752 results on '"Angiostatins"'
Search Results
2. Role of Angiogenesis in Chronic Radiation Proctitis: New Evidence Favoring Inhibition of Angiogenesis Ex Vivo.
- Author
-
Wu P, Li L, Wang H, Ma T, Wu H, Fan X, Yang Z, Chen D, and Wang L
- Subjects
- Adult, Aged, Angiogenesis Inhibitors pharmacology, Female, Gene Expression Regulation radiation effects, Humans, Male, Middle Aged, Neovascularization, Pathologic, Proctitis etiology, Radiation Injuries, Transcriptome, Angiostatins
- Abstract
Background: Chronic radiation proctitis (CRP), a common complication after radiotherapy for pelvic malignancies, compromises patient quality of life. Vascular damage and aberrant angiogenesis in the mucosal layer are essential histological features, but changes to the submucosal layer are unclear. Thus, we evaluated the histological characteristics and distribution changes of key angiogenic factors in full-layered human CRP samples., Methods: Thirty paraffin-embedded CRP and twenty-nine non-CRP tissues were used to evaluate histopathological changes. Immunohistochemistry with anti-CD34 antibody was performed to calculate microvascular density (MVD). Frozen tissues from eight CRP patients and five non-CRP controls were collected and analyzed by antibody array, which contained sixty human angiogenesis-related factors. Quality controls with positive and negative controls were performed during antibody array analysis. Two differentially expressed factors were confirmed by ELISA., Results: CRP lesions showed vasculopathy, fibrosis, mucosal ulceration, edema, and inflammatory cell infiltration. Human angiogenesis antibody array and ELISA confirmed the increased angiostatin in CRP lesions. Immunohistochemical staining showed dispersed distribution of angiostatin throughout the mucosal and submucosal layers in CRP lesions, while angiostatin accumulated within the vessel lumens in non-CRP tissues. MVD significantly decreased in the submucosal layer of CRP, suggesting a potential association with increased angiostatin., Conclusions: Angiostatin increased and had a distinct distribution in CRP lesions. Compensatory telangiectasia in the mucosa, vessel stenosis, and reduced MVD might attenuate blood flow in the submucosa and contribute to CRP progression. Restoration of vascular functionality by promoting angiogenesis in the submucosal layer may help alleviate CRP in clinical practice.
- Published
- 2018
- Full Text
- View/download PDF
3. Poly(ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors Reduce Reactive Gliosis and Improve Angiostatin Levels in Retina of Diabetic Rats.
- Author
-
Guzyk MM, Tykhomyrov AA, Nedzvetsky VS, Prischepa IV, Grinenko TV, Yanitska LV, and Kuchmerovska TM
- Subjects
- Animals, Down-Regulation drug effects, Male, Rats, Wistar, Retina metabolism, Angiostatins metabolism, Diabetes Mellitus, Experimental metabolism, Gliosis metabolism, Poly (ADP-Ribose) Polymerase-1 antagonists & inhibitors, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Retina drug effects
- Abstract
Diabetic retinopathy (DR) is a multifactorial disease characterized by reactive gliosis and disbalance of angiogenesis regulators, contributing to endothelial dysfunction and microvascular complications. This study was organized to elucidate whether poly(ADP-ribose) polymerase-1 (PARP-1) inhibition could attenuate diabetes-induced damage to macroglia and correct angiogenic disbalance in diabetic rat retina. After 8 weeks of streptozotocin (STZ)-induced diabetes, Wistar male rats were treated with PARP-1 inhibitors, nicotinamide (NAm) or 3-aminobenzamide (3-AB) (100 and 30 mg/kg/daily i.p., respectively), for 14 days. After the 10-weeks experiment period, retinas were undergone an immunohistochemical staining for glial fibrillary acidic protein (GFAP), while western blots were performed to evaluate effects of PAPR-1 inhibitors on the levels of PARP-1, poly(ADP-ribosyl)ated proteins (PARs), GFAP, and angiostatin isoforms. Diabetes induced significant up-regulation and activation of retinal PARP-1, reactive gliosis development, and GFAP overexpression compared to non-diabetic control. Moreover, extensive fragmentation of both PARP-1 and GFAP (hallmarks of apoptosis and macroglia reactivation, respectively) in diabetic retina was also observed. Levels of angiostatin isoforms were dramatically decreased in diabetic retina, sustaining aberrant pro-angiogenic condition. Both NAm and 3-AB markedly attenuated damage to macroglia, evidenced by down-regulation of PARP-1, PARs and total GFAP compared to diabetic non-treated group. PARP-1-inhibitory therapy prevented formation of PARP-1 and GFAP cleavage-derived products. In retinas of anti-PARP-treated diabetic animals, partial restoration of angiostatin's levels was shown. Therefore, PARP-1 inhibitors counteract diabetes-induced injuries and manifest retinoprotective effects, including attenuation of reactive gliosis and improvement of angiogenic status, thus, such agents could be considered as promising candidates for DR management.
- Published
- 2016
- Full Text
- View/download PDF
4. [Role of angiostatins in diabetic complications].
- Author
-
Tykhomyrov AA, Shram SI, and Grinenko TV
- Subjects
- Animals, Diabetic Angiopathies pathology, Humans, Angiostatins metabolism, Diabetic Angiopathies metabolism
- Abstract
Angiogenesis is a process through which new blood vessels form from pre-existing vessels. Angiogenesis is regulated by a number of factors of peptide nature. Disbalance of angiogenic system appears to be the major causative factor contributing vascular abnormalities in diabetes mellitus, resulting in various complications. Angiostatins, which are kringle-containing fragments of plasminogen/plasmin, are known to be powerful physiological inhibitors of neovascularization. In the present review, current literature data on peculiarities of production of angiostatins and their functioning at diabetes mellitus are summarized and analyzed for the first time. Also, role of angiostatins in the pathogenesis of typical diabetic complications, including retinopathies, nephropathies and cardiovascular diseases, is discussed. Data presented in this review may be useful for elaboration of novel effective approaches for diagnostics and therapy of vascular abnormalities in diabetes mellitus.
- Published
- 2015
- Full Text
- View/download PDF
5. Multiple effects of angiostatins in injured cornea
- Author
-
V. L. Bilous and A. O. Tykhomyrov
- Subjects
alkali burn ,angiostatins ,beclin-1 ,cornea ,hif-1α ,mmp-9 ,neovascularization ,vegf ,zo-1 ,Biochemistry ,QD415-436 ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Prolonged inflammation and excessive neovascularization of the cornea due to severe injury can impair optical clarity and lead to vision impairment. Plasminogen kringle (K) fragments, known as angiostatins (AS), play a well-established role as inhibitors of neovascularization by suppressing pro-angiogenic signaling. However, AS effects in the cornea, beyond inhibiting the angiogenesis, are still unexplored. In this study, we estimate the protective effect of two AS variants (K1-3 and K5) against alkali burn injury induced in rabbit and rat corneas. AS K1-3 in the single doses of 0.075 or 0.75 μg (0.1 or 1.0 μM, respectively) or 0.3 μg of AS K5 (1.0 μM) were applied locally as eye drops daily for 14 days after the injury. A significant regression of corneal vessels in-growth in injured eyes treated with AS was revealed. Western blot analysis of corneal tissue lysates revealed that injury-induced overexpression of protein markers of hypoxia (HIF-1α), angiogenesis (VEGF), tissue remodeling and fibrosis (MMP-9), autophagy (beclin-1) and endoplasmic reticulum stress (GRP-78) was significantly reduced under AS treatment. Besides, the level of tight junctions protein ZO-1 was shown to be up-regulated after the treatment of the damaged cornea with AS K1-3. Summarizing, our study uncovered novel biological functions of the kringle-containing plasminogen fragments indicating its beneficial effects during corneal healing in the experimental model of alkali burn. The data obtained can be helpful for the development of novel efficient formulations to manage complications of ocular surface injuries.
- Published
- 2024
- Full Text
- View/download PDF
6. BIOMEDICAL APPLICATION OF K5 PLASMINOGEN FRAGMENT
- Author
-
L.G. Kapustianenko and A.O. Tykhomyrov
- Subjects
angiostatins ,plasminogen fragment kringle 5 ,angiogenesis ,endothelial cells ,neovascular diseases ,tumor growth ,retinopathy. ,Biotechnology ,TP248.13-248.65 - Abstract
Aim. Plasminogen kringle 5 is an endogenous angiogenic inhibitor. The purpose of the present review was to highlight the potential biomedical application of kringle 5 in the regulation of angiogenesis and tumor growth. Methods. Angiogenesis is a complex process that involves endothelial cell proliferation, migration, basement membrane degradation, and neovessel organization. Since the uncontrolled growth of new blood vessels causes the progression of many common diseases, first of all, oncological diseases, autoimmune disorders, neovascular damage of the eye, the use of angiostatins can be a promising pharmacotherapeutic approach to the prevention and adjuvant therapy of these pathological conditions. The advantages of angiostatins application are their non-toxicity even at high doses, non-immunogenicity, lack of tolerance of target cells to their action. Angiostatins comprise a group of kringle-containing proteolytically-derived fragments of plasminogen/plasmin, which act as potent inhibitory mediators of endothelial proliferation and migration. Among all known angiostatin species, isolated K5 plasminogen fragment was shown to display the most potent inhibitory activity against proliferation of endothelial cells via triggering multiple signaling pathways, which lead to cell death and resulting angiogenesis suppression. Results. Current literature data suggest that in addition to expressed and highly specific cytotoxicity in relation to endotheliocytes and some types of tumor cells, the kringle domain 5 of human plasminogen has other advantages as an antiangiogenic and antitumor regulator, including its specific inhibitory activity, which affects only activated, proliferating endothelial cells, and therefore is non-toxic to other types of normal cells. As an endogenous protein, which is formed in the human organism, K5 does not provoke an immune response. K5 as a small polypeptide molecule with a stable structure can be obtained as a recombinant protein in E. coli cells, and can also be used in pharmacokinetic systems of targeted delivery and sustained release. Conclusions. The prospect of successful use of K5 as a therapeutic agent to manage pathological processes associated with dysregulation of angiogenesis makes it necessary to develop and improve methods of its production and to further test its plausible pleiotropic biological activities.
- Published
- 2023
- Full Text
- View/download PDF
7. BIOMEDICAL APPLICATION OF K5 PLASMINOGEN FRAGMENT.
- Author
-
KAPUSTIANENKO, L. G. and TYKHOMYROV, A. O.
- Subjects
- *
PLASMINOGEN , *ESCHERICHIA coli , *RECOMBINANT proteins , *BASAL lamina , *PLASMIN , *ENDOTHELIAL cells , *SMALL molecules - Abstract
Aim. Plasminogen kringle 5 is an endogenous angiogenic inhibitor. The purpose of the present review was to highlight the potential biomedical application of kringle 5 in the regulation of angiogenesis and tumor growth. Methods. Angiogenesis is a complex process that involves endothelial cell proliferation, migration, basement membrane degradation, and neovessel organization. Since the uncontrolled growth of new blood vessels causes the progression of many common diseases, first of all, oncological diseases, autoimmune disorders, neovascular damage of the eye, the use of angiostatins can be a promising pharmacotherapeutic approach to the prevention and adjuvant therapy of these pathological conditions. The advantages of angiostatins application are their non-toxicity even at high doses, non-immunogenicity, lack of tolerance of target cells to their action. Angiostatins comprise a group of kringle-containing proteolytically-derived fragments of plasminogen/plasmin, which act as potent inhibitory mediators of endothelial proliferation and migration. Among all known angiostatin species, isolated K5 plasminogen fragment was shown to display the most potent inhibitory activity against proliferation of endothelial cells via triggering multiple signaling pathways, which lead to cell death and resulting angiogenesis suppression. Results. Current literature data suggest that in addition to expressed and highly specific cytotoxicity in relation to endotheliocytes and some types of tumor cells, the kringle domain 5 of human plasminogen has other advantages as an antiangiogenic and antitumor regulator, including its specific inhibitory activity, which affects only activated, proliferating endothelial cells, and therefore is non-toxic to other types of normal cells. As an endogenous protein, which is formed in the human organism, K5 does not provoke an immune response. K5 as a small polypeptide molecule with a stable structure can be obtained as a recombinant protein in E. coli cells, and can also be used in pharmacokinetic systems of targeted delivery and sustained release. Conclusions. The prospect of successful use of K5 as a therapeutic agent to manage pathological processes associated with dysregulation of angiogenesis makes it necessary to develop and improve methods of its production and to further test its plausible pleiotropic biological activities. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
8. Angiostatins modulate ACE2 and GFAP levels in injured rat cornea and do not affect viability of retinal pigment epithelial cells.
- Author
-
Bilous, V. L., Kapustianenko, L. G., Yusova, O. I., Korsa, V. V., Nedzvetsky, V. S., Ağca, C. A., Ziablitsev, S. V., and Tykhomyrov, A. O.
- Subjects
- *
RHODOPSIN , *ANGIOTENSIN converting enzyme , *CHROMATOPHORES , *CORNEA , *EPITHELIAL cells , *DOWNREGULATION - Abstract
Angiostatins (AS) are proteolytically derived fragments of plasminogen with the established antiangiogenic and anti-inflammatory capacities, which can be useful for ocular surface relief after injury. Aim. To investigate the effects of AS K1-3 and K5 on the protein levels of SARSCoV- 2 receptor, ACE2, and marker of activated satellite glia, GFAP, in the injured rat cornea, and to assess if AS could affect the viability of retinal pigment epithelial (RPE) cells. Methods. AS (K1-3 and K5) were produced by limited proteolysis of plasminogen isolated from human plasma followed by affine chromatography purification. AS (K1-3 0.1 or 1.0 µM, K5 0.1 µM) were applied topically as eye drops in rat model of alkali burn of cornea. The protein levels of ACE2 and GFAP were evaluated in corneal tissue lysates by western blot and expressed as arbitrary units (a.u.). The effects of AS on the viability of RPE cells were evaluated by MTT test. Results. The ocular injury caused by alkali burn induced overexpression of both ACE2 (by 7.7 fold vs. control, P < 0.001) and GFAP (by 62 folds vs. control, P < 0.001). Application of K5 or K1-3 (1.0 µM) reduced the expression level of ACE2 in injured corneas by two-folds (P < 0.05 vs. Burn group), whereas K1-3 (0.1 µM) lowered the content of ACE2 by 3.4-folds compared with the Burn group (P < 0.05) suggesting that AS can decrease a potential risk of SARS-CoV-2 entry due to the down-regulation of its receptor expression. Interestingly, K5 appeared to be more effective in suppressing the GFAP overexpression (by 10.9-fold vs. Burn group, P < 0.01) indicating that AS may act as neuroprotective substances via alleviating excessive response of satellite glia in injured cornea. AS had no cytotoxic effects on retinal pigment endothelium in the range of concentrations 2-100 nM. Conclusions. Collectively, our data may pave the way for a possible application of AS in designing an ophthalmic drug as an effective and safe supplementary with combined protective effects. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
9. The levels of hypoxia- and angiogenesis-related regulators and matrix metalloproteinase 9 activity in tear fluid of patients with non-penetrating ocular traumas
- Author
-
I.V. Gavrylyak, N.K. Greben, V.L. Bilous, V.V. Korsa, D.G. Zhaboiedov, C.A. Ağca, and A.O. Tykhomyrov
- Subjects
tear fluid ,corneal trauma ,d-dimer ,hif-1α ,angiostatins ,matrix metalloproteinase 9 ,Medicine - Abstract
This article was focused on the evaluation of protein biomarkers related to thrombosis, hypoxia, angiogenesis, and tissue remodeling in tear fluid of patients with non-penetrating corneal trauma. 32 patients with non-penetrating corneal injures were enrolled in the study, the control group consisted of 15 healthy patients. Samples of tear fluid were collected from the patients and control volunteers with the use of a disposable end micropipette. Protein levels of D-dimer, hypoxia-inducible factor 1α (HIF-1α), angiostatins, and matrix metalloproteinase 9 (MMP-9) in tear fluids were determined by western blot analysis. Proteolytic activity values of MMP-9 were measured by gelatin zymography. Results of western blot and zymography assay were calculated by densitometry analysis and expressed as arbitrary units. Significant increase of D-dimer and HIF-1α levels in tear fluid of patients with injured cornea by 7.3 (p
- Published
- 2022
- Full Text
- View/download PDF
10. The Roles of Vascular Endothelial Growth Factor, Angiostatin, and Endostatin in Nasal Polyp Development
- Author
-
Tae Ui Hong and Seong Kook Park
- Subjects
nasal polyps ,angiostatins ,endostatins ,vascular endothelial growth factor ,Medicine ,Otorhinolaryngology ,RF1-547 - Abstract
Background and Objectives Microvascular remodeling and angiogenesis are elements of tissue remodeling characteristic of chronic inflammatory diseases, including nasal polyps (NPs). Angiogenesis reflects the balance between the actions of pro- and anti-angiogenic factors. Many pro-angiogenic factors are known, including vascular endothelial growth factor (VEGF). A number of anti-angiogenic factors (e.g., angiostatin and endostatin) also has been identified. Our objective was to assess the roles of VEGF, angiostatin, and endostatin in NP development. Methods The expression levels of VEGF, angiostatin, and endostatin were measured in NPs harvested during endoscopic endonasal surgery and compared with those in inferior turbinate mucosa (control) samples acquired from patients with hypertrophic rhinitis without allergy. Western blotting and immunohistochemical staining were used to analyze all samples. Results The levels of VEGF and angiostatin were significantly higher in the NP subjects than in the controls. Neither the VEGF/angiostatin ratio nor the endostatin level differed significantly between the two groups. However, the VEGF/endostatin ratio was significantly higher in the NP than in the control group. Both the NP and control tissues were diffusely immunoreactive for VEGF, angiostatin, and endostatin. Conclusion NP-associated hypoxia can elevate angiostatin level; moreover, an imbalance in the VEGF/endostatin ratio can contribute to NP formation.
- Published
- 2022
- Full Text
- View/download PDF
11. THE LEVELS OF HYPOXIAAND ANGIOGENESIS-RELATED REGULATORS AND MATRIX METALLOPROTEINASE 9 ACTIVITY IN TEAR FLUID OF PATIENTS WITH NON-PENETRATING OCULAR TRAUMAS.
- Author
-
Gavrylyak, I. V., Greben, N. K., Bilous, V. L., Korsa, V. V., Zhaboiedov, D. G., Ağca, C. A., and Tykhomyrov, A. O.
- Subjects
- *
MATRIX metalloproteinases , *WESTERN immunoblotting , *HYPOXIA-inducible factors , *TISSUE remodeling , *CORNEA injuries - Abstract
This article was focused on the evaluation of protein biomarkers related to thrombosis, hypoxia, angiogenesis, and tissue remodeling in tear fluid of patients with non-penetrating corneal trauma. 32 patients with non-penetrating corneal injures were enrolled in the study, the control group consisted of 15 healthy patients. Samples of tear fluid were collected from the patients and control volunteers with the use of a disposable end micropipette. Protein levels of D-dimer, hypoxia-inducible factor 1α (HIF-1α), angiostatins, and matrix metalloproteinase 9 (MMP-9) in tear fluids were determined by western blot analysis. Proteolytic activity values of MMP9 were measured by gelatin zymography. Results of western blot and zymography assay were calculated by densitometry analysis and expressed as arbitrary units. Significant increase of D-dimer and HIF-1α levels in tear fluid of patients with injured cornea by 7.3 (p<0.05) and 56 (p<0.001) folds, respectively, was shown compared with control, indicating thrombotic events and hypoxia condition to be involved in pathogenesis of ocular trauma. Dramatically elevated levels/activity of MMP-9 enzyme (by 105 folds vs. control, p<0.001) suggest intense tissue remodeling and degradation of extracellular matrix in the damaged cornea. Up-regulation of angiostatin level, products of proteolytical cleavage of plasminogen, in tear fluid collected from patients with traumatic eye in comparison with healthy volunteers (by 7.3 folds, p<0.05), could represent an adaptive mechanism, which counteracts excessive hypoxia-induced neovascularization in injured cornea. It is summarized that there was a strong association between elevation of D-dimer, HIF-1α, angiostatins, and MMP-9 levels suggesting thrombosis- and hypoxia-mediated mechanisms triggering wound healing of injured cornea. The findings of this study are novel and provide a basis for further investigations of the reparation mechanisms during non-penetrating ocular trauma. Studied proteins of the tear fluid can serve as relevant biomarkers of corneal wound healing and are appropriate for diagnostic and prognostic purposes. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
12. Reports from Tokyo University of Agriculture and Technology Add New Study Findings to Research in Beta-Globulins (Anti-angiogenic activity of a novel angiostatin-like plasminogen fragment produced by a bacterial metalloproteinase).
- Abstract
A recent report from Tokyo University of Agriculture and Technology discusses new research on beta-globulins and their role in tumor growth and angiogenesis. The researchers have developed a method for producing and purifying an angiostatin-like plasminogen fragment called BL-angiostatin, which has shown anti-angiogenic activity in vitro and inhibited tumor growth in mice. The fragment contains unique features not found in other angiostatins tested for cancer treatment. The study suggests that BL-angiostatin has potential therapeutic applications. For more information, the full article can be accessed for free at the provided link. [Extracted from the article]
- Published
- 2024
13. General Hospital of Ningxia Medical University Researchers Provide New Data on Liver Cancer (Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular...).
- Abstract
A study conducted by researchers at the General Hospital of Ningxia Medical University in China explores the anti-angiogenic effects of a fusion protein called BDS-hEA on hepatocellular carcinoma (HCC), a highly vascularized liver cancer. The researchers found that BDS-hEA induced autophagy in vascular endothelial cells, leading to a decrease in angiogenesis. They also discovered that BDS-hEA modulated the AMPK/AKT/mTOR signaling pathway, resulting in cytotoxic effects against HCC. These findings suggest that BDS-hEA has potential as a therapeutic approach for inhibiting angiogenesis in liver cancer. [Extracted from the article]
- Published
- 2024
14. PRODUCTION AND APPLICATION OF ANGIOSTATINS FOR THE TREATMENT OF OCULAR NEOVASCULAR DISEASES
- Author
-
Bilous V. L., Kapustianenko L. G., and Tykhomyrov A. A.
- Subjects
angiostatins ,ocular neovascular diseases ,retinopathy ,corneal neovascularization ,antiangiogenic therapy ,local gene delivery. ,Biotechnology ,TP248.13-248.65 - Abstract
Angiostatins comprise a group of kringle-containing proteolytically-derived plasminogen/plasmin fragments, which act as potent inhibitory mediators of endothelial sells proliferation and migration. Angiostatins are involved in modulation of vessel growth in healthy tissues and various pathological conditions associated with aberrant neovascularization. The aim of the present paper was to summarize available information, including our own experimental data, on prospects of angiostatin application for treatment of ocular neovascular diseases (OND), focusing on retinal pathologies and corneal injury. In particular, literature data on prospective and retrospective studies, clinical trials and animal models relating to the pathophysiology, investigation and management of OND are described. Special emphasis was made on the laboratory approaches of production of different angiostatin isoforms, as well as comparison of antiangiogenic capacities of native and recombinant angiostatin polypeptides. Several studies reported that angiostatins may completely abolish pathologic angiogenesis in diabetic proliferative retinopathy without affecting normal retinal vessel development and without exhibiting adverse side effects. Angiostatins have been tested as a tool for corneal antiangiogenesis target therapy in order to manage diverse ocular surface pathological conditions induced by traumas, chemical burns, previous surgery, chronic contact lens wear, autoimmune diseases, keratitis and viral infections (herpes, COVID-19), corneal graft rejection, etc. Among all known angiostatin species, isolated K5 plasminogen fragment was shown to display the most potent inhibitory activity against proliferation of endothelial cells via triggering multiple signaling pathways, which lead to cell death and resulting angiogenesis suppression. Application of adenoviral genetic construct encoding angiostatin K5 as a promising tool for OND treatment illustrates a vivid example of upcoming revolution in local gene therapy. Further comprehensive studies are necessary to elucidate the clinical potential and optimal regimes of angiostatin-based intervention modalities for treating ocular neovascularization.
- Published
- 2021
- Full Text
- View/download PDF
15. Plasminogen modulates formation and release of platelet angiogenic regulators
- Author
-
A. A. Tykhomyrov, D. D. Zhernosekov, and T. V. Grinenko
- Subjects
angiogenesis ,angiostatins ,plasminogen ,platelets ,vascular endothelial growth factor (vegf) ,Biochemistry ,QD415-436 ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Platelets store, produce and release a variety of angiogenesis regulators, which can contribute to both normal tissue repair and angiopathy-associated pathologies. Plasminogen has been earlier shown to regulate some platelet functions, but if it is able to modulate angiogenic capacities of platelets is still poorly studied. Thus, the aim of the present study was to evaluate the effects of different plasminogen forms on the formation and secretion of angiogenic protein regulators by platelets. Human washed platelets were obtained by gel-filtration on Sepharose-2B. The levels of P-selectin (CD-62P) exposed on the plasma membrane of untreated and activated platelets was monitored by flow cytometry. Secretion of platelet-derived vascular endothelial growth factor (VEGF) as well as plasminogen fragmentation and angiostatin formation by intact platelets and platelet plasma membranes were analyzed by immunoblotting. It was shown that thrombin or collagen exposure resulted in enhanced P-selectin surface expression by platelets, while Lys-form of plasminogen reduced agonist-induced platelet secretion. Lys-plasminogen, but not Glu-form, inhibited agonist-induced VEGF release from platelets. Activation of platelets significantly accelerated plasminogen cleavage and angiostatin formation. Anti-actin antibodies inhibited plasminogen fragmentation during incubation with platelet plasma membranes indicating surface-exposed actin participation in plasminogen conversion to angiostatins. The present study uncovers a novel function of plasminogen to limit angiogenic potential of platelets via angiostatin formation and inhibition of VEGF secretion.
- Published
- 2020
- Full Text
- View/download PDF
16. Treatment of medulloblastoma with oncolytic measles viruses expressing the angiogenesis inhibitors endostatin and angiostatin
- Author
-
Hutzen, Brian, Bid, Hemant Kumar, Houghton, Peter J, Pierson, Christopher R, Powell, Kimerly, Bratasz, Anna, Raffel, Corey, and Studebaker, Adam W
- Subjects
Genetics ,Brain Cancer ,Gene Therapy ,Pediatric ,Cancer ,Neurosciences ,Brain Disorders ,Rare Diseases ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Good Health and Well Being ,Angiogenesis Inhibitors ,Angiostatins ,Animals ,Cell Line ,Tumor ,Chlorocebus aethiops ,Endostatins ,HEK293 Cells ,Human Umbilical Vein Endothelial Cells ,Humans ,Measles virus ,Medulloblastoma ,Mice ,Neoplasms ,Experimental ,Oncolytic Virotherapy ,Oncolytic Viruses ,Vero Cells ,Xenograft Model Antitumor Assays ,Oncolytic measles virus ,Angiogenesis ,Endostatin ,Angiostatin ,Oncology and Carcinogenesis ,Public Health and Health Services ,Oncology & Carcinogenesis - Abstract
BackgroundMedulloblastoma is the most common type of pediatric brain tumor. Although numerous factors influence patient survival rates, more than 30% of all cases will ultimately be refractory to conventional therapies. Current standards of care are also associated with significant morbidities, giving impetus for the development of new treatments. We have previously shown that oncolytic measles virotherapy is effective against medulloblastoma, leading to significant prolongation of survival and even cures in mouse xenograft models of localized and metastatic disease. Because medulloblastomas are known to be highly vascularized tumors, we reasoned that the addition of angiogenesis inhibitors could further enhance the efficacy of oncolytic measles virotherapy. Toward this end, we have engineered an oncolytic measles virus that express a fusion protein of endostatin and angiostatin, two endogenous and potent inhibitors of angiogenesis.MethodsOncolytic measles viruses encoding human and mouse variants of a secretable endostatin/angiostatin fusion protein were designed and rescued according to established protocols. These viruses, known as MV-hE:A and MV-mE:A respectively, were then evaluated for their anti-angiogenic potential and efficacy against medulloblastoma cell lines and orthotopic mouse models of localized disease.ResultsMedulloblastoma cells infected by MV-E:A readily secrete endostatin and angiostatin prior to lysis. The inclusion of the endostatin/angiostatin gene did not negatively impact the measles virus' cytotoxicity against medulloblastoma cells or alter its growth kinetics. Conditioned media obtained from these infected cells was capable of inhibiting multiple angiogenic factors in vitro, significantly reducing endothelial cell tube formation, viability and migration compared to conditioned media derived from cells infected by a control measles virus. Mice that were given a single intratumoral injection of MV-E:A likewise showed reduced numbers of tumor-associated blood vessels and a trend for increased survival compared to mice treated with the control virus.ConclusionsThese data suggest that oncolytic measles viruses encoding anti-angiogenic proteins may have therapeutic benefit against medulloblastoma and support ongoing efforts to target angiogenesis in medulloblastoma.
- Published
- 2014
17. Levels of angiogenic regulators and MMP-2, -9 activities in Martorell ulcer: a case report
- Author
-
O. M. Petrenko and A. A. Tykhomyrov
- Subjects
angiogenic regulators ,angiostatins ,chronic wounds ,Martorell ulcer ,MMP ,VEGF ,Biochemistry ,QD415-436 ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Martorell hypertensive ischemic leg ulcers (HYTILU) represent a unique form of lower extremity non-healing ulcers that develop in association with poorly controlled high blood pressure. The present study was performed in order to assess levels of protein regulators of angiogenesis (vascular endothelial growth factor, or VEGF, and angiostatins) and to evaluate activities of matrix metalloproteinases (MMPs) (gelatinases MMP-2 and -9) in wound cutaneous tissue in the case of patient with 2-years HYTILU history. VEGF and angiostatin levels were analyzed by Western blot, MMP activities were evaluated by gelatin zymography. We report here for the first time that wound tissue in HYTILU is characterized with increased levels of VEGF (by 75 folds vs. histologically normal tissue, P < 0.01) and dramatic overproduction of angiostatin levels, which are undetectable in healthy cutaneous tissue. Approximately 10-fold elevation in MMP-2 and -9 activities is observed in wound tissue as compared with uninjured cutaneous tissue. Obtained results indicate that increased production of angiogenic inhibitors, angiostatins, may counteract VEGF-induced pro-angiogenic signaling, and together with MMP overactivation, contributes to failed healing of ischemic ulcer. Further extended studies are needed to clarify how changes of angiogenic profile and imbalance of proteolytic activities in non-healing Martorell ulcers can be considered during their management procedures to improve efficacy of surgery debridement and/or skin grafting.
- Published
- 2019
- Full Text
- View/download PDF
18. The levels of hypoxia- and angiogenesis-related regulators and matrix metalloproteinase 9 activity in tear fluid of patients with non-penetrating ocular traumas
- Author
-
Gavrylyak, I.V., Greben, N.K., Bilous , V.L., Korsa , V.V., Zhaboiedov , D.G., Ağca , C.A., and Tykhomyrov, A.O.
- Subjects
angiostatins ,tear fluid ,D-dimer ,HIF-1α ,matrix metalloproteinase 9 ,General Medicine ,corneal trauma ,tear fluid, corneal trauma, D-dimer, HIF-1α, angiostatins, matrix metalloproteinase 9 - Abstract
This article was focused on the evaluation of protein biomarkers related to thrombosis, hypoxia, angiogenesis, and tissue remodeling in tear fluid of patients with non-penetrating corneal trauma. 32patients with non-penetrating corneal injures were enrolled in the study, the control group consisted of 15 healthy patients. Samples of tear fluid were collected from the patients and control volunteers with the use of a disposable end micropipette. Protein levels of D-dimer, hypoxia-inducible factor 1α (HIF-1α), angiostatins, and matrix metalloproteinase 9 (MMP-9) in tear fluids were determined by western blot analysis. Proteolytic activity values of MMP-9 were measured by gelatin zymography. Results of western blot and zymography assay were calculated by densitometry analysis and expressed as arbitrary units. Significant increase of D-dimer and HIF-1α levels in tear fluid of patients with injured cornea by 7.3 (p
- Published
- 2022
19. Researchers from Department of Cardiology Detail New Studies and Findings in the Area of Fabry Disease (Overexpression of VEGFa as a biomarker of endothelial dysfunction in aortic tissue of a-GAL-Tg/KO mice and its upregulation in the serum of...).
- Abstract
A recent study conducted by researchers from the Department of Cardiology focused on Fabry disease, an X-linked lysosomal storage disorder that can lead to organ failure. The study examined the expression of angiogenic factors, VEGFa and angiostatin, in aortic tissue of mice with Fabry disease and measured their levels in the serum of patients with the disease. The results showed an overexpression of VEGFa and a decrease in angiostatin in the aortic tissue of mice with Fabry disease, suggesting endothelial dysfunction. Additionally, elevated levels of VEGFa were found in the serum of patients with Fabry disease and were associated with markers of organ manifestation. These findings indicate that VEGFa may serve as a potential biomarker for detecting endothelial dysfunction in Fabry disease. [Extracted from the article]
- Published
- 2024
20. Reports Summarize Epilepsy Findings from Zunyi Medical University [Phosphoglycerate Kinase (Pgk) 1 Succinylation Modulates Epileptic Seizures and the Blood-brain Barrier].
- Abstract
A recent study conducted by researchers at Zunyi Medical University in Guizhou, China, has explored the role of phosphoglycerate kinase (PGK) 1 succinylation in epilepsy. The study found that the expression of PGK1 succinylation was decreased in a rat model of acute epilepsy, and that mutations in the K15 site of PGK1 affected the expression of succinylation and the integrity of the blood-brain barrier. These findings suggest that PGK1 succinylation may be a potential target for new treatment strategies for epilepsy. The study was funded by the National Natural Science Foundation of China and the Science and Technology Project in Guizhou Province. [Extracted from the article]
- Published
- 2024
21. Angiostatin-functionalized collagen scaffolds suppress angiogenesis but do not induce chondrogenesis by mesenchymal stromal cells in vivo.
- Author
-
Helgeland, Espen, Pedersen, Torbjørn O., Rashad, Ahmad, Johannessen, Anne C., Mustafa, Kamal, and Rosén, Annika
- Abstract
Tissue engineering for fibrocartilage regeneration using mesenchymal stromal cells (MSC) and biomaterial scaffolds is emerging as a promising strategy, but inhibiting vascularization to prevent endochondral ossification is important to develop stable implants. The objective of this study was to investigate the effect of angiostatin on inhibition of angiogenesis and promotion of chondrogenesis by collagen scaffolds with or without MSC implanted subcutaneously in rats. One scaffold from the following groups was implanted in each animal: Collagen scaffolds only, scaffolds functionalized with angiostatin, scaffolds loaded with MSC and scaffolds functionalized with angiostatin and loaded with MSC. The various scaffolds were harvested after 2 and 8 weeks for histological analysis, Real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence quantification. Results demonstrated significantly decreased expression of inflammatory (interleukin 1 alpha and beta) and angiogenic genes (platelet and endothelial cell adhesion molecule 1) in scaffolds functionalized with angiostatin after 2 weeks in vivo. Histologically, after 8 weeks, the scaffolds with angiostatin had less inflammatory cells and more collagen matrix formation, but no fibrocartilage formation was detected. Thus, although angiostatin suppressed angiogenesis, it did not stimulate ectopic chondrogenesis in tissue engineered constructs in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
22. Safety and Efficacy Study of rhAngiostatin Administered in Combination With Paclitaxel and Carboplatin to Patients With Non-Small-Cell Lung Cancer
- Published
- 2009
23. Synergistic Effect of Baculovirus-Mediated Endostatin and Angiostatin Combined with Gemcitabine in Hepatocellular Carcinoma
- Author
-
Yonggan, Ji, Hongli, Fan, Mengmeng, Yang, Changcai, Bai, Wen, Yang, and Zhisheng, Wang
- Subjects
Pharmacology ,Carcinoma, Hepatocellular ,Liver Neoplasms ,Mice, Nude ,Pharmaceutical Science ,Angiogenesis Inhibitors ,General Medicine ,Deoxycytidine ,Gemcitabine ,Endostatins ,Mice ,Animals ,Humans ,Angiostatins ,Baculoviridae - Abstract
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.
- Published
- 2022
24. Experimental study on anti angiogenesis of recombinant mouse angiostatin gene in mice with gallbladder carcinoma
- Author
-
Chunlin, Wang, Tao, Jiang, and Yunxie, Zhu
- Subjects
Mice ,Animals ,Endothelial Cells ,Gallbladder Neoplasms ,Genetic Therapy ,General Medicine ,Angiostatins ,Peptide Fragments ,Cell Proliferation - Abstract
Gallbladder cancer is one of the gastrointestinal tumors with an extremely poor prognosis. Its incidence rate is gradually increasing worldwide, and the rate of radical resection surgery is extremely low. Not sensitive to radiotherapy and chemotherapy, with a very poor prognosis. This study aimed to investigate whether the recombinant mouse angiostatin gene transfected anti-angiogenic gallbladder cancer cells can express angiostatin protein with the activity of inhibiting the growth of vascular endothelial cells and the inhibitory effect on the growth of gallbladder cancer. The recombinant mouse angiostatin gene eukaryotic expression plasmid was transfected into the gallbladder cancer cell line by applying liposome LIPOFECTAMINE 2000, and its activity was detected by vascular endothelial cell proliferation analysis. The results show that angiostatin can inhibit the growth of transplanted gallbladder cancer, and as the number of injections increases, the inhibition rate of gallbladder cancer growth also increases. At the end of the experiment, the total inhibition rate of gallbladder cancer growth reached 95% 5%, 20%, 30%, 40% gradually increase. Therefore, angiostatin has potential clinical application value in gene therapy of gallbladder cancer.
- Published
- 2022
25. Angiostatin levels in diabetes mellitus patients receiving insulin treatment: associations with laboratory findings, comorbidities, and medications.
- Author
-
ERTÜRK, İsmail, SERTOĞLU, Erdim, YEŞİLDAL, Fatih, ACAR, Ramazan, ÖZGÜRTAŞ, Taner, and SAĞLAM, Kenan
- Subjects
- *
ANGIOSTATINS , *PEOPLE with diabetes , *INSULIN , *METFORMIN , *NEOVASCULARIZATION - Abstract
Background/aim: The clinical effect of angiostatin in diabetes mellitus (DM) patients receiving insulin is a meaningful gap in the literature. In this study, we aimed to show the levels and the clinical significance of angiostatin in DM patients receiving insulin. Materials and methods: This is a case-control study. Serum angiostatin levels were determined by ELISA. A total of 83 people consisting of healthy subjects (n = 36) and patients with a diagnosis of DM receiving insulin therapy (n = 47) were included in this study. Results: The mean angiostatin levels of the DM group were significantly higher than those of the control group (86.0 ± 68.1 ng/mL and 58.0 ± 22.4 ng/mL, respectively; P = 0.011). Significantly lower angiostatin levels were determined in the DM patients receiving metformin with respect to those not receiving metformin (97.2 ± 74.4 ng/mL and 49.3 ± 7.0 ng/mL, respectively; P = 0.021). Significantly higher levels of angiostatin were observed among the DM patients using a beta-blocker (BB) than the DM patients not using a BB (115.5 ± 78.71 ng/mL and 73.44 ± 60.08 ng/mL, respectively; p = 0.029). Conclusion: This is the first study evaluating and demonstrating the serum angiostatin levels in DM patients receiving insulin. Further studies are required to understand the effect of angiostatin in diabetics and the effect of medications on angiogenesis in these patients.q [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
26. Serum Biomarkers of Endothelial Dysfunction in Fabry Associated Cardiomyopathy
- Author
-
Jefferson Loso, Natalie Lund, Maxim Avanesov, Nicole Muschol, Susanne Lezius, Kathrin Cordts, Edzard Schwedhelm, and Monica Patten
- Subjects
matrix metalloproteinase 9 ,angiostatins ,SDMA ,homoarginine ,Fabry disease ,Fabry cardiomyopathy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: Fabry disease (FD) is characterized by early development of vasculopathy and endothelial dysfunction. However, it is unclear whether these findings also play a pivotal role in cardiac manifestation. As Fabry cardiomyopathy (FC) is the leading cause of death in FD, we aimed to gather a better insight in pathological mechanisms of the disease.Methods: Serum samples were obtained from 17 healthy controls, 15 FD patients with and 7 without FC. FC was defined by LV wall thickening of >12 mm in cardiac magnetic resonance imaging and serum level of proBNP, high sensitive Troponin T (hsT), and globotriaosylsphingosine (lyso-GB3) were obtained. A multiplex ELISA-Assay for 23 different angiogenesis markers was performed in pooled samples. Markers showing significant differences among groups were further analyzed in single samples using specific Elisa antibody assays. L-homoarginine (hArg), L-arginine, asymmetric (ADMA), and symmetric Dimethylarginine (SDMA) were quantified by liquid chromatography—mass spectrometry.Results: Angiostatin and matrix metalloproteinase 9 (MMP-9) were elevated in FD patients compared to controls independently of the presence of FC (angiostatin: 98 ± 25 vs. 75 ± 15 ng/mL; p = 0.001; MMP-9: 8.0 ± 3.4 vs. 5.0 ± 2.4 μg/mL; p = 0.002). SDMA concentrations were highest in patients with FC (0.90 ± 0.64 μmol/l) compared to patients without (0.57 ± 0.10 μmol/l; p = 0.027) and vs. controls (0.58 ± 0.12 μmol/l; p = 0.006) and was positively correlated with indexed LV-mass (r = 0.61; p = 0.003), hsT (r = 0.56, p = 0.008), and lyso-Gb3 (r = 0.53, p = 0.013). Accordingly, the ratio of L-homoarginine to SDMA (hArg/SDMA) was lowest in patients with FC (2.63 ± 1.78) compared to controls (4.16 ± 1.44; p = 0.005). For L-arginine, hArg and ADMA no significant differences among groups could be detected, although a trend toward higher ADMA and lower hArg levels could be observed in the FC group. Furthermore, a significant relationship between kidney and cardiac function could be revealed (p = 0.045).Conclusion: Elevated MMP-9 and angiostatin levels suggest an increased extracellular matrix turnover in FD patients. Furthermore, endothelial dysfunction may also be involved in FC, as SDMA and hArg/SDMA are altered in these patients.
- Published
- 2018
- Full Text
- View/download PDF
27. Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), angiostatin, and endostatin are increased in radiotherapy-induced gastrointestinal toxicity.
- Author
-
Stansborough, Romany L., Bateman, Emma H., Al-Dasooqi, Noor, Bowen, Joanne M., Wignall, Anthony, Keefe, Dorothy M., Yeoh, Ann S., Logan, Richard M., Yeoh, Eric E. K., Stringer, Andrea M., and Gibson, Rachel J.
- Subjects
- *
RADIOTHERAPY complications , *VASCULAR endothelial growth factors , *TRANSFORMING growth factors-beta , *ANGIOSTATINS , *ENDOSTATIN , *RADIOTHERAPY - Abstract
Purpose: Radiotherapy-induced gut toxicity (RIGT) is a debilitating effect of radiotherapy for cancer, often resulting in significant diarrhea and pain. Previous studies have highlighted roles of the intestinal microvasculature and matrix metalloproteinases (MMPs) in the development of RIGT. We hypothesized vascular mediators would be significantly altered in a dark agouti (DA) rat model of RIGT. Additionally, we aimed to assess the effect of MMP-2 and -9 inhibition on the response of tumor-associated microvascular endothelial cells (TAMECs) to radiation. Methods: DA rats were administered 2.5 Gy abdominal irradiation (3 times/week over 6 weeks). Vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFβ), von Willebrand factor (VWF), angiostatin, and endostatin expression was assessed at 3, 6, and 15 weeks. Additionally, DA rat mammary adenocarcinoma tumor-associated microvascular endothelial cells (TAMECs) were used to assess the effects of radiation (12 Gy) and the MMP inhibitor SB-3CT on MMP, VEGF, and TGFβ expression, and cell viability. Results: VEGF mRNA expression was significantly increased in the colon at week 15 (p = .0012), and TGFβ mRNA expression was significantly increased in both the jejunum and colon at week 3 (p = .0280 and p = .0310, respectively). Endostatin immunostaining was significantly increased at week 3 (p = .0046), and angiostatin at 3 and 6 weeks (p = .0022 and p = .0135, respectively). MMP-2 and -9 mRNA and total protein levels were significantly increased following irradiation of TAMECs. Although this increase was significantly attenuated by SB-3CT, it did not significantly alter endothelial cell viability or VEGF and TGFβ mRNA expression. Conclusions: Findings of this study support the involvement of VEGF, TGFβ, angiostatin, endostatin, and MMP-2 in the pathobiology of RIGT. However, the relationship between these mediators is complex and needs further investigation to improve understanding of their therapeutic potential in RIGT. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
28. Gene-based antiangiogenic applications for corneal neovascularization.
- Author
-
Liu, Siyin, Romano, Vito, Steger, Bernhard, Kaye, Stephen B., Hamill, Kevin J., and Willoughby, Colin E.
- Subjects
- *
ANGIOSTATINS , *NEOVASCULARIZATION inhibitors , *CORNEA diseases , *VISION disorders , *TREATMENT effectiveness - Abstract
Corneal avascularity is maintained by angiogenic privilege, an active process involving the production of higher level of angiostatic factors to offset the effect of angiogenic factors. A wide range of pathological insults to the cornea can disrupt this intricate equilibrium and promote angiogenesis and corneal neovascularization with resultant visual impairment. Corneal neovascularization is also a major risk factor for graft failure after keratoplasty. Current treatment options for corneal neovascularization are restricted by limited efficacy, adverse effects, and a short duration of action. The unique anatomical position and relative immune privilege of cornea make it an ideal tissue for gene-based therapies. Gene transfer vectors have been used to deliver or target genes involved in the pathogenesis of corneal neovascularization in animal models. Several proangiogenic and antiangiogenic factors have been targeted and assessed in experimentally induced corneal neovascularization. Antisense oligonucleotides targeting corneal neovascularization have entered human clinical trials and have not required vector delivery systems. The emergence of these RNA-based strategies heralds a new era in the management of corneal neovascularization and ocular therapeutics. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
29. Circulating angiostatin serum level in patients with systemic sclerosis.
- Author
-
Gerlicz-Kowalczuk1, Zofia, Dziankowska-Zaborszczyk, Elzbieta, and Dziankowska-Bartkowiak, Bożena
- Subjects
- *
ANGIOSTATINS , *NEOVASCULARIZATION , *SYSTEMIC scleroderma , *APOPTOSIS , *VASCULAR endothelial cells , *PATIENTS , *THERAPEUTICS - Abstract
Introduction: Systemic sclerosis (SSc) is achronic connective tissue disease characterized by microangiopathy with inadequate angiogenesis. Angiostatin (AS) is a potent antiangiogenic factor specifically inhibiting proliferation and inducing apoptosis of vascular endothelial cells. Aim: To evaluate the level of angiostatin in the serum of patients with SSc. Material and methods: Serum levels of AS were measured in 20 SSc patients and 12 healthy controls. Results: A statistically significant difference in the serum levels of AS in SSc patients was observed compared to the control group (636.51 vs. 869.20 ng/ml; p = 0.012). Significant correlations between limited and disseminated SSc (lSSc/dSSc) were not found, however, a difference between lSSc and the control group was demonstrated (620.00 vs. 869.20 ng/ml; p = 0.011). The serum level of AS was not associated positively with organ changes caused by SSc. However, a statistically significant lower serum level of AS was observed in patients with SSc and no esophageal (p = 0.008) or pulmonary changes (p = 0.007) compared to the control group. Conclusions: Our results reveal significant differences in AS level in SSc patients compared to the healthy controls, and suggest that a low level of AS may occur as a result of impaired angiogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
30. Urine angiostatin and VCAM‐1 surpass conventional metrics in predicting elevated renal pathology activity indices in lupus nephritis.
- Author
-
Soliman, Samar, Mohamed, Fatma A., Ismail, Faten M., Stanley, Samantha, Saxena, Ramesh, and Mohan, Chandra
- Subjects
- *
LUPUS nephritis , *ANGIOSTATINS , *VASCULAR cell adhesion molecule-1 , *RENAL cancer diagnosis , *NONPARAMETRIC estimation , *DIAGNOSIS - Abstract
Abstract: Aim: The goal of this study is to investigate how urinary angiostatin, vascular cell adhesion molecule 1 (VCAM‐1) and established measures of renal function relate to specific histologic findings in paired kidney biopsy samples from patients with lupus nephritis (LN). Method: Urine samples were collected from 54 LN patients together with paired kidney biopsy samples and examined for urinary angiostatin and VCAM‐1 protein levels. Nonparametric tests were used to examine the association of both urinary biomarkers and established traditional laboratory markers of renal function with nine specific renal histologic features seen in LN, including glomerular leukocyte infiltration, endocapillary proliferation, cellular crescents, fibrinoid necrosis, wire loops, interstitial inflammation, glomerulosclerosis, fibrous crescents, tubular atrophy and interstitial fibrosis. Results: Compared to traditional renal disease metrics, both urinary angiostatin and VCAM‐1 exhibited outstanding potential (area under the curve 0.97, 0.98, respectively) to predict renal biopsy activity index score ≥ 7, which is associated with poor long‐term prognosis. Whereas urine VCAM‐1 was most significantly associated with fibrous crescents, urine angiostatin was most significantly associated with endocapillary proliferation, cellular crescents, fibrinoid necrosis and fibrous crescents in concurrent renal biopsies. Conclusion: Urinary angiostatin and VCAM‐1 are predictive of specific histological changes in concurrent LN renal biopsies. Both urinary biomarkers are good candidates for use as noninvasive measures of renal pathology activity changes in LN. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
31. A genomic screen for angiosuppressor genes in the tumor endothelium identifies a multifaceted angiostatic role for bromodomain containing 7 (BRD7).
- Author
-
Beijnum, Judy, Nowak-Sliwinska, Patrycja, Berkel, Maaike, Wong, Tse, and Griffioen, Arjan
- Subjects
ANGIOSTATINS ,NEOVASCULARIZATION ,BROMODOMAIN-containing proteins ,ANTINEOPLASTIC agents ,ENDOTHELIAL cells - Abstract
Tumor angiogenesis is characterized by deregulated gene expression in endothelial cells (EC). While studies until now have mainly focused on overexpressed genes in tumor endothelium, we here describe the identification of transcripts that are repressed in tumor endothelium and thus have potential suppressive effects on angiogenesis. We identified nineteen putative angiosuppressor genes, one of them being bromodomain containing 7 (BRD7), a gene that has been assigned tumor suppressor properties. BRD7 was studied in more detail, and we demonstrate that BRD7 expression is inversely related to EC activation. Ectopic expression of BRD7 resulted in a dramatic reduction of EC proliferation and viability. Furthermore, overexpression of BRD7 resulted in a bromodomain-dependent induction of NFκB-activity and NFκB-dependent gene expression, including ICAM1, enabling leukocyte-endothelial interactions. In silico functional annotation analysis of genome-wide expression data on BRD7 knockdown and overexpression revealed that the transcriptional signature of low BRD7 expressing cells is associated with increased angiogenesis (a.o. upregulation of angiopoietin-2, VEGF receptor-1 and neuropilin-1), cytokine activity (a.o. upregulation of CXCL1 and CXCL6), and a reduction of immune surveillance (TNF-α, NFκB, ICAM1). Thus, combining in silico and in vitro data reveals multiple pathways of angiosuppressor and anti-tumor activities of BRD7. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
32. Associations of plasma angiostatin and amyloid-β and tau levels in Alzheimer’s disease
- Author
-
Yuan Cheng, Jun-Rong Ren, Jie-Ming Jian, Chen-Yang He, Man-Yu Xu, Gui-Hua Zeng, Cheng-Rong Tan, Ying-Ying Shen, Wang-Sheng Jin, Dong-Wan Chen, Hui-Yun Li, Xu Yi, Yuan Zhang, Xian-Le Bu, and Yan-Jiang Wang
- Subjects
Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Amyloid beta-Peptides ,Cross-Sectional Studies ,Alzheimer Disease ,Humans ,Cognitive Dysfunction ,tau Proteins ,Angiostatins ,Biomarkers ,Peptide Fragments ,Biological Psychiatry - Abstract
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.
- Published
- 2022
33. ISOLATION AND PURIFICATION OF A KRINGLE 5 FROM HUMAN PLASMINOGEN USING AH-SEPHAROSE
- Author
-
Kapustianenko L. G., Iatsenko T. A., Iusova O. I., and Grinenko T. V.
- Subjects
plasminogen ,fragments of plasminogen ,kringle 5 ,angiostatins ,Biotechnology ,TP248.13-248.65 - Abstract
Our aim was to develop a method for isolation of human plasminogen kringle 5 possessing functional activity. The proposed method includes the following steps: hydrolysis of plasminogen with elastase, separation of mini-plasminogen from kringle fragments 1–3 and 4 on Lys-Sepharose, mini-plasminogen hydrolysis with pepsin, affinity chromatography on AH-Sepharose and polyacrilamide gel electrophoresis. We obtained the electrophoretically pure fragment of human plasminogen kringle 5 showing functional activity towards the ligands with high and low molecular mass. Weight yield was 3.8% that corresponds to 25.3% of the theoretically possible. It was established that affinity chromatography on AH-Sepharose was the sufficient step to isolate kringle 5 from mini-plasminogen hydrolysate with pepsin. This approach does not require additional purification steps while the ability of kringle 5 to bind specifically to AH-Sepharose demonstrates the functional activity of the kringle.
- Published
- 2014
- Full Text
- View/download PDF
34. PRODUCTION AND APPLICATION OF ANGIOSTATINS FOR THE TREATMENT OF OCULAR NEOVASCULAR DISEASES
- Author
-
V. L. Bilous, L. G. Kapustianenko, and A. A. Tykhomyrov
- Subjects
0301 basic medicine ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,lcsh:Biotechnology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Virology ,angiostatins ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,corneal neovascularization ,antiangiogenic therapy ,lcsh:TP248.13-248.65 ,retinopathy ,local gene delivery ,030221 ophthalmology & optometry ,Medicine ,business ,ocular neovascular diseases - Abstract
Angiostatins comprise a group of kringle-containing proteolytically-derived fragments of plasminogen/plasmin, which act as potent inhibitory mediators of endothelial cells proliferation and migration. Angiostatins are involved in modulation of vessel growth in healthy tissues and various pathological conditions associated with aberrant neovascularization. The aim of the present paper was to summarize available information, including our own experimental data, on prospects of angiostatin application for treatment of ocular neovascular diseases (OND), focusing on retinal pathologies and corneal injury. In particular, literature data on prospective and retrospective studies, clinical trials and animal models relating to the pathophysiology, investigation and management of OND are described. Special emphasis was made on the laboratory approaches of production of different angiostatin isoforms, as well as comparison of antiangiogenic capacities of native and recombinant angiostatin polypeptides. Several studies reported that angiostatins may completely abolish pathologic angiogenesis in diabetic proliferative retinopathy without affecting normal retinal vessel development and without exhibiting adverse side effects. Angiostatins have been tested as a tool for corneal antiangiogenesis target therapy in order to manage diverse ocular surface pathological conditions induced by traumas, chemical burns, previous surgery, chronic contact lens wear, autoimmune diseases, keratitis and viral infections (herpes, COVID-19), corneal graft rejection, etc. Among all known angiostatin species, isolated K5 plasminogen fragment was shown to display the most potent inhibitory activity against proliferation of endothelial cells via triggering multiple signaling pathways, which lead to cell death and resulting angiogenesis suppression. Application of adenoviral genetic construct encoding angiostatin K5 as a promising tool for OND treatment illustrates a vivid example of upcoming revolution in local gene therapy. Further comprehensive studies are necessary to elucidate the clinical potential and optimal regimes of angiostatinbased intervention modalities for treating ocular neovascularization.
- Published
- 2021
35. The essential anti-angiogenic strategies in cartilage engineering and osteoarthritic cartilage repair
- Author
-
Yixuan Amy Pei, Song Chen, and Ming Pei
- Subjects
Vascular Endothelial Growth Factor A ,Serine Proteinase Inhibitors ,Angiogenesis Inhibitors ,Apoptosis ,Article ,Mice ,Cellular and Molecular Neuroscience ,Chondrocytes ,Osteogenesis ,Osteoarthritis ,Animals ,Humans ,Regeneration ,Aggrecans ,Angiostatins ,Molecular Biology ,Inflammation ,Pharmacology ,Tissue Engineering ,Tissue Extracts ,Stem Cells ,Troponin I ,Cell Biology ,Endostatins ,Cartilage ,Cytokines ,Molecular Medicine ,Thrombospondins ,Low Density Lipoprotein Receptor-Related Protein-1 - Abstract
In the cartilage matrix, complex interactions occur between angiogenic and anti-angiogenic components, growth factors, and environmental stressors to maintain a proper cartilage phenotype that allows for effective load bearing and force distribution. However, as seen in both degenerative disease and tissue engineering, cartilage can lose its vascular resistance. This vascularization then leads to matrix breakdown, chondrocyte apoptosis, and ossification. Research has shown that articular cartilage inflammation leads to compromised joint function and decreased clinical potential for regeneration. Unfortunately, few articles comprehensively summarize what we have learned from previous investigations. In this review, we summarize our current understanding of the factors that stabilize chondrocytes to prevent terminal differentiation and applications of these factors to rescue the cartilage phenotype during cartilage engineering and osteoarthritis treatment. Inhibiting vascularization will allow for enhanced phenotypic stability so that we are able to develop more stable implants for cartilage repair and regeneration.
- Published
- 2022
36. THREE-DIMENSIONAL MODEL OF METASTATIC TUMOR ANGIOGENESIS IN RESPONSE TO ANTI-ANGIOGENIC FACTOR ANGIOSTATIN.
- Author
-
ZHAO, GAIPING, CHEN, ERYUN, YU, XIAOLI, CUI, HAIPO, LV, JIE, and WU, JIE
- Subjects
- *
NEOVASCULARIZATION , *TUMOR diagnosis , *ANGIOSTATINS , *THREE-dimensional modeling , *BLOOD vessels , *MATHEMATICAL models - Abstract
Surgeons observed that primary tumors are capable of suppressing the growth of their metastases by generating anti-angiogenic factor angiostatin. A three-dimensional (3D) mathematical model of development of the metastatic tumor vasculature is presented to simulate the morphology and construction of 3D microvascular networks under the inhibitory effect of anti-angiogenic factor angiostatin excreted by the primary tumor. The simulation results demonstrate that metastatic tumor microvascular density (MVD) decreases by about 60%, 58% and 52%, respectively, at , 7 and 14 days under the effect of anti-angiogenic factor angiostatin. The abnormal geometric and morphological features of 3D microvasculature networks inside and outside the metastatic tumor improve in the presence of angiostatin. The present model may allow to simulate experimental tests and may provide theoretical models for clinical research of anti-angiogenic therapy strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
37. Effects of a Propolis Extract on the Viability of and Levels of Cytoskeletal and Regulatory Proteins in Rat Brain Astrocytes: an In Vitro Study.
- Author
-
Agca, C., Tykhomyrov, A., Baydas, G., and Nedzvetsky, V.
- Subjects
- *
PROPOLIS , *PHYSIOLOGICAL effects of proteins , *LABORATORY rats , *ASTROCYTES , *GLIAL fibrillary acidic protein , *NF-kappa B , *ANGIOSTATINS , *THERAPEUTICS - Abstract
A potential for the use of propolis in preventive and therapeutic purposes has been acknowledged, but little attention has been paid to estimation of possible propolis cytotoxicity with respect to astrocytes. We tried to estimate how a propolis ethanol extract (PEE) affects rat brain astrocytes in vitro and also to uncover crucial molecular targets of the PEE action. Primary astrocytes were exposed to PEE in doses of 10, 25, or 100 μg/ml for 24 h, and then the cell viability was monitored by MTT assay. Levels of glial fibrillary acidic protein (GFAP), transcriptional nuclear factor-κB (NF-κB), poly(ADPribose) polymerase (PARP), and angiostatins were measured using Western blot to identify the molecular mechanisms underlying cell responses to PEE. The PEE treatment exerted a dose-dependent cytotoxic effect on cultured astrocytes. The PEE modulated astrocyte signaling pathways through inducing the expression of NF-κB and PARP. At the same time, the PEE stimulated GFAP synthesis and fibrillogenesis, which was indicative for activation of astrocytes preceding their suppression. The PEE significantly increased the production of angiostatin isoforms by astrocytes, thus contributing to an antiangiogenic potential of these cells. In summary, our results indicated that exposure to the PEE exerts certain cytotoxic effects on astrocytes in a dose-dependent manner; these effects are realized through modulation of cytoskeleton rearrangements and pro-apoptotic signaling pathways. A widely available, safe, and inexpensive substance, propolis, and its components and derivatives may be used in the prevention and treatment of neuronal impairments, including malignant tumors and neurodegenerative disorders associated with excessive astrocytic activation. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
38. Epigenetic approach for angiostatic therapy: promising combinations for cancer treatment.
- Author
-
Berndsen, Robert, Abdul, U., Weiss, Andrea, Zoetemelk, Marloes, te Winkel, Marije, Dyson, Paul, Griffioen, Arjan, and Nowak-Sliwinska, Patrycja
- Subjects
CANCER treatment ,NUCLEOTIDE sequence ,EPIGENETICS ,ANGIOSTATINS ,COMBINATION drug therapy - Abstract
Cancer cells are often dependent on epigenetic pathways for their survival. Consequently, drugs that target the epigenome, rather than the underlying DNA sequence, are currently attracting considerable attention. In recent years, the first epigenetic drugs have been approved for cancer chemotherapy, mainly for hematological applications. Limitations in single-drug efficacies have thus far limited their application in the treatment of solid tumors. Nevertheless, promising activity for these compounds has been suggested when combined with other, distinctly targeted agents. In this review, we discuss the anti-angiogenic activity of histone deacetylase and DNA methyltransferase inhibitors and their combinations with other targeted (anti-angiogenic) therapeutics in treatment of solid tumors. The role that these inhibitors play in the inhibition of tumor angiogenesis, particularly in combination with other targeted agents, and the advantages they present over broad acting anticancer agents, are critically discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
39. Lentiviral Vector Gene Transfer of Endostatin/Angiostatin for Macular Degeneration (GEM) Study.
- Author
-
Campochiaro, Peter A., Lauer, Andreas K., Sohn, Elliott H., Mir, Tahreem A., Naylor, Stuart, Anderton, Matthew C., Kelleher, Michelle, Harrop, Richard, Ellis, Scott, and Mitrophanous, Kyriacos A.
- Subjects
- *
ENDOSTATIN , *RETINAL degeneration , *LENTIVIRUSES , *GENETIC transformation , *ANGIOSTATINS - Abstract
Neovascular age-related macular degeneration (NVAMD) is a prevalent cause of vision loss. Intraocular injections of VEGF-neutralizing proteins provide benefit, but many patients require frequent injections for a prolonged period. Benefits are often lost over time due to lapses in treatment. New treatments that sustain anti-angiogenic activity are needed. This study tested the safety and expression profile of a lentiviral Equine Infectious Anemia Virus (EIAV) vector expressing endostatin and angiostatin (RetinoStat®). Patients with advanced NVAMD were enrolled at three centers in the United States, and the study eye received a subretinal injection of 2.4 × 104 ( n = 3), 2.4 × 105 ( n = 3), or 8.0 × 105 transduction units (TU; n = 15). Each of the doses was well-tolerated with no dose-limiting toxicities. There was little or no ocular inflammation. There was one procedure-related serious adverse event (AE), a macular hole, which was managed without difficulty and resolved. There was a vector dose-related increase in aqueous humor levels of endostatin and angiostatin with high reproducibility among subjects within cohorts. Mean levels of endostatin and angiostatin peaked between 12 and 24 weeks after injection of 2.4 × 105 TU or 8.0 × 105 TU at 57-81 ng/mL for endostatin and 15-27 ng/mL for angiostatin, and remained stable through the last measurement at week 48. Long-term follow-up demonstrated expression was maintained at last measurement (2.5 years in eight subjects and >4 years in two subjects). Despite an apparent reduction in fluorescein angiographic leakage that broadly correlated with the expression levels in the majority of patients, only one subject showed convincing evidence of anti-permeability activity in these late-stage patients. There was no significant change in mean lesion size in subjects injected with 8.0 × 105 TU. These data demonstrate that EIAV vectors provide a safe platform with robust and sustained transgene expression for ocular gene therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
40. PRODUCTION AND CHARACTERISTICS OF ANTIBODIES AGAINST K1-3 FRAGMENT OF HUMAN PLASMINOGEN
- Author
-
A. A. Tykhomyrov, E. I. Yusova, S. I. Diordieva, V. V. Corsa, and T. V. Grinenko
- Subjects
plasminogen ,kringle domains ,plasminogen fragments ,angiostatins ,polyclonal antibodies. ,Biotechnology ,TP248.13-248.65 - Abstract
Components of plasminogen/plasmin system play crucial role in fibrinolytic rocesses. They are also involved in regulation of cell activity in normalcy and various pathological conditions. In particular, kringle-containing proteolityc plasminogen fragments, which are denoted as angiostatins, participate in processes during neovascularization, metastasis, tumor growth, inflammation. Angiostatins are considered to be potential markers of diseases associated with vascular pathologies. Therefore, elaboration of specific and sensitive methods for their detection is still important area of inquiry. In the present study, approaches for obtaining of plasminogen fragments through its limited proteolysis by pancreatic elastase and further purification of proteolytic derivates by means of gel filtration and affinity chromatography on Lys-Sepharose are described. Polyclonal antibodies raised to fragment K1-3 have been produced, and their principal immunochemical properties have been studied. It has been found that antibodies purified on immunoaffine sorbent demonstrate different affinity toward plasminogen and its fragment, as follows: Glu-Pg > Lys-Pg > К1-3 > mini-Pg > К4. Based on the data obtained, immunological features of plasminogen kringle domains are discussed. Antibodies against fragment K1-3 could be applied in immunochemical analysis, in particular, Western blot, for detection of angiostatins as markers of tumor growth, metastasis, cardiovascular diseases and inflammation processes, and used as molecular tool for investigation of plasminogen/plasmin system functioning in health and disease.
- Published
- 2013
- Full Text
- View/download PDF
41. Endorepellin-evoked Autophagy Contributes to Angiostasis.
- Author
-
Goyal, Atul, Gubbiotti, Maria A., Chery, Daphney R., Lin Han, and Iozzo, Renato V.
- Subjects
- *
AUTOPHAGY , *C-terminal residues , *ANGIOSTATINS , *VASCULAR endothelial growth factor receptors , *ENDOTHELIAL cells - Abstract
Endorepellin, the C-terminal domain of perlecan, is an angiostatic molecule that acts as a potent inducer of autophagy via its interaction with VEGFR2. In this study, we examined the effect of endorepellin on endothelial cells using atomic force microscopy. Soluble endorepellin caused morphological and biophysical changes such as an increase in cell surface roughness and cell height. Surprisingly, these changes were not accompanied by alterations in the endothelial cell elastic modulus. We discovered that endorepellin-induced autophagic flux led to co-localization of mammalian target of rapamycin with LC3-positive autophagosomes. Endorepellin functioned upstream of AMPactivated kinase α, as compound C, an inhibitor of AMP-activated kinase α, abrogated endorepellin-mediated activation and co-localization of Beclin 1 and LC3, thereby reducing autophagic progression. Functionally, we discovered that both endorepellin and Torin 1, a canonical autophagic inducer, blunted ex vivo angiogenesis. We conclude that autophagy is a novel mechanism by which endorepellin promotes angiostasis independent of nutrient deprivation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
42. 重组人血管内皮抑制素联合肝动脉介入治疗对中晚期肝癌无疾病进展生存期的影响
- Author
-
郝明志, 林海澜, 陈起忠, and 胡育斌
- Abstract
Objective To investigate the effect of recombinant human endostatin (Endostar) combined with hepatic artery interventional therapy on the progression-free survival (PFS) of patients with advanced hepatocellular carcinoma (HCC). MethodsA total of 86 patients with advanced HCC who were admitted to Fujian Provincial Tumor Hospital from March 2011 to May 2015 were selected and divided into treatment group and control group according to a matched pair design. The treatment group (43 patients) was given Endostar combined with hepatic artery interventional therapy, and the control group (43 patients) was given hepatic artery interventional therapy combined with oral administration of Ganfule. The chi-square test was applied for comparison of categorical data between the two groups, and the t-test was applied for comparison of continuous data between the two groups. The Kaplan-Meier method was applied for survival analysis, the Log-rank test was applied for univariate analysis, and Cox proportional hazards model was applied for multivariate analysis. ResultsThe median PFS in the treatment group and the control group was 154 d [95% confidence interval (CI): 94-214 d] and 70 d (95%CI: 39-101 d), respectively, with a significant difference between the two groups (χ2=10.741, P=0.001). Univariate analysis showed that the severity of liver cirrhosis, number of tumors, and main portal vein tumor thrombus/inferior vena cava tumor thrombus were the prognostic factors for patients with advanced HCC (χ2=8.182, 9.150, and 6.565, P=0.004, 0.027, and 0.038); multivariate analysis showed that the severity of liver cirrhosis and main portal vein tumor thrombus/inferior vena cava tumor thrombus were the independent prognostic factors for PFS in patients with advanced HCC who were treated with Endostar combined with hepatic artery interventional therapy (P=0.028 and 0.013). ConclusionEndostar can effectively prolong the PFS of patients with advanced HCC after hepatic artery interventional therapy, but it does not have a clear advantage in patients with severe liver cirrhosis or main portal vein tumor thrombus/inferior vena cava tumor thrombus. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
43. MicroRNA-497 inhibits cell proliferation, migration, and invasion by targeting AMOT in human osteosarcoma cells.
- Author
-
Wen-Dong Ruan, Pei Wang, Shiqing Feng, Yuan Xue, and Bin Zhang
- Subjects
- *
OSTEOSARCOMA , *MICRORNA , *INHIBITION of cellular proliferation , *CELL migration inhibition , *ANGIOSTATINS , *CANCER invasiveness , *GENE expression , *PREVENTION , *THERAPEUTICS - Abstract
MicroRNAs (miRNAs) have a role in the development and progression of human malignancy. The expression of miR-497 is decreased in malignant tumors, which suggests a role for miR-497 as a tumor suppressor. Angiomotin is encoded by the AMOT gene, which is a target for miR-497. Angiomotin has a role in angiogenesis, cell proliferation, and invasion in human malignancies, including osteosarcoma. However, the role of miR-497 in human osteosarcoma is unknown. This preliminary study included human osteosarcoma tissues and normal tissues from 20 patients, the osteosarcoma cell lines, MG-63, SAOS-2, U-2 OS, and the human osteoblast cell line hFOB (OB3). Western blots for angiomotin and quantitative real-time polymerase chain reaction for the expression of miR-497 and AMOT were performed. Knockdown studies were performed using RNA interference and transfection studies used miR-497 mimics. Quantitative cell migration assays were performed, and cell apoptosis was studied by flow cytometry. Osteosarcoma cells and cell lines showed reduced expression of miR-497 and increased expression of angiomotin. Transfection of osteosarcoma cells with miR-497 mimics suppressed the expression of angiomotin. Results from a dual-luciferase reporter system supported AMOT as a direct target gene of miR-497. Knockdown of AMOT using RNA interference resulted in inhibition of osteosarcoma cell proliferation, migration, and invasion. These preliminary studies support a role for miR-497 as a suppressor of AMOT gene expression in human osteosarcoma cells, resulting in suppression of tumor cell proliferation and invasion. Further studies are recommended to investigate the role of miR-497 in osteosarcoma and other malignant mesenchymal tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
44. New Mathematical Biosciences and Engineering Findings from K.N. Toosi University of Technology Described (Investigation of the evolution of tumor-induced microvascular network under the inhibitory effect of anti-angiogenic factor, angiostatin:...).
- Abstract
Keywords: Angiogenesis; Angiology; Angiostatins; Health and Medicine; Life Sciences; Mathematical Biosciences and Engineering; Mathematics EN Angiogenesis Angiology Angiostatins Health and Medicine Life Sciences Mathematical Biosciences and Engineering Mathematics 1341 1341 1 03/24/23 20230228 NES 230228 2023 MAR 3 (NewsRx) -- By a News Reporter-Staff News Editor at Drug Week -- Fresh data on mathematical biosciences and engineering are presented in a new report. Angiogenesis, Angiology, Angiostatins, Health and Medicine, Life Sciences, Mathematical Biosciences and Engineering, Mathematics Angiostatin-induced microvascular network reformation is investigated in a two-dimensional space by considering two parent vessels around a circular tumor by a modified discrete angiogenesis model in different tumor sizes. [Extracted from the article]
- Published
- 2023
45. Bogomolets National Medical University Researchers Further Understanding of Biomarkers (The levels of hypoxia- and angiogenesis-related regulators and matrix metalloproteinase 9 activity in tear fluid of patients with non-penetrating ocular ...).
- Subjects
MATRIX metalloproteinases ,MEDICAL research personnel ,PROTEOLYTIC enzymes ,BIOMARKERS ,METALLOPROTEINS - Abstract
Angiogenesis, Angiology, Angiostatins, Biomarkers, Collagenases, Diagnostics and Screening, Endopeptidases, Enzymes and Coenzymes, Gelatinases, Health and Medicine, Matrix Metalloproteinase, Matrix Metalloproteinase 9, Matrix Metalloproteinases, Metalloproteases, Metalloendopeptidases, Metalloproteinases, Metalloproteins, Peptide Hydrolases, Peptides and Proteins, Proteomics, Secreted Matrix Metalloproteinases Studied proteins of tear fluid can serve as relevant biomarkers of corneal wound healing and are appropriate for diagnostic and prognostic purposes." Keywords: Angiogenesis; Angiology; Angiostatins; Biomarkers; Collagenases; Diagnostics and Screening; Endopeptidases; Enzymes and Coenzymes; Gelatinases; Health and Medicine; Matrix Metalloproteinase; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Metalloendopeptidases; Metalloproteases; Metalloproteinases; Metalloproteins; Peptide Hydrolases; Peptides and Proteins; Proteomics; Secreted Matrix Metalloproteinases EN Angiogenesis Angiology Angiostatins Biomarkers Collagenases Diagnostics and Screening Endopeptidases Enzymes and Coenzymes Gelatinases Health and Medicine Matrix Metalloproteinase Matrix Metalloproteinase 9 Matrix Metalloproteinases Metalloendopeptidases Metalloproteases Metalloproteinases Metalloproteins Peptide Hydrolases Peptides and Proteins Proteomics Secreted Matrix Metalloproteinases 2023 JAN 30 (NewsRx) -- By a News Reporter-Staff News Editor at Hematology Week -- New research on biomarkers is the subject of a new report. [Extracted from the article]
- Published
- 2023
46. The Role of Angiogenesis in Hepatocellular Carcinoma
- Author
-
Weijing Sun, Michelle Mynderse, Michael A. Morse, Richard D. Kim, Paolo Abada, Aiwu Ruth He, and Richard S. Finn
- Subjects
Vascular Endothelial Growth Factor A ,0301 basic medicine ,Cancer Research ,Carcinoma, Hepatocellular ,Angiogenesis ,Vascular Endothelial Growth Factor Receptor ,Angiogenesis Inhibitors ,Neovascularization ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma ,Humans ,Medicine ,Clinical significance ,Angiostatins ,Protein Kinase Inhibitors ,Predictive biomarker ,Neovascularization, Pathologic ,business.industry ,Liver Neoplasms ,Sorafenib ,Prognosis ,medicine.disease ,digestive system diseases ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cancer research ,medicine.symptom ,business - Abstract
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.
- Published
- 2019
47. Levels of angiogenic regulators and MMP-2, -9 activities in Martorell ulcer: a case report
- Author
-
A. A. Tykhomyrov and O. M. Petrenko
- Subjects
MMP ,business.industry ,Matrix metalloproteinase ,VEGF ,Biochemistry ,angiostatins ,Martorell ulcer ,lcsh:Biochemistry ,chronic wounds ,Cancer research ,Medicine ,lcsh:QD415-436 ,angiogenic regulators ,business - Abstract
Martorell hypertensive ischemic leg ulcers (HYTILU) represent a unique form of lower extremity non-healing ulcers that develop in association with poorly controlled high blood pressure. The present study was performed in order to assess levels of protein regulators of angiogenesis (vascular endothelial growth factor, or VEGF, and angiostatins) and to evaluate activities of matrix metalloproteinases (MMPs) (gelatinases MMP-2 and -9) in wound cutaneous tissue in the case of patient with 2-years HYTILU history. VEGF and angiostatin levels were analyzed by Western blot, MMP activities were evaluated by gelatin zymography. We report here for the first time that wound tissue in HYTILU is characterized with increased levels of VEGF (by 75 folds vs. histologically normal tissue, P < 0.01) and dramatic overproduction of angiostatin levels, which are undetectable in healthy cutaneous tissue. Approximately 10-fold elevation in MMP-2 and -9 activities is observed in wound tissue as compared with uninjured cutaneous tissue. Obtained results indicate that increased production of angiogenic inhibitors, angiostatins, may counteract VEGF-induced pro-angiogenic signaling, and together with MMP overactivation, contributes to failed healing of ischemic ulcer. Further extended studies are needed to clarify how changes of angiogenic profile and imbalance of proteolytic activities in non-healing Martorell ulcers can be considered during their management procedures to improve efficacy of surgery debridement and/or skin grafting.
- Published
- 2019
48. Exercise Training Ameliorates Cognitive Dysfunction in Amyloid Beta-injected Rat Model: Possible Mechanisms of Angiostatin/VEGF Signaling
- Author
-
Hamid Rajabi, Reza Gharakhanlu, Yoonjung Park, Aliasghar Zarezadehmehrizi, Jonghae Lee, Junyoung Hong, Mohammad Azimi, and Naser Naghdi
- Subjects
Male ,Vascular Endothelial Growth Factor A ,0301 basic medicine ,medicine.medical_specialty ,Amyloid beta ,Morris water navigation task ,Hippocampus ,Biochemistry ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Alzheimer Disease ,Internal medicine ,medicine ,Animals ,Hippocampus (mythology) ,Cognitive Dysfunction ,Rats, Wistar ,Maze Learning ,Angiostatins ,Cognitive deficit ,Amyloid beta-Peptides ,Angiostatin ,biology ,business.industry ,Neurogenesis ,Kinase insert domain receptor ,Rats ,Vascular endothelial growth factor ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,chemistry ,biology.protein ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Vascular endothelial growth factor (VEGF) regulates angio/neurogenesis and also tightly links to the pathogenesis of Alzheimer's disease (AD). Although exercise has a beneficial effect on neurovascular function and cognitive function, the direct effect of exercise on VEGF-related signaling and cognitive deficit in AD is incompletely understood. Therefore, the purpose of this study was to investigate the protective effect of exercise on angiostatin/VEGF cascade and cognitive function in AD model rats. Wistar male rats were randomly divided into five groups: control (CON), injection of DMSO (Sham-CON), CON-exercise (sham-EX), intrahippocampal injection of Aβ (Aβ), and Aβ-exercise (Aβ-EX). Rats in EX groups underwent treadmill exercise for 4 weeks, then the cognitive function was measured by the Morris Water Maze (MWM) test. mRNA levels of hypoxia-induced factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and angiostatin were determined in hippocampus by RT-PCR. We found that spatial learning and memory were impaired in Aβ-injected rats, but exercise training improved it. Moreover, exercise training increased the reduced mRNA expression level of VEGF signaling, including HIF1α, VEGF, and VEGFR2 in the hippocampus from Aβ-injected rats. Also, the mRNA expression level of angiostatin was elevated in the hippocampus from Aβ-injected rats, and exercise training abrogated its expression. Our findings suggest that exercise training improves cognitive function in Aβ-injected rats, possibly through enhancing VEGF signaling and reducing angiostatin.
- Published
- 2021
49. Assessment of selected angiogenesis markers in the serum of middle‐aged male patients with plaque psoriasis
- Author
-
Aldona Pietrzak, Paweł Kiciński, Marcin Feldo, Mateusz Socha, and Tomasz Zubilewicz
- Subjects
Adult ,Male ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Angiogenesis ,Inflammation ,Dermatology ,Gastroenterology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Psoriasis Area and Severity Index ,Psoriasis ,Internal medicine ,medicine ,Humans ,Clinical significance ,Angiogenic Proteins ,Angiostatins ,Skin ,Angiostatin ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Endostatins ,Vascular endothelial growth factor A ,030220 oncology & carcinogenesis ,Fibroblast Growth Factor 1 ,medicine.symptom ,Endostatin ,business - Abstract
Local angiogenesis accompanies inflammation in psoriasis-affected skin. To determine the serum concentrations of selected pro- and anti-angiogenic factors and their interrelationships in patients with plaque psoriasis. The study included 41 men diagnosed with psoriasis, aged 43.5 ± 11.7 years. The Psoriasis Area and Severity Index score was 23.4 ± 5.2 points. The control group consisted of 38 healthy, age-matched men. The levels of pro-angiogenic cytokines and angiogenesis inhibitors, including fibroblast growth factor 1 (FGF-1), vascular endothelial growth factor A (VEGF-A), endostatin, and angiostatin, were determined from the serum of patients and controls using enzyme-linked immunosorbent assays. Compared with controls, patients with psoriasis had a significantly lower concentration of FGF-1 (P = .01) but higher concentrations of endostatin (P = .04) and angiostatin (P = .02). The concentration of VEGF-A was also higher in patients with psoriasis but not significantly (P = .25). The concentration of C-reactive protein (CRP) was significantly higher among patients with psoriasis than controls (P < .0001). Among controls, CRP concentrations did not correlate significantly with the concentrations of FGF-1, VEGF-A, endostatin, or angiostatin. Among patients with psoriasis, CRP concentrations correlated moderately with the concentrations of VEGF-A (r = .35; P = .02) and angiostatin (r = .31; P = .04). The concentration of VEGF-A correlated positively with PASI (r = .05; P = .0009) and BSA values (r = .39; P = .01). Psoriasis is associated with an altered systemic balance between pro-angiogenic and anti-angiogenic factors. The increase in serum angiogenesis inhibitors may be associated with unfavorable changes in the development of coronary collateral circulation. However, the clinical significance of this has not yet been established.
- Published
- 2021
50. Development of Recombinant Adeno-Associated Virus Serotype 2/8 Carrying Kringle Domains of Human Plasminogen for Sustained Expression and Cancer Therapy.
- Author
-
Kuo, Cheng-Hsiang, Chang, Bi-Ing, Lee, Fang-Tzu, Chen, Po-Ku, Lee, Jeng-Shin, Shi, Guey-Yueh, and Wu, Hua-Lin
- Subjects
- *
ADENO-associated virus , *SEROTYPES , *PLASMINOGEN , *CANCER treatment , *ANGIOSTATINS - Abstract
Angiostatin and other plasminogen derivatives exhibit antitumor activities directly or indirectly, have demonstrated promising anticancer effects in preclinical studies, but have mostly failed in clinical trials partly due to their short serum half-lives. Our previous studies demonstrated that recombinant human plasminogen kringle 1-5 (K1-5) has superior antitumor activity compared with angiostatin. In addition, optimization of recombinant K1-5 with three amino acid substitutions enhances its antitumor effect. The current study was thus undertaken to evaluate prolonged expression of optimized K1-5 as cancer gene therapy. The recombinant adeno-associated virus (AAV) vector was used to express a secreted form of the optimized K1-5 (AAV-sK15tm) to improve its pharmacokinetic profile, which was considered to be the hurdle in angiostatin treatment of cancer. We successfully generated high-titer recombinant AAV vectors and observed sustained transgene expression for 567 days after a single injection of virus. The treated animals did not display any visible signs of abnormalities and showed normal serum biochemistry. The therapeutic potential of this treatment modality was demonstrated by both a strong inhibition of lung metastasis in the mouse B16F10 melanoma model and significant growth retardation of Lewis lung carcinoma xenografts in C57BL/6N mice as well as human A2058 melanoma xenografts in NOD/SCID (nonobese diabetic/severe combined immunodeficient) mice. Taken together, our results suggested that AAV-sK15tm produced long-term suppressive effects on cancer growth in vivo and should warrant serious consideration for clinical development. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.