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Applied Mathematics and Mechanics(English Edition) 2011年第10期32卷 1287-1296页

作者：蔡彦吴洁许世雄龙泉姚伟 Department of Mechanics and Engineering Science Fudan University School of Naval Architecture Ocean and Civil Engineering Shanghai Jiao Tong University Brunel Institute for Bioengineering Brunel University Uxbridge Middlesex UB8 3PH UK

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.

关键词： mathematical tumour angiogenesis tumour growth anti-angiogenic therapy coupled model

Essence of resistance to anti-angiogenic therapy in tumors

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Chinese Medical Journal 2011年第24期124卷 4363-4363页

作者： CHEN Zhong-ping Sun Yat Sen Univ State Key Lab Oncol S China Ctr Canc Guangzhou 510060 Guangdong Peoples R China Sun Yat Sen Univ Dept Neurosurg Neurooncol Ctr Canc Guangzhou 510060 Guangdong Peoples R China

To the Editor： Recently, I read, with great interest, the article Patterns in the occurrence and development of tumors by Lin1 published in your honored journal. The author of the paper suggests that the mechanism of the occurrence and progress of tumors could involve the self-renewal of the cells and repair of injured tissue. The key players are the responding cells,

关键词： Tumor anti-angiogenic therapy vascular mimicry

Progress of Immunotherapy Combined with anti-Angiogenesis therapy in Lung Cancer

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Journal of Biosciences and Medicines 2024年第9期12卷 183-195页

作者： Chenyang Zuo Jinyuan Xie Meng Wang Jun Cai Qingqing Ye Department of Oncology First Affiliated Hospital of Yangtze University Jingzhou China Department of Joint Surgery and Sports Medicine Jingmen Central Hospital Jingmen China Department of Breast Surgery First Affiliated Hospital of Yangtze University Jingzhou China

Lung cancer is the most prevalent and fatal cancer in China and even around the world, and many patients are found in the late stage of lung cancer. For the treatment of advanced lung cancer, in addition to traditional chemotherapy modalities, many emerging treatments are increasingly significant, such as immunotherapy, anti-angiogenic therapy, and targeted therapy. An increasing number of studies have now shown that anti-angiogenic therapy improves the immune microenvironment by enhancing tumor immunity through normalization of tumor vessels. Immunization combined with anti-angiogenic therapy can exert synergistic effects and improve the prognosis of patients. This article summarizes the extent of benefit, current clinical study data, and future prospects of immunotherapy combined with anti-angiogenic agents in the treatment of advanced NSCLC.

关键词： Immunotherapy anti-angiogenic therapy Lung Cancer Tumor Immune Microenvironment

Angiogenesis in hepatocellular carcinoma:mechanisms and anti-angiogenic therapies

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Cancer Biology & Medicine 2023年第1期20卷 25-43页

作者： Changyu Yao Shilun Wu Jian Kong Yiwen Sun Yannan Bai Ruhang Zhu Zhuxin Li Wenbing Sun Lemin Zheng Department of Hepatobiliary Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100043China Department of Pathology Peking University People's HospitalPeking UniversityBeijing 100044China Department of Hepatobiliary Pancreatic Surgery Shengli Clinical Medical College of Fujian Medical UniversityFujian Provincial HospitalFuzhou 350001China The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine School of Basic Medical SciencesKey Laboratory of Molecular Cardiovascular Sciences of Ministry of EducationHealth Sciences CenterPeking UniversityBeijing 100083China Beijing Tiantan Hospital China National Clinical Research Center of Neurological DiseasesAdvanced Innovation Center for Human Brain ProtectionCapital Medical UniversityBeijing 100050China

Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-associated death ***,the process of formation of new blood vessels,is required for cancer cells to obtain nutrients and *** is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth,progression,invasion,and *** anti-angiogenic therapies target mainly tyrosine kinases,vascular endothelial growth factor receptor(VEGFR),and plateletderived growth factor receptor(PDGFR),and are considered effective strategies for HCC,particularly advanced ***,because the survival benefits conferred by these anti-angiogenic therapies are modest,new anti-angiogenic targets must be *** recent studies have determined the underlying molecular mechanisms,including pro-angiogenic factors secreted by HCC cells,the tumor microenvironment,and cancer stem *** this review,we summarize the roles of pro-angiogenic factors;the involvement of endothelial cells,hepatic stellate cells,tumor-associated macrophages,and tumor-associated neutrophils present in the tumor microenvironment;and the regulatory influence of cancer stem cells on angiogenesis in ***,we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC.A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.

关键词： Angiogenesis hepatocellular carcinoma pro-angiogenic factors tumor microenvironment anti-angiogenic therapy

Targeting angiogenesis for liver cancer: Past, present, and future

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Genes & Diseases 2020年第3期7卷 328-335页

作者： Xiao-Dong Zhu Zhao-You Tang Hui-Chuan Sun Department of Liver Surgery and Transplantation Liver Cancer Institute and Zhongshan HospitalFudan UniversityShanghai200032China

Liver cancer,mostly hepatocellular carcinoma(HCC),is the second leading cause of cancer mortality *** patients were diagnosed at an advanced stage,and systemic therapy is the standard of *** the approved systemic therapies for HCC are molecular targeted therapies with anti-angiogenic effects targeting the vascular endothelial growth factor signaling *** and lenvatinib are the first-line treatment,and regorafenib,ramucirumab,and cabozantinib are second-line treatment *** anti-PD-1 antibodies,including nivolumab and pembrolizumab,demonstrated promising anti-tumor effects as monotherapy for advanced HCC in phase II clinical trials,both failed in phase III ***-angiogenic treatment remains the backbone of systemic therapy for *** this review,we summarized the approved anti-angiogenic medicines and discussed the potential strategies to improve the efficacy of anti-angiogenic therapy,including combination therapy with other treatments,and discussed the approaches to overcome the drawbacks of anti-angiogenic therapies.

关键词： anti-angiogenic therapy Combinational therapy Hepatocellular carcinoma Molecular targeted therapy Systemic therapy

Sarcomatoid Intrahepatic Cholangiocarcinoma After Immunotherapy:A Case Report and Review of the Literature

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1240-1249页

作者： Zheng Zeng Yu Liu Jing Yu Qiang Xu Yong Wang Chang Zhao Ou Jiang Department of Abdominal Oncology The Second People’s Hospital of NeijiangNeijiangSichuanChina Department of Pathology The Second People’s Hospital of NeijiangNeijiangSichuanChina

Sarcomatoid carcinoma is a rare tumor that is composed of a mixture of malignant epithelial cells and mesenchymal *** studies have reported that sarcomatoid carci-noma occurs in multiple organs including the ***-matoid intrahepatic cholangiocarcinoma(S-iCCA)is an ex-tremely rare tumor that primarily occurs in the *** case occurred in a middle-aged man who was admitted to our hospital with abdominal *** computed to-mography of the abdomen showed a low-density mass in the upper right posterior lobe of the liver with enhancement in the *** and immunohistochemical examination indicated that the tumor was malignant,with both cancer and sarcoma components,and was positive for cytokeratin and *** patient was diagnosed with *** appeared in the liver and lung 4 months after *** cycles of chemotherapy were *** of enlargement of the tumor,anti-angiogen-ic agents combined with immunotherapy were subsequently given to achieve disease *** the best of our knowl-edge,this is the first reported case of a programmed cell death-1 inhibitor used in a S-iCCA *** purpose of this case report and literature review is to enhance clinician understanding of S-iCCA and to explore safe and effective treatment methods.

关键词： Sarcomatoid intrahepatic cholangiocarcinoma Sarcomatoid degen-eration PD-1 inhibitors anti-angiogenic therapy

Targeting endothelial cell metabolism： new therapeutic prospects？

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Frontiers in Biology 2015年第2期10卷 125-140页

作者： Annalisa Zecchin Laboratory of Angiogenesis and Neurovascular Link Vesalius Research Center VIB Leuven Belgium Laboratory of Angiogenesis and Neurovaseular Link Department of Oncology KU Leuven Leuven Belgium

Endothelial cells （ECs） line blood vessels and function as a vital conduit for oxygen and nutrients, but can also form vascular niches for various types of stem cells. While mostly quiescent throughout adult life, ECs can rapidly switch to a highly active state, and start to sprout in order to form new blood vessels. ECs can also become dysfunctional, as occurs in diabetes and atherosclerosis. Recent studies have demonstrated a key role for EC metabolism in the regulation of angiogenesis, and showed that EC metabolism is even capable of overriding genetic signals. In this review, we will review the basic principles of EC metabolism and focus on the metabolic alterations that accompany EC dysfunction in diabetes and vessel overgrowth in cancer. We will also highlight how EC metabolism influences EC behavior by modulating post-translational modification and epigenetic changes, and illustrate how dietary supplementation of metabolites can change EC responses. Finally, we will discuss the potential of targeting EC metabolism as a novel therapeutic strategy.

关键词： angiogenesis metabolism endothelial cell dysfunction anti-angiogenic therapy

Atezolizumab and bevacizumab as first line therapy in advanced hepatocellular carcinoma:Practical considerations in routine clinical practice

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World Journal of Hepatology 2021年第9期13卷 1132-1142页

作者： Ankit Jain Shivakumar Chitturi Geoffrey Peters Desmond Yip Department of Medical Oncology The Canberra HospitalGarran 2605ACTAustralia ANU Medical School Australian National UniversityCanberra 0200ACTAustralia Gastroenterology and Hepatology Unit Canberra HospitalCanberra 2605ACTAustralia

Hepatocellular carcinoma(HCC)is the most common primary liver *** advanced HCC,sorafenib was considered the standard of care for more than ten *** the atezolizumab and bevacizumab combination has become standard of care for these patients without contraindications to either immune checkpoint inhibitors or antiangiogenic *** now review the practical aspects of the atezolizumab and bevacizumab combination,including current evidence,indications,contraindications,management of adverse events,sequencing of this combination,areas of current knowledge gaps and future areas of active clinical research of this combination for busy clinicians in clinical practice.

关键词： Hepatocellular carcinoma Atezolizumab Bevacizumab Immunotherapy Child Pugh cirrhosis anti-angiogenic therapy

Direct cytosolic siRNA delivery by reconstituted high density lipoprotein for target-specific therapy of tumor angiogenesis

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Direct cytosolic siRNA delivery by reconstituted high densit...

Flk-1 specific kinase inhibitor SU5416 blocked angiogenesis of Lewis carcinoma in mouse and prolonged the survival

第十二届全国青年药学工作者最新科研成果交流会

作者： Yang Ding Yazhe Wang Wei Wang Xiaochen Gu Jianping Zhou Qiang Zhang State Key Laboratory of Natural Medicines Department of PharmaceuticsChina Pharmaceutical University Faculty of Pharmacy University of Manitoba750 McDermot AvenueWinnipegMBCanada R3E 0T5 State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking University

We described here the mechanisms by which small interfering RNA（siRNA） molecules incorporated in reconstituted high density lipoprotein（rHDL） were efficiently transferred into the cytoplasm of cells to perform target-specific therapy of tumor *** fluorescent-tagged apolipoprotein A-I（apoA-1） and cholesterol-conjugated siRNA（Chol-siRNA）,it was confirmed with FACS and confocal microscopic measurements that Chol-siRNA-loaded rHDL nanoparticles（rHDL/Chol-siRNA complexes） were successfully established and apoA-I certainly was attached to the surface of Chol-siRNA-loaded lipoplexes（Lipos/Chol-siRNA complexes）.Stably assembled rHDL/Chol-siRNA complexes demonstrated proper nanosize,quasi-spherical shape and improved nuclease protection over naked *** was also interesting to note that rHDL provided a highly effective approach to transfer Chol-siRNA across the membrane directly into the cytoplasm via the scavenger receptor BI（SR-BI）-mediated non-endocytotic mechanism,thereby bypassing endo-lysosomal *** also showed clear evidence that the in vitro implementation of rHDL for Chol-siRNA-VEGF（Chol-siRNA targeting vascular endothelial growth factor gene） delivery markedly promoted RNA interference（RNAi）-mediated degradation of VEGF mRNA,resulting in down-regulation of secreted VEGF *** vivo fluorescence imaging indicated that near-infrared（MR） dye Cy5 labeled Chol-siRNA-loaded rHDL nanoparticles（rHDL/Cy5-Chol-siRNA complexes） displayed long circulation time,SR-BI positive tumor-selective targeting,and efficient cytosolic delivery ***,intravenous administration of Chol-siRNA-VEGF-loaded rHDL nanoparticles（rHDL/Chol-siRNA-VEGF complexes） significantly enhanced anti-tumor efficacy against breast cancer,decreased VEGF expression level,and inhibited formation of intratumoral microvessels at the tumor *** was concluded that rHDL possessed therapeutic potential and versatility in mediating Chol-siRNA-VEGF direct cytosoli

关键词： Reconstituted high density lipoprotein Cholesterol-conjugated siRNA Direct cytosolic delivery Vascular endothelial growth factor Tumor-selective accumulation anti-angiogenic therapy

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The Chinese-German Journal of Clinical Oncology 2008年第7期7卷 420-423页

作者： Yizhou Luo Shukui Q in Xiaoqiang Gu Guanzheng Yu Jianxin Q ian Jiejun Wang Postdoctoral Workstation of Nanjing Military Area General Hospital of PLA Nanjing 210002 China Department of Oncology The 81th Hospitalof PLA Nanjing 210002 China Department of Oncology Changzheng hospital Shanghai 260433 China

Objective: To reveal the mechanism and effect of SU5416 in the treatment of mouse Lewis cancer in vivo. Methods: Lewis cell was transplanted into groin of C57/B6 mouse by subcutaneous injection, then SU5416 was administrated intraperitoneally to investigate the impact of SU5416 on tumor angiogenesis and growth in vivo. 32 mice were treated with SU5416 at two different doses every day until the end-point. As a control, 8 mice received no treatment and 8 mice were treated with vehicle (DMSO) only after implantation. Results: Median survival in the treated group was statistically longer compared to that in the control groups (P < 0.05) and no significant systemic adverse was observed. Histological analysis of the treated tumors showed an increase in necroses and reduced in angiogenesis compared to the control tumors. Furthermore, the percent of apoptotic cells increased in the treated tumors by FCM, the expressions of VEGF and KDR had no change after SU5416 administration by western blot. Conclusion: SU5416 may be useful therapeutics drug that specifically inhibits the enzymatic activity of KDR kinase and could down regulate the tumor angiogenesis.

关键词： fetal liver kinase-1 (FIk-1) FIk-1 specific kinase inhibitor vascular endothelial growth factor (VEGF) anti-angiogenic therapy