Deoxypodophyllotoxin not only has pharmacological effects such as anti-allergy,anti-angiogenesis and liver protection,but also has good anti-tumor activity.It can play an anti-tumor role by inhibiting cell viability,i...Deoxypodophyllotoxin not only has pharmacological effects such as anti-allergy,anti-angiogenesis and liver protection,but also has good anti-tumor activity.It can play an anti-tumor role by inhibiting cell viability,inducing apoptosis,blocking cell cycle and inhibiting cell migration.In this paper,the related research on pharmacological effect and mechanism of deoxypodophyllotoxin is reviewed,to lay a foundation for the follow-up study of deoxypodophyllotoxin and drug development.展开更多
Background:Small cell lung cancer(SCLC)is an aggressive malignant tumor with strong immunosuppressive effects,characterized by rapid doubling time and poor prognosis.Currently,effective therapeutic options are urgentl...Background:Small cell lung cancer(SCLC)is an aggressive malignant tumor with strong immunosuppressive effects,characterized by rapid doubling time and poor prognosis.Currently,effective therapeutic options are urgently needed for Extensive-stage small-cell lung Cancer.Case description:In the present case,a combination therapy of anlotinib,envolizumab,and etoposide was administered to treat an 80-year-old female patient with extensive-stage SCLC accompanied by mediastinal lymph node and bone metastasis.After two cycles of treatment,the tumor lesions in the right lungs decreased from 5.04*3.44 cm to 1.65*1.42 cm.As of now,no significant mass is seen there and no serious adverse reactions in this patient.Until September 2023,she has survived for 18 months with no disease progression.Conclusions:Research shows that Alectinib,in combination with evolocumab plus etoposide,could be an original,viable therapeutic option for the treatment option of patients with extensive-stage SCLC.展开更多
Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidati...Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)production and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1a(HIF-1a),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H_(2)O_(2) signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1a,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.展开更多
Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effec...Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effective treatment now. As an active research direction at present, anti-angiogenic drugs are not only widely used in non-small cell lung cancer and other tumors, but also have certain effects in small cell lung cancer combined with chemotherapy. As one of the effective treatment methods for small cell lung cancer, related research is not rare, but there is still inadequacy, such as side effects can not be tolerated, and the timing of treatment can not be accurately assessed. This article will briefly describe the research progress of anti-angiogenic drugs combined with chemotherapy in the first-line treatment of extensive small cell lung cancer.展开更多
Chemotherapy has limited efficacy in the treatment of advanced and metastatic pancreatic cancer(PC), and has serious side effects. The development of novel effective agents, especially targeted therapy, is essential f...Chemotherapy has limited efficacy in the treatment of advanced and metastatic pancreatic cancer(PC), and has serious side effects. The development of novel effective agents, especially targeted therapy, is essential for patients with PC. We present a 58-year-old Chinese woman initially diagnosed with locally advanced PC. As the disease progressed to Stage Ⅳ, the patient was unable to tolerate chemotherapy after the fourth-line treatment. She was then treated with apatinib, a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 and achieved a progression-free-survival of 7 mo. All drug-related side effects were well controlled with medication. To the best of our knowledge, this is the first case of PC which responded to apatinib. Considering this remarkable response, apatinib may be a promising agent in the treatment of PC. We also reviewed the literature on chemotherapy and targeted therapy, especially the anti-angiogenesis therapy for patients with PC, and investigated the effect of apatinib in other solid tumors as well.展开更多
Objective:To explore the in vivo anticancer,anti-angiogenesis and immunomodulatory efficacies of the bioactive polysaccharide isolated from cold aqueous extract of Jania rubens(JCEM) and Pterocladia capillacea(PCEM) a...Objective:To explore the in vivo anticancer,anti-angiogenesis and immunomodulatory efficacies of the bioactive polysaccharide isolated from cold aqueous extract of Jania rubens(JCEM) and Pterocladia capillacea(PCEM) as well as hot aqueous extract of Enteromorpha intestinalis(EHEM) against hepatocellular carcinoma rat model(HCC) and to study their chemical composition.Methods:The sugars and amino acids composition of the bioactive polysaccharides of JCEM,PCEM and EHEM were determined using gas liquid chromatography and amino acid analyzer,respectively.These polysaccharide extracts(20 mg/kg b.wt.for 5 weeks) were assessed on hepatocarcinogenesis in rats and α-fetoprotein(AFP),carcinoembryonic antigen(CEA),glypican-3(GPC-3),hepatocyte growth factor(HGF) and vascular endothelial growth factor(VEGF) and Ig G levels were evaluated.Results:The GLC analysis of JCEM,PCEM and EHEM polysaccharide revealed the presence of 10,9 and10 sugars,in addition the amino acid analyser enable identification of 16,15 and 15 amino acids,respectively.These polysaccharide extracts of JCEM,PCEM and EHEM produced significant decrease in serum AFP,CEA,GPC-3,HGF and VEGF compared with untreated HCC group.JCEM,PCEM and EHEM had an immunostimulatory responses by increasing the IgG levels as compared by naive value(1.23,1.53 and 1.17 folds),respectively.The bioactive polysaccharides in HCC induced rats improved the humoral immune response.The photomicrographs of liver tissue sections of the groups of HCC treated with polysaccharide extracts of Jania rubens and Enteromorpha intestinalis showed intact histological structure.Moreover,fractions HE1,HE4,HE7 obtained from polysaccharide of EHEM showed moderate cytotoxic activity against Hep G2 in vitro with IC_(50) 73.1,42.6,76.2 μg/mL.However,fractions of PCEM and JCEM show no or weak cytotoxicity against Hep G2 in vitro where the cytotoxic activity of their crude polysaccharide extract proved synergetic effect.Conclusions:The pronounced antitumor activity of sulphated polysaccharide-protein complexes of JCEM and EHEM is due to direct cytotoxic activity,anti-hepatocarcinogensis,and anti-angiogenesis.In addition,JCEM,PCEM and EHEM had an immunostimulatory response and improved the humoral immune response in HCC induced rats.展开更多
Despite improvements in the early diagnosis,prognosis and therapeutic strategies for gastric cancer(GC),human GC remains one of the most frequently diagnosed malignant tumors in the world,and the survival rate of GC p...Despite improvements in the early diagnosis,prognosis and therapeutic strategies for gastric cancer(GC),human GC remains one of the most frequently diagnosed malignant tumors in the world,and the survival rate of GC patients remains very poor.Thus,a suitable therapeutic strategy for GC is important for prolonging survival.Both tumor cells themselves and the tumor microenvironment play an important role in tumorigenesis,including angiogenesis,inflammation,immunosuppression and metastasis.Importantly,these cells contribute to gastric carcinogenesis by altering the angiogenic phenotype switch.The development,relapse and spreading of tumors depend on new vessels that provide the nutrition,growth factors and oxygen required for continuous tumor growth.Therefore,a state of tumor dormancy could be induced by blocking tumor-associated angiogenesis.Recently,several antiangiogenic agents have been identified,and their potential for the clinical management of GC has been tested.Here,we provide an up-to-date summary of angiogenesis and the angiogenic factors associated with tumor progression in GC.We also review antiangiogenic agents with a focus on the anti-vascular endothelial growth factor receptor(VEGFR)-mediated pathway for endothelial cell growth and their angiogenesis ability in GC.However,most antiangiogenic agents have reported no benefit to overall survival(OS)compared to chemotherapy alone in local or advanced GC.In phase III clinical trials,only ramucirumab(anti-VEGFR blocker)and apatinib(VEGFR-TKI blocker)have reported an improved median overall response rate and prolonged OS and progression-free survival outcomes as a 2 nd-line agent combined with chemotherapy treatment in advanced GC.By providing insights into the molecular mechanisms of angiogenesis associated with tumor progression in GC,this review will hopefully aid the optimization of antiangiogenesis strategies for GC therapy in combination with chemotherapy and adjuvant treatment.展开更多
Objective:To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the antiangiogenesis therapy.Methods:The siRNA tech...Objective:To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the antiangiogenesis therapy.Methods:The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor(VEGF) in A549 cells and simulate the clinical course of anti-angiogencsis therapy.Real-time PCR and western-blot were used to study the change in the expression of Wnt/β-catenin signaling molecules at the mRNA and protein level respectively,as well as the effect on the epithelial mesenchymal transition in A549 cells.The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy.Results:The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy.Under the action of 50 nM VEGF siRNA,the proliferation ability of A549 significantly increased(P<0.05).After being treated with VEGF siRNA,the invasion ability of cells increased.Twenty-four hours after the transcription of 50 nM siRNA into cells,the number of cells that come through the membrane was278.3 ± 12.9.Compared with the Ctrl siRNA group,when VEGF was inhibited,the expression ofβ-catenin and Cyclin D1 increased by 86%and 55%respectively.Meanwhile,the expression of E-cadherin decreased,while the one of vimentin increased.Conclusions:siRNA can significantly inhibit the expression of VEGF.For the anti-angiogencsis therapy,the inhibited expression of VEGF can activate the Wnt/β-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer.展开更多
Objective To investigate the clinical effects and safety of bevacizumab combined with S-1 as the second-line treatment of recurrent and/or metastatic esophageal cancer after chemoradiation. Methods Patients with recur...Objective To investigate the clinical effects and safety of bevacizumab combined with S-1 as the second-line treatment of recurrent and/or metastatic esophageal cancer after chemoradiation. Methods Patients with recurrent or metastatic esophageal cancer after chemoradiation were treated with bevacizumab and S-1. Bevacizumab was used by intravenous infusion, 7.5mg/kg body weight on day 1; S-1 was used by oral at 80mg/m^2·d on day 1-14, 21 days as a cycle of treatment and repeated until either progressive disease or intolerable toxicity occurred. Chest CT were performed and RECIST 1.1 was used for response evaluation. Kaplan-Meier method was used for survival analysis. Side effects were recorded and analyzed. Results Totally 78 patients were enrolled in the study, including 67 squamous cell carcinoma and 11 adenocarcinoma histologically. The overall response(CR+PR) rate was 22.4%(17/76) and disease control(CR+PR+SD) rate was 61.8%(47/76) respectively. The median follow-up time was 20 months(range from 9 to 44 months). The median progression-free survival(PFS) was 4.9 months(95% CI 4.4-5.5) and the median overall survival(OS) was 8.1 months(95% CI 7.6-9.2). The median PFS and OS of patients with metastasis diseases were 6.2 months(95% CI 3.3 to 6.3) and 8.5 months(95% CI 5.8 to 11.2), where PFS was longer than that of patients with local regional recurrence(median 5.0 months, 95% CI 3.0 to 5.5, P=0.017) and OS was longer than that of patients with regional disease and metastasis(median 8.0 months, 95% CI 4.6 to 9.5, P=0.010). The common adverse effects were mild to moderate neutropenia(84.2%), grade Ⅰ -Ⅱ hand and foot syndrome(51.3%), grade Ⅰ -Ⅱ nausea(48.7%), mild epistaxis(30.1%) and mild vomiting(14.5%). Esophageal bleeding occurred in 7.9% of patients. One patient(1.3%) died from massive bleeding which was caused by esophageal perforation. Conclusion Bevacizumab combined with S-1 was effective and safe for esophageal cancer patients who had recurrent or metastatic diseases after chemoradiation.展开更多
Objective To construct lentivirus vectors carrying alphastatin gene,test its secretion expression in human umbilical vein endothelia cells(HUVECs)and observe its effects on growth,migration and tube formation of HUVEC...Objective To construct lentivirus vectors carrying alphastatin gene,test its secretion expression in human umbilical vein endothelia cells(HUVECs)and observe its effects on growth,migration and tube formation of HUVECs.Methods We constructed recombinant lentivirus vectors of NT4-alphastatin fusion gene containing neurotrophin-4 signal peptide,pro-region sequences and alphastatin,then transfected the recombinant lentivirus vectors into HUVECs to obtain secretory protein alphastatin and test its anti-angiogenic activities in vitro.Results Our data showed that recombinant self-inactivating lentivirus vectors of NT4-alphastatin were successfully constructed,and stable NT4-alphastatin transduced HUVECs were capable of sustainably secreting alphastatin which significantly suppressed HUVECs migration and differentiation but not VEGF-induced proliferation.Conclusion This report represents the first time on the use of lentivirus-based vectors to deliver alphastatin,the endogenous angiogenesis inhibitor,and reveals the potential utility of anti-angiogenic gene therapy with lentivirus vectors for treating cancer.展开更多
Over the past couple of decades considerable progress has been made in the management of metastatic colorectal cancers(mCRC) leading to a significant improvement in five-year survival. Although part of this success ha...Over the past couple of decades considerable progress has been made in the management of metastatic colorectal cancers(mCRC) leading to a significant improvement in five-year survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of cancer and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article we will discuss various targeted therapies in the management of mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well.展开更多
A mathematical optimal-control tumor therapy framework consisting of radio- and anti-angiogenesis control strategies that are included in a tumor growth model is investigated. The governing system, resulting from the ...A mathematical optimal-control tumor therapy framework consisting of radio- and anti-angiogenesis control strategies that are included in a tumor growth model is investigated. The governing system, resulting from the combination of two well established models, represents the differential constraint of a non-smooth optimal control problem that aims at reducing the volume of the tumor while keeping the radio- and anti-angiogenesis chemical dosage to a minimum. Existence of optimal solutions is proved and necessary conditions are formulated in terms of the Pontryagin maximum principle. Based on this principle, a so-called sequential quadratic Hamiltonian (SQH) method is discussed and benchmarked with an “interior point optimizer—a mathematical programming language” (IPOPT-AMPL) algorithm. Results of numerical experiments are presented that successfully validate the SQH solution scheme. Further, it is shown how to choose the optimisation weights in order to obtain treatment functions that successfully reduce the tumor volume to zero.展开更多
In human patients,drugs that block tumor vessel growth are widely used to treat a variety of cancer types.Many rigorous phase 3 clinical trials have demonstrated significant survival benefits;however,the addition of a...In human patients,drugs that block tumor vessel growth are widely used to treat a variety of cancer types.Many rigorous phase 3 clinical trials have demonstrated significant survival benefits;however,the addition of an anti-angiogenic component to conventional therapeutic modalities has generally produced modest survival benefits for cancer patients.Currently,it is unclear why these clinically available drugs targeting the same angiogenic pathways produce dissimilar effects in preclinical models and human patients.In this article,we discuss possible mechanisms of various anti-angiogenic drugs and the future development of optimized treatment regimens.展开更多
The disease burden related to hepatocellular carcinoma(HCC) is increasing. Most HCC patients are diagnosed at the advanced stage and multikinase inhibitors have been the only treatment choice for them. Recently, the a...The disease burden related to hepatocellular carcinoma(HCC) is increasing. Most HCC patients are diagnosed at the advanced stage and multikinase inhibitors have been the only treatment choice for them. Recently, the approval of immune checkpoint inhibitors(ICIs) has provided a new therapeutic strategy for HCC. It is noteworthy that the positive outcomes of the phase Ⅲ clinical trial IMBrave150 [atezolizumab(anti-programmed cell death ligand 1 antibody) combined with bevacizumab(anti-vascular endothelial growth factor monoclonal antibody)],showed that overall survival and progression-free survival were significantly better with sorafenib. This combination therapy has become the new standard therapy for advanced HCC and has also attracted more attention in the treatment of HCC with anti-angiogenesis-immune combination therapy. Currently, the synergistic antitumor efficacy of this combination has been shown in many preclinical and clinical studies. In this review, we discuss the mechanism and clinical application of anti-angiogenics and immunotherapy in HCC, outline the relevant mechanism and rationality of the combined application of antiangiogenics and ICIs, and point out the existing challenges of the combination therapy.展开更多
The effects of anti-angiogenesis treatment by angiostatin and endostatin on normalization of tumor microvasculature and microenvironment are investigated,based on mathematical modeling and numerical simulation of tumo...The effects of anti-angiogenesis treatment by angiostatin and endostatin on normalization of tumor microvasculature and microenvironment are investigated,based on mathematical modeling and numerical simulation of tumor anti-angiogenesis and tumor haemodynamics.The results show that after anti-angiogenesis treatment:(i) the proliferation,growth,and branching of neo-vessels are effectively inhibited,and the extent of vascularization in tumors is accordingly reduced.(ii) the overall blood perfusion inside of tumor is declined,the plateau of tumor interstitial fluid pressure(IFP) is relieved,the interstitial fluid oozing out from the tumor periphery into the surrounding normal tissue is reduced,the reduction of overall extravasation across vasculature to tumor interstium is much less than the decreased overall blood perfusion,due to the decline of IFP,the intravasations is remarkablely effected by the change,in some cases there are no intravasation flow appear.展开更多
In light of the intriguing potential of anti-angiogenic approach in suppressing choroidal neovascularization, we attempted to elaborate synthetic gene delivery systems encapsulating anti-angiogenic plasmid DNA as alte...In light of the intriguing potential of anti-angiogenic approach in suppressing choroidal neovascularization, we attempted to elaborate synthetic gene delivery systems encapsulating anti-angiogenic plasmid DNA as alternatives of clinical antibody-based therapeutics. Herein, block copolymer of cyclic Arg-Gly-Asp-poly(ethylene glycol)-poly(lysine-thiol) [RGD-PEG-PLys(thiol)] with multifunctional components was tailored in manufacture of core-shell DNA delivery nanoparticulates. Note that the polycationic PLys segments were electrostatically complexed with anionic plasmid DNA into nanoscaled core, and the tethered biocompatible PEG segments presented as the spatial shell(minimizing non-specific reactions in biological milieu). Furthermore, the aforementioned self-assembly was introduced with redox-responsive disulfide crosslinking due to the thiol coupling. Hence, reversible stabilities, namely stable in extracellular milieu but susceptible to disassemble for liberation of the DNA payloads in intracellular reducing microenvironment, were verified to facilitate transcellular gene transportation. In addition, RGD was installed onto the surface of the proposed self-assemblies with aim of targeted accumulation and internalization into angiogenic endothelial cells given that RGD receptors were specifically overexpressed on their cytomembrane surface. The proposed anti-angiogenic DNA therapeutics were validated to exert efficient expression of anti-angiogenic proteins in endothelial cells and elicit potent inhibition of ocular neovasculature post intravitreous administration. Hence, the present study approved the potential of gene therapy in treatment of choroidal neovascularization. In light of sustainable gene expression properties of DNA therapeutics, our proposed synthetic gene delivery system inspired prosperous potentials in long-term treatment of choroidal neovascularization, which should be emphasized to develop further towards clinical translations.展开更多
In search of synthetic chemotherapeutic substances capable of inhibiting, retarding, or reversing the process of multi-stage carcinogenesis, we synthesized a series of novel 5-amino pyrazole derivatives 11(a-h) by a n...In search of synthetic chemotherapeutic substances capable of inhibiting, retarding, or reversing the process of multi-stage carcinogenesis, we synthesized a series of novel 5-amino pyrazole derivatives 11(a-h) by a nucleophilic substitution reaction and characterized by 1H nuclear magnetic resonance (NMR), liquid chromatography mass spectrometry (LC/MS), Fourier-transform infrared (FTIR), and elemental analysis. These novel compounds were evaluated for their efficacy in inhibiting Ehrlich ascites tumor [EAT] cells in-vivo. In the present study we designed, synthesized, characterized and investigate the anti-angiogenic effects of these compounds, on Ehrlich ascites tumor [EAT] cells in-vivo. The compounds were subsequently tested for their ability to inhibit neovascularisation in chorio allantoin membrane (CAM) model. From the Structure Activity Relationship (SAR) studies, it reveals that, the substitution at N-terminal in pyrazole ring plays key role in the antitumor and anti-angiogenic effects.展开更多
Novel heterocyclic analogs of resveratrol, (E)-stilbene analogs, were readily prepared by conjugation of a heterocyclic benzothiazolium moiety with the core styrene structure of resveratrol and evaluated for their bio...Novel heterocyclic analogs of resveratrol, (E)-stilbene analogs, were readily prepared by conjugation of a heterocyclic benzothiazolium moiety with the core styrene structure of resveratrol and evaluated for their biological properties. The results showed that these analogs were superior to resveratrol in 1) anti-angiogenesis in vitro, 2) nitric oxide inhibition in vitro, and 3) inhibition of carrageenan-induced edema in vivo. In summary, introduction of a heterocyclic benzothiazolium moiety to replace one of two aromatic rings from the core stilbene structure of resveratrol provided beneficial biological properties and is worthy of further investigation.展开更多
The global burden of ovarian cancer is gradually increasing while patients still suffer from relatively limited treatment options.With recent advances in the decoding of the molecular landscape of ovarian cancer,more ...The global burden of ovarian cancer is gradually increasing while patients still suffer from relatively limited treatment options.With recent advances in the decoding of the molecular landscape of ovarian cancer,more options in targeted strategy were offered and can therefore be tailored in different clinical settings for individual patient.Targeting of the abnormal angiogenesis process is the first significant clinical breakthrough which revolutionized the treatment of advanced ovarian cancer,followed by the advent of poly-(ADP)-ribose polymerase(PARP)inhibitors.These two strategies represented by bevacizumab and olaparib respectively underwent tests of numerous clinical trials.In recent years,immune checkpoint inhibitors(ICIs)have been incorporated into the blueprint of ovarian cancer treatment though the effectiveness still left much to be desired.Herein,we systematically outlined recent advances in targeted therapy for ovarian cancer and summarized the landmark clinical trials for each targeted therapy including angiogenesis inhibitors,PARP inhibitors and ICIs.展开更多
Tetrandrine (1 μM), a bis-benzylisoquinoline alkaloid isolated from Stephania tetrandra S Moore, signifi-cantly decreased tumor necrosis factor alpha (TNFα;10 ng/ml)-induced increase in the number of micro vessels t...Tetrandrine (1 μM), a bis-benzylisoquinoline alkaloid isolated from Stephania tetrandra S Moore, signifi-cantly decreased tumor necrosis factor alpha (TNFα;10 ng/ml)-induced increase in the number of micro vessels that budded from cultured rat choroidal explants. Tetrandrine also decreased the TNFα-induced in-crease in the number of cells composing the microvessels. Ammonium pyrrolidine dithiocarbamate (APDC;0.1-0.3 μM), an inhibitor of nuclear factor-κB (NF-κB), decreased the TNFα-induced increase in the number of microvessels in a concentration-dependent manner. TNFα increased the phosphorylation and degradation of inhibitor of NF-κB (IκBα), as well as increasing the DNA-binding activity of NF-κB in choroidal explants. TNF? induced an increase of vascular endothelial growth factor (VEGF)-A mRNA, but not VEGF-C mRNA or VEGF-D mRNA. TNFα-induced angiogenic action was inhibited by treatment of VEGF-A antibody in cultured choroidal capillaries. Tetrandrine inhibited the TNFα-induced increases of phosphorylation and degradation of IκBα, and reduced the TNFα-induced increase of DNA-binding activity of NF-κB in chor-oidal explants. In conclusion, tetrandrine inhibits TNFα-induced activation of NF-κB in the choroidal capil-laries via inhibition of TNFα-induced phosphorylation of IκBα.展开更多
基金Supported by the Talent Training Program for the Reform and Development of Local Colleges and University of the Central Government(2020GSP16)Innovation and Entrepreneurship Training Program for College Students in Heilongjiang Province(202210223048)。
文摘Deoxypodophyllotoxin not only has pharmacological effects such as anti-allergy,anti-angiogenesis and liver protection,but also has good anti-tumor activity.It can play an anti-tumor role by inhibiting cell viability,inducing apoptosis,blocking cell cycle and inhibiting cell migration.In this paper,the related research on pharmacological effect and mechanism of deoxypodophyllotoxin is reviewed,to lay a foundation for the follow-up study of deoxypodophyllotoxin and drug development.
文摘Background:Small cell lung cancer(SCLC)is an aggressive malignant tumor with strong immunosuppressive effects,characterized by rapid doubling time and poor prognosis.Currently,effective therapeutic options are urgently needed for Extensive-stage small-cell lung Cancer.Case description:In the present case,a combination therapy of anlotinib,envolizumab,and etoposide was administered to treat an 80-year-old female patient with extensive-stage SCLC accompanied by mediastinal lymph node and bone metastasis.After two cycles of treatment,the tumor lesions in the right lungs decreased from 5.04*3.44 cm to 1.65*1.42 cm.As of now,no significant mass is seen there and no serious adverse reactions in this patient.Until September 2023,she has survived for 18 months with no disease progression.Conclusions:Research shows that Alectinib,in combination with evolocumab plus etoposide,could be an original,viable therapeutic option for the treatment option of patients with extensive-stage SCLC.
文摘Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)production and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1a(HIF-1a),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H_(2)O_(2) signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1a,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.
文摘Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effective treatment now. As an active research direction at present, anti-angiogenic drugs are not only widely used in non-small cell lung cancer and other tumors, but also have certain effects in small cell lung cancer combined with chemotherapy. As one of the effective treatment methods for small cell lung cancer, related research is not rare, but there is still inadequacy, such as side effects can not be tolerated, and the timing of treatment can not be accurately assessed. This article will briefly describe the research progress of anti-angiogenic drugs combined with chemotherapy in the first-line treatment of extensive small cell lung cancer.
基金Supported by The National Natural Science Foundation of China,No.81402299the Project of Postdoctoral Innovation of Shandong Province,No.201501010the Project of Postdoctoral Science Foundation of China,No.2016M590640
文摘Chemotherapy has limited efficacy in the treatment of advanced and metastatic pancreatic cancer(PC), and has serious side effects. The development of novel effective agents, especially targeted therapy, is essential for patients with PC. We present a 58-year-old Chinese woman initially diagnosed with locally advanced PC. As the disease progressed to Stage Ⅳ, the patient was unable to tolerate chemotherapy after the fourth-line treatment. She was then treated with apatinib, a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 and achieved a progression-free-survival of 7 mo. All drug-related side effects were well controlled with medication. To the best of our knowledge, this is the first case of PC which responded to apatinib. Considering this remarkable response, apatinib may be a promising agent in the treatment of PC. We also reviewed the literature on chemotherapy and targeted therapy, especially the anti-angiogenesis therapy for patients with PC, and investigated the effect of apatinib in other solid tumors as well.
基金the National Research Centre for the financial support with Grant No.9080104
文摘Objective:To explore the in vivo anticancer,anti-angiogenesis and immunomodulatory efficacies of the bioactive polysaccharide isolated from cold aqueous extract of Jania rubens(JCEM) and Pterocladia capillacea(PCEM) as well as hot aqueous extract of Enteromorpha intestinalis(EHEM) against hepatocellular carcinoma rat model(HCC) and to study their chemical composition.Methods:The sugars and amino acids composition of the bioactive polysaccharides of JCEM,PCEM and EHEM were determined using gas liquid chromatography and amino acid analyzer,respectively.These polysaccharide extracts(20 mg/kg b.wt.for 5 weeks) were assessed on hepatocarcinogenesis in rats and α-fetoprotein(AFP),carcinoembryonic antigen(CEA),glypican-3(GPC-3),hepatocyte growth factor(HGF) and vascular endothelial growth factor(VEGF) and Ig G levels were evaluated.Results:The GLC analysis of JCEM,PCEM and EHEM polysaccharide revealed the presence of 10,9 and10 sugars,in addition the amino acid analyser enable identification of 16,15 and 15 amino acids,respectively.These polysaccharide extracts of JCEM,PCEM and EHEM produced significant decrease in serum AFP,CEA,GPC-3,HGF and VEGF compared with untreated HCC group.JCEM,PCEM and EHEM had an immunostimulatory responses by increasing the IgG levels as compared by naive value(1.23,1.53 and 1.17 folds),respectively.The bioactive polysaccharides in HCC induced rats improved the humoral immune response.The photomicrographs of liver tissue sections of the groups of HCC treated with polysaccharide extracts of Jania rubens and Enteromorpha intestinalis showed intact histological structure.Moreover,fractions HE1,HE4,HE7 obtained from polysaccharide of EHEM showed moderate cytotoxic activity against Hep G2 in vitro with IC_(50) 73.1,42.6,76.2 μg/mL.However,fractions of PCEM and JCEM show no or weak cytotoxicity against Hep G2 in vitro where the cytotoxic activity of their crude polysaccharide extract proved synergetic effect.Conclusions:The pronounced antitumor activity of sulphated polysaccharide-protein complexes of JCEM and EHEM is due to direct cytotoxic activity,anti-hepatocarcinogensis,and anti-angiogenesis.In addition,JCEM,PCEM and EHEM had an immunostimulatory response and improved the humoral immune response in HCC induced rats.
基金Supported by the Ministry of Science and Technology,Taiwan,No.MOST 106-2320-B-255-005 and No.MOST 107-2320-B-255-003Chang Gung Medical Research Foundation,Taoyuan,Taiwan,No.CMRPF1G0011,No.CMRPF1G0251,No.CMRPF1I0031,No.CMRPF1H0051,and No.CMRPF1I0041Chang Gung University of Science and Technology,Taoyuan,Taiwan,No.ZRRPF3H0131
文摘Despite improvements in the early diagnosis,prognosis and therapeutic strategies for gastric cancer(GC),human GC remains one of the most frequently diagnosed malignant tumors in the world,and the survival rate of GC patients remains very poor.Thus,a suitable therapeutic strategy for GC is important for prolonging survival.Both tumor cells themselves and the tumor microenvironment play an important role in tumorigenesis,including angiogenesis,inflammation,immunosuppression and metastasis.Importantly,these cells contribute to gastric carcinogenesis by altering the angiogenic phenotype switch.The development,relapse and spreading of tumors depend on new vessels that provide the nutrition,growth factors and oxygen required for continuous tumor growth.Therefore,a state of tumor dormancy could be induced by blocking tumor-associated angiogenesis.Recently,several antiangiogenic agents have been identified,and their potential for the clinical management of GC has been tested.Here,we provide an up-to-date summary of angiogenesis and the angiogenic factors associated with tumor progression in GC.We also review antiangiogenic agents with a focus on the anti-vascular endothelial growth factor receptor(VEGFR)-mediated pathway for endothelial cell growth and their angiogenesis ability in GC.However,most antiangiogenic agents have reported no benefit to overall survival(OS)compared to chemotherapy alone in local or advanced GC.In phase III clinical trials,only ramucirumab(anti-VEGFR blocker)and apatinib(VEGFR-TKI blocker)have reported an improved median overall response rate and prolonged OS and progression-free survival outcomes as a 2 nd-line agent combined with chemotherapy treatment in advanced GC.By providing insights into the molecular mechanisms of angiogenesis associated with tumor progression in GC,this review will hopefully aid the optimization of antiangiogenesis strategies for GC therapy in combination with chemotherapy and adjuvant treatment.
基金supported by National Natural Science Foundation(No.81372530)
文摘Objective:To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the antiangiogenesis therapy.Methods:The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor(VEGF) in A549 cells and simulate the clinical course of anti-angiogencsis therapy.Real-time PCR and western-blot were used to study the change in the expression of Wnt/β-catenin signaling molecules at the mRNA and protein level respectively,as well as the effect on the epithelial mesenchymal transition in A549 cells.The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy.Results:The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy.Under the action of 50 nM VEGF siRNA,the proliferation ability of A549 significantly increased(P<0.05).After being treated with VEGF siRNA,the invasion ability of cells increased.Twenty-four hours after the transcription of 50 nM siRNA into cells,the number of cells that come through the membrane was278.3 ± 12.9.Compared with the Ctrl siRNA group,when VEGF was inhibited,the expression ofβ-catenin and Cyclin D1 increased by 86%and 55%respectively.Meanwhile,the expression of E-cadherin decreased,while the one of vimentin increased.Conclusions:siRNA can significantly inhibit the expression of VEGF.For the anti-angiogencsis therapy,the inhibited expression of VEGF can activate the Wnt/β-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer.
基金Supported by Medical Technology Research Center for Health Development Grant[W2012FZ007(YJ)]
文摘Objective To investigate the clinical effects and safety of bevacizumab combined with S-1 as the second-line treatment of recurrent and/or metastatic esophageal cancer after chemoradiation. Methods Patients with recurrent or metastatic esophageal cancer after chemoradiation were treated with bevacizumab and S-1. Bevacizumab was used by intravenous infusion, 7.5mg/kg body weight on day 1; S-1 was used by oral at 80mg/m^2·d on day 1-14, 21 days as a cycle of treatment and repeated until either progressive disease or intolerable toxicity occurred. Chest CT were performed and RECIST 1.1 was used for response evaluation. Kaplan-Meier method was used for survival analysis. Side effects were recorded and analyzed. Results Totally 78 patients were enrolled in the study, including 67 squamous cell carcinoma and 11 adenocarcinoma histologically. The overall response(CR+PR) rate was 22.4%(17/76) and disease control(CR+PR+SD) rate was 61.8%(47/76) respectively. The median follow-up time was 20 months(range from 9 to 44 months). The median progression-free survival(PFS) was 4.9 months(95% CI 4.4-5.5) and the median overall survival(OS) was 8.1 months(95% CI 7.6-9.2). The median PFS and OS of patients with metastasis diseases were 6.2 months(95% CI 3.3 to 6.3) and 8.5 months(95% CI 5.8 to 11.2), where PFS was longer than that of patients with local regional recurrence(median 5.0 months, 95% CI 3.0 to 5.5, P=0.017) and OS was longer than that of patients with regional disease and metastasis(median 8.0 months, 95% CI 4.6 to 9.5, P=0.010). The common adverse effects were mild to moderate neutropenia(84.2%), grade Ⅰ -Ⅱ hand and foot syndrome(51.3%), grade Ⅰ -Ⅱ nausea(48.7%), mild epistaxis(30.1%) and mild vomiting(14.5%). Esophageal bleeding occurred in 7.9% of patients. One patient(1.3%) died from massive bleeding which was caused by esophageal perforation. Conclusion Bevacizumab combined with S-1 was effective and safe for esophageal cancer patients who had recurrent or metastatic diseases after chemoradiation.
基金supported by the National Natural Science Foundation of China(No.30672162)
文摘Objective To construct lentivirus vectors carrying alphastatin gene,test its secretion expression in human umbilical vein endothelia cells(HUVECs)and observe its effects on growth,migration and tube formation of HUVECs.Methods We constructed recombinant lentivirus vectors of NT4-alphastatin fusion gene containing neurotrophin-4 signal peptide,pro-region sequences and alphastatin,then transfected the recombinant lentivirus vectors into HUVECs to obtain secretory protein alphastatin and test its anti-angiogenic activities in vitro.Results Our data showed that recombinant self-inactivating lentivirus vectors of NT4-alphastatin were successfully constructed,and stable NT4-alphastatin transduced HUVECs were capable of sustainably secreting alphastatin which significantly suppressed HUVECs migration and differentiation but not VEGF-induced proliferation.Conclusion This report represents the first time on the use of lentivirus-based vectors to deliver alphastatin,the endogenous angiogenesis inhibitor,and reveals the potential utility of anti-angiogenic gene therapy with lentivirus vectors for treating cancer.
文摘Over the past couple of decades considerable progress has been made in the management of metastatic colorectal cancers(mCRC) leading to a significant improvement in five-year survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of cancer and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article we will discuss various targeted therapies in the management of mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well.
文摘A mathematical optimal-control tumor therapy framework consisting of radio- and anti-angiogenesis control strategies that are included in a tumor growth model is investigated. The governing system, resulting from the combination of two well established models, represents the differential constraint of a non-smooth optimal control problem that aims at reducing the volume of the tumor while keeping the radio- and anti-angiogenesis chemical dosage to a minimum. Existence of optimal solutions is proved and necessary conditions are formulated in terms of the Pontryagin maximum principle. Based on this principle, a so-called sequential quadratic Hamiltonian (SQH) method is discussed and benchmarked with an “interior point optimizer—a mathematical programming language” (IPOPT-AMPL) algorithm. Results of numerical experiments are presented that successfully validate the SQH solution scheme. Further, it is shown how to choose the optimisation weights in order to obtain treatment functions that successfully reduce the tumor volume to zero.
基金supported by European Research Council advanced grant ANGIOFAT(Project No.250021)the Swedish Research Council+5 种基金the Swedish Cancer Foundationthe Karolinska Institute Foundationthe Karolinska Institute Distinguished Professor Awardthe Torsten Soderberg Foundationthe Novo Nordisk Foundationthe Knut and Alice Wallenberg Foundation
文摘In human patients,drugs that block tumor vessel growth are widely used to treat a variety of cancer types.Many rigorous phase 3 clinical trials have demonstrated significant survival benefits;however,the addition of an anti-angiogenic component to conventional therapeutic modalities has generally produced modest survival benefits for cancer patients.Currently,it is unclear why these clinically available drugs targeting the same angiogenic pathways produce dissimilar effects in preclinical models and human patients.In this article,we discuss possible mechanisms of various anti-angiogenic drugs and the future development of optimized treatment regimens.
基金Guangdong Basic and Applied Basic Research Foundation,No.2019A1515110654the National Natural Science Foundation of China,No.82103448China Organ Transplantation Development Foundation,No.YZLC-2021-003.
文摘The disease burden related to hepatocellular carcinoma(HCC) is increasing. Most HCC patients are diagnosed at the advanced stage and multikinase inhibitors have been the only treatment choice for them. Recently, the approval of immune checkpoint inhibitors(ICIs) has provided a new therapeutic strategy for HCC. It is noteworthy that the positive outcomes of the phase Ⅲ clinical trial IMBrave150 [atezolizumab(anti-programmed cell death ligand 1 antibody) combined with bevacizumab(anti-vascular endothelial growth factor monoclonal antibody)],showed that overall survival and progression-free survival were significantly better with sorafenib. This combination therapy has become the new standard therapy for advanced HCC and has also attracted more attention in the treatment of HCC with anti-angiogenesis-immune combination therapy. Currently, the synergistic antitumor efficacy of this combination has been shown in many preclinical and clinical studies. In this review, we discuss the mechanism and clinical application of anti-angiogenics and immunotherapy in HCC, outline the relevant mechanism and rationality of the combined application of antiangiogenics and ICIs, and point out the existing challenges of the combination therapy.
基金supported by the National Natural Science Foundation of China (No. 10772051)the Postdoctral Foundation of China (No. 20100470702)
文摘The effects of anti-angiogenesis treatment by angiostatin and endostatin on normalization of tumor microvasculature and microenvironment are investigated,based on mathematical modeling and numerical simulation of tumor anti-angiogenesis and tumor haemodynamics.The results show that after anti-angiogenesis treatment:(i) the proliferation,growth,and branching of neo-vessels are effectively inhibited,and the extent of vascularization in tumors is accordingly reduced.(ii) the overall blood perfusion inside of tumor is declined,the plateau of tumor interstitial fluid pressure(IFP) is relieved,the interstitial fluid oozing out from the tumor periphery into the surrounding normal tissue is reduced,the reduction of overall extravasation across vasculature to tumor interstium is much less than the decreased overall blood perfusion,due to the decline of IFP,the intravasations is remarkablely effected by the change,in some cases there are no intravasation flow appear.
基金funded by National Natural Science Foundation of China(81900869,81730026,81802482)National Key R&D Program(2019YFC0840607,2017YFA0105301)+3 种基金Science and Technology Commission of Shanghai Municipality(17411953000,19495800700)Shanghai Sailing Program(19YF1439500)Talent Project of Revitalizing Liaoning(XLYC1807184)Dalian Science&Technology Innovation Fund(2020JJ26SN050)。
文摘In light of the intriguing potential of anti-angiogenic approach in suppressing choroidal neovascularization, we attempted to elaborate synthetic gene delivery systems encapsulating anti-angiogenic plasmid DNA as alternatives of clinical antibody-based therapeutics. Herein, block copolymer of cyclic Arg-Gly-Asp-poly(ethylene glycol)-poly(lysine-thiol) [RGD-PEG-PLys(thiol)] with multifunctional components was tailored in manufacture of core-shell DNA delivery nanoparticulates. Note that the polycationic PLys segments were electrostatically complexed with anionic plasmid DNA into nanoscaled core, and the tethered biocompatible PEG segments presented as the spatial shell(minimizing non-specific reactions in biological milieu). Furthermore, the aforementioned self-assembly was introduced with redox-responsive disulfide crosslinking due to the thiol coupling. Hence, reversible stabilities, namely stable in extracellular milieu but susceptible to disassemble for liberation of the DNA payloads in intracellular reducing microenvironment, were verified to facilitate transcellular gene transportation. In addition, RGD was installed onto the surface of the proposed self-assemblies with aim of targeted accumulation and internalization into angiogenic endothelial cells given that RGD receptors were specifically overexpressed on their cytomembrane surface. The proposed anti-angiogenic DNA therapeutics were validated to exert efficient expression of anti-angiogenic proteins in endothelial cells and elicit potent inhibition of ocular neovasculature post intravitreous administration. Hence, the present study approved the potential of gene therapy in treatment of choroidal neovascularization. In light of sustainable gene expression properties of DNA therapeutics, our proposed synthetic gene delivery system inspired prosperous potentials in long-term treatment of choroidal neovascularization, which should be emphasized to develop further towards clinical translations.
文摘In search of synthetic chemotherapeutic substances capable of inhibiting, retarding, or reversing the process of multi-stage carcinogenesis, we synthesized a series of novel 5-amino pyrazole derivatives 11(a-h) by a nucleophilic substitution reaction and characterized by 1H nuclear magnetic resonance (NMR), liquid chromatography mass spectrometry (LC/MS), Fourier-transform infrared (FTIR), and elemental analysis. These novel compounds were evaluated for their efficacy in inhibiting Ehrlich ascites tumor [EAT] cells in-vivo. In the present study we designed, synthesized, characterized and investigate the anti-angiogenic effects of these compounds, on Ehrlich ascites tumor [EAT] cells in-vivo. The compounds were subsequently tested for their ability to inhibit neovascularisation in chorio allantoin membrane (CAM) model. From the Structure Activity Relationship (SAR) studies, it reveals that, the substitution at N-terminal in pyrazole ring plays key role in the antitumor and anti-angiogenic effects.
文摘Novel heterocyclic analogs of resveratrol, (E)-stilbene analogs, were readily prepared by conjugation of a heterocyclic benzothiazolium moiety with the core styrene structure of resveratrol and evaluated for their biological properties. The results showed that these analogs were superior to resveratrol in 1) anti-angiogenesis in vitro, 2) nitric oxide inhibition in vitro, and 3) inhibition of carrageenan-induced edema in vivo. In summary, introduction of a heterocyclic benzothiazolium moiety to replace one of two aromatic rings from the core stilbene structure of resveratrol provided beneficial biological properties and is worthy of further investigation.
文摘The global burden of ovarian cancer is gradually increasing while patients still suffer from relatively limited treatment options.With recent advances in the decoding of the molecular landscape of ovarian cancer,more options in targeted strategy were offered and can therefore be tailored in different clinical settings for individual patient.Targeting of the abnormal angiogenesis process is the first significant clinical breakthrough which revolutionized the treatment of advanced ovarian cancer,followed by the advent of poly-(ADP)-ribose polymerase(PARP)inhibitors.These two strategies represented by bevacizumab and olaparib respectively underwent tests of numerous clinical trials.In recent years,immune checkpoint inhibitors(ICIs)have been incorporated into the blueprint of ovarian cancer treatment though the effectiveness still left much to be desired.Herein,we systematically outlined recent advances in targeted therapy for ovarian cancer and summarized the landmark clinical trials for each targeted therapy including angiogenesis inhibitors,PARP inhibitors and ICIs.
文摘Tetrandrine (1 μM), a bis-benzylisoquinoline alkaloid isolated from Stephania tetrandra S Moore, signifi-cantly decreased tumor necrosis factor alpha (TNFα;10 ng/ml)-induced increase in the number of micro vessels that budded from cultured rat choroidal explants. Tetrandrine also decreased the TNFα-induced in-crease in the number of cells composing the microvessels. Ammonium pyrrolidine dithiocarbamate (APDC;0.1-0.3 μM), an inhibitor of nuclear factor-κB (NF-κB), decreased the TNFα-induced increase in the number of microvessels in a concentration-dependent manner. TNFα increased the phosphorylation and degradation of inhibitor of NF-κB (IκBα), as well as increasing the DNA-binding activity of NF-κB in choroidal explants. TNF? induced an increase of vascular endothelial growth factor (VEGF)-A mRNA, but not VEGF-C mRNA or VEGF-D mRNA. TNFα-induced angiogenic action was inhibited by treatment of VEGF-A antibody in cultured choroidal capillaries. Tetrandrine inhibited the TNFα-induced increases of phosphorylation and degradation of IκBα, and reduced the TNFα-induced increase of DNA-binding activity of NF-κB in chor-oidal explants. In conclusion, tetrandrine inhibits TNFα-induced activation of NF-κB in the choroidal capil-laries via inhibition of TNFα-induced phosphorylation of IκBα.
