Numerical simulation of solid tumor angiogenesis with Endostatin treatment:a combined analysis of inhibiting effect of anti-angiogenic factor and micro mechanical environment of extracellular matrix

To investigate the influence of anti-angiogenesis drug Endostatin on solid tumor angiogenesis, a mathematical model of tumor angiogenesis was developed with combined influences of local extra-cellular matrix mechanical environment, and the inhibiting effects of Angiostatin and Endostatin. Simulation results show that Angiostatin and Endostatin can effectively inhibit the process of tumor angiogenesis, and decrease the number of blood vessels in the tumor. The present model could be used as a valid theoretical method in the investigation of anti-angiogenic therapy of tumors.

Mechanism of Wnt/β-catenin signaling pathway in enhanced malignant phenotype of non-small cell lung cancer induced by antiangiogenesis therapy

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.

Numerical simulation of inhibiting effects on solid tumour cells in anti-angiogenic therapy: application of coupled mathematical model of angiogenesis with tumour growth

To investigate the inhibiting effects of the anti-angiogenic factor andostatin and the anti-angiogenic drug endostatin on turnout angiogenesis and turnout cells, a coupled mathematical model of tumor angiogenesis with tumour growth and blood perfusion is developed. Simulation results show that angiostatin and endostatin can improve the abnormal microenvironment inside the tumour tissue by effectively inhibiting the process of tumor angiogenesis and decreasing tumour cells. The present model can be used as a valid theoretical method in the investigation of the tumour anti-angiogenic therapy.

PD-1/PD-L1抑制剂联合抗血管内皮生长因子药物免疫治疗晚期肝癌的研究进展

肝细胞癌(hepatocellular carcinoma,HCC)是全球高发的恶性肿瘤。程序性死亡蛋白-1(programmed death protein-1,PD-1)/程序性死亡蛋白配体-1(programmed death protein ligand-1,PD-L1)抑制剂可通过阻断T细胞负调节信号,抑制肿瘤细胞免疫逃逸途径,重新激活抗肿瘤免疫应答过程,成为晚期HCC治疗的新手段。然而,长期临床结果显示,采用PD-1/PD-L1抑制剂单药治疗晚期HCC的病人仍存在较高的复发率和转移率。免疫联合疗法是目前针对晚期HCC患者的新的治疗策略,其中PD-1/PD-L1抑制剂联合抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物在晚期HCC治疗中显示出了良好的疗效和安全性。PD-1/PD-L1抑制剂联合抗VEGF药物可通过参与癌症免疫循环途径抑制肝癌细胞的生长。该文就PD-1/PD-L1抑制剂联合抗VEGF药物在晚期HCC治疗中的临床研究作一综述。

Tumor progression-dependent angiogenesis in gastric cancer and its potential application

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.

Influence of bioactive sulphated polysaccharide-protein complexes on hepatocarcinogenesis, angiogenesis and immunomodulatory activities

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.

Research Progress of Anti-Angiogenic Drugs in First-Line Treatment of Small Cell Lung Cancer

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.

忍冬花中一种RG-I多糖的抗血管生成活性研究

目的本研究对忍冬花中均一多糖结构和抗新生血管生成活性进行研究,为忍冬的活性物质基础研究提供新的理论数据。方法水提醇沉并结合阴离子交换色谱和凝胶渗透色谱法获得忍冬均一多糖LF-02-2,并通过分子量检测、单糖组成分析、糖残基连接方式分析、部分酸水解、糖醛酸还原结合核磁共振数据推导出LF-02-2的结构。同时,运用人微血管内皮细胞管腔形成实验测定其体外抗新生血管活性。结果对LF-02-2的结构解析表明,均一多糖LF-02-2的重均分子量为74.1 kDa,其单糖组成由鼠李糖(Rha)、半乳糖(Gal)、半乳糖醛酸(GalA)和阿拉伯糖(Ara)组成,摩尔比分别为10.43∶14.94∶6.66∶67.97。其主链由1,4-连接的α-Galp A、1,2-连接的α-Rhap和1,2,4-连接的α-Rhap组成。分支由末端连接和1,4,6-连接的β-Galp,末端连接和1,5-连接的α-Araf连接,取代发生在1,2,4-连接的α-Rhap的O-4位。管腔形成实验结果表明LF-02-2能显著抑制人微血管内皮细胞(Human Microvascular Endothelial Cell,HMEC)的管腔形成。结论忍冬花中一种类RG-I型果胶多糖LF-02-2具有显著抗血管生成活性,具有开发为抗血管生成药物的潜力。

Correlation of SphK1, FAK, Musashi 1 and CA199 expression with angiogenesis and epithelial-mesenchymal transition in surgically removed colon cancer lesions

Objective: To investigate the correlation of SphK1, FAK, Musashi 1 and CA199 expression with angiogenesis and epithelial-mesenchymal transition in surgically removed colon cancer lesions. Methods: A total of 60 patients with colon cancer who underwent radical operation in our hospital between August 2015 and August 2017 were selected, intraoperative colon cancer tissue samples were collected as colon cancer group, and normal tissue specimens adjacent to carcinoma were collected as adjacent tissue group. Fluorescence quantitative PCR was adopted to determine the expression levels of SphK1, FAK, Musashi 1, CA199 as well as the genes related to angiogenesis and epithelial-mesenchymal transition in colon tissues with different properties. Results: SphK1, FAK, Musashi 1 and CA199 mRNA expression in colon cancer group were higher than those in adjacent tissue group;angiogenesis-related genes ANGPTL4, Apelin-13, DLL1, VEGF and HIF-α mRNA expression were higher than those in adjacent tissue group whereas TSP-1 mRNA expression was lower than that in adjacent tissue group;epithelial-mesenchymal transition-related gene E-cadherin mRNA expression was lower than that in adjacent tissue group whereas Vimentin, N-cadherin, Twist and Snail mRNA expression were higher than those in adjacent tissue group. Correlation analysis showed that the SphK1, FAK, Musashi 1 and CA199 expression in colon cancer tissues were directly correlated with the angiogenesis genes and epithelial-mesenchymal transition genes. Conclusion: SphK1, FAK, Musashi 1 and CA199 genes are abnormally expressed in colon cancer tissues and their expression levels are directly correlated with tumor angiogenesis and epithelial-mesenchymal transition process.

基于3,5-二溴水杨醛席夫碱镍配合物-氧化石墨烯电化学免疫传感器检测Anti-IgG含量的研究

应用物理吸附法将羊抗人IgG抗原直接固定于3,5-二溴水杨醛席夫碱镍配合物-氧化石墨烯修饰的金电极表面,制备电化学免疫传感器。采用循环伏安法和交流阻抗法对传感器进行表征,结果表明该传感器适合检测Anti-IgG浓度。同时探讨了缓冲液pH值、扫描速度、免疫反应温度、抗原与抗体配比对循环伏安峰电流的影响,结果表明在5-100mV/s扫速范围内,峰电流与扫速呈线性。孵育最优条件为25℃,h-IgG与Anti-IgG配比为1∶1。循环伏安法研究还表明Anti-IgG浓度在0.01-260μg/L范围内,线性关系良好,相关系数r^2=0.993,检出限（S/N=3）为0.006μg/L,据此建立了检测Anti-IgG浓度的新方法。

信号分子IRAK1/4在antiβ-2GPI/β2GPI复合物诱导THP-1细胞表达TF中的作用探讨

目的:探讨IRAK1和IRAK4在antiβ-2GPI/β2GPI复合物诱导单核细胞株THP-1表达组织因子(TF)中的作用。方法:利用荧光定量PCR(Real-time PCR)、TF活性试剂盒分别检测THP-1细胞表达TF mRNA及TF活性;Western blot检测anti-β2GPI/β2GPI复合物诱导THP-1细胞表达IRAK1、磷酸化-IRAK1(p-IRAK1)、IRAK4情况;观察IRAK1/4抑制物是否干预anti-β2GPI/β2GPI复合物诱导THP-1表达TF。结果:Antiβ-2GPI/β2GPI复合物(100μg/ml)诱导THP-1细胞表达TF显著增加(P<0.05 vs control);Antiβ-2GPI/β2GPI复合物(100μg/ml)刺激THP-1细胞表达IRAK1、p-IRAK1、IRAK4(蛋白)显著升高(P<0.05 vscontrol);IRAK1/4抑制物(50μmol/L)能够阻断antiβ-2GPI/β2GPI复合物(100μg/ml)诱导THP-1表达TF及IRAK1磷酸化的效应。结论:antiβ-2GPI/β2GPI复合物诱导THP-1细胞表达TF过程中,信号分子IRAK1/4被激活进而发挥重要作用。

三维Anti de Sitter空间中Lorentzian曲面的S_t^1×S_s^1-值光锥Gauss映射的奇点分类

利用Arnol'd的Legendrian理论,对三维Anti de Sitter空间中Lorentzian曲面进行了研究.引入光维高度函数概念研究了三维Anti de Sitter空间Lorentzian曲面的S1t×S1s-值、光锥Gauss映射的奇点,进行了奇点分类,揭示了类光Causs-kronecker曲率之间的关系;并研究了Lorentzian曲面的一些基本几何性质.

Lymphangiogenesis:A new player in cancer progression

Lymph node metastasis is the hallmark of colon cancer progression,and is considered one of the most important prognostic factors.Recently,there has been growing evidence that tumor lymphangiogenesis(formation of new lymphatic vessels) plays an important role in this process.Here,we review the latest f indings of the role of lymphangiogenesis in colorectal cancer progression,and discuss its clinical application as a biomarker and target for new therapy.Understanding the molecular pathways that regulate lymphangiogenesis is mandatory to pave the way for the development of new therapies for cancer.In the future,tailored treatments consisting of combinations of chemotherapy,other targeted therapies,and anti-lymphangiogenesis agents will hopefully improve patient outcomes.This progression to the clinic must be guided by new avenues of research,such as the identif ication of biomarkers that predict response to treatment.

Inhibitory Effect of Recombinant Endostatin on Angiogenesis and Tumor Growth of Hepatoma

To study the influence of recombinant endostatin on angiogenesis and tumor growth of mice H22 hepatoma, tumor models were constructed by injecting H22 hepatoma cells into the leg muscle of mice Recombinant endostatin was produced by gene engineering in E coli The recombinant protein was injected subcutaneously to treat transplanted hepatoma faraway The weight of tumors was measured, and the changes of necrosis of tumor cells and vessel density were observed by immunohistochemistry The results suggested that the growth of hepatoma models transplanted in the muscle of legs was suppressed by recombinant endostatin The density of vacularity was decreased, but the necrosis of tumor cells increased The inhibitory effect of recombinant endostatin on angiogenesis and tumor growth of hepatoma was not affected after chemotherapy

LRG1 promotes corneal angiogenesis and lymphangiogenesis in a corneal alkali burn mouse model

AIM:To investigate the potential effect and mechanism of leucine-richα-2-glycoprotein-1(LRG1)on corneal angiogenesis and lymphangiogenesis.METHODS:Corneal neovascularization and lymphatics were induced by establishing alkali burn mouse model.Immunofluorescence staining was performed to detect the location of LRG1 in cornea tissues and to verify the source of LRG1-positive cells.Corneal whole-mount staining for CD31(a panendothelial cell marker)and lymphatic endothelial hyluronan receptor-1(LYVE-1;lymphatic marker)was performed to detect the growth of blood and lymphatic vessels after local application of exogenous LRG1 protein or LRG1 si RNA.In addition,expressions of the proangiogenic vascular endothelial growth factor(VEGF)related proteins were detected using Western blot analysis.RESULTS:LRG1 was dramatically increased in alkali burned corneal stroma in both the limbal and central areas.LRG1-positive cells in the corneal stroma were mainly derived from Vimentin-positive cells.Local application ofexogenous LRG1 protein not only aggravated angiogenesis but also lymphangiogenesis significantly(P<0.01).LRG1 group upregulated the levels of VEGF and the vascular endothelial growth factor receptor(VEGFR)family when compared with the phosphate-buffered saline(PBS)control group.We also found that LRG1-specific si RNA could suppress corneal angiogenesis and lymphangiogenesis when compared with the scramble si RNA-treated group(P<0.01).CONCLUSION:LRG1 can facilitate corneal angiogenesis and lymphangiogenesis through heightening the stromal expression of VEGF-A,B,C,D and VEGFR-1,2,3;LRG1-specific si RNA can suppress corneal angiogenesis and lymphangiogenesis in corneal alkali burn mice.

Anti-angiogeneic Target Therapy for Cancer with Vaccine Based on the Recombinant Chicken FGFR-1 in Tumor-bearing Mice

To explore the anti-tumor effect of immunotherapy with recombinant protein vaccine based on FGFR-1 of chicken （cFR-1） in a mouse Meth A fibrosarcoma model, tumor volume and survival rate of the mice were observed at a 3-day interval. Microvessel density （MVD） was detected by immunohistochemistry. Auto-antibodies against self-FGFR-1 were detected by Western blotting and ELISA, respectively. The anti-FGFR-1 antibody-producing B cells （APBCs） were detected by enzyme-linked immunospot （ELISPOT） assay. Eighteen days after inoculation of tumor cells, the tumor volume was significantly smaller in cFR-l-immunized group than in mouse FGFR-1 （mFR-1） immunized group and normal saline （NS） control group （P〈0.05）, and the survival time was significantly longer in cFR-l-immunized group than in the control groups （P〈0.01）. MVD was significantly lower in cFR-l-immunized group than in mFR-1-immunized group and NS group （16.8 ±5.6 vs 64.6±1.8 and 59.6±8.7, P〈0.01）. Antibodies against self-FGFR-1 were found in mFR-1-immunized group, the major antibody subclasses were IgG1 and IgG2b. Compared with the two control groups, the numbers of APBCs in cFR-l-immunized group were significantly increased （P〈0.01） These results demonstrated that the cFR-1-related anti-angiogenesis protein vaccine could induce the production of auto-antibodies against self-FGFR-1, which futher inhibit angiogenesis and growth of solid tumor.

胃复方调控HIF-1α/VEGF信号通路抑制胃癌细胞增殖及血管生成机制研究

目的:观察不同浓度胃复方水提物(WFF)对人胃癌HGC-27细胞的增殖抑制作用,进一步探讨WFF调控HIF-1α/VEGF信号通路的作用机制。方法:采用不同浓度(1.2 mg/mL、1.3 mg/mL、1.4 mg/mL、1.5 mg/mL、1.6 mg/mL、1.7 mg/mL、1.8 mg/mL)的WFF,CCK-8法寻找最佳干预浓度并观察不同的干预组别[非特异性对照组(NC组)、WFF组、WFF+HIF-1α过表达质粒组、WFF+2-MeOE2 (HIF-1α抑制剂)组、HIF-1α过表达质粒组、2-MeOE2组、甲磺酸阿帕替尼组]对HGC-27细胞增殖的影响;运用血管生成实验观察不同组别对胃癌细胞血管生成能力的影响;进一步采用Western blot法观察不同组别[NC组、WFF组、WFF+HIF-1α过表达质粒组、WFF+2-MeOE2组(HIF-1α抑制剂)、HIF-1α过表达质粒组、2-MeOE2组]对HIF-1α/VEGF信号通路相关蛋白表达的影响。结果:CCK-8法验证了WFF与NC组比较,对HGC-27细胞增殖具有抑制作用,差异有统计学意义(P<0.01),且呈剂量依赖性。与NC组比较,WFF组、WFF+HIF-1α过表达质粒组、WFF+2-MeOE2 (HIF-1α抑制剂)组、2-MeOE2组、甲磺酸阿帕替尼组对HGC-27细胞增殖具有抑制作用,差异有统计学意义(P<0.01);与WFF组比较,WFF+HIF-1α过表达质粒组细胞活性增高,差异有统计学意义(P<0.01),WFF+2-MeOE2组活性降低,差异有统计学意义(P<0.01)。与HIF-1α过表达质粒组比较,WFF+HIF-1α过表达质粒组有效抑制了HGC-27细胞增殖,差异有统计学意义(P<0.01);与2-MeOE2组比较,WFF+2-MeOE2组有效抑制了HGC-27细胞增殖,差异有统计学意义(P<0.01)。血管生成实验验证了WFF有效降低了人胃癌HGC-27细胞血管生成能力,除HIF-1α过表达质粒组外,其余各组与NC组比较,均降低了HGC-27细胞血管生成能力,差异有统计学意义(P<0.05,P<0.01)。与WFF组比较,WFF+HIF-1α过表达质粒组,成管数目、交叉点、网眼数及长度增多,差异有统计学意义(P<0.01),WFF+2-MeOE2组,成管数目、交叉点、网眼数及长度减少,差异有统计学意义(P<0.01)。与HIF-1α过表达质粒组比较,WFF+HIF-1α过表达质粒组成管数目、交叉点、网眼数及长度减少,差异有统计学意义(P<0.01);与2-MeOE2组比较,WFF+2-MeOE2组成管数目、网眼数及长度减少,差异有统计学意义(P<0.01)。Western blot法验证了WFF下调了HIF-1α、VEGFA、VEGFR-2、Ki-67、PCNA的蛋白表达(P<0.05),并分别与HIF-1α过表达质粒、2-MeOE2有不同程度的拮抗、协同作用。结论:WFF可能通过抑制HIF-1α/VEGF信号通路发挥抑制胃癌细胞增殖及抗血管生成的作用。

On the Construction of Deepening Anti - corruption Mechanism

It needs the foundation of system and the guarantee of organizational system for anti-corruption,but it is more necessary to build and form an effective anti-corruption mechanism,so that the anti-corruption can be really put into practice. Anti-corruption mechanism refers to a organic operation system of the interaction,interconnection and constraint between the constituent elements( parts) and elements of national anti-corruption,and as a system,anti-corruption mechanism should have the characteristics of system aticness,comprehensiveness,transparency,legalization,public participation,scientific dynam ic,and internationalism. The construction of deepening anti-corruption mechanism is the need for reconstructing the ruling legitimacy of the party and the governm ent. Adhering to the principle of treating both root causes and symptoms is necessary in the construction of anti-corruption m echanism,com bating and punishing corruption is an important part of anti-corruption,and the prevention and control of corruption is the basic project of anti-corruption. Therefore,the construction of prevention and control mechanism in the anti-corruption mechanism has a more far-reaching significance.

Future options of anti-angiogenic cancer therapy

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.

Simulation of tumor microvasculature and microenvironment response to anti-angiogenic treatment by angiostatin and endostatin

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.