack of favorable gene vector and the reduction of "bystander effect". Consequently, scientists all over the world focus their main experimental research on the following four aspects: targeted gene, vector, transfer means and comprehensive therapy. In this paper, we reviewed the latest advances of experimental research on targeted gene therapy for prostate cancer.
基金supported by the National Program on Key Basic Research Project of China(973 Program)(2017YFA0303100)the National Natural Science Foundation of China(11888101)+2 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(XDB28000000)the support from the start-up grant of IOP-CASsupported by the U.S.Department of Energy,Basic Energy Sciences Grant No.DE-FG02-99ER45747。
文摘We argue that the topological charge density wave phase in the quasi-2D Kagome superconductor AV3Sb5 is a chiral flux phase.Considering the symmetry of the Kagome lattice,we show that the chiral flux phase has the lowest energy among those states which exhibit 2×2 charge orders observed experimentally.This state breaks the time-reversal symmetry and displays anomalous Hall effect.The explicit pattern of the density of state in real space is calculated.These results are supported by recent experiments and suggest that these materials are new platforms to investigate the interplay between topology,superconductivity and electron–electron correlations.
