Validated preclinical studies have provided evidence that anti-vascular endothelial growth factor(VEGF) compounds enhance the activity of subsequent antitumor therapy, but the mechanism of this potentiation is far fro...Validated preclinical studies have provided evidence that anti-vascular endothelial growth factor(VEGF) compounds enhance the activity of subsequent antitumor therapy, but the mechanism of this potentiation is far from clear. The most widespread explanation is enhanced delivery of therapeutics due to vascular remodeling, lower interstitial pressure, and increased blood flow. While the antiangiogenic efects on vascular morphology have been fairly consistent in both preclinical and clinical settings, the improvement of tumor vessel function is debated. This review focuses on the efect of anti-VEGF therapy on tumor microenvironment morphology and functions, and its therapeutic beneits when combined with other therapies. The uptake and spatial distribution of chemotherapeutic agents into the tumor after anti-VEGF are examined.展开更多
BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.Howev...BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.展开更多
Canstatin is a novel inhibitor of angiogenesis and tumor growth, derived from the C-terminal globular non-collageneous (NCl) domain of the a2 chain of type IV collagen. It inhibits endothelial cell proliferation and m...Canstatin is a novel inhibitor of angiogenesis and tumor growth, derived from the C-terminal globular non-collageneous (NCl) domain of the a2 chain of type IV collagen. It inhibits endothelial cell proliferation and migration in a dose-dependent manner, and induces endothelial cell apoptosis. In vivo experiments show that canstatin significantly inhibits solid tumor growth. The canstatin mediated inhibition of tumor is related to apoptosis. Canstatin- induced apoptosis is associated with phosphatidylinositol 3-kinase/Akt inhibition and is dependend upon signaling events transduced trough membrane death receptor.展开更多
Objective Immune checkpoint inhibitor(ICI)plus angiogenesis inhibitor(AI)combination therapy is a novel treatment model for multiple cancers that normalizes vascular-immune crosstalk to potentiate cancer immunity.In t...Objective Immune checkpoint inhibitor(ICI)plus angiogenesis inhibitor(AI)combination therapy is a novel treatment model for multiple cancers that normalizes vascular-immune crosstalk to potentiate cancer immunity.In this review,we summarize the characteristics of adverse effects(AEs)and all fatal cases reported in clinical studies involing ICI+AI therapy.Methods Four databases were systematically searched for eligible studies,and 28 relevant studies were selected for inclusion.Results Of the patients included,58.1%developed grade≥3 AEs.The most common fatal AEs were cardiovascular events,severe infections,and hemorrhage.Compared with AI alone,ICI+AI therapy resulted in more cases of grade≥3 proteinuria,liver injury,and fatal AEs(2.49%vs.1.28%,P=0.0041),especially respiratory toxicities and severe infections;however,ICI+AI therapy reduced hematological toxicity.Conclusion We shared comprehensive and practical safety data to review the adverse events associated with ICI+AI treatment.展开更多
Liver cancer is one of the most common causes of cancer death globally,and its incidence in the United States is increasing.Patients with advanced hepatocellular carcinoma(HCC)who are not candidates for surgical resec...Liver cancer is one of the most common causes of cancer death globally,and its incidence in the United States is increasing.Patients with advanced hepatocellular carcinoma(HCC)who are not candidates for surgical resection,liver transplant,or locoregional therapies can be treated with systemic therapies.Multiple agents,including sorafenib,lenvatinib,and regorafenib are approved for use as either first-or second-line therapy in this patient population,but all have relatively modest survival benefits.HCC is potentially susceptible to therapy with checkpoint inhibitors,including agents such as nivolumab and pembrolizumab,which are both approved by the Food and Drug Administration for patients previously treated with sorafenib but have not demonstrated superior overall survival in phase III trials.It is clear that more effective approaches are needed to potentiate the effects of checkpoint inhibitors in patients with HCC.This review will outline and appraise the current literature on the use of checkpoint inhibitors in HCC as part of a combination treatment involving an additional mode of therapy.The list of agents that can be paired with checkpoint inhibitors includes an additional checkpoint inhibitor,vascular endothelial growth factor or vascular endothelial growth factor receptor inhibitors,tyrosine kinase inhibitors,OX-40 agonists,and PT-112 inhibitors.The main non-pharmacologic therapies currently being studied for inclusion in a combination strategy include radiation therapy,trans-arterial chemoembolization,and ablation.展开更多
Bevacizumab, an angiogenesis inhibitor, is a recombined humanized monoclonal antibody against vascular endothelial growth factor and a promising therapeutic option for angiosarcoma management. This is a ease report an...Bevacizumab, an angiogenesis inhibitor, is a recombined humanized monoclonal antibody against vascular endothelial growth factor and a promising therapeutic option for angiosarcoma management. This is a ease report and review of the literature using bevacizumab and combination chemotherapy for angiosarcoma. The understanding of the effectiveness of combined therapy of bevacizumab and chemotherapy agents is still limited. The benefits of bevacizumab treatment for angiosarcoma will need to be weighed against the risks of venous thromboembolism in this population.展开更多
The title compound, C18H17BrO6 (Mr = 409.23), was synthesized as angiogenesis inhibitor and structurally characterized by ^1H-NMR, ^13C-NMR, MS, elemental analysis and X-ray single-crystal diffraction. Structure ana...The title compound, C18H17BrO6 (Mr = 409.23), was synthesized as angiogenesis inhibitor and structurally characterized by ^1H-NMR, ^13C-NMR, MS, elemental analysis and X-ray single-crystal diffraction. Structure analysis indicates that the title compound is of triclinic, space group P1^-, with a = 8.100(3), b = 10.536(4), c = 11.689(5)A, a = 67.405(7), βl = 69.736(3), γ = 88.510(5)°, V = 857.3(5) A^3, Z = 2, Dc = 1.585 g/cm^3, μ = 2.429 mm^-1, F(000) = 416, the finial R = 0.0356 and wR = 0.0929 for 2541 observed reflections. The bond lengths of C(7)-C(16) proved that the title compound possesses coumarin rather than flavone scaffold.展开更多
Background Tumstatin is a recently developed endogenous vascular endothelial growth inhibitor that can be applied as an anti-angiogenesis and antineoplastic agent. The study aimed to design and synthesize the small mo...Background Tumstatin is a recently developed endogenous vascular endothelial growth inhibitor that can be applied as an anti-angiogenesis and antineoplastic agent. The study aimed to design and synthesize the small molecular angiogenesis inhibition-related peptide (peptide 21), to replicate the structural and functional features of the active zone of angiogenesis inhibition using tumstatin and to prove that synthesized peptide 21 has a similar activity: specifically inhibiting tumor angiogenesis like tumstatin. Methods Peptide 21 was designed and synthesized using biological engineering technology. To determine its biological action, the human umbilical vein endothelial cell line ECV304, the human ovarian cancer cell line SKOV-3 and the mouse embryo-derived NIH3T3 fibroblasts were used in in vitro experiments to determine the effect of peptide 21 on proliferation of the three cell lines using the MTT test and growth curves. Transmission electron microscopy (TEM) and flow cytometry (FCM) were applied to analyze the peptide 21-induced apoptosis of the three cell lines qualitatively and quantitatively. In animal experiments, tumor models in nude mice subcutaneously grafted with SKOV-3 were used to observe the effects of peptide 21 on tumor weight, size and microvessel density (MVD). To initially investigate the role of peptide 21, the effect of peptide 21 on the expression of vascular endothelial growth factors (VEGFs) by tumor tissue was semi-quantitatively analyzed. Results The in vitro Ml-r test and growth curves all indicated that cloned peptide 21 could specifically inhibit ECV304 proliferation in a dose-dependent manner (P 〈0.01); TEM and FCM showed that peptide 21 could specifically induce ECV304 apoptosis (P 〈0.01). Results of in vivo experiments showed that tumors in the peptide 21 group grew more slowly. The weight and size of the tumors after 21 days of treatment were smaller than those in the control group (P 〈0.05), with a mean tumor inhibition rate of 67.86%; MVD of the tumor tissue in the peptide 21 group was significantly lower than in the control group (P 〈0.05); the number of cells positive for VEGF in the peptide 21 group was significantly fewer than in the control group (P 〈0.01). Conclusions Similar to the activity of tumstatin in specifically inhibiting tumor angiogenesis, peptide 21 may specifically inhibit tumor endothelial cell proliferation and induce their apoptosis, thereby suppressing tumor angiogenesis and indirectly inhibit the growth, infiltration and metastasis of tumors. Peptide 21 may exert its effect through down-regulating the VEGF expression of tumor cells and vascular endothelial cells.展开更多
Background:The prognosis of patients with small cell lung cancer(SCLC)and brain metastases(BM)was poor.This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM....Background:The prognosis of patients with small cell lung cancer(SCLC)and brain metastases(BM)was poor.This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM.Methods:This was a subgroup analysis of the ALTER1202 trial,which was a randomized,placebo-controlled trial aimed to evaluate the role of anlotinib as third-line treatment or above in patients with SCLC.This study included patients with BM at baseline.The efficacy and safety outcomes included progression-free survival(PFS),overall survival(OS),central nervous system(CNS),objective response rate(ORR),CNS disease control rate(DCR),time to CNS progression,and adverse events(AEs).Results:Twenty-one and nine patients with BM were included in the anlotinib and placebo groups,respectively.The median PFS and OS were 3.8 months(95%confidence interval[CI]:1.8-6.1)and 6.1 months(95%CI:4.1-8.0)in the anlotinib group.Anlotinib was associated with a significant improvement in PFS(hazard ratio[HR]=0.15,95%CI:0.04-0.51,p=0.0005)and OS(HR=0.26,95%CI:0.09-0.73,p=0.0061)than placebo.Anlotinib significantly prolonged the time to CNS progression(p<0.0001).The anlotinib group had a higher CNS DCR than placebo(95.2%vs.22.2%,p=0.0001).The most common grade 3 or higher AEs were increased lipase(19.0%),hypertension(14.3%),and hyponatremia(14.3%)in the anlotinib group.Conclusions:Anlotinib proved to have potential CNS activity and a manageable toxicity profile in patients with SCLC and BM,significantly delaying CNS progression.展开更多
Background The prognosis of unresectable large hepatocellular carcinomas is poor. This study evaluated the efficacy and safety of sorafenib combined with transcatheter arterial chemoembolization and radiofrequency abl...Background The prognosis of unresectable large hepatocellular carcinomas is poor. This study evaluated the efficacy and safety of sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation in the treatment of hepatocellular carcinomas larger than 5 cm. Methods The treatment of 22 patients with large, unresectable hepatocellular carcinomas (5.0-16.5 cm) treated with sorafenib after transcatheter arterial chemoembolization combined with radiofrequency ablation between 2007 and 2011 was reviewed. The local effects, survival rates, toxicity, and prognostic factors were analyzed. Results During a follow-up of 9-49 months, 19 patients died and three survived. The median overall survival was 32 months. The overall cumulative 12, 24, and 36-month survival rates were 85.9%, 66.8%, and 23.5% respectively. Technical effectiveness was achieved in 12 out of 28 lesions (42.85%) at the first CT check. The median time to tumor progression was 21 months. The progression-free survival rates at 6, 12, and 24 months were 90.9%, 72.0%, and 38.4%, respectively. Combined therapy was generally well tolerated. There was only one major procedure-related complication, biloma (4.5%). Sorafenib-related adverse events exceeding grade 3 were hand-foot skin reaction (2/22, 9.1%), gastrointestinal hemorrhage (1/22, 4.5%), and diarrhea (2/22, 9.1%). The absence of vascular invasion before treatment was found to be the best prognostic factor in the univariate analysis. Conclusions Sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation is a promising approach to the treatment of large, unresectable hepatocellular carcinomas. However, large-scale randomized clinical trials are needed to determine the future role of this treatment.展开更多
OBJECTIVE: To investigate the efficacy of Ciji Hua'ai Baosheng formula(CHBF) on microvessel density(MVD) and vascular endothelial growth factor(VEGF), kinase insert domain-containing receptor(KDR) and basic fibrob...OBJECTIVE: To investigate the efficacy of Ciji Hua'ai Baosheng formula(CHBF) on microvessel density(MVD) and vascular endothelial growth factor(VEGF), kinase insert domain-containing receptor(KDR) and basic fibroblast growth factor(b FGF) expression in serum and tumor tissue of mice receiving chemotherapy for the treatment of H22 hepatocellular carcinoma.METHODS: Sixty Kunming mice were injected subcutaneously with H22 hepatoma carcinoma cell suspensions into the right anterior armpit. Seven days later, all transplanted tumor were formed and the mice were intraperitoneally injected 200 mg/kg cytoxan(CTX) to establish the models of tumor-bearing mouse chemotherapy, then they were randomly divided into model group, continuing CTX chemotherapy group(CTX group), and three CHBF(117, 58.5 and 29.25 g/kg) groups. After ten days of treatments, histology was observed, contents of VEGF, KDR and b FGF in serum and tumor tissue were measured by enzyme-linked immunosorbent assay(ELISA), VEGF and b FGF protein expression and MVD tagged by CD34 were detected by immunohistochemisty.RESULTS: MVD in CHBF(117, 58.5 g/kg) and CTX groups was significantly lower than that in model group(P < 0.01); expressions of VEGF, KDR and b FGF in serum and tumor tissue in CHBF(117 g/kg)group were less than those in model group(P <0.05; P < 0.01); the expressions of MVD, VEGF and b FGF in tumor tissue of CHBF(117 g/kg) groupwere also less than those in CTX group(P < 0.05;P < 0.01).CONCLUSION: CHBF can effectively reduce the expression of VEGF, KDR and b FGF in serum and tumor tissue, and decrease MVD and delay tumor progression.展开更多
Chinese Medicine(CM)has been used for several thousand years,playing an important role in the prevention and treatment of diseases including cancer.In the recent four decades,a number of CM herbs have aroused extrem...Chinese Medicine(CM)has been used for several thousand years,playing an important role in the prevention and treatment of diseases including cancer.In the recent four decades,a number of CM herbs have aroused extreme interest in the world-isolating anticancer components from medicinal herbs,using them as biological response modifiers,and most recently as angiogenesis inhibitors.The present review reports both the experimental and clinical results obtained in the field of clinical oncology,especially conducted by our group.The review also presents the possible future of integration of CM and modern medicine in basic research and clinical practice,especially when CM used as adjuvant and maintenance therapy.展开更多
The eukaryotic expression vector of human arresten gene was constructed and its secretive expression in human embryonic kidney(HEK 293)cells was detected.Human arresten gene was amplified from recombinant plasmid pGEM-...The eukaryotic expression vector of human arresten gene was constructed and its secretive expression in human embryonic kidney(HEK 293)cells was detected.Human arresten gene was amplified from recombinant plasmid pGEM-Arr by polymerase chain reaction(PCR),and then digested with restriction endonucleases BamH I and EcoR I.The target fragment was inserted into the BamH I and EcoR I restriction sites of eukaryotic expression vector pSecTag2 to construct pST-AT.Restric-tion analysis and DNA sequencing indicated that the arresten gene was successfully inserted into pSecTag2.The recombinant plasmid was subsequently transfected into HEK 293 cells with LipofectAMINETM2000 Reagent,and the expression of the target gene was detected.Reverse transcription PCR(RT-PCR)revealed that the mRNA of the target gene was transcribed in the transfected HEK 293 cells.Western blot analysis verified that the recombinant protein in supernatants was correct.The supernatants of transfected cells were prepared,and 3-(4,5)-dimethylthiazol(-2-y1)-3,5-di-phenyltetrazoliumbromide(MTT)assay was carried out to assess their effects on the proliferation of human umbilical vein endothelial cells,which showed that the recombinant protein could significantly suppress the proliferation of human umbilical vein endothelial cells in vitro.These results provided a solid foundation to explore the usage of arresten in tumor anti-angiogenic gene therapy.展开更多
基金supported by Grants from the Italian Association for Cancer Research(IG14532 and 12182 to RG)the Fondazione CARIPLO(No.2011-0614 to MC)
文摘Validated preclinical studies have provided evidence that anti-vascular endothelial growth factor(VEGF) compounds enhance the activity of subsequent antitumor therapy, but the mechanism of this potentiation is far from clear. The most widespread explanation is enhanced delivery of therapeutics due to vascular remodeling, lower interstitial pressure, and increased blood flow. While the antiangiogenic efects on vascular morphology have been fairly consistent in both preclinical and clinical settings, the improvement of tumor vessel function is debated. This review focuses on the efect of anti-VEGF therapy on tumor microenvironment morphology and functions, and its therapeutic beneits when combined with other therapies. The uptake and spatial distribution of chemotherapeutic agents into the tumor after anti-VEGF are examined.
基金Supported by Natural Science Foundation of Guangdong Province,No.2020A1515011539.
文摘BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.
文摘Canstatin is a novel inhibitor of angiogenesis and tumor growth, derived from the C-terminal globular non-collageneous (NCl) domain of the a2 chain of type IV collagen. It inhibits endothelial cell proliferation and migration in a dose-dependent manner, and induces endothelial cell apoptosis. In vivo experiments show that canstatin significantly inhibits solid tumor growth. The canstatin mediated inhibition of tumor is related to apoptosis. Canstatin- induced apoptosis is associated with phosphatidylinositol 3-kinase/Akt inhibition and is dependend upon signaling events transduced trough membrane death receptor.
文摘Objective Immune checkpoint inhibitor(ICI)plus angiogenesis inhibitor(AI)combination therapy is a novel treatment model for multiple cancers that normalizes vascular-immune crosstalk to potentiate cancer immunity.In this review,we summarize the characteristics of adverse effects(AEs)and all fatal cases reported in clinical studies involing ICI+AI therapy.Methods Four databases were systematically searched for eligible studies,and 28 relevant studies were selected for inclusion.Results Of the patients included,58.1%developed grade≥3 AEs.The most common fatal AEs were cardiovascular events,severe infections,and hemorrhage.Compared with AI alone,ICI+AI therapy resulted in more cases of grade≥3 proteinuria,liver injury,and fatal AEs(2.49%vs.1.28%,P=0.0041),especially respiratory toxicities and severe infections;however,ICI+AI therapy reduced hematological toxicity.Conclusion We shared comprehensive and practical safety data to review the adverse events associated with ICI+AI treatment.
文摘Liver cancer is one of the most common causes of cancer death globally,and its incidence in the United States is increasing.Patients with advanced hepatocellular carcinoma(HCC)who are not candidates for surgical resection,liver transplant,or locoregional therapies can be treated with systemic therapies.Multiple agents,including sorafenib,lenvatinib,and regorafenib are approved for use as either first-or second-line therapy in this patient population,but all have relatively modest survival benefits.HCC is potentially susceptible to therapy with checkpoint inhibitors,including agents such as nivolumab and pembrolizumab,which are both approved by the Food and Drug Administration for patients previously treated with sorafenib but have not demonstrated superior overall survival in phase III trials.It is clear that more effective approaches are needed to potentiate the effects of checkpoint inhibitors in patients with HCC.This review will outline and appraise the current literature on the use of checkpoint inhibitors in HCC as part of a combination treatment involving an additional mode of therapy.The list of agents that can be paired with checkpoint inhibitors includes an additional checkpoint inhibitor,vascular endothelial growth factor or vascular endothelial growth factor receptor inhibitors,tyrosine kinase inhibitors,OX-40 agonists,and PT-112 inhibitors.The main non-pharmacologic therapies currently being studied for inclusion in a combination strategy include radiation therapy,trans-arterial chemoembolization,and ablation.
基金supported by the Wu Jieping Medical Foundation Grant (No. 320.6750.11074)
文摘Bevacizumab, an angiogenesis inhibitor, is a recombined humanized monoclonal antibody against vascular endothelial growth factor and a promising therapeutic option for angiosarcoma management. This is a ease report and review of the literature using bevacizumab and combination chemotherapy for angiosarcoma. The understanding of the effectiveness of combined therapy of bevacizumab and chemotherapy agents is still limited. The benefits of bevacizumab treatment for angiosarcoma will need to be weighed against the risks of venous thromboembolism in this population.
基金Supported by NNSFC (No. 30500631)Graduate Innovative Research Foundation of Fudan University
文摘The title compound, C18H17BrO6 (Mr = 409.23), was synthesized as angiogenesis inhibitor and structurally characterized by ^1H-NMR, ^13C-NMR, MS, elemental analysis and X-ray single-crystal diffraction. Structure analysis indicates that the title compound is of triclinic, space group P1^-, with a = 8.100(3), b = 10.536(4), c = 11.689(5)A, a = 67.405(7), βl = 69.736(3), γ = 88.510(5)°, V = 857.3(5) A^3, Z = 2, Dc = 1.585 g/cm^3, μ = 2.429 mm^-1, F(000) = 416, the finial R = 0.0356 and wR = 0.0929 for 2541 observed reflections. The bond lengths of C(7)-C(16) proved that the title compound possesses coumarin rather than flavone scaffold.
基金This work was supported by a grant from the National Natural Science Foundation of China (No. 30472035).
文摘Background Tumstatin is a recently developed endogenous vascular endothelial growth inhibitor that can be applied as an anti-angiogenesis and antineoplastic agent. The study aimed to design and synthesize the small molecular angiogenesis inhibition-related peptide (peptide 21), to replicate the structural and functional features of the active zone of angiogenesis inhibition using tumstatin and to prove that synthesized peptide 21 has a similar activity: specifically inhibiting tumor angiogenesis like tumstatin. Methods Peptide 21 was designed and synthesized using biological engineering technology. To determine its biological action, the human umbilical vein endothelial cell line ECV304, the human ovarian cancer cell line SKOV-3 and the mouse embryo-derived NIH3T3 fibroblasts were used in in vitro experiments to determine the effect of peptide 21 on proliferation of the three cell lines using the MTT test and growth curves. Transmission electron microscopy (TEM) and flow cytometry (FCM) were applied to analyze the peptide 21-induced apoptosis of the three cell lines qualitatively and quantitatively. In animal experiments, tumor models in nude mice subcutaneously grafted with SKOV-3 were used to observe the effects of peptide 21 on tumor weight, size and microvessel density (MVD). To initially investigate the role of peptide 21, the effect of peptide 21 on the expression of vascular endothelial growth factors (VEGFs) by tumor tissue was semi-quantitatively analyzed. Results The in vitro Ml-r test and growth curves all indicated that cloned peptide 21 could specifically inhibit ECV304 proliferation in a dose-dependent manner (P 〈0.01); TEM and FCM showed that peptide 21 could specifically induce ECV304 apoptosis (P 〈0.01). Results of in vivo experiments showed that tumors in the peptide 21 group grew more slowly. The weight and size of the tumors after 21 days of treatment were smaller than those in the control group (P 〈0.05), with a mean tumor inhibition rate of 67.86%; MVD of the tumor tissue in the peptide 21 group was significantly lower than in the control group (P 〈0.05); the number of cells positive for VEGF in the peptide 21 group was significantly fewer than in the control group (P 〈0.01). Conclusions Similar to the activity of tumstatin in specifically inhibiting tumor angiogenesis, peptide 21 may specifically inhibit tumor endothelial cell proliferation and induce their apoptosis, thereby suppressing tumor angiogenesis and indirectly inhibit the growth, infiltration and metastasis of tumors. Peptide 21 may exert its effect through down-regulating the VEGF expression of tumor cells and vascular endothelial cells.
基金Province Development and Reform Commission,Grant/Award Numbers:2021C042-7,2021C043-1Chia-tai Tianqing 264 Pharmaceutical Group Co.,LtdProvincial Health and Family Planning。
文摘Background:The prognosis of patients with small cell lung cancer(SCLC)and brain metastases(BM)was poor.This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM.Methods:This was a subgroup analysis of the ALTER1202 trial,which was a randomized,placebo-controlled trial aimed to evaluate the role of anlotinib as third-line treatment or above in patients with SCLC.This study included patients with BM at baseline.The efficacy and safety outcomes included progression-free survival(PFS),overall survival(OS),central nervous system(CNS),objective response rate(ORR),CNS disease control rate(DCR),time to CNS progression,and adverse events(AEs).Results:Twenty-one and nine patients with BM were included in the anlotinib and placebo groups,respectively.The median PFS and OS were 3.8 months(95%confidence interval[CI]:1.8-6.1)and 6.1 months(95%CI:4.1-8.0)in the anlotinib group.Anlotinib was associated with a significant improvement in PFS(hazard ratio[HR]=0.15,95%CI:0.04-0.51,p=0.0005)and OS(HR=0.26,95%CI:0.09-0.73,p=0.0061)than placebo.Anlotinib significantly prolonged the time to CNS progression(p<0.0001).The anlotinib group had a higher CNS DCR than placebo(95.2%vs.22.2%,p=0.0001).The most common grade 3 or higher AEs were increased lipase(19.0%),hypertension(14.3%),and hyponatremia(14.3%)in the anlotinib group.Conclusions:Anlotinib proved to have potential CNS activity and a manageable toxicity profile in patients with SCLC and BM,significantly delaying CNS progression.
基金This research was supported by grants from the Guangdong Natural Science Foundation (No. S2012010010569) and the Guangdong Science and Technology Projects (No. 2011A030400009).
文摘Background The prognosis of unresectable large hepatocellular carcinomas is poor. This study evaluated the efficacy and safety of sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation in the treatment of hepatocellular carcinomas larger than 5 cm. Methods The treatment of 22 patients with large, unresectable hepatocellular carcinomas (5.0-16.5 cm) treated with sorafenib after transcatheter arterial chemoembolization combined with radiofrequency ablation between 2007 and 2011 was reviewed. The local effects, survival rates, toxicity, and prognostic factors were analyzed. Results During a follow-up of 9-49 months, 19 patients died and three survived. The median overall survival was 32 months. The overall cumulative 12, 24, and 36-month survival rates were 85.9%, 66.8%, and 23.5% respectively. Technical effectiveness was achieved in 12 out of 28 lesions (42.85%) at the first CT check. The median time to tumor progression was 21 months. The progression-free survival rates at 6, 12, and 24 months were 90.9%, 72.0%, and 38.4%, respectively. Combined therapy was generally well tolerated. There was only one major procedure-related complication, biloma (4.5%). Sorafenib-related adverse events exceeding grade 3 were hand-foot skin reaction (2/22, 9.1%), gastrointestinal hemorrhage (1/22, 4.5%), and diarrhea (2/22, 9.1%). The absence of vascular invasion before treatment was found to be the best prognostic factor in the univariate analysis. Conclusions Sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation is a promising approach to the treatment of large, unresectable hepatocellular carcinomas. However, large-scale randomized clinical trials are needed to determine the future role of this treatment.
基金the National Natural Science Foundation of China(From Regulating Pathological Angiogenesis and the Hepatic Fibrosis Way to Compare the Effects and Mechanisms between Taohongsiwu Decoction and its Absorbed Bioactive Compound,No.81202659)the Xiamen Science and Technology Key Program Plan Grant(Prevention and Treatment Mechanism Study of Traditional Chinese Medicine on Common Digestive Tract Cancer of Fujian and Taiwan,No.3502Z20100006)+2 种基金the Xiamen Science and Technology Program Plan Grant(the Development and Application and Basic Research of Ciji Hua'ai Baosheng Soluble Granules,No.3502Z20153027)the Natural Science Foundation of Fujian(China)(Negative Effect of Safflower Ingredient and Taohong formula on Mechanism of Pathological Angiogenesis and PI3K-Akt Signaling,No.2014J01373)the Scientific Research Start Foundation for New Teacher of Xiamen University(Correlated Mechanism Study of Safflower Ingredient Regulating Digestive Tract Tumor,No.ZK1014)
文摘OBJECTIVE: To investigate the efficacy of Ciji Hua'ai Baosheng formula(CHBF) on microvessel density(MVD) and vascular endothelial growth factor(VEGF), kinase insert domain-containing receptor(KDR) and basic fibroblast growth factor(b FGF) expression in serum and tumor tissue of mice receiving chemotherapy for the treatment of H22 hepatocellular carcinoma.METHODS: Sixty Kunming mice were injected subcutaneously with H22 hepatoma carcinoma cell suspensions into the right anterior armpit. Seven days later, all transplanted tumor were formed and the mice were intraperitoneally injected 200 mg/kg cytoxan(CTX) to establish the models of tumor-bearing mouse chemotherapy, then they were randomly divided into model group, continuing CTX chemotherapy group(CTX group), and three CHBF(117, 58.5 and 29.25 g/kg) groups. After ten days of treatments, histology was observed, contents of VEGF, KDR and b FGF in serum and tumor tissue were measured by enzyme-linked immunosorbent assay(ELISA), VEGF and b FGF protein expression and MVD tagged by CD34 were detected by immunohistochemisty.RESULTS: MVD in CHBF(117, 58.5 g/kg) and CTX groups was significantly lower than that in model group(P < 0.01); expressions of VEGF, KDR and b FGF in serum and tumor tissue in CHBF(117 g/kg)group were less than those in model group(P <0.05; P < 0.01); the expressions of MVD, VEGF and b FGF in tumor tissue of CHBF(117 g/kg) groupwere also less than those in CTX group(P < 0.05;P < 0.01).CONCLUSION: CHBF can effectively reduce the expression of VEGF, KDR and b FGF in serum and tumor tissue, and decrease MVD and delay tumor progression.
文摘Chinese Medicine(CM)has been used for several thousand years,playing an important role in the prevention and treatment of diseases including cancer.In the recent four decades,a number of CM herbs have aroused extreme interest in the world-isolating anticancer components from medicinal herbs,using them as biological response modifiers,and most recently as angiogenesis inhibitors.The present review reports both the experimental and clinical results obtained in the field of clinical oncology,especially conducted by our group.The review also presents the possible future of integration of CM and modern medicine in basic research and clinical practice,especially when CM used as adjuvant and maintenance therapy.
基金supported by the National Natural Science Foundation of China(Grant Nos.30271242 and 30371396).
文摘The eukaryotic expression vector of human arresten gene was constructed and its secretive expression in human embryonic kidney(HEK 293)cells was detected.Human arresten gene was amplified from recombinant plasmid pGEM-Arr by polymerase chain reaction(PCR),and then digested with restriction endonucleases BamH I and EcoR I.The target fragment was inserted into the BamH I and EcoR I restriction sites of eukaryotic expression vector pSecTag2 to construct pST-AT.Restric-tion analysis and DNA sequencing indicated that the arresten gene was successfully inserted into pSecTag2.The recombinant plasmid was subsequently transfected into HEK 293 cells with LipofectAMINETM2000 Reagent,and the expression of the target gene was detected.Reverse transcription PCR(RT-PCR)revealed that the mRNA of the target gene was transcribed in the transfected HEK 293 cells.Western blot analysis verified that the recombinant protein in supernatants was correct.The supernatants of transfected cells were prepared,and 3-(4,5)-dimethylthiazol(-2-y1)-3,5-di-phenyltetrazoliumbromide(MTT)assay was carried out to assess their effects on the proliferation of human umbilical vein endothelial cells,which showed that the recombinant protein could significantly suppress the proliferation of human umbilical vein endothelial cells in vitro.These results provided a solid foundation to explore the usage of arresten in tumor anti-angiogenic gene therapy.