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Oncology Letters Jul 2018When Folkman first suggested a theory about the association between angiogenesis and tumor growth in 1971, the hypothesis of targeting angiogenesis to treat cancer was... (Review)
Review
When Folkman first suggested a theory about the association between angiogenesis and tumor growth in 1971, the hypothesis of targeting angiogenesis to treat cancer was formed. Since then, various studies conducted across the world have additionally confirmed the theory of Folkman, and numerous efforts have been made to explore the possibilities of curing cancer by targeting angiogenesis. Among them, anti-angiogenic gene therapy has received attention due to its apparent advantages. Although specific problems remain prior to cancer being fully curable using anti-angiogenic gene therapy, several methods have been explored, and progress has been made in pre-clinical and clinical settings over previous decades. The present review aimed to provide up-to-date information concerning tumor angiogenesis and gene delivery systems in anti-angiogenic gene therapy, with a focus on recent developments in the study and application of the most commonly studied and newly identified anti-angiogenic candidates for anti-angiogenesis gene therapy, including interleukin-12, angiostatin, endostatin, tumstatin, anti-angiogenic metargidin peptide and endoglin silencing.
PubMed: 29963134
DOI: 10.3892/ol.2018.8733 -
Nature Aging May 2021The plasma proteomic changes that precede the onset of dementia could yield insights into disease biology and highlight new biomarkers and avenues for intervention. We...
The plasma proteomic changes that precede the onset of dementia could yield insights into disease biology and highlight new biomarkers and avenues for intervention. We quantified 4,877 plasma proteins in nondemented older adults in the Atherosclerosis Risk in Communities cohort and performed a proteome-wide association study of dementia risk over five years (n = 4,110; 428 incident cases). Thirty-eight proteins were associated with incident dementia after Bonferroni correction. Of these, 16 were also associated with late-life dementia risk when measured in plasma collected nearly 20 years earlier, during mid-life. Two-sample Mendelian randomization causally implicated two dementia-associated proteins (SVEP1 and angiostatin) in Alzheimer's disease. SVEP1, an immunologically relevant cellular adhesion protein, was found to be part of larger dementia-associated protein networks, and circulating levels were associated with atrophy in brain regions vulnerable to Alzheimer's pathology. Pathway analyses for the broader set of dementia-associated proteins implicated immune, lipid, metabolic signaling and hemostasis pathways in dementia pathogenesis.
Topics: Humans; Aged; Proteomics; Alzheimer Disease; Brain; Proteome
PubMed: 37118015
DOI: 10.1038/s43587-021-00064-0 -
Biomedicine & Pharmacotherapy =... Jun 2020Angiogenesis is considered as a major progenitor in the progression of obesity. The current manuscript enumerates the extrinsic role of angiogenesis in obesity. (Review)
Review
PURPOSE
Angiogenesis is considered as a major progenitor in the progression of obesity. The current manuscript enumerates the extrinsic role of angiogenesis in obesity.
RESULT
High caloric diet and lack of physical exercise are the most common causes of obesity and related metabolic conditions. A grossly elevated levels of fat in adipose tissue escalate certain complications which further worsen the state of obesity. Enlargement of white adipose tissue (WAT), deposition of fat mass, proliferation of endothelial cells, production of inflammatory cytokines induces the formation of denovo capillaries from parent microvasculature. Also, several intracellular signaling pathways precipitate obesity. Though, angiostatic molecules (endostatin, angiostatin and TNP-470) have been designed to combat obesity and associated complications.
CONCLUSION
Adipose tissue trigger growth of blood capillaries, and in turn adipose tissue endothelial cells promote pre-adipocyte proliferation. Modulation of angiogenesis and treatment with angiostatic substances may have the potential to impair the progression of obesity.
Topics: Adipocytes; Adipose Tissue; Animals; Biomarkers; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic; Obesity; Receptors, Notch; Vascular Endothelial Growth Factor A
PubMed: 32200253
DOI: 10.1016/j.biopha.2020.110103 -
Seminars in Thrombosis and Hemostasis Sep 2019Cancer-related venous thromboembolism (VTE) is frequent and constitutes the second leading cause of death in patients with cancer. High platelet count is one of... (Review)
Review
Cancer-related venous thromboembolism (VTE) is frequent and constitutes the second leading cause of death in patients with cancer. High platelet count is one of independent predictive factors of cancer-associated VTE. Besides the implication of platelets in cancer-associated VTE, recent clinical and experimental evidences support that platelets play several roles in the progression of malignancies and inversely, cancer can also influence platelet count and activity. The objective of this report is to review the current literature regarding the role of platelets in cancer through experimental results and population-based studies. Platelets are implicated in cancer progression and metastasis through proangiogenic factors (growth factors and signaling pathways), antiangiogenic factors (angiostatin, endostatin, thrombospondin-1), and matrix metalloproteinases. In addition, platelets are involved in cancer-associated thrombosis and thus tumor cell-induced platelet activation, through anionic phospholipids on their surface, released soluble factors, such as P-selectin, CD40 ligand, platelet factor 4, thrombospondin-1 or beta-thromboglobulin, tumor cell procoagulant proteins (tissue factor, urokinase-type plasminogen activator, plasminogen activator inhibitor type 1), and microparticles. Due to these different mechanisms, platelets may represent a potential therapeutic target. The main current treatments against platelets are: (1) acetylsalicylic acid (aspirin) and nonsteroidal anti-inflammatory drugs, nonselective cyclo-oxygenase (COX)-1 and COX-2 inhibitors, which are associated with decreased cancer incidence and better overall survival and (2) irreversible inhibitor of P2Y12 subtype which decreases cancer incidence. Platelets are key players in tumor growth, metastasis, and cancer-associated thrombosis. This multifaceted role identifies them as a relevant therapeutic target for prevention of cancer occurrence and treatment of cancer.
Topics: Blood Platelets; Humans; Neoplasms
PubMed: 31382305
DOI: 10.1055/s-0039-1693475 -
Translational Psychiatry May 2022Angiostatin, an endogenous angiogenesis inhibitor generated by the proteolytic cleavage of plasminogen, was recently reported to contribute to the development of...
Angiostatin, an endogenous angiogenesis inhibitor generated by the proteolytic cleavage of plasminogen, was recently reported to contribute to the development of Alzheimer's disease (AD). However, whether there are pathological changes in angiostatin levels in individuals with AD dementia is unclear, and whether plasma angiostatin has a relationship with major AD pathological processes and cognitive impairment remains unknown. To examine plasma angiostatin levels in patients with AD dementia and investigate the associations of angiostatin with blood and cerebrospinal fluid (CSF) AD biomarkers, we conducted a cross-sectional study including 35 cognitively normal control (CN) subjects and 59 PiB-PET-positive AD dementia patients. We found that plasma angiostatin levels were decreased in AD dementia patients compared to CN subjects. Plasma angiostatin levels were negatively correlated with plasma Aβ42 and Aβ40 levels in AD dementia patients and positively correlated with CSF total tau (t-tau) levels and t-tau/Aβ42 in AD dementia patients with APOE-ε4. In addition, plasma angiostatin levels had the potential to distinguish AD from CN. These findings suggest a link between angiostatin and AD pathogenesis and imply that angiostatin might be a potential diagnostic biomarker for AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Angiostatins; Biomarkers; Cognitive Dysfunction; Cross-Sectional Studies; Humans; Peptide Fragments; tau Proteins
PubMed: 35538065
DOI: 10.1038/s41398-022-01962-6 -
FEBS Letters Aug 2014Angiomotins were originally identified as angiostatin binding proteins and implicated in the regulation of endothelial cell migration. Recent studies have shed light on... (Review)
Review
Angiomotins were originally identified as angiostatin binding proteins and implicated in the regulation of endothelial cell migration. Recent studies have shed light on the role of Angiomotins and other members of the Motin protein family in epithelial cells and in pathways directly linked to the pathogenesis of cancer. In particular, Motins have been shown to play a role in signaling pathways regulated by small G-proteins and the Hippo-YAP pathway. In this review the role of the Motin protein family in these signaling pathways will be described and open questions will be discussed.
Topics: Angiomotins; Animals; Disease; Endothelial Cells; Gene Expression Regulation; Humans; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Microfilament Proteins; Neovascularization, Physiologic; Signal Transduction
PubMed: 24548561
DOI: 10.1016/j.febslet.2014.02.006 -
Expert Opinion on Biological Therapy Oct 2017In neovascular age related macular degeneration (nAMD), gene therapy to chronically express anti-vascular endothelial growth factor (VEGF) proteins could ameliorate the... (Review)
Review
In neovascular age related macular degeneration (nAMD), gene therapy to chronically express anti-vascular endothelial growth factor (VEGF) proteins could ameliorate the treatment burden of chronic intravitreal therapy and improve limited visual outcomes associated with 'real world' undertreatment. Areas covered: In this review, the authors assess the evolution of gene therapy for AMD. Adeno-associated virus (AAV) vectors can transduce retinal pigment epithelium; one such early application was a phase I trial of AAV2-delivered pigment epithelium derived factor gene in advanced nAMD. Subsequently, gene therapy for AMD shifted to the investigation of soluble fms-like tyrosine kinase-1 (sFLT-1), an endogenously expressed VEGF inhibitor, binding and neutralizing VEGF-A. After some disappointing results, research has centered on novel vectors, including optimized AAV2, AAV8 and lentivirus, as well as genes encoding other anti-angiogenic proteins, including ranibizumab, aflibercept, angiostatin and endostatin. Also, gene therapy targeting the complement system is being investigated for geographic atrophy due to non-neovascular AMD. Expert opinion: The success of gene therapy for AMD will depend on the selection of the most appropriate therapeutic protein and its level of chronic expression. Future investigations will center on optimizing vector, promoter and delivery methods, and evaluating the risks of the chronic expression of anti-angiogenic or anti-complement proteins.
Topics: Dependovirus; Genetic Therapy; Genetic Vectors; Humans; Macular Degeneration; RNA Interference; RNA, Small Interfering; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1
PubMed: 28726562
DOI: 10.1080/14712598.2017.1356817 -
Phytomedicine : International Journal... Sep 2023A proprietary Chinese herbal product called Dan-Deng-Tong-Nao softgel capsule (DDTNC) is used to treat ischemic stroke. However, the preventive mechanisms of DDTNC...
Dan-Deng-Tong-Nao softgel capsule promotes angiogenesis of cerebral microvasculature to protect cerebral ischemia reperfusion injury via activating HIF-1α-VEGFA-Notch1 signaling pathway.
BACKGROUND
A proprietary Chinese herbal product called Dan-Deng-Tong-Nao softgel capsule (DDTNC) is used to treat ischemic stroke. However, the preventive mechanisms of DDTNC against cerebral ischemia reperfusion injury (CIRI) haven not been characterized.
OBJECTIVE
To explore the mechanisms of protective effects of DDTNC against CIRI from both internal and external levels.
METHODS
Chemical characterization was performed using UPLC. The potential protective mechanisms of DDTNC against CIRI were predicted using network pharmacology. Model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established in rats. An model of brain microvascular endothelial cells (BMECs) induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was also established. We evaluated neurological deficits, cerebral infarct volume, cortical neuron damage, and mitochondrial swelling in vivo. We evaluated the expression of VEGFR2, VEGFA, HIF-1α, CD31, and CD34 in ischemic cortex, and VEGF, bFGF, BDNF, angiostatin, and endostatin in serum of rats and in BMEC supernatants. We also evaluated cell viability, cytotoxicity, intracellular ROS, apoptosis, and migration ability in vitro.
RESULTS
Seven components were detected in DDTNC. KEGG enrichment analysis showed that DDTNC may modulate angiogenesis via the HIF-1 signaling pathway. DDTNC treatment reduced neurological score and infarct volume, and improved cell morphology of damaged neurons. Transmission electron microscopy showed that DDTNC reduced mitochondria swelling in cortical neurons. Furthermore, DDTNC reduced intracellular ROS and inhibited apoptosis. DDTNC boosted the expression of CD31, CD34, VEGFR2, VEGFA and HIF-1α, highlighting its involvement in angiogenesis, according to immunofluorescence studies. Furthermore, DDTNC enhanced tube formation and migration of BMECs in vitro. ELISA and western blotting indicated that DDTNCCSF induced the expression of VEGF, BDNF and bFGF, reduced the level of angiostatin and endostatin, increased the protein expression of VEGFA, Notch1 and HIF-1α in vitro and in vivo.
CONCLUSIONS
DDTNC promoted angiogenesis to protect brain tissue against MCAO/R, and exerted protective effects against OGD/R in BMECs via activating HIF-1α-VEGFA-NOTCH1 signal transduction pathway.
Topics: Rats; Animals; Endothelial Cells; Vascular Endothelial Growth Factor A; Angiostatins; Brain-Derived Neurotrophic Factor; Endostatins; Reactive Oxygen Species; Signal Transduction; Brain Ischemia; Infarction, Middle Cerebral Artery; Reperfusion Injury; Microvessels; Receptor, Notch1
PubMed: 37487254
DOI: 10.1016/j.phymed.2023.154966 -
International Journal of Molecular... Jan 2019Systemic sclerosis (SSc) is a connective tissue disease of autoimmune origin characterized by vascular dysfunction and extensive fibrosis of the skin and visceral... (Review)
Review
Systemic sclerosis (SSc) is a connective tissue disease of autoimmune origin characterized by vascular dysfunction and extensive fibrosis of the skin and visceral organs. Vascular dysfunction is caused by endothelial cell (EC) apoptosis, defective angiogenesis, defective vasculogenesis, endothelial-to-mesenchymal transition (EndoMT), and coagulation abnormalities, and exacerbates the disease. Fibrinolytic regulators, such as plasminogen (Plg), plasmin, α2-antiplasmin (α2AP), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA) and its receptor (uPAR), plasminogen activator inhibitor 1 (PAI-1), and angiostatin, are considered to play an important role in the maintenance of endothelial homeostasis, and are associated with the endothelial dysfunction of SSc. This review considers the roles of fibrinolytic factors in vascular dysfunction of SSc.
Topics: Angiostatins; Apoptosis; Endothelium; Fibrinolysin; Fibrinolytic Agents; Humans; Plasminogen; Plasminogen Activator Inhibitor 1; Receptors, Urokinase Plasminogen Activator; Scleroderma, Systemic; Signal Transduction; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator; alpha-2-Antiplasmin
PubMed: 30709025
DOI: 10.3390/ijms20030619 -
Clinical Cancer Research : An Official... Feb 2019Hepatocellular carcinoma (HCC) accounts for about 90% of all primary liver cancers and is the second leading cause of cancer-related deaths worldwide. The hypervascular... (Review)
Review
Hepatocellular carcinoma (HCC) accounts for about 90% of all primary liver cancers and is the second leading cause of cancer-related deaths worldwide. The hypervascular nature of most HCC tumors underlines the importance of angiogenesis in the pathobiology of these tumors. Several angiogenic pathways have been identified as being dysregulated in HCC, suggesting they may be involved in the development and pathogenesis of HCC. These data provide practical targets for systemic treatments such as those targeting the vascular endothelial growth factor receptor and its ligand. However, the clinical relevance of other more recently identified angiogenic pathways in HCC pathogenesis or treatment remains unclear. Research into molecular profiles and validation of prognostic or predictive biomarkers will be required to identify the patient subsets most likely to experience meaningful benefit from this important class of agents.
Topics: Angiogenesis Inhibitors; Angiostatins; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Neovascularization, Pathologic; Prognosis; Protein Kinase Inhibitors; Sorafenib; Vascular Endothelial Growth Factor A
PubMed: 30274981
DOI: 10.1158/1078-0432.CCR-18-1254