Relationship Between Metabolic Remodeling of Endothelial Cells and Tumor Angiogenesis Based on "Yin Fire" Theory and Intervention of Chinese Medicine / 中国实验方剂学杂志

Endothelial cells in the inner wall of blood vessels respond to physical and chemical signals of the body by regulating vascular homeostasis， vascular tension， cell adhesion， cell proliferation， coagulation resistance and inflammatory factors， to maintain the stability of blood vessels. Angiogenesis is the key condition for tumor evolution， and the pathological mode of tumor angiogenesis provides nutrients and oxygen for tumor growth and promotes its proliferation. In recent years， endothelial cells have participated in tumor vascular infiltration and driven angiogenesis， which is considered to be the point link in tumor metastasis. By regulating metabolic remodeling， vascular endothelial cells provide the materials and energy needed in the process of tumor angiogenesis， and their abnormal metabolic characteristics facilitate their adaption to the changes of tumor microenvironment， which is often regarded as an important basis for tumor angiogenesis. The ''Yin fire'' theory in traditional Chinese medicine， originating from Huangdi's Internal Classic （Huang Di Nei Jing）， originally meant Yin deficiency generates internal heat， and belonged to the category of fire of internal injury. After the deduction and changes by physicians over the ages， the pathogenesis of ''spleen and stomach Qi deficiency-Yin fire rising-Qi and fire disharmony'' was gradually formed. The pathogenesis of metabolic remodeling of endothelial cells manifests the pathological characterization of Yin fire in an objective way， which is consistent with the disease state of uncontrolled and hyperactive tumor neovascularization. Changes in spleen and stomach Qi deficiency as well as imbalance of Qi movement lead to the failure of water and food in distribution， and thus metabolic disorders occur. Long term retention turns in phlegm and blood stasis， which combat with blood vessels， and result in abnormal local environment （formation of tumor microenvironment）， adverse pulse channel （imbalance of endothelial cell metabolism）， and tumor neovascularization. Under the guidance of ''Yin fire'' syndrome elements and by focusing on the correlation between Qi and fire， prescriptions are made based on the treatment method of ''strengthening the body and regulating Qi'' to regulate the metabolic function of endothelial cells， thus achieving a relatively balanced state of the body and inhibiting tumor angiogenesis. As a result， this study， centering on the metabolic remodeling of endothelial cells and ''Yin fire'' theory， elucidated the academic ideas， with the purpose of providing some theoretical support for the intervention of tumor vascularization by Chinese medicine.

Research progress on role of angiopoietin-like 4 in tumor progression / 中国生物制品学杂志

@#Angiopoietin-like 4(ANGPTL4)is one of the angiopoietin family members and plays a regulatory role in lipid metabolism,glucose homeostasis,inflammatory signal transduction,angiogenesis and vascular permeability.Inflammatory reaction in tumor microenvironment regulates tumor progression,and tumor angiogenesis plays a vital role in tumor growth and metastasis,so ANGPTL4 is closely related to tumor occurrence and development.Many studies have shown that ANGPTL4 plays an important regulatory role in tumor growth,anoikis resistance,tumor angiogenesis and tumor metastasis.This paper reviews the role of ANGPTL4 in tumor progression.

An epidermal growth factor motif of developmental endothelial locus 1 protein inhibits efficient angiogenesis in explanted squamous cell carcinoma in vivo

ABSTRACT Background: Cancer gene therapy using a nonviral vector is expected to be repeatable, safe, and inexpensive, and to have long-term effectiveness. Gene therapy using the E3 and C1 (E3C1) domain of developmental endothelial locus-1 (Del1) has been shown to improve prognosis in a mouse transplanted tumor model. Objective: In this study, we examined how this treatment affects angiogenesis in mouse transplanted tumors. Materials and methods: Mouse transplanted tumors (SCCKN human squamous carcinoma cell line) were injected locally with a nonviral plasmid vector encoding E3C1 weekly. Histochemical analysis of the transplanted tumors was then performed to assess the effects of E3C1 on prognosis. Results: All mice in the control group had died or reached an endpoint within 39 days. In contrast, one of ten mice in the E3C1 group had died by day 39, and eight of ten had died or reached an endpoint by day 120 (p < 0.01). Enhanced apoptosis in tumor stroma was seen on histochemical analyses, as was inhibited tumor angiogenesis in E3C1-treated mice. In addition, western blot analysis showed decreases in active Notch and HEY1 proteins. Conclusion: These findings indicate that cancer gene therapy using a nonviral vector encoding E3C1 significantly improved life-span by inhibiting tumor angiogenesis. (REV INVEST CLIN. 2021;73(1):39-51)

Research Progress on Anti-tumor Effect and Mechanism of Cucurbitacins / 中国实验方剂学杂志

Cancer is a major global public health problem. Statistics from the national cancer center of China also show that cancer has become a major disease threatening human health with increasing morbidity and mortality. The occurrence and development mechanism of cancer is complex， involving multiple stages， multiple genes and multiple signaling pathways. Conventional chemoradiotherapy and emerging targeted therapy methods are the main methods in treatment of tumor. However， the quality of life of patients as well as the sustained and effective therapeutic effect are seriously affected due to the toxic side effects and drug resistance. Therefore， it is the global focus to find safe and effective anti-cancer drugs. The research and development and application of anti-cancer herbal medicines such as paclitaxel， vinblastine， podophyllin， ginsenoside and ginseng polysaccharide have brought new hope for the treatment of cancer. Cucurbitacine from Chinese medicine cucurbitaceae plantsare is a kind of highly oxidized tetracyclic triterpene compound with extensive pharmacological effects and complex mechanism. In the family of cucurbitacines， cucurbitin B， D， E and I have been studied most frequently on anticancer effect， and in a large number of studies， they have been found to play an important role in tumor diseases of the digestive system， respiratory system， reproductive system， blood system， urinary system and so on. With significant effect in inhibiting tumor cells proliferation， blocking the cell cycle， inducing apoptosis and autophagy death， inhibiting cell migration and invasion， inhibiting tumor angiogenesis， regulating the levels of reactive oxygen species and regulating immune system， such cucurbitacins are expected to be developed as a new kind of anti-cancer drugs. The authors of this study aim to provide reference for the further research and development of new anti-cancer drugs about cucurbitines by summarizing the anti-tumor effect and mechanism of the cucurbitacins.

REC8 suppresses tumor angiogenesis by inhibition of NF-κB-mediated vascular endothelial growth factor expression in gastric cancer cells

BACKGROUND: Tumor angiogenesis is an essential event for tumor growth and metastasis. It has been showed that REC8, a component of the meiotic cohesion complex, played a vital role in Epithelial-Mesenchymal Transition (EMT) in gastric cancer. However, the role of REC8 in gastric cancer angiogenesis remains to be identified. RESULTS: Inhibition of REC8 expression in gastric cancer cells contributed to tumor angiogenesis in the gastric cancer microenvironment. The clinical analysis demonstrated that the loss of REC8 in gastric cancer with enrichment of MVD. Depletion of REC8 expression in gastric cancer cells significantly increased tube formation of human umbilical vein endothelial cells (HUVECs), which is attributed to enhancement of vascular endothelial growth factor (VEGF) secretion caused by REC8 slicing. While addition of neutralizing antibody targeted VEGF into supernatant drastically reversed the effect of REC8 loss in gastric cancer cells on tube formation. Mechanistic analyses indicated that ablation of REC8 promotes nuclear factor-κB (NF-κB) p65 activity and its downstream gene VEGF expression, leading to tube formation. CONCLUSIONS: These results demonstrated a novel REC8 function that suppressed tumor angiogenesis and progression by attenuation of VEGF in gastric cancer microenvironment.

Recombinant Maspin Protein Inhibits the Tumor Angiogenesis by Regulating SIRT3-Mediated Glycolysis in Cervical Cancer / 中国药学杂志

OBJECTIVE: To investigate the effect of recombinant mammary serine protease inhibitor (Maspin) on tumor angiogenesis and tumor metabolism of HeLa cervical cancer and its mechanisms. METHODS: MTS was used to test the effect of recombinant Maspin on proliferation of HeLa cells. Western blotting was used to determine the effect of recombinant Maspin on the expression of SIRT3 in HeLa cells. SIRT3 siRNA was constructed by commercial and then transfected into HeLa cells. Tube formation assay was used to study the effect of SIRT3 intervene on tumor angiogenesis. Detection kits were used to examine the effects of recombinant Maspin on the glucose consumption and the generation of pyruvic acid, lactic acid as well as ATP after SIRT3 intervene, respectively. Western blotting was used to study the effect of SIRT3 intervene on expression of glucose transporter 1 (GLUT1), monocarboxylate transporter-1 (MCT-1), hexokinase (HK2), fructokinase 6-phosphate(PFK1) and pyruvic acid 2 (PKM2). RESULTS: Compared with the control group, the proliferation of HeLa cervical cancer cells was significant inhibited by recombinant Maspin in vitro. SIRT3 siRNA transfection could significantly decrease the inhibition effect of recombinant Maspin on tumor angiogenesis. SIRT3 siRNA transfection could significantly ameliorate the inhibition effect of recombinant Maspin on glucose consumption and the contents of pyruvic acid, lactic acid as well as ATP, respectively. Recombinant Maspin inhibited the expressions of GLUT1, MCT-1, HK2, PFK1 and PKM2, however, SIRT3 siRNA transfection significantly reversed the expression of above glycolysis-related proteins. CONCLUSION: Recombinant Maspin inhibits the tumor angiogenesis by suppressing glycolysis in HeLa cells, and such effect is dependent on SIRT3 expression.

Effect of conditioned medium of vascular endothelial cells on the epithelial-mesenchymal transition of hepatocellular carcinoma cells / 生物医学工程学杂志

This study aims to investigate the effect of substances secreted or metabolized by vascular endothelial cells on epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma cells under indirect co-culture condition. Human hepatocellular carcinoma cell line QGY-7703 was cultured , and then was co-cultured with conditioned medium of human umbilical vein endothelial cells (HUVEC). The morphological changes of QGY-7703 cells were observed by inverted phase contrast microscopy. The migration ability of QGY-7703 cells was analyzed by scratch-wound assays. The effect of conditioned medium on the expression and distribution of EMT related proteins was detected by Western blot and immunofluorescence assays, respectively. The results showed that the QGY-7703 cells gradually changed from polygonal to spindle shape, the migration ability promoted significantly, and both the expression and distribution of EMT related marker changed in a time-dependent manner after co-culturing. The results confirm that vascular endothelial cells can induce EMT in hepatocellular carcinoma cells under indirect co-culture condition.

Research advancement in vascular endothelial cell metabolism and tumor angiogenesis / 药学学报

Vascular endothelial cells play a major role in maintaining the oxygen and nutrient supply to all tissues in the body. Endothelial cells, together with vascular endothelial growth factor, are also the driving forces of tumor angiogenesis, a process describing the growth of blood vessels from the existing vasculature in tumor tissues. Reprogramming of endothelial cell metabolism satisfied the needs for biomass and energy in the process of tumor angiogenesis, which are known to involve the aspects of glucose metabolism, amino acid metabolism, and fatty acid metabolism. Recently, with the increasing interest to understand the metabolic regulation in cancer, the investigation into the metabolism of endothelial cells has made progress. We herein review the role of endothelial cell metabolism in angiogenesis, with a particular focus on the metabolic regulation of endothelial cells in tumor angiogenesis, which hopes to provide insights for the intervention of tumor angiogenesis in cancer therapy.

Study on synergistic anti-tumor effect of Shuangdan Capsules combined with 5-FU on hepatocellular carcinoma cells Huh-7 and xenograft mice / 中国中药杂志

This paper discussed the synergistic anti-tumor effect of Shuangdan Capsules combined with 5-fluorouracil(5-FU) on human liver cancer cell line Huh-7 and tumor bearing mice. The effects of Shuangdan Capsules combined with 5-FU on the activity and vascular endothelial growth factor(VEGF) receptor protein expression of Huh-7 cells were investigated, and the effects of drug combination on tube formation of HUVEC cell were also verified. In addition, the mice model of Huh-7 was established to observe the anti-tumor effect of drug combination and the distribution of tumor blood flow in tumor bearing mice by using molecular imaging. HPLC analysis showed that Shuangdan Capsules mainly consisted of danshensusodium, protocatechuic aldehyde, paeoniflorin, rosmarinic acid, alkannic acid, salvianolic acid B, and paeonol. In MTT experiment, the inhibition rate of Shuangdan Capsules(20 mg·L~(-1)) and 5-FU(1 μmol·L~(-1)) on Huh-7 cells was 60%, and the CI value was 0.59, suggesting that these two drugs had synergistic anti-hepatoma cells effect. The expression of VEGF receptor in Huh-7 cells was inhibited by the combination of these two drugs. In addition, the process of HUVEC was slow, and the number, length and area of the lumen branches decreased significantly. In vivo, Shuangdan Capsules combined with 5-FU inhibited the growth and prolongation of survival of Huh-7 cells in subcutaneous transplanted tumor nude mice; serum expression of CD31 and VEGF in nude mice were decreased, while caspase-3 was increased. Meanwhile, the drug combination significantly inhibited the expressions of MMP2 and VEGF in tumor tissues. Ultrasound showed that Shuangdan Capsules combined with 5-FU also inhibited tumor angiogenesis and reduced blood flow of tumor tissue. The results showed that Shuangdan Capsules combined with 5-FU may inhibit tumor angiogenesis by inhibiting VEGF and MMP2 expressions, thereby blocking tumor growth.

MicroRNA in tumor angiogenesis and target therapy / 中华实验眼科杂志

Angiogenesis is a complex process and plays an important role in tumor growth and metastasis.Among the factors of angiogenesis, vascular endothelial growth factor (VEGF) is most widely studied factor in the regulation of tumor angiogenesis.MicroRNAs (miRNAs) are a class of small non-coding RNAs that play a vital role in tumor angiogenesis and metastasis through post-transcriptional regulation.They can function in diverse biological processes via regulating multiple pathways, such as VEGF, to promote or inhibit tumor angiogenesis.Uveal melanoma (UM) is the most common primary intraocular malignant tumor.It seriously threatens vision, eyeballs and even life of patient.Since angiogenesis plays an important role in UM tumor growth, invasion and metastasis, understanding the regulation of tumor angiogenesis has become important for tumor therapy.In this review, we summarized the regulatory role of miRNAs and their targets in tumor angiogenesis and discussed the potential therapeutic interventions of miRNAs for tumor angiogenesis, including nanoparticles and cell-derived membrane vesicles.

Stachydrine Inhibits the Growth of Colon Cancer by Regulating the Expression of ACTG2 / 中国药学杂志

OBJECTIVE: To investigate the effect of stachydrine on tumor growth of colon cancer and its mechanisms. METHODS: MTS was used to test the effect of stachydrine on proliferation of HCT116 colon cancer cell. HCT116 colon cancer xenograft model was used to detect the effect of stachydrine on tumor growth in vivo. Immunohistochemical was used to determine the effect of stachydrine on expression of smooth muscle actin 2 (ACTG2) in subcutaneous transplantation tumor. The transfection of ACTG2 siRNA into HCT116 cells was conducted to study the effect of ACTG2 intervene on tumor angiogenesis by tube formation experiment in colon cancer. The protein expression of VEGF, bFGF, TNF-α and PDGF after ACTG2 intervene were examined by Western blotting to explore the potential mechanisms of stachydrine on regulation of tumor angiogenesis. RESULTS: Compared with the control group, the proliferation and growth of HCT116 colon cancer cells were significant inhibited by stachydrine in vitro and in vivo. Immunohistochemical showed that the expression of ACTG2 was significantly decreased by treatment with stachydrine. ACTG2 siRNA transfection could significantly decreased the inhibition effect of stachydrine on tumor angiogenesis. Mechanistic study found that stachydrine could inhibit the expression of VEGF, bFGF, TNF-α and PDGF, however, ACTG2 siRNA transfection could significantly reverse the expression of above mentioned angiogenesis-related factors. CONCLUSION: Stachydrine could inhibit the growth of colon cancer by suppressing tumor angiogenesis, and such effect is dependent on ACTG2 expression.

Role of BV8 and its antibody in angiogenesis / 上海交通大学学报（医学版）

BV8, a lately defined secreted protein, is proved to play an important role in the angiogenesis process of endocrine, cardiovascular system, kidney and other organs. Moreover, it contributes to the CD11b+Gr1+ myeloid cell-dependent tumor neo-vascularization. Meanwhile, anti-BV8 antibody therapy has been shown to be against solid tumors via inhibition of angiogenesis in animal models. This review systematically introduced the current knowledge on BV8 from structure to function, from mechanism to its role in diseases. Consequently, this review will probably provide new ideas and direction to the new target of the current anti-vascular therapy for cancer and to the future investigation.

Role of BV8 and its antibody in angiogenesis / 上海交通大学学报（医学版）

BV8,a lately defined secreted protein,is proved to play an important role in the angiogenesis process of endocrine,cardiovascular system,kidney and other organs.Moreover,it contributes to the CD1 lb+Grl+ myeloid cell-dependent tumor neo-vascularization.Meanwhile,anti-BV8 antibody therapy has been shown to be against solid tumors via inhibition of angiogenesis in animal models.This review systematically introduced the current knowledge on BV8 from structure to function,from mechanism to its role in diseases.Consequently,this review will probably provide new ideas and direction to the new target of the current anti-vascular therapy for cancer and to the future investigation.

Application of cNGR functionalized gold nanoparticle probe in CT imaging of breast cancer angiogenesis / 国际生物医学工程杂志

Objective To prepare polyethylene glycol/cyclic asparagines-glycine-arginine functionalized gold nanoparticles (GNPs-PEG@cNGR) and evaluate their effectiveness in CT imaging of breast cancer angiogenesis.Methods The GNPs were synthesized by one-step reduction of chloroauric acid by sodium citrate.The thiolated PEG and cysteine-modified cNGR were coupled to the surface of GNPs through Au-S bonds,respectively.The GNPs-PEG@cNGR was characterized by transmission electron microscopy,Zeta potential/hydration particle size analyzer,and Fourier transform infrared spectrometer.The uptake and CT imaging effect of GNPs-PEG@cNGR were assessed by human umbilical vein endothelial cells (HUVEC) and human hepatoma cells (HepG2) positively expressed for aminopeptidase N (APN/CD 13).The in vivo CT imaging effects on tumor angiogenesis and biocompatibility in mice of GNPs-PEG@cNGR were studied by BALB/c mouse model of 4T1 breast cancer.Results A specific CT molecular probe,i.e.GNPs-PEG@cNGR,was successfully constructed,which can target angiogenesis.The probe was spherical,with a hydration particle size of (35.7± 1.0) nm and a Zeta potential of (-13.54± 1.12) mV,and had good stability and biocompatibility.The GNPs-PEG@cNGR has good CT imaging results and can specifically target CD13-positive HUVEC and HepG2 cells.The CT imaging results in 4T1 breast cancer mice indicated that GNPs-PEG@cNGR could be specifically enriched in the tumor tissue after injection.The CT value of tumors in GNPs-PEG@cNGRz group was higher than that of GNPs-PEG group,and the difference was statistically significant (P＜0.05).Conclusions GNPs-PEG@cNGR can specifically target CD13 positive cells and can be used as a CT contrast agent for imaging tumor angiogenesis.

Role of PD 0332991 on the Proliferation and Apoptosis of Vascular Endothelial Cells / 中国肺癌杂志

BACKGROUND@#Angiogenesis is an important process in the development of tumor. PD 0332991, a cell cycle inhibitor, can specifically inhibit CD4/6 phosphorylation and cell cycle progression. In xeongraft mice models, PD 0332991 treated mice had significantly decreased angiogenesis and vascular density compared with the control group, but the mechanism remains unknown. The purpose of this study is to investigate the role and molecular mechanism of PD 0332991 on vascular endothelial cells.@*METHODS@#EA.hy926 cells, a kind of vascular endothelial cell, were used as the research model. The effects of PD 0332991 on the activity and proliferation of EA.hy926 cells were detected by the MTT, EdU assays. Wound-healing assays and transwell assays were used to determine the effects of PD 0332991 on the mobility of EA.hy926. The influence of PD 0332991 on cell cycle and apoptosis of endothelial cells was tested by flow cytometry, and the Western blot was applied to observe the expression of cell cycle related proteins in EA.hy926 cells treated by PD 0332991.@*RESULTS@#PD 0332991 significantly inhibited the proliferation and mobility of EA.hy926 cells, caused cell cycle arrest and apoptosis. At the same time, PD 0332991 inhibited the expression of CDK4/6 and phosphorylation of Rb, and thus inhibited the cell cycle progression of EA.hy926 cells.@*CONCLUSIONS@#PD 0332991 can inhibit the proliferation and activity of endothelial cells and induces apoptosis.

A Systematic Comparative Evaluation of ⁶⁸Ga-Labeled RGD Peptides Conjugated with Different Chelators / 대한핵의학회잡지

PURPOSE: The present paper reports a systematic study on the effect of bifunctional chelators (BFC) namely, NOTA, DOTA, and DTPA, on the radiochemical formulation, in vitro stability, and in vivo biological properties of ⁶⁸Ga-labeled RGD peptide derivatives.METHODS: The three RGD conjugates namely, NOTA-Bn-E-[c(RGDfk)]₂, DOTA-Bn-E-[c(RGDfk)]₂, and DTPA-Bn-E-[c(RGDfk)]₂ were radiolabeled with ⁶⁸Ga and the radiolabeling was optimized with respect to the ligand amount, radiolabeling time, and temperature. Further, the ⁶⁸Ga complexes were assessed for their in vitro and in vivo stabilities. The biodistribution studies of the three radiolabeled conjugates were carried out in C57BL/6 mice bearing melanoma tumor at 30 min and 1 h post-adimistration.RESULTS: NOTA-Bn-E-[c(RGDfk)]₂ could be radiolabeled with ⁶⁸Ga at room temperature while DOTA-Bn-E-[c(RGDfk)]₂ and DTPA-Bn-E-[c(RGDfk)]₂ were radiolabeled at high temperature. ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ was found to be the most kinetically rigid in in vitro stability assay. The uptake of the three radiolabeled peptide conjugates in melanoma tumor was comparable at 1 h post-administration (NOTA; DOTA; DTPA (% I.D./g):: 2.78 ± 0.38; 3.08 ± 1.1; 3.36 ± 0.49). However, the tumor/background ratio of ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ was the best amongst the three radiotracers. ⁶⁸Ga-complexes of NOTA-Bn-E-[c(RGDfk)]₂ and DOTABn-E-[c(RGDfk)]₂ showed excellent in vivo stability while ⁶⁸Ga-DTPA-Bn-E-[c(RGDfk)]₂ showed significant metabolic degradation.CONCLUSION: These studies show that ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ would be the most appropriate ⁶⁸Ga-labeled radiotracer and the most amenable for kit formulation.

The role of IL-17 in tumor angiogenesis and metastasis / 医学研究生学报

Th17 cells have recently emerged as a third independent helper T(Th) cell subset that is different from the classical Th1 and Th2 cells.Th17 cells can specifically secrete IL-17 and play an important role in tumorigenesis and metastasis.In this article, we review the origin and differentiation regulation of Th17 cells, the relationship between IL-17 and tumor microenvironment, angiogenesis and metastasis, and try to provide a new direction for the diagnosis and treatment of tumor.

Research progress of FBLN-5 in the role of tumorigensis / 天津医药

Fibulin protein family has widely existed in the extracellular matrix, and plays an important role in maintain the stable of basement membrane, elastic fibers and loose connective tissue. Fibulin-5 (FBLN-5) is one of the members of the Fibulin protein family, which is essential to the structure function and cell mediated action. The lack of FBLN-5 will cause many diseases such as internal organ deformity. Current research suggests that changes of expression level of FBLN-5 are associated with the occurrence of tumors such as lung cancer, and also can influence the tumor proliferation, invasion and prognosis, thus may become a new molecular marker for cancer diagnosis. Therefore, in this review, we summarize and update biological characteristics and functions of FBLN-5, and its role in the development of tumor formation mechanism.

HSYA inhibits angiogenesis of H 22 transplanted tumor tissue and down-regulation of MMP-3 expression in mice / 基础医学与临床

Objective To investigate the inhibitory effect of hydroxy safflor yellow A ( HSYA ) on angiogenesis of H22 tumor-bearing mice and it's effects on the protein expression of MMP-3 .Methods After establishing the hep-atoma model for 24 h, the mice were randomly divided into control group , sorafenib group and HSYA group , the dose HSYA group received intraperitoneal injection at different dosages (1.125 and 2.25 mg/kg).The pathologi-cal changes were examined with HE staining , immunohistochemical staining and Western blot were applied to meas-ure the expression of angiogenesis related factor ( MMP-3 ) and we also detected the microvessel density with CD 34 . Results Compared with control group , the tumor cells proliferation and the new angiogenesis in HSYA group were suppressed .The expression of MMP-3 in HSYA group was significant reduced .Especially the dose of 2.25 mg/kg HSYA group ( P<0.01 ) , and tumor MVD-CD34 was also significantly reduced ( P<0.01 ) .But the effect is not better than sorafenib group .Conclusions HSYA may inhibit angiogenesis of tumor tissue in a certain concentration range and the anti-angiogenesis effect of HSYA may be related to inhibition of the protein expression of matrix met-alloproteinase-3 .

Progress on radionuclide-labeled small peptides in targeting tumor angiogenesis / 中国肿瘤临床

Early diagnosis and precision medicine generally show significant differences in the prognosis of patients with carcinoma. Angiogenesis not only plays a key role in tumor pathophysiology but also acts as an important drug target. Peptides with specific se-quences can target specific molecules on the endothelial cellular membrane during tumor angiogenesis. Radionuclide-labeled molecu-lar probes exhibit many advantages in oncotherapy. This article focuses on the progress of radionuclide-labeled RGD and RRL in radio-immunoimaging and radioimmunotherapy targeting tumor angiogenesis.