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Biomaterials Aug 2021Different from chemical (small molecular inhibitor) and biological (monoclonal antibody) drugs, herein, based on angiogenesis-related neuropilin-1 (NRP-1), we develop a...
Different from chemical (small molecular inhibitor) and biological (monoclonal antibody) drugs, herein, based on angiogenesis-related neuropilin-1 (NRP-1), we develop a biomimetic superstructure drug, i.e. an antibody-like peptidic network (ALPN) to achieve the high-efficient treatment of choroidal neovascularization (CNV). The ALPN in nanoparticulated formulation (ALPN-NP) can bind NRP-1 through targeting unit and form fibrous peptidic networks trapping NRP-1 on the surface of endothelial cells (ECs), leading to anti-angiogenesis. The ALPN shows high-efficacy against angiogenesis in CNV rat model ascribed to the superstructure-enhanced binding and blockage of NRP-1. The very low dose of ALPN (0.263 μg/Kg) exhibits similar anti-angiogenesis effect comparing with monoclonal antibody bevacizumab (23.5 μg/Kg), which shows potential advantages over traditional monoclonal antibodies.
Topics: Angiogenesis Inhibitors; Animals; Choroidal Neovascularization; Endothelial Cells; Neuropilin-1; Peptides; Rats
PubMed: 34051670
DOI: 10.1016/j.biomaterials.2021.120900 -
International Journal of Cancer Aug 2023Treatments for NSCLC patients with EGFR-TKI resistance are limited. Given that immunotherapy and antiangiogenic agents may have synergistic antitumor effects, we aimed...
Treatments for NSCLC patients with EGFR-TKI resistance are limited. Given that immunotherapy and antiangiogenic agents may have synergistic antitumor effects, we aimed to analyze the effect of multi-target angiogenesis inhibitor anlotinib and immune checkpoint inhibitors (ICIs) combination therapy in NSCLC patients who failed EGFR-TKI. The medical records of lung adenocarcinoma (LUAD) patients with EGFR-TKI resistance were reviewed. After EGFR-TKI resistance, patients who simultaneously received anlotinib and ICIs were enrolled in the observation group, and those who received platinum-pemetrexed chemotherapy were included in the control group. A total of 80 LUAD patients were reviewed and allocated to the anlotinib and ICIs combination therapy (n = 38) and chemotherapy (n = 42) groups. A re-biopsy was performed in all patients in the observation group before the administration of anlotinib and ICIs. The median follow-up was 15.63 months (95% CI: 12.19-19.08). Combination therapy exhibited better PFS (median PFS: 4.33 months [95% CI: 2.62-6.05] vs 3.60 months [95% CI: 2.48-4.73], P = .005), and better OS (median OS: 14.17 months [95% CI: 10.17-18.17] vs 9.00 months [95% CI: 6.92-11.08], P = .029) than chemotherapy. Most patients (73.7%) received combination therapy as fourth and later lines of therapy, with a median PFS of 4.03 months (95% CI: 2.05-6.02) and a median OS of 13.80 months (95% CI: 8.25-19.36). The disease control rate was 92.1%. Four patients discontinued the combination therapy due to adverse events, but the other adverse reactions were manageable and reversible. The combination of anlotinib and PD-1 inhibitors is a promising regimen for the late-line treatment of LUAD patients with EGFR-TKI resistance.
Topics: Humans; Adenocarcinoma of Lung; Angiogenesis Inhibitors; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Immune Checkpoint Inhibitors; Lung Neoplasms; Mutation; Protein Kinase Inhibitors
PubMed: 37078587
DOI: 10.1002/ijc.34536 -
Current Drug Targets 2017Specific blocking of interactions between ligands and receptors along the angiogenic pathways represents an effective approach for enhancing the efficacy as well as... (Review)
Review
Specific blocking of interactions between ligands and receptors along the angiogenic pathways represents an effective approach for enhancing the efficacy as well as reducing adverse effects of chemotherapy. Over the past decade, there was a rapid progression in the application of this therapeutic strategy in cancer treatment. Anti-angiogenic therapy is the most promising targeted therapy for ovarian cancer. The addition of bevacizumab to conventional chemotherapy, either in the first-line setting or at disease relapse, may improve overall survival (OS) of ovarian cancer patients, at least in a subset of patients with poor prognosis. In this article, we summarize published data on the major agents used for anti-angiogenic therapy in ovarian cancers. We will review the molecular mechanisms, results of clinical trial of existing agents and describe the development of new agents. The limitations and side effects of angiogenesis inhibitor are also discussed.
Topics: Angiogenesis Inhibitors; Bevacizumab; Clinical Trials as Topic; Female; Humans; Indazoles; Molecular Targeted Therapy; Niacinamide; Ovarian Neoplasms; Phenylurea Compounds; Pyrimidines; Sorafenib; Sulfonamides; Survival Analysis; Treatment Outcome
PubMed: 28443505
DOI: 10.2174/1389450118666170329095807 -
Critical Reviews in Oncology/hematology Aug 2018Currently in cancer treatment, one premise is to use antiangiogenic therapies in association with chemotherapy or radiotherapy to augment their efficacy by benefiting... (Review)
Review
Currently in cancer treatment, one premise is to use antiangiogenic therapies in association with chemotherapy or radiotherapy to augment their efficacy by benefiting from the vascular "normalization" induced by antiangiogenic therapy. This concept defines the time during which the tumor blood vessels adopt normal-like morphology and functionality, i.e. the blood vessels become more mature, the perfusion augments and hypoxia decreases. To date, there is such a diversity of treatment protocols where the type of antiangiogenic to adopt, its dose and duration of administration are different, that knowing when and how to treat is problematic. In this review, we analyzed thoroughly preclinical and clinical studies that use antiangiogenic treatments to benefit from the "normalization" and showed that the effects depend on the type of antiangiogenic administrated (anti-VEGF, anti-VEGFR, Multi-Kinase Inhibitor) and on the duration of treatment. Finally, biomarkers of "normalization" and resistance that could be used in the clinic are presented.
Topics: Angiogenesis Inhibitors; Animals; Humans; Neoplasms; Neovascularization, Pathologic
PubMed: 29958627
DOI: 10.1016/j.critrevonc.2018.06.001 -
International Journal of Molecular... Feb 2023Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease and remains without specific treatment. To identify new events during FSGS...
Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease and remains without specific treatment. To identify new events during FSGS progression, we used an experimental model of FSGS associated with nephroangiosclerosis in rats injected with L-NAME (N-nitro-L-arginine methyl ester). After transcriptomic analysis we focused our study on the role of Isthmin-1 (ISM1, an anti-angiogenic protein involved in endothelial cell apoptosis. We studied the renal expression of ISM1 in L-NAME rats and other models of proteinuria, particularly at the glomerular level. In the L-NAME model, withdrawal of the stimulus partially restored basal ISM1 levels, along with an improvement in renal function. In other four animal models of proteinuria, ISM1 was overexpressed and localized in podocytes while the renal function was degraded. Together these facts suggest that the glomerular expression of ISM1 correlates directly with the progression-recovery of the disease. Further in vitro experiments demonstrated that ISM1 co-localized with its receptors GRP78 and integrin αvβ5 on podocytes. Treatment of human podocytes with low doses of recombinant ISM1 decreased cell viability and induced caspase activation. Stronger ISM1 stimuli in podocytes dropped mitochondrial membrane potential and induced nuclear translocation of apoptosis-inducing factor (AIF). Our results suggest that ISM1 participates in the progression of glomerular diseases and promotes podocyte apoptosis in two different complementary ways: one caspase-dependent and one caspase-independent associated with mitochondrial destabilization.
Topics: Animals; Humans; Rats; Angiogenesis Inhibitors; Caspases; Disease Models, Animal; Glomerulosclerosis, Focal Segmental; NG-Nitroarginine Methyl Ester; Podocytes; Proteinuria
PubMed: 36769045
DOI: 10.3390/ijms24032723 -
Journal of Natural Products Feb 2023Angiogenesis and vasculogenic mimicry (VM) are crucial for the growth and metastasis of non-small-cell lung cancer (NSCLC). Most tumor angiogenesis inhibitors mainly...
Angiogenesis and vasculogenic mimicry (VM) are crucial for the growth and metastasis of non-small-cell lung cancer (NSCLC). Most tumor angiogenesis inhibitors mainly target endothelial cell-mediated angiogenesis, ignoring tumor-cell-mediated VM and frequently leading to tumor recurrence and metastasis. Thus, development of bioactive molecules interfering with both tumor angiogenesis and VM is necessary. Identifying novel angiogenesis inhibitors from natural products is a promising strategy. Scoparasin B, a pimarane diterpene extracted from a marine-derived fungus, sp. F0219, has an antibacterial effect. However, its effect on angiogenesis and VM remains unexplored. In this study, we first certified that scoparasin B showed a strong inhibition effect on angiogenesis and the VM process in vitro and ex vivo. Moreover, scoparasin B prominently impeded tumor growth, angiogenesis, and VM in an NCI-H1299 xenograft model. Further study revealed that scoparasin B restrained tumor angiogenesis and VM by reducing the VEGF-A level and suppressing the VEGF-A/VEGFR2 signaling pathway. This study first demonstrated scoparasin B inhibited tumor angiogenesis, VM, and tumor growth of NSCLC and revealed its underlying mechanism. These new findings further support the potential of scoparasin B as a novel angiogenesis inhibitor and give a hint for further exploring potential angiogenesis inhibitors from natural products.
Topics: Humans; Angiogenesis Inhibitors; Biological Products; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Lung Neoplasms; Neoplasm Recurrence, Local; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A
PubMed: 36692021
DOI: 10.1021/acs.jnatprod.2c00979 -
Expert Review of Gastroenterology &... Aug 2016Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2, has demonstrated encouraging anti-cancer activity in gastric cancer within both in... (Review)
Review
INTRODUCTION
Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2, has demonstrated encouraging anti-cancer activity in gastric cancer within both in vitro and in vivo models.
AREAS COVERED
Apatinib's efficacy, tolerability and safety have been evaluated in one Phase II and one Phase III study in metastatic/advanced gastric cancer. In this review, we focus on the mechanism of action of apatinib, its pharmacokinetic profile and its clinical activity in the treatment of advanced/metastatic gastric cancer. Expert commentary: Unfortunately, as yet, there is no definitive biomarker data for apatinib in gastric cancer.
Topics: Angiogenesis Inhibitors; Animals; Humans; Molecular Targeted Therapy; Neovascularization, Pathologic; Protein Kinase Inhibitors; Pyridines; Signal Transduction; Stomach Neoplasms; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-2
PubMed: 27376400
DOI: 10.1080/17474124.2016.1209407 -
Biomedicine & Pharmacotherapy =... Sep 2018Angiogenesis appears to be intrinsically associated with the progression of chronic liver diseases, which eventually leads to the development of cirrhosis and related... (Review)
Review
Angiogenesis appears to be intrinsically associated with the progression of chronic liver diseases, which eventually leads to the development of cirrhosis and related complications, including hepatocellular carcinoma. Several studies have suggested that this association is relevant for chronic liver disease (CLD) progression, with angiogenesis. The fact that angiogenesis plays a pivotal role in CLDs gives rise to new opportunities for treating CLDs. Inhibitor of angiogenesis has proved effective for the treatment of patients suffering from CLD. However, it is limited in diagnosis. The last decade has witnessed a plethora of publications which elucidate the potential of angiogenesis inhibitors for the therapy of CLD. The close relationship between the progression of CLDs and angiogenesis emphasizes the need for anti-angiogenic therapy to block/slow down CLD progression. The present review summarizes all these discussions, the results of the related studies carried out to date and the future prospects in this field. We discuss liver angiogenesis in normal and pathophysiologic conditions with a focus on the role and future use of angiogenic factors as second-line treatment of CLD. This review compiles relevant findings and offers opinions that have emerged in last few years relating liver angiogenesis and its treatment using anti-angiogenic factors.
Topics: Angiogenesis Inhibitors; Chronic Disease; Humans; Liver Diseases; Molecular Targeted Therapy; Neovascularization, Pathologic; Translational Research, Biomedical
PubMed: 29859468
DOI: 10.1016/j.biopha.2018.05.102 -
Expert Opinion on Pharmacotherapy Oct 2019: Investigational anti-VEGF treatments for neovascular age-related macular degeneration (nAMD) aim to improve visual outcomes and reduce treatment burden; these include... (Review)
Review
: Investigational anti-VEGF treatments for neovascular age-related macular degeneration (nAMD) aim to improve visual outcomes and reduce treatment burden; these include long-acting agents, combination strategies, topical agents, sustained-release, and genetic therapies. : The authors provide a comprehensive review of investigational therapies for nAMD, focusing on therapies currently in clinical trial. : Long-acting anti-VEGF agents have demonstrated promising results in phase 3 studies, and include Brolucizumab, a single-chain antibody fragment, and Abicipar, a designed ankyrin repeat protein (DARPin). Other unique anti-VEGF agents in current trials include Conbercept - a fusion protein of the VEGF receptor domains, KSI-301 - an anti-VEGF antibody biopolymer conjugate, and OPT-302 - an inhibitor of VEGF-C/D. Strategies to activate the Tie-2 receptor, some in combination with VEGF inhibition, are of interest, with recent trials of Faricimab, ARP-1536, and nesvacumab. Topical anti-VEGF ± anti-PDGF agents, such as pazopanib, squalamine lactate, regorafenib, and LHA510 have shown limited efficacy and/or have not been advanced, although PAN-90806 continues to advance with promising initial results. Sustained-release anti-VEGF treatments, to address treatment burden, include the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305. Similarly, genetic therapies, including RGX-314 and ADVM-022, aim to provide sustained anti-VEGF expression from the retina.
Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Humans; Macular Degeneration
PubMed: 31298960
DOI: 10.1080/14656566.2019.1636031 -
Journal For Immunotherapy of Cancer Nov 2019Hepatocellular carcinoma (HCC) is the second deadliest cancer worldwide, due to its high incidence and poor prognosis. Frequent initial presentation at advanced stages... (Review)
Review
Hepatocellular carcinoma (HCC) is the second deadliest cancer worldwide, due to its high incidence and poor prognosis. Frequent initial presentation at advanced stages along with impaired liver function limit the use of a broad therapeutic arsenal in patients with HCC. Although main HCC oncogenic drivers have been deciphered in recent years (TERT, TP53, CTNNB1 mutations, miR122 and CDKN2A silencing), therapeutic applications derived from this molecular knowledge are still limited. Given its high vascularization and immunogenicity, antiangiogenics and immune checkpoint inhibitors (ICI), respectively, are two therapeutic approaches that have shown efficacy in HCC. Depending on HCC immune profile, combinations of these therapies aim to modify the protumoral/antitumoral immune balance, and to reactivate and favor the intratumoral trafficking of cytotoxic T cells. Combination therapies involving antiangiogenics and ICI may be synergistic, because vascular endothelial growth factor A inhibition increases intratumoral infiltration and survival of cytotoxic T lymphocytes and decreases regulatory T lymphocyte recruitment, resulting in a more favorable immune microenvironment for ICI antitumoral activity. First results from clinical trials evaluating combinations of these therapies are encouraging with response rates never observed before in patients with HCC. A better understanding of the balance and interactions between protumoral and antitumoral immune cells will help to ensure the success of future therapeutic trials. Here, we present an overview of the current state of clinical development of antitumoral therapies in HCC and the biological rationale for their use. Moreover, translational studies on tumor tissue and blood, prior to and during treatment, will help to identify biomarkers and immune signatures with predictive value for both clinical outcome and response to combination therapies.
Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Hepatocellular; Clinical Trials as Topic; Combined Modality Therapy; Disease Susceptibility; Humans; Immunomodulation; Liver Neoplasms; Molecular Targeted Therapy; Neovascularization, Pathologic; Treatment Outcome; Tumor Microenvironment
PubMed: 31783782
DOI: 10.1186/s40425-019-0824-5