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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 -
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 -
Biological & Pharmaceutical Bulletin Mar 2022Anti-angiogenic gene therapy is a promising strategy in treating cancer. Endostatin and angiostatin are widely used in tumor anti-angiogenesis therapy. Our previous...
Anti-angiogenic gene therapy is a promising strategy in treating cancer. Endostatin and angiostatin are widely used in tumor anti-angiogenesis therapy. Our previous studies have shown that the BDS-hEA, a baculovirus long-term expressing the fusion protein of human endostatin and angiostatin, has a favorable effect in inhibiting the growth and angiogenesis of hepatocellular carcinoma. The purpose of this study was to further investigate its synergistic antitumor efficiency in combination with low-dose chemotherapeutic gemcitabine (GEM) on the subcutaneous hepatocellular carcinoma xenograft model in nude mice. The results showed that the combined group significantly inhibited (p < 0.05 or p < 0.01 or p < 0.001) the growth of tumor weight and volume, reduced the expression of ki67 (cell proliferation marker), CD31 (angiogenic marker) and Matrix metalloproteinase 9 (MMP-9, tumor invasion and metastasis marker) and increased the apoptosis of tumor cells compared with the monotherapy and control groups, respectively. Synergistic index results showed that BDS-hEA combined with GEM had a synergistic effect in inhibiting tumor volume, proliferation, microvessel density, metastasis and promoting tumor apoptosis. Furthermore, there were no metastatic nodules and obvious pathological changes in liver tissue of the combined group, and the serum liver function indicators aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-BIL), alkaline phosphatase (ALP) and glutamyl transpeptidase (GGT) were significantly reduced (p < 0.05 or p < 0.01 or p < 0.001) in the BDS-hEA or GEM groups compared with the control group. Notably, the combined therapy showed lower levels of liver function indicators than the GEM group. These data support the view that the combination of BDS-hEA and GEM has a synergistic anti-tumor properties and can reduce the damage of liver to certain extent.
Topics: Angiogenesis Inhibitors; Angiostatins; Animals; Baculoviridae; Carcinoma, Hepatocellular; Deoxycytidine; Endostatins; Humans; Liver Neoplasms; Mice; Mice, Nude; Gemcitabine
PubMed: 34937830
DOI: 10.1248/bpb.b21-00857 -
The Journal of Investigative... Dec 2000Vascular tumors occur in approximately 10% of infants, and range from small cherry-red lesions to large, life-threatening tumors. Although the majority of these tumors... (Review)
Review
Vascular tumors occur in approximately 10% of infants, and range from small cherry-red lesions to large, life-threatening tumors. Although the majority of these tumors involute after several years, there are few therapeutic options and their use is limited by the risk of side-effects. The recent increase in understanding of angiogenesis has led to investigations of new antiangiogenic treatment options using models of vascular tumors in mice. These studies have demonstrated the success of a variety of antiangiogenic approaches, including systemic administration of the antiangiogenic proteins AGM-1470 and angiostatin or of the matrix metalloproteinase inhibitor batimastat, and gene gun therapy with interleukin-12. Although these trials provide further evidence of the role of angiogenesis in the enlargement of these vascular tumors, their potential utility and safety await future trials in patients.
Topics: Angiogenesis Inhibitors; Angiostatins; Animals; Cyclohexanes; Disease Models, Animal; Hemangioma; Humans; Neovascularization, Pathologic; O-(Chloroacetylcarbamoyl)fumagillol; Peptide Fragments; Plasminogen; Sesquiterpenes; Skin Neoplasms
PubMed: 11147681
DOI: 10.1046/j.1087-0024.2000.00011.x -
Autoimmunity Nov 2009Angiogenesis is the formation of new capillaries from pre-existing vessels. A number of soluble and cell-bound factors may stimulate neovascularization. The perpetuation... (Review)
Review
Angiogenesis is the formation of new capillaries from pre-existing vessels. A number of soluble and cell-bound factors may stimulate neovascularization. The perpetuation of angiogenesis involving numerous soluble and cell surface-bound mediators has been associated with rheumatoid arthritis (RA). These angiogenic mediators, among others, include growth factors, primarily vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIFs), as well as pro-inflammatory cytokines, various chemokines, matrix components, cell adhesion molecules, proteases and others. Among the several potential angiogenesis inhibitors, targeting of VEGF, HIF-1, angiogenic chemokines, tumor necrosis factor-alpha and the alpha(V)beta(3) integrin may attenuate the action of angiogenic mediators and thus synovial angiogenesis. In addition, some naturally produced or synthetic compounds including angiostatin, endostatin, paclitaxel, fumagillin analogues, 2-methoxyestradiol and thalidomide may be included in the management of RA.
Topics: Angiogenesis Inhibitors; Animals; Arthritis, Rheumatoid; Blood Vessels; Cell Adhesion Molecules; Cytokines; Extracellular Matrix; Humans; Inflammation Mediators; Neovascularization, Pathologic; Receptors, Chemokine; Vascular Endothelial Growth Factor A
PubMed: 19863375
DOI: 10.1080/08916930903143083